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(PDF) Microalbuminuria does not reflect increased systemic capillary permeability in septic shock
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Microalbuminuria does not reflect increased systemic capillary permeability in septic shock
April 2003
Intensive Care Medicine 29(3):391-5
DOI: 10.1007/s00134-003-1651-0
Abstract and Figures
To investigate the correlation between microalbuminuria and extravascular lung water in patients in septic shock who require mechanical ventilation for severe respiratory failure.
Prospective, observational, clinical study in the 20-bed intensive care unit of a university hospital.
25 consecutive patients in septic shock and also in severe respiratory failure requiring mechanical ventilation.
Hemodynamic parameters and extravascular lung water were determined by single arterial thermodilution. Together with each hemodynamic measurement the PaO(2)/FIO(2) ratio and urinary microalbumin to creatinine ratio (M:Cr) was measured. Serum C-reactive protein (CRP) and procalcitonin (PCT) levels were also determined daily.
The EVLW index was significantly higher than normal throughout the study. Microalbuminuria was in the normal range on entry and remained so for the rest of the study period. Serum PCT and CRP levels were significantly higher than normal at every assessment points. No significant correlation was found between M:Cr and either EVLW or PaO(2)/FIO(2).
In this study patients in septic shock with significantly elevated EVLW had normal urinary M:Cr, and there was no correlation between M:Cr and EWLV, and PaO(2)/FIO(2). Therefore based on the current results routine measurements of microalbuminuria to determine endothelial permeability cannot be recommended in critically ill patients.
Demographic data (n=25). Data are presented as median (interquartile ranges); Simplified Acute Physiology Score II (SAPS II) and diagnoses indicate the severity score and diagnosis on admission to ICU (ARDS acute respiratory distress syndrome, S survivors, NS nonsurvivors) …
Daily MODS, PCT, CRP, serum albumin, and edema score. Data are presented as: median (interquartile range) …
Figures - uploaded by
Tamas Szakmany
Content uploaded by Tamas Szakmany
Received: 18 June 2002
Accepted: 6 December 2002
Published online: 31 January 2003
© Springer-V erlag 2003
Abstract Objective: To investigate
the correlation between microalbu-
minuria and extravascular lung water
in patients in septic shock who re-
quire mechanical ventilation for se-
vere respiratory failure. Design and
setting: Prospective, observational,
clinical study in the 20-bed intensive
care unit of a university hospital.
Patients and participants: 25 con-
secutive patients in septic shock and
also in severe respiratory failure re-
quiring mechanical ventilation.
Interventions: Hemodynamic param-
eters and extravascular lung water
were determined by single arterial
thermodilution. Together with each
hemodynamic measurement the
PaO 2 /FIO 2 ratio and urinary microal-
bumin to creatinine ratio (M:Cr) was
measured. Serum C-reactive protein
(CRP) and procalcitonin (PCT) lev-
els were also determined daily.
Measurements and r esults: The
EVL W index was significantly high-
er than normal throughout the study.
Microalbuminuria was in the normal
range on entry and remained so for
the rest of the study period. Serum
PCT and CRP levels were signifi-
cantly higher than normal at every
assessment points. No significant
correlation was found between M:
Cr and either EVL W or PaO 2 /FIO 2 .
Conclusions: In this study patients in
septic shock with significantly ele-
vated EVL W had normal urinary
M:Cr, and there was no correlation
between M:Cr and EWL V , and
PaO 2 /FIO 2 . Therefore based on the
current results routine measurements
of microalbuminuria to determine
endothelial permeability cannot be
recommended in critically ill pa-
tients.
Keywords Microalbuminuria ·
Sepsis · Multiple system organ
failure · Critical illness
Intensive Care Med (2003) 29:391–395
DOI 10.1007/s00134-003-1651-0 ORIGINAL
Zsolt Molnár
T amás Szakmány
Péter Heigl
Microalbuminuria does not reflect increased
systemic capillary permeability in septic shock
Introduction
The syndrome of septic shock is characterized by hypo-
tension and multiple organ failure resulting from system-
ic release of inflammatory cytokines [1]. This inflamma-
tory response can lead to the damage of cell membrane
structures, which at the endothelial level gives rise to in-
creased capillary permeability [2, 3]. The increased sys-
temic vascular permeability may occur within hours of
an acute event such as surgery or sepsis, causing an ex-
travasation of albumin and water leading to interstitial
edema. Clinically such an increase in permeability can-
not be easily identified [4]. An accurate method of using
radiolabeled albumin is invasive, time consuming, and
expensive. However, it has been suggested that small in-
creases in glomerular permeability are amplified by large
changes in renal albumin excretion since the tubular re-
absorptive mechanisms for albumin are close to satura-
tion [5]. Therefore increased systemic endothelial per-
meability might be detected and monitored by this in-
crease in urinary albumin loss, termed microalbuminuria
[6]. Indeed, microalbuminuria occurs after various acute
pathological states such as pancreatitis, trauma, isch-
emia, and major surgery [7, 8, 9]. In such conditions mi-
Z. Molnár ( ✉ ) · T. Szakmány · P . Heigl
Department of Anaesthesiology
and Intensive Care,
University of Pécs, Pécs, Hungary
e-mail: z_molnar@hotmail.com
Tel.: +36-72-536440
Fax: +36-72-536441
croalbuminuria has a rapid onset and typically lasts for
less than 48 h unless complications occur. However, lit-
tle is known about the diagnostic value of microalbumin-
uria regarding increased vascular permeability in severe
sepsis and septic shock.
Patients with sepsis are put at high risk of developing
pulmonary edema as part of the generalized capillary leak-
age. In the past 20 years the transpulmonary indicator di-
lution technique has become an interesting alternative to
the pulmonary artery catheter in hemodynamic monitor-
ing. This technique enables us to estimate the intrathoracic
blood volume (ITBV) and the extravascular lung water
(EVL W). The measurement of EVLW has been shown to
be a more sensitive indicator of detecting noncardiogenic
pulmonary edema than pulmonary artery occlusion pres-
sure, chest radiography, or oxygenation [10, 11]. More re-
cently, single arterial thermodilution derived EVLW and
ITBV measurements have been shown to agree closely
with the corresponding double-indicator technique, mak-
ing it a promising simple method for the bedside [12].
This study had two objectives: to evaluate (a) the
course of microalbuminuria in a group of critically ill pa-
tients in septic shock who also required mechanical ven-
tilation for severe respiratory failure, and (b) whether
there is a correlation between microalbuminuria and the
degree of EVL W.
Materials and methods
Patients
The study protocol was approved by the local ethics committee.
Between December 2000 and March 2002 25 consecutive patients
(19 men, 6 women) in septic shock were enrolled. Of the 25 pa-
tients 19 died on the ICU (3 on day 2, 1 on day 3, 15 after the
completion of the study). Demographics and admission diagnoses
are summarized in Table 1. All patients had to fulfill the following
criteria of severe cardiovascular and respiratory system failure: (a)
Early reversible septic shock. Septic shock as defined by the
American College of Chest Physicians/Society of Critical Care
Medicine Consensus Conference (i.e., signs of sepsis and pro-
longed systolic hypotension of <90 mmHg for >1 h, despite ade-
quate fluid resuscitation without inotropic support) [13]. “Early”
was defined as time from diagnosis of septic shock to study entry
less than 24 h. “Reversible” meant that patients had to become sta-
ble as a response to inotropic and vasopressor support as moni-
tored by invasive hemodynamic measurements within a few hours.
(b) The criterion of severe respiratory failure was defined as the
requirement of mechanical ventilation with a PaO 2 /FIO 2 ratio less
than 225 mmHg (the limit was decided as determined by the respi-
ratory organ dysfunction score of 2 or greater as monitored by the
Multiple Organ Dysfunction Scoring system, MODS) [14]. (c)
Apart from the cardiorespiratory failure patients had to be free of
other system failure such as renal, hepatic, and hematological im-
pairment as indicated by organ dysfunction scores lower than 2 as
determined by the MODS. Patients with chronic cardiovascular
system failure (New York Heart Association class IV), chronic
respiratory failure (chronic hypoxia, hypercapnia), chronic renal
failure requiring renal replacement therapy, chronic liver failure
(biopsy-confirmed cirrhosis or portal hypertension), and those
with insulin-dependent diabetes mellitus, with known aortic aneu-
rysm were excluded or withdrawn from the study. Patients who
did not stabilize following the commencement of inotropic sup-
port were also withdrawn.
Clinical parameters
The MODS was calculated from the respiratory (PaO 2 /FIO 2 ), car-
diovascular (HR × CVP/MAP), renal (serum creatinine), hepatic
(serum bilirubin), and hematological (platelet count) organ dys-
function parameters. As all patients were sedated with propofol
and fentanyl, and due to their critical general condition their men-
tal status was not assessed daily; therefore the central nervous
system dysfunction score was not taken into account. The MODS
scores were obtained daily during the first 3 days of septic shock
( t 1 , t 2 , t 3 ). Multiple system organ failure was defined as MODS of
4 or higher.
All patients received mechanical ventilation in pressure-con-
trolled mode, and positive end-expiratory pressure (minimum of
5c m H
2 O) was adjusted individually according to blood gas val-
ues. None of the patients received continuous infusion or intermit-
tent boluses of muscle relaxants during the study period. The de-
gree of subcutaneous peripheral edema was assessed daily using
the pitting score as described by Diskin et al. [15]. Depth of “pit”
was measured following a 10-s compression on the ankle and hand
by one finger (score: 1=no edema, 2=pit: 1–2 mm, 3=pit: 3–4 mm,
4=pit: ≥ 4 mm).
Hemodynamic parameters
The trial period started following the placement of the arterial
thermodilution catheter. Hemodynamic measurements were made
every 8 h for 72 h ( t 1 – t 9 ). Hemodynamic parameters were deter-
mined in each patient by single arterial thermodilution, for which
a flexible catheter with an integrated thermistor (PiCCO, Pulsio-
cath 4F, PV 2024L, Pulsion Medical Systems, Munich, Germany)
was introduced via the femoral artery. ITBV and EVLW measure-
ments were obtained by injections of a 10-ml bolus of 0.9% saline
at less than 10°C via a central venous catheter. The mean value of
three consecutive measurements was used for analysis. For inter-
individual comparison absolute values for ITBV and EVLW were
normalized as indexed by body surface area (ITBVI, normal range
850–1000 ml/m) and body weight (EVLWI, normal range
5–7 ml/kg). All injections were made manually and not synchro-
392
Ta b l e 1 Demographic data ( n =25). Data are presented as median
(interquartile ranges); Simplified Acute Physiology Score II
( SAPS II ) and diagnoses indicate the severity score and diagnosis
on admission to ICU ( ARDS acute respiratory distress syndrome, S
survivors, NS nonsurvivors)
Age (years) 57 (47–66)
Sex: M/F 19/6
SAPS II 32 (18–51)
Major surgery
Esophagectomy 5
Total gastrectomy 4
Whipple’s operation 3
Pneumonia 8
ARDS 2
Pancreatitis 1
Acute myocardial infarction 1
Peritonitis 1
ICU stay (days) 20 (9–28)
Survival: S/NS 6/19
nized with the respiratory cycle. Cardiac index (CI) and systemic
vascular resistance index (SVRI) were also recorded.
For fluid resuscitation Hartmann’s solution and hydroxyethyl
starch was used as indicated by hemodynamic parameters. When
hypotension persisted, inotropic support was commenced. Dobuta-
mine was administered up to 20 µg/kg per minute to increase CI,
and norepinephrine was added to increase SVRI and blood pres-
sure if needed.
Biochemical investigations
Together with each hemodynamic measurement arterial blood
samples were taken for blood gas analysis, and urine samples to
determine microalbuminuria. Urine albumin concentrations were
measured by immunoturbidimetry (Turbox, Orion Diagnostica,
Finland). To correct for intraindividual variation in the urine flow
rate microalbumin levels were quantified to the urine creatinine
concentration (analyzed by the Jaffe method), and expressed as the
ratio of microalbumin to creatinine (M:Cr). The assigned laborato-
ry reference range was less than 10 mg/mmol [16].
Blood samples (approximately 5 ml) for measuring serum C-
reactive protein (CRP) and procalcitonin (PCT) levels were taken
from an indwelling arterial cannula into serum separator tubes to-
gether with the first hemodynamic measurement and then daily
( t 1 – t 3 ). Samples were immediately spun; the serum was separated
and stored at − 70°C. CRP levels were determined by nephelomet-
ric assay (Orion Diagnostica; normal range <10 mg/l). Serum PCT
levels were measured by immunoluminometric assay (LUMItest,
Brahms Diagnostica, Berlin, Germany; normal range <0.5 ng/ml).
Full blood count, serum bilirubin, creatinine, and albumin levels
were determined by routine methods.
Statistical analysis
All data are presented as median (interquartile range). To test nor-
mal distribution the Kolgomorov-Smirnov test with the Lilliefors
modification was used. Changes in the investigated parameters
over the study period in the whole sample were statistically evalu-
ated by Wilcoxon rank sum test. T o investigate the relationship be-
tween the observed variables Spearman’s ρ test and linear regres-
sion analysis was performed. For statistical analysis the Statistical
Program for Social Sciences version 10.0 software for Windows
was used. Statistical significance was considered at p <0.05.
Results
MODS was determined daily showing multiple system
organ failure which did not change significantly during
the three days of observation (Table 2). Regarding hemo-
dynamic variables neither the CI, SVRI, nor required
catecholamine support changed significantly during the
study period (Table 3). Preload as monitored by ITBVI
remained in the normal range. EVLWI values were
significantly higher than normal throughout the study ,
without significant differences compared to baseline
(Table 3). Microalbuminuria was in the normal range on
entry and remained so for the rest of the study period
393
Ta b l e 2 Daily MODS, PCT, CRP , serum albumin, and edema
score. Data are presented as: median (interquartile range)
MODS (normal value: 0)
t 1 7 (4–8)*
t 2 7 (5–8)*
t 3 7 (4–8)*
PCT (normal value: <0.5 ng/ml)
t 1 4.86 (2.07–15.20) *
t 2 2.7 (1.32–14.80) *
t 3 3.66 (1.4–12.19) *
CRP (normal value: <10 mg/l)
t 1 168 (83.7–222.5) *
t 2 147 (104–265) *
t 3 165 (109.5–221.75) *
Albumin (normal value: 35–45 g/l)
t 1 16.05 (13.13–18.95) *
t 2 17.00 (12.90–18.95) *
t 3 15.60 (14.30–18.50) *
Edema score (normal value: 0=no edema)
t 1 3 (2–4)*
t 2 3 (3–4)*
t 2 3 (3–4)*
* p <0.05 vs. normal values (Wilcoxon rank sum test)
Ta b l e 3 Changes in hemodynamics, microalbuminuria, and cate-
cholamine requirement in septic shock patients ( n =25). Data are
presented as: median (interquartile range) ( CI cardiac index, SVRI
systemic vascular resistance index, ITBVI intrathoracic blood vol-
ume index, EVLWI extravascular lung water index, M:Cr microal-
bumin: creatinine ratio)
CI (l m − 2 ) SVRI ITBVI EVLWI M:Cr Dobutamine Noradrenaline
(dyne s cm − 5 )( m l m − 2 )( m l k g − 1 ) (mg mmol − 1 )( µ g kg − 1 min − 1 )( µ gm i n − 1 )
t 1 4.16 (3.64–4.65) 1213 (1028–1469) 919 (838–1198) 11 (8–15) * 3.37 (1.37–7.47) 5 (3–8) 8 (5–14)
t 2 4.00 (3.14–4.52) 1257 (1085–1536) 909 (860–1107) 11 (8–14) * 2.75 (2.05–8.88) 5 (3–9) 8 (6–12)
t 3 4.44 (4.02–4.72) 1330 (1043–1536) 950 (841–1120) 11 (8–14) * 5.60 (1.64–14.25) 4 (3–8) 7 (4–13)
t 4 4.21 (3.48–4.54) 1368 (995–1474) 864 (811–1052) 11 (7–15) * 3.70 (1.40–7.40) 5 (3–9) 8 (4–13)
t 5 4.40 (3.23–5.23) 1200 (1000–1438) 917 (865–1062) 10 (8–14) * 2.85 (2.03–8.60) 5 (4–8) 9 (5–15)
t 6 3.94 (3.09–4.63) 1245 (1052–1586) 921 (813–1106) 11 (9–15) * 2.82 (1.28–8.60) 4 (3–8) 9 (4–13)
t 7 4.17 (3.33–4.86) 1523 (1092–1864) 936 (872–1051) 12 (9–15) * 3.75 (1.65–7.58) 6 (4–9) 9 (5–14)
t 8 4.49 (3.56–5.00) 1197 (1043–1410) 901 (845–1070) 10 (8–14) * 3.49 (2.00–6.33) 6 (3–8) 8 (4–12)
t 9 4.64 (3.66–5.24) 1513 (1018–1848) 976 (917–1068) 10 (8–13) * 3.89 (1.57–16.05) 5 (4–9) 8 (5–14)
* p <0.05, vs. baseline (Wilcoxon rank sum test)
(Table 3). Serum PCT and CRP levels were significantly
higher than normal at every assessment points (Table 2).
Serum albumin levels were significantly lower than
normal throughout the study (Table 2). The edema score
showed a “pit” greater than 2–4 mm in all cases
(Table 2). No significant correlation was found between
the M:Cr ratio and EVL WI ( r = − 0.044, p =0.599), or be-
tween the M:Cr and PaO 2 /FIO 2 ratios ( r =0.285, p =0.078).
Discussion
Endothelial dysfunction cannot be measured directly in
the clinical setting. V arious methods have been proposed
to evaluate changes in vascular permeability, but many
of them have been abandoned because they were not ap-
plicable or sufficiently reliable [17]. In this study we in-
vestigated three parameters: microalbuminuria, EVL W ,
and peripheral edema, which may indirectly reflect sys-
temic capillary leakage in critically ill patients. However,
we found normal urinary M:Cr levels in septic shock de-
spite significantly elevated EVL W , and in the presence
of severe peripheral edema. Furthermore, microalbumin-
uria showed a significant correlation neither with EVLW
nor with the PaO 2 /FIO 2 ratio.
It has been suggested that the kidneys are uniquely
placed to mirror changes in capillary permeability as
they receive about 25% of the cardiac output, and small
changes in glomerular permeability lead to large changes
in microalbuminuria [5]. Indeed, increased renal albumin
excretion was found in several acute conditions. An ear-
ly report from Gosling et al. [9] found that the urinary
concentration of total proteins increased in proportion to
the magnitude of the surgical insult. Studies with similar
results including our recent report following esophagec-
tomy have confirmed their data [18, 19]. Several investi-
gations also support the presence of increased microal-
buminuria following trauma [8, 20]. Most authors em-
phasize that microalbuminuria measured within 6–48 h
after the initiating insult is of particular value [8, 9, 18,
19, 20, 21, 22]. In this study we did not observe in-
creased M:Cr. One could argue that this was due to the
low serum albumin levels. However, in our previous in-
vestigation in patients following esophageal tumor resec-
tion we observed elevated microalbuminuria immediate-
ly postoperatively, 23 mg/mmol (15–51), despite severe-
ly low serum albumin levels at 19 g/l (18–24) [18]. One
of the reasons that we found conflicting results could be
that the previous investigations took place after an acute
insult of trauma, surgery, or ICU admission. The patients
in the current study, however, had already been critically
ill on the ICU, as indicated by the high MODS, and the
presence of an ongoing acute inflammatory response was
also likely as indicated by high PCT and CRP levels. Se-
rum PCT and CRP usually reaches maximum response
to an inflammatory insult within 24 and 48 h respective-
ly, while microalbuminuria increases within hours [18].
As PCT and CRP values did not change significantly
over the study period, we suggest that the inflammatory
response had been ongoing for longer than 48 h before
patients even entered the study. Therefore microalbumin-
uria was unable to detect the acute insult.
Microalbuminuria may be an important predictor of
outcome and the development of organ failure. It shows
good correlation with the Injury Severity Score [20] and
with the Sequential Organ Failure Assessment score in
postoperative patients with sepsis [19]. A recent pilot
study found that increasing microalbuminuria has a good
sensitivity and specificity for predicting the development
of acute respiratory failure and multiple system organ
failure during the first 48 h in medical ICU patients [21].
W e have shown in a heterogeneous critical care popula-
tion that the M:Cr ratio measured 6 h after admission to
the ICU significantly differentiates survivors from non-
survivors [22]. One small study found a significant cor-
relation between the M:Cr and PaO 2 /FIO 2 ratios [, 8].
Our current results, in accord with those of De Gaudio et
al. [19], did not include a significant correlation between
microalbuminuria and the PaO 2 /FIO 2 ratio.
In most cases this relationship between microalb-
unimuria and illness severity and outcome is explained
by systemic capillary leak, which, if severe, can result in
multiple system or gan failure. Unfortunately, this state-
ment is lacking of clear evidence. Namely, little is
known about the correlation between microalbuminuria
and increased systemic vascular permeability in severe
sepsis or septic shock. There is some evidence that sup-
ports its role as a predictor in the development of postop-
erative sepsis and multiple system organ failure in medi-
cal ICU patients [19, 21]. However, it has never been in-
vestigated in the context of interstitial pulmonary and
subcutaneous peripheral edema in septic shock patients.
This is the first study, to our knowledge, challenging the
hypothesis that microalbuminuria is an indirect indicator
of systemic vascular permeability. One could argue that
our laboratory reference range was higher (<10mg/mmol)
than those used by others (<3 mg/mmol), and that we
therefore did find increased microalbuminuria (range of
medians: 2.75–5.60 mg/mmol). However, in our previ-
ous study in heterogeneous ICU patients the M:Cr with a
cutoff of 3 mg/mmol showed only 50% sensitivity and
85% specificity for mortality [22]. W e feel that higher
“normal” value is desirable in a general ICU setting, as
patients do have multiple medical problems, such as age
(>40 years), hypertension, smoking, and postoperative
condition, and each of these on its own could be respon-
sible for abnormal levels of microalbuminuria [5].
Regarding the problem of systemic capillary perme-
ability it would be very difficult to find an explanation
based on our results. There are several factors to look at.
First, permeability may differ with the organ. For exam-
ple, the so-called “capillary permeability surface area
394
product” for albumin is: 0.20 ml/100 g per minute for the
lungs, 0.10 for subcutaneous tissue, but only 0.01 for the
kidneys and 0 for the brain [23]. Therefore increased
systemic capillary permeability may have different mani-
festations in different organs in time as well as in magni-
tude. Therefore the question raised by De Gaudio et al.
[20], “Is an increase in glomerular permeability always
related to an increase in systemic vascular permeabili-
ty?” remains unanswered, although our data do support a
“not always” answer. On the other hand, none of the pre-
vious studies reported the serum albumin levels of the
patients, which was very low in the current study .
Whether hypoalbumanemia may also have influenced re-
nal albumin excretion requires further investigations,
preferably by using radiolabeled albumin.
To evaluate increased EVL W and peripheral edema in
the context of generalized capillary leak is beyond the
task of this study, as other factors than changes in endo-
thelial permeability could play an important role in their
development.
Conclusion
In this study patients in septic shock with significantly
elevated EVLW and peripheral edema score, with a uri-
nary M:Cr ratio less than 10 mg/mmol (our normal refer-
ence range), and there was no correlation between mi-
croalbuminuria and EWL V or PaO 2 /FIO 2 ratio. Therefore
based on the current results routine measurements of mi-
croalbuminuria to determine endothelial permeability
cannot be recommended in critically ill patients. Further
studies are required to have a better understanding of the
pathophysiology of systemic edema development in sep-
tic patients and to find the ideal method of monitoring
changes in vascular permeability.
395
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Futura, Armonk, pp 59–92
... Microalbuminuria may indirectly quantify changes in systemic vascular permeability
[26]
. ...
... It was supposed that the underlying mechanism was proposed to be the increase in systemic capillary leakage [41]. However, another study conducted on 25 septic patients showed that ACR did not correlate to extra vascular lung water and PaO2/FiO2 ratio, concluding that microalbuminuria does not reflect increased systemic capillary permeability in septic shock
[26]
. This was explained by the fact that in this study, the population had very low serum albumin that may influence urinary albumin excretion. ...
Prognostic Value of Urine Albumen/Creatinin Ratio in Sepsis in Critical Care Patients
... Microalbuminuria may indirectly quantify changes in systemic vascular permeability
[26]
. ...
... It was supposed that the underlying mechanism was proposed to be the increase in systemic capillary leakage [41]. However, another study conducted on 25 septic patients showed that ACR did not correlate to extra vascular lung water and PaO2/FiO2 ratio, concluding that microalbuminuria does not reflect increased systemic capillary permeability in septic shock
[26]
. This was explained by the fact that in this study, the population had very low serum albumin that may influence urinary albumin excretion. ...
Prognostic Value of Urine Albumen/Creatinin Ratio in Sepsis in Critical Care Patients
... Due to the pathophysiology of pneumonia, a considerable advantage of PiCCO is a possibility of determining volumetric parameters, such as the volume of extravascular lung water (EVLW) and pulmonary blood volume (PBV). In addition, the ratio of EVLW to PVB called the pulmonary vascular permeability index (PVPI) may be useful for the differentiation of pulmonary edema etiologyin ARDS, the cut-off value is 3
[5]
. Apart from physical examination, laboratory tests and invasive monitoring, physicians have a number of diagnostic imaging tools. ...
... For clinical practice, PiCCO is a source of invaluable hemodynamic and volumetric data such as stroke volume (SV) and cardiac output (CO), maximum left ventricular contractility (dPmax), systemic vascular resistance (SVR), global end-diastolic volume (GEDV), extravascular lung water (EVLW), or finally pulmonary vascular permeability index (PVPI). Extravascular lung water assessed using thermodilution is comparable to the lung weight measured posthumously and with the use of gravimetry; however, there is no correlation between EVLW and PaO2/FiO2 in patients with ALI/ARDS
[5,
13,14]. The large volume of extravascular lung water is closely associated with the increase in mortality (65-85%), while a strict control of fluid therapy and EVLW leads to a considerable reduction of mechanical ventilation time and patient's hospitalization [15][16][17]. ...
Comparing Transpulmonary Thermodilution Monitoring to Lung Ultrasound during Pneumonia: An Observational Study
Introduction: Monitoring of lung function during pneumonia is essential for the evaluation of the effectiveness of therapy in ICU patients. Among various bedside techniques, two particularly interesting are the lung ultrasound and the transpulmonary thermodilution technique. In this observational single center study we wanted to assess the correlation between the lung ultrasound examination (LUS) and transpulmonary thermodilution volumetric parameters such as extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI). Material and methods: We analyzed data obtained from medical history of twelve patients requiring mechanical ventilation and hemodynamics monitoring with PICCO catheter due to newly diagnosed pneumonia. We compared lung ultrasound examination performed on the first and third day of new antimicrobial therapy with results of transpulmonary thermodilution examination made on the same day. We also calculated the difference between values obtained on first and third day to compare the trends. Results: We did not find any association between tested variables, except a correlation between PVPI and EVLWI, both measured at the same day (Rho = 0.3; 95%CI -0.02-0.59; p = 0.03), and trends in the period of 3 days (Rho = 0.6; 95%CI 0.2-0.8; p = 0.005). Conclusions: The results of the study indicate that volumetric values achieved using the PiCCO method as well as lung ultrasound should be interpreted with care and related to the clinical state of a patient, keeping in mind that no correlation between the result achieved and the actual state of inflammatory changes in the lungs may be possible.
... Another study conducted on 25 patients with sepsis contradicted these results and showed that ACR did not correlate with extravascular lung water and PaO 2 / FiO 2 ratio, reaching to the conclusion that microalbuminuria does not reflect increased systemic capillary permeability in septic shock
[31]
, as they supposed that the pulmonary vascular permeability is not the only determinant of the extravascular lung water and that volume status, cardiac function, and severity of lung injury contribute to extravascular lung water. At the same time, the authors in that study criticized their conclusion by the very low serum albumin in their patient population that may influence urinary albumin excretion [31]. ...
... Another study conducted on 25 patients with sepsis contradicted these results and showed that ACR did not correlate with extravascular lung water and PaO 2 / FiO 2 ratio, reaching to the conclusion that microalbuminuria does not reflect increased systemic capillary permeability in septic shock [31], as they supposed that the pulmonary vascular permeability is not the only determinant of the extravascular lung water and that volume status, cardiac function, and severity of lung injury contribute to extravascular lung water. At the same time, the authors in that study criticized their conclusion by the very low serum albumin in their patient population that may influence urinary albumin excretion
[31]
. ...
Urine albumin/creatinine ratio as an early predictor of outcome in critically ill patients with sepsis
... Basu et al. also found an inverse relationship between the degree of change in microalbuminuria and the lowest PaO2/FiO2 ratio [29]. Another study conducted on 25 septic patients contradicted these results and showed that ACR did not correlate to extra vascular lung water and PaO2/FiO2 ratio, concluding that microalbuminuria does not reflect increased systemic capillary permeability in septic shock
[33]
. They considered that the pulmonary vascular permeability is not the only determinant of the extra vascular lung water. ...
... Volume status, cardiac function and severity of lung injury may also contribute to extra vascular lung water. The authors of that study criticized their conclusion by the very low serum albumin in their population that may influence urinary albumin excretion
[33]
. Out of the 40 patients of our study, 7 patients (17.5%) needed RRT and 33 patients (82.5%) didn't need RRT. ...
Urinary albumin/creatinine ratio as an early predictor of outcome in critically-ill septic patients
Several cumbersome scoring systems were developed for prognosis and outcome prediction in sepsis. We intended in this study to evaluate the urinary albumin/creatinine ratio (ACR) as a prognostic predictor in sepsis.
We included 40 adult septic patients in a prospective observational study. We excluded patients with preexisting chronic kidney disease or diabetes mellitus.
After clinical evaluation, urine spot samples were collected on admission and 24 h later for ACR1 and ACR2. Admission APACHE IV score and the highest recorded SOFA score of their daily estimation were considered. We also evaluated the need for mechanical ventilation, inotropic and/or vasoactive support, renal replacement therapy (RRT), and in-hospital mortality.
In a population with 63 (55–71) year old with 29 (72.5%) males, we found that the ACR2 is correlated with the SOFA score (r = 0.4, P = 0.03). SOFA was higher in patients with increasing ACR [14(4.8–16.8) vs 5(3–8), P = 0.01]. None of the ACR measures was correlated with APACHE IV score. ACR2 was higher in patients who needed mechanical ventilation and inotropic and/or vasoactive support [140(125–207) and 151(127–218) mg/g respectively] compared to [65(47–174) and 74(54–162) mg/g], P = 0.01 and 0.009. None of the measured parameters was related to the need of RRT. ACR1, ACR2, APACHE IV and increasing ACR were predictors of mortality. The AUC for mortality prediction was largest for APACHE IV (0.90) then ACR2 (0.88). ACR2 of 110.5 mg/g was 100% sensitive and 86% specific to predict mortality.
We concluded that the urinary ACR may be used as a simple test for prognosis and mortality prediction in sepsis.
... Microalbuminuria has been proposed as a prognostic marker in the ICU, for acute kidney injury in septic patients and in pediatric intensive care [4]
[5]
[6][7][8][9]. Critical illness is associated with endothelial dysfunction that results from a cytokine cascade following injury and /or infection. ...
Albuminuria in Critically Ill Patients: A Prospective Cohort Study
Purpose: To establish the behaviour of albuminuria over time and its relation to APACHE II score, SOFA score, infection parameters and outcome in critically ill patients.
Methods: In a prospective cohort study, we measured albumin creatinine ratio (MACR) for all consecutively admitted patients at the ICU. We recorded the following baseline variables: gender, age, admission diagnosis, type of admission (medical, surgical), length of stay, days of follow up. The cohort was divided into two pairs of subgroups medical and surgical; diabetes and non-diabetes. Patients were followed for ten days when possible.
Results: A hundred and fifty patients were included with a median age of 68.6 yrs. The patients had a mean APACHE II score of 20.5 and a mean SOFA score of 5.0. In all patients the ACR increases in the first five days. Median ACR on day 1 was 29.2mg/mmol; median ACR on day 5 was 45.5 mg/mmol. For all subgroups except for the diabetes patients the ACR decreased after day five. Spearman rho correlation showed a significant correlation between mean ACR per patient and age (r=0.19), APACHE II (r=0.48), mean SOFA score (r=0.41) and serum creatinine (r=0.25). Only in surgical patients a relation was found between ACR and CRP.
Serum creatinine is found to have a relation with ACR and is a confounder in the relation between ACR and the SOFA score. There was no significant difference found in mean microalbuminuria at the first day between survivors versus non-survivors.
Conclusions: ACR increases in the first five days in all critically ill patients. A relation between ACR and physiologic scores of severity of disease was established, except for diabetes and medical patients.
Pathophysiology of Acute Kidney Injury in Critical Illness: A Narrative Review
Acute kidney injury (AKI) is a syndrome that entails a rapid decline in kidney function with or without injury. The consequences of AKI among acutely ill patients are dire and lead to higher mortality, morbidity, and healthcare cost. To prevent AKI and its short and long-term repercussions, understanding its pathophysiology is essential. Depending on the baseline kidney histology and function reserves, the number of kidney insults, and the intensity of each insult, the clinical presentation of AKI may differ. While many factors are capable of inducing renal injury, they can be categorized into a few processes. The three primary processes reported in the literature are hemodynamic changes, inflammatory reactions, and nephrotoxicity. The majority of patients with AKI will suffer from more than one during their development and/or progression of AKI. Moreover, the development of one usually leads to the instigation of another. Thus, the interactions and progression between these mechanisms may determine the severity and duration of the AKI. Other factors such as organ crosstalk and how our concurrent therapies interact with these mechanisms complicate the pathophysiology of the progression of the AKI even further. In this narrative review article, we describe these three main pathophysiological processes that lead to the development and progression of AKI. © 2022 American Physiological Society. Compr Physiol 12: 1-14, 2022.
Acute kidney injury (AKI) is associated with subsequent chronic kidney disease (CKD), but the mechanism is unclear. To clarify this, we examined the association of AKI and new-onset or worsening proteinuria during the 12 months following hospitalization in a national retrospective cohort of United States Veterans hospitalized between 2004-2012. Patients with and without AKI were matched using baseline demographics, comorbidities, proteinuria, estimated glomerular filtration rate, blood pressure, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (ACEI/ARB) use, and inpatient exposures linked to AKI. The distribution of proteinuria over one year post-discharge in the matched cohort was compared using inverse probability sampling weights. Subgroup analyses were based on diabetes, pre-admission ACEI/ARB use, and AKI severity. Among the 90,614 matched AKI and non-AKI pairs, the median estimated glomerular filtration rate was 62 mL/min/1.73m(2). The prevalence of diabetes and hypertension were 48% and 78%, respectively. The odds of having one plus or greater dipstick proteinuria was significantly higher during each month of follow-up in patients with AKI than in patients without AKI (odds ratio range 1.20-1.39). Odds were higher in patients with Stage II or III AKI (odds ratios 1.32-1.81) than in Stage I AKI (odds ratios 1.18-1.32), using non-AKI as the reference group. Results were consistent regardless of diabetes status or baseline ACEI/ARB use. Thus, AKI is a risk factor for incident or worsening proteinuria, suggesting a possible mechanism linking AKI and future CKD. The type of proteinuria, physiology, and clinical significance warrant further study as a potentially modifiable risk factor in the pathway from AKI to CKD.
Sepsis causes multiple organs failures and eventually death. Changes in blood constituents due to sepsis lead to alterations in hemorheological properties, and cell adhesiveness. In this study, a new microfluidic system is proposed to measure temporal variations in biophysical properties of blood after injecting lipopolysaccharide (LPS) into a rat extracorporeal model under ex vivo condition. To measure blood viscosity, the interfacial line between blood and a reference fluid is formed in a Y-shaped channel. Based on the relation between interfacial width and pressure ratio, the temporal variation in blood viscosity is estimated. Optical images of blood flows are analyzed by decreasing flow rate for examination of red blood cell (RBC) aggregation. Platelets initiated by shear acceleration around the stenosis adhere to the post-stenosed region. By applying a correlation map that visualizes the decorrelation of the streaming blood flow, the area of adhered platelets can be quantitatively attained without labeling of platelets. To assess sepsis inflammation, conventional biomarkers (PCT and IL-8) are also monitored. The increasing tendency for blood viscosity, RBC aggregation, platelet adhesion, and septic biomarkers are observed after LPS injection. This microfluidic system would be beneficial for monitoring the changes in hemorheological properties and platelet activation caused by sepsis.
Microalbuminuria in intensive care unit
| https://www.researchgate.net/publication/10922779_Microalbuminuria_does_not_reflect_increased_systemic_capillary_permeability_in_septic_shock |
IJERPH | Free Full-Text | Ten Lessons for Good Practice for the INHERIT Triple Win: Health, Equity, and Environmental Sustainability
The world& rsquo;s challenges of climate change, damage to ecosystems, and social and health inequalities require changes in human behaviours at every level of organisation, among governments, business, communities, and individuals. An important question is how behaviour change can be enabled and supported at the scale and speed required. The research reported in this paper describes important lessons for good practice in changing contexts to modify behaviours for a triple win for health, equity and environmental sustainability. Authors synthesised learning from qualitative, quantitative and cost benefit evaluations of 15 case studies conducted in 12 countries in Europe. The case studies address ways of living (green spaces and energy efficient housing), moving (active transport) and consuming (healthy and sustainable diets) that support the triple win. Ten lessons for good practice were identified. These include bringing a triple win mindset to policy and practice in planning interventions, with potential to improve environmental sustainability, health and equity at the same time. The lessons for good practice are intended to support governmental and non-governmental actors, practitioners and researchers planning to work across sectors to achieve mutual benefits for health and environmental sustainability and in particular to benefit poorer and more socio-economically disadvantaged groups.
Ten Lessons for Good Practice for the INHERIT Triple Win: Health, Equity, and Environmental Sustainability
1
Institute of Health Equity, UCL, London WC1E 7HB, UK
2
EuroHealthNet, 1000 Brussels, Belgium
3
European Centre for Environment and Human Health, University of Exeter Medical School, Truro TR1 3HD, UK
4
National Institute for Public Health and the Environment (RIVM), Centre for Sustainability, Environment and Health, 3720 BA Bilthoven, The Netherlands
5
Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, 7030 Trondheim, Norway
6
Department of Public Health and Nursing, NTNU Center for Health Promotion Research, Norwegian University of Science and Technology, 7030 Trondheim, Norway
7
Basque Centre for Climate Change, Biscaya, 48004 Pais Vasco, Spain
8
Department of Economics, Universidad de Alcalá, 28801 Alcalá, Spain
9
Health Economics Group, University of Exeter Medical School, Exeter EX1 2LU, UK
10
Environment Centre (CUNI), Charles University, 162 00 Prague, Czech Republic
11
Instituto Universitário de Lisboa (ISCTE-IUL), CIS-IUL, 1649-026 Lisboa, Portugal
12
Philips Research, Brain, Behavior and Cognition Group, 5656 AE Eindhoven, The Netherlands
13
Human-Technology Interaction Group, Eindhoven University of Technology (TUe), 5612 AE Eindhoven, The Netherlands
14
Prolepsis Institute, 151 25 Athens, Greece
15
Collaborating Centre on Sustainable Consumption and Production, 42107 Wuppertal, Germany
16
Public Health Agency of Sweden, Solna, 171 82, Sweden
17
Federal Centre for Health Education, (BZgA) Cologne, 50825 Cologne, Germany
18
Department of Marketing, Innovation and Organisation, University of Ghent, 9000 Ghent, Belgium
19
The Institute of Public Health of the Republic of North Macedonia (IJZRM), 1000 Skopje, North Macedonia
20
Riga City Council, 1010 Riga, Latvia
Int. J. Environ. Res. Public Health 2019 , 16 (22), 4546; https://doi.org/10.3390/ijerph16224546
Received: 16 October 2019 / Revised: 7 November 2019 / Accepted: 14 November 2019 / Published: 17 November 2019
(This article belongs to the Special Issue A More Sustainable and Healthier Future for All: What Works? )
Abstract
:
The world’s challenges of climate change, damage to ecosystems, and social and health inequalities require changes in human behaviours at every level of organisation, among governments, business, communities, and individuals. An important question is how behaviour change can be enabled and supported at the scale and speed required. The research reported in this paper describes important lessons for good practice in changing contexts to modify behaviours for a triple win for health, equity and environmental sustainability. Authors synthesised learning from qualitative, quantitative and cost benefit evaluations of 15 case studies conducted in 12 countries in Europe. The case studies address ways of living (green spaces and energy efficient housing), moving (active transport) and consuming (healthy and sustainable diets) that support the triple win. Ten lessons for good practice were identified. These include bringing a triple win mindset to policy and practice in planning interventions, with potential to improve environmental sustainability, health and equity at the same time. The lessons for good practice are intended to support governmental and non-governmental actors, practitioners and researchers planning to work across sectors to achieve mutual benefits for health and environmental sustainability and in particular to benefit poorer and more socio-economically disadvantaged groups.
Keywords:
policy and practice
;
health
;
equity
;
environmental sustainability
;
behaviour change
;
urban settings
;
co-creation
;
living
;
moving
;
consuming
1. Introduction
Climate change and environmental degradation pose unprecedented threats to human health and wellbeing. All too often, poorer communities suffer the most from the widespread consequences of these problems, and benefit the least from measures taken to address them.
The challenges of climate change, damage to ecosystems, and social and health inequalities require changes in human behaviours at every level of organisation, among governments, business, communities, and individuals [ 1 ]. An important question is how behaviour change can be enabled and supported at the scale and speed required.
Aligning with the imperatives for action to address these challenges, the EU HORIZON 2020 INHERIT project (2016–2019) focused on identifying policies and practices that contribute to a triple win, in terms of improvements to health, equity and environmental sustainability, by creating conditions that enable people to adopt more sustainable behaviours in ways of living, moving and consuming [ 2 ].
Within the INHERIT project, we evaluated 15 case studies based on intersectoral interventions with potential to deliver the triple win. Based on these evaluations, this paper synthesises lessons learned about how to create an effective intervention that can create the conditions to enable behaviour change to promote a triple win, with the aim of informing governmental and non-governmental actors, practitioners, and researchers that are interested in designing such interventions.
The 15 case studies were developed based on different interventions which might deliver ‘triple win’ solutions by enabling behaviour change in the domains of living (with a focus on green space and energy efficient housing), moving (with a focus on active transport, specifically cycling and walking) and consuming (with a focus on consumption of a healthy and sustainable diet). These interventions provide examples of measures that can be implemented to contribute to achieving the triple win. Many of these promising practices represent efforts made by, inter alia, citizens, schools, community-based organisations, non-governmental organisations, small enterprises and municipalities.
Learning from the INHERIT cases studies is useful and relevant not only to the scaling up of actions, where feasible, but also to transferring promising actions to new contexts and introducing further innovative approaches towards a healthier, more equitable and sustainable future for Europe. Indeed, an individual action multiplied across society, stimulated by many small initiatives as well as national policy tools, can shift social norms. Behavioural changes at a social scale in the way we live, move and consume are needed if societies are to become healthier, more equitable and live in a more sustainable way.
2. Materials and Methods
The lessons for good practice were developed using an iterative methodology, based on learning from the implementation [ 3 ] and evaluations of INHERIT’s 15 case studies [ 4 , 5 , 6 ]. Table 1 shows 15 INHERIT case studies.
This section describes how the 15 case studies were selected, how they were evaluated, with reference to the theoretical framework provided by the INHERIT model, and how the INHERIT partners identified the ten lessons for good practice.
2.1. Selection of INHERIT’s 15 Case Studies
We first carried out a literature review [
7
], and developed a conceptual model to guide the INHERIT project’s analytical approach. Next we collected information about 96 initiatives (promising practices) around Europe to create a database of promising practices [
8
]. Each INHERIT partner proposed several promising practices based on a set of criteria, including that the practices are inter-sector policies and interventions, that they address key environmental stressors, and foster the conditions that support healthy and environmentally sustainable lifestyles and behaviours, although specific evaluations may be lacking. In addition, the promising practices should be in INHERIT’s domains of interest, living (green space and energy efficient housing), moving (active transport), and consuming (healthy and sustainable food).
From the database of promising practices, INHERIT partners identified 15 case studies to be selected as INHERIT studies that would undergo qualitative, quantitative and/or cost benefit evaluations.
Table 1
provides a summary of INHERIT’s 15 case studies. The 15 INHERIT case studies were selected based on a set of criteria developed by the INHERIT partners [
3
]. These criteria are summarized here: (i) the chosen INHERIT case studies could be implemented in the INHERIT project’s timeframe and budget; (ii) the case studies should be knowledge based, have an underlying theory of change that could be linked to the INHERIT model, and be amenable to scientifically sound evaluations; (iii) the case studies should target or have an impact on people facing socioeconomic disadvantages, and can potentially contribute to a triple win; (iv) the case studies should involve cooperation across sectors, and involve user groups; (v) the case studies should be geographically spread around Europe, and thematically spread across the areas of living, moving and consuming.
The 15 case studies were of different types and implemented at different scales. Some were relatively small scale initiatives implemented by INHERIT partners, for example, Place Standard piloted the Place Standard tool in new contexts (Latvia and North Macedonia). Others studied large-scale interventions that were already being implemented, for example, STOEMP is part of Ghent en Garde, a city wide policy promoting health and sustainable food, and Sustainable food in public nursery schools, which is city policy in Madrid. One case study combined elements of two promising practices (Gardening with Green Gym and Meat Free Monday) to create an innovative school based intervention. Details about the different types of case studies are reported elsewhere [
3
].
2.2. Evaluation of INHERIT’s 15 Case Studies
In order to evaluate the diverse case studies in a coherent way, INHERIT partners developed a generic INHERIT logic model (
Figure 1
), to integrate with the INHERIT model [
9
]. The logic model represents the theory of how an intervention produces its outcomes. INHERIT partners used the generic INHERIT logic model to develop specific logic models for each of the case studies. The logic models were used as planning tools, which enabled partners to identify key aspects of the intervention in preparation for the case study. These included: the kinds of inputs and resources required to enable the intervention functions (staff, money, evidence base, equipment, technology, partners); expected outputs and activities (including multiple strategies, intersectoral cooperation, stakeholder engagement, citizen participation, behavioural change of policy-makers); and outcomes. The generic logic model describes outcomes and proposed indicators to be assessed in four temporal divisions: (1) Short-term outcomes: behavioural determinants in the domains of capability (e.g., building knowledge and awareness), motivation (intention to do something), opportunity (changes to the environment that enable people to change behaviours). (2) Intermediate-term outcomes: changes in behaviours, health and wellbeing, environmental change, and behaviours of decision-/policy-makers and influencers. (3) Long-term or end outcomes: impacts on health and wellbeing, quality of life, material conditions, social conditions, environment and inequalities. (4) Distal effects: impacts on population health and wellbeing, environmental sustainability and health inequity.
Qualitative evaluations of intersectoral cooperation were carried out on 12 of the 15 case studies to investigate success factors, barriers, and the future of intersectoral cooperation in each case. For each of the 12 case studies, partners conducted one focus group, comprising partners cooperating in developing and implementing the case studies. The methodology used in the qualitative evaluation was informed by Appreciative Inquiry, an asset based approach based on questions such as what works well, and how to do more of what works well in the future [ 4 ].
Quantitative evaluations of nine out of the 15 INHERIT case studies were conducted to investigate their impacts on the targeted populations [
5
]. These evaluations were based upon the INHERIT model [
9
], which integrates theory about the environmental determinants of health and health inequalities with behaviour change theory [
10
]. Quantitative methods included two randomised control studies (using pre-post design and questionnaire survey), several quasi-experimental studies, cross-sectional questionnaire surveys related to the case studies, a questionnaire survey representative for five European countries [
11
] and observations of use and activity level. Quantitative methods were complemented by qualitative studies with target groups in some case studies.
Given the complexities involved in measuring health outcomes, particularly given the short amount of time to implement/evaluate the INHERIT interventions, we did not expect to see measurable changes in health outcomes. Therefore, the focus of the evaluations was on short term and intermediate outcomes. Quantitative evaluations in some case studies examined how interventions might influence people’s capabilities, opportunities and motivation to change their behaviours. Most evaluations assessed health related behaviours (e.g. physical activity or aspects of healthy eating depending on the nature of the intervention). Some cases studies assessed well-being or life satisfaction. INHERIT partners developed an evaluation framework, which identified from the literature validated and reliable tools to assess physical activity, dietary behaviours, and well being, as well as demographic and socioeconomic indicators [
5
]. Partners used these tools where relevant to their case studies, or identified others by searching the literature.
Cost benefit analyses (CBA) were conducted on four case studies [
6
]. The CBA quantified in monetary terms social costs and benefits of these interventions, in order to find out their social desirability, following economic efficiency criteria. Short-term and future medium-term impacts were accounted for, using appropriate ranges of discount rates to derive present value equivalents. A participatory methodology was used in the case of Thinking Fadura, using citizens’ surveys and stakeholders’ workshops to identify which items should be evaluated as societal impacts, as well as which further intangible (not monetized) impacts should be taken into account.
2.3. Synthesis of Learning from INHERIT’s Case Studies
INHERIT partners identified and synthesized lessons learned from the implementation and evaluations of the case studies using an iterative and deliberative methodology. To facilitate discussions about what the main elements of good practice are, we grouped the INHERIT case studies by the following themes:
Community-based initiatives around food. Case studies: De Voedseltuin, PROVE, STOEMP.
School-based initiatives. Case studies: GemüseAckerdemie, Gardening with Green Gym and Meat Free Monday, Sustainable Food in Public Schools.
Open/green space initiatives. Case studies: Malvik Path, Restructuring Green Spaces, Restructuring Residential Outdoor Areas, Thinking Fadura.
Energy efficiency in homes. Case studies: Eco Inclusion, Retrospective Analysis of Energy Efficient Investments.
E-coaching applications around moving. Case studies: UrbanCyclers (active transport) and Lifestyle-coaching (physical activity).
Participatory governance approaches towards the triple win. Case study: Place Standard.
Short summaries of all the case studies were prepared that described the target groups, what inspired the creation of the initiative, success factors, outcomes and impact, and ideas for future development. Then we conducted an expert workshop in Brussels, to review the compiled evidence and draw conclusions about what can be considered as overarching lessons for good practice. This workshop brought together 10 experts from a wide range of backgrounds (including public health, environmental research, social psychology, environment and health economics, policy and epidemiology) from across the INHERIT consortium. Before the workshop, each participant read the selected reports. During the workshop, all participants familiarised themselves with at least two of the case studies. Participants were assigned into two groups. One group discussed findings from the implementation report on the 15 INHERIT case studies [
3
] and the qualitative evaluations [
4
] that focused on intersectoral cooperation in implementing the case studies. The second group deliberated on implications of the findings from the impact evaluations [
5
] and the cost benefit analyses [
6
], both of which included qualitative and quantitative methodologies. The findings from the two group discussions were then fed back into plenary discussions for further deliberation. Subsequently, the lead author (R.B.) prepared a draft report detailing the identified lessons for good practice, based on deliberations during the expert workshop on the evidence from the implementation and evaluations of the case studies. The draft report was circulated to a wider group of INHERIT researchers (including all co-authors) for review and feedback. The 10 lessons for good practice were validated by the INHERIT project steering group at an INHERIT consortium meeting, with minor amendments.
3. Findings
Here we describe the overarching lessons for good practice ( Figure 2 ), identified from evaluations of INHERIT’s 15 case studies, all of which have potential to modify behaviours of policymakers, the private sector and citizens by changing the contexts in which people live, move and consume.
3.1. A Triple Win Mindset for Innovation
We identified a triple win mindset as crucial in taking an approach that breaks down traditional sectoral silos and enables innovation in intersectoral cooperation. A triple win mindset means setting out with the intention of creating synergies across sectors to create a triple win for health, equity and environmental sustainability.
All INHERIT case studies are considered to be triple win initiatives. Yet the potential for a triple win was not explicit in the original objectives of all interventions. Often, it was their engagement in INHERIT that made them recognise their potential to have multiple societal benefits. Taking as an example that might traditionally be thought of as a health intervention, the activity tracker and associated smart phone application used in the Lifestyle e-coaching case study can exist as a stand-alone system to support individuals in tracking their activity levels. Yet bringing a triple win mindset to this case study opens out wider questions such as: is the technology effective among all social groups and those with low activity level (the basis of the INHERIT research on this case study), and, if so, how can the technology be made more widely available? Taking the environment into account leads to further questions, for example: are there usable parks and safe areas for people to be more active near their homes? Such questions contribute to systems thinking that is fundamental to create conditions that enable behavioural change for the triple win.
As another example, the Place Standard Tool was designed to guide discussions about what needs to be targeted to improve a place [ 12 ], but applying it with a triple win mindset in North Macedonia identified different key indicators (air quality, waste, water quality) for possible inclusion. This would further develop the Place Standard Tool as a tool to guide thinking and planning for a triple win for health, equity and environmental sustainability.
Triple win thinking, and the awareness of those engaged that they are contributing to the health and well-being of community members as well as to broader ambitions related to the urgent climate crisis, can strengthen the commitment and motivation for action of those involved.
Bringing a triple win mindset to the table demands creative thinking and discussions to plan the necessary steps that can bring different sectors together to make a triple win happen. Yet, as evidenced in several INHERIT case studies, impacts of interventions may not always be unambiguously positive, and there may be trade-offs as well as synergies across sectors. For example, as noted in the case of Sustainable Food in Public Nursery Schools, organic food production in the area local to Madrid is not at the scale needed to supply Madrid’s public nursery schools, therefore a trade-off needs to be made between providing organic food and the environmental cost of transport.
In the case of Energy Efficient Investments, while the environmental benefits are likely to be positive due to energy and carbon savings, the targeting of lower socioeconomic groups and those in social housing for energy efficiency investments may exacerbate health inequalities, unless the measures put in place are appropriately designed to avoid the sealing of properties and the negative health impacts associated with this [
6
,
7
,
13
,
14
]. Identification of trade-offs and adverse consequences, as well as potential positive impacts, gives extra weight to the imperative for applying a triple win mindset to a broad range of initiatives such as those investigated in the INHERIT project.
3.2. Ensure (inter)National/Regional/Local Strategies are in Place that can Spark Action
The presence of (inter)national/regional/local strategies for improving health inequalities, and environmental sustainability creates a supportive environment for local action. The UN Sustainable Development Goals [
15
] are a useful framework to work within because they set out an internationally agreed direction for development that requires action across different sectors towards multiple goals, including health, equity and environmental sustainability goals. In this context, European, national, and local strategies can provide enabling and supportive environments in which the kinds of initiatives that are needed to achieve these goals can flourish. For example, the STOEMP network is part of Ghent en Garde, the municipality’s response to the Milan Urban Food Policy Pact (MUFP) [
16
] which aims to develop sustainable food systems and healthy diets for citizens [
17
].
However, governments can do more to provide a facilitating policy environment in which small scale initiatives can thrive. Individuals and organisations have a role in advocating for the kinds of international, regional, national and local strategies that stimulate or regulate actions needed for a triple win. In turn, governments at all levels can facilitate the broad stakeholder engagement necessary to develop policies and strategies to deliver the triple win through local initiatives.
In this context, impacts of school-based initiatives such as Gardening with Green Gyms and Meat free Monday in the UK would be boosted if outdoor learning were to be institutionalized by integrating it within the mandatory national curriculum. Furthermore, national public procurement regulations could be used to support healthier and more sustainable food in schools. This would support the shift to more sustainable farming practices, and consumption of less meat and more plant-based food, which has been called for by the International Panel on Climate Change.
3.3. Anchor Initiative to International/National/Local Priorities
Anchoring initiatives to international, national and local priorities can help embed local level initiatives in a whole systems approach that is necessary to address complex challenges. This point is linked to ‘Ensure (inter)national/regional/local strategies are in place that can spark action’ (
Section 3.2
above). We include both because one enables the other. So while these two lessons are linked, they are separate. Individuals and communities wishing to develop local level action for a triple win can generate greater momentum by linking the initiative to higher level priorities of improving health, reducing inequalities and promoting environmental sustainability. This depends on the existence of (inter)national/regional/local policies and strategies that enable triple win initiatives. International, national and local priorities help support powerful arguments that can bring together diverse sectors around common interests. For example, an idea for a new initiative, such as a food garden in a disadvantaged area in Ghent, can gain traction by arguing that it contributes to the aims of STOEMP in reaching disadvantaged groups, the overall Ghent en Garde objectives, and the MUFP for healthier and more sustainable food. As another example, in the context of England, where the prevalence of child obesity (ages 10/11) was 20% in 2017/18 [
18
], the National Childhood Obesity Strategy recognises that schools have a fundamental part to play in supporting healthy lifestyles for children [
19
]; this provided an anchor for the Gardening with Green Gym and Meat free Monday pilot initiative. Nevertheless, enabling this practice to be maintained and potentially scaled up nationally would require integration of outdoor learning in the national curriculum, as was raised above (
Section 3.2
).
3.4. Bring Together Different Sectors around Common Interests
Bringing together different sectors around common interests is a further key element in creating triple win initiatives. This is demonstrated by INHERIT’s case studies in the context of developing green and open spaces, and in sustainable food initiatives, such as STOEMP and Sustainable Food in Nursery Public Schools. An effective approach in developing interventions requires both horizontal collaboration, between groups with more or less equal power, as well as vertical linkages between those with differing levels of power (which can include anchoring in higher level priorities).
The importance of multisectoral action and intersectoral cooperation to achieve common goals is widely accepted but may be difficult to do in practice. Common interest regarding local challenges was a pronounced theme in INHERIT initiatives and is related to personal commitment. One of the success factors was a common goal shared among people from different sectors.
While common interest can bring people together, lack of coordination can affect the success of the intervention. Bringing people together at an early stage to identify areas of common interest and to develop common goals is a crucial part of the process. However, it can take time to build up the necessary rapport and trust between stakeholders to facilitate cooperation; trust must be nurtured as a valuable resource.
In the INHERIT team’s experience, the process of using the INHERIT model [
9
] as a tool in stakeholder workshops has proved highly influential in opening up discussions among stakeholders about the opportunities for multiple benefits of initiatives of various kinds. The INHERIT model combines environmental impact assessment with health impact assessment and equity impact assessment in a way that enables people and stakeholders from multiple sectors to identify potential impacts and risks for any particular initiative. The use of an adapted form [
20
] of the INHERIT model to inform the participatory methodology and, through this, to derive a set of potential positive and negative impacts for cost benefit analysis in the Thinking Fadura initiative provides a good example of how this way of thinking can contribute to cooperation across sectors. It is crucial that this step is carried out before going on to think about how potential impacts and risks can be quantified or evaluated.
The INHERIT model as a tool for health, environment and equity impact assessment provides a way of identifying potential positive as well as adverse impacts, and therefore diverges from standard regulatory environmental impact assessments used, for example, in infrastructure development projects, and designed to identify environmental risks to health.
3.5. Engage People and Communities of Interest for Co-creation
Engaging people and communities with the mindset of co-creation should be a central theme in triple win initiatives. This is important because people need to be involved in the decisions that affect their lives and living environment. Being involved in decisions that affect one’s life is fundamental to participatory governance models at the local level that aim to ensure social inclusion. In addition, the opportunity to be involved in decisions that affect one’s life is a core element of empowerment. This has been positioned by the WHO Commission on Social Determinants of Health as being key to enabling people to live healthy and flourishing lives [
21
]. In addition, being involved in decision-making gives people a vested interest in the success of the initiatives and encourages active participation in a way that creates a positive feedback loop. We see that in INHERIT initiatives such as Restructuring Green Space and Malvik Path, where involving people in a meaningful way in planning and developing processes creates places that local people actually use in ways that improve their lives and creates more engaged residents who want to protect and enhance the places they use.
We also see that it is not always easy to engage people. INHERIT has developed some fundamental requirements in this respect, and proposes possible solutions. It is important to engage the community from the inception of an intervention and engagement should be continued throughout the process. Co-creation is also important for securing a sense of ownership among participants, but that will only happen when the participation is meaningful and not tokenistic. The level of success of co-creation depends on addressing the actual needs of residents and the extent to which communities are engaged in processes of design and implementation. How much the community participates also depends on creating rapport and trust [
22
]. It takes a long time to build trust and a very short time to lose it.
Every kind of community engagement requires some kind of commitment from those involved. The extent of commitment varies along a sliding scale, from attending meetings to share opinions to volunteering labour, as, for example, in De Voedseltuin (Food Garden). It is important, then, that those wishing to engage residents provide a good rationale for people to be engaged. Incentives can vary from providing refreshments and a welcoming environment at meetings to providing more official recognition of roles. Local campaigns, news coverage, and events (as in Malvik Path) that help create an identity can raise the profile of initiatives and give recognition to engaged communities. Furthermore, such campaigns may provide sources of information that inform people about what is happening and how they can become involved and give them confidence to join new initiatives. In some cases, there may be a need to develop participatory skills in the communities, for instance through educational programmes.
Several INHERIT case studies have worked with volunteers based on the notion that volunteers are crucial for maintaining the project longer term. However, recruiting volunteers can be challenging. Some practices found it difficult to recruit volunteers, as in the case of the GemüseAckerdemie where volunteers were needed in the daytime during the week. Furthermore, recruitment of volunteers from across the social spectrum can be difficult where the benefits of volunteering are not explicit. It is important to avoid the act of volunteering being a luxury, affordable only by the more advantaged in society. Some initiatives are intrinsically beneficial for volunteers, for example De Voedseltuin where volunteers receive training and produce from the food garden, and for others, there are benefits of volunteering that might not be apparent or visible in the short term, such as self esteem and enhanced wellbeing [
23
], and health/environmental literacy. However, the association between volunteering and wellbeing may not always be causal [
24
].
Supporting volunteers includes developing infrastructure that facilitates capacity-building through knowledge exchanges. For example, training can be video recorded and widely distributed, online courses can be developed, and existing teaching programmes for volunteers can be replicated. Volunteers are sometimes involved in peer delivered interventions in public health [
25
], and in other kinds of peer training too, such as the operating model of Eco Inclusion. Further scaling-up or transferring of the peer training model to other areas should be informed by existing peer training models developed in the area of public health [
26
]. Experiences from INHERIT show that training that helps volunteers develop transferable life skills is beneficial [
7
]. For example, De Voedseltuin offers workshops to volunteers that also help them reintegrate into the job market.
3.6. Ensure Initiatives are Inclusive
Initiatives should be inclusive so that everyone can potentially benefit. This aligns with the concept of ‘proportional universalism’ used in discussing how to combat social inequalities in health; it means actions or initiatives should benefit everyone across the social scale and be deployed at a scale and intensity proportionate to the level of disadvantage [ 27 ].
Therefore, to gain the greatest benefits, interventions for the INHERIT triple win may need to take into account the specific needs of groups facing different disadvantages (e.g. older people, refugees), which are not homogeneous in themselves, so differentiated action may be needed. For example, it is important to pay attention to age, gender and cultural diversity and sensitivity when implementing and evaluating interventions. This was demonstrated to good effect in the Restructuring Green Space case study in which an underused green space was restructured, using inclusive participatory methods, into an attractive green space widely used by all members of a diverse community.
INHERIT case studies showed that interventions that have a positive impact on health and the environment which take a settings approach, such as schools and green spaces, are effective ways of also addressing health equity. More targeted approaches that focus on specific groups facing disadvantages may also be needed, as reflected in the STOEMP case study, and Eco Inclusion. In such cases, it is crucial not to stereotype or stigmatise people, as this can place an additional burden on people suffering from relative deprivation.
3.7. Secure Funding over the Longer Term
Secure funding over the longer term was identified as necessary, and challenging. Of course, no initiative can operate in the absence of funding, from inception through to maintenance and sustainability. In this regard, government funding for local initiatives is vital, and should be built in to national and local government strategies linked with achieving the SDGs, climate change mitigation and adaptation, population health, social inclusion, and environmental sustainability.
That being said, local initiatives that gain funding from national or local government schemes are at risk in the event that other funding priorities emerge. Alternative funding sources should be explored. One solution for financial sustainability of community-based initiatives might be, therefore, to have a hybrid business model, with diverse funding partners, including public, private and collective sources. Another funding solution is to merge the funding for environmental and social initiatives, recognising that there are mutual environmental and social benefits.
In addition to funding, there is a need for adaptation of legislation or policy frameworks in such a way that it facilitates local intersectoral initiatives and co-creation processes. In the case of Restructuring Residential Outdoor Areas, the property owner received 50% of the restructuring costs from a fund set up by the Swedish government to support upgrades of outdoor areas in socially deprived residential areas in a way that involved multiple stakeholders, including residents.
Cost benefit analyses can support decisions regarding investing in initiatives. However, while these analyses are useful, they should not be the only basis for decision-making, bearing in mind that not all potential benefits and risks can be quantified, and that some perceived impacts might not be beneficial across the social spectrum, or distributed evenly across various population segments [
7
]. As demonstrated in the case of Thinking Fadura, cost benefit analyses can provide an intersectoral engagement process to help identify potential positive impacts as well as adverse consequences of initiatives, which can be valuable inputs to planning and development.
3.8. Integrate Ways of Evaluating Initiatives
Evaluation of initiatives is all too often seen as an optional extra, or something that is done as an academic exercise. INHERIT’s experience is that evaluation of initiatives not only helps to understand the processes of implementation, intersectoral cooperation, impacts and benefits, but also to learn about what could be done better to build synergies across sectors and to enhance outcomes. Evaluations are both summative and formative.
Evaluation of projects and programmes in real world settings is challenging and time-consuming. The evaluation methodology can be improved in a scenario with more time and resources. For example, in PROVE a combination of longitudinal quantitative and qualitative data collections, following consumers after baseline measurements, would allow better understanding of how PROVE influences behaviour, critical moments for change, or even the interplay of different determinants at the different stages of behaviour change.
Researchers also need to take into account the demands made by the research on stakeholders and survey respondents. It is important to take time to engage stakeholders, and to explain the purpose and potential benefits of the research to participants invited to respond to surveys.
Despite the inherent challenges of real world evaluations, they are highly valuable to project and programme managers, not least because they bring out important issues for reflection that can influence further developments and improvements. To enable this to happen, it is important that researchers report results of evaluations to project partners and stakeholders. Indeed, PROVE partners and implementers have already developed an idea to extend the PROVE initiative to schools, which may help to promote consumption of fruit and vegetables across a wider range of social groups.
Long-term evaluation plans should be in place with plans for maintenance and sustainability of each initiative. Interventions that might be successful in the short term might not work out longer term; again, short-term evaluation might not yield measurable outcomes. INHERIT’s quantitative evaluations [
5
] were, by necessity, given the funding period of the project, based on short-term evaluations, but our experience suggests that it is important to conduct long-term evaluation. The duration of the evaluation will need to vary from case to case, depending on the particular health outcomes being addressed, and to reflect the extent to which the impacts of any intervention may change over time.
3.9. Create Postive Feedback Loops to Regenerate Action
INHERIT case-studies can create positive feedback loops that can regenerate action or stimulate further action. A case in point is UrbanCyclers which supports more commuter cycling on the roads. More urban cycling creates incentives for cities to improve cycling infrastructure, which encourages more commuter cycling, creating a positive feedback loop. Similarly, having an activity tracker, as in the case of Lifestyle e-coaching, and being motivated to walk more, might encourage people to seek out green space and tree-lined roads. Building a need among people for more green space and more pleasant environments for cycling and walking should be an incentive for municipalities to give higher priority to restructuring areas to create more usable green spaces. Again, as discussed above, engaging people and communities in planning and development of settings-based interventions, as in Malvik Path and Restructuring Green Space, as well as more broadly in applying the Place Standard Tool, can reinforce the value of participating in community development processes and create a sense of ownership. It is important, however, to demonstrate to people and communities that their engagement is worthwhile and results in tangible changes to settings that improves lives.
3.10. Embed the Triple Win from an Early Age
Giving children the best start in life has been identified as crucial for improving health and reducing health inequalities across the life course [ 27 ]. Healthy behaviour at a young age will provide health benefits later in life [ 7 ]. For example, a relationship between active travel behaviour during childhood and walking during adulthood has been observed [ 28 ], suggesting that policies to encourage active transport among children could result in benefits not only during childhood but also throughout the life cycle of the individual.
Several INHERIT case studies demonstrate how it is possible to embed the triple win at an early age by working with children in school-based or community based settings. Involving children and young people in such initiatives is important in creating positive feedback loops across generations as a way of embedding environmental sustainability, intergenerational equity and future population health. Experiences in early life lay the foundation for future attitudes to eating a healthy diet and being physically active, for respecting and protecting the natural environment and for cooperative social behaviour [
7
]. Additional societal benefits accrue because children influence their parents’ and peers’ attitudes and behaviours. Therefore, initiatives that involve children and young people in school and community settings can have long term benefits towards the triple win.
The involvement of parents in a school based programme is also perceived as being important by teachers [ 29 ]. In the case of Gardening with Green Gyms and Meat free Monday, there are several ways to involve parents, such as sending newsletters, providing homework tasks for parents and children and involving them in the maintenance of gardening during holidays [ 30 ]. There is evidence that linking with the wider community is a success factor for school-based interventions [ 31 ] and local organisations can take care of the school garden out of school hours [ 29 ]
Links between school and community can go both ways. Discussion among stakeholders can provide opportunities to achieve an extra win if they consider children and young people. For example, in discussions about PROVE, partners and stakeholders discussed the possibility of piloting a subscription to PROVE in a school, which would simultaneously widen the market reach of PROVE farmers, increase availability of fresh local fruit and vegetables to children in a school setting, and make the initiative more socially inclusive.
4. Discussion
This paper has identified lessons for good practice to support actions intended to change the contexts and conditions in which people live, move and consume in order to enable behaviour changes in ways that contribute to a triple win for health, equity and environmental sustainability. Despite extensive studies in the areas of living, consuming, and moving separately [ 7 ], to our knowledge, these aspects have not been investigated together before under an overarching common analytical framework.
The key lessons derived from INHERIT case studies distil essential elements from heterogeneous practices undertaken in different countries across Europe, at different levels, involving different actors, and using different interventions. This diversity should ensure that these key lessons capture the most relevant elements that were identified either over multiple contexts, actors, policy levels, INHERIT domains or by using different evaluation methods.
All INHERIT case studies enable behaviours that have the potential to improve health, equity and environmental sustainability. It is worth emphasising that in evaluating complex programmes in real life settings it is necessary to gather information from different sources with both quantitative and qualitative methodologies. At the same time, it is necessary to understand the limitations imposed by complexity on the level of certainty that can be achieved in undertaking evaluations of real-world activities.
Several limitations have been identified that might impact the findings used to synthesise the lessons for good practice. The selection of case studies was affected by the project timeframe and the available budget for their evaluation. The case studies were at different scales, in different contexts, and involved a range of methodological approaches. Some case studies were evaluated in more detail than others. In some cases, the limited duration of the intervention meant that results were inconclusive. This indicates the need for longer intervention periods with long-term evaluation plans and multiple follow-ups. In addition, the work in INHERIT shows the challenges inherent in quantifying all the potential impacts of case studies, and demonstrates the importance of working within the INHERIT conceptual model and grounding evaluations in the wider literature.
Clearly, more research is needed to build on INHERIT’s findings. In particular, it is important to understand the implications for health equity of triple win interventions. These we have only been able to assess in largely qualitative terms, based on expert judgment. Longer term funding for triple win interventions is needed, with evaluation embedded alongside to help monitor the impacts over time of these. In addition, it is important to identify potential hurdles and bottlenecks in transferability and scaling up of triple win practices to different contexts and circumstances.
Furthermore, focusing on behaviour change of the business sector (e.g., food industry) and working towards new business models may help to realize the triple win.
Overall, INHERIT’s research contributes to the case for investing in interventions for a triple win, since even small steps can lead to significant impacts. Indeed, localisation, meaning local control and implementation of interventions, is vital if countries are to transition to sustainability.
5. Conclusions
This paper synthesises lessons for good practice in developing interventions intended to enable people to adopt more sustainable behaviours in ways of living, moving and consuming, and thereby contribute to a triple win for health, equity and environmental sustainability. These findings contribute to and align with wider discussions about the kinds of synergistic approaches needed to improve population health and address climate change [
32
]. They also contribute to discussions that are gaining pace in the face of growing alarm about the environmental crisis about how to shift away from economies based primarily on the growth imperative to economies focusing on well-being [
33
]. Such discussions also reflect a growing awareness of the synergies between climate change mitigation policies and other societal goals that contribute to well-being, including health, education, jobs, environmental quality, and social inclusion [
34
].
There is, for example, a large and expanding literature that reports how green space contributes to well-being, and how creating more readily accessible and good quality green space can provide opportunities to socialise and be active, and at the same contribute to climate change mitigation by providing protection against high temperature, and buffering the effect of heavy rainfall [ 7 , 35 ].
At the heart of these discussions about societal goals is the need to shift to integrated rather than ‘sector based’ objectives and approaches to achieve multiple objectives and to mainstream concepts of ‘fairness’ and redistribution. This means reframing measures of progress and reassessing and re-focusing policy priorities.
The INHERIT project has contributed to this by spearheading an innovative approach that intended to disrupt traditional disciplinary boundaries, developing a broad evaluation framework, based on the INHERIT model. It also provides a unique contribution through its study of a range of local initiatives that aim to deliver multiple societal objectives. Localised action can be a powerful force of change, since it gives people ownership and provides them with direct experience of the benefits of the initiative, which can motivate them to press for the maintenance and expansion of such actions. It is also clear, however, that cohesive and coherent policies at higher levels of government to support, spread and scale such ‘triple win’ actions are needed. Experience with and evidence on the multiple benefits of such actions, like that gathered through INHERIT, can help to achieve this.
Author Contributions
Conceptualization: R.B., M.K., M.R.-V., I.S., C.C., T.T., G.M., B.S., N.v.d.V., K.S.A., M.L., A.C., S.G.D.J.; Methodology: R.B., M.K., M.R.-V., I.S., C.C., T.T., G.M., B.S., N.v.d.V., K.S.A., M.L., A.C., S.G.d.J.; Writing—original draft, R.B.; Writing—review & editing: R.B., M.K., M.R.-V., I.S., A.G., C.C., T.T., G.M., B.S., N.v.d.V., H.K., K.S.A., M.L., G.A.E., A.C., S.G.d.J., S.Q., P.M.-J., V.M., I.Z., M.Š.,S.M., D.C., J.W., H.S., P.K., R.S., A.-S.M., M.F., N.B., M.V., D.G., I.U.
Funding
The lessons for good practice for a triple win were developed as part of EuroHealthNet coordinated INHERIT project ( www.inherit.eu ) funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 667364.
Acknowledgments
The authors would like to thank Revolve Media for their visualization of the lessons for good practice in Figure 2 .
Conflicts of Interest
The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.
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Figure 1. The INHERIT generic logic model.
Figure 2. Overarching lessons for good practice for the INHERIT triple win.
Figure 2. Overarching lessons for good practice for the INHERIT triple win.
Table 1. Summary descriptions of the 15 INHERIT case studies.
Table 1. Summary descriptions of the 15 INHERIT case studies.
Name of Case Study, Country Nature of Case Study Type of Evaluation The Food Garden (De Voedseltuin), the Netherlands An urban community gardening initiative in a disadvantaged area Qualitative PROVE, Portugal Sustainable farming practices creating closer links among producers and consumers Qualitative, Quantitative STOEMP (within Ghent en Garde policy), Belgium Local food initiatives for healthier and more sustainable food Qualitative Gemüse Ackerdemie (Vegetable Academy), Germany Increasing the number of volunteers to support vegetable academy programs for school aged children to connect with nature and origins of food Qualitative Gardening with Green Gym and Meat Free Monday, United Kingdom Gardening activities with children in a primary school and promotion of a meat free day/week Qualitative, Quantitative Sustainable food in public nursery schools, Spain Introducing sustainable foods in public nurseries in Madrid Qualitative, CBA Malvik Path, Norway Reconstruction of a disused railway track into a recreational path connecting two communities Quantitative, CBA Restructuring Residential Outdoor Areas, Sweden Regeneration of and improved access to an open space Qualitative, Quantitative Restructuring Green Space, the Netherlands Regeneration of an open green space in a housing estate in a disadvantaged area Qualitative, Quantitative Thinking Fadura, Spain Providing access to previously private green spaces to the general public Quantitative, CBA Eco-inclusion, Germany Capacity building and awareness program among migrants about energy efficiency in housing Qualitative, Quantitative Retrospective Analysis of Energy Efficiency Investment, United Kingdom Energy efficiency investments including double-glazing, insulation and improved heating systems CBA Lifestyle e-coaching, the Netherlands and Greece A lifestyle e-coaching application including a physical activity tracker and smartphone application Quantitative UrbanCyclers (now known as Cyclers), Czech Republic A smartphone application to promote regular cycling in cities Qualitative, Quantitative Place Standard, Latvia and North Macedonia Implementation of Place Standard Tool: a framework to structure conversations about place and community Qualitative
Bell, Ruth, Matluba Khan, Maria Romeo-Velilla, Ingrid Stegeman, Alba Godfrey, Timothy Taylor, George Morris, Brigit Staatsen, Nina van der Vliet, Hanneke Kruize, Kirsti Sarheim Anthun, Monica Lillefjell, Geir Arild Espnes, Aline Chiabai, Silvestre García de Jalón, Sonia Quiroga, Pablo Martinez-Juarez, Vojtěch Máca, Iva Zvěřinová, Milan Ščasný, Sibila Marques, Daniela Craveiro, Joyce Westerink, Hanne Spelt, Pania Karnaki, Rosa Strube, Anne-Sophie Merritt, Marita Friberg, Nathalie Bélorgey, Marjolijn Vos, Dragan Gjorgjev, Inese Upelniece, and Caroline Costongs. 2019. "Ten Lessons for Good Practice for the INHERIT Triple Win: Health, Equity, and Environmental Sustainability" International Journal of Environmental Research and Public Health16, no. 22: 4546.
https://doi.org/10.3390/ijerph16224546
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Bell, R.; Khan, M.; Romeo-Velilla, M.; Stegeman, I.; Godfrey, A.; Taylor, T.; Morris, G.; Staatsen, B.; van der Vliet, N.; Kruize, H.; Anthun, K.S.; Lillefjell, M.; Espnes, G.A.; Chiabai, A.; García de Jalón, S.; Quiroga, S.; Martinez-Juarez, P.; Máca, V.; Zvěřinová, I.; Ščasný, M.; Marques, S.; Craveiro, D.; Westerink, J.; Spelt, H.; Karnaki, P.; Strube, R.; Merritt, A.-S.; Friberg, M.; Bélorgey, N.; Vos, M.; Gjorgjev, D.; Upelniece, I.; Costongs, C. Ten Lessons for Good Practice for the INHERIT Triple Win: Health, Equity, and Environmental Sustainability. Int. J. Environ. Res. Public Health 2019, 16, 4546.
https://doi.org/10.3390/ijerph16224546
AMA Style
Bell R, Khan M, Romeo-Velilla M, Stegeman I, Godfrey A, Taylor T, Morris G, Staatsen B, van der Vliet N, Kruize H, Anthun KS, Lillefjell M, Espnes GA, Chiabai A, García de Jalón S, Quiroga S, Martinez-Juarez P, Máca V, Zvěřinová I, Ščasný M, Marques S, Craveiro D, Westerink J, Spelt H, Karnaki P, Strube R, Merritt A-S, Friberg M, Bélorgey N, Vos M, Gjorgjev D, Upelniece I, Costongs C. Ten Lessons for Good Practice for the INHERIT Triple Win: Health, Equity, and Environmental Sustainability. International Journal of Environmental Research and Public Health. 2019; 16(22):4546.
https://doi.org/10.3390/ijerph16224546
Chicago/Turabian Style
Bell, Ruth, Matluba Khan, Maria Romeo-Velilla, Ingrid Stegeman, Alba Godfrey, Timothy Taylor, George Morris, Brigit Staatsen, Nina van der Vliet, Hanneke Kruize, Kirsti Sarheim Anthun, Monica Lillefjell, Geir Arild Espnes, Aline Chiabai, Silvestre García de Jalón, Sonia Quiroga, Pablo Martinez-Juarez, Vojtěch Máca, Iva Zvěřinová, Milan Ščasný, Sibila Marques, Daniela Craveiro, Joyce Westerink, Hanne Spelt, Pania Karnaki, Rosa Strube, Anne-Sophie Merritt, Marita Friberg, Nathalie Bélorgey, Marjolijn Vos, Dragan Gjorgjev, Inese Upelniece, and Caroline Costongs. 2019. "Ten Lessons for Good Practice for the INHERIT Triple Win: Health, Equity, and Environmental Sustainability" International Journal of Environmental Research and Public Health16, no. 22: 4546.
https://doi.org/10.3390/ijerph16224546
| https://www.mdpi.com/1660-4601/16/22/4546/xml |
Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies - Full Text View - ClinicalTrials.gov
Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies (PDX+Romi)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01947140 Recruitment Status :
Completed First Posted : September 20, 2013 Last Update Posted : November 23, 2022
Sponsor:
Jennifer Amengual
Information provided by (Responsible Party):
Jennifer Amengual, Columbia University
Study Details
Study Description
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
This is a study to test how safe the combination of the drugs Romidepsin and Pralatrexate are in patients with lymphoid malignancies and to determine the dose of the combination of drugs that is safest. If the combination is determined to be safe, the study will continue accrual patients with peripheral T-Cell lymphoma (PTCL).
Condition or disease Intervention/treatment Phase Lymphoid Malignancies Multiple Myeloma Lymphoma Hodgkin Lymphoma Non-hodgkin Lymphoma Drug: Pralatrexate Drug: Romidepsin Phase 1 Phase 2
Detailed Description:
The non- Hodgkin lymphomas (NHL) represent a heterogeneous group of malignancies. Under the rubric of lymphoma exist some of the fastest growing cancers known to science, (Burkett's lymphoma, lymphoblastic lymphoma/leukemia), as well as some of the most indolent (small lymphocytic lymphoma, follicular lymphoma, and marginal zone lymphoma). This remarkable diversity of biology imposes significant challenges. Researchers are seeking to understand the cell of origin and differentiate what are sometimes subtle differences between the related sub-types of disease; and to identify the best treatments for these subtypes, with the ever-increasing likelihood that new understanding of the molecular pathogenesis of these diseases will result in an increase in new drugs for specific target populations.
Study Design
Layout table for study information Study Type : Interventional
(Clinical Trial) Actual Enrollment : 57 participants Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment Official Title: Phase I/IIA Study of the Novel Antifolate Agent Pralatrexate in Combination With the Histone Deacetylase Inhibitor Romidepsin for the Treatment of Patients With Peripheral T-cell Lymphoma Actual Study Start Date : September 9, 2013 Actual Primary Completion Date : September 1, 2022 Actual Study Completion Date : September 1, 2022
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics: Multiple myeloma
MedlinePlus related topics: Lymphoma
Drug Information available for: Romidepsin Pralatrexate
Genetic and Rare Diseases Information Center resources: Multiple Myeloma Lymphosarcoma Follicular Lymphoma B-cell Lymphoma Diffuse Large B-Cell Lymphoma Chronic Lymphocytic Leukemia Mantle Cell Lymphoma Peripheral T-cell Lymphoma Cutaneous T-cell Lymphoma Hodgkin Lymphoma Chronic Graft Versus Host Disease Marginal Zone Lymphoma Burkitt Lymphoma Anaplastic Large Cell Lymphoma Waldenstrom Macroglobulinemia
U.S. FDA Resources
Arms and Interventions
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Arm Intervention/treatment Experimental: Phase I: Schedule A Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 8 of each 21 day cycle Drug: PralatrexatePhase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 10 mg/m2 to 25 mg/m2Phase II - 25 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle. Other Name: Folotyn Drug: RomidepsinPhase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 12 mg/m2 to 14 mg/m2.Phase II - 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle. Other Name: Istodax Experimental: Phase I: Schedule B Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 15 of each 28 day cycle Drug: PralatrexatePhase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 10 mg/m2 to 25 mg/m2Phase II - 25 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle. Other Name: Folotyn Drug: RomidepsinPhase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 12 mg/m2 to 14 mg/m2.Phase II - 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle. Other Name: Istodax Experimental: Phase II Subjects will receive Pralatrexate 25 mg/m2 and Romidepsin 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle Drug: PralatrexatePhase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 10 mg/m2 to 25 mg/m2Phase II - 25 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle. Other Name: Folotyn Drug: RomidepsinPhase I - Schedule A: Intravenous drug given on days 1 and 8 of each 21 day cycle Schedule B: Intravenous drug given on days 1 and 15 of each 28 day cycle Dose escalation from 12 mg/m2 to 14 mg/m2.Phase II - 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle. Other Name: Istodax
Outcome Measures
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Primary Outcome Measures
:
Maximum tolerated dose (MTD) of the combination of pralatrexate and romidepsin [ Time Frame: Up to 1.5 years ]
For Phase I
Overall response rate (ORR) (complete + partial response) of the combination of pralatrexate and romidepsin in patients with relapsed/refractory T-Cell Lymphoma [ Time Frame: Up to 3 years ]
For Phase II
Secondary Outcome Measures
:
Maximum number of cycles received [ Time Frame: Up to 1.5 years ]
For Phase II
Number of dose delays at the MTD [ Time Frame: Up to 1.5 years ]
For Phase I
Overall response rate (ORR) of the study population [ Time Frame: Up to 1.5 years ]
For Phase I
Duration of response (DOR) of the combination in patients with T-Cell Lymphoma [ Time Frame: Up to 3 years ]
For Phase II
Overall survival (OS) of patients with T-Cell Lymphoma on study [ Time Frame: Up to 3 years ]
For Phase II
Progression free survival (PFS) of the combination in patients with T-Cell Lymphoma [ Time Frame: Up to 3 years ]
For Phase II
Number of dose reductions at the MTD [ Time Frame: Up to 1.5 years ]
For Phase I
Progression free survival (PFS) of the study population [ Time Frame: Up to 1.5 years ]
For Phase I
Duration of response (DOR) of the study population. [ Time Frame: Up to 1.5 years ]
For Phase I
Eligibility Criteria
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Layout table for eligibility information Ages Eligible for Study: 18 Years and older (Adult, Older Adult) Sexes Eligible for Study: All Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:
Phase I: Patients must have histologically confirmed relapsed or refractory Non-Hodgkin's lymphoma, Hodgkin's Disease or multiple myeloma (defined by World Health Organization (WHO) criteria).
Phase II: Patients must have histologically confirmed relapsed or refractory T-Cell Lymphoma (as defined by WHO criteria).
Must have received first line chemotherapy. No upper limit for the number of prior therapies
Evaluable Disease
Age ≥18 years
Eastern Cooperative Oncology Group (ECOG) performance status ≤2
Patients must have adequate organ and marrow function as defined in the protocol
Adequate Contraception
Ability to understand and the willingness to sign a written informed consent document
Inclusion Criteria for Multiple Myeloma patients specified in the protocol
Exclusion Criteria:
Prior Therapy
Exposure to chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
Systemic steroids that have not been stabilized to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs
No other investigational agents are allowed
Central nervous system metastases, including lymphomatous meningitis
History of allergic reactions to Pralatrexate or Romidepsin
Uncontrolled intercurrent illness
Pregnant women
Nursing women
Current malignancy or history of a prior malignancy, as outlined in the protocol
Patient known to be Human Immunodeficiency Virus (HIV)-positive
Active Hepatitis A, Hepatitis B, or Hepatitis C infection
Contacts and Locations
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01947140
Locations
Layout table for location information United States, Massachusetts Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215 United States, New York Columbia University Irving Medical Center New York, New York, United States, 10019 United States, Pennsylvania Fox Chase Cancer Center Philadelphia, Pennsylvania, United States, 19111
Sponsors and Collaborators
Jennifer Amengual
Investigators
Layout table for investigator information Principal Investigator: Jennifer Amengual, MD Columbia University
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Amengual JE, Lichtenstein R, Lue J, Sawas A, Deng C, Lichtenstein E, Khan K, Atkins L, Rada A, Kim HA, Chiuzan C, Kalac M, Marchi E, Falchi L, Francescone MA, Schwartz L, Cremers S, O'Connor OA. A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma. Blood. 2018 Jan 25;131(4):397-407. doi: 10.1182/blood-2017-09-806737. Epub 2017 Nov 15.
Layout table for additonal information Responsible Party: Jennifer Amengual, Assistant Professor of Medicine, Columbia University ClinicalTrials.gov Identifier: NCT01947140 History of Changes Other Study ID Numbers: AAAJ5656 First Posted: September 20, 2013 Key Record Dates Last Update Posted: November 23, 2022 Last Verified: November 2022 Individual Participant Data (IPD) Sharing Statement: Plan to Share IPD: Undecided
Layout table for additional information Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jennifer Amengual, Columbia University:
Lymphoid Malignancies Multiple Myeloma Lymphoma Hodgkin Lymphoma Non-hodgkin Lymphoma Follicular Lymphoma Diffuse Large B-Cell Lymphoma Anaplastic Large Cell Lymphoma Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Mantle Cell Lymphoma Marginal Zone Lymphoma Burkitt Lymphoma Waldenstrom Macroglobulinemia Peripheral T-cell Lymphoma Cutaneous T-cell Lymphoma
Additional relevant MeSH terms:
Layout table for MeSH terms Lymphoma Multiple Myeloma Neoplasms Lymphoma, Non-Hodgkin Hodgkin Disease Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Neoplasms, Plasma Cell Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Romidepsin Antibiotics, Antineoplastic Antineoplastic Agents Histone Deacetylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action
HHS Vulnerability Disclosure
| https://clinicaltrials.gov/ct2/show/NCT01947140 |
JCM | Free Full-Text | Does ADHD Symptomatology Influence Treatment Outcome and Dropout Risk in Eating Disorders? A longitudinal Study
Attention-deficit/hyperactivity disorder (ADHD) and its symptoms have been shown to be present in patients with eating disorders (EDs) and are associated with increased psychopathology and more dysfunctional personality traits. This study aimed to assess if the presence of ADHD symptoms in patients with EDs affects their short and long-term therapy outcome. A total of 136 consecutively treated ED patients were considered in this study. Baseline pre-treatment evaluation included the Adult ADHD Self-Report Scale (ASRS v1.1) for ADHD symptoms and the assessment of eating symptomatology using the Eating Disorders Inventory (EDI-2). Treatment outcome was evaluated in terms of ED symptoms after cognitive behavioral therapy (CBT) and dropout rate during treatment. Furthermore, we evaluated ED symptoms in treatment completers after a follow-up of 8 years on average. Path analyses assessed the potential mediational role of the EDI-2 total score in the relationship between ADHD and treatment outcome. Results showed that baseline symptoms of ADHD indirectly affected treatment outcome after CBT; the ASRS positive screening was related to higher eating symptomatology (standardized coefficient B = 0.41, p = 0.001, 95% CI: 0.26 to 0.55), and the presence of high ED levels contributed to the increase of dropout (B = 0.15, p = 0.041, 95% CI: 0.03 to 0.33) and a worse treatment outcome (B = 0.18, p = 0.041, 95% CI: 0.01 to 0.35). No direct effect was found between the ASRS positive screening with the risk of dropout (B = −0.08, p = 0.375) and worse treatment outcome (B = −0.07, p = 0.414). These results suggest the relevance of identifying specific treatment approaches for patients with ADHD symptoms and severe eating symptomatology.
Does ADHD Symptomatology Influence Treatment Outcome and Dropout Risk in Eating Disorders? A longitudinal Study
Giulia Testa 1,2,† ,
Isabel Baenas 1,2,† ,
Cristina Vintró-Alcaraz 1,2 ,
Roser Granero 1,3 ,
Zaida Agüera 1,2,4 ,
Isabel Sánchez 1,2 ,
Nadine Riesco 1,2 ,
Susana Jiménez-Murcia 1,2,5 and
Fernando Fernández-Aranda 1,2,5,*
Ciber Physiopathology, Obesity and Nutrition (CIBERObn), Instituto de Salud Carlos III, 08907 Barcelona, Spain
Department of Psychobiology and Methodology of Health Sciences, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
4
Department of Public Health, Mental Health and Maternal-Child Nursing, School of Nursing, University of Barcelona, 08907 Barcelona, Spain
5
Department of Clinical Sciences, School of Medicine, University of Barcelona, 08907 Barcelona, Spain
*
Author to whom correspondence should be addressed.
†
Share first authorship.
J. Clin. Med. 2020 , 9 (7), 2305; https://doi.org/10.3390/jcm9072305
Received: 4 June 2020 / Revised: 8 July 2020 / Accepted: 15 July 2020 / Published: 20 July 2020
(This article belongs to the Special Issue Advances in Eating Disorders )
Abstract
:
Attention-deficit/hyperactivity disorder (ADHD) and its symptoms have been shown to be present in patients with eating disorders (EDs) and are associated with increased psychopathology and more dysfunctional personality traits. This study aimed to assess if the presence of ADHD symptoms in patients with EDs affects their short and long-term therapy outcome. A total of 136 consecutively treated ED patients were considered in this study. Baseline pre-treatment evaluation included the Adult ADHD Self-Report Scale (ASRS v1.1) for ADHD symptoms and the assessment of eating symptomatology using the Eating Disorders Inventory (EDI-2). Treatment outcome was evaluated in terms of ED symptoms after cognitive behavioral therapy (CBT) and dropout rate during treatment. Furthermore, we evaluated ED symptoms in treatment completers after a follow-up of 8 years on average. Path analyses assessed the potential mediational role of the EDI-2 total score in the relationship between ADHD and treatment outcome. Results showed that baseline symptoms of ADHD indirectly affected treatment outcome after CBT; the ASRS positive screening was related to higher eating symptomatology (standardized coefficient B = 0.41,
p
= 0.001, 95% CI: 0.26 to 0.55), and the presence of high ED levels contributed to the increase of dropout (B = 0.15,
p
= 0.041, 95% CI: 0.03 to 0.33) and a worse treatment outcome (B = 0.18,
p
= 0.041, 95% CI: 0.01 to 0.35). No direct effect was found between the ASRS positive screening with the risk of dropout (B = −0.08,
p
= 0.375) and worse treatment outcome (B = −0.07,
p
= 0.414). These results suggest the relevance of identifying specific treatment approaches for patients with ADHD symptoms and severe eating symptomatology.
Keywords:
attention-deficit/hyperactivity disorder
;
ADHD
;
eating disorders
;
longitudinal
;
treatment outcome
;
dropout
1. Introduction
Attention-deficit/hyperactivity disorder (ADHD), which is characterized by symptoms of impulsivity, hyperactivity and inattention, has been described in relation to several psychiatric disorders including eating disorders (EDs) [ 1 , 2 , 3 , 4 ]. Accordingly, a higher prevalence of ADHD symptoms in EDs has been reported in many studies, in comparison with the general population [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Likewise, ADHD has been related with increased risk of disordered eating in childhood and adulthood [ 11 , 12 , 13 , 14 ], obesity [ 15 ] and behavioral addictions [ 16 , 17 ].
From a neurobiological perspective, a recent study examined the genetic factors common to both disorders and observed a stronger genetic association between ADHD and binge-eating behaviors [ 18 ]. From a clinical view, ADHD symptoms in ED were associated with higher ED symptomatology [ 19 ], specifically binge ED subtypes, with greater psychopathology [ 19 , 20 , 21 ], and increased levels of motor and cognitive impulsivity [ 22 , 23 ], as well as impulsive personality traits [ 24 , 25 ].
Despite the evidence linking ADHD and EDs, there is a lack of studies investigating whether ADHD symptoms may impact treatment response in patients with EDs, both in terms of treatment adherence (i.e., dropout rate) and outcome. To the best of our knowledge, there is only one previous study in female patients with EDs reporting higher ADHD symptoms at baseline as a predictor of non-recovery from eating-related symptomatology one year after treatment, especially for patients with loss of control overeating, bingeing and purging [
26
]. However, a high dropout rate (61%) was shown in that study, highlighting the need for future studies examining the impact of ADHD symptoms over dropout rate in EDs treatment.
The first aim of the present study was to evaluate if the initial presence of ADHD symptomatology impacts the therapy outcome after a cognitive behavioral therapy (CBT) treatment for EDs and dropout rate during treatment. The second aim was to analyze whether the baseline ADHD symptomatology had an impact on long-term therapy outcome (after eight years on average). Furthermore, we assessed the influence of EDs severity over the relationship between ADHD symptoms and treatment results.
2. Materials and Methods
2.1. Participants
The initial sample was comprised of 191 adult women diagnosed with an ED and presented for treatment to the Eating Disorder Unit within the Department of Psychiatry at Bellvitge University Hospital (HUB) (Barcelona, Spain) from 16 April 2009 to 31 January 2011. The baseline data of the initial sample was previously reported by Fernández-Aranda et al. (2013). Patients were diagnosed according to the DSM-IV-TR criteria [
27
], and diagnoses were reanalyzed and recodified post hoc using the DSM-5 criteria [
28
]. In the present study, we analyzed this sample of patients following a CBT treatment and after a longer follow-up (mean = 8.81 years; SD = 1.5). To that end, clinical records and an online shared medical network were analyzed retrospectively throughout the region of Catalonia (Spain). Thirty-three patients who did not start treatment were excluded from the original sample (
n
= 191); however, neither online nor paper clinical records were available for 22 out of 158 patients who started treatment. Thus, a final sample of 136 patients was included in the principal analysis. There were no baseline differences between patients who were included in this study and those who were not. Sixty-four participants included in the final sample did not complete treatment sessions (dropout) whereas 72 patients out of 136 completed the treatment (see flowchart;
Figure 1
).
2.2. Assessment
Adult ADHD Self-Report Scale (ASRS-v1.1) [
29
]: The ASRS-v1.1 is a self-administered scale designed to screen ADHD in the adult population (aged 18 years and older). It comprises 6 items that are consistent with the DSM-IV-TR [
27
] criteria and address the manifestation of ADHD in adults; the first 4 questions examine the inattention component of ADHD, and the final 2, the hyperactivity component. Each item is assessed using a 5-point Likert scale (0–4). The total score ranges between 0 and 24, with the cut-off being set at 12. The Spanish validation reported good psychometric properties [
30
]. Internal consistency in the sample analyzed in this work was good (Cronbach’s alpha α = 0.77).
Eating Disorders Inventory-2 (EDI-2) [ 31 ]: This self-report questionnaire consists of 91 items, answered on a 6-point Likert scale, that assess different cognitive and behavioral characteristics related to ED. The EDI-2 provides standardized subscale scores as well as a global measure of ED severity, which can be obtained based on the sum of all the items. A Spanish version of this questionnaire [ 32 ] has been validated and it obtained excellent psychometrical properties as an external global measure of ED severity. Internal consistency for the total score in this study was good (Cronbach’s alpha α = 0.85).
2.3. Treatment
As described elsewhere [
33
,
34
], all patients received cognitive behavioral therapy (CBT) at HUB, which was carried out by clinical psychology experts in the field. The CBT group therapy intervention for bulimia nervosa (BN), binge eating disorder (BED) and other specified feeding or eating disorders (OSFED) consisted of 16 weekly outpatient sessions lasting 90 minutes each and a follow-up period of about two years’ duration that was carried out in a group format. Patients with BN first received six sessions of psychoeducational brief group therapy to offer information and psychoeducation about the negative consequences of BN. Patients diagnosed with anorexia nervosa (AN) completed a day hospital treatment program, which included two daily group CBT sessions during an average of 3 months. If they were severely underweight (IMC < 15 kg/m
2
), they were offered an in-patient treatment with a maximum duration of three months. Patients with AN also had a two-year follow-up period with individual/group sessions. The goals of the treatment were to train patients to implement CBT strategies to reduce eating symptoms and to enable patients to acquire good healthy habits.
Patients were re-evaluated at discharge and categorized into the following three categories: full remission, partial remission and non-remission. According to DSM-5 criteria [
28
], the definition of full remission is a total absence of symptoms meeting diagnostic criteria for at least 4 consecutive weeks; partial remission is defined as a substantial symptomatic improvement but with residual symptoms; and patients who present poor outcomes are defined as non-remission. These categories were previously used to assess treatment outcome in threshold ED in other published studies [
33
,
34
]. Voluntary treatment discontinuation was categorized as dropout (i.e., not attending treatment for at least three consecutive sessions).
2.4. Follow-Up
A longitudinal follow-up of the patients was collected during an average period of 8.8 years (SD = 1.5), from the end of the first contact made in our unit to April 2020. This first contact coincided with the assessment using the ASRS screening questionnaire. By searching through centralized Catalonian clinical records and an online shared medical network, we assessed clinical evolution of all ED patients over the time, in terms of symptomatological remission (categorized as positive follow-up) or clinical non-remission of eating symptomatology (categorized as negative follow-up). From the total sample, clinical records were available for 123 patients, while 13 patients were missing (10.5% attrition rate).
2.5. Ethics
The present study was carried out in accordance with the latest version of the Declaration of Helsinki. The Bellvitge University Hospital Clinical Research Ethics Committee approved the study and signed informed consent was previously obtained from all participants.
2.6. Statistical Analyses
Stata16 for Windows was used to carry out statistical analyses [ 35 ]. A comparison between the groups defined by the risk of dropout during the CBT (yes/no) and the classification of the therapy outcome (full/partial remission versus dropout/non-remission) was done with a chi-square test ( χ 2 ).
Survival function (Kaplan–Meier product-limit estimator) modeled the rate of dropout during the therapy. This procedure is usually used to describe the probability of the patients “living/surviving” for a certain amount of time after one concrete intervention [ 36 ]. In this study, “surviving” was defined for patients without dropout after the beginning of the CBT.
Path analyses assessed the potential mediational role of the ED severity level (EDI-2 total score) in the relationship between ADHD and treatment outcome (i.e., therapy outcome after a CBT treatment and dropout rate during treatment). This procedure was defined in this work as a case of structural equation modeling (SEM), with the maximum-likelihood estimation method of parameter estimation, adjusting by the covariates participants’ age and the duration of the ED. The goodness-of-fit was evaluated using a standard statistical test, and it was considered adequate fitting for [
37
]: non-significant result (
p
> 0.05) in the
χ
2
test, root mean square error of approximation (RMSEA) < 0.08, Bentler’s comparative fit index (CFI) > 0.90, Tucker–Lewis Index (TLI) > 0.90 and standardized root mean square residual (SRMR) < 0.10. In this study, the relatively low sample size and the high correlations between the EDI-2 scores did not allow the SEM to be included in all the EDI-2 subscales registered for the participants (goodness-of-fit was not achieved).
3. Results
3.1. Characteristics of the Sample
No statistical differences between participants selected for the study and those excluded were found for marital status (
χ
2
= 0.07,
p
= 0.982), education level (
χ
2
= 1.03,
p
= 0.317), socioeconomic status (
χ
2
= 2.67,
p
= 0.446), age (
T
= 1.04,
p
= 0.300), duration of the eating problems (
T
= 0.62,
p
= 0.535), onset of the ED (
T
= 0.70,
p
= 0.487), ED-symptom levels (
T
= 0.52,
p
= 0.603) and ADHD-symptom levels (
T
= 0.74,
p
= 0.462).
Table 1
shows the descriptive for the sociodemographic and clinical variables of the final sample included in the study. All participants were women, with a mean age of 28.7 years (SD = 9.6), most were single (66.9%) and had achieved a secondary education level (61.0%). The number of patients within the ASRS positive screening group was
n
= 46 (point prevalence estimate equal to 33.8%). Regarding CBT outcomes, the dropout rate in the total sample was 47.0%, non-remission was registered for 11.8%, partial remission for 18.4% and full remission for 22.8%. Within the completers subsample (
n
= 72), non-remission was registered for 22.2% of the participants, partial remission for 34.7% and full remission for 43.1%.
Table 2
includes the correlation matrix (Pearson correlation coefficients, R) between the ADHD level (measured through the ASRS scales) with the ED symptom level (EDI-2 scales). Due the strong relationship between the significance test for the correlation model and the sample size (high coefficients estimated in low samples sizes tend to show non-significance, while low coefficients tend to show significance obtained in samples with a large number of participants),
Table 2
shows in bold the coefficients with an effect size that is in the moderate-mild (|R| > 0.24) to high-large range (|R| > 0.37). While moderate to high correlations were found between most EDI-2 scales, low correlation was found between ASRS inattention with hyperactive scores (R = 0.166). ASRS inattention positively correlated with all the EDI-2 scales, except for maturity fears, perfectionism and impulse regulation. ASRS hyperactivity also positively correlated with drive for thinness, body dissatisfaction, interoceptive awareness, impulse regulation and total. ASRS total correlated with all the EDI-2 scales (except for perfectionism), achieving the highest R-coefficient with the EDI-2 total (R = 0.497).
The ADHD level was not directly related to the short-term therapy outcomes in the study; the prevalence of the ASRS positive screening score was statistically equal for completers and dropouts, as well as for participants with partial remission and full remission versus those with dropout and non-remission ( Table 3 ). No association was found even when stratified by the diagnostic subtype ( Supplementary Table S1 ). Regarding data registered after the follow-up, neither was there any statistical association found between the ASRS positive screening with therapy outcome.
Figure 2 includes the cumulate survival function for the time to dropout. The higher proportion of dropouts was registered during the two weeks after the beginning of the treatment (12.1% for the total sample), followed by the next two weeks (at the end of the first month 24.1% had followed). No statistical contribution was found between ASRS score with the rate to dropout (log rank test = 0.01, p = 0.995).
Supplementary Table S2 includes the associations between the ADHD levels (registered in the ASRS inattention, hyperactivity and total score) and the ED symptom levels (registered in the EDI-2 scores) with the treatment outcomes (during therapy, at short-term and in the follow-up). No statistical differences were found comparing the mean scores in the ASRS and the EDI-2 between the groups of the study.
3.2. Path Analysis
Figure 3
shows the results of the SEM assessing the mediational link of the ED severity into the relationship between ADHD and the CBT outcomes. Goodness of fit was achieved for both models (risk of dropout:
χ
2
= 0.807 (
p
= 0.848), RMSEA = 0.001, CFI = 0.999, TLI = 0.998, SRMR = 0.015; better CBT outcome:
χ
2
= 0.029 (
p
= 0.864), RMSEA = 0.001, CFI = 0.999, TLI = 0.998, SRMR = 0.004). These results confirmed the indirect effect of ADHD on the therapy outcome; being in the ASRS positive screening group is related to higher ED severity (higher EDI-2 total), and this worse ED level contributed to the increase in the risk of dropout and a worse treatment outcome.
Figure 4 shows the results of the SEM adding the patients’ state at the end of the follow-up (adequate fitting was achieved: χ 2 = 0.519 ( p = 0.771), RMSEA = 0.001, CFI = 0.999, TLI = 0.998, SRMR = 0.016). This new model indicates that the ADHD screening score was not related (through a direct or indirect link) to the clinical condition measured in the follow-up.
4. Discussion
This study investigated whether the presence of ADHD symptoms in patients with EDs may impact treatment outcome and dropout for EDs. The second aim was to examine the influence of EDs severity on the relationship between ADHD symptoms and treatment outcome/dropout rate. Finally, a long-term follow-up was included to assess the effect of ADHD symptoms at baseline on the clinical evolution of EDs.
ADHD screening at baseline did not directly predict treatment outcome or dropout rate in patients attending a CBT for EDs. However, our results highlighted that the severity of eating symptomatology mediates the relation between ADHD and treatment outcome/dropout rate. Specifically, positive screening for ADHD symptoms was directly associated with the severity of EDI-2, which in turn is related to a higher dropout rate and a worse treatment outcome, in terms of dropout during treatment and non-remission of ED symptomatology.
The only previous study investigating the effect of ADHD over treatment for ED suggested that patients with higher ADHD symptoms presented a higher risk of poor post-treatment outcome, although the impact of ED severity on this relation was not assessed [ 26 ]. Interestingly, a high dropout from treatment was also reported in that study (61%), further suggesting the importance of taking into account dropout as a negative outcome of ED treatment. Considering that patients with ADHD tend to act impulsively, they may be more likely to abandon treatment, although limited information has been reported linking the effect of ADHD symptomatology in the treatment of comorbid psychopathology, in terms of dropout. These studies were mostly focused on substance use disorder (SUD), such as tobacco [ 38 ] or cocaine [ 39 , 40 , 41 ]. When SUD and ADHD are co-morbid, some factors seem to increase the risk of dropout, including: disruptive behaviors related to ADHD [ 40 ], cognitive deficit (e.g., executive dysfunctions) and the type of substance of abuse [ 41 ]. Concerning EDs, this is the first study suggesting that higher severity of EDs and co-occurring ADHD symptoms increase the risk of dropout.
In spite of the higher proportion of dropouts registered within the first two weeks of treatment, the ASRS score does not differ between early or later dropout, suggesting that ADHD symptoms may increase the dropout rate at different stages of treatment. Furthermore, we included a longer follow-up of the majority of the patients, showing that positive screening for ADHD symptoms at baseline did not affect the longer terms evolution of EDs. This is the first retrospective study which allows the evaluation of the impact of ADHD symptoms on EDs with a longitudinal follow-up of roughly 8 years.
This study must be interpreted in light of its limitations. First, a self-reporting instrument was used to measure the frequency of adult ADHD symptoms, which may lead to an overestimation of this symptomatology. Therefore, future studies should focus on EDs patients with comorbidity with ADHD, not only taking into account ADHD symptomatology. Furthermore, comorbidity with others psychiatric disorders often associated with EDs (e.g., anxiety, depression) should be addressed by future studies in larger samples. Second, only female EDs patients were included in this study, so further studies would benefit from including male population as men report a higher prevalence of ADHD in adult life [
42
]. Third, it would have been advisable to have objective measures available after the follow-up. Finally, the retrospective nature of the design should be considered.
In conclusion, the present findings suggest a higher risk for dropout of treatment (i.e., CBT for EDs) and worse treatment outcomes in patients with more severe ED-symptoms, and an indirect effect of ADHD symptomatology on the treatment outcomes mediated by the ED severity levels. This was the first study to examine the effect of ADHD over the risk of dropout in patients treated for EDs, suggesting the relevance of identifying specific treatment approaches for patients with greater degrees of ADHD symptoms and severe EDs.
Supplementary Materials
The following are available online at https://www.mdpi.com/2077-0383/9/7/2305/s1 , Table S1: Description of ADHD measures within the groups defined by the short-term therapy outcome ( n = 136), Table S2: Description of ADHD measures within the groups defined by the short term therapy outcomes ( n = 136) and the follow-up ( n = 123).
Author Contributions
G.T., I.B. and C.V.-A. contributed to the conceptualization and writing of the present study; S.J.-M. and F.F.-A. supervised the study; R.G. performed the formal analysis; Z.A., I.B., I.S. and N.R. aided with data collection and also with the interpretation of data; G.T. and I.B. shared first authorship. All authors have read and agreed to the published version of the manuscript.
Funding
Acknowledgments
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Flow chart for the sampling procedure.
Figure 2. Survival function for dropout ( n = 136).
Figure 2. Survival function for dropout ( n = 136).
Figure 3. Path-diagrams: standardized coefficients in the SEM for the short-term therapy outcome ( n = 136). Continuous line: significant coefficient. Dash line: non-significant coefficient. Results adjusted by age and duration of the ED.
Figure 3. Path-diagrams: standardized coefficients in the SEM for the short-term therapy outcome ( n = 136). Continuous line: significant coefficient. Dash line: non-significant coefficient. Results adjusted by age and duration of the ED.
Figure 4. Path-diagrams: standardized coefficients in the SEM for the follow-up ( n = 123). Continuous line: significant coefficient. Dash line: non-significant coefficient. Results adjusted by age and duration of the ED.
Figure 4. Path-diagrams: standardized coefficients in the SEM for the follow-up ( n = 123). Continuous line: significant coefficient. Dash line: non-significant coefficient. Results adjusted by age and duration of the ED.
Table 1. Descriptive for the sample ( n = 136).
Table 1. Descriptive for the sample ( n = 136).
Sociodemographic n % Therapy Outcomes n % Marital Single 91 66.9% Total sample ( n = 136) Married/Partner 34 25.0% Dropout 64 47.0% Divorced/Separated 11 8.1% Non-remission 16 11.8% Education Primary 32 23.5% Partial remission 25 18.4% Secondary 83 61.0% Full remission 31 22.8% University 21 15.5% Completers subsample ( n = 72) Age and ED severity level Mean SD Non-remission 16 22.2% Chronological age (years) 28.74 9.59 Partial remission 25 34.7% EDI-2 total score 97.91 44.52 Full remission 31 43.1% ADHD (ASRS screening) n % Positive screening 46 33.8% Negative screening 90 66.2%
Note. SD: standard deviation.
Table 2. Correlation matrix for the Adult ADHD Self-Report Scale (ASRS) and Eating Disorders Inventory (EDI-2) scores ( n = 136).
Table 2. Correlation matrix for the Adult ADHD Self-Report Scale (ASRS) and Eating Disorders Inventory (EDI-2) scores ( n = 136).
2 3 4 5 6 7 8 9 10 11 12 13 14 15 1. ASRS: inattention 0.166 0.882 † 0.252 † 0.356 † 0.384 † 0.287 † 0.287 † 0.425 † 0.183 0.033 0.220 0.312 † 0.419 † 0.420 † 2. ASRS: hyperactive --- 0.609 † 0.372 † 0.282 † 0.341 † 0.226 0.086 0.207 0.214 0.116 0.336 † 0.210 0.149 0.342 † 3. ASRS: total --- 0.379 † 0.419 † 0.474 † 0.337 † 0.267 0.438 † 0.246 † 0.078 0.337 † 0.346 † 0.402 † 0.497 † 4. EDI-2: Drive.thinness --- 0.622 † 0.582 † 0.367 † 0.341 0.483 † 0.297 † 0.339 † 0.364 † 0.628 † 0.440 † 0.720 † 5. EDI-2: Body.dissatisf. --- 0.503 † 0.483 † 0.383 0.596 † 0.283 † 0.211 0.429 † 0.506 † 0.457 † 0.751 † 6. EDI-2: Interoc.awar. --- 0.508 † 0.500 0.700 † 0.371 † 0.305 † 0.604 † 0.666 † 0.637 † 0.838 † 7. EDI-2: Bulimia --- 0.238 0.430 † 0.032 0.056 0.385 † 0.486 † 0.262 † 0.562 † 8. EDI-2: Interp.distrust --- 0.561 † 0.306 † 0.168 0.347 † 0.385 † 0.697 † 0.626 † 9. EDI-2: Ineffectiveness --- 0.503 † 0.296 † 0.568 † 0.650 † 0.749 † 0.865 † 10. EDI-2: Maturity fears --- 0.277 † 0.366 † 0.279 † 0.496 † 0.549 † 11. EDI-2: Perfectionism --- 0.331 † 0.314 † 0.299 † 0.438 † 12. EDI-2: Impulse.regul. --- 0.541 † 0.576 † 0.717 † 13. EDI-2: Ascetic --- 0.503 † 0.768 † 14. EDI-2: Social.insec. --- 0.790 † 15. EDI-2: Total score ---
Table 3. Description of ADHD measures within the groups defined by the short term therapy outcomes ( n = 136) and the follow-up ( n = 123).
Table 3. Description of ADHD measures within the groups defined by the short term therapy outcomes ( n = 136) and the follow-up ( n = 123).
Treatment Outcome Completers ( n = 72) Dropout ( n = 64) p ADHD screening (+); n -% 25 34.7% 21 32.8% 0.814 Short-term therapy outcome Full/partial remission ( n = 56) Dropout/non-remission ( n = 80) p ADHD screening (+); n -% 21 37.5% 25 31.3% 0.448 Outcome at follow-up Remission ( n = 87) Non-remission ( n = 36) p ADHD screening (+); n -% 29 33.3% 12 33.3% 1.00
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spinecor - National Scoliosis Foundation Forums
10 to 17 Years Old
spinecor
Spinecor Hi Everyone, I know some of you have tried to send me private messages. I just deleted some old ones. Sorry about that. We are going to N.Y. to our Spinecor Doc on Tuesday. We actually talked to 2 orthos at Shriner's in Phila because there was a mix-up. So we had 2 appts. Even though Nicole's main curve is holding at 41 after such a crucial growing time, neither ortho would credit or recommend the Spinecor brace. We are continuing with the Spinecor because we believe it is still the best option for Nicole. Does anyone know what can be done for a thoracic curve of 39. Other than a hard brace. Nicole now has two curves. The other is a thoracic-lumbar of 41. The next 6 months are very important. She has to make it through without increasing. Then most of her growing should be done. Of course, we wish the Spinecor would have brought her curve down. The ortho uses a different instrument to measure the x-rays. So when Dr. D in N.Y. said she was at a 32, they measured it a 36. So basically, she went up from 36 to 41 in 4 months. Of course there is always room for error. But I would rather the error in the other direction. Melissa
Melissa From Bucks County, Pa., USA Mom to Matthew,19, Jessica, 17, and Nicole, 14 Nicole had surgery with Dr. Dormans on 9/12/07 at Children's Hospital of Phila. She is fused T-2 - L-3
Spinecor I forgot to mention that I took your advice, Gerbo, and threw the entire brace in the washing machine (wrapped in a pillow case). I threw the top in the dryer for a short time and let the bottom air dry. Of course, this was right before her x-rays, so she wasn't going to wear it for 24 hours. The brace survived. So I will probably continue to do it like this. Soon the weather will be hot enough to hang it outside. Melissa
Melissa From Bucks County, Pa., USA Mom to Matthew,19, Jessica, 17, and Nicole, 14 Nicole had surgery with Dr. Dormans on 9/12/07 at Children's Hospital of Phila. She is fused T-2 - L-3
Melissa, I'm not sure if I should be jumping for joy or not ? I know you wanted to see some improvement but if she has grown three inches within the last 6 months and her curve is stable (?) we couldn't ask for any better, right ? Let us know how the appointment goes on Tuesday.... Crazy question.....has anyone had trouble with the snaps coming undone ?? Strap # 1 is not holding as of today and as you know it's a long weekend and I doubt anyone will be in the office - I left a message with Dr. Rivard nevertheless. I'm kicking myself for not having spare straps on hand, what a horrible situation to be in.... Cheryl, How did the appointment go ?
Canadian eh Daughter, Deirdre born Oct 2000. Diagnosed with 60 degree curve at the age of 19 months. Serial casting by Dr. Hedden at Sick Kid's Hospital. Currently being treated by Dr. Rivard and Dr. Coillard in Montreal with the Spinecor brace and curve is holding at "2" degrees. Next appointment 2008
One month Spinecor brace check went well! Upon talking to LATigner, she helped make it possible to go to California and see Andrew Mills, the orthotist, a head of Spinecor from England today. My 12 year old daughter went down 10 degrees from original curve to a 28 with no compensating curve. I quote Mr. Mills stating a positve "significant change" to a "unique" European curve. Very positive result we wanted to share. Thanks to Lori, for all your support in every way possible! Mr. Mills commented his agreeing with all Dr. D in NY did before we even Xrayed today.
Shirley Mom to Amanda, 18, Scoliosis T58, previous Spinecor bracing for 9 months before diagnosed with Chiari I CM, and Syringomyelia (Syrinx) SM. CM/SM decompression surgery 12/4/06, Spinal fusion surgery with titanium rods and hardware and full correction 8/1/07 at Texas Scottish Rite Hospital for Children. Also mom to Megan, 14, with diagnosis PDD-NOS on the autism spectrum
Originally posted by MATJESNIC
. Does anyone know what can be done for a thoracic curve of 39. Other than a hard brace. Nicole now has two curves. The other is a thoracic-lumbar of 41. The next 6 months are very important. She has to make it through without increasing. Then most of her growing should be done. Of course, we wish the Spinecor would have brought her curve down. The ortho uses a different instrument to measure the x-rays. So when Dr. D in N.Y. said she was at a 32, they measured it a 36. So basically, she went up from 36 to 41 in 4 months. Of course there is always room for error. But I would rather the error in the other direction. Melissa
I would think that you will get a re-adjustement on Tuesday so that the straps hold the thoracic curve more. Maybe a new type of exercise? Let us know what the Spinecor docs say. Wasn't Nicole found with a double curve from the beginning? If so what was the degrees then?
I hope she stays stable now that you know her growth is about to slow down. It will be a tough 6 months but all worth it.
Good luck
Pola
Celia, We are pleased that her curve held during that crucial 6 month growth spurt. However, the compensatory curve in her thoracic has gone up 10 degrees in 4 months and is now considered a real curve. The ortho at Shriner's said there is nothing that can be done for that curve because they would not recommend a brace ring and Nicole wouldn't wear it anyway. So she basically has 2 40-degree curves. We have no control of the thoracic. That is very frustrating. Melissa
Melissa From Bucks County, Pa., USA Mom to Matthew,19, Jessica, 17, and Nicole, 14 Nicole had surgery with Dr. Dormans on 9/12/07 at Children's Hospital of Phila. She is fused T-2 - L-3
Pola, Nicole never had a double curve. We just heard of the top one in Dec when Dr. Deutchman mentioned that it went up. When she had her initial diagnosis with a top ortho, only one curve was mentioned. In Dec, her top was at a 29 and now it is at a 39. She now has an S curve. Pola, the school nurse recommended a book for Nicole called Growing Up With Scoliosis by Michelle Spray. I bought it from Amazon. Nicole has been reading it. This true story takes you through the teen years of Michelle, all the way past her surgery. Perhaps Anastasia would like to read it. Melissa
Melissa From Bucks County, Pa., USA Mom to Matthew,19, Jessica, 17, and Nicole, 14 Nicole had surgery with Dr. Dormans on 9/12/07 at Children's Hospital of Phila. She is fused T-2 - L-3
[QUOTE=Celia Vogel] Crazy question.....has anyone had trouble with the snaps coming undone ?? Strap # 1 is not holding as of today and as you know it's a long weekend and I doubt anyone will be in the office - I left a message with Dr. Rivard nevertheless. I'm kicking myself for not having spare straps on hand, what a horrible situation to be in.... QUOTE] This is a frustrating situation....I know we had one come off and it was replaced immediately cause it was indeed faulty. Yours might be worn out.
Pola, the school nurse recommended a book for Nicole called Growing Up With Scoliosis by Michelle Spray. I bought it from Amazon. Nicole has been reading it. This true story takes you through the teen years of Michelle, all the way past her surgery. Perhaps Anastasia would like to read it. Melissa[/QUOTE] Thanks for he recommendation Melissa, I saw that book on Amazon a long time ago, I wasn't sure back then if I should get it for her...you know, having secret hopes that scoliosis would not be in our life for long The time is right now and she is a bookworm so thanks for reminding me of it. Pola
[QUOTE=cyprusmom]
Originally posted by Celia Vogel
Crazy question.....has anyone had trouble with the snaps coming undone ?? Strap # 1 is not holding as of today and as you know it's a long weekend and I doubt anyone will be in the office - I left a message with Dr. Rivard nevertheless. I'm kicking myself for not having spare straps on hand, what a horrible situation to be in.... QUOTE] This is a frustrating situation....I know we had one come off and it was replaced immediately cause it was indeed faulty. Yours might be worn out.
Pola,
Guess what ?!!! I took Deirdre to the local shoe repair shop and he replaced two snaps that had been worn out and was charged a whopping $5.00 !!!!
So the brace is good as new.....yahoooooo !
Canadian eh Daughter, Deirdre born Oct 2000. Diagnosed with 60 degree curve at the age of 19 months. Serial casting by Dr. Hedden at Sick Kid's Hospital. Currently being treated by Dr. Rivard and Dr. Coillard in Montreal with the Spinecor brace and curve is holding at "2" degrees. Next appointment 2008
Spinecor checkup My daughter had her check-up on Thursday with Dr. Gorrie and Andrew Mills. Andrew was there to train Dr.Gorrie as he is now doing Spinecor in his Tustin office. Very nice not to have to drive 2-3 hours! Anways, my husband & I were quite impressed with Mr. Mills and his calm, very educated approach to reading the x-rays, the brace, etc. He told us some things we did not know such as that she has a true double curve that is very well balanced - both in the mid to upper 40's. Because she has no pain and her posture is very good he said that he would not recommend chasing down a surgeon at this point. He said if we saw orthopedic surgeons here in the US they would be more likely recommend surgey for a curve her size than doctors in England and Europe. But because of the double curve any fusion would be really long and very limiting movement wise. She has made some progress in the SpineCor brace but he said because of her age (almost 16), risser sign and physical maturity we would probably not be looking at a tremendous amount of correction but are shooting for stabilization of the curve. He declined to x-ray her again saying that in girls her age the changes come slowly and not over just 30 days of more time in the brace and it was not worth the x-ray exposure to take another one now. He adjusted her brace to fit a little more comfortably and measured with the scoliometer. There is about 5 degrees correction just between being in the brace and out and quite a bit of correction in her rotation. He was amazed that all of Dr.Gorries patients (he saw 4 of them) are extremely flexible and their curves are not rigid (even the two older ones with curves in the high 60's). This is apparently due to the chiropractic care and physical therapy that Anna has done since diagnosed 3 years ago. Because of this she may actually get more correction than he expects of a person her age. He also explained to us that it's not just the curve degrees that are important but where the curve is and the type of curve, apparently a single curve in the 30's might be operated on but a double curve in the 40's might be ok if it is balanced and can be stabilized. So a very informative visit. Of course, I would have liked to have an x-ray that showed 50% improvement (especially since during the last 6 weeks she's actually worn the brace almost the recommended hours per day) but we probably won't be x-raying for another couple of months and 50% correction is more than likely only my stress- induced day dream. To all of you who have younger children and kids with lesser curves - check out Spinecor if you haven't already!
Originally posted by Mom37
Upon talking to LATigner, she helped make it possible to go to California and see Andrew Mills, the orthotist, a head of Spinecor from England today. My 12 year old daughter went down 10 degrees from original curve to a 28 with no compensating curve. I quote Mr. Mills stating a positve "significant change" to a "unique" European curve. Very positive result we wanted to share. Thanks to Lori, for all your support in every way possible! Mr. Mills commented his agreeing with all Dr. D in NY did before we even Xrayed today.
That is amazing news!!! I thought you mentioned in a previous post that the initial the correction was less than 5 degrees ? Has it improved with time ?
Canadian eh Daughter, Deirdre born Oct 2000. Diagnosed with 60 degree curve at the age of 19 months. Serial casting by Dr. Hedden at Sick Kid's Hospital. Currently being treated by Dr. Rivard and Dr. Coillard in Montreal with the Spinecor brace and curve is holding at "2" degrees. Next appointment 2008
Originally posted by MATJESNIC
Celia, We are pleased that her curve held during that crucial 6 month growth spurt. However, the compensatory curve in her thoracic has gone up 10 degrees in 4 months and is now considered a real curve. The ortho at Shriner's said there is nothing that can be done for that curve because they would not recommend a brace ring and Nicole wouldn't wear it anyway. So she basically has 2 40-degree curves. We have no control of the thoracic. That is very frustrating. Melissa
I'm really sorry to hear about the compensatory curve....has it become rigid ? What is a brace ring ?
Canadian eh Daughter, Deirdre born Oct 2000. Diagnosed with 60 degree curve at the age of 19 months. Serial casting by Dr. Hedden at Sick Kid's Hospital. Currently being treated by Dr. Rivard and Dr. Coillard in Montreal with the Spinecor brace and curve is holding at "2" degrees. Next appointment 2008
Originally posted by LATigner
she has a true double curve that is very well balanced - both in the mid to upper 40's. Because she has no pain and her posture is very good he said that he would not recommend chasing down a surgeon at this point. He said if we saw orthopedic surgeons here in the US they would be more likely recommend surgey for a curve her size than doctors in England and Europe. But because of the double curve any fusion would be really long and very limiting movement wise. She has made some progress in the SpineCor brace but he said because of her age (almost 16), risser sign and physical maturity we would probably not be looking at a tremendous amount of correction but are shooting for stabilization of the curve.
Lori,
What a difficult situation to be in....
Canadian eh Daughter, Deirdre born Oct 2000. Diagnosed with 60 degree curve at the age of 19 months. Serial casting by Dr. Hedden at Sick Kid's Hospital. Currently being treated by Dr. Rivard and Dr. Coillard in Montreal with the Spinecor brace and curve is holding at "2" degrees. Next appointment 2008
Thanks Celia - I do have hope that her curve will still go down because of her flexibility and if it stabilizes she should be ok for many years. Fortunately, my daughter is very strong-minded and not willing to let scoliosis get in the way of living her life to the fullest. It is hard to accept as a parent that there are things we can't fix for our kids, things they have to suffer through and learn to live with. We watched our friends daughter go through treatment after treatment for a brain tumor from ages 6 to 12 - and then lose the battle so every day I am thankful that it is scoliosis we are dealing with and not cancer. Thanks for the support and encouragement. Lori
| https://www.scoliosis.org/forum/forum/parents-family-members/idiopathic-scoliosis/adolescent/2724-spinecor/page31?s=6b4812d62fe0367c5f04e497b1701133 |
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Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics | Protocol (Translated to Hebrew)
Scientific Article | מחקר זה מדגים את השירות ואת קלות מדידה הרחבה כמותית קרום התא שלה מתאם קיבולת דבק של תאים. בתור דוגמא מייצגת, אנחנו מראים כאן את...
Cancer Research
אפיון של קרום התא הרחבות ולימוד תפקידיהם סרטן התא אדהזיה דינמיקה
doi: 10.3791/56560
Taylor C. Brown 1 , Norman G. Nicolson 2 , Joyce Cheng 1 , Reju Korah 1 , Tobias Carling 1
1 Department of Surgery & Yale Endocrine Neoplasia Laboratory, Yale University School of Medicine , 2 Yale New Haven Hospital
Summary
מחקר זה מדגים את השירות ואת קלות מדידה הרחבה כמותית קרום התא שלה מתאם קיבולת דבק של תאים. בתור דוגמא מייצגת, אנחנו מראים כאן את הפרוטאין הקשורות Dickkopf 3 (DKK3) מעודד היווצרות מוגברת lobopodia תא adhesiveness ב adrenocortical קרצינומה של תאים במבחנה.
Abstract
הרחבת רפרטואר קרום התא של ממיקרו התנהגויות ממאירים שונים של תאים סרטניים, כולל פוטנציאל דבק, הנדידה שלהם. היכולת במדויק לסווג, לכמת תא הרחבות, למדוד את ההשפעה על קיבולת דבק של התא חיוני לקבוע איך איתות התא בהתנהגות התא סרטן ההשפעה של אירועים, תוקפנות. כאן, אנו מתארים את עיצוב במבחנהואת השימוש תא סיומת כימות שיטה בשיתוף עם assay קיבולת אדהזיה במודל הוקמה במבחנהadrenocortical קרצינומה (ACC). באופן ספציפי, אנו לבחון את ההשפעות של DKK3, מדכאי בשם ולא גורם פרו-בידול, על פנוטיפ סיומת הממברנה של הקו הסלולרי ACC, SW-13. אנו מציעים מבחני אלה כדי לספק פשוטה יחסית, אמין, מדדים interpretable בקלות כדי מודד את המאפיינים הבאים בתנאים שונים ניסיוני.
Introduction
חגיגת Dysregulated איתות ממלא תפקיד קריטי ממאירות adrenocortical 1. בין השיטות במחקר זה לחקור אם להחרשת DKK3, מווסת שלילי של חגיגת איתות, מייצג אירוע dedifferentiation בקליפת יותרת הכליה ומעודדת היווצרות הגידול בהקשר של התא-הרחבת רפרטואר שינויים. DKK3 הוא kDa 38 מופרש גליקופרוטאין עם פפטיד האות N-מסוף מחקרים קודמים הדגימו כי ביטויה נאכפים, גרמו מחזור מעצר התא עכבות התנהגות תוקפנית ממאיר, הפוך אפיתל-mesenchymal מעבר 2.
ההתנהגות ממאיר של קרצינומה של adrenocortical (ACC) ואת סוגי סרטן אחרים, בחלק, מושפע את היכולת של תאים סרטניים ממשק עם המשטחים שמסביב, כולל של מטריצה חוץ-תאית, אשר בתורו מקלה על גידול התא הפלישה, הגירה 3. תפקידו של קרום התא הספציפי של הרחבות בהתקדמות סרטן הוא להיות הפגינו יותר ויותר בהקשרים שונים, בעיקר דרך היווצרות של filopodia. לדוגמה, ביטוי של תעלות סידן מסוג L נמצאה זירוז היווצרות filopodia ולקדם גידול התא הפלישה 4. באופן דומה, תמונה מרתקת, אקטין מחייב חלבון מינימלית לידי רקמה נורמלית, היא גם overexpressed בתאי סרטן בשיתוף עם היווצרות filopodia 5. היווצרות Lobopodia מאפשרת fibroblasts שאינם ממאירים להעביר ביעילות דרך המטריקס הסלולר במיוחד, עם זאת, הוכח כי fibrosarcoma תאים להסתמך על פעילות מטאלופרוטאז במקום lobopodia כדי להקל על נדידת תאים ו הפלישה 6. הראינו את הגידול הזה מדכאי, כולל ראס האגודה תחום המשפחה 1 isoform (RASSF1A), DKK3, יכול פונקציה כדי לשנות אלמנטים cytoskeletal, לקדם היווצרות lamellipodia ו stymie 7 ,מאפיינים פולשני 8.
ככזה, חיוני כדי לאפיין את ההשפעות של גנים המעורבים carcinogenesis והקשר שלהן כדי שינויים סיומת קרום התא, במיוחד הערכת היווצרות filopodia, lobopodia ו- lamellipodia בתנאי מבחן. טכניקות המדינה-של-באמנות הנוכחי כוללים את השימוש שיטות מיקרוסקופ משוכללים, תיוג פלורסנט, ו/או מחשב מורכבת אלגוריתמים עבור רכישת נתונים ופרשנות. בעוד ששיטות אלה מספקים כלים אנליטיים חדש ורב עוצמה, המורכבות שלהם מגבילה את השימוש הנרחב שלהם והתאמה של ניסויים בביולוגיה של התא. יתר על כן, כימות מדויק של התבוננות לשינויים תא סיומת מורפולוגיה אינו נמדד בדרך כלל 9 , 10. לעומת זאת, אנחנו מציגים כאן טכניקה במדויק מכמתת תא סיומת שינויים באמצעות טכניקות מיקרוסקופיים סטנדרטיים ושיטות בקלות להתאמה במבחנה. שיטות אלה גם לכמת כל סוג סיומת תא בו-זמנית עבור כל תא ניתח וקבע שינויים כוללים בהתאם לדרישה ברפרטואר סיומת קרום התא. אנו גם מראים כיצד שינויים אלו יכולים להתחבר מאפייני אדהזיה תא.
כדוגמה ניסיוני, אנו נשתמש קו תא שנוצרה בעבר של SW-13, איזור SW-DDK3, אשר יש stably transfected עם pCMV6-הכניסה/DKK3 פלסמיד וקטורים צורונים overexpresses DKK3, גורם המבדילים בלוטת יותרת הכליה. Non-transfected SW-13 תאים ותאים SW-13 stably transfected עם וקטור ריק (pCMV6-ערך), המיועד SW-ניאו, ישמש פקדים ניסיוני.
Protocol
1. מאפייני השלוחה תא
לשמור על SW-13, SW-Neo ותאים SW-DKK3 ב תקן humidified החממה ב 37.0 ° C ו- 5% CO
2
בינוני נשר שונה של Dulbecco בתוספת 10% סרום שור בעובר ו 10,000 U/mL פניצילין סטרפטומיצין (יועד 'מדיום הגידול').
לספור תאים באמצעות hemocytometer, צלחת תאים 5,000 לכל בשביל SW-13, SW-Neo וקווים SW-DKK3 לתוך צלחות נפרדות 6-ובכן, גדלים בין לילה במדיום הגידול על coverslips זכוכית סטריליים דקה.
לאחר צמיחה לילה, במשך כל, תשאף מדיום הגידול, לשטוף תאים עם 1 מ ל תמיסת מלח חמה באגירה פוספט (PBS) ולאחר מכן לתקן את התאים עם 1 מ"ל של 3.7% פורמלדהיד למשך 10 דקות.
פורמלדהיד וביופסיה ותאי כתם לכל היטב עם 1 מ"ל של 0.05% קריסטל סגול במשך 30 דקות לשטוף עודף לצבוע משם באמצעות שלושה שוטף של יונים 1 מ"ל מים.
הערה: בהתאם לרמת צבע ספיגת, מספר שוטף נוספים עשוי להיות נחוץ כדי להסיר רקע מכתים לקדם ויזואליזציה תא.
בעזרת מלקחיים משופעת בסדר, לאחזר coverslips ולמקם אותם הפנים למטה על משטח זכוכית שכותרתו עם טיפה של ריאגנט הרכבה ברורות.
תחת מיקרוסקופ אור, בחר באופן אקראי 20 צפיות של תאים שאינם חופפים כל coverslip עבור תא סיומת וזמינותו.
קח photomicrographs-400 x הגדלה של כל שדה ראייה. ישירות לספור את המספר לכל סוג של סיומת עבור כל התאים נציג 20. הערה: ככזה, 20 תאים מבודדים צריך להיבדק עבור כל תנאי שנבדקו להבטיח תוצאות אמינות. Filopodia הוגדרו על ידי הרחבות הסלולר עם בסיס של 5 מיקרון או פחות, של איפקס יחיד. Lobopodia הוגדרו על ידי הרחבות הסלולר עם בסיס של 5 עד 20 מיקרון של הרחבות המכיל אורך עם apices מרובים. Lamellipodia הוגדרו על ידי הרחבות תא שגדולים מ 20 מיקרונים אורך, עם או בלי apices. בהתאם לסוג התא שנבדקו, הגדלים של הרחבות התא עשויים להיות שונים ועשויה עידון של זיהוי הפרמטרים.
לקבוע את המספר הממוצע של כל סיומת תא בכל סוג התא ( קרי , SW-13, SW-Neo, SW-DDK) על פני הבארות 6 בחן.
באמצעות מבחן סטטיסטי חד-כיווני השונות (ANOVA), להשוות הבדלים האחוז הממוצע של קרום התא הרחבות בין סוגי תאים בדיקה שונים.
2. אדהזיה Assay
לשמור על SW-13, SW-Neo ותאים SW-DKK3 ב חממה humidified סטנדרטי-37.0 ° C ו- 5% CO
2
במדיום הגידול.
משתמש של hemocytometer, נחשב צלחת 100,000 תאים של SW-13, SW-Neo SW-DKK3 לכל טוב לתוך צלחות נפרדות 6-ובכן, גדלים בין לילה מדיום הגידול.
זרע צלחות. ובכן 6 עבור כל סוג התא בדקה, באמצעות לוח אחד לכל אחד הנקודות הייעודית 6 נבדק מתחת. הערה: הנקודות הזמן עשויים להשתנות עבור סוגי תאים שונים.
לאחר דגירה לילה, שטיפת תאים עם החמים PBS פעם לאחר מכן להוסיף 0.5 מ ל 1 x תא הלא-אנזימטי דיסוציאציה פתרון טוב לכל.
מערבולת את הצלחת להפיץ את הפתרון דיסוציאציה התא. וארוקן את הצלחת המיועד בנקודות זמן מוגדר ( קרי, 1, 2, 3, 5, 10 ו- 15 דקות) ולאחר מכן לשטוף עם פתרון PBS חמים 1 מ ל שלוש פעמים.
בין שוטף, טפח בעדינות את הצלחות להתנתק תאים המחוברים באופן רופף.
תשאף כל PBS הנותרים, תיקון התאים הנותרים מחובר לצלחת עם 1 מ"ל של 3.7% פורמלדהיד למשך 10 דקות.
כתם תאים עם 1 מ"ל של 0.05% קריסטל סגול במשך 30 דקות ולאחר מכן לשטוף את עודף צבע עם 1 מ ל מים יונים. Titrate השטיפה כדי לקדם את התא חזותי. הערה: בהתאם לרמת צבע ספיגת, מספר שוטף נוספים עשוי להיות נחוץ כדי לקדם את התא להדמיה.
באמצעות מיקרוסקופ אור בהגדלה x 100, לספור תאים המצורפת כל היטב על כל צלחת. הערה: שימוש בסרגלים שקוף או סימון עט בסדר מדריכים בצד התחתון של הצלחת יסייע למנוע ספירת חוזרת ונשנית לאותם התאים.
לקבוע את המספר הממוצע של תאים המצורפת לכל טוב על כל צלחת.
להשוות את הקצב של ניתוק התא בין SW-13, SW-Neo ותאים SW-DDK3 על פני תקופת זמן נתון באמצעות מבחן סטטיסטי דו-כיווני ANOVA.
Representative Results
באמצעות את מבחני לעיל, ההשפעות של ביטוי DKK3 על מורפולוגיה השלוחה תא והמאפיינים תא אדהזיה נבדקו הקו תא ACC הוקמה SW-13, במבחנה. תאים overexpressing DKK3 נוצרו כתוצאה stably transfecting SW-13 תאים עם Myc-DDK מתויגות pCMV6-הכניסה/DKK3 פלסמיד המומנט ואת איזור בשם SW-DKK3. באופן דומה, תאים stably transfected עם וקטור ריק pCMV6-כניסה היו שנוצר כפקד תרביות תאים, passaging ומוגדר בשם SW-Neo. SW-13 תאים שימשו פקד האב תאים נוספים. ביטוי של DKK3 ב- SW-DKK3 אושר ע י ה-PCR כמותי בזמן אמת, ווסטרן כתם טכניקות 8.
בקצרה, נבדקו תאים SW-13, SW-Neo SW-DKK3 היו גדל בין לילה 6 צלחות היטב על שער גולשת. התאים היו לאחר מכן קבועה עם פורמלין, מוכתם קריסטל ויולט. מאפייני השלוחה תא היו אז לכמת תחת מיקרוסקופ לכל שאר הפרמטרים המתוארים לעיל. על ניתוח, SW-DKK3 התאים מוצג פנוטיפ יותר הבדיל שהצהיר lobopodia מוגברת, קוטביות תא רב-כיווני (p = 0.01, חד-כיווני אנובה,איור 1,איור 2), רמיזות של חוסר תנועתיות כיוונית. לעומת זאת, SW-13 הורים ותאי SW-Neo מתוחזק קוטביות ומוצגים filopodia גדולה יותר מסודרים כיוון מישורי (p = 0.01, חד-כיווני אנובה,איור 1,איור 2) 8.
כדי לקבוע שאם היווצרות מוגברת lobopodia שונה מאפייני קובץ מצורף תא, ביצענו assay אדהזיה של התא. בקצרה, התאים גדלו בן לילה ובוצע ניתוק התא עם תא אנזימטי דיסוציאציה פתרון בזמן מתקדמת מרווחי עד 15 דק תאים היו ולאחר מכן קבועה עם פורמלין, מוכתם קריסטל ויולט, וספרתי באמצעות אור מיקרוסקופ. SW-DKK3 תאים הראה משיכה מצורף גדול יותר באופן משמעותי לעומת תאים SW-13 ו- SW-ניאו (p < 0.01, 2-way ANOVA,איור 3). תוצאות אלו מצביעות על DKK3 מקדמת את היווצרות lobopodia, אשר בתורו מקדם התא מצורף 8.
איור 1: ביטוי שנאכפת DKK3 הפיצולים הרחבות קרום התא.SW-13(א), SW-ניאו(B)ו- SW-DKK3(ג)התאים היו גדל על coverslips זכוכית דקה, קבוע עם פורמלין, מוכתם קריסטל ויולט, עם תמונה. Photomicrographs נלקחים באמצעות מיקרוסקופ אור בהגדלה x 400. תאים SW-13 ו- SW-Neo נוצרו בעיקר filopodia (חץ אדום) והרחבות תא lamellipodia (arc כחול). לעומת זאת, תאים SW-DKK3 נוצרו יותר lobopodia (arcs ירוק קטן), עם היעדר ליד lamellipodia, מעט מאוד filopodia. בעוד התאים(B)SW-13(א)ו- SW-Neo מופיע להיות מקוטב (כתום חצים) עם filopodia בחוד, lamellipodia בקצה לקרטע, SW-DKK3 תאים(ג)הראה המתפלג lobopodia רב-כיווני. הניסויים בוצעו ב כפילויות.אנא לחץ כאן כדי להציג גירסה גדולה יותר של הדמות הזאת.
איור 2: DKK3 מקדמת את היווצרות lobopodia.הייצוג היחסי של filopodia, lobopodia ו- lamellipodia עבור כל תא עבור כל סוג התא חושבו באמצעות ליווח תא שלוחות תאים בודדים. בתאים photomicrographs עשרים בתחום מיקרוסקופיים נלקח באופן אקראי של תצוגות (400 x הגדלה) של SW-13, SW-Neo SW-DKK שימשו כמת. קווי שגיאה המצוין סטיית תקן ומציין (*) p < 0.01 באמצעות של אנובה בכיוון אחד המייצג עלייה משמעותית במספר lobopodia בתאים SW-DKK. סכום כולל של 20 תאים נבדקו עבור כל סוג התא שנבדקו, הניסויים בוצעו ב כפילויות.אנא לחץ כאן כדי להציג גירסה גדולה יותר של הדמות הזאת.
איור 3: DKK מקדמת אדהזיה תא.מאה אלף SW-13, SW-Neo ותאים SW-DKK3 לכל טוב של לוחות 6-ובכן היו מותר לגדל בן לילה וטופלו על ניתוק בנקודות הייעודית (ציר x). התאים הנותרים המצורפת היו קבועים, צבעונית, נספרים, האחוזים של התאים הנותרים המצורפת היו המותווים (ציר y). קווי שגיאה מציינות סטיית תקן ומציין (*) p < 0.01 ו (*) מציינת p < 0.001 שימוש של 2-way ANOVA המייצג לעליה משמעותית SW-DKK תא הכוח המצורף. ניסוי התחיל עם 100,000 תאים, הניסויים בוצעו ב כפילויות.אנא לחץ כאן כדי להציג גירסה גדולה יותר של הדמות הזאת.
Discussion
כאן נתאר במבחנהכמותיים שיטה לאפיון תא הרחבות עם נוחות, כמה נפילות בור הפארמצבטית אמין זה יכול להיות מיושם בתנאים שונים. יתר על כן, מבחני אדהזיה ו/או תנועתיות פשוטות, הניתנות לכימות, ניתן לבצע בו זמנית לתאם פוטנציאליים תפקודית משמעות השינויים שנצפו בהרחבות קרום התא.
עם זאת, שיטות אלה עשויים להציג כמה מגבלות אפשריות. ראשית, הקריטריונים שצוינו כאן כדי לזהות סוגים שונים של תאים הרחבות מבוססים על מורפולוגיה תאים SW-13 adrenocortical, ולכן סביר להניח שיהיה עליך עידון בסיווג פרמטרים כאשר חל על סוגי תאים אחרים ו/או תנאי הניסוי. יתר על כן, בניסויים זמן-קורס מורחב, ההשפעות פוטנציאלי של קרום התא סיומת. שינויים על מחזור התא ומוות תא צריכים לקחת בחשבון.
שנית, הפרוטוקול עשוי להסתמך על תגובותיהם פוטנציאלי מתקשר על ידי הבודק, אשר יכול להגביל הפארמצבטית של וזמינותו עקב הבין-הצופה וריאציה. המספר הגבוה של תאים נבדקים עבור כל קבוצה המבחן סביר מתגבר על חלק הנטיה הזו; באופן ספציפי, כאשר תאים 20 נבדקים עבור כל וזמינותו. הכללת אנשים מרובים לבצע הרחבה מתקשר באופן עיוור הוא הציע לצמצם הטיה קורא סובייקטיבית פוטנציאליים.
לבסוף, כדאי לשים לב כאשר שיוך שינויים במאפייני הקובץ המצורף, איפה גרסה מפושטת של מאפייני אדהזיה יכול להיות התוצאה של שינויים בבורר מחלקה השלוחה תא שינה העדפה מצורף תשתית במקום הקרבה שינו תשתית שנבדקו. צימוד בבורר מחלקה סיומת תא עם הגירה או פלישה בהקשר של רכיבים שונים של מטריקס הסלולר במיוחד יכול להבהיר את המאפיינים אדהזיה שנצפו.
לסיכום, פרוטוקול שמפורטות כאן מספק שיטה פשוטה ואמינה למדידת משמעות תפקודית של קרום התא מתג סיומת בתנאים מבחן שונים.
Disclosures
Acknowledgments
קרן גרנט Ohse ממומנת עבודה זו.
Materials
Name
Company
Catalog Number
Comments
Dulbecco's Modified Eagle Medium (DMEM)
ThermoFisher
11965-092
Supplemented with fetal bovine serum and penicllin and streptomycin
Deulbeco's Phosphate Buffered Saline
Sigma-Aldrich
D8537
1X solution, used directly
3.7% formaldehyde
Sigma-Aldrich
F8775
Dilute stock solution
0.05% crystal violet
Harleco
192-12
Dilute stock solution
De-ionized water
NA
NA
NA
Microscope with 400X magnification
NA
NA
NA
6-well plates
Corning
353046
NA
Cell dissociation solution non-enzymatic 1X
Sigma-Aldrich
C5914
1X solution, used directly
References
Libe, R., Fratticci, A., Bertherat, J. Adrenocortical cancer: pathophysiology and clinical management. Endocrine-related cancer . 14 (1), 13-28 (2007).
Veeck, J., Dahl, E. Targeting the Wnt pathway in cancer: the emerging role of Dickkopf-3. Biochimica et biophysica acta . 1825 (1), 18-28 (2012).
Friedl, P., Gilmour, D. Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol . 10 (7), 445-457 (2009).
Jacquemet, G., et al. L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling. Nat Commun . 7 , 13297 (2016).
Machesky, L. M., Li, A. Fascin: Invasive filopodia promoting metastasis. Commun Integr Biol . 3 (3), 263-270 (2010).
Petrie, R. J., Harlin, H. M., Korsak, L. I., Yamada, K. M. Activating the nuclear piston mechanism of 3D migration in tumor cells. J Cell Biol . 216 (1), 93-100 (2017).
Korah, R., et al. Epigenetic silencing of RASSF1A deregulates cytoskeleton and promotes malignant behavior of adrenocortical carcinoma. Molecular cancer . 12 , 87 (2013).
Cheng, J. Y., et al. A novel FOXO1-mediated dedifferentiation blocking role for DKK3 in adrenocortical carcinogenesis. BMC cancer . 17 (1), 164 (2017).
Barry, D. J., Durkin, C. H., Abella, J. V., Way, M. Open source software for quantification of cell migration, protrusions, and fluorescence intensities. J Cell Biol . 209 (1), 163-180 (2015).
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Occupational Therapist Pediatrics Providers - FLORIDA - Page 8 of 11
Browse or search the list of 1,061 registered providers whose primary or secondary taxonomy code is 225XP0200X - Occupational Therapist Pediatrics.
Occupational Therapist Pediatrics Providers - FLORIDA - Page 8 of 11
225XP0200X - Occupational Therapist Pediatrics
Occupational therapists provide services to infants, toddlers and children who have or who are at risk for developmental delays or disabilities. Occupational therapy is concerned with a child's ability to participate in daily life activities or occupations. Occupational therapists use their unique expertise to help children with social-emotional, physical, cognitive, communication, and adaptive behavioral challenges and to help children to be prepared for and perform important learning and school-related activities and to fulfill their rule as students. Through an understanding of the impact of disability, illness, and impairment on a child's development, plan, ability to learn new skills, and overall occupational performance, occupational therapists design interventions that promote healthy development, establish needed skills, and/or modify environments, all in support of participation in daily activities.
List of 1,061 registered providers with a business address in Florida whose primary or secondary health provider taxonomy code is Occupational Therapist Pediatrics, of which 295 are registered as organizations and 766 as individuals.
72% Individuals
28% Organizations
69% Female
3% Male
72%
Individual Providers (766)
28%
Medical Organizations (295)
69%
Female Providers (735)
3%
Male Providers (31)
List of Providers
Provider Name Type Address
SINDY ROBIN PASSALACQUA Individual 410 10TH AVE W
PALMETTO, FL 34221
TASVIRA PATEL Individual 8254 118TH AVE STE 100
LARGO, FL 33773
RIPAL PATEL Individual 643 LANCE CT
OVIEDO, FL 32765
JYOTI PATEL Individual 1290 WESTON RD SUITE 200
WESTON, FL 33326
ALLISON PATERSON Individual 2955 CORAL WAY
CORAL GABLES, FL 33145
VALERIE PATTERSON Individual 14391 METROPOLIS AVE SUITE 101
FORT MYERS, FL 33912
PAMELA JOY PATTON Individual 3066 JOG RD
GREENACRES, FL 33467
EILEEN ELIZABETH PAUST Individual 2178 SW MAINSAIL TER
STUART, FL 34997
PEDIATRIC CENTER FOR EXCELLENCE, LLC Organization 13241 BARTRAM PARK BLVD UNIT 209
JACKSONVILLE, FL 32258
PEDIATRIC PHYSICIAN SERVICES, INC.
ALL CHILDREN'S SPECIALTY PHYSICIANS Organization 3440 W MLK BLVDTAMPA, FL 33607
PEDIATRIC THERAPT CONNECTIONS Organization 3312 NW WILLOW CREEK DR
JENSEN BEACH, FL 34957
PEDIATRIC THERAPY ASSOCIATES Organization 15026 SOUTHFORK DR
TAMPA, FL 33624
PEDIATRIC THERAPY ASSOCIATES LLC Organization 12276 SAN JOSE BLVD SUITE 508
JACKSONVILLE, FL 32223
PEDIATRIC THERAPY ASSOCIATES OF SOUTH FLORIDA, INC.
PEDIATRIC THERAPY ASSOCIATES
Organization
447 NW 73RD AVEPLANTATION, FL 33317
PEDIATRIC THERAPY CENTER Organization 1166 KANE CONCOURSE STE 202
BAY HARBOR ISLANDS, FL 33154
PEDIATRIC THERAPY GROUP Organization 4440B 26TH ST WBRADENTON, FL 34207
PEDIATRIC THERAPY GROUP SERVICES Organization 4440B 26TH ST WBRADENTON, FL 34207
PEDIATRIC THERAPY GROUP SERVICES
MARTIN PICKETT Organization 4440 26TH ST W STE B
BRADENTON, FL 34207
PEDIATRIC THERAPY LINKS, LLC Organization 1151 SW 30TH ST STE E
PALM CITY, FL 34990
PEDIATRIC THERAPY SERVICES INC Organization 1215 E ORANGE ST
LAKELAND, FL 33801
PEDIATRIC THERAPY SERVICES, INC. Organization 206 RIDGEWOOD AVE
BRANDON, FL 33510
PEDIATRIC THERAPY SOLUTIONS, INC. Organization 5899 WHITFIELD AVE SUITE # 203
SARASOTA, FL 34243
PEDIATRICS PLUS Organization 927 GRACE AVE
PANAMA CITY, FL 32401
PEDITHERAPY INC Organization 4155 NW 64TH AVE
CORAL SPRINGS, FL 33067
PEDS & CARROTS THERAPY SERVICES, INC. Organization 8340 65TH ST
VERO BEACH, FL 32967
PEDS TO GO INC
CHILDRENFIRST HOME HEALTH CARE SERVICES Organization 4448 EDGEWATER DR
ORLANDO, FL 32804
LAURA S PELHAM Individual 1555 HOWELL BRANCH RD STE B1
WINTER PARK, FL 32789
LISA MARIE PELON Individual 12425 RACE TRACK RD SUITE 100
TAMPA, FL 33626
FANIA PENA Individual 1525 S ALAFAYA TRL SUITE 101
ORLANDO, FL 32828
HEIDI COOMER PENNELLA Individual 16546 N DALE MABRY HWY
TAMPA, FL 33618
GINA PEREA Individual 4501 MANATEE AVE W
BRADENTON, FL 34209
DANIEL PEREIRA Individual 13733 OFFICE PARK CT
HUDSON, FL 34667
DAYANA PEREZ Individual 19740 SW 116TH AVE
MIAMI, FL 33157
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PHYSICALLY SPEAKING, INC. Organization 10125 W COLONIAL DR SUITE 216
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HOLLYWOOD, FL 33026
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LONGWOOD, FL 32779
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LONGWOOD, FL 32779
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Disastrous end of Ukraine war could make EA a superpower - The East African
The world must pray it doesn't happen, but we can't rule out a nuclear response if Russia feels it is facing ruin.
Disastrous end of Ukraine war could make EA a superpower
Russian soldiers walk along a street in Mariupol on April 12, 2022. PHOTO | ALEXANDER NEMENOV | AFP
On our shores, the Russian-Ukrainian war has so far meant sharply increased food, fertiliser, and fuel prices.
In recent days, however, things have become thick. The Ukrainians seem to have put Russians on the run, though it might be temporary. In September so far, they have retaken more than 6,000 square kilometres of their land from Russian control.
Russian President Vladimir Putin has now called for the mobilisation of 300,000 troops and hinted darkly that what he sees as a western-led scheme to destroy Russia via Ukraine might be met with nuclear weapons. Putin's mobilisation has sent Russians in flight, with long queues into the countries neighbouring it and a scramble for flights out of Moscow as ticket prices skyrocket.
In April, US Defence Secretary Lloyd Austin, after visiting the Ukrainian capital Kyiv, said America wants Russia weakened so it can't invade another country again.
Russia seems to have played into America's hands, and a long-drawn war of attrition in Ukraine might be slowly bleeding it. The world must pray it doesn't happen, but we can't rule out a nuclear response if Russia feels it is facing ruin.
Until it happens, we won't know whether Russia will use nuclear weapons only in Europe, the US, or both. Also, whether the West would respond in a limited way or try to take the whole of Russia out. The whole world, too, of course, could also be nuked.
However, if the rest of the world is spared, it could alter the fate of Africa. The northern Asian continent and eastern Europe would be badly damaged and set back centuries.
If China and India are spared, they will have to recoil southward and shift everything — including most of their trade and investment — toward the Indian Ocean. A substantial chunk of it will land on Africa's eastern coast.
We would see a dramatic economic rise of the swath beginning from Port Elizabeth in South Africa, on to Durban, Maputo in Mozambique, Dar es Salaam and Tanga in Tanzania, Mombasa and Lamu in Kenya, on to Kismayo and Mogadishu in Somalia, Djibouti, Asmara in Eritrea, and Port Sudan.
The African countries that will profit from the tragedy will be those that are best prepared. The race to build and modernise ports along the East African coast might pay off then.
But that is only a small part. Countries need to invest more in logistics, lay down more fibre optic cable, build roads, and millions of houses, educate their populations, spend big on health, reform business laws, modernise banking and, most importantly, integrate their economies and open their borders to each other.
The African Continental Free Trade Area is just what the gods of Africa ordered when they peered into the future a few years ago and saw a Russia-Ukraine war on the horizon.
There will be diplomatic spoils too. A hugely disastrous end to the Russian invasion of Ukraine could leave Europe weakened, although America might emerge more imperious. That would be Africa's opportunity to seize more global power and get one of ours at the table of superpowers. But, we are a peace-loving people. We don't want to win this way.
| https://www.theeastafrican.co.ke/tea/oped/comment/disastrous-end-of-ukraine-war-could-make-ea-a-superpower-3960084 |
Beatle Girl | National Galleries of Scotland
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Vietnam Home Furniture Market - Growth, Trends, Covid-19 Impact, and Forecasts (2022 - 2027)
Vietnam Home Furniture Market - Growth, Trends, Covid-19 Impact, and Forecasts (2022 - 2027) Vietnam Home Furniture Market - Growth, Trends, Covid-19 Impact, and Forecasts - Market research report and industry analysis - 30718245
Vietnam Home Furniture Market - Growth, Trends, Covid-19 Impact, and Forecasts (2022 - 2027)
Best Price Guarantee Price from $4,750 Length 150 Pages Publisher Mordor Intelligence Inc Published Date January, 2022 SKU MOI16948141
Table of Contents
Description
Vietnam Home Furniture Market - Growth, Trends, Covid-19 Impact, and Forecasts (2022 - 2027)
Vietnam has become a preferred location to set up furniture factories and is a major base for furniture exports. Furniture from Vietnam is now exported to over 120 countries, of which the main markets are the United States, the United Kingdom, Canada, Australia, and Japan. Vietnamese furniture is also exported to China. Vietnamese consumers use a wide range of furniture products, with wooden furniture being the most common. Vietnam’s indoor and outdoor furniture industry continues to stay strong, and it is expected to remain the same in the coming years. Compared to other large furniture exporters in the world, Vietnam’s furniture industry holds production advantages in terms of the potential to expand its global market share.
Disruptions in supply chains and slowed global trade have severely impacted the Vietnamese furniture sector amidst the COVID 19 pandemic. Vietnam exported nearly USD 1 billion worth of timber products to China in 2019, but the trade faced a steep decline as a result of the coronavirus outbreak. The Vietnamese timber sector is also equally suffering as in 2019, the large value of timber products was exported from Vietnam to China with an overall trade surplus. COVID-19 conversion has caused difficulties for many businesses due to dependence on imported raw materials in the home furniture segments in the country. However, in recent years, the rise in real estate of Vietnam is clearly observed, and in the past five years, approximately 400,000-500,000 townhouses and villas have been constructed in the market studied. Domestic companies have been focusing on exports, which may open opportunities for furniture designers in the medium to long term when things return to normalcy.
This growth has been driven by greater demand from North America, Europe, and the Asia-Pacific region. Customers in the Middle East and India are particularly helping to propel the sector’s development. Furthermore, with the increasing urbanization and construction of houses, apartments, and buildings, the Vietnamese home furniture market is expected to grow during the forecast period.
Key Market Trends
Kitchen Furniture Segment
The kitchen furniture segment includes fitted kitchen units and other wooden furniture. The kitchen furniture segment is driven by increasing urbanization and remodeling of residential kitchens. Kitchen furniture and fixtures are gaining momentum in terms of investments, with consistent growth in the hotel industry, which thrives on the rise in travel and tourism.
Modular kitchen trends are also leading to higher investments in kitchen furniture in the Vietnamese home furniture market. Hoi An, in North Vietnam, is famous for offering kitchen and sophisticated hand-made kitchenware products made of bamboo or coconuts such as plate mats, wine holders, coconut bowls, and porcelain spoons.
Rise in Furniture Exports From Vietnam
Timber and furniture have become the sixth-largest export category in Vietnam, accounting for 6% of the world market share. According to the Ministry of Industry and Trade’s Import and Export Department of Vietnam, in 2020, starting seven months, the value of the wood industry rose to around USD 6.1 billion, and the majority came from the export of wooden furniture, which accounted for USD 4.4 billion(72%), up 8.5 % Y-o-Y. In June 2020, products were exported to the United States (up by 43.1 % to USD 590.9 million), China (15.6 % to USD 88.3 million), Canada (19.5 % to USD 18.8 million), and Australia (28.8 % to USD 15.3 million). The United States was the top market for Vietnam’s wood and wood product.
The industry’s strong export growth is attributed to Vietnam’s existing free trade agreements (FTAs) and ongoing trade negotiations, which provide opportunities for manufacturers of furniture and other wooden products to enhance competitiveness and boost sales.
The main challenge for the manufacturers of furniture and other wooden products is the shortage of raw materials amid the closure of natural forests and the other measures being implemented by various countries to protect their timber resources.
Competitive Landscape
The report covers major manufacturers and Vietnamese players operating in the Vietnamese home furniture market. In terms of market share, some of the major players currently dominate the market. However, with technological advancement and product innovation, mid-size to smaller companies are increasing their market presence by securing new contracts and tapping new markets. Local manufacturers face stiff competition from luxurious foreign brands entering the market, which might increase competition for already existing players.
Additional Benefits:
The market estimate (ME) sheet in Excel format
3 months of analyst support
Companies Mentioned
Market Concentration Overview
Company Profiles
1 INTRODUCTION
1.1 Study Assumptions and Market Definition
1.2 Scope of the Study
2 RESEARCH METHODOLOGY
3 EXECUTIVE SUMMARY
4 MARKET INSIGHTS AND DYNAMICS
4.1 Market Overview
4.2 Market Drivers
4.3 Market Restraints/Challenges
4.4 Market Opportunities
4.5 Porter's Five Forces Analysis
4.6 Technological Innovations in the Vietnamese Home Furniture Market
4.7 Insights on Latest Trends in Home Furniture Products
5 MARKET SEGMENTATION
5.1 By Type
5.1.1 Kitchen Furniture
5.1.2 Living-room Furniture
5.1.3 Dining-room Furniture
5.1.4 Bedroom Furniture
5.1.5 Other Furniture
5.2 By Distribution Channel
5.2.1 Home Centers
5.2.2 Specialty Stores
5.2.3 Flagship Stores
5.2.4 Online
5.2.5 Other Distribution Channels
6 COMPANY PROFILES
6.1 Market Concentration Overview
6.2 Company Profiles
6.2.1 AA Corporation
6.2.2 Truong Thanh Furniture Corporation
6.2.3 Min Duong Furniture Corporation
6.2.4 BO Concept
6.2.5 Tai Anh Import Export Company Limited
6.2.6 Woodnet
6.2.8 Ashley Furniture Industries
6.2.9 Kaiser Furniture
6.2.10 Nitori Furniture
6.2.11 Hoang MOC Furniture
6.2.12 Cam Ha Furniture
6.2.13 Duc Thanh Wood Processing JSC*
7 FUTURE OF THE VIETNAMESE HOME FURNITURE MARKET
8 DISCLAIMER
Vietnam Furniture Market - Growth, Trends, COVID-19 Impact, and Forecasts (2022 - 2027)
Vietnam Kitchen Furniture Market - Growth, Trends, COVID-19 Impact, and Forecasts (2022 - 2027)
Vietnam Home Textile Market - Growth, Trends, COVID-19 Impact, and Forecasts (2022 - 2027)
Vietnam Home Improvement Market - Growth, Trends, COVID-19 Impact, and Forecasts (2022 - 2027)
GCC Home Furniture Market - Growth, Trends, COVID-19 Impact, and Forecasts (2022 - 2027)
Poland Home Furniture Market - Growth, Trends, COVID-19 Impact, and Forecasts (2022 - 2027)
30718246 PDF E-mail From Publisher: $4,750 Multi User License (2-5 Users) Fulfilled by Publisher: $5,250 Site License Fulfilled by Publisher: $6,500 Global Site License Fulfilled by Publisher: $8,750
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2009 Trustees Report: Section V.B, Economic assumptions & methods
2009 OASDI Trustees Report
B. ECONOMIC ASSUMPTIONS AND METHODS
The basic economic assumptions are embodied in three alternatives that are
designed to provide a reasonable range of effects on Social Security’s financial status. The intermediate assumptions reflect the Trustees’ consensus expectation of an underlying general trend toward moderate economic growth throughout the projection period and the expected levels of various economic parameters. The low-cost assumptions represent a more optimistic outlook and assume relatively strong economic growth and relatively optimistic levels for other parameters. The high-cost assumptions represent a relatively pessimistic scenario, with weak economic growth, two
recessions
in the short-range period and relatively pessimistic levels for other parameters. For this report, all three sets of assumptions include an extension into the projection period of the recession that started in December 2007 with lower productivity in 2009 and unemployment peaking in 2010.
Actual economic data was available through the third quarter of 2008 at the
time the assumptions for this report were set. The data indicated that economic activity peaked in December 2007
1
with the level of output (GDP) above the long-term sustainable trend level. Economic growth subsequently weakened with the level of output reaching the sustainable trend level by the middle of 2008. The actual growth rate in real GDP was slightly negative for the third quarter of 2008 and was projected to be significantly negative for the fourth quarter in all three alternatives. For the intermediate and low-cost alternatives, the current recession was projected to be followed by a recovery period with economic growth sufficient to return output to the sustainable level, but not beyond that level. For the high-cost alternative, the economy is assumed to experience a second recession before returning only to the sustainable level of output. Under all three sets of assumptions the economy is assumed to reach and maintain a sustainable, potential trend level of output by the end of the short-range period. Economic cycles are not included in the assumptions beyond the first 10 years of the projection period because complete cycles have little effect on the long-range estimates of financial status.
For this year’s intermediate projections, real GDP growth is assumed to
decline through the second quarter of 2009. The recovery from the recession brings economic activity to the projected stable, sustainable path by the end of 2015. For 2017 and later, real GDP is projected to be about 1.4 percent lower than in the 2008 report, based on recent data and the effects of the recession. These revised economic assumptions account for about half of the estimated reduction in the program’s actuarial balance relative to last year’s report. The effect of the recession on the actuarial balance would be smaller than projected in this report if the recovery were such that economic output substantially overshoots the projected sustainable path, a phenomenon observed in some past business cycles.
The following sections 1 through 4 present the principal economic assumptions for the three alternatives that are summarized in table V.B1 . The subsequent sections 5 through 7 present additional economic factors, summarized in table V.B2 , that are critical to the projections of the future financial status of the combined OASI and DI Trust Funds.
1. Productivity Assumptions
Total U.S. economy productivity is defined as the ratio of real gross domestic
product (GDP) to hours worked by all workers.
2
The rate of change in total- economy productivity is a major determinant in the growth of average earnings. For the 40 years from 1967 to 2007, annual increases in total productivity averaged 1.7 percent, the result of average annual increases of 2.0, 1.3, 1.3, and 2.1 percent for the 10-year periods 1967-77, 1977-87, 1987-97, and 1997‑2007, respectively. However, it should be noted that this growth rate of 1.7 percent reflects a shift of employment from low (farm) to high (nonfarm) productivity sectors that is not expected to continue in the future.
Because productivity growth can vary substantially within economic cycles,
it is most useful to consider historical average growth rates for complete economic cycles. The annual increase in total productivity averaged 1.6 percent over the last five complete economic cycles (measured from peak to peak), covering the 41-year period from 1966 to 2007. The annual increase in total productivity averaged 2.2, 1.2, 1.2, 1.6, and 2.0 percent over the economic cycles 1966-73, 1973-78, 1978-89, 1989-2000, and 2000-07, respectively.
The ultimate annual increases in productivity are assumed to be 2.0, 1.7, and
1.4 percent for the low-cost, intermediate, and high-cost assumptions, respectively, and are consistent with ultimate annual increases in non-farm productivity of 2.4, 2.0, and 1.7 percent. These rates of increase are the same as those used in the 2008 report, and reflect the belief that recent strong growth in non‑farm business productivity, after the relatively poor performance from 1973 to 1995, is consistent with future long-term growth that mirrors the long-term trends of the past.
In the near term for the intermediate assumptions, the negative growth in real
GDP is assumed to continue through the first half of 2009. The quarterly change in real GDP (on an annual basis) is assumed to be ‑0.5, ‑6.0, ‑4.0, and ‑1.5 percent for 2008Q3 (i.e., the third calendar quarter of 2008), 2008Q4, 2009Q1, and 2009Q2, respectively. The total decline in real GDP from 2008Q2 to 2009Q2 is assumed to be 3.0 percent, giving this recession the largest consecutive quarterly decline in real output since the 1957‑58 recession. The economy is assumed to begin recovering in 2010 and reach its full-employment or sustainable trend level of output in 2015. The annual change in real GDP is assumed to be 1.1 percent for 2008, ‑2.2 percent for 2009, 2.4 percent for 2010, and to average about 3.6 percent over the 5‑year recovery period from 2010 to 2015. Following this pattern, the annual change in total‑economy productivity is assumed to be 1.8 percent for 2008, 0.3 percent for 2009, 2.8 percent for 2010, and to average about 1.9 percent over the 5‑year recovery period from 2010 to 2015. The annual change in total‑economy productivity then falls to its assumed ultimate annual rate of 1.7 percent in 2018 and later.
For the low-cost assumptions, the economy is assumed to experience a
milder recession and a faster recovery. The annual change in total‑economy productivity is assumed to be 1.8, 0.6, 2.9, 2.5, and 2.2 percent for 2008, 2009, 2010, 2011, and 2012, respectively, and to average the assumed ultimate annual rate of 2.0 percent thereafter. For the high-cost assumptions, the annual change in productivity decreases from 1.7 percent for 2008 to 0.0 percent for 2009. Thereafter, the annual change in productivity varies with economic cycles until reaching its ultimate growth rate of 1.4 percent for 2020.
2. Price Inflation Assumptions
Future changes in the
Consumer Price Index
for Urban Wage Earners and Clerical Workers (CPI) will directly affect the OASDI program through the
automatic cost-of-living benefit increases
. Future changes in the GDP price index (GDP deflator) affect the nominal levels of GDP, wages, self-employment income, average earnings, and
taxable payroll
.
Historically, the CPI increased at an average annual rate of 4.6
percent for the 40 years from 1967 to 2007, the result of average annual increases of 6.1, 6.3, 3.4, and 2.6 percent for the 10-year periods 1967-77, 1977-87, 1987-97, and 1997-2007, respectively. The GDP deflator increased at an average annual rate of 4.1 percent from 1967 to 2007, the result of average annual increases of 6.0, 5.5, 2.7, and 2.3 percent for the same respective 10-year periods.
The ultimate annual increases in the CPI are assumed to be 1.8, 2.8, and
3.8 percent for the low-cost, intermediate, and high-cost assumptions, respectively. These rates of increase are the same as those used in the 2008 report, and reflect a belief that future inflationary shocks will likely be offset by succeeding periods of relatively slow inflation due to persistent international competition, and that future monetary policy will be similar to that of the last 20 years, with its strong emphasis on holding the growth rate in prices to relatively low levels.
For each alternative in the 2008 report, the ultimate annual increase in the
GDP deflator was assumed to be equal to the annual increases in the CPI minus a 0.4 percentage point price differential. The price differential is based primarily on methodological differences in the construction of the two indices. For the 2009 report, the ultimate annual increase in the GDP deflator is assumed to be equal to the annual increases in the CPI minus a 0.3, 0.4, and 0.5 percentage point price differential for the low-cost, intermediate, and high-cost alternatives, respectively. Varying the ultimate projected price differential across alternatives better recognizes the historical variation in this concept. Hence, for the 2009 report, the ultimate annual increase in the GDP deflator is assumed to be 1.5 (1.8 less 0.3), 2.4 (2.8 less 0.4), and 3.3 (3.8 less 0.5) percent for the low-cost, intermediate, and high-cost alternatives, respectively.
For the intermediate assumptions, the annual change in the CPI is assumed to
decrease from 4.3 percent for 2008 to ‑1.0 and 1.7 percent for 2009 and 2010, respectively, due to the effects of the recession and a decline in the price of a barrel of oil in late 2008. The annual change in the CPI is assumed to gradually increase to 3.1 percent for 2013 as the economy recovers and the demand for oil increases. The annual change in the CPI is assumed to recede to its assumed ultimate annual increase of 2.8 percent for 2015 and later. Because the level of the CPI in 2009Q3 and 2010Q3 is not assumed to be above the level of the CPI in 2008Q3, the automatic cost‑of‑living benefit increase for 2009 and 2010 is projected to be 0.0 percent. The price differential, defined as the percent change in the CPI less the percent change in the GDP deflator, is estimated to be 2.1 percentage points for 2008 and projected to be ‑2.1 percentage points for 2009. This swing in the price differential is due to the dramatic rise of oil prices for 2008 and the subsequent fall to lower average prices for 2009. The rise and fall in oil prices affected CPI much more than the GDP deflator because oil is a much larger share of what we consume than of what we produce in the U.S. As the economy recovers, the relative price of oil rises and the price differential is assumed to average about 0.8 percentage point over the 4‑year period from 2010 to 2013. After the economy returns to full employment, the relative price of oil stabilizes and the price differential is assumed to fall to its ultimate assumed value of 0.4 percentage point for 2015 and later.
For the low-cost assumptions, the annual change in the CPI is assumed to
decrease from 4.3 percent for 2008 to ‑1.2 and 1.3 percent for 2009 and 2010, respectively. Thereafter, the annual change in the CPI is assumed to gradually increase to 2.1 percent for 2013 and then decrease to its assumed ultimate annual change of 1.8 percent for 2015. For the high-cost assumptions, the annual change in the CPI is assumed to decrease from 4.3 percent for 2008 to ‑0.4 and 2.2 percent for 2009 and 2010, respectively. Thereafter, the annual change in the CPI is assumed to gradually increase to 6.0 percent for 2013 and then decrease to its assumed ultimate annual change of 3.8 percent for 2015.
3. Average Earnings Assumptions
The average level of nominal earnings in OASDI covered employment for
each year has a direct effect on the size of the taxable payroll and on the future level of average benefits. In addition, under the automatic-adjustment provisions in the law, growth in the average wage in the U.S. economy directly affects certain parameters used in the OASDI benefit formulas and additional parameters used for the computation of the contribution and benefit base, the exempt amounts under the retirement
earnings test
, the amount of earnings required for a quarter of coverage, and under certain circumstances, the automatic cost-of-living benefit increases.
Average U.S. earnings is defined as the ratio of the sum of total U.S. wage
and salary disbursements and proprietor income to the sum of total U.S. military and total civilian household employment. The growth rate in average U.S. earnings for any period is equal to the combined growth rates for total U.S. economy productivity, average hours worked, the ratio of earnings to compensation (which includes fringe benefits), the ratio of compensation to GDP, and the GDP deflator. Assumed future growth rates in productivity and the GDP deflator are discussed in the previous two sections.
The average annual change in average hours worked was
‑0.2 percent over the last 40 years, and -0.7, -0.1, 0.3, and -0.4 percent for the 10-year periods 1967-77, 1977-87, 1987‑97, and 1997‑2007, respectively. The average annual change in average hours worked was -0.3 percent over the last five complete economic cycles covering the period from 1966 to 2007. The annual change in average hours worked averaged -0.7, -0.6, 0.0, 0.1, and ‑0.6 percent over the economic cycles 1966-73, 1973-78, 1978-89, 1989-2000, and 2000‑07, respectively.
For the 2009 report, the ultimate annual rates of change for average hours
worked are assumed to be 0.1, 0.0, and -0.1 percent for the low-cost, intermediate, and high-cost assumptions, respectively. These ultimate annual rates of change for average hours worked are the same as those assumed for the 2008 report.
The average annual change in the ratio of earnings to compensation was
‑0.2 percent from 1967 to 2007. For wage workers, the assumed ultimate annual rates of change in the ratio of earnings to compensation are -0.1, -0.2, and ‑0.3 percent for the low-cost, intermediate, and high-cost assumptions, respectively. Under the intermediate assumptions, the ratio of wages to employee compensation is projected to decline from 0.813 for 2008 to 0.695 for 2083. The ratio of compensation to GDP is assumed to be stable.
Thus, the ultimate projected annual growth rate in average U.S. earnings is
about 3.9 percent for the intermediate assumptions. This growth rate reflects assumed ultimate annual growth rates of about 1.7, -0.2, 0.0, and 2.4 percent for productivity, the ratio of earnings to compensation, average hours worked, and the GDP deflator, respectively. Similarly, the ultimate projected annual growth rate in average nominal U.S. earnings is 3.5 percent for the low-cost assumptions and 4.3 percent for the high-cost assumptions.
Over long periods of time the average annual growth rates in average U.S.
earnings and average earnings in OASDI covered employment are expected to be very close to the average annual growth rates in the average wage in OASDI covered employment (henceforth the “average covered wage”). Thus, the assumed ultimate annual growth rates in the average covered wage are 3.5, 3.9, and 4.3 percent for the low-cost, intermediate, and high-cost assumptions, respectively. For the intermediate assumptions, the annual rate of change in the average covered wage is assumed to decrease from 3.3 percent for 2008 to 0.7 percent for 2009, following the recession to its low point. As the economy recovers, the annual rate of change in the average covered wage is assumed to increase to 3.4 percent in 2010 and to average about 4.1 percent over the 5‑year period from 2011 to 2015. Thereafter, the annual rate of change in the average covered wage decreases and reaches its assumed ultimate rate of change of 3.9 percent for 2018.
4. Assumed Real-Wage Differentials
For simplicity, real increases in the average OASDI covered wage have tradi
tionally been expressed in the form of real-wage differentials—i.e., the percentage change in the average covered wage minus the percentage change in the CPI. This differential is closely related to assumed growth rates in average earnings and productivity, which are discussed in the previous sections. Over the 40-year period, 1968-2007, the real-wage differential averaged 0.8 percentage point, the result of averages of 0.5, 0.7, 0.8, and 1.4 percentage points for the 10-year periods 1968-77, 1978-87, 1988-97, and 1998‑2007, respectively. The assumed ultimate annual average covered real-wage differentials are 1.7, 1.1, and 0.5 percentage point(s) for the low-cost, intermediate, and high-cost assumptions, respectively.
Based on preliminary data, the real-wage differential is estimated to be
‑1.0 percentage point for 2008. For the intermediate assumptions, the real‑wage differential is projected to rise to 1.8 percentage points for 2009, 2010, and 2011. Thereafter, the real‑wage differential is projected to average the assumed ultimate differential of 1.1 percentage points. For the low-cost assumptions, the real‑wage differential is projected to average 2.3 percentage points for the 2009 to 2011 period, and thereafter to average the assumed ultimate differential of 1.7 percentage points. For the high-cost assumptions, the real‑wage differential is projected to average 1.4 percentage points for the 2009 to 2011 period vary with a second recession and recovery over the 2012 to 2018 period, and average the assumed ultimate differential of 0.5 percentage point thereafter.
Table V.B1.— Principal Economic Assumptions Calendar year Annual percentage change a in— Real- wage differ- ential b Productivity (Total U.S. economy) Earnings as a percent of compensation Average hours worked GDP price index Average annual wage in covered employment Consumer Price Index Historical data: 1960 to 1965 3.2 -0.2 0.2 1.4 3.2 1.2 2.0 1965 to 1970 2.0 -.4 -.7 4.1 5.8 4.2 1.6 1970 to 1975 2.1 -.7 -.9 6.7 6.6 6.8 -.2 1975 to 1980 .9 -.6 -.2 7.3 8.9 8.9 -.1 1980 to 1985 1.7 -.2 .0 5.2 6.5 5.2 1.3 1985 to 1990 1.3 .1 -.1 3.2 4.7 3.8 .9 1990 to 1995 1.1 -.2 .4 2.5 3.6 3.0 .6 1995 to 2000 2.1 .4 .1 1.7 5.3 2.4 2.9 2000 to 2005 2.4 -.6 -.8 2.5 2.7 2.5 .2 1998 2.0 .2 .7 1.1 6.1 1.3 4.7 1999 2.4 .1 .4 1.4 4.9 2.2 2.7 2000 2.2 .1 -1.1 2.2 6.1 3.5 2.6 2001 2.1 -.3 -1.3 2.4 2.0 2.7 -.7 2002 2.9 -1.5 -1.0 1.7 .7 1.4 -.7 2003 3.0 -1.0 -1.5 2.1 2.6 2.2 .4 2004 2.5 .4 .1 2.9 4.5 2.6 1.9 2005 1.4 -.4 -.2 3.3 3.6 3.5 .1 2006 .9 .4 .0 3.2 4.8 3.2 1.6 2007 1.3 .4 -.4 2.7 4.2 2.9 1.3 2008 c 1.8 -.2 -.2 2.2 3.3 4.3 -1.0 Intermediate: 2009 .3 -.2 -.1 1.1 .7 -1.0 1.8 2010 2.8 -.5 .0 1.1 3.4 1.7 1.8 2011 2.3 -.2 .0 1.5 4.1 2.3 1.8 2012 1.9 -.2 .0 1.9 4.1 2.7 1.4 2013 1.9 -.3 .0 2.2 4.2 3.1 1.1 2014 1.8 -.3 .0 2.5 4.1 3.1 1.0 2015 1.7 -.1 .0 2.4 4.2 2.8 1.4 2016 1.6 -.2 .0 2.4 3.7 2.8 .9 2017 1.6 -.2 .0 2.4 3.8 2.8 1.0 2018 1.7 -.2 .0 2.4 3.9 2.8 1.1 2015 to 2020 1.6 -.2 .0 2.4 3.8 2.8 1.0 2020 to 2083 1.7 -.2 .0 2.4 3.9 2.8 1.1 Low-cost: 2009 .6 -.2 -.1 1.0 1.3 -1.2 2.5 2010 2.9 -.4 .1 .7 3.3 1.3 2.1 2011 2.5 -.2 .1 .7 3.8 1.4 2.4 2012 2.2 -.2 .1 1.0 3.7 1.7 2.0 2013 2.0 -.2 .1 1.3 3.7 2.1 1.6 2014 1.8 -.3 .1 1.6 3.3 2.1 1.2 2015 1.9 .0 .1 1.5 3.6 1.8 1.8 2016 1.9 -.1 .1 1.5 3.4 1.8 1.6 2017 2.0 -.1 .1 1.5 3.5 1.8 1.7 2018 2.1 -.1 .1 1.5 3.6 1.8 1.8 2015 to 2020 2.0 -.1 .1 1.5 3.5 1.8 1.7 2020 to 2083 2.0 -.1 .1 1.5 3.5 1.8 1.7 High-cost: 2009 .0 -.1 -.2 1.7 .9 -.4 1.3 2010 2.7 -.5 -.1 1.4 3.4 2.2 1.2 2011 2.2 -.3 -.1 1.6 4.2 2.5 1.6 2012 .0 -.4 -.1 3.4 3.0 4.3 -1.3 2013 1.8 -.4 -.1 5.0 6.0 6.0 .0 2014 2.3 -.5 -.1 5.2 7.1 5.8 1.3 2015 1.8 -.2 -.1 4.2 6.1 4.7 1.4 2016 1.7 -.3 -.1 3.4 4.9 3.9 1.0 2017 1.3 -.3 -.1 3.3 4.3 3.8 .5 2018 1.1 -.3 -.1 3.3 4.0 3.8 .2 2015 to 2020 1.3 -.3 -.1 3.3 4.3 3.8 .5 2020 to 2083 1.4 -.3 -.1 3.3 4.3 3.8 .5
a
For rows with a single year listed, the value is the annual percentage change from the prior year. For rows
with a range of years listed, the value is the compound average annual percentage change.
b
For rows with a single year listed, the value is the unrounded annual percentage change in the average
annual wage in covered employment less the unrounded annual percentage change in the Consumer Price Index. For rows with a range of years listed, the value is the average of unrounded annual values of the differential.
c
Historical data are not available for the full year. Estimated values vary slightly by alternative and are shown for the intermediate alternative.
5. Labor Force and Unemployment Projections
The civilian labor force is projected by age, sex, marital status, and presence
of children. Projections of the labor force participation rates for each subgroup take into account the percentages of the
population
that are disabled or in the military, the levels of Social Security retirement benefits, the state of the economy, and changes in life expectancy. The projections also include a “cohort effect” that applies differences in participation rates for a cohort at a specific age (relative to earlier cohorts at the same age) to participation rates for that cohort at older ages.
The annual rate of growth in the size of the labor force decreased from an
average of about 2.1 percent during the 1970s and 1980s to about 1.1 percent from 1990 to 2008. Further slowing of labor force growth is projected due to a substantial slowing of growth in the working age population in the future—a natural consequence of the
baby-boom generation
approaching retirement and the succeeding lower-birth-rate cohorts reaching working age. Under the intermediate assumptions, the labor force is projected to increase by about 0.7 percent per year, on average, through 2018. Thereafter, the labor force is projected to increase much more slowly, averaging 0.5 percent over the 2018 to 2050 period, and 0.4 percent over the remainder of the 75-year projection period.
The ultimate projected labor force participation rates are not basic assump
tions. They are derived from a historically-based structural relationship using demographic and economic assumptions specific to each alternative. However, the participation rates are not highly sensitive to most of the demographic and economic assumptions. Thus, the projected labor force participation rates vary modestly into the future and across alternatives.
Historically, labor force participation rates have been influenced substan
tially by trends in demographics and pensions. Between the mid‑1960s and the mid‑1980s, labor force participation rates at ages 50 and over declined for males and were fairly stable for females. These overall declines were facilitated by the large numbers of workers entering the labor force from the baby-boom generation, and from the female population in general, during this period. This increasing supply of labor allowed employers to offer early-retirement options that were attractive. Between the mid‑1980s and about 1995, participation rates roughly stabilized for males and increased for females. Since 1995, however, participation rates for both sexes at ages 50 and over have generally risen significantly, reflecting a decrease in early-out options and relatively strong economic growth.
For the future, changes in available benefit levels from Social Security,
increases in the normal retirement age, and the effects of modifying the earnings test are expected to encourage work at older ages. Some of these factors are modeled directly. However, other factors, like the trend away from private defined-benefit pension plans (that often provided incentives to retire) toward defined-contribution plans, are expected to provide additional upward pressure on labor force participation rates. In addition to this shift in private pensions, the aging of the population is expected to both increase the demand for workers and, through improved health associated with greater life expectancy, improve the ability of the older population to work. Longer life expectancy will also increase the amount of assets that will be needed to live comfortably through retirement years, thus encouraging workers to stay employed longer. In order to account for these effects, which are directly or indirectly related to increases in life expectancy, projected participation rates for prime age and older males and females are adjusted upward in relation to assumed increases in life expectancy. For the intermediate projections, this adjustment for changes related to life expectancy adds about 1.4 percent to the total labor force by 2083.
For men age 16 and over, the projected age-adjusted labor force participation
rates for 2083 are 72.6, 73.0, and 73.6 percent for the low-cost, intermediate, and high-cost assumptions, respectively, compared to the 2007 level of 73.2 percent. (Age-adjusted labor force participation rates are adjusted to the 2007 age distribution of the civilian noninstitutional U.S. population.) These rates reflect the net effect of increases due to assumed improvements in life expectancy, and decreases due to higher assumed disability prevalence rates and an increasing proportion of males who are never married. For women age 16 and over, the projected age-adjusted labor force participation rates for 2083 are 60.3, 60.4, and 60.3 percent, for the low-cost, intermediate, and high-cost assumptions, respectively, compared to the 2007 level of 59.3 percent. These projections reflect the combination of decreases due to higher assumed disability prevalence rates, increases due to assumed improvements in life expectancy, and increases due to assumed changes in the proportion of females who are separated, widowed, divorced, or never married.
The unemployment rate presented in table
V.B2
is in the most commonly cited form, the civilian rate. For years through 2018, total rates are presented without adjustment for the changing age-sex distribution of the population. For years after 2018, unemployment rates are presented as total age-sex- adjusted rates (using the age-sex distribution of the 2007 civilian labor force). Age-sex-adjusted rates allow for more meaningful comparisons across longer time periods.
The total unemployment rate reflects the projected levels of unemployment
for various age-sex subgroups of the population. The unemployment rate for each subgroup is projected based on a specification (consistent with Okun’s Law) relating changes in the unemployment rate to the changes in the economic cycle, as measured by the ratio of the actual to potential GDP. For each alternative, the total unemployment rate is projected to move toward the ultimate assumed rate as the economy moves toward the long-range sustainable growth path.
The ultimate age-sex-adjusted unemployment rate for each alternative is
assumed to be reached by 2018. The ultimate assumed unemployment rates are 4.5, 5.5, and 6.5 percent for the low-cost, intermediate, and high-cost assumptions, respectively. These are the same values assumed for the 2008 report.
6. Gross Domestic Product Projections
The real growth rate in gross domestic product (GDP) equals the combined
growth rates for total employment, productivity, and average hours worked. Total employment is the sum of the U.S. Armed Forces and total civilian employment, which is based on the projected total civilian labor force and unemployment rates. For the 40-year period from 1967 to 2007, the average growth rate in real GDP was 3.0 percent, combining the approximate growth rates of 1.6, 1.7, and ‑0.2 percent for its components—total employment, productivity, and average hours worked, respectively.
For the intermediate assumptions, the average annual growth in real GDP is
projected to be 2.4 percent from 2008 to 2018, a slower rate than the 3.0 percent average observed over the historical 40‑year period from 1967 to 2007. This slowdown is primarily due to slower projected growth in total employment. For the low-cost assumptions, annual growth in real GDP is projected to average 3.1 percent over the decade ending in 2018. The relatively faster growth is due mostly to higher assumed rates of growth for employment and worker productivity. For the high-cost assumptions, real GDP is assumed to fall in the third and fourth quarters of 2008 and in the first three quarters of 2009, resulting in a total decline in real GDP for these five quarters of 4.0 percent. After 10 quarters of recovery, a second recession, with a total decline in real GDP of 2.1 percent, is assumed to begin in the second quarter of 2012 and last two quarters. After the second recession, a moderate economic recovery is assumed through 2015, with continued modest economic growth thereafter. For the high-cost assumptions, annual growth in real GDP is projected to average 1.8 percent for the decade ending in 2018.
After 2018, no economic cycles are assumed for the three alternatives.
Accordingly, projected rates of growth in real GDP are determined by the projected full-employment rate of growth for total employment, and the assumed full-employment rates of growth for total U.S. economy productivity and average hours worked. For the intermediate assumptions, the projected rate of growth for real GDP falls toward the assumed productivity growth rate because of the projected decline in labor force growth over the period. At the end of the 75‑year projection period, the annual growth in real GDP is 2.1 percent, due to the assumed ultimate percent changes of about 0.4, 1.7, and 0.0 for total employment, productivity, and average hours worked, respectively.
7. Interest Rates
The average annual nominal and real interest rates are presented in table
V.B2
. The nominal rate is the average of the nominal interest rates for special U.S. Government obligations issuable to the trust funds in each of the 12 months of the year. Interest for these securities is generally compounded semiannually. The real interest rate (ex post) is defined to be the annual compound yield rate for investments in these securities divided by the annual rate of growth in the CPI for the first year after issuance. The real rate shown for each year reflects the actual realized (historical) or expected (future) annual real yield on securities issuable in the prior year.
In developing a reasonable range of assumed ultimate future real interest
rates for the three alternatives, historical experience was examined for the 40 years, 1968-2007, and for each of the 10-year subperiods, 1968-77, 1978-87, 1988-97, and 1998-2007. For the 40-year period, the real interest rate averaged 2.8 percent per year. For the four 10-year subperiods, the real interest rates averaged 0.4, 4.1, 4.2, and 2.6 percent, respectively. The assumed ultimate real interest rates are 3.6 percent, 2.9 percent, and 2.1 percent for the low-cost, intermediate, and high-cost assumptions, respectively, and are unchanged from the 2008 report. These ultimate real interest rates, when combined with the ultimate CPI assumptions of 1.8, 2.8, and 3.8 percent, yield ultimate nominal interest rates of about 5.4 percent for the low-cost assumptions, about 5.7 percent for the intermediate assumptions, and about 5.9 percent for the high-cost assumptions. These ultimate nominal rates are assumed to be reached by the end of the short-range period.
The actual average annual nominal interest rate is 4.7
percent for 2007. The annual rate of change in the CPI is assumed to be 4.3 percent for 2008. Hence, the annual real interest rate is 0.4 percent for 2008. For the next 10-year short-range projection period, nominal interest rates are projected based on changes in the business cycle and in the CPI. Under the intermediate assumptions, the nominal interest rate is projected to decline from an actual value of 3.6 percent for 2008 to 3.0 percent for 2009, reflecting a weak economy along with a negative rate of inflation. Thereafter, the nominal interest rate rises to the ultimate assumed level of 5.7 percent for 2018. For the low-cost assumptions, the average annual nominal interest rate is assumed to reach an ultimate level of about 5.4 percent for 2017. For the high-cost assumptions, it is assumed to peak at 8.6 percent for 2014, and then decline to an ultimate rate of about 5.9 percent by 2018.
Table V.B2.— Additional Economic Factors Calendar year Average annual unemployment rate a Annual percentage change b in— Average annual interest rate Labor force c Total employment d Real GDP e Nominal f Real g Historical data: 1960 to 1965 5.5 1.3 1.6 5.0 4.0 2.5 1965 to 1970 3.9 2.2 2.1 3.4 5.9 1.0 1970 to 1975 6.1 2.5 1.5 2.7 6.7 .0 1975 to 1980 6.8 2.7 2.9 3.7 8.5 -.9 1980 to 1985 8.3 1.5 1.5 3.2 12.1 6.9 1985 to 1990 5.9 1.7 2.0 3.3 8.5 5.1 1990 to 1995 6.6 1.0 .9 2.5 7.0 4.3 1995 to 2000 4.6 1.5 1.8 4.1 6.2 3.9 2000 to 2005 5.4 .9 .7 2.3 4.6 2.4 1998 4.5 1.0 1.4 4.2 5.6 5.3 1999 4.2 1.2 1.5 4.4 5.9 3.4 2000 4.0 2.3 2.5 3.7 6.2 2.4 2001 4.7 .8 .0 .8 5.2 3.5 2002 5.8 .8 -.3 1.6 4.9 3.9 2003 6.0 1.1 1.0 2.5 4.1 2.6 2004 5.5 .6 1.1 3.6 4.3 1.5 2005 5.1 1.3 1.7 2.9 4.3 .8 2006 4.6 1.4 1.8 2.8 4.8 1.1 2007 4.6 1.1 1.1 2.0 4.7 1.9 2008 h 5.7 .8 -.4 1.1 3.6 .4 Intermediate: 2009 8.2 .3 -2.3 -2.2 3.0 4.7 2010 8.8 .3 -.4 2.4 4.0 1.3 2011 7.9 1.0 2.0 4.3 5.0 1.6 2012 6.8 1.1 2.2 4.2 5.7 2.3 2013 6.2 1.0 1.7 3.6 6.0 2.6 2014 5.8 .9 1.2 3.0 6.0 3.0 2015 5.6 .7 .9 2.7 5.7 3.2 2016 5.5 .6 .6 2.2 5.6 2.9 2017 5.5 .6 .6 2.2 5.6 2.8 2018 5.5 .5 .5 2.2 5.7 2.8 2020 5.5 .4 .5 2.1 5.7 2.9 2025 5.5 .5 .5 2.1 5.7 2.9 2030 5.5 .5 .5 2.2 5.7 2.9 2035 5.5 .5 .5 2.2 5.7 2.9 2040 5.5 .5 .5 2.2 5.7 2.9 2045 5.5 .5 .5 2.2 5.7 2.9 2050 5.5 .5 .5 2.1 5.7 2.9 2055 5.5 .4 .4 2.1 5.7 2.9 2060 5.5 .4 .4 2.1 5.7 2.9 2065 5.5 .4 .4 2.1 5.7 2.9 2070 5.5 .4 .4 2.1 5.7 2.9 2075 5.5 .4 .4 2.1 5.7 2.9 2080 5.5 .4 .4 2.1 5.7 2.9 2085 5.5 .4 .4 2.1 5.7 2.9 Low-cost: 2009 7.8 .5 -1.7 -1.2 3.3 4.9 2010 8.2 .5 .1 3.1 3.8 2.0 2011 7.1 1.2 2.4 5.1 4.6 2.4 2012 5.8 1.3 2.6 5.0 5.2 2.9 2013 5.0 1.2 2.0 4.2 5.5 3.1 2014 4.8 1.0 1.2 3.1 5.3 3.4 2015 4.7 .8 .9 3.0 5.1 3.5 2016 4.6 .7 .8 2.9 5.3 3.3 2017 4.5 .7 .7 2.8 5.4 3.5 2018 4.5 .6 .6 2.8 5.4 3.6 Low-cost: (Cont.) 2020 4.5 0.6 0.6 2.7 5.4 3.6 2025 4.5 .5 .5 2.6 5.4 3.6 2030 4.5 .6 .6 2.7 5.4 3.6 2035 4.5 .7 .6 2.8 5.4 3.6 2040 4.5 .7 .7 2.8 5.4 3.6 2045 4.5 .8 .8 2.9 5.4 3.6 2050 4.5 .8 .8 2.9 5.4 3.6 2055 4.5 .8 .8 2.9 5.4 3.6 2060 4.5 .8 .8 2.9 5.4 3.6 2065 4.5 .8 .8 2.9 5.4 3.6 2070 4.5 .8 .8 2.9 5.4 3.6 2075 4.5 .8 .8 2.9 5.4 3.6 2080 4.5 .8 .8 2.9 5.4 3.6 2085 4.5 .8 .8 2.9 5.4 3.6 High-cost: 2009 8.5 .1 -2.8 -3.0 3.3 4.1 2010 9.3 .1 -.8 1.8 4.1 1.1 2011 8.3 .8 1.9 4.1 5.1 1.6 2012 7.9 .8 1.2 1.1 5.5 .8 2013 8.5 .4 -.2 1.5 7.6 -.3 2014 7.9 .6 1.3 3.5 8.6 1.8 2015 7.3 .7 1.3 3.0 7.3 3.9 2016 6.9 .6 1.0 2.6 6.5 3.4 2017 6.6 .6 1.0 2.2 6.2 2.7 2018 6.5 .5 .6 1.6 5.9 2.4 2020 6.5 .4 .4 1.6 5.9 2.1 2025 6.5 .4 .4 1.7 5.9 2.1 2030 6.5 .4 .4 1.7 5.9 2.1 2035 6.5 .4 .4 1.7 5.9 2.1 2040 6.5 .3 .3 1.6 5.9 2.1 2045 6.5 .2 .2 1.5 5.9 2.1 2050 6.5 .1 .1 1.4 5.9 2.1 2055 6.5 .1 .1 1.3 5.9 2.1 2060 6.5 .0 .0 1.3 5.9 2.1 2065 6.5 .0 .0 1.3 5.9 2.1 2070 6.5 -.1 -.1 1.2 5.9 2.1 2075 6.5 -.1 -.1 1.2 5.9 2.1 2080 6.5 -.1 -.1 1.2 5.9 2.1 2085 6.5 -.1 -.1 1.2 5.9 2.1
a
The unemployment rates for 2019 and later are adjusted to the age-sex distribution of the civilian labor force in 2007. All other rates are unadjusted.
b
For rows with a single year listed, the value is the annual percentage change from the prior year. For rows
with a range of years listed, the value is the compounded average annual percentage change.
c
The U.S. civilian labor force concept is used here.
d
Total of civilian and military employment in the U.S. economy.
e
The real GDP (gross domestic product) is the value of total output of goods and services in 2000 dollars.
f
The average annual nominal interest rate is the average of the nominal interest rates, which, in practice, are
compounded semiannually, for
special public-debt obligations
issuable to the trust funds in each of the 12 months of the year.
g
The average annual real interest rate reflects the realized or expected annual real yield for each year on securities issuable in the prior year.
h
Historical data are not available for the full year. Estimated values vary slightly by alternative and are shown for the intermediate assumptions.
1
Determination of the December 2007 Peak in Economic Activity
, Business Cycle Dating Committee, National Bureau of Economic Research (NBER). Access date March 3, 2009.
http://www.nber.org/cycles/dec2008.html
2
Historical levels of real GDP are from the Bureau of Economic Analysis’ (BEA) National Income and
Product Accounts (NIPA). Historical total hours worked is an unpublished series provided by the Bureau of Labor Statistics (BLS), and is for all U.S. Armed Forces and civilian employment.
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Journal of Historical Sociology
Journal of Historical Sociology | Citations: 163 | The Journal of Historical Sociology was founded in 1988 on the conviction that historical and social studies ultimately have a common subject matter and can only benefit from the interchange of ideas and perspectives. Edited by a distinguished international panel of... | Read 605 articles with impact on ResearchGate, the professional network for scientists.
Journal of Historical Sociology
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Online ISSN: 1467-6443
Print ISSN: 0952-1909
Publications
Criminal Sittings - Rape in the Colony, New Zealand, 1862
Article
Michelle Erai
In 1862 His Honor, Justice Johnston, issued his instructions to the jury of the New Zealand Supreme Court for two simultaneous rape trials – the alleged rape of a European woman by two Māori men, and an alleged “assault with intent to commit a rape” of a Māori woman by a European man. This article argues that those instructions should be read within an historiographical critique of British colonial expansion, print capitalism and violence. Drawing on feminist postcolonial theorizing the question posed here, is, “What is the historical, ideological context for a newspaper reporting of the possible rape of a Māori woman in 1862?
The Civilizing and Sportization of Gaelic Football in Ireland: 1884-2009
Article
John Connolly
Paddy Dolan
Over the course of the last 125 years the sport of Gaelic football in Ireland has undergone a sportization and civilizing process as the rules governing the sport became stricter and players developed greater levels of self-control. However, the civilizing of Gaelic football was a particularly fragile and uneven process. The growing social desire to diminish displays of violence was moderated by ambivalence towards violence. Gradually the external social controls on players increased and, greater and more stable levels of internalization occurred reflected by more advanced levels of player self-restraint in the control of violence. At the same time the threshold of shame toward displays of violence advanced. This transformation was shaped by lengthening chains of social interdependencies in Ireland.
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"A Strike of Girls": Gender and Class in the British Metal Trades, 1913
Article
Clifford L. Staples
William G. Staples
Our intent is to investigate the nature of capitalist patriarchy by writing women workers back into the story of the Black Country Strike. Conventional accounts of this important conflict in the British midlands have depicted the outcome as a “victory for the workpeople,” but such claims have failed to capture how gender hierarchies and cross-class allegiances produced this “victory.” Specifically, we argue that unquestioned assumptions about the subordinate status of women provided the point of agreement around which working-class men, their union, and their employers worked out their (class) differences, resulting in both the preservation of capitalism and the reassertion of male superiority and authority.
A Special Kind of Married Man: Notions of Marriage and Married Men in the Swedish Gay Press, 1954-1986
Article
Hanna Bertilsdotter Rosqvist
There has long been ambivalence in the LGBT movement and related research as to the meaning of gay identity in relation to marriage. The article explores changing homonormative discourses of marriage and married men within the Swedish gay press from the mid 1950s to the mid 1980s. Expressions of the changes are a shift in language and in views of extramarital relationships, openness, and gay male identity. As a result of the shift, “married men,” including both “married homosexuals” and “bisexuals,” came to be distinguished from “gays.”
13 Citations
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Outdoor Brothel Culture: The Un/Making of a Transsexual Stroll in Vancouver's West End, 1975-1984
Article
Becki L. Ross
In the mid-1970s, following a series of police raids on prostitution inside downtown nightclubs, a community of approximately 200 sex workers moved into Vancouver's West End neighborhood, where a small stroll had operated since the early 1970s. This paper examines the contributions made by three male-to-female (MTF) transsexuals of color to the culture of on-street prostitution in the West End. The trans women's stories address themes of fashion, working conditions, money, community formation, violence, and resistance to well-organized anti-prostitution forces. These recollections enable me to bridge and enrich trans history and prostitution history – two fields of inquiry that have under-represented the participation of trans women in the sex industry across the urban West. Acutely familiar with the hazards inherent in a criminalized, stigmatized trade, trans sex workers in the West End manufactured efficacious strategies of harm reduction, income generation, safety planning, and community building. Eschewing the label of “victim”, they leveraged their physical size and style, charisma, contempt towards pimps, earning capacity, and seniority as the first workers on the stroll to assume leadership within the broader constituency of “hookers on Davie Street”. I discover that their short-lived outdoor brothel culture offered only a temporary bulwark against the inevitability of eviction via legal injunction in July 1984, and the subsequent rise in lethal violence against all prostitutes in Vancouver, including MTF transsexuals.
Accounting for the Contribution of Vitamin B to Canada's WWII Effort
Article
Robyn Braun
Canada began to fortify its flour and bread with vitamin B when it entered the Second World War. The decision was informed by the biology of vitamin B and therefore I suggest that the complexity of this political maneuver can best be understood by considering the specificity of the biochemistry of vitamin B. In this paper I will show that the specific biology of vitamin B allowed the Canadian government the possibility of a healthier population under wartime conditions but also allowed the government a variety of means by which to develop and organize food processing practices to this end.
"That was Then, but This is Now": Historical Perspectives on Intercountry Adoption and Domestic Child Adoption in Australian Public Policy
Article
Denise Cuthbert
Ceridwen Spark
Kate Murphy
This paper brings historical perspectives to bear on the ambivalent and contradictory position of adoption in Australian public policy. It examines the divergent histories of Australian domestic and intercountry adoption (ICA) since the mid-1970s and the impact of these histories on adoption policy in Australia. It identifies tendencies in contemporary ICA to repeat elements of pre-reform era domestic adoption. In particular, it is argued that the resistance of ICA to the move to openness in local adoption has been an unacknowledged driver of ICA for many Australian families. We offer corrective readings of the rise of ICA in relation to domestic adoption and conclude by offering alternatives for adoption policy which better align the two kinds of adoption, focusing on the needs of children, as distinct from the desires of adults.
“The Necessity for Better Bodies to Perpetuate Our Institutions, Insure a Higher Development of the Individual, and Advance the Conditions of the Race.” Physical Culture and the Formation of the Self in the Late Nineteenth and Early Twentieth Century USA
Article
Jürgen Martschukat
This article explores the significance of sports and physical exercise in the turn-of-the-century culture and society of the U.S. It depicts how physical fitness became a decisive feature of collective and individual self-perception and was understood as being at the core of a successful shaping of both the self and of the American body politic. I concentrate in particular on paradigms and strategies of human resources management to exemplify the overarching significance of physical fitness as it established itself at the heart of the USA's enterprise culture that began to emerge in the later nineteenth century. American peculiarities will be considered, alongside ties and allusions to European, and particularly British, developments.
The Lips of the Dead and the ‘Kiss of Life’: The Contemporary Deathbed and the Aesthetic of CPR
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John Tercier
Over the last four decades, cardiopulmonary resuscitation (CPR) has become the medical, legal and media standard for behaviour in the face of sudden death. The key therapeutic techniques of CPR: mouth–to–mouth ventilation, external–cardiac–compressions and defibrillation – with their origins in the eighteenth century, strange peregrinations in the nineteenth, and consolidation in the twentieth – are central to what may be seen as a newly dominant form of deathbed ritual.
Anti-Racism in Movement: Afro-Brazilian Afoxe and Contemporary Black Brazilian Struggles for Equality
Alexandre Emboaba da Costa
This paper examines the Afro-Brazilian afoxé as a form of cultural struggle that critically contests narratives and practices that reproduce racial inequality in contemporary Brazil. Through their afoxé in the interior of São Paulo, the Orùnmilá Cultural Center mobilizes Afro-Brazilian knowledge and cultural practices to challenge culturalist treatments of Afro-Brazilian "difference" in the management and representation of carnaval. I explore how such treatments reflect broader state-orchestrated attempts to undermine black anti-racism and the implementation of substantive policies to address racial inequality in various spheres, including education and culture. The afoxé and the Orùnmilá Center's broader work constitute an important, contemporary means through which black organizations in Brazil make visible and vocal public claims for representation and self-determination. Such work pushes policy-makers and academics to reinterpret the terms of black inclusion vis-à-vis subaltern or "other" cultures, historical experiences, perspectives, and participation in societal transformation.
Freud: instinctivist or behaviorist? The mirages of American sociology.
H Sebald
1 Citation
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Society and Housing Form: Home-Centredness in England vs. Family-Centredness in Japan
Ritsuko Ozaki
This paper demonstrates some of the ways in which culture affects house form by considering the premise that increased privatised living leads to increased demarcation of private living space. Historical data from England and Japan make it evident that Japanese privatised living was family-centred as compared with English home-centredness, and was reflected in observable differences in the evolution of house forms. While supporting the premise that cultural values influence house forms, the paper concludes that the original framework is too simple, but can be developed to accommodate data from different cultures.
The 'Liberal State': Civil Society and Social Welfare in Nineteenth-Century England
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Alan Kidd
Alan J. Kidd. The "liberal state": civil society and social welfare in nineteenth-century England. Journal of Historical Sociology, 2002, vol. 15, no. 1, pp. 114-119. Published by and copyright Wiley-Blackwell Publishing. The definitive version of this article is available from http://www.blackwell-synergy.com/
The Medicalization of Sunlight in the Early Twentieth Century
Simon Carter
This paper traces the emergence of the therapeutic use of sunlight in medicine during the first half of the twentieth century. This was a period of considerable flux in medicine with various strands of practice and theory competing. Drawing on two case studies of sunlight therapy, both artificial (actinotherapy) and natural (heliotherapy), in the treatment of rickets and tuberculosis this paper will explore how medicine was constituted within these regimes. The paper will argue that therapeutic and clinical applications of sunlight helped establish an association between sunlight and health but also defined a particular and specific performance of medicine.
Professions and the Identification of Mental Incapacity in Eighteenth-Century Scotland
Robert Houston
Eighteenth-century Scottish legal procedures to investigate the mental capacity of an individual to manage his or her own affairs are examined to discover the relative significance of different professional and lay groups in identifying disabilities. The role of medical men, lawyers and non-professionals is set in the context of contemporary social and political priorities in order to question simple models of medicalisation. A substantial body of empirical evidence is used to reveal the subtle gradations of power in different domestic, legal and institutional domains.
"To Rid Oneself of the Uninvited Guest": Robert Koch, Sergei Winogradsky and Competing Styles of Practice in Medical Microbiology
Frederick Thomas Attenborough
Does an infectious disease have one, singular pathogenic cause, or many interacting causes? In the discipline of medical microbiology, there is no definitive theoretical answer to this question: there, the conditions of aetiological possibility exist in a curious tension. Ever since the late 19th century, the “germ theory of disease”–“one disease, one cause”– has co-existed with a much less well known theory of “multifactorality”–“one disease, many interacting causes”. And yet, in practice, it is always a singular and never a multifactorial aetiology that emerges once the pathogenic world is brought into the field of medical perception. This paper seeks to understand why. Performing a detailed, genealogical reading of the 2003 severe acute respiratory syndrome (SARS) outbreak, it foregrounds a set of links that connect the practical diagnostic tools at work within contemporary, 21st century laboratories to the philosophical assumptions at work within late-19th century understandings of the “germ theory of disease”.
Life Insurance, the Medical Examination and Cultural Values
Ray Jureidini
Kevin White
This paper is concerned with the commodification of the risk of death which occurred with the development of life insurance and with the role of the medical examination in making life insurance a viable commodity. Using British and Australian data, it shows how the medical profession and the medical examination were crucial to nineteenth century life insurance institutions in the calculation of the value of human lives. Life insurance institutions combined a developing ideology of health with the knowledge of health statistics and applied both for a developing institutional finance market. The calculation and preservation of the value of individual human lives by the pooling of risks on selected lives is the service which life insurance sells and which underpins finance capital. The knowledge developed from health and morbidity statistics was a process both of social surveillance and of market-oriented monitoring for economic risk-reduction. At the level of the individual the necessity for life insurance was the dissolution of traditional community and familial support as industrial capitalism developed.
What Was Social Medicine? An Historiographical Essay
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Dorothy Porter
Roy Porter
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42 Citations
The English State and the ‘Celtic’ Peoples 1100–1400
Article
REES DAVIES
Abstract The Medieval English state had been studied by historians largely on its own terms and from its own records, enriched by an occasional reference to continental comparisons and contrasts. This will no doubt remain the primary approach; but it can be usefully supplemented by also looking at the English state through its impact on other ‘Celtic’ countries in the rest of Britain and Ireland which it brought, either permanently or temporarily, within the ambit of its power. English rule in Wales, Ireland and, briefly, Scotland can thereby serve as a mirror in which one may see refracted some of the essential qualities and mentalités of the English state itself—notably its increasingly self-consiously English character in terms of its own identity and institutions and the growing assumption that there should be a good measure of governmental uniformity and bureaucratic answerability in the lands which it had annexed. English rule in the ‘Celtic’ countries also brings into sharp focus how dependent the medieval English state was for its operation on an effective relationship between state and society; the failure to replicate that relationship substantially in Wales and Ireland showed that there was more to successful political integration than military might and governmental uniformity.
The Rise of the Information State: The Development of Central State Surveillance of the Citizen in England, 1500–2000
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Edward Higgs
This essay examines existing sociological explanations of the development of the central surveillance of citizens in the light of the English experience, and finds them wanting. Sociologists see the state using surveillance for the benefit of capitalist elites, to reimpose social control over the “society of strangers” created by industrialisation. But surveillance pre-dated industrialisation, and the development of information gathering by state elites had more to do with their own need to preserve their position both within the English polity, and international geo-politics.
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Continuity and change in a patronage society: the social mobility of British autobiographers, 1600–1750
Article
MICHAEL MASCUCH
Abstract This article describes rates and modes of intergenerational social mobility among the middle sort of people, using data derived from analysis of a sample of British autobiographical texts from the period 1600–1750. It adduces evidence indicating a strong propensity for social reproduction between generations within the group, and accounts for this propensity by looking at the ways in which individuals pursued careers throughout their lifetimes. The article shows how a network of social associations comprised largely of family and effective kin was the decisive factor in making a career, and how the basic framework of this network rarely extended beyond a person's native social-cultural milieu. I conclude that because the network was so limited, there was little opportunity for significant social mobility among the middle sort in early modern Britain.
Presbyterian Social Ties and Mobility in the Irish Sea Culture Area, 1610–1690
Article
Barry Vann
Abstract While most scholars recognize the relationship between the Scottish Kirk and the establishment of Ulster and Irish Presbyterianism in the seventeenth-century, few studies have examined the specific institutional and social ties, including the communities of the imagination, of the ministers who served in Ireland during that time. Moreover, few studies have considered the reverse flow of ministers to Scotland from Ireland and how their experiences in Ulster (the nine northern-most counties in Ireland) impacted the political landscape in south-western Scotland. This study addresses those voids in the literature.
Quakers, Tithe Opposition, and the Presbyterian National Church: The Case of Cartmel, Lancashire, c.1644–16601
Article
JAMES MAWDESLEY
This article will examine the development of the early Quaker movement in England during the 1650s, and by focusing on one north Lancashire parish, Cartmel, will seek to answer the question: why did people convert to a religious movement that undermined traditional communal worship, and which required a very public separation from one's neighbours? Disillusionment at the slow pace of religious reform, both nationally and locally, during the late 1640s and early 1650s will be highlighted as an explanation as to why a minority of inhabitants enduring a particular set of religious circumstances may have found Quakerism an attractive faith.
Virtus on Whitehall: The Politics of Palladianism in William Kent's Treasury Building, 1733–61
Article
Francis Dodsworth
Abstract The development of the modern state in the eighteenth century had a material as well as a socio-political dimension. The 1730s saw the domination of neo-Palladianism in the Office of Works and the establishment of a prominent and permanent administrative centre whose style made an architectural statement about the conduct of Walpole's government. The nature of this statement is only comprehensible when viewed in the context of contemporary political debate. William Kent's Treasury invoked antique Rome in order to emphasise the government's competence and assert the independence of its officers from patronage and their commitment to the common good.
State Form, Social Order and the Social Sciences: Urban Space and Politico‐Economic Systems 1760–1850
Article
Ann Firth
Abstract In The Pristine Culture of Capitalism, Ellen Wood argues that the English urban landscape is characterised by lack of elegance, absence of charm and neglect of public services. She traces the origins of this impoverishment to the eradication of pre-industrial capitalist urban culture in the eighteenth century. The paper investigates the claim that English urban culture underwent a significant transformation in the later eighteenth and early nineteenth century. A concern with the public magnificence of London as a means of representing the wealth and power of England is characteristic of eighteenth century treatise on urban improvement. The most influential of which, John Gwynn's London and Westminster Improved, published in 1766, draws upon the spatial linkage of economy, government and power typical of mercantilist thought. The paper argues that as the principles and practices of mercantilism were displaced by the spread of industrial capitalism and the liberal state, a concern with grandeur, elegance and embellishment in urban form was subordinated to the provision of the physical and social infrastructure necessary for the reproduction of labour.
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A “Small Great National State”: An Analysis of the Cultural and Political Factors that shaped Danish Nationalism 1760–1870
Article
Benedikte Brincker
Abstract This article provides an analysis of the cultural and political factors that shaped Danish nationalism in the late eighteenth and nineteenth century. Throughout the analysis of the development of Danish nationalism, parallels are drawn to nationalism in late eighteenth and nineteenth century Britain. Finally, consideration is given to the question of whether studies of nationalism can contribute to an understanding of national states’ attitudes towards and willingness to engage in international cooperation.
Dutchman Ghosts and the History Mystery: Ritual, Colonizer, and Colonized Interpretations of the 1763 Berbice Slave Rebellion
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BRACKETTE F. WILLIAMS
Abstract In colonial orders the most impoverished and least powerful subordinates had few opportunities to store their images of the past in forms traditionally used by historians. In this essay I explore historical interpretations of the 1763 Berbice slave rebellion presented in three rituals, the majority of whose participants are impoverished residents of rural Guyanese communities. I contrast the issues addressed in these images with those addressed in accounts of the rebellion presented in colonial and post-colonial accounts written by the colonizers and the colonized. The focus of my description and analysis is the relation between historical accounts and the social identities of those who produce them.
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Quebec and the Irish Catholic Relief Act of 1778: An Institutional Approach
KAREN STANBRIDGE
Abstract The following attempts to clarify the origins and character of the “movement” toward Catholic emancipation in the British empire by examining the negotiation of two early relief measures, the Quebec Act (1774) and the Irish Catholic Relief Act (1778), from an institutional perspective. It explores how institutions structuring Anglo-Quebec and Anglo-Irish political relations affected policy outcomes in each case, and what influence the Quebec case had on the Irish act four years later. While the Quebec Act offered a response to the Catholic question that was to assist supporters of the Irish bill, both were hard won against the inertia of institutional precedent. Neither act was accompanied by indications that greater freedoms were forthcoming. An institutional analysis thus challenges leading approaches that can represent the “movement” toward Catholic emancipation as more spontaneous and less contested than is sustained by actual events.
Identity and Nationalism in Mexico: Guerrero, 1780–18401
PETER GUARDINO
Abstract Nationalisms do not form at the expense of all previous solidarities and identities. Often nationalisms are instead based upon foundations laid by class, ethnicity, gender, or other identities. Nationalists stress identities which reinforce the unity they seek and simultaneously deny those that threaten that unity. An important part of this process consists of singling out foreigners as radically different ‘others.’The national identity constructed in late eighteenth and early nineteenth-century Guerrero, Mexico, stressed opposition to newly-defined foreigners and was intertwined with class, ethnic, religious, and political solidarities.
Soup and Supervision: the Metropolitan Watch and Clock Making Trade 1797–18171
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PAUL SUTTON
Abstract In this paper Foucaultian theory is deployed to elucidate the significance of philanthropy as a channel of power through which artisanal culture was transformed. It is my contention that in the period 1797–1817 the transformative effects of war, government taxation policy and ‘trade adventurers’ upon London's artisanal culture were reinforced by the discourse and practice of philanthropy. In order to illustrate the transformative power effects of philanthropy two significant moments in the historical sociology of metropolitan artisanal culture are examined; the 1797 and 1817 crises in the clock and watch trade.
"The Learned Br?hmen, Who Assists Me": Changing Colonial Relationships in the 18 th and 19 th Century India
Alena Alamgir
Abstract This article examines the process through which the varied and fluid relationships between English East India Company servants and Indians in the eighteenth-century transformed into rigidly racist ones in the nineteenth. At the outset, the Company's position in India was precarious and impossible to sustain without intensive help from various Indian elites and experts. Relationships created through these collaborative ties were often (but not always) accompanied by prejudice. Prejudice was frequently expressed as mistrust on the part of the Company servants who complained about Indians' untrustworthiness. Yet for decades prejudice was only one possible modality for relationships between Company servants and Indians; relational fluidity was the default. However, the steps that the Company took on to solve their “mistrust dilemma”– namely, codification of Indian knowledge and modification of Indian institutions in terms of their staffing and methods – set in motion processes that eventually eliminated relational fluidity and replaced it with prejudice as a binding social norm, thus creating a rigidly racist regime.
Sugar, Technology, and Colonial Encounters: Refashioning the Industry in the Netherlands Indies, 1800–1942
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IJMS | Free Full-Text | Nutrient-Dependent Changes of Protein Palmitoylation: Impact on Nuclear Enzymes and Regulation of Gene Expression
Diet is the main environmental stimulus chronically impinging on the organism throughout the entire life. Nutrients impact cells via a plethora of mechanisms including the regulation of both protein post-translational modifications and gene expression. Palmitoylation is the most-studied protein lipidation, which consists of the attachment of a molecule of palmitic acid to residues of proteins. S-palmitoylation is a reversible cysteine modification finely regulated by palmitoyl-transferases and acyl-thioesterases that is involved in the regulation of protein trafficking and activity. Recently, several studies have demonstrated that diet-dependent molecules such as insulin and fatty acids may affect protein palmitoylation. Here, we examine the role of protein palmitoylation on the regulation of gene expression focusing on the impact of this modification on the activity of chromatin remodeler enzymes, transcription factors, and nuclear proteins. We also discuss how this physiological phenomenon may represent a pivotal mechanism underlying the impact of diet and nutrient-dependent signals on human diseases.
Nutrient-Dependent Changes of Protein Palmitoylation: Impact on Nuclear Enzymes and Regulation of Gene Expression
by Matteo Spinelli 1 , Salvatore Fusco 1,2,* and Claudio Grassi 1,2,*
Institute of Human Physiology, Università Cattolica del Sacro Cuore, Rome 00168, Italy
Fondazione Policlinico Universitario A. Gemelli IRCSS, Rome 00168, Italy
Int. J. Mol. Sci. 2018 , 19 (12), 3820; https://doi.org/10.3390/ijms19123820
Abstract
:
Diet is the main environmental stimulus chronically impinging on the organism throughout the entire life. Nutrients impact cells via a plethora of mechanisms including the regulation of both protein post-translational modifications and gene expression. Palmitoylation is the most-studied protein lipidation, which consists of the attachment of a molecule of palmitic acid to residues of proteins.
S
-palmitoylation is a reversible cysteine modification finely regulated by palmitoyl-transferases and acyl-thioesterases that is involved in the regulation of protein trafficking and activity. Recently, several studies have demonstrated that diet-dependent molecules such as insulin and fatty acids may affect protein palmitoylation. Here, we examine the role of protein palmitoylation on the regulation of gene expression focusing on the impact of this modification on the activity of chromatin remodeler enzymes, transcription factors, and nuclear proteins. We also discuss how this physiological phenomenon may represent a pivotal mechanism underlying the impact of diet and nutrient-dependent signals on human diseases.
Keywords:
protein palmitoylation
;
nutrient-dependent signals
;
chromatin remodelers
;
transcription factors
;
epigenetics
;
It is widely established that diet- and nutrient-related signals impinge on cell physiology and play a pivotal role in the health/disease balance of human bodies [ 1 ]. Diet-derived molecules such as insulin, glucose, and fatty acids (FA) influence cell signaling and regulate both enzyme activity and gene expression through a plethora of only partially known mechanisms [ 2 , 3 , 4 ].
Carbohydrates and lipids are the main energy sources for cells and their catabolism produces metabolic intermediates such as adenosine triphosphate (ATP) and acetyl-CoA, which are also fundamental donor molecules for protein phosphorylation and acetylation, respectively [ 5 , 6 ]. Moreover, FA represent the substrate for protein acylation (also named protein lipidation), a group of post-translational modifications (PTMs) including myristoylation, prenylation, and palmitoylation ( Figure 1 ). Protein lipidation dynamically regulates cell response to extrinsic and intrinsic environmental cues [ 7 , 8 ], modulating protein stability and interaction, enzymatic activities, and protein localization [ 9 , 10 , 11 , 12 , 13 ].
In the following sections, we first summarize how FA and nutrient-dependent signals regulate protein palmitoylation. Then, we discuss the mechanisms underlying gene expression modulation by protein palmitoylation, with particular focus on nuclear proteins such as chromatin remodeler enzymes, transcription factors, and histone proteins. An increasing body of evidence from experimental models highlights the role of environmental epigenetics in disease susceptibility [
14
]. An intriguing hypothesis is that aberrant palmitoylation might represent a mechanism underlying the effects of metabolic stress on human diseases. The role of protein palmitoylation in cancer and neurological diseases will be also discussed.
2. Biochemistry of Palmitoylation and Biological Functions
Protein acylation consists in the binding of saturated or unsaturated FA to glycine, serine, lysine, or cysteine residues of proteins. The number of carbons in the fatty acid substrate determines the kind of fatty acylation. The main protein acylations occurring in cells are myristoylation, prenylation, and palmitoylation.
Myristoylation consists in the attachment of a molecule of myristate, a 14-carbon saturated fatty acid, to N-terminal glycine residues via an irreversible amide linkage, catalyzed by the ubiquitous eukaryotic enzyme
N
-myristoyltransferase (NMT) [
15
]. Point mutation experiments performed in vitro on synthetic peptides resembling the N-terminal sequences of known
N
-myristoylated proteins allowed the identification of the putative amino acid motif targeted by myristoylation (Met–Gly–X–X–X–Ser/Thr) [
16
]. Recent studies suggested that many proteins are myristoylated in human cells [
17
]. Typically, myristoylation facilitates the protein–membrane association that is required for targeting proteins in specific organelles for their biological function.
Prenylation involves the addition of prenyl groups via a thioether bond to a cysteine residue and is commonly considered an irreversible PTM [ 18 ]. Most prenylated proteins contain a conserved CAAX motif at the C-terminus (C: cysteine; A: aliphatic amino acid; X: any amino acid), where the consensus cysteine residue can be modified by the addition of farnesyl (15-carbon) or geranylgeranyl (20-carbon) groups by two different enzymes, farnesyltransferase or geranylgeranyltransferase I, respectively [ 19 ] ( Figure 1 ). About 2% of eukaryotic proteins are supposed to be prenylated [ 20 ]. Interestingly, prenylation increments the hydrophobicity of the C-terminus of proteins, increasing their capacity to interact with other proteins and cellular membranes [ 21 , 22 ].
Palmitoylation is the most studied fatty acylation, consisting in the attachment of a palmitic acid (PA) molecule, a 16-carbon saturated FA, to proteins. Palmitoylation is the only reversible fatty acylation finely modulated by a class of enzymes named palmitoyl acyltransferases (PATs) [ 23 ].
About 10% of the genome codifies for palmitoylable proteins, which all together constitute the so-called “palmitoylome”. High-throughput screening using mass spectrometry has revealed that human diseases including cancer, viral infections, and immunological and neurodegenerative disorders are associated with severe alterations in the palmitoylome [ 24 ]. Moreover, recent studies have demonstrated that nutrient-derived molecules such as insulin and fatty acids may critically change protein palmitoylation [ 25 , 26 ].
Palmitoylation was first studied for its impact on protein trafficking between the plasma membrane and the cytosol (or Golgi apparatus) but, over the years, several nuclear proteins have been identified as targets of palmitoylation, suggesting a potential role of this acylation in the control of gene expression.
Palmitoylation targets several proteins residues, including cysteine ( S -palmitoylation or N -palmitoylation when it occurs at the N-terminus of the protein) and serine ( O -palmitoylation), as illustrated in Figure 1 . The most studied enzymatic reaction involving PA is S -palmitoylation, in which PA is reversibly linked to cysteine residues using palmitoyl coenzyme A as a substrate [ 27 ] ( Figure 2 ).
Conversely, both O -palmitoylation and N -palmitoylation appear to be irreversible [ 28 , 29 , 30 ]. Finally, the epsilon-amino group of lysine has also been proposed as a possible target of palmitoylation [ 31 ].
PATs are characterized by four to six transmembrane domains and by the presence of a 51-amino acid zinc finger-like domain including an aspartate-histidine-histidine-cysteine (DHHC) motif [ 32 ]. The highly conserved DHHC domain is inside the catalytic domain and mutations of this motif box impair the palmitoyl-transfer reaction [ 33 ].
To date, seven PATs (also named DHHC proteins) expressed in yeast [ 34 , 35 ] and 23 DHHC in mammalian cells have been discovered [ 36 ].
The biochemistry of palmytoilation is still not sufficiently understood, but it has been demonstrated that PAT enzymes catalyze the addition of palmitate to proteins via a two-step mechanism. First, they bind and hydrolyze the palmitoyl-CoA, forming a chemical intermediate between enzyme and palmitate. Subsequently, the acyl group is transferred to the target protein [ 32 , 37 ].
On the other side, acyl protein thioesterases catalyze the thioester hydrolysis of palmitoylated cysteines. These enzymes are usually localized in two cellular compartments: lysosomes, as the Palmitoyl-Protein Thioesterase 1 (PPT1), or the cytosol, such as acyl-protein thioesterase 1 (APT1) and 2 (APT2) [
38
,
39
]. Recently, the α/β-Hydrolase domain-containing protein 17 (ABHD17) family has been shown to remove palmitate from NRAS [
40
]. Notably, APT1 and APT2 inhibition reduces palmitate turnover on some proteins but has no effect on NRAS or postsynaptic density (PSD)-95. Similarly, the overexpression of ABHD16A, ABHD6, or APT1/2 had a weak effect on NRAS and PSD-95 depalmitoylation. However, the expression of ABHD17A, ABHD17B, or ABHD17C accelerated the hydrolysis of palmitate. These data have also been confirmed by ABHD17A/B/C knockdown in human embryonic kidney 293T cells since NRAS palmitate turnover was strongly inhibited when all three ABHD17 proteins were simultaneously silenced [
40
].
Cycles of protein palmitoylation/depalmitoylation are essential for the modulation of many aspects of cell physiology. Moreover, the development of click chemistry-based FA probes has revealed the dynamic processes underlying several signaling pathways [
41
,
42
]. For instance, palmitoylation of the tyrosine kinase Lck induces the recruitment of the enzyme to the plasma membrane and is essential for the activation of T cell receptor signaling in human T lymphocytes [
43
]. Furthermore, the glutamate receptor activation-dependent turnover of PSD-95 palmitoylation is fundamental for the modulation of synaptic strength and plasticity in neurons [
44
].
Cycles of acylation and deacylation are also required for the plasma membrane association of RAS-family and guanine nucleotide-binding (G) proteins. The pharmacological inhibition of thioesterases is able to block RAS trafficking and repress RAS oncogenic activity [ 45 ].
Actually, the S -palmitoylated proteins lack a specific sequence motif. This peculiarity makes it difficult to predict which proteins will undergo this PTM and, therefore, requires empirical identification. In this regard, the proteomic approach has highlighted an increasing number of identified palmitoylated proteins, opening up many exciting avenues for research [ 46 ].
3. Nutrient-Dependent Regulation of Protein Palmitoylation
Diet-derived molecules can impact cell physiology through multiple mechanisms including the regulation of both protein PTM and gene expression [ 1 , 3 , 4 ]. Recently, several studies have highlighted how nutrient-dependent signals may influence metabolism by changing protein palmitoylation in several tissues. Insulin is the most important hormone controlling both carbohydrate and lipid metabolism. The main mechanism by which insulin regulates glucose uptake and energy storage involves the exposure of glucose transporter (GLUT) 4 on the plasma membrane surface [ 47 ]. The cellular localization of GLUT4 is governed by a finely regulated process of vesicle recycling [ 48 ]. This glucose transporter is predominantly expressed in adipose and muscle tissues and plays a critical role in the maintenance of glucose homeostasis and peripheral insulin sensitivity [ 49 ]. During fasting, GLUT4 is mainly maintained in intracellular compartments, but postprandial insulin stimulation promotes its translocation to the plasma membrane via the palmitoylation of cysteine 233 [ 50 ]. Accordingly, the deletion of DHHC7, the main PAT involved in GLUT4 palmitoylation, induces hyperglycemia and glucose intolerance in mice [ 51 ]. More generally, insulin can affect the palmitoylation of more than 300 proteins in human endothelial cells and defects of palmitoylation affect endothelial cell migration [ 52 ].
Proteomic analyses in adipocytes revealed a wide range of palmitoylated proteins including those involved in GLUT4 membrane translocation (e.g., insulin-regulated aminopeptidase) and the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway (e.g., JAK1 and 2; STAT1, 3, and 5A; Src homology- 2 domain containing phosphatase) [ 53 ]. This study also showed that the palmitoylation of GLUT4, IRAP, and JAK1 plays a regulatory role in adipose function and is impaired in obesity and insulin resistance.
In line with these observations, we demonstrated that feeding mice with a high-fat diet (HFD) increased the deposition of PA and altered insulin signaling in the hippocampus [
26
]. The insulin desensitization in the brain led to DHHC3 overexpression via FoxO3a activation that, together with PA accumulation, induced the hyper-palmitoylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor subunit GluA1. These molecular changes were responsible for the synaptic plasticity impairment and cognitive deficits observed in HFD-fed mice. The critical role of aberrant GluA1 palmitoylation in the HFD-related alteration of synaptic plasticity was confirmed through the overexpression of palmitoylation-deficient GluA1 and the hippocampus-specific silencing of
Zdhhc3
. Both experimental approaches prevented the impairment of synaptic plasticity and cognitive deficits in HFD-fed mice. Interestingly, the intranasal delivery of the palmitoyltransferase inhibitor 2-Bromopalmitate (2-BP) restored normal levels of GluA1 palmitoylation in the hippocampus and counteracted the impairment of learning and memory in HFD-fed mice [
26
]. This was the first evidence that the alteration of insulin signaling may impinge on the palmitoylation of neuronal proteins. Moreover, our findings revealed that preventing aberrant protein palmitoylation may counteract the brain insulin resistance-dependent impairment of synaptic plasticity.
The tight relationship between lipid metabolism and protein palmitoylation is also indicated by the high
S
-depalmitoylation activity detected in the mitochondria of mammalian cells [
54
]. These findings confirm that palmitoylation may occur in cellular compartments other than the cytosol and Golgi apparatus and suggest a role of this PTM in the regulation of mitochondrial lipid homeostasis. Accordingly, it has been demonstrated that the palmitoylation of the FA translocase CD36 modulates both its localization and activity [
55
]. Moreover, increased CD36 palmitoylation was observed in livers of mice with non-alcoholic fatty liver disease (NASH) [
53
] and was directly related to intracellular lipid accumulation in human liver biopsies obtained from patients with NASH [
56
].
Finally, protein palmitoylation is also modulated by glucose concentration in rat pancreatic islets [ 57 ]. Specifically, protein S -depalmitoylation is involved in glucose-dependent insulin secretion in β-cells [ 58 ]. Accordingly, signaling pathways inducing insulin secretion in β-cells involve numerous protein targets for acylation including receptors [ 59 ], ion channels [ 60 , 61 ], soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins [ 62 ], and G-proteins [ 63 ].
In summary, nutrient-related molecules may affect the palmitoylation of numerous proteins in different organs and cell types. Palmitoylated proteins have been mainly described in the cytosol and Golgi apparatus, although several targets have been identified in all intracellular organelles. Therefore, protein palmitoylation may represent a novel signal transduction mechanism underlying the effect of metabolic stimuli on cell physiology. Considering the pivotal role of this post-translational modification in regulating both the localization and activity of targeted proteins, emerging interest is turning to the palmitoylation of nuclear proteins in the regulation of gene expression.
4. Palmitoylation of Transcription Factors
Lipid modifications increase the proteins’ hydrophobicity and thus their tendency to associate with membranes. This may facilitate the proteins’ propensity to anchor any membranes and, in the case of transcription factors, to reach the nucleus.
This scenario occurs for all sex steroid receptors (SR), such as estrogen, progesterone, and androgen receptors, which have a highly conserved palmitoylation motif of nine amino acids [ 64 ]. Estrogen receptor (ER) α, the most characterized among the palmitoylated SR, translocates from the plasma membrane to the nucleus upon de- S -palmitoylation [ 65 ]. Proteomic studies showed that the heat shock protein 27 (Hsp27) impinges on ERα palmitoylation by promoting its interaction with the acyl transferase DHHC7 and/or DHHC21 [ 66 ]. The palmitoylation of ERα induces its binding to Caveolin-1 [ 67 ], followed by localization in lipid rafts [ 66 ] and the activation of steroid signaling leading to DNA transcription [ 68 ]. The critical role of palmitoylation in steroid signaling has been demonstrated by the transgenic mouse model of palmitoylation-deficient ERα. These animals showed fertility impairment, veins vasodilation, and endothelial repair due to the loss of receptor localization to the membrane and diminished estrogen pathway activation [ 69 ].
Recent studies have also identified the TEA domain transcription factor family (TEAD1-4) as targets of S -palmitoylation [ 70 ]. TEAD is known as a transcriptional effector of the Hippo signaling pathway, which is involved in tissue homeostasis, proliferation, and cell growth. TEADs contain three evolutionarily conserved cysteine residues (C53S, C327S, and C359S), which are palmitoylated without affecting the localization of the transcription factors [ 71 ]. Crystallography revealed that the palmitoyl group is located inside a hydrophobic pocket of TEAD2 [ 71 ]. Palmitoylation regulates the protein stability of TEADs, facilitating their interaction with the transcription co-activators Yes-associated protein (YAP) and Tafazzin (TAZ) [ 71 ]. Once activated, TEADs co-localize with YAP/TAZ in the nucleus. ChiP-seq experiments pointed out that both transcription factors co-localize on the enhancer regions of DNA [ 72 ].
Moreover, the palmitoylation of TEADs on three cysteine residues occurs in vitro even in PAT-free conditions, suggesting that these transcription factors may undergo enzyme-independent autopalmitoylation [ 70 , 73 ]. However, in vivo TEAD palmitoylation may require specific enzymes because bacterially expressed TEAD is not efficiently palmitoylated [ 71 ]. A more in-depth knowledge of the functional role of TEAD palmitoylation would be very important considering the implications of the Hippo signaling pathway in cell proliferation and cancer.
The palmitoylation of transcription factors also plays a critical role in stress-dependent gene activation [
73
]. In plants, the palmitoylation of the transcription factor MfNACsa, a member of the NAM, ATAF1/2, and CUC2 (NAC) family, regulates its localization and is part of an orchestrated signaling cascade leading to drought tolerance. In particular,
S
-palmitoylation anchors MfNACsa to the plasma membrane, whereas under drought stress MfNACsa is de-
S
-palmitoyled by the thioesterase APT1 and translocates to the nucleus [
74
]. Similarly, the fatty acylation of nuclear factor of activated T cells 5α (NFAT5a) affects its nuclear import and modulates high salt stress-mediated transcriptional activity in mammals [
75
]. Since changes of protein palmitoylation may occur in response to metabolic stress [
76
], it would be interesting to deepen the knowledge of the transcription factors whose localization and interaction with the regulatory sequences can be influenced by this post-translational modification.
5. Palmitoylation of Chromatin Remodelers and Histone Proteins
Gene expression is finely modulated through both the transcription factor activity and the chromatin organization [
77
]. Chromatin remodelers (e.g., enzymes regulating acetylation and/or methylation of histone proteins) influence the assembly of transcriptional machinery by inducing histone post-translational modifications changing the DNA architecture [
78
]. Moreover, chromatin remodelers undergo enzymatic modifications regulating their activity and localization [
79
]. The
S
-palmitoylation of histone acetyltransferase p300 is required for its accumulation at the nuclear compartment, since cell treatment with 2-BP inhibits the differentiation of neuronal cells by blocking the nuclear import of p300 [
80
].
The switch from self-renewal to the differentiation of neural stem cells is also modulated by the S -palmitoylation of the adenovirus early region 1A (E1A)-like inhibitor of differentiation 1 (EID1). Indeed, the inhibition of EID1 palmitoylation reduces its proteasome-dependent degradation and promotes its interaction with CREB-binding protein (CBP)/p300 complex, leading to decreased histone acetyltransferases activity and the suppression of differentiation genes [ 81 ].
Recently, it has been demonstrated that sirtuins, which are members of a highly conserved family of nicotinamide adenine dinucleotide (NAD + )-dependent protein deacetylases, catalyze the hydrolysis of long-chain fatty acyl groups from the lysine residues of proteins [ 82 , 83 ]. The first sirtuin discovered with the ability of removing long-chain fatty acyl groups was Plasmodium falciparum Sir2A (PfSir2A). The structure of PfSir2A revealed that this sirtuin has a hydrophobic pocket that allows interaction with the acyl group of proteins [ 84 ]. The ability of sirtuins (SIRT) to remove hydrophobic acyl modifications seems to also be conserved in mammalians. SIRT1, SIRT2, SIRT3, and SIRT6 contain a hydrophobic pocket similarly to PfSir2A, indicating that the de-fatty acylation activity is maintained among different species [ 82 , 83 , 85 ]. The de-fatty acylation activity of SIRT6 has been shown to regulate tumor necrosis factor α (TNFα) secretion [ 83 ] and RAS2/phosphatidylinositol 3-kinase (PI3K) signaling [ 86 ]. These studies highlighted the role of lysine fatty acylation in the control of protein–protein interactions. Considering the nuclear localization of SIRT1 and SIRT6 [ 87 ], the emerging the de-acylating activity of sirtuins lays the foundations for a potential novel mechanism of gene expression regulation.
Accordingly, proteomic analysis in mammalian cells revealed that several variants of histone H3 were
S
-palmitoylated at cysteine 110 [
88
]. However, the functional role of H3 palmitoylation is still unclear, as it might modulate the stability of the H3/H4 tetramer or modify the interaction between chromatin and the nuclear membrane. In addition, Zou et al. found that, upon calcium stimulation, the enzyme acyl-CoA:lysophosphatidylcholine acyltransferase (Lpcat1) catalyzed the palmitoylation of serine 47 on histone H4 (
O
-palmitoylation) [
89
]. Interestingly, this modification was found to regulate RNA polymerase II activity and to activate transcription [
89
].
However, the effects of palmitoylation on chromatin organization are not limited to histone proteins. A recent study performed in
Saccharomyces cerevisiae
showed that palmitoyltransferase Pfa4 is implicated in heterochromatin formation via the palmitoylation of the telomere-binding protein Rif1 [
90
]. The telomeres, which contain domains of heterochromatin, are bound to a fibrillar network known as the nuclear lamina. The authors found that, upon palmitoylation, Rif1 reduced the silencing of chromatin by competing with Silent Information Regulator/Repressor Activator Protein 1 (SIR/RAP1) complex for telomeric DNA binding. Thereby, Rif1palmitoylation may influence telomere anchoring, nuclear organization, and heterochromatin silencing [
91
]. Collectively, experimental evidence indicates that protein palmitoylation can be modulated by metabolic signals and may represent a novel mechanism regulating chromatin structure and gene expression. Considering both the well-established role of aberrant palmitoylation in cancer and the emerging interest toward protein palmitoylation in neurological diseases, the following sections focus on palmitoylation targets potentially linking altered metabolic signals and human diseases.
6. Palmitoylation and Cancer
Protein S -palmitoylation is implicated in a plethora of cellular mechanisms underlying the control of homeostasis in human physiology, and inappropriate regulation of this PTM results in the aberrant activation of different signaling cascades potentially involved in human diseases. The aberrant activation of PATs has been reported in a wide variety of human cancers [ 92 ]. Palmitoylated proteins include enzymes regulating proliferation, apoptosis, angiogenesis, and invasiveness [ 92 ]. Cross-referencing of a list of cancer driver genes with the results of palmitoylome studies suggests that 26% of the encoded proteins may be palmitoylated, highlighting the implication of this modification in cancer development [ 93 ]. The most studied palmitoylated protein, among those associated with cancer, is the guanosine triphosphate hydrolase (GTPase) RAS family [ 94 ]. Aberrant activation of the oncogene RAS, due to the defective regulation of palmitoylation, is present in up to 30% of cancer cases, resulting in uncontrolled cell growth and proliferation [ 95 ]. In vivo, anomalous processing of NRAS palmitoylation, a protein of the RAS family, is involved in leukemogenesis. Specifically, bone marrow cells transplanted in a mouse model are incapable of inducing cancer if they are transfected with the palmitoylation-deficient NRAS mutant [ 96 ]. The inhibition of NRAS palmitoylation prevents its normal membrane localization and hyper-activation of its downstream signaling effectors (Erk, Akt, Raf, and Ral) [ 96 ], demonstrating that oncogenic NRAS signaling requires palmitoylation-dependent membrane localization. The palmitoylation of both NRAS and H-RAS occurs in the Golgi compartment, and this PTM is regulated by a complex of PATs formed by zinc finger DHHC domain containing (ZDHHC)9 and Golgin (GOLG)A7 [ 97 ]. In mice lacking Zdhhc9 , both NRAS-mediated T-cell acute lymphocytic leukemia and chronic myelomonocytic leukemia are significantly attenuated but not completely prevented. This incomplete phenotypic suppression implicates the action of multiple PATs to palmitoylate NRAS in vivo [ 98 ]. The involvement of several PATs in the control of the RAS family activity hinders the development of a pharmacology strategy against RAS-dependent cancer progression.
In recent years, it has become well known that dysregulation of the Hippo pathway results in a cancerous phenotype. Aberrant Hippo signaling is induced by mutations or altered expression levels and activity of several Hippo pathway components [ 99 ]. Equally, deactivation of the Hippo pathway impinges on cell growth and tumors [ 100 ]. A further instance of aberrant palmitoylation-dependent control over cancer-associated proteins is provided by Scribble (SCRIB), which is implicated in the Hippo pathway. SCRIB is a tumor-suppressor protein that regulates epithelial cell polarity [ 101 , 102 ]. Hippo kinase cascade is inactivated by the loss of SCRIB, leading to the accumulation of YAP and TAZ in the nucleus, and the activation of the mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) pathways [ 103 , 104 , 105 ]. Once palmitoylated, SCRIB is stabilized in the membrane, where activates the Hippo kinase cascade and represses MAPK and AKT signaling [ 103 , 104 ]. DHHC7 has been identified, through co-immunoprecipitation (co-IP) experiments, as a primary SCRIB palmitoyltransferase [ 103 ]. Interestingly, knockout of DHHC7 led to a SCRIB mislocalization through the loss of palmitoylation and increased YAP nuclear localization and activation, causing a switch of SCRIB function from tumor-suppressor to oncoprotein [ 103 ]. Moreover, enhancing SCRIB palmitoylation by the inhibition of thioesterases caused an increase of SCRIB stability in the membrane, resulting in a decrease of tumorigenicity [ 104 ].
Another important palmitoylated factor involved in the Hippo pathway is TEADs, which have been found to be overexpressed in different types of tumors [ 106 , 107 , 108 , 109 ]. High TEAD expression levels have been observed in colorectal, breast, and prostate cancers [ 109 ]. In breast cancer cells, an upregulation of TEAD2 and a marked increase in YAP/TAZ nuclear accumulation have been observed in spite of the overall reduction of YAP/TAZ protein levels [ 110 ]. The increased expression TEAD2 resulted in an augmented binding of YAP/TAZ complex, which was retained in the nucleus leading TEAD transcriptional activity. Higher levels of TEAD2 and TEAD4 were also found in colorectal cancer, specifically in metastatic tissues, and experiments performed in vivo and in vitro have shown that knockdown of TEAD4 reduces metastasis and cell migration [ 109 ].
TEAD levels are a useful prognostic marker in cancer, and their modulation could be helpful to develop a strategy against cancer progression. In a transgenic mouse model of liver cancer mediated by YAP overexpression, transfection with a mutant TEAD lacking the DNA binding domain counteracted the YAP-induced tumor [ 111 ].
Because of the relevant roles that TEADs plays in cancer development and progression, TEAD proteins are being considered as promising therapeutic targets for antagonizing Hippo transcription under oncogenic conditions. Furthermore, a new strategy could be the development of compounds targeting the TEAD hydrophobic pocket. However, the specific acyl-transferase modulating the Hippo pathway and the target-specific effect of aberrant palmitoylation in tumor growth and invasiveness remain to be understood.
Using both computational and experimental approaches, a recent study showed that flufenamate (a nonsteroidal anti-inflammatory drug) binds a lipid pocket and inhibits TEAD transcriptional activity without disrupting YAP–TEAD interaction, but leads to decreased cell proliferation and migration [ 112 ]. Since flufenamate binds the hydrophobic pocket of TEAD, which is the portion where palmitoylation occurs, this drug may counteract cancer development and inhibit TEAD activity by preventing its palmitoylation.
7. Palmitoylation and Neurodegenerative Diseases
Palmitoylation is implicated in a series of pathologies beyond cancer, involving processes not fully understood yet. Currently, emerging evidence points to the role of aberrant palmitoylation in the onset of several neurodegenerative disorders such as Parkinson′s, Huntington (HD), and Alzheimer′s (AD) disease [
113
]. For instance, the dysfunction of D2 dopamine receptor (D2R), a G protein-coupled receptor (GPCR) crucial for the regulation of mood, reward, motor control, and cognition, is linked to schizophrenia and Parkinson’s disease [
114
,
115
]. Mutagenesis studies on D2R have identified Cys 443 as palmitoylation site required for plasma membrane-retention and protein stability of receptors [
116
]. The aberrant palmitoylation of D2R leads to dopamine dysregulation syndrome.
HD is an adult-onset neurodegenerative pathology characterized by progressive cognitive decline, motor dysfunction, and psychiatric deficit [ 117 , 118 ]. HD is an autosomal dominant disease caused by a mutation in the Huntingtin gene due to an expansion of the CAG trinucleotide repeat to more than 35 repeats, leading to an abnormal huntingtin protein (HTT) with an expanded polyglutamine in its N-terminal domain, and toxic gain of function.
HTT protein is palmitoylated at cysteine 214 (C214) by DHHC17 (also named HIP14) and DHHC13. However, upon HD mutation, the interaction between HTT and its PATs is impaired, resulting in a strong reduction of HTT palmitoylation [
119
,
120
]. It has also been demonstrated that HTT may act as a modulator of DHHC17 activity, because the activity of palmitoyl-transferase appears to be compromised upon HD mutation [
121
]. Consequently, PAT substrates are less palmitoylated, leading to neuronal toxicity. These evidences suggest that altered interactions between PATs and mutant HTT reduce palmitoylation and promote the mislocalization of HTT and other PAT substrates [
121
].
A recent study provided evidence on the involvement of palmitoylation in AD pathogenesis by proving that amyloid precursor protein (APP) is palmitoylated in vitro and in vivo, and this PTM regulates the amyloidogenic process [ 122 ]. AD is the most common form of neurodegenerative disorders characterized by the accumulation of the β-amyloid peptide (Aβ) within the brain, leading to neuronal dysfunctions, cognitive decline, and progressive memory loss [ 123 , 124 ]. Aβ peptide is generated by the sequential proteolysis of APP, and it is widely recognized that this is the crucial step in the development of AD [ 124 ]. APP is palmitoylated at C186 and C187 in the N-terminal region and regulates the trafficking of APP to the membrane, since palmitoylation-deficient APP mutants are retained in the endoplasmic reticulum. APP is palmitoylated by DHHC7 and DHHC21, and overexpression of this PAT leads to an increase of Aβ production as well as APP palmitoylation [ 122 ].
Furthermore, it has also been reported that the neuron-specific membrane-associated amyloid-precursor protein-cleaving enzyme 1 (BACE1) may be palmitoylated in several cysteine residues (C478, C474, C482, C485) by different PATs (DHHC3, DHHC4, DHHC7, DHHC15, and DHHC20) [ 125 , 126 ]. Therefore, the aberrant palmitoylation of BACE1 might promote the localization of secretase within lipid rafts and increase Aβ production [ 127 ]. Actually, APP metabolism was not affected by palmitoylation-deficient BACE1 mutants, thus indicating that BACE1 palmitoylation is not involved in Aβ production [ 128 ]. Strikingly, drugs inhibiting PAT activity decreased Aβ production, supporting the hypothesis that the palmitoylation of enzymes involved in Aβ production would be required for Aβ accumulation [ 129 , 130 ]. However, to date, the role of protein palmitoylation in AD onset and progression has still not been completely clarified. More importantly, aberrant palmitoylation might also influence neurodegeneration by targeting proteins other than APP, BACE1, and the canonical Aβ synthesis pathway.
For instance, estrogens have a wide range of beneficial actions in brain and other tissues, and alterations of the molecular pathways downstream from ER activation may increase the risk of AD [ 131 ]. An altered distribution of ERs has been observed in postmortem brains fromAD patients [ 132 ]. Furthermore, changes of ER localization from the nucleus to the cytoplasm inhibit the onset of AD in transgenic mice and in humans [ 133 , 134 ]. Studies of endogenous sex steroids depletion in wild-type female rodents have shown a significant increase of levels of soluble Aβ in the brain [ 135 ]. Furthermore, ovariectomies in numerous transgenic mouse models of AD result in the significant acceleration of Aβ pathology and the worsening of behavioral performance [ 136 ]. Moreover, female rodents treated with 17β-estradiol exhibit significantly lower Aβ accumulation as compared to females treated with a vehicle [ 137 ].
Several evidences link chromatin remodelers including sirtuins, CBP/P300, and EID1 to neurodegenerative disorders. The sirtuin pathways are strongly compromised in dementia, since a reduction of SIRT1 and SIRT3 protein levels have been observed in the AD brain. [ 138 ]. Also, in mouse models of APP and presenilin 1 overexpression, the reduction of SIRT3 has been observed [ 139 ]. The modulation of SIRT1 by activation or overexpression interferes with Aβ toxicity through its capacity to inhibit nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling [ 140 ]. Besides, CBP and P300 are mechanistically involved in the formation of amyloid-like aggregates [ 141 ] and the depletion of CBP/P300 is linked to neurodegenerative diseases [ 142 ].
SIRT1 also contributes to the pathogenesis of AD via the accumulation of the microtubule-associated protein tau. In the AD brain, tau is hyper-phosphorylated (p-tau) and forms neurofibrillary tangles. The acetylation of tau contributes to the accumulation of p-tau and the downregulation of SIRT1 increases the acetylation of tau [ 143 ] mediated by acetyltransferase p300.
Moreover, the nuclear translocation of EID1 is increased in neurons of AD brains, and EID1 overexpression in mice increments its nuclear translocation, impairing long-term potentiation (LTP) and memory. Moreover, the overexpression of EID1 results in the inhibition of CBP/p300 acetyltransferase activity and disrupts the neuronal structure, altering III-tubulin [ 144 ].
The abovementioned proteins have a role in the onset and development of neurological diseases, and, interestingly, these pathways are modulated by palmitoylation.
In recent years, an increasing number of studies have focused on the correlation between dementia and metabolic disorders such as obesity, insulin resistance, and type 2 diabetes (T2D). T2D induced the development of amyloid plaques similar to non-diabetic AD, while the pharmacological treatment of T2D reduced amyloid plaques compared to non-diabetics with similar levels of dementia [ 145 ]. Furthermore, obese patients show deficits in learning and memory as AD patients.
As discussed above, recent studies have demonstrated that diet-dependent signals may affect protein palmitoylation in different tissues, including brain areas regulating learning and memory. Moreover, restoring aberrant palmitoylation has been demonstrated to counteract brain insulin resistance-dependent cognitive decline. Based on these premises, protein palmitoylation may be a potential link between metabolic and neurodegenerative diseases. However, the lack of a specific sequence motif and the absence of a robust enrichment method hinders a more accurate understanding of palmitoylation and its regulation. Therefore, an important point is to develop high-throughput dedicated methods to study palmitoylation. The proteomic approach paired with the development of new and reliable methodologies for the recognition of palmitoylated proteins will facilitate the comprehension of the role of palmitoylation in biological functions as well as its impact on the nuclear compartment and gene regulation.
8. Conclusion and Future Perspectives
Emerging evidence indicates that protein palmitoylation is modulated by nutrient-dependent signals and may impact the regulation of gene expression. Palmitoylation plays a pivotal role in enzymatic activation and trafficking to the nucleus of proteins critically involved in chromatin organization. The idea that diet-derived molecules may directly change the chromatin architecture, as well as influence both gene activation and repression, opens the way to the study of novel mechanisms underlying the gene–environment interaction. Finally, aberrant palmitoylation has been linked to many human diseases including cancer, neurodegenerative diseases, and metabolic disorders [ 13 , 76 , 146 ]. Future studies revealing the impact of nutrients on protein palmitoylation will probably add novel layers to the knowledge on the link between nutrigenomics and age-related diseases.
Author Contributions
M.S., S.F., and C.G. conceived this review, wrote the paper, and shared the comments. All the authors approved the final version of the manuscript.
Funding
This research was funded by Università Cattolica del Sacro Cuore (Linea D.3.2-2015 and D.3.2-2017 to C.G.) and the Italian Ministry of University and Research (SIR 2014 RBSI14ZV59 to S.F.).
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Lipid modifications. Prenylation, myristoylation, and palmitoylation are the most relevant protein lipidation processes regulating the interaction of modified proteins with cellular membranes. Protein prenylation involves the transfer of either a farnesyl or a geranylgeranyl moiety to the C-terminal cysteine(s) (C, yellow) of the target protein. Myristoylation occurs on an N-terminal glycine (G, blue), while palmitoylation may target different amino acids including cysteine, serine (S, green), or lysine (K, violet). a, aliphatic amino acid; M, methionine; X, undefined amino acid; T, threonine.
Figure 1. Lipid modifications. Prenylation, myristoylation, and palmitoylation are the most relevant protein lipidation processes regulating the interaction of modified proteins with cellular membranes. Protein prenylation involves the transfer of either a farnesyl or a geranylgeranyl moiety to the C-terminal cysteine(s) (C, yellow) of the target protein. Myristoylation occurs on an N-terminal glycine (G, blue), while palmitoylation may target different amino acids including cysteine, serine (S, green), or lysine (K, violet). a, aliphatic amino acid; M, methionine; X, undefined amino acid; T, threonine.
Figure 2. Protein S -palmitoylation biochemistry. Protein S -palmitoylation is a reversible modification dynamically regulated by palmitoyl acyltransferases, which add a molecule of palmitic acid to proteins, and acylthioesterases, which catalyze protein deacylation by removing the acyl moiety.
Figure 2. Protein S -palmitoylation biochemistry. Protein S -palmitoylation is a reversible modification dynamically regulated by palmitoyl acyltransferases, which add a molecule of palmitic acid to proteins, and acylthioesterases, which catalyze protein deacylation by removing the acyl moiety.
Spinelli, M.; Fusco, S.; Grassi, C. Nutrient-Dependent Changes of Protein Palmitoylation: Impact on Nuclear Enzymes and Regulation of Gene Expression. Int. J. Mol. Sci. 2018, 19, 3820.
https://doi.org/10.3390/ijms19123820
Spinelli M, Fusco S, Grassi C. Nutrient-Dependent Changes of Protein Palmitoylation: Impact on Nuclear Enzymes and Regulation of Gene Expression. International Journal of Molecular Sciences. 2018; 19(12):3820.
https://doi.org/10.3390/ijms19123820
Spinelli, Matteo, Salvatore Fusco, and Claudio Grassi. 2018. "Nutrient-Dependent Changes of Protein Palmitoylation: Impact on Nuclear Enzymes and Regulation of Gene Expression" International Journal of Molecular Sciences19, no. 12: 3820.
https://doi.org/10.3390/ijms19123820
| https://www.mdpi.com/1422-0067/19/12/3820 |
(PDF) Fully quantum algorithm for lattice Boltzmann methods with application to partial differential equations
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Fully quantum algorithm for lattice Boltzmann methods with application to partial differential equations
Fatima Ezahra Chrit
Bryan Gard
Show all 6 authors Hide
Abstract and Figures
Fluid flow simulations marshal our most powerful computational resources. In many cases, even this is not enough. Quantum computers provide an opportunity to speedup traditional algorithms for flow simulations. We show that lattice-based mesoscale numerical methods can be executed as efficient quantum algorithms due to their statistical features. This approach revises a quantum algorithm for lattice gas automata to eliminate classical computations and measurements at every time step. For this, the algorithm approximates the qubit relative phases and subtracts them at the end of each time step, removing a need for repeated measurements and state preparation (encoding). Phases are evaluated using the iterative phase estimation algorithm and subtracted using single-qubit rotation phase gates. This method delays the need for measurement to the end of the computation, so the algorithm is better suited for modern quantum hardware. We also demonstrate how the checker-board deficiency that the D1Q2 scheme presents can be resolved using the D1Q3 scheme. The algorithm is validated by simulating two canonical PDEs: the diffusion and Burgers' equations on different quantum simulators. We find good agreement between quantum simulations and classical solutions of the presented algorithm.
QLGA with classical streaming [26]. Ry is a rotation gate by the angle θα = 2 arccos 1 − fα(xi, t) for the qubit of state |qα(xi, t). The controlled √ x gate is a native IBM gate, decomposed as a two-qubit controlled phase rotation P (π/2) gate …
QLBM solution to the diffusion equation using the Qiskit mps simulator and its comparison to classical results using 102 qubits. …
Figures - available via license: Creative Commons Attribution 4.0 International
2.3+ billion citations
F ully quantum algorithm for lattice Boltzmann methods
with application to partial differential equations
F atima Ezahra Chrit,
1, 2
Sriharsha Kocherla,
2
Bryan Gard,
3
Eugene F. Dumitrescu,
4
Alexander Alexeev,
1
and Spencer H. Bryngelson
2
1
Geor ge W. Woodruff Scho ol of Mechanic al Engineering,
Geor gia Institute of Te chnology, Atlanta, GA 30332, USA
2
School of Computational Scienc e & Engineering,
Geor gia Institute of Te chnology, Atlanta, GA 30332, USA
3
CIPHER, Geor gia Te ch Resear ch Institute, Atlanta, GA 30332, USA
4
Oak Ridge National Lab oratory, Oak Ridge, T ennessee 37831, USA
(Dated: May 15, 2023)
Fluid flow simulations marshal our most pow erful computational resources. In many cases, even
this is not enough. Quantum computers provide an opportunity to speedup traditional algorithms
for flow simulations. We show that lattice-based mesoscale numerical methods can be executed as
efficient quantum algorithms due to their statistical features. This approach revises a quantum
algorithm for lattice gas automata to eliminate classical computations and measurements at every
time step. For this, the algorithm appro ximates the qubit relative phases and subtracts them at the
end of each time step, removing a need for repeated measurements and state preparation (encoding).
Phases are evaluated using the iterativ e phase estimation algorithm and subtracted using single-qubit
rotation phase gates. This method delays the need for measurement to the end of the computation,
so the algorithm is better suited for modern quantum hardware. We also demonstrate how the
check er-board deficiency that the D1Q2 scheme presents can be resolved using the D1Q3 scheme.
The algorithm is validated b y simulating two canonical PDEs: the diffusion and Burgers’ equations
on different quantum sim ulators. We find good agreement between quantum sim ulations and classical
solutions of the presented algorithm.
I. INTRODUCTION
Solving partial differential equations (PDEs) is necessary for modeling most scientific problems. Howev er, it is
computationally expensive, especially for large domains and high-dimensional configuration spaces. F or example,
in computational fluid dynamics, the cost of performing a direct numerical simulation of turbulence increases with
Reynolds number, representing the ratio of inertial to viscous effects in the flow, as
O
(
Re 3
) [
1
]. Such high computational
expense motivates a broad category of work on ac hieving algorithmic speedups for PDE solvers.
Quantum computers are emerging as an increasingly viable tool for algorithm speedup enabled by the principles of
quantum mechanics, such as superposition and entanglement. In some cases, exponential speedups over classical
computer architectures (like that of v on Neumann) are possible [
2
,
3
]. In the sciences, algorithmic complexity
improvemen ts are seen in quantum chemistry [ 4 ], machine learning [ 5 – 7 ], finance [ 8 , 9 ], and more.
Quantum algorithms for solving PDEs hav e also gained attention. Harrow et al.
[ 10 ]
demonstrated the first quantum
algorithm, HHL, for solving linear systems of equations with exponential speedup. Such improvements can be marshaled
in the PDE space for solving discretized systems of equations via, for example, the method of lines. Childs and Liu
[ 11 ]
proposed a quantum algorithm for linear ordinary differential equations (ODEs) based on spectral methods, providing
a global approximation to the solution using linear combinations of basis functions. Childs et al.
[ 12 ]
improved the
complexity of quantum algorithms for linear PDEs using adaptiv e-order finite difference and spectral metho ds. Other
Corresponding author: shb@gatech.edu
This manuscript has been authored by UT-Battelle, LLC, under Contract No. DE-AC0500OR22725 with the U.S. Department of
Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United
States Government retains a non-exclusiv e, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this
manuscript, or allow others to do so, for the United States Gov ernment purposes. The Department of Energy will provide public access
to these results of federally sponsored research in accordance with the DOE Public Access Plan.
arXiv:2305.07148v1 [physics.comp-ph] 11 May 2023
2
approaches to solving PDEs were proposed by Berry
[ 13 ]
; for example, reducing an ODE system via discretization
and solving it via the appropriate quantum algorithms. Gaitan
[ 14 ]
used this approach to solve the 1D Na vier–Stokes
equations for the flow through a conv ergent-divergent nozzle. However, these methods require deep circuits and many
quantum gates to achiev e results comparable to what one can solve on even a modern laptop. This proves prohibitive
for most of the above-mentioned algorithms but pain ts a bright future for larger, fault-tolerant quantum devices that
can better reject gate noise.
In the near term, variational quan tum algorithms are well-suited for current NISQ (noisy intermediate-scale quan tum)
devices. For example, hybrid quan tum–classical procedures can evaluate the solution quality via a cost function using
a quantum computer and optimize v ariational parameters using a classical computer. Thus, variations methods enable
quantum algorithms with relatively shallo w gate depths and qubit counts. Bravo-Prieto et al.
[ 15 ]
introduced the
variational quan tum linear solver (VQLS), which uses the Hadamard test to solv e a linear system. Liu et al.
[ 16 ]
showed that a P oisson problem can be solved by first converting it to a linear system amenable to the Quan tum
Alternating Operator Ansatz (QAOA) algorithm. However, v ariation algorithms require a (sometimes) unclear ansatz
and do not guarantee conv ergence or speedup. The continued tension betw een these quantum algorithm threads has
contributed to improving eac h.
Because of the linearity of quantum mec hanics, quantum algorithms aiming to solve nonlinear PDEs are immature
compared to the linear case. Liu et al.
[ 17 ]
proposed the first quantum algorithm for dissipative nonlinear differential
equations using the method of Carleman linearization, which maps the system of nonlinear equations to an infinite-
dimensional system of linear differential equations, which are then solv ed using quantum linear system algorithms.
Their algorithm was tested to solve the 1D Burgers’ equation. Kyriienko et al.
[ 18 ]
used the variational method
based on differentiable quantum circuits to solv e nonlinear differential equations. Their metho d solved a quasi-1D
approximation of Navier–Stok es equations. Lubasch et al.
[ 19 ]
used multiple copies of v ariational quantum states and
tensor networks to solv e nonlinear PDEs.
Other promising numerical methods include mesoscale methods, which operate between molecular and continuum
scales. Lattice metho ds are a common example and are well suited for quantum computation because they are
intrinsically statistical, resolving only samples or probabilities of the fictitious particles they comprise. Moreover, they
are based on simple mathematical calculations and are suitable for parallel computation because interactions between
lattice nodes are linear, and non-linearity enters during a local collision step. The lattice Boltzmann method (LBM) is
a common such approach that solv es the Boltzmann transport equation. Mezzacapo et al.
[ 20 ]
developed the first
quantum simulator follo wing a lattice kinetic formalism to solve fluid dynamics transport phenomena. Todorova and
Steijl
[ 21 ]
solved the collisionless Boltzmann equation on a quantum computer, inspired b y quantum algorithms solving
the Dirac equation. Budinski
[ 22 ]
proposed a novel quantum algorithm that solv es the advection–diffusion equation by
the LBM and extended it to solve the 2D Navier–Stok es equations using stream function–vorticity formulation [
23
].
Itani and Succi
[ 24 ]
explored the Carleman linearization of the collision term of the lattice Boltzmann equation. Using
this linearization technique, Itani et al.
[ 25 ]
proposed a quantum lattice Boltzmann algorithm where collision and
streaming are both achieved by unitary ev olution.
The LBM originates from the lattice gas automata (LGA), a cellular automaton that can simulate fluid flows. A
quantum computer can be viewed as a quantum cellular automaton (QCA), where eac h cell is a quantum system with
a state depending on neighboring cells. Quantum LGA is a subclass of QCA that represents particles interacting
under physical constraints and ev olving on a lattice. The main drawback of the LGA is statistical noise, though this
vanishes when crafted for mesoscopic scales. Yepez
[ 26 ]
introduced the first quantum LGA (QLGA) algorithm for
simulating fluid flow at the mesoscopic scale using a discretized Boltzmann transport equation. This algorithm was
designed for a specialized Type-II quantum computer, proposed in the early 2000s [ 27 ]. Such computers consisted of
several small quantum computers connected b y classical communication channels, allowing qubit shifts during the
algorithm’s streaming step [
27
]. The algorithm also requires estimating the distribution functions needed to re-prepare
the quantum states at each time step. Re-preparation entails measuring each qubit at the end of each time step, a
process that substantially increases computational time on current superconducting quantum computers.
Herein, we present an approach that o vercomes the limitations of previous lattice-based quantum algorithms and
is more suitable for modern quantum hardware. The algorithm uses a quantum implementation of the streaming
step, approximates the qubit relative phases, and subtracts them at the end of each time step, a voiding repeated
encoding operations and delaying the need for measurement to the end of the computation. Validation is achiev ed via
3
collision
streaming
f 0
f 1
f 1
f 1
f 4
f 4
f 4
f 3
f 2
f 2
f 2
f 3
f 3
f 0
f 0
FIG. 1. Illustration of the two main LBM operations: collision and streaming.
implementation in Qiskit [ 28 ] and tested the diffusion and Burgers’ equations.
This manuscript contin ues as follows. Section II describ es the classical lattice gas automata and lattice Boltzmann
method. Section I II introduces the quantum counterpart of the classical LGA. Section IV presents the QLGA v ariants
we propose, including quantum streaming, the D1Q3 scheme, and a measuremen t-avoiding algorithm. W e validate
these varian ts by testing them to solve the 1D diffusion and Burgers’ equations. Last, section V compares different
quantum simulation strategies for the proposed algorithm using Qiskit and XACC.
II. CLASSICAL LA TTICE GAS
The lattice gas automata (LGA) method is a cellular automaton used to simulate fluids [
29
,
30
]. The LGA state
is described by oc cupation numb ers : Boolean variables indicating whether or not a fictitious particle is present at
a specific lattice node, moving in a certain lattice direction at a specific time. These fictitious particles obey lo cal
collision rules that conserve mass and momentum.
The main drawback of LGA is noise, whic h can be reduced by coarse-graining over large domains or time interv als,
but remains costly in computing time and memory . Instead, the LGA can be directly modeled at the mesoscopic scale
with the Boltzmann equation [
31
,
32
]. This approach is called the lattice Boltzmann method (LBM), which eliminates
the LGA noise by replacing Boolean variables with con tinuous distributions, i.e., the mean occupation numbers, also
called density distribution functions. The LBM approach replaces the collision rule with a continuous fu nction called
the collision operator. The distribution functions f α (0 ≤ f α ≤ 1) evolve in time according to the kinetic equation
f α ( r + c α ∆ t, t + ∆ t ) = f α ( r , t )+Ω α [ f α ( r , t )] , (1)
where
r
is the position of a lattice site,
c α
is the lattice velocity , ∆
t
is the time step,
t
is time, Ω
α
is the collision operator,
and
α
refers to the velocity discretization index. During one time step, the computation evolves through tw o processes:
collision, where particles meet at the same lattice site and their distribution functions are evaluated according to the
collision operator Ω
α
, and streaming, where particles shift to the neighboring sites following their lattice directions.
Collision causes the relaxation of all local distribution functions to an equilibrium where Ω α [ f α = f eq
α ] = 0.
Each discretization of the velocity space is described by its n umber of spatial dimensions
a
and velocity directions
b
, with scheme notation D
a
Q
b
. For example, a D1Q2 scheme uses a 1D lattice with tw o velocity directions, i.e., a
right-going particle and a left-going particle for each lattice site.
Macroscopic variables, like the fluid density or v elocity, are determined from the moments of the distribution
functions [ 33 ]. For example, the densit y at lattice site i corresponds to
ρ i =
b
X
α =1
f α,i . (2)
Herein, we divide 1D spatial domains into
N s
uniformly spaced lattice sites
i
= 0
, . . . , N s −
1. For example, domain
4
X ∈ [0 , L ] has site locations x i = i ∆ x where ∆ x = L/N s is the lattice spacing, usually set to 1.
III. QUANTUM LATTICE GAS
The quantum LGA (QLGA) is a measurement-based algorithm that in troduces a sup erposition of qubit states within
a small spatial region and for a short period. It directly maps the bits used in a classical lattice gas to qubits and
models the lattice gas at the mesoscopic scale, which can be described using the lattice Boltzmann equation. Figure 2
shows an example of the associated quantum circuit used to solve the 1D diffusion equation using the D1Q2 sc heme
defined in the previous section. The algorithm has four operations: (re)initializing the qubit states via enco ding ,
collision at each lattice site, measuring the qubit occupancy via loc alization , and stre aming the qubits on the lattice
appropriately . Enco ding and collision are performed in the quantum space, but the measurement step and classical
streaming computation mean the quantum state must be re-encoded.
| 0 ⟩ ⊗ n
Ry √ x
Ry
Ry √ x
Ry
FIG. 2. QLGA with classical streaming [
26
].
R y
is a rotation gate by the angle
θ α
= 2
arccos p 1 − f α ( x i , t )
for the qubit of
state
| q α ( x i , t ) i
. The controlled
√ x
gate is a native IBM gate, decomposed as a two-qubit con trolled phase rotation
P
(
π/
2) gate
between tw o Hadamard gates on the target qubit [ 34 ].
The system wav efunction can be written as
| Ψ( x 0 , x 1 , . . . , x N s − 1 , t ) i =
N s − 1
O
i =0 | Ψ( x i , t ) i . (3)
F ollowing Dirac’s bra-ket notation, the ket vector
| Ψ( x i , t ) i
represents the on-site state, i.e., at the lattice site of
coordinate
x i
, of dimension 2
b
. In the D1Q2 scheme, each lattice site comprises two particles, one mo ving to the right
and the other to the left. QLGA maps the two particles to qubits, denoted by
| q α ( x i , t ) i
where
α
= 1
,
2. The
α
-th
qubit encodes an occupancy probability f α ( x i , t ) at lattice site x i and time t .
In the first step of the QLGA algorithm, qubits encode the occupancy probabilities via this expression:
| q α ( x i , t ) i = p 1 − f α ( x i , t ) | 0 i + p f α ( x i , t ) | 1 i for i = 0 , . . . , N s − 1 and α = 1 , 2 . (4)
The on-site ket vector represen ting the quantum state at each lattice site x i is
| Ψ( x i , t ) i = | q 1 ( x i , t ) i⊗| q 2 ( x i , t ) i for i = 0 , . . . , N s − 1 . (5)
This step is implemented via the
R y
(
θ α
) rotation gate by the angle
θ α
= 2
arccos p 1 − f α ( x i , t )
for the qubit of state
| q α ( x i , t ) i
. The relative phase of the qubits is set to zero in this step. Then, QLGA applies the collision lo cally to each
lattice site, a unitary operation that relaxes the distribution functions to equilibrium. The p ost-collision state is
| Ψ 0 ( x i , t ) i = U | Ψ( x i , t ) i (6)
where
U
is the collision operator that causes local quantum entanglement of the on-site qubits. It is implemented via a
5
unitary gate with a block-diagonal entangling U (2) matrix:
1 0 0 0
0 e iφ e iξ cos θ e iφ e iζ sin θ 0
0 − e iφ e − iζ sin θ e iφ e − iξ cos θ 0
0 0 0 1
(7)
where
φ
,
ξ
,
ζ
, and
θ
are Euler angles chosen to satisfy the PDE of interest in the con tinuum limit. We c hoose
φ
=
− π/
4,
ξ
= 0,
ζ
=
π/
2 and
θ
=
π/
4 to model the diffusion equation and
φ
= 0,
ξ
=
ζ
and
θ
=
π/
4 to model Burgers’
equation [ 35 , 36 ].
Next, all qubits are measured, and the post-collision occupancy probabilities
f 0
α
(
x i , t
) are computed from measurement
outcomes. The non-unitary measurement operation destroys the quantum superposition and entanglement that the
collision step may hav e caused. The p ost-collision occupancy probability is
f 0
α ( x i , t ) = h Ψ 0 ( x i , t ) | n α | Ψ 0 ( x i , t ) i (8)
where n α are the number operators for α = 1 , 2.
Then, streaming is performed by shifting the qubits to their neighboring positions according to their right or left
lattice directions. The post-streaming o ccupancy probabilities can be written as
f α ( x i , t + ∆ t ) = f 0
α ( x i + e α ∆ x, t ) , (9)
where e 1 = − 1 and e 2 = 1 are the qubits directions, ∆ x is the spacing, and ∆ t is the time step.
These four operations can be encapsulated in the following equation:
f α ( x i + e α ∆ x, t + ∆ t ) = f α ( x i , t )+Ω α [ f α ( x i , t )] (10)
which is in the form of the classical lattice Boltzmann equation with the collision operator given by:
Ω α [ f α ( x i , t )] = h Ψ( x i , t ) | U † n α U − n α | Ψ( x i , t ) i (11)
Equilibrium distributions can be found by satisfying the equilibrium condition: Ω
α
[
f α
=
f eq
α
] = 0. For the diffusion
equation, we get equal equilibrium probabilities
f eq
α
=
ρ/
2 for
α
= 1
,
2. For Burgers’ equation, the equilibrium
distribution corresponds to f eq
α = ρ/ 2 + e α / 2( √ 2 − p 1+( ρ − 1) 2 ).
This streaming step was designed to run classically on Type-II quantum computers [
27
]. One time step of QLGA
consists of the four operations described ab ove. Unlike most quantum gate models, where measurement is performed
at the end of the computation, QLGA requires measurement at each time step to extract the distribution functions,
which are then used to encode the next time step. The recurrent decoherence at each lattice site is necessary to allow
qubits to shift to neighboring sites classically . We next present a method for avoiding these unnecessary computations
on modern quantum hardware.
IV. A FULL Y-QUANTUM LA TTICE BOLTZMANN ALGORITHM
This section presents a single-quantum computer v ersion of QLGA that avoids the Type-II quantum computers of
previous studies. We form ulate a fully-quantum lattice Boltzmann method algorithm (QLBM) and verify it against
known, classical solutions. Since the QLGA solves the lattice Boltzmann equation at the mesoscopic scale, we shall
name our QLGA varian ts as QLBM.
6
| 0 ⟩ ⊗ n
Ry √ x
Permutation
Ry
Ry √ x
Ry
(a) QLBM circuit solving the diffusion equation
| 0 ⟩ ⊗ n
Ry H
Permutation
Ry
Ry H
Ry
(b) QLBM circuit solving Burgers’ equation
FIG. 3. QLBM with quantum streaming solving (a) the diffusion equation and (b) Burgers’ equation. The permutation block
encapsulates a sequence of swap gates that shift the qubits during the streaming step.
A. Quantum streaming
The first revision to the QLGA algorithm performs the streaming step using quantum states, not classically . It can
be implemented before the measurement step via the permutation function that applies a sequence of swap gates to
shift the qubits to their neighbors. The corresponding quantum circuit is shown in fig. 3 for the diffusion and Burgers’
equations.
W e validate the proposed varian t by solving the 1D diffusion equation and Burgers’ equation using Gaussian and
sinusoidal distributions as the initial condition, respectively . Periodic boundary conditions are used. W e compare the
two QLBM solutions, i.e., with classical streaming and quan tum streaming, with the classical solution using the D1Q2
scheme and 26 simulated qubits. The simulations were performed using Qiskit AerSimulator with the statevector
simulation method, and the counts were sampled from the statev ector using 10
5
shots. The spatial domain consists of
N s = 13 lattice sites corresponding to 26 qubits. Results are shown after 10 time steps.
The results of fig. 4 demonstrate good agreement with the classical solution. This variant remov es the need for classical
communication between lattice sites and does not cause global entanglemen t, as swap gates merely interchange the
qubit quantum states.
In terms of complexity , we examine the relationship between the circuit depth and the system size by analyzing the
different operations of the algorithm separately . The enco ding step consists of applying one rotation gate simultaneously
to each qubit. Thus, changing the grid resolution and the qubit n umber does not affect the circuit depth. The same
unitary operator is applied to each pair of qubits for the collision step. Thus, the circuit depth scales as
O
(1) with the
number of qubits
n
. For the streaming step implemen ted using the permutation function, the number of swap gates
applied to one of the qubits increases linearly with the number of qubits. Therefore, the complexity of the algorithm is
given by O ( n ).
B. 1-dimension, three-velocities: D1Q3 scheme
The implementations of the QLBM mentioned abov e used the D1Q2 scheme, which uses two mo ving particles per
lattice site. This scheme shows check er-board pathologies when using a sharp function as the initial condition because
it simulates tw o independent sub-lattice [
26
]. Y epez
[ 35 ]
presents a cure for this, allowing only one qubit to mo ve
while the other remains stationary . However, this requires two collision and streaming procedures per time step. We
show that a quantum D1Q3 sc heme, which adds a stationary qubit to each lattice site, solves this problem. A similar
solution was demonstrated on three-qubit Type-II quantum computers by Sco ville [ 37 ].
Figure 5 compares the quantum solution of the diffusion equation using the D1Q2 scheme with the D1Q3 sc heme
for a delta function as the initial condition. These simulations were performed using the Qiskit matrix product state
simulator, 45 qubits for the D1Q3 scheme, and the sampling procedure used 10
6
shots. The spatial domain consists of
N s
= 15 lattice sites, and results are sho wn after 10 time steps. The result shows the agreement of the quantum D1Q3
solution with the classical one and how the D1Q3 version remedies the c hecker-board effect. We note that the D1Q3
scheme does not affect algorithm complexity .
7
0 . 0 2 . 5 5 . 0 7 . 5 10 . 0 12 . 5
Lattice site i
0 . 52
0 . 54
0 . 56
0 . 58
Densit y ρ i
Classical
Quan tum - classical streaming
F ully quan tum
(a) Diffusion equation
0 . 0 2 . 5 5 . 0 7 . 5 10 . 0 12 . 5
Lattice site i
0 . 8
0 . 9
1 . 0
1 . 1
1 . 2
1 . 3
Densit y ρ i
Classical
Quan tum - classical streaming
F ully quan tum
(b) Burgers’ equation
FIG. 4. QLBM solutions to the diffusion equation (a) and Burgers’ equation (b) using the D1Q2 scheme. “Quantum - classical
streaming” is associated with the classical streaming algorithm discussed in previous work [
26
],“F ully quantum” refers to the
present algorithm, and “Classical” is the classical implementation of the lattice method.
0 5 10
Lattice site i
0 . 0
0 . 1
0 . 2
0 . 3
Densit y ρ i
Classical - D1Q2 Classical - D1Q3
Quan tum - classical streaming
F ully quan tum
FIG. 5. QLBM solutions to the diffusion equation using the D1Q3 scheme. “Quantum - classical streaming” is associated
with the classical streaming algorithm discussed in previous work [
26
], “F ully quantum” refers to the present algorithm, and
“Classical” is the classical implementation of the lattice methods as labeled.
C. Measurement-a voiding QLBM
The quantum state collapses due to measurements performed during each time step, requiring re-encoding. Howev er,
we should allow the qubits to explore more complex states to ac hieve truly quantum computation. Furthermore,
measurement on superconducting quantum computers can typically tak e an order of magnitude longer than gate times,
adding significant time to the algorithm [
38
]. Thus, the goal is to eliminate repeated initialization of the quantum
state and repeated measurements, which destroy the quan tum superp osition and entanglement.
W e attempted a unitary transformation using random rotations to reset the qubit relative phases after each time step.
Howev er, this random phase kicking leads to dephasing, where the expected value of the off-diagonal elements of the
density matrix decay to zero with time [ 39 ]. Therefore, a different approach is needed.
T o this end, our algorithm adds a phase-correction step, approximating the qubit relative phases and subtracting
them at the end of each time step, delaying the need for measuremen t until the end of the computation. This can be
achieved b y using the quantum phase estimation (QPE) algorithm as a sub-routine to estimate the eigen-phases of the
encoding and collision unitaries [
39
]. These eigen-phases are then used to classically estimate the qubit relative phases,
subtracted at the end of each time step. The accuracy of the QPE depends on the number of ancillary qubits it uses.
Thus, we use the iterativ e phase estimation (IPE) algorithm, which only requires a single auxiliary qubit and evaluates
8
0 1
m
| 0 ⟩ H H | 0 ⟩ H P ( − π
2 ) H
| 00 ⟩ U 2 m − 1 U 2 m − 2
c
(a) First two iterations of IPE algorithm
√ x
Permutation
P ( α 0 )
P ( α 1 )
√ x P ( α 2 )
P ( α 3 )
(b) Measurement-av oiding QLBM circuit
FIG. 6. (a) IPE circuit used to estimate the qubits relative phase
α i
and (b) Measurement-av oiding QLBM circuit solving the
diffusion equation.
0 . 0 2 . 5 5 . 0 7 . 5 10 . 0 12 . 5
Lattice site i
0 . 50
0 . 52
0 . 54
0 . 56
0 . 58
0 . 60
Densit y ρ i
Measuremen t-a v oiding quan tum
Classical
FIG. 7. Measurement-av oiding QLBM (present work) solution to the diffusion equation using the IPE algorithm and its
comparison to classical results for the same method and resolution.
the phase bit by bit through a repetitive process [
40
]. The accuracy of the IPE algorithm is determined by the number
of iterations instead of the number of ancillary qubits. Therefore, they are of great importance for near-term quantum
computing. The IPE algorithm still requires measurement to estimate the phase. However, only one qubit, i.e. the
auxiliary qubit is measured and not all qubits in the quantum register.
In the context of QLBM, we apply the IPE algorithm to ev ery lattice site, i.e., to a two-qubit unitary for the D1Q2
scheme. W e set the unitary
U
to be the product of the enco ding and the collision operations since the streaming
step only swaps the qubits and does not change their phases. F or a total number of iterations
m
, the IPE algorithm
estimates the phase
ϕ
= 0
.ϕ 1 ...ϕ m
, where
ϕ k
are the phase bits (1
≤ k ≤ m
). At each iteration
k
, the IPE algorithm
applies the unitary
U
2
m − k
times controlled on the auxiliary qubit. Due to phase kickback, the relativ e phase of the
auxiliary qubit becomes
exp
(
i
2
π
0
.ϕ m − k +1 ϕ m − k +2 ...ϕ m
). Thus, to estimate the phase bit
ϕ m − k +1
, a phase correction
of
−
2
π
(
ϕ m − k +2 /
2
2
+
...
+
ϕ m /
2
m
) is performed, controlled on the measurement outcome of the previously estimated
phase bits
ϕ m − k +2 , ..., ϕ m
. The phase bit
ϕ m − k +1
is then estimated by measuring the auxiliary qubit in the
x
-basis.
The first two iterations of the IPE, whic h estimates the two least significant bits of the phase
ϕ m
and
ϕ m − 1
, is
illustrated in fig. 6 (a). One time step of the measurement-avoiding QLBM circuit is shown in the circuit of fig. 6 (b),
which consists of collision, streaming, and phase correction operations.
Figure 7 presents the numerical sim ulation of our variant using the IPE algorithm to solv e the 1D diffusion equation.
The simulation uses the D1Q2 scheme with 26 qubits and runs on the statev ector simulator. The spatial domain
consists of
N s
= 13 lattice sites, and results are shown after 6 time steps. A go od agreement is found between the
quantum solution and the classical one. This varian t improves the efficiency of the QLGA algorithm as the encoding is
used only once at the beginning of the computation to prepare the quantum states, and measurement is only performed
at the end of the computation. However, this algorithm is hybrid since the qubits phases are classically computed
from the eigenv alues estimated using the IPE. In terms of complexity , having only one ancillary qubit comes with the
cost of O (2 m − 1 ) gates, where m is the number of IPE iterations related to the precision of the estimated phases.
9
5 10 15 20
Num b er of qubits
0 . 000
0 . 005
0 . 010
0 . 015
RMSE
statev ector
mps
qpp
exatn-mps
(a) RMSE compared to the classical solution using
10 4 shots
10 1 10 2 10 3 10 4 10 5
Num b er of shots
10 − 2
10 − 1
RMSE
statev ector
mps
qpp
exatn-mps
(b) RMSE compared to the classical solution using 18
qubits
5 10 15 20
Num b er of qubits
10 0
10 1
10 2
10 3
10 4
W all-clo c k time (s)
statev ector
mps
qpp
exatn-mps
(c) W all-clock time in seconds using 10 4 shots
FIG. 8. RMSE and wall-clock time of the quantum solution solving the diffusion equation compared to the classical one. Qiskit
(solid lines, ——) statevector and mps simulators and XACC sim ulators (dashed lines, – – –) qpp and exatn-mps are shown.
The colors correspond to (blue) statevector-like and (orange) matrix product state simulators.
V. QUANTUM SIMULA TORS
W e test different quantum simulator implemen tations of our QLBM algorithm and its circuit. Simulators include
statevector-based and tensor-netw ork types that use the matrix product state (mps) metho d [
41
]. Two different
simulation frameworks are tested: Qiskit and XACC [
42
]. Statevector and mps simulators are part of the Qiskit Aer
backend. The XACC qpp (Quan tum++) simulator is based on a C++ general-purpose quantum computing library [
43
].
XACC exatn-mps simulator is a part of the TNQVM (tensor-net work quantum virtual machine) sim ulation backend
and uses a noiseless, matrix product state wave function decomposition for the quantum circuit [
44
]. The wall-clock
times of fig. 8 (c) were obtained via simulation on an AMD EPYC 7742 (64-core) processor.
W e run the QLBM circuit of fig. 3 on the four different simulators and compare their performance. Figure 8 shows the
wall-clock time and the root-mean-squared error (RMSE),
RMSE =
v
u
u
t P N s − 1
i =0 ρ (quant . )
i − ρ (classic . )
i 2
N s
, (12)
where
N s
is the number of lattice sites of the quantum solution compared to the classical one as a function of the
number of shots (samples from the underlying density functions). The errors are rep orted from simulations using 10
4
10
0 10 20 30 40 50
Lattice site i
0 . 50
0 . 55
0 . 60
0 . 65
0 . 70
Densit y ρ i
F ully quan tum
Classical
FIG. 9. QLBM solution to the diffusion equation using the Qiskit mps simulator and its comparison to classical results using
102 qubits.
shots in fig. 8 (a) and using 18 qubits in fig. 8 (b). We find that the results are shot-noise limited and all quan tum
simulators obtain the same accuracy in terms of RMSE, which decreases from less than 10% for 10
2
shots to less than
1% for 10
4
shots. However, the Qiskit mps sim ulator is at least one order of magnitude faster than the statevector
ones. This behavior is expected. The Qiskit statevector and XA CC (qpp) simulators generate the full state vector,
which scales exponentially with the num ber of qubits. In contrast, the mps simulator uses a local representation in a
factorized form of tensor products [
45
]. The mps method ensures that the overall structure remains small as long as
the circuit has a low degree of entanglemen t, enabling more simulated qubits. To demonstrate this, we run the QLBM
circuit of fig. 3 a on Qiskit mps simulator for the resolution of 51 lattice sites corresponding to 102 qubits using 10
6
shots. Results after 10 time steps are shown in fig. 9 and demonstrate good agreement with the classical solution.
VI. CONCLUSION AND DISCUSSION
In this work, we present a revised quan tum lattice gas algorithm that can be used to simulate fluid flows. The algorithm
of Y epez
[ 46 ]
was designed for Type-II quantum computers that are no longer used. The presented algorithm uses
a full-quantum implementation of the streaming step to eliminate classical comm unication between lattice sites. In
addition, it avoids repetitive measurements and encoding operations by estimating the qubit relative phases and
subtracting them at the end of each time step. This eliminates the need for state re-preparation between time steps and
delays the need for measurement to the end of the computation. The algorithm is tested to solve canonical PDEs: the
diffusion and Burgers’ equations. We explored differen t quantum simulators av ailable on Qiskit and XACC quantum
computing frameworks and compare their performance and wall-clock time. Matrix pro duct state simulators are
most efficient for the presented quan tum circuits, as they have low and local entanglemen t. These strategic algorithm
improvemen ts enable the execution of the quantum lattice gas algorithm on quantum hardware, a subject of future
work.
An important limitation of the current algorithm is the size of the required quantum register, whic h scales linearly
with the number of lattice sites. F or example, the number of required qubits in a two-dimensional
M × M
lattice is
5
M 2
using the D2Q5 scheme. This requirement constrains the ability to extend this algorithm to higher dimensions
due to the limited number of qubits av ailable on current quantum hardw are. Thus, one needs to use more appropriate
encoding schemes, such as one that scales logarithmically with the number of lattice sites, like amplitude-based
encoding. F or example, Budinski
[ 22 ]
implements the streaming step via a quantum random w alk, similar to the
collisionless Boltzmann equation solved on a quantum computer of T odorov a and Steijl
[ 21 ]
. Indeed, in principle, one
could design an algorithm that uses a quantum random walk for both the collision and streaming operations, which we
will investigate in future w ork.
11
ACKNOWLEDGEMENTS
W e thank Dr. Jeffrey Yepez for numerous fruitful discussions of this work. S.H.B. acknowledges support from
the Georgia T ech Quantum Alliance and a Georgia T ech Seed Grant. E.F.D. acknowledges DOE ASCR funding
under the Quantum Computing Application T eams program, FWP number ERKJ347. This work used Bridges2
at the Pittsburgh Supercomputing Center through allocation PHY210084 from the Advanced Cyberinfrastructure
Coordination Ecosystem: Services & Supp ort (ACCESS) program, which is supported by National Science F oundation
grants #2138259, #2138286, #2138307, #2137603, and #2138296.
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| https://www.researchgate.net/publication/370763603_Fully_quantum_algorithm_for_lattice_Boltzmann_methods_with_application_to_partial_differential_equations |
Expression of PD‑L1 and CD4+ tumor‑infiltrating lymphocytes predict survival in head and neck squamous cell carcinoma
Expression of PD‑L1 and CD4+ tumor‑infiltrating lymphocytes predict survival in head and neck squamous cell carcinoma
Authors:
Ze-Ming Fu
De-Jun Zhang
Shuang Han
Fang Guo
Jie Bai
Yi-Ning Wan
Guo-Fang Guan
Ke-Wei Sun
Na Yang
Published online on: January 10, 2022 https://doi.org/10.3892/mco.2022.2492
Article Number: 59
Abstract
+
and CD4
+
TILs and the expression of PD‑L1 were detected by immunohistochemistry. PD‑L1 mRNA levels were evaluated by reverse transcription‑quantitative PCR analysis. The association of TILs and PD‑L1 with patient clinicopathological characteristics was also assessed. CD3
+
and CD4
+
TILs were detected in 100% of the samples. CD3
+
was the predominant subset of TILs. PD‑L1 was expressed in 53 of 61 (86%) patients when a score of ≥1 on tumor cells was considered positive and in 28 patients (45.2%) when a score of >5 on tumor cells was considered positive. PD‑L1 mRNA levels were determined to be significantly correlated with PD‑L1 protein expression. Survival analysis demonstrated that high CD4
+
TILs were associated with improved overall survival (OS) and disease‑free survival (DFS), and furthermore, the association of high PD‑L1 expression with unfavorable OS and DFS was statistically significant. Multivariate analysis identified CD4
+
TILs and PD‑L1 as prognostic markers for HNSCC. The results of the present study suggested that increased CD4
+
TILs in HNSCC may be associated with improved outcomes, while high expression of PD‑L1 may indicate unfavorable OS and DFS; thus, these factors may serve as predictors of the response to immune checkpoint therapy.
Introduction
Head and neck squamous cell carcinoma (HNSCC) is the
sixth most common malignant tumor type worldwide and the most
common malignancy originating in the mucosal epithelium of the oral
cavity, pharynx, larynx and hypopharynx (
1
). Smoking and excessive alcohol
consumption have been associated with the tumorigenesis of HNSCC
(
2
). Human papillomavirus has been
associated with tumors arising in the oropharynx (
3
). Various cases are usually diagnosed at
a later stage, which is associated with high mortality and
morbidity rates (
2
). Although
multimodality approaches, such as EGFR monoclonal antibody in
combination with chemotherapy, are used for more advanced-stage
disease, 30-40% of patients develop distant metastases within 5
years (
3
); therefore,
understanding the molecular characteristics and immunological
profile of HNSCC may help overcome certain obstacles associated
with targeted therapies and prove beneficial for the patients.
The tumor microenvironment significantly affects
tumor aggressiveness and response to treatment (
4
). Tumor-infiltrating lymphocytes (TILs)
are an important histopathological characteristic of HNSCC
(
5
). Tumor infiltration by T
lymphocytes is a highly informative prognostic factor for
predicting the clinical outcome of the disease. In several studies,
TILs of different types and locations in primary tumors are of
prognostic value for overall survival (OS) and disease-free
survival (DFS) (
6
,
7
). However, different subsets of
lymphocytes have different functions. CD4
+
T-helper
cells stimulate cytotoxic CD8
+
T cells to enhance the
antitumor immune response (
8
),
while CD4
+
regulatory T cells (Tregs) are considered to
serve as suppressors of antitumor immune response (
9
). CD3
+
T cells have been
considered as an important T-cell marker for the classification of
malignant lymphomas and leukemias (
10
). Although TILs have been extensively
investigated, the prognostic significance of specific TIL
subgroups, such as CD3
+
or CD4
+
, is different
due to the complexity of the composition and function of TILs, and
has been inconsistent across different studies. The role of TILs in
immune surveillance in HNSCC remains to be clarified and previous
studies have reported conflicting results.
The immune checkpoint molecules programmed death 1
(PD-1) and programmed death 1 ligand 1 (PD-L1) have been evaluated
in a number of cancer types (
11
,
12
).
PD-1 is mainly expressed on the surface of T and B cells during
activation. PD-1 signaling is mediated through binding to its two
ligands, PD-L1 and PD-L2, which are mainly expressed by cancer
cells (
13
). As an inhibitory
immune checkpoint molecule, PD-1 mediates the immune escape of
tumor cells (
14
). PD-L1 is also
referred to as cluster of differentiation 274, which is a protein
encoded by the CD274 gene (
15
).
There is increasing evidence that tumor cells express various
levels of PD-L1 in numerous types of cancer, including HNSCC.
However, the currently available results remain controversial. The
clinical prognostic significance of PD-L1 expression in HNSCC
tissues varies across different studies, which may be due to
different sample sources and intratumor heterogeneity, different
antibodies and staining protocols, and inconsistent cut-off values,
among others (
16
). In three
recent randomized phase III trials, the PD-1 targeting antibodies
nivolumab and pembrolizumab, which have been used to treat patients
with advanced HNSCC, exhibited superior efficacy and lower toxicity
compared with traditional chemotherapy and radiotherapy alone
(
17
). Pembrolizumab combined with
chemotherapy was determined to be superior to cisplatin and
5-fluorouracil (
18
). Furthermore,
pembrolizumab monotherapy was more effective as a first-line
treatment in patients with HNSCC whose tumors express PD-L1
compared with those with non-PD-L1-expressing tumors (
17
). However, a large proportion of
patients do not respond to treatment, while certain initial
responders eventually develop resistance; thus, further research is
required.
The aim of the present study was to investigate the
frequency of TILs expressing CD3 and CD4 and the expression of
PD-L1 in tumor cells using formalin-fixed paraffin-embedded (FFPE)
samples from patients with HNSCC. Furthermore, the association of
TILs and PD-L1 with clinical characteristics and prognosis was
assessed in order to evaluate the predictive value of TILs and
PD-L1 expression.
Materials and methods
Patient cohort
A total of 63 FFPE tissue specimens were collected
from patients with pathologically confirmed HNSCC at the Second
Hospital of Jilin University (Changchun, China) between May 2008
and July 2019. Patients who had previously received conventional
radiotherapy and/or chemotherapy prior to surgery were excluded.
All tumor specimens were obtained from primary resections. The
study protocol was approved by the Medical Ethics Committee of
Jilin University (Changchun, China; no. 2021-157). Approximately
half of the patients provided written informed consent for the
study. For the other half of the patients, a telephone interview
was conducted and verbal consent was obtained.
The clinical characteristics of the patients are
summarized in
Table I
. The
majority of the patients were male [45 (71.4%)] and the median age
was 64.6 years (range, 40-76.8 years). Approximately half of the
patients had advanced disease with T stage 3/4 (52.4%), N stage 2/3
(54%) and clinical stage III/IV (55.6%). All studied tumour
specimens were assessed on HE-stained slides using standard
diagnostic criteria.
Table I Patient characteristics.
Table I
Patient characteristics.
Characteristic Value Age, years [median
(range)] 64.6 (40-76.8) Sex Male 45 (71.4) Female 18 (28.6) T
classification T1 11 (17.5) T2 19 (30.1) T3/4 33 (52.4) N
classification N0 13 (20.6) N1 16 (25.4) N2/3 34(54) Clinical stage I 3 (0.05) II 25 (39.7) III/IV 35 (55.6) PD-L1 expression
score High,
>5 28 (45.2) Low, ≤5 34 (56.8) CD3 expression
score High,
>26.8 30(50) Low,
≤26.8 30(50) CD4 expression
score High,
>17.3 29 (48.3) Low,
≤17.3 31 (51.7)
[i]Values are
expressed as n (%) unless otherwise specified. PD-L1, programmed
death ligand 1.
Immunohistochemistry (IHC)
CD3
+
and CD4
+
TILs were
determined by IHC. Archival FFPE HNSCC tumor blocks were cut into
4-µm sections, deparaffinized with xylene and rehydrated through a
decreasing ethanol gradient. Boiling in 10 mM citrate buffer, pH
6.0 (Novocastra; Leica Microsystems, Ltd.) in a microwave was used
for epitope retrieval. After endogenous peroxidase blocking (0.3%
H
2
O
2
; Thermo Fischer Scientific, Inc.) at
room temperature for 30 min, the sections were incubated with
primary antibodies against CD3 (1:200 dilution; clone A0452; cat.
no. A045229-2; Dako; Agilent Technologies, Inc.) and CD4 (1:500
dilution; clone 4B12; cat. no. NCL-L-CD4-368; Novocastra; Leica
Microsystems, Ltd.) at 4˚C overnight. The CD4 antibody was used to
stain all CD4
+
-expressing cells, including Tregs.
Secondary detection was performed using the Level-2 Ultra
Streptavidin (horseradish peroxidase) system (Dako; Agilent
Technologies, Inc.) at room temperature, which included anti-rabbit
for CD3 or anti-mouse for CD4 for 30 min. Streptavidin was applied
to all sections for 30 min at room temperature. Color detection was
performed by using 3,3'-diaminobenzidine for 5 min at room
temperature. The slides were counterstained with hematoxylin and
mounted with coverslips.
PD-L1 was detected by using the mouse monoclonal
anti-human PD-L1 antibody (1:100 dilution; CD274, clone UMAB229;
cat. no. UM800121; OriGene Technologies, Inc.) at 4˚C overnight.
Accel Retrieval Solution (GBI Labs) was used for antigen retrieval.
Human tonsillar samples known to be positive for CD3, CD4 and PD-L1
expression served as positive controls. Sections without primary
antibodies were used as negative controls.
Evaluation of TILs and PD-L1
expression
A semi-quantitative method was utilized to assess
the CD3 and CD4 expression of TILs inside the infiltrated tumor
tissues. As described previously (
6
,
19
),
three of the most densely stained fields were randomly selected,
with necrotic areas excluded. The proportion of cells with positive
staining (range, 0-100%) and staining intensity (0, negative; 1,
weak; 2, moderate; and 3, strong) were assessed and recorded. The
final score was calculated by multiplying the percentage of
positive cells with the average staining intensity.
The abundance and location of PD-L1 expression
within the tumor were also determined semi-quantitatively. PD-L1
expression was membranous, with variable cytoplasmic staining. A
four-level score was used to quantify the proportion of total cells
stained and the staining intensity on the membrane: 0 (0-<5%
positive cells), 1 (5-10% positive cells), 2 (10-20% positive
cells), 3 (20-50% positive cells) and 4 (>50% positive cells).
The staining intensity was determined as 0, 1, 2 or 3(
20
). The final score was calculated by
multiplying the proportion of stained cells (scored as 0, 1-4) by
the staining intensity (scored as 0, 1-3) (
21
). A Leica light microscope linked with
a camera was used for capturing and analysing images
(magnification, x200). All evaluations were performed in a blinded
manner regarding the clinical outcome of the patients.
RNA extraction and quantification of
PD-L1 expression by reverse transcription-quantitative
(RT-q)PCR
A total of 60 available FFPE surgical samples from
the same cohort of patients with HNSCC and 10 adjacent normal
tissue samples were collected. Based on HE-stained tissue sections,
only samples containing >60% tumor cells were considered. The
expression of PD-L1 at the mRNA level was measured by using
RT-qPCR. A total of 5-10 8-µm sections were obtained from each
sample and total RNA was extracted from the samples using the
Recover All Total Nucleic Acid Isolation kit for FFPE (Thermo
Fisher Scientific, Inc.). In brief, the sections were
deparaffinized with xylene and rehydrated through a decreasing
ethanol gradient. After washing with 100% ethanol, the air-dried
pellets were incubated with 200 µl digestion buffer and 4 µl of
protease K (included in the kit) in heat blocks for 15 min at 50˚C
and then 15 min at 80˚C. After adding 100% ethanol, the mixture was
loaded onto a filter cartridge, centrifuged, the flow-through was
discarded and the filter cartridge was washed twice. Subsequently,
60 µl DNase was added, followed by incubation at room temperature
for 30 min. After two additional washes, the RNA was eluted with
nuclease-free water. According to the manufacturer's protocol, RT
of RNA was performed with Super Script III reverse transcriptase
(Invitrogen; Thermo Fisher Scientific, Inc.). Primer 3 (v.0.4.0;
https://bioinfo.ut.ee/primer3-0.4.0/
)
was used to design the primers. The primers for PD-L1 were as
follows: Forward, 5'-GTGGCATCCAAGATACAAACTCAA-3' and reverse,
5'-TCCTTCCTCTTGTCACGCTCA-3'. The primers for GAPDH were as follows:
Forward, 5'-GTCTCCTCTGACTTCAACAGCG-3' and reverse,
5'-ACCACCCTGTTGCTGTAGCCAA-3'. Amplification was performed using
SYBR Green Master Mix (Applied Biosystems; Thermo Fisher
Scientific, Inc.) and the ABI PRISM 7900 Sequence Detection System
(Applied Biosystems; Thermo Fisher Scientific, Inc.). The 10-µl
reaction volume contained 50 ng cDNA (either from FFPE tumor
samples or normal adjacent tissue samples), 200 nmol/l of each
primer and 5 µl of SYBR Green Master Mix (Thermo Fisher Scientific,
Inc.). The thermocycling conditions included initial denaturation
at 94˚C for 2 min; 40 cycles of denaturation at 94˚C for 15 sec;
and annealing and extension at 60˚C for 1 min. Relative
quantification of PD-L1 mRNA levels was performed by using the
2
-∆∆Cq
method (
22
). As
calculated from the duplicate reactions for each tested sample, the
mean Cq value was used. The relative fold change of mRNA
expression, in which the mean of the ∆Cq values of the target
amplicon was normalized to the endogenous gene GAPDH, compared with
normal tissue specimens. Each experiment was performed three
times.
Statistical analysis
Fisher's exact test was used to assess differences
between categorical variables. The associations between the
expression of each detected biomarker and various
clinicopathological parameters were assessed. The Kaplan-Meier
method was used to calculate OS and DFS and the log-rank test was
used for comparisons. The Cox proportional hazard model was used to
perform univariate and multivariate analyses. Factors with
prognostic significance in the univariate model were further
analyzed in a multivariate Cox proportional hazards regression
model. P<0.05 was considered to indicate statistically
significant differences. Pearson's correlation coefficient analysis
was used to determine the correlation between PD-L1 expression and
CD3
+
or CD4
+
TILs. Analyses were performed
using the R 4.1.2 package (R Foundation for Statistical
Computing).
Results
TILs in HNSCC
The expression of CD3 and CD4 on TILs was evaluated
in the tumor parenchyma of patients with HNSCC. Of the 63 tumor
samples, 61 were available for CD3 and CD4 assessment. A total of
two samples were excluded due to the small sample size or poor
tissue morphology after staining. CD3 and CD4 were expressed in
100% of the samples. With a range of 9.0-61.3 for CD3 and 2.3-42.3
for CD4, the median score of CD3 and CD4 expression was 26.8 and
17.3, respectively. As a dichotomous variable, patients were
divided into CD3 expression high and low groups. According to the
median, high was defined as a score >26.8 and low was defined as
a score ≤26.8. Using a similar method, patients were assigned to
CD4 high (>17.3) and low (≤17.3) groups (
Table I
). IHC analysis revealed that the
expression of CD3 was abundant in tumors, while the expression of
CD4 was relatively low.
Evaluation of PD-L1 expression by
IHC
Of the 61 available tumors, PD-L1 was expressed in
53 (86.0%, score ≥1). According to the median score, PD-L1
expression was divided into low and high groups, with 28 samples
(45.2%) exhibiting high PD-L1 expression (score >5) and 34
samples exhibiting low expression (score ≤5;
Table I
). In addition, PD-L1 expression
was observed in 53 samples in which TILs were present.
Representative results on CD3, CD4 and PD-L1 immunostaining and
quantification in tumor cells are provided in
Fig. 1
.
Figure 1Immunohistochemistry for
tumor-infiltrating lymphocytes and PD-L1 staining in head and neck
squamous cell carcinoma. Representative images and quantification
of PD-L1, CD3+ and CD4+ cells (magnification,
x200). **P<0.001. PD-L1, programmed death ligand
1.
Evaluation of PD-L1 expression by
RT-qPCR
The mRNA expression of PD-L1 was evaluated by
RT-qPCR in 60 available patient samples. By comparing with 10
normal tissue samples, the mean expression level of PD-L1 in HNSCC
was 2.07-fold higher compared with that in normal tissues (range,
-3.69- to 6.84-fold). PD-L1 mRNA expression was detected in 49 of
60 patients (81.7%;
Fig. 2A
),
highlighting the overexpression of PD-L1 gene in tumor cells.
Furthermore, PD-L1 mRNA levels were indicated to be significantly
correlated with PD-L1 protein levels (R=0.461; P<0.001;
Fig. 2B
). However, there was no
significant association between PD-L1 mRNA levels and patient
clinicopathological characteristics.
Figure 2Evaluation of PD-L1 mRNA expression
in patients with HNSCC. (A) Bar plot representing the relative fold
change of PD-L1 mRNA levels in HNSCC compared with adjacent normal
tissues. (B) Correlation analysis of PD-L1 protein levels with
PD-L1 mRNA levels (P<0.001). R, Spearman correlation
coefficient; HNSCC, head and neck squamous cell carcinoma; PD-L1,
programmed death ligand 1.
Association of TILs and PD-L1
expression with clinicopathological characteristics
The clinical value of TILs and PD-L1 protein
expression was further evaluated. With a mean follow-up of 72
months (range, 3-151 months), constructed Kaplan-Meier curves
revealed that patients with high CD4 expression were associated
with improved OS (P=0.004) and DFS (P=0.004), which was confirmed
by univariate Cox regression analysis [HR=0.31, 95% confidence
interval (CI): 1.13-0.72, P=0.004 for OS; and HR=0.30, 95% CI:
0.13-0.71, P=0.006 for DFS;
Fig.
3A
and
B
;
Table II
].
Figure 3Prognostic significance of
CD4+ TILs and PD-L1 protein expression in patients with
head and neck squamous cell carcinoma. (A and B) Kaplan-Meier
curves indicated that the number of CD4+ TILs was
associated with (A) OS (P=0.0042) and (B) DFS (P=0.0037). (C and D)
Association of PD-L1 expression with (C) OS and (D) DFS. The
P-value was calculated by using the log-rank test. PD-L1,
programmed death ligand 1; OS, overall survival; DFS, disease-free
survival; TIL, tumor-infiltrating lymphocyte.
Table II Univariate and multivariate analyses
of factors associated with survival in patients with head and neck
squamous cell carcinoma.
Table II
Univariate and multivariate analyses
of factors associated with survival in patients with head and neck
squamous cell carcinoma.
Overall
survival Disease-free
survival Univariate
analysis Multivariate
analysis Univariate
analysis Multivariate
analysis Variable HR (95% CI) P-value HR (95% CI) P-value HR (95% CI) P-value HR (95% CI) P-value Age (> vs. ≤64.6
years) 2.62
(1.09-6.27) 0.03 1.45
(0.56-3.71) 0.003 2.29
(0.98-5.27) 0.05 1.32
(0.53-3.27) 0.004 Sex (female vs.
male) 0.67
(0.28-1.56) 0.357 0.83
(0.36-1.91) 0.667 T classification
(T1/2 vs. T3/4) 0.76
(0.20-2.93) 0.698 0.66
(0.17-2.53) 0.548 N classification
(N0/1 vs. N2/3) 1.94
(0.86-4.37) 0.11 1.71
(0.76-3.87) 0.193 Clinical stage
(I/II vs. III/IV) 1.65
(0.73-3.71) 0.229 1.65
(0.74-3.69) 0.223 CD3 expression
(score > vs. ≤26.8) 0.59
(0.27-1.29) 0.183 0.56
(0.27-1.26) 0.175 CD4 expression
(score > vs. ≤17.3) 0.31
(1.13-0.72) 0.004 0.35
(0.15-0.86) 0.006 0.30
(0.13-0.71) 0.006 0.33
(0.14-0.80) 0.009 PD-L1 expression
(score > vs. ≤5) 2.47
(1.12-5.46) 0.024 2.29
(0.89-5.86) 0.025 2.57
(1.17-5.66) 0.015 2.24
(0.90-5.57) 0.051
[i]HR, hazard
ratio; PD-L1, programmed death ligand 1.
As a categorical variable, PD-L1 was also used to
divide the patients into low and high expression groups.
Kaplan-Meier survival analysis demonstrated that high PD-L1
expression was significantly associated with unfavorable OS and DFS
(P=0.024 and P=0.025, respectively;
Fig. 3C
and
D
), compared with low PD-L1 expression.
Univariate Cox regression analysis revealed significant differences
between the high and low expression groups, [HR=2.47, 95%
confidence interval (CI): 1.12-5.46, P=0.024 for OS; and HR=2.57,
95% CI: 1.17-5.66, P=0.015 for DFS (
Table II
).
Furthermore, multivariate analysis using the Cox
proportional hazards model indicated that CD4 and PD-L1 were
significantly associated with OS and DFS after adjusting for age
(for OS, CD4: HR=0.35, 95% CI: 0.15-0.86 and P=0.006; and PD-L1:
HR=2.29, 95% CI: 0.89-5.86, P=0.025; for DFS, CD4: HR=0.33, 95% CI:
0.14-0.80 and P=0.009; and PD-L1: HR=2.24, 95% CI: 0.90-5.57 and
P=0.051;
Table II
). However, CD3
expression was not indicated to be significantly associated with
disease outcome. Furthermore, no significant associations of
patient sex and tumor stage with CD4 or PD-L1 expression were
observed.
To elucidate the correlation between PD-L1
expression and CD3
+
or CD4
+
TILs, a Pearson's
correlation coefficient analysis was performed. The scatter plot
demonstrated that the expression of CD4
+
TILs had a
negative, if insignificant, correlation with the PD-L1 score
(R=-0.22, P=0.08). No significant correlation between
CD3
+
TILs and PD-L1 expression was obtained (
Fig. S1
). Overall, these results
indicated that CD4
+
TILs and PD-L1 have a role as
independent prognostic factors for patients with HNSCC.
Discussion
The infiltration of the tumor parenchyma by a large
number of TILs has been associated with clinical outcomes in
various types of cancer. Tumor immune checkpoint-targeted therapies
have achieved responses in multiple cancer types (
23
), including HNSCC (
16
). However, the clinical response rates
vary widely and the reasons for this have yet to be fully
elucidated. In the present study, the distribution of TILs and the
expression of PD-L1 were quantitatively analyzed in a population of
patients with HNSCC. Both PD-L1 protein and mRNA levels were
analyzed. The clinical significance of these immune parameters and
the clinical characteristics of the patients were assessed. It was
demonstrated that CD3
+
and CD4
+
TILs were
present in 100% of the samples. Patients whose tumors were
infiltrated by high numbers of CD4
+
T cells exhibited
significantly improved OS and DFS compared with patients exhibiting
poor tumor infiltration. In addition, when a score of >1 of
tumor cells was considered positive, PD-L1 expression was detected
in 86% of the samples and when a score of >5 of cells was
considered positive, PD-L1 expression was observed in 45% of the
samples. Of note, PD-L1 mRNA levels were indicated to be
significantly associated with PD-L1 protein levels (R=0.461;
P<0.001). It is worth noting that high PD-L1 expression was
significantly associated with unfavorable OS and DFS. These results
were independent of clinicopathological characteristics and were of
predictive value for disease outcome.
There is growing interest in evaluating TILs in
solid tumors. It has been demonstrated that the immune attack or
immune escape of tumor cells induces the immune response in the
tumor microenvironment and serves an important role in the response
to cancer therapy (
1
). However, as
different subsets of lymphocytes have different functions in the
tumor microenvironment, there is currently no standardized method
for evaluating TILs. Previous studies analyzed the peritumoral
stroma and tumor core area separately, and evaluated the numbers
and percentage of TILs in solid tumors with different results. In
many cancers, CD3
+
or CD8
+
TILs is positively
correlated with favorable clinical outcomes (
6
,
24
,
25
),
whereas others suggest that CD4
+
or CD8
+
TILs
is associated with better prognosis (
26
) or has no directly correlation with
patient survival, independent of HPV status (
27
). Therefore, the focus of the present
study was to assess the numbers of CD3
+
and
CD4
+
TILs in the tumor parenchyma and determine their
association with the clinical variables of the patients.
It has been indicated that CD3
+
T cells
are the major subtype of TILs in gastric cancer (
28
). In laryngeal squamous cell
carcinoma, a high density of CD3
+
cells in the tumor
core area was associated with a lower risk of metastasis (
29
). CD3
+
and CD8
+
T cells were observed to be associated with improved disease
outcome in patients with head and neck cancer treated with
chemoradiotherapy (
30
). The
results of the present study consistently demonstrated that
CD3
+
cells were the predominant TIL subtype in the
present HNSCC cohort, although the results did not exhibit any
clinical significance, possibly due to the small sample size.
The complexity of the CD4
+
T cell
response has led to ambiguous results. CD4
+
T cells are
able to promote antitumor immunity through Th1 and Th2 cells
(
31
). Other subtypes, such as
Th17 cells, are mainly characterized by the production of high
cytokine IL-17A levels, which has been linked to antitumor immunity
in mouse models (
32
). However,
CD4
+
forkhead box (Fox)p3
+
Tregs contribute
to the inhibition of autoimmunity and prevent excessive immune
response to pathogens (
33
).
CD4
+
TIL infiltration has been evaluated in several
studies on HNSCCs. RT-qPCR analysis indicated that CD4 mRNA
expression levels were significantly correlated with the
CD4
+
cell infiltration score in cancer epithelium and
cancer stroma (
8
). Higher
CD4
+
TIL numbers in patients with HNSCC are associated
with improved OS and relapse-free survival (
26
,
34
).
This phenomenon was also observed in the present study. The present
results indicated that patients whose tumors were infiltrated by
high numbers of CD4
+
T cells had superior OS and DFS
compared with patients exhibiting lower tumor infiltration. By
contrast, another study demonstrated that neither CD4 nor Foxp3
expression intratumoral or in the stroma area showed significance
for the clinical outcome (
6
).
Immunotherapy by using PD-1 and PD-L1 immune
checkpoint blockade has been used in different cancer clinical
trials with certain success. With regard to HNSCC, Schneider
et
al
(
35
) reported that PD-L1
expression was present in 36% of primary carcinomas and the
presence of lymph node metastasis further indicated that PD-L1
expression may be associated with reduced OS and DFS. However, in a
meta-analysis of 3,105 patients from 23 studies, no significant
difference between patients with PD-L1-positive and -negative HNSCC
was obtained in terms of OS and DFS (
36
), while a recently reported randomized
phase III clinical study (KEYNOTE-048) (
18
) demonstrated that pembrolizumab
(anti-PD-L1) plus platinum treatment is suitable for PD-L1-positive
recurrent or metastatic HNSCC. The results of the present study
supported this evidence, as it was demonstrated that >80% of
tumors have a PD-L1 score ≥1 and indicated that increased PD-L1
expression may be associated with unfavorable OS and DFS in
HNSCC.
PD-1/PD-L1 immune checkpoint therapy has
revolutionized the traditional cytotoxic anticancer treatments in
recent years and has achieved a long-lasting therapeutic response
in various types of cancer (
37
).
However, these therapies still pose significant clinical challenges
for patients with HNSCC. In order to further understand the
mechanism of the PD-1/PD-L1 pathway, the associations between
PD-L1, CD3 and CD4 were investigated, but there were limitations in
detecting PD-1 expression due to the availability of samples;
hence, a new cohort of patients may be required for further
study.
In conclusion, the data of the present study
demonstrated that the numbers of CD4
+
TILs as detected
by IHC were associated with the clinical outcome of patients with
HNSCC. PD-L1 is commonly expressed in HNSCC at the protein and mRNA
levels. In particular, high expression of PD-L1 on IHC examination
may reflect the deterioration of OS and DFS and indicate the
opportunity for immune checkpoint blocking therapy in patients with
HNSCC.
Supplementary Material
Correlation between PD-L1 expression
and CD3+ or CD4+ tumor-infiltrating
lymphocytes. (A) CD3+ vs. PD-L1; (B) CD4+ vs.
PD-L1. PD-L1, programmed death ligand 1.
Acknowledgements
Not applicable.
Funding
Funding: The present study was funded by the Health Special
Project of Jilin Province (grant no. 2020SCZT002).
Availability of data and materials
The datasets used and/or analyzed during the present
study are available from the corresponding author upon reasonable
request.
Authors' contributions
GFG designed the study. ZMF and GFG are responsible
for confirming the integrity and authenticity of the data and the
accuracy of the data analysis. ZMF, DJZ, YYG, KWS and NY collected
and analyzed the patient data. SH, FG and YNW evaluated and
interpreted the clinicopathological data. DJZ, YYG and JB were
responsible for immunohistochemically staining and evaluated the
results. FG and YNW performed the statistical analysis and
interpreted the results. ZMF and DJZ wrote the manuscript. ZMF and
GFG revised the manuscript. All authors have read and approved the
final manuscript.
Ethics approval and consent to
participate
The authors are accountable for all aspects of the
work in ensuring that questions related to the accuracy or
integrity of any part of the work are appropriately investigated
and resolved. The study protocol was approved by the Medical Ethics
Committee of Jilin University (no. 2021-157) and all patients
consented to participate in the study.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing
interests.
References
| https://www.spandidos-publications.com/10.3892/mco.2022.2492 |
Mining | Free Full-Text | Required Plug Strength for Continuously Poured Cemented Paste Backfill in Longhole Stopes
Continuously poured paste backfill dramatically improves underground mining efficiency through reduced stope cycle time and simplified logistics. For longhole stopes, a backfill “plug” is poured to a few meters above the undercut brow and must gain sufficient strength to prevent failure through the plug when the “main” pour begins. A novel, rational engineering design approach that determines the required plug strength is developed. The potential failure mechanism during continuous pouring is identified and the theoretical solution and its numerical validation/calibration are discussed. Four field case histories are then used, three of them involving continuous pours, to demonstrate the theoretical solution’s validity in back-analysis. These case studies are unique in the extent and quality of total stress and water pressure measurements made throughout backfilling. Additionally, comprehensive laboratory data are available to characterize strength development during binder hydration in the first few days, which are critical to the back-analyses. Results indicate that continuous backfilling is feasible with reasonably attainable backfill strengths at most mines. However, mines must undertake comprehensive early strength laboratory testing, and must carry out field measurements during the pour to ensure the placed backfill behaviour is consistent with the analysis assumptions.
Required Plug Strength for Continuously Poured Cemented Paste Backfill in Longhole Stopes
by Murray Grabinsky 1,* , Will Bawden 2 and Ben Thompson 3
1
Department of Civil & Mineral Engineering, Faculty of Applied Science and Engineering, University of Toronto, Toronto, ON M5S 1A4, Canada
2
Bawden Engineering, Toronto, ON M4S 3H7, Canada
3
Mine Backfill Geomechanics Inc., London, ON N6A 2X1, Canada
*
Author to whom correspondence should be addressed.
Mining 2021 , 1 (1), 80-99; https://doi.org/10.3390/mining1010006
Abstract
:
Continuously poured paste backfill dramatically improves underground mining efficiency through reduced stope cycle time and simplified logistics. For longhole stopes, a backfill “plug” is poured to a few meters above the undercut brow and must gain sufficient strength to prevent failure through the plug when the “main” pour begins. A novel, rational engineering design approach that determines the required plug strength is developed. The potential failure mechanism during continuous pouring is identified and the theoretical solution and its numerical validation/calibration are discussed. Four field case histories are then used, three of them involving continuous pours, to demonstrate the theoretical solution’s validity in back-analysis. These case studies are unique in the extent and quality of total stress and water pressure measurements made throughout backfilling. Additionally, comprehensive laboratory data are available to characterize strength development during binder hydration in the first few days, which are critical to the back-analyses. Results indicate that continuous backfilling is feasible with reasonably attainable backfill strengths at most mines. However, mines must undertake comprehensive early strength laboratory testing, and must carry out field measurements during the pour to ensure the placed backfill behaviour is consistent with the analysis assumptions.
Keywords:
cemented paste backfill
;
continuous pouring
;
Prandtl analysis
;
cohesion
;
strength analysis
;
field instrumentation
1. Introduction
No rational process exists to determine required CPB plug strength before starting the main pour (including for the most desirable scenario, a continuous pour). Some mines continuously pour CPB using empirically developed procedures [
1
], but these do not provide insight into the factors controlling CPB plug stability and cannot be universally applied. One well-cited industry handbook suggests the CPB should attain a “strength” (presumably unconfined compressive strength,
U
C
S
) 150 kPa [
2
], but no explanation or substantiating case histories are provided. Whether mines use
U
C
S
= 150 kPa or some other target strength, there are trade-offs to how such strength is achieved. Some mines use higher binder content in the CPB plug to realize higher early strength, while others use a “cure period” after the plug pour (in some cases, several days) prior to backfilling the remainder of the stope. Regardless, if the target CPB strength is higher than necessary, either too much binder is being consumed or the stope cycle time is unnecessarily long, respectively.
The implications of insufficient CPB plug strength leading to barricade failure include fatality, damaged plant, and production delays. Four CPB failures reported by [ 3 ] and five by [ 4 ] highlight various potential contributing factors, but in all cases the failure mechanism through the CPB plug is washed out once the barricade is breached, making it impossible to identify progressive failure details. There is, therefore, urgent need to develop rational engineering design procedures (laboratory test methods, analysis methods, and field monitoring methods) to continuously pour CPB safely and economically.
The problem just described falls into the “data-limited, understanding-limit” class considered by [
5
], where numerical modeling should be used to explore potential failure mechanisms, understand the impact of different material behaviour assumptions, and identify the data and understanding further needed to better analyze the problem. An important step in this process is making appropriate simplifying assumptions: Start with the simplest model that seems to capture essential system behaviour, and only add complexity as needed. Therefore, field data that motivates the developed system idealization, and which facilitates analytical and numerical solutions is initially considered. Subsequently the solution is applied to four case histories where sufficient field monitoring and laboratory testing data exists to reasonably assess the predictive solution’s validity. Steps that other mines can take towards rationally engineering continuously poured CPB are then discussed.
2. Predictive Model Development, Validation, and Calibration
The simplifying assumptions used in developing the analytic solution are considered first. These motivate an analytic solution based in part on the Prandtl solution for footing bearing capacity in undrained clay. Numerical analysis is then used to validate and calibrate the analytic solution. Finally, a design procedure based on the solution is proposed.
2.1. Effective Stress Development during Field Pours
The CPB literature typically cites several examples of field monitoring, but most [ 6 , 7 , 8 , 9 , 10 ] do not collect data frequently enough, do not combine total stress and pore water pressure measurements, or do not have instrumentation in the appropriate backfill plug location to be relevant to the continuous CPB pour analyses considered here. The field monitoring studies undertaken by the authors at Williams, Kidd, and Cayeli mines [ 11 , 12 ] involved deploying up to five instrumentation clusters throughout the stope (two in the undercut and three throughout the height), with each cluster containing a minimum three orthogonal total earth pressure cells (TEPCs), a pore water pressure transducer (PWP, or piezometer), and a thermistor (TEMP) and electrical conductivity (EC) transducers. Figure 1 shows an example instrumentation cluster and deployment at Kidd mine. The TEMP and EC transducers help identify onset of significant binder (Portland cement and cement extenders, including fly ash and granulated ground blast furnace slag) hydration reactions. Additional TEPC and PWP transducers were installed on the barricade. Data was logged every five minutes throughout pouring, and every 15 minutes after pour completion.
Ref. [ 13 ] describe a similar approach at Casa Berardi mine, but using two clusters with TEPCs and PWPs. [ 14 ] give results from Kanowna Bell mine using one TEPC oriented for vertical total stress, and one PWP.
Published field monitoring results from the above mines were digitized in approximating linear segments (estimated precision generally ±0.5 h (hour) and ±5 kPa) for the instrument clusters closest to the stope’s middle base, in the CPB plug. As will be shown later, this is the critical location for formation of a potential failure surface through the plug, which could then lead to barricade failure.
Figure 2
shows field test results in terms of vertical effective stress development with respect to time after the CPB covers the transducers, for up to the subsequent 48 h (two days), which is generally sufficient time to complete the plug pour. Initial zero effective stress periods in which the CPB remains in an essentially fluid state (
σ
v
′
=
σ
h
′
=
P
W
P
) ranges between ~3 h (i.e., for Williams) and ~14 h. Horizontal effective stresses for the same mines and time periods remain below 25 kPa (see the previously cited studies for full monitoring results). Typical CPB rise rates range from 0.25 m/h to 0.40 m/h, so a ~5 m high undercut would fill in 12–20 h. For most of the mines shown in
Figure 2
, very little effective stress develops in either vertical or horizontal directions during this initial CPB plug pour period.
In these field studies the main CPB pours featured higher rise rates or lower binder contents, and the monitoring results indicated zero effective stress over much longer time periods, typically to the end of backfilling (see previously cited studies). For example, Figure 2 shows at Kidd the zero effective stress period within the CPB plug persisted for ~7 h, while in the main pour (which had half the binder concentration compared to the plug) the zero effective stress period existed for greater than 48 hours after the transducers in the main CPB pour were covered [ 11 ].
2.2. Strength Development during Field Pours
The field monitoring results reported by [ 11 , 12 ] show increasing TEMP measurements during the zero effective stress periods, which indicate binder hydration is occurring and so the CPB plug is gaining strength. [ 15 ] used direct shear tests to determine strengths at 4 h and at 1, 2, 4, 7 days and beyond. The CPB plug pours often take less than 24 h and occur under essentially zero effective stress which means material friction cannot contribute to backfill strength. Therefore, only material cohesion data is considered ( Figure 3 ).
The Williams binder is a blend of 50 wt% Portland Type I (GU) cement and 50 wt% Type C fly ash and shows relatively continuous cohesion development with cure time. In contrast, the Kidd binder is a blend of 10 wt% cement and 90 wt% ground blast furnace slag, and the Cayeli binder is CEM V from a Turkish manufacturer which is equivalent to 60 wt% cement and 40 wt% extenders. These binders show cohesion developing in stages, with significant increases after one day and again after four days for Kidd, and after two days for Cayeli. These stages probably correspond to the secondary reactions of the slag and other extenders, although this was not investigated in detail.
Although others have considered CPB strength increases due to self-weight consolidation during deposition [ 16 , 17 , 18 , 19 , 20 ], the slow start to effective stress development ( Figure 2 ) compared to material cohesion development ( Figure 3 ) suggests minimum potential for self-weight consolidation and associated strength gain at the studied mines. Indeed, [ 21 , 22 ] show that the as-placed bulk properties at Williams, Kidd, and Cayeli mines are the same as the as-mixed properties, except that occluded air was mixed into the paste during deposition which had the effect of slightly increasing void ratio and decreasing degree of saturation. Similar results are reported by [ 13 ] at Casa Berardi where cores from the CPB plug had void ratios similar to the as-mixed design. Therefore, the strengths shown in Figure 3 should be considered indicative of CPB curing under field conditions.
2.3. Preliminary Analytical Model for CPB Plug Strength
A vertical cross section through a typical stope and undercut are illustrated in Figure 4 , with indicated dimensions that will be used in formulating the analytical model. With reference to this figure, the following simplifying assumptions are made:
The undercut has square cross section with height
H
u
, and the distance between the backfill barricade and the undercut brow is
L
u
;
The undercut walls are rough so that shear occurs through the CPB across asperities, rather than along the CPB-rock interface;
The CPB plug has height
H
p
with height above the undercut brow
H
b
;
The height of main pour at any given time is
H
m
above the plug, and the main pour exerts fluid-like pressure on the plug
γ
H
m
where
γ
is the backfill’s unit weight;
The total backfill height at any time is
H
t
=
H
p
+
H
m
;
The average CPB plug undrained cohesion
c
at the end of the plug pour must be sufficient to create a “self-supporting” condition, such that the CPB plug no longer relies on the barricade for stability; and
The average CPB plug undrained cohesion
c
must continue to increase sufficiently during the main pour to support the surcharge
γ
H
m
and prevent failure through the CPB plug which would otherwise then exert further pressure on the barricade and potentially fail it.
In terms of barricade design, a worse-case loading scenario assumes the binder does not hydrate during the plug pour, in which case the barricade must safely resist the full slurry pressure head (i.e.,
γ
H
b
at the top of the barricade, increasing linearly to
γ
H
p
at the base of the barricade). If this happens, or if the self-supporting strength has not yet developed, then the pouring must stop upon plug completion and a cure period be used to allow for CPB plug strength gain before starting the main pour. Pressure monitoring at the barricade and within the CPB plug are therefore essential requirements for making informed decisions to ensure pouring continuously can be performed safely.
The idealization of the CPB plug shown in
Figure 5
incorporates these assumptions and shows the postulated failure mechanism through the plug, induced by the main pour. The out-of-plane extent of the failure mechanism is limited by the undercut width (assumed same as undercut height,
H
u
, although this could be generalized). Therefore, the failure zone above the brow (Zone 1 in
Figure 5
) has plan dimensions
H
u
×
2
H
u
.
Note that if the distance from the undercut brow to the opposing stope wall is less than
2
H
u
, then the postulated failure mechanism cannot be fully developed. This would imply an increased plug stability, although the issue is not further investigated here. Zones 2 and 3 can be considered a ½-Prandtl mechanism as used in analyzing shallow foundation bearing capacity for footings in undrained clay, for which the analysis when the out-of-plane footing dimension is finite follows Skempton’s method [
23
].
Table 1
shows each zone’s contribution to driving and resisting effects, with approximations noted (~). The ½-Prandtl mechanism’s self-weight driving effect assumes moment equilibrium about its rotation center, the brow. The ½-Prandtl mechanism’s resistance arises from Skempton’s simplifications regarding theoretical bearing capacity factor
(
2
+
π
)
≈
5
and out-of-plane shape factor 1.2; thus, the bearing capacity factor becomes 6, and for a ½-mechanism is 3.
Equation (1) expresses the above in limiting form: driving effects = resisting effects:
γ
(
H
m
+
H
b
+
0.65
H
u
)
=
c
(
4
H
b
H
u
+
3
+
4
L
u
H
u
)
(1)
2.4. Numerical Validation/Calibration
Three-dimensional (3D) nonlinear analyses were carried out using Rocscience finite element software (RS3) to validate the postulated failure mechanism, and to calibrate the coefficients in Equation (1). Additional calibration details are given in [ 24 ]. Figure 6 shows a sample result on a cross section through mid-undercut, and the emerging ½-Prandtl mechanism can be identified in the zones of high plastic shear strain. Note that a barricade is not included in the model, as previously explained. The critical pressure on the plug’s top surface was evaluated by incrementally increasing this pressure and monitoring (i) the out-of-balance force; (ii) the displacement at mid-point on the free face of the material in the undercut; and (iii) the evolution of plastic shear strain. The result shown in Figure 6 is very close to the ultimate applied pressure, and on the next pressure increment the plastic strain fully develops in the ½-Prandtl zones and instability ensues. This result implies there will be very little warning prior to an actual failure in an underground mine, which is consistent with observations from previous failures [ 3 , 4 ]. The 3D models also confirmed that the failure mechanism is limited in the out-of-plane direction by the lateral extents (i.e., width) of the undercut.
The coefficients in Equation (1) were tested using parametric studies to ensure agreement between numerical results and the predictive equation’s results. For example, a model with no material above the brow,
H
b
=
0
, was used with varying distances
L
u
, thereby determining that the ½-Prandtl zone’s self-weight effect should be 0.55 (not 0.65). Note that this self-weight term is irrelevant in the footing analysis for a full Prandtl mechanism, considered by Skempton, due to the mechanism’s symmetry about the rotation point, i.e., the footing’s edge which is analogous to the brow in the undercut. Also note that the mechanism in the material above the brow shown in
Figure 6
is not entirely vertical as assumed in
Figure 5
, however, this did not significantly affect the coefficients used in
Table 1
. The remaining coefficients were deemed appropriate. Therefore, Equation (2) shows the calibrated design equation that will be used (in modified forms) for subsequent back-analyses of field data:
γ
(
H
m
+
H
b
+
0.55
H
u
)
=
c
(
4
H
b
H
u
+
3
+
4
L
u
H
u
)
(2)
2.5. Non-Uniform Strength Effects
At the completion of the CPB plug pour, the backfill at the plug’s top surface will still be fluid while layers deeper into the plug have had longer to cure and should have increasing strength with depth. This was tested using a model like that shown in
Figure 6
, except that the cohesion varied linearly from 1 kPa at the plug’s top surface to a maximum value at the plug’s bottom surface. The cohesion at height ½
H
u
was then used in a uniform strength model, with similar ultimate capacity predicted. Therefore, the reference cohesion value used in Equation (2) should be based on cohesion developed at ½
H
u
. The implication of this is that the “cure time” (
Figure 3
) needs to be referenced with respect to the time when the backfill reached ½
H
u
, and not with respect to when pouring started.
2.6. Recommended Analysis Procedure
The first analysis step determines if there is sufficient cohesion at elevation ½
H
u
at the end of the CPB plug pour to make the plug self-supporting, i.e., as if the barricade could be removed and the CPB plug would not fail (although any mining operation would be imprudent to venture removing the barricade at this point). Under these circumstances
H
m
=
0
and Equation (2) can be rearranged to obtain Equation (3) for the limiting self-supporting cohesion,
c
s
s
, normalized as follows:
c
s
s
γ
H
u
=
0.55
+
H
b
H
u
3
+
4
H
b
H
u
+
4
L
u
H
u
(3)
When the main pour starts and as it continues, the CPB plug’s strength must continue to increase to support the additional load on the plug’s top surface arising from the main pour’s pressure. The second analysis stage therefore considers evolving CPB plug strength and imposed plug surcharges. The analysis procedure involves computing the maximum main pour height
H
m
,
m
a
x
supportable for the available cohesion developed at ½
H
u
. This can then be compared to the planned
H
m
, or actual
H
m
if used in a back-analysis. Rather than defining a conventional Strength Factor (e.g., available-cohesion/required-cohesion) it is recommended instead to use an “excess fill height capacity”,
H
m
,
m
a
x
—
H
m
, because techniques exist to determine
H
m
during the main pour. The time variable
t
is referenced with respect to start of plug pour. The CPB plug’s cure time is (
t
−
t
r
e
f
) where
t
r
e
f
is when the plug pour reaches ½
H
u
. The time-varying quantities of interest during the main pour are cohesion
c
(
t
−
t
r
e
f
)
, maximum supportable main pour height
H
m
,
m
a
x
(
t
)
, and actual main pour height
H
m
(
t
)
.
H
m
,
m
a
x
(
t
)
depends on cohesion developed greater than
c
s
s
. Therefore, Equation (4) shows Equation (3) rearranged to incorporate this increasing strength effect.
H
m
,
m
a
x
(
t
)
=
1
γ
(
c
(
u
H
u
)
(4)
The maximum total backfill height with time is then simply
H
t
,
m
a
x
(
t
)
=
H
p
+
H
m
a
x
(
t
)
. The next section uses Equation (3) in the case study back-analyses to determine each CPB plug’s self-supporting condition, and then uses Equation (4) to assess ongoing CPB plug stability during the main pours.
3. Back-Analyses of Field Case Histories
The distinction between plug and main pours depends on the mine, with variations including (i) use a cure period after plug pour to allow for plug strength gain before main pour, and (ii) use higher binder content in the plug to achieve higher early strength and enable continuous pouring. It must be noted that each case study involved multiple measurement locations within the backfill and at the barricade, and the pressures were monitored in real time to ensure continuous pouring was safe.
3.1. Case History Analysis Parameters
Deciding appropriate
H
u
,
H
b
,
L
u
values requires judgment, since real mine geometries are never exactly as assumed in the preceding analysis. When in doubt, parametric studies are needed to determine the computed
H
m
a
x
(
t
)
sensitivity to assumed parameter values. [
11
,
12
] provide fuller information related to each case study, but
Figure 7
illustrates the most problematic geometry of these, Cayeli Stope 685. This involved a continuous pour with binder transition at
H
p
=
9.0 m. By choosing
L
u
=
1.8 m and determining the overlying brow location (which is an approximation made from a cavity monitoring survey) it is estimated
H
5.5 m and
H
b
=
3.5 m for a combined
H
p
=
9.0 m.
Table 2
gives the geometric parameters for all case studies.
The distinctions between the plug and main pours in the case studies are as follows: Cayeli 685, Kidd 67-SL1, and Williams L70-5 use higher binder content in the CPB plug and a continuous pour; Cayeli 715 uses the same binder throughout and featured a cure period after the CPB plug pour.
The analysis also requires backfill unit weight, backfill rise rate in the plug pour
r
r
p
l
u
g
, time
t
r
e
f
when the backfill reaches height ½
H
u
, time
t
p
l
u
g
when the plug pour finishes, time
t
m
a
i
n
when the main pour starts (=
t
p
l
u
g
if a continuous pour), backfill rise rate in the main pour
r
r
m
a
i
n
, and time
t
f
i
n
a
l
when the stope is filled.
Table 3
gives values for these parameters. The times referenced are based on field recorded filling data and are actual times, and the rise rates represent averages in the plug and main pours. According to the idealized geometry used,
t
r
e
f
=
1
2
H
u
/
r
r
p
l
u
g
, although this is an approximation because the actual undercut geometry varies from the idealization.
3.2. Self-Supporting CPB Plug Strength Requirements
In terms of material strength, only undrained cohesion can be relied upon under zero effective stress conditions. An assumption used in some backfill design methods is that the material’s cohesion equals one-half the unconfined compressive strength,
c
=
1
2
U
C
S
. However, this assumption can be confused with the undrained shear strength of unstructured clay which may be written
s
u
=
1
2
U
C
S
, with the corresponding undrained friction angle
ϕ
u
=
0
. While unstructured clays do not dilate when sheared, CPB (which is predominantly silt) does dilate and so the
ϕ
u
=
0
assumption is invalid for CPB; the failure envelopes in the drained and undrained states are virtually identical for CPB. This has important implications that are considered in the Discussion section, and an appropriate relationship between
U
C
S
,
c
,
and
ϕ
is considered in this section. For the remainder of the article the terms cohesion (
c
) and friction (
ϕ
) are used with the understanding that the values for these parameters could be determined from drained tests, or from undrained tests with pore water pressure measurements, with identical results.
Mines inevitably assess strength using
U
C
S
, which is a strength parameter that depends on both cohesion and friction. [
15
] determined that for curing times up to 48 h, which is longer than all the plug pour times in
Table 3
, the friction angle
ϕ
varied between 35° and 37°. Equation (5) expresses the relation between these parameters, and for the given range of
ϕ
a reasonable approximation is
U
C
S
= 4
c
, as shown in
Figure 8
for tests on Williams CPB. This provides a straightforward basis to convert the self-supporting cohesion from Equation (3) to a self-supporting unconfined compressive strength,
U
C
S
s
s
.
U
C
S
=
2
c
cos
ϕ
1
−
sin
ϕ
(5)
The dimensionless parameters in Equation (3) facilitate general consideration of CPB plug strength requirement for a range of undercut geometries, shown graphically in
Figure 9
. Note that this is the equation for limiting strength (Strength Factor = 1.0) for a self-supporting plug, and the strength must continue to increase to support the main pour as considered in subsequent analysis.
Figure 9
considers the plausible extreme range of
H
b
/
H
u
and
L
u
/
H
u
and indicates the more usual design range for these parameters. The four case histories are also shown.
Table 4
shows available cohesion (interpolated from
Figure 3
) and the required self-supporting cohesion and corresponding
U
C
S
s
s
. When comparing the available cohesion to the required self-supporting cohesion, only Cayeli 715 did not meet the indicated strength requirement at the end of the plug pour. However, as shown in
Table 2
this was the only case study not involving a continuous pour. The difference between Cayeli 685 and 715 backfill performance is apparently due to differences in tailings mineralogy (Cayeli separates the tailings into “clastic” and “non-clastic” streams that are processed separately to maximize recovery). The delayed binder hydration reaction is reflected in the slow cohesion development shown in
Figure 3
. For sake of comparison,
Table 4
also shows the Strength Factor at the end of the plug pours, defined as the ratio of available cohesion to that required for the self-supporting condition,
S
F
=
c
(
t
p
l
u
g
−
t
r
e
f
)
/
c
s
s
. For the successful continuous pours, the required plug
U
C
S
ranges from 24 kPa (Williams) to 80 kPa (Cayeli 685). The implications of these strength requirements are considered in the Discussion section.
3.3. Main Pour Back Analyses to Determine Continuous Pour Viability
Figure 10
shows maximum main pour heights computed using Equation (4) and actual main pour heights from the field monitoring data for Kidd and Cayeli 685 stopes; and
Figure 11
shows the same for Williams and Cayeli 715 stopes. To use Equation (4) in calculating the supportable main pour heights, cohesion development with time data shown in
Figure 3
was moved forward in time by
t
r
e
f
(
Table 3
) to reflect the representative cohesion developed at ½
H
u
with respect to pour time. The linearization in the
H
m
,
m
a
x
(
t
)
curves reflect the frequency of cohesion measurements (see
Figure 3
); more frequent cohesion determinations would be desirable. The calculation sequence can start at
t
=
0
, but results
H
m
,
m
a
x
(
t
)
<
0
mean the plug has yet to achieve self-supporting strength.
Figure 10
shows the successful continuous pours at Kidd and Cayeli 685 stopes. At Kidd, the as-placed main pour height was always less than the maximum supportable height by at least 5 m. The sudden increase in capacity at 29 h is due to the cohesion increase seen in
Figure 3
at 24 h (the time difference being
t
r
e
f
to reflect cohesion acting at ½
H
u
). In contrast, the analysis for Cayeli 685 suggests at 57 h there was only ~1.5 m extra main fill capacity, however by this time, close to the end of pour, effective stresses developed within the CPB plug (see
Figure 2
for vertical effective stress; full stress results are given in (Thompson, et al., 2012)). These effective stresses mobilize the frictional strength components which contribute significantly to CPB plug stability.
Figure 11
shows the Cayeli 715 main fill height analysis with the actual fill height reflecting the three-day CPB plug cure period routinely used at the mine for this backfill type. However, the analysis in
Figure 11
indicates the main pour could have safely started at least one shift (12 h) earlier based on the limiting strength having been reached before 60 h.
Figure 10
also shows the Williams pour and the analysis indicates that CPB plug instability should be expected ~6 h after the start of the main pour (~
t
= 24 h). However, there are two factors mitigating potential failure. Firstly, the undercut’s height was 4.5 m and the distance from its brow to the opposite stope wall was about 6 m (see [
12
] for detailed geometry). Compared to the mechanism shown in
Figure 5
and
Figure 6
, the proximity of the opposite wall could interfere with development of the assumed failure mechanism. The other cases studied had significantly larger distances to opposing stope walls. Secondly, and likely more significantly, Williams CPB was the fastest of the cases studied to develop effective stresses, which started ~3 h after CPB reached the transducers in the CPB plug location (which was about 3 h into the pour (not shown)), and
Figure 2
shows that at 21 h (24 h into the pour) there was about 68 kPa vertical effective stress. At 24 h pour time, or 17 h cure time with respect to the reference location, there was already ~16 kPa cohesion, equivalent to
U
C
S
=
64 kPa, and even greater vertical effective stress could have been supported by the CPB plug with the developing effective horizontal stresses. Therefore, CPB plug strength was developing fast enough to withstand the effective stresses applied to the plug backfill. To understand backfill pour stability with fast effective stress development requires much more sophisticated analyses, such as the techniques demonstrated in [
9
,
14
,
15
,
26
,
27
,
28
,
29
,
30
]. These sophisticated analysis techniques are not warranted for routine designs.
3.4. Final CPB Plug Strength Requirement
The analysis presented herein can also be applied to calculate the final CPB plug strength required at the completion of backfilling,
U
C
S
f
i
n
a
l
. To determine
U
C
S
f
Finding the corresponding
U
C
S
at these later cure times may need to account for a changing friction angle. For Williams CPB [
15
] found that the friction angle remained ~37° throughout curing up to 28 days, and so
U
C
S
=
4
c
. However, the Cayeli 715 CPB had a progressively reducing friction angle to ~28° by 7 days, the Cayeli 685 CPB’s friction angle progressively decreased to about ~27° by four days, and the Kidd CPB’s friction angle started decreasing after 4 days and fell to ~26° by seven days. From Equation (5),
U
C
S
=
3.25
c
when the friction angle is ~27°. Therefore, for these other mines the equivalent
U
C
S
f
i
n
a
l
is between 3.25
c
f
i
n
a
l
and 4
c
f
i
n
a
l
.
Table 5
shows the ranges of these required strengths along with the equivalent cure time at which these strengths would have to be achieved.
Note that the strengths shown in
Table 5
assume no effective stress development in the CPB plug, but this assumption is increasingly tenuous with longer cure times (see
Figure 2
) and so these unfactored strength estimates are conservative from a safety perspective. This is particularly the case for Williams, as discussed in the previous section, and the assessed strength 333 kPa is unrealistically high for that operation. Field monitoring in the CPB plug is required to demonstrate when, and the extent to which effective stresses develop for a given mining operation. For mines embarking on stress measurement campaigns with the view to achieving continuous pours, a starting point for consideration (assuming site specific assessment) would require the CPB plug to achieve an appropriately factored
U
C
S
f
i
n
a
l
before starting the main pour (i.e., to ensure stability throughout the main pour), and the mine could then work towards achieving a plug strength
U
C
S
s
s
with a reasonable strength factor to facilitate continuous pouring.
4. Discussion: Application at Other Mine Sites
Notwithstanding the apparent agreement between the proposed analysis methods and results from the four cases studied, the potential consequences of a plug failure mean that future applications of the presented framework must be approached cautiously. This section discusses some requirements in applied design.
Many mines collect
U
C
S
data at 3, 7, 14, 28 days (sometimes less frequently, and sometimes for longer cure periods if cement extenders such as slag and fly ash are used, or if there is concern about long-term strength deterioration due to sulfate attack, for example). However, the cases studied demonstrate that the critical time for continuous pour analysis is before three days. Furthermore, cohesion cannot be determined from
U
C
S
unless
ϕ
is also known (or assumed). Therefore, mines interested in performing rational continuous pour analysis must consider alternate strength testing programs.
Figure 9
shows that a single empirically derived CPB plug strength is not universally applicable. More importantly, it demonstrates the sensitivity of required strength to (i) the setback from the undercut’s brow to the barricade,
L
u
; and (ii) to the height of plug backfill above the brow
H
b
. It also shows how the relationships between these parameters scale with the undercut’s absolute height,
H
u
. Of particular note, the required strength is sensitive to
L
u
: many operations want to minimize
L
u
so that they do not have to subsequently mine out the paste in the undercut when developing the adjacent stope, but this has consequences for increasing binder content (and strength development with time) if a continuous pour is to be achieved.
No empirically derived CPB plug strength is widely accepted, but one well-cited design handbook recommends the following:
“In bulk mining stopes, the paste fill should be placed approximately 1 m above the draw point brow and permitted to cure to approximately 150 kPa strength before filling the remainder of the stope.”
([ 2 ], p.92)
Note that this recommendation does not indicate
where
in the plug this strength should be achieved, nor does it account for the effects of the main pour height, or different main pour rise-rates on the CPB plug. Given that the 150 kPa strength is a general recommendation, it is presumably empirically validated under normal operating conditions and deemed to be safely conservative, although to an unknown extent. As an aside, note that the suggested 1 m height above the brow is significantly less than the corresponding
H
b
values shown in
Table 2
.
For comparison with the design approach for
U
C
S
s
s
suggested here, consider the
U
C
S
= 150 kPa heuristic in the context of
Figure 9
. If a reasonably conservative Strength Factor = 2.0 is assumed so that the limiting
U
C
S
s
s
is 75 kPa, and assuming a large
H
u
= 7.5 m and a typical
γ
= 20 kN/m
3
, then
U
C
S
s
s
/
γ
H
u
= 0.5 and this corresponds to a range of
L
u
/
H
u
from 0.4 to 1.3 (see
Figure 9
), which many operations would consider unsafely close to the brow. (For reference, note that Kidd’s
L
u
/
H
u
= 1.5 is achieved using a frame that remotely pushes the barricade framework into place prior to shotcreting.) Most operations have more conservative operating parameters (smaller
H
u
, larger
L
u
/
H
u
) and so would have Strength Factors > 2.0 if they strictly adhered to the recommended heuristic. On the other hand, in comparison with the
U
C
S
f
i
n
a
l
values shown in
Table 5
, the recommended
U
C
S
= 150 kPa strength before starting the main pour falls within the range of calculated
U
C
S
f
i
n
a
l
values.
As mentioned, mines wishing to use the analysis approach described in this work need to carry out backfill strength testing at frequent intervals in the first few days representing the duration of CPB plug pour and start of main pour. These tests must focus on determining cohesion, either using direct shear tests combined with
U
C
S
as shown in
Figure 8
(the preferred method), or by combining
U
C
S
and confined triaxial tests with confining stresses up to
1
2
U
C
S
.
In addition, mines should determine typical effective stress development rates by carrying out field stress measurements prior to attempting continuous pours. This instrumentation should include PWP and vertical TEPC transducers at minimum, but preferably two orthogonal horizontal TEPCs as well, since this combination provides more reliable interpretation of effective stress development [ 11 , 12 ]. The instrumentation cage shown in Figure 1 is robust and straightforward for underground construction crews to install, as demonstrated by [ 13 ]. The transducers have internal thermistors to capture TEMP data that is helpful to ascertain when binder hydration becomes significant at the measurement point. The mid-point at the base of the stope, ~1.5 m off the stope floor is an ideal measurement point since this is where a potential failure mechanism would be expected to form ( Figure 6 ). If potential rock fall prior to stope filling is a concern, then the cage can also be placed at the undercut’s brow although its proximity to blasted host rock provides better drainage potential and so the PWPs may be lower than at mid-stope and, therefore, the interpreted effective stresses higher, which could lead to unsafe estimates of plug stability. When continuous pouring attempts begin, the same field monitoring strategies can be used to verify that the backfill behaviour corresponds to the analysis assumptions. While not strictly part of the CPB plug design, barricade monitoring is also strongly recommended to ensure safe barricade loading limits are adhered to throughout the pour. It should be cautioned that barricade pressure measurements of effective stress likely are not representative of the effective stress state within the plug; [ 11 ] reported that effective stress at the barricade developed significantly more quickly than at the brow (C1 location, Figure 7 ). As such, barricade pressure measurements alone are not recommended for verifying the conditions of this analysis.
The approach considered here only addresses plug stability under pressures arising from the main pour. Other design considerations may also need to be addressed. One of these is liquefaction resistance, for which an often-referred to heuristic is
U
C
S
=
100 kPa [
31
]. However, [
32
] found that after 12 h the Golden Giant CPB (similar to Williams CPB, because both operations mine the same orebody) could not be liquefied using the highest cyclic loading possible from the available MTS load frame. Similar results have been found by [
33
] for Kidd tailings after 7 h binder cure time. As mentioned, the barricade should be designed to withstand the full slurried CPB pressure during the plug pour, and in 12 h only the top 3 m would be prone to liquefaction (assuming deposition rate 0.33 m/h), so the liquefaction concern is overstated in this specific design case.
Finally, the strength assumption stated in
Section 3.2
requires discussion in the context of the proposed plug strength analysis method. The common undrained strength assumption, that
ϕ
=
0
and therefore the undrained cohesion is
1
2
U
C
S
, only applies to materials that do not dilate during shearing (i.e., unstructured clays). [
34
] used miniature tensiometers installed in the base platen of a triaxial cell to monitor a CPB’s pore water pressure and suction changes during
U
C
S
tests, as well as in non-backpressure saturated consolidated-undrained (CU) tests. The test results showed how dilation potential during shear induced more than 60 kPa incremental suction and therefore increased the effective stress, leading to measured shear resistance larger than for the assumed confining stress level. [
35
] showed the same effects in conventional backpressure saturated undrained (CU) and drained (CD) tests on Williams materials, results for which are shown in
Figure 12
. Further, [
35
] demonstrated that the failure envelopes determined from drained and undrained testing were virtually identical (angles within about 1°) for unamended tailings (shown in
Figure 12
) as well as for the mine’s CPB. Similar results were obtained by [
33
] for tests on Kidd mine materials including (i) mine tailings alone, (ii) tailings blended with esker sand, and (iii) the mine’s CPB (tailings, sand, and binder).
Some authors [
36
,
37
,
38
] have tested CPB under undrained, but non-backpressure saturated conditions and without using pore water pressure measurements. In these cases, the induced suction during shearing at low confining stress levels leads to increases in effective confining pressure (to an unmeasured degree) and, therefore, artificially high interpretations of mobilized shear resistance, as shown in [
34
]. Studies on Kidd tailings [
33
] and Williams tailings [
35
] found backpressures of at least 400 kPa were required for saturation. Therefore, tests by [
36
,
37
,
38
] at higher confining pressure levels would result in closer to saturated conditions. However, as shown in
Figure 12
, the mobilized shear resistance in undrained testing is not as high as in drained testing. The combined result of over-interpreted shear resistance at low confining stresses and under-interpreted shear resistance at high confining stresses leads to lower estimates of friction angle and higher estimates of cohesion, potentially resulting in the interpreted friction angle being zero and undrained cohesion being
1
2
U
C
S
. An extreme example is shown by some of the test results using Kidd CPB in [
38
] where stress deviator decreases with increasing confining stress, implying a negative friction angle in total stress space. This result is inconsistent with results of [
33
] which used backpressure saturation and pore water pressure measurements when testing the same Kidd CPB. The authors in [
36
] note that results from tests without backpressure saturation and pore water pressure measurements must be used carefully in design and could lead to overestimating backfill strength in some cases. Estimating plug strength requirements is such a case, where using
c
=
1
2
U
C
S
would reduce the calculated strength (
U
C
S
) requirement by a factor of two. If the recently placed backfill remains close to saturated, as was determined from field tests by [
21
,
22
], then
c
=
1
4
U
C
S
must be used. It is therefore recommended that the assumption
c
=
1
4
U
C
S
continue to be used until it can be demonstrated that greater estimates of cohesion are warranted.
5. Conclusions
The proposed CPB plug stability assessment method is the first attempt to provide a framework for rational engineering analysis of CPB strength required for continuous pouring. The case studies used to compare against the developed approach’s predictions are unique in terms of (i) the extent and quality of field monitoring data available, and (ii) the frequency and type of laboratory strength testing carried out as part of a larger previous research program at these mine sites. However, mines have the capacity to carry out field instrumentation of the kind illustrated in the case studies, albeit in a focused way at select stope locations. Consulting companies should generally have the equipment for the needed strength testing procedures, and with further research some improvement and simplification of these test methods may result in equipment that also can be used routinely at mine sites along with slump/viscometer testing,
U
C
S
testing, etc.
The proposed analysis method correctly assessed the continuous pour potential for Kidd and Cayeli 685 stopes. It also correctly assessed that the Cayeli 715 stope required a cure period after completing the CPB plug pour, and the results indicated that the CPB plug cure duration used by the mine was likely conservative and could have been shortened by at least one shift (12 h). For Williams mine the analysis results correctly indicated the potential for continuous pour, but then incorrectly indicated that the CPB plug strength was insufficient ~6 h into the main pour. However, in this case the narrow stope geometry relative to the undercut height, and the quickly developing CPB strength relative to the developing effective stress imposed by self-weight helped to mitigate against failure, and a continuous pour was successful. It will be important in future to determine similar mining scenarios where the CPB plug strength analysis is overly-conservative from a strength perspective.
The self-supporting CPB plug strength assessment (Equation (3),
Figure 9
) suggests that the recommended
U
C
S
=
150 kPa heuristic likely over-estimates required CPB self-supporting plug strength (in the context of a continuous pour) for most backfilling cases, even if a reasonable Strength Factor is applied to the analysis. The backfilling cases studied indicate that if the self-supporting strength has been achieved then the remainder of the pour is likely to be successful, although this cannot be assured, and Equation (4) should still be used as a check. The final case study, Williams, shows the limitations of the analysis approach when the stope geometry infringes on development of the potential failure surface, or when effective stress development occurs. Even in these cases, however, the initial CPB plug strength assessment (Equation (3),
Figure 9
) will give a reasonable upper-bound strength estimate that in many cases will be lower than
U
C
S
=
150 kPa.
If the suggested analysis and design approach is used at other mines that are willing to share their experience, the rational engineering approach recommended here can be improved and confidence will increase in carrying out continuous pours of cemented paste backfill under properly controlled conditions.
Author Contributions
All authors contributed to the iterative refinement of postulated failure mechanism and to recommended design procedures for other mines. M.G. developed the analytic solution and oversaw numerical calibration. W.B. contributed to contextualization of results in an operating mine environment. B.T. oversaw the original field instrumentation at Williams, Kidd, and Cayeli mines and contributed to field data processing and interpretation. M.G. provided first manuscript draft and colleagues contributed to reviewing and editing. All authors have read and agreed to the published version of the manuscript.
Funding
This original work received no external funding, however it arose out of a multi-year research project originated by the authors at the University of Toronto involving partnership with Williams, Kidd, and Cayeli mines (and their parent companies at the time, Barrick, Xstrata, and Inmet) and the Natural Sciences and Engineering Research Council (NSERC) Canada.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
All data supporting reported results has been included.
Acknowledgments
A preliminary version of this work appears as a conference paper at Minefill 2020 (postponed to the last week of May 2021). Flac3D models presented in that work were carried out by Jeff Oke while at Mine Design Engineering (MDE) in Kingston, Ontario, under supervision of the first author. Compared to the conference paper, the work here provides additional case studies and a more practical recommended analysis and design approach.
Conflicts of Interest
The authors declare no conflict of interest.
References
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Figure 1. University of Toronto fieldwork instrumentation: ( a ) cluster with TEPCs and PWP (photo credit: Ben Thompson while a Research Associate with University of Toronto); ( b ) clusters deployed in stope at Kidd mine (photo credit: Ryan Veenstra while a PhD candidate at the University of Toronto).
Figure 1. University of Toronto fieldwork instrumentation: ( a ) cluster with TEPCs and PWP (photo credit: Ben Thompson while a Research Associate with University of Toronto); ( b ) clusters deployed in stope at Kidd mine (photo credit: Ryan Veenstra while a PhD candidate at the University of Toronto).
Figure 2. Vertical effective stress development at the indicated mines (referenced with respect to time when backfill covers the TEPC and PWP transducers). Adapted from data presented in [ 11 , 12 , 13 , 14 ].
Figure 2. Vertical effective stress development at the indicated mines (referenced with respect to time when backfill covers the TEPC and PWP transducers). Adapted from data presented in [ 11 , 12 , 13 , 14 ].
Figure 3. Cohesion development with curing time for Williams, Kidd, and Cayeli mines. Adapted from data presented in [ 15 ].
Figure 3. Cohesion development with curing time for Williams, Kidd, and Cayeli mines. Adapted from data presented in [ 15 ].
Figure 4. Idealized plug and main pour geometry and dimensions for developing an analytic solution.
Figure 4. Idealized plug and main pour geometry and dimensions for developing an analytic solution.
Figure 5. Simplified geometry and postulated plug failure mechanism defined as four discrete zones.
Figure 5. Simplified geometry and postulated plug failure mechanism defined as four discrete zones.
Figure 6. Sample failure mechanism from numerical analysis (plastic shear strain contours, dark blue being elastic, with increasing plastic strain magnitude to the red and white zones).
Figure 6. Sample failure mechanism from numerical analysis (plastic shear strain contours, dark blue being elastic, with increasing plastic strain magnitude to the red and white zones).
Figure 7. Undercut geometry at Cayeli Stope 685; dimensions in meters. From [ 11 ].
Figure 7. Undercut geometry at Cayeli Stope 685; dimensions in meters. From [ 11 ].
Figure 8. Relationship between cohesion, friction angle, and UCS , shown in Mohr’s stress space. Dashed circles are from UCS tests, solid dot markers are from direct shear tests [ 25 ].
Figure 8. Relationship between cohesion, friction angle, and UCS , shown in Mohr’s stress space. Dashed circles are from UCS tests, solid dot markers are from direct shear tests [ 25 ].
Figure 9. Self-supporting plug strength UCS ss based on plug geometry and assuming UCS = 4 c (∅ ≈ 37°). Contours based on Equation (3), mine’s values from Table 2 .
Figure 9. Self-supporting plug strength UCS ss based on plug geometry and assuming UCS = 4 c (∅ ≈ 37°). Contours based on Equation (3), mine’s values from Table 2 .
Figure 10. Main pour analysis for Kidd and Cayeli 685 stopes. Hm , max ( t ) values determined using Equation (4).
Figure 10. Main pour analysis for Kidd and Cayeli 685 stopes. Hm , max ( t ) values determined using Equation (4).
Figure 11. Main pour analysis for Williams and Cayeli 715 stopes. Hm , max ( t ) values determined using Equation (4).
Figure 11. Main pour analysis for Williams and Cayeli 715 stopes. Hm , max ( t ) values determined using Equation (4).
Figure 12. Triaxial test effective stress paths for Williams Mine Tailings in undrained (CU) testing (MTCUn, curved stress paths) and drained (CD) testing (MTCDn, linear stress paths). FL is failure line for drained tests. CSRL is constant stress ratio line for undrained tests (interpreted as FL in the undrained condition). PTL is the phase transition line for undrained tests (PT, phase transition, is the point in undrained testing where incremental pore water pressure changes from positive to negative and corresponds to the onset of dilation in drained tests). Figure from [ 35 ].
Figure 12. Triaxial test effective stress paths for Williams Mine Tailings in undrained (CU) testing (MTCUn, curved stress paths) and drained (CD) testing (MTCDn, linear stress paths). FL is failure line for drained tests. CSRL is constant stress ratio line for undrained tests (interpreted as FL in the undrained condition). PTL is the phase transition line for undrained tests (PT, phase transition, is the point in undrained testing where incremental pore water pressure changes from positive to negative and corresponds to the onset of dilation in drained tests). Figure from [ 35 ].
Table 1. Driving and resisting effects for zones in Figure 5 . Geometric parameters are defined in Figure 4 .
Table 1. Driving and resisting effects for zones in Figure 5 . Geometric parameters are defined in Figure 4 .
Zone Driving Effect Resisting Effect plug’s top surface γ H m n/a above brow, Zone 1 γ H b ~4 c H b / H u ½-Prandtl, Zones 2 and 3 ~0.65 γ H u ~3 c undercut, Zone 4 n/a 4 c L u / H u
Some quantities approximated; see text.
Table 2. Geometric parameters for all case studies (all dimensions in m, see Figure 4 ).
Table 2. Geometric parameters for all case studies (all dimensions in m, see Figure 4 ).
Mine/Stope L u H u H b H p H m f i n a l H t f i n a l Cayeli 685 1.8 5.5 3.5 9.0 7.4 16.4 Cayeli 715 1.8 4.5 2.0 6.5 8.5 15.0 Kidd 67-SL1 6.75 4.4 2.0 6.4 25.6 32.0 Williams L70-5 9.3 4.5 1.5 6.0 49.0 55.0
Table 3. Fill analysis parameters for all case studies, with values determined from [ 11 , 12 ].
Table 3. Fill analysis parameters for all case studies, with values determined from [ 11 , 12 ].
Mine/Stope γ r r p l u g t r e f t p l u g t m a i n r r m a i n t f i n a l (kN/m 3 ) (m/h) (h) (h) (h) (m/h) (h) Cayeli 685 21.4 0.23 9 39 39 0.24 70 Cayeli 715 22.4 0.33 8 20 93 0.39 115 Kidd 67-SL1 20.6 0.36 5 18 18 0.31 101 Williams L70-5 19.8 0.33 7 18 18 1.00 67
Table 4.
Developed cohesion at elevation ½
H
u
at end of plug pours versus self-supporting strength requirements (cohesion and
U
C
S
). The Cayeli 715 case is italicized as the only considered non-continuous pour.
c
s
s
values determined using Equation (3).
Table 4.
Developed cohesion at elevation ½
H
u
at end of plug pours versus self-supporting strength requirements (cohesion and
U
C
S
). The Cayeli 715 case is italicized as the only considered non-continuous pour.
c
s
s
values determined using Equation (3).
Mine/Stope t p l u g − t r e f c ( t p l u g − t r e f ) c s s SF U C S s s (h) (kPa) (kPa) (kPa ϕ = 36°) Cayeli 685 30 31 20 1.6 80 Cayeli 715 12 5 16 0.3 64 Kidd 67-SL1 13 20 8 2.5 32 Williams L70-5 11 14 6 2.3 24
Table 5.
CPB plug strength requirements at end of backfilling (Strength Factor = 1). The equivalent curing time (
t
f
i
n
a
l
−
t
r
e
f
) for Cayeli 715 includes the plug cure period and would be about 36 h less if the pour had been continuous.
c
f
i
n
a
l
values determined using Equation (6).
Table 5.
CPB plug strength requirements at end of backfilling (Strength Factor = 1). The equivalent curing time (
t
f
i
n
a
l
−
t
r
e
f
f
i
n
a
l
values determined using Equation (6).
Mine/Stope H m f i n a l c f i n a l U C S f i n a l U C S f i n a l t f i n a l − t r e f (m) (kPa) (kPa, ϕ = 27°) (kPa, ϕ = 36°) (h) Cayeli 685 7.4 43.5 141 174 61 Cayeli 715 8.5 45.6 148 182 107 Kidd 67-SL1 25.6 56.5 184 226 96 Williams L70-5 49.0 83.2 n/a 333 60
No
MDPI and ACS Style
Grabinsky, M.; Bawden, W.; Thompson, B. Required Plug Strength for Continuously Poured Cemented Paste Backfill in Longhole Stopes. Mining 2021, 1, 80-99.
https://doi.org/10.3390/mining1010006
AMA Style
Grabinsky M, Bawden W, Thompson B. Required Plug Strength for Continuously Poured Cemented Paste Backfill in Longhole Stopes. Mining. 2021; 1(1):80-99.
https://doi.org/10.3390/mining1010006
Chicago/Turabian Style
Grabinsky, Murray, Will Bawden, and Ben Thompson. 2021. "Required Plug Strength for Continuously Poured Cemented Paste Backfill in Longhole Stopes" Mining1, no. 1: 80-99.
https://doi.org/10.3390/mining1010006
| https://www.mdpi.com/2673-6489/1/1/6/htm |
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Frequently requested statistics for: Middlesex County, New Jersey; New Jersey; Atlantic County, New Jersey; Hunterdon County, New Jersey; Somerset County, New Jersey; United States
U.S. Census Bureau QuickFacts: Middlesex County, New Jersey; New Jersey; Atlantic County, New Jersey; Hunterdon County, New Jersey; Somerset County, New Jersey; United States
Please note that new Connecticut county level geographies are not availabe within the map.
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QuickFacts
Middlesex County, New Jersey; New Jersey; Atlantic County, New Jersey; Hunterdon County, New Jersey; Somerset County, New Jersey; United States
QuickFacts provides statistics for all states and counties, and for cities and towns with a
population of 5,000 or more
.
6
Table
Map
Middlesex County, New Jersey New Jersey Atlantic County, New Jersey Hunterdon County, New Jersey Somerset County, New Jersey United States
What's New & FAQs
What's New? (data release dates)
Facts Updated for Places and Minor Civil Divisions on 5/18/23 Population Estimates, July 1, 2022 (V2022) Population Estimates base, April 1, 2020 (V2022) Population, Percent Change - April 1, 2020 (estimates base) to July 1, 2022, (V2022)
Facts Updated for U.S., States, and Counties on 5/18/23 Housing Units, July 1, 2022 (V2022)
Fact updated for U.S., States, and Counties on 5/11/23 Building permits, 2022
Facts updated for U.S., States, Puerto Rico, Counties, and Municipios on 4/27/23 Total employer establishments, 2021 Total employment, 2021 Total annual payroll, 2021 ($1,000) Total employment, percent change, 2020-2021
Facts updated for Counties and Municipios on 3/30/23 Population estimates, July 1, 2022, (V2022) Population estimates base, April 1, 2020, (V2022) Population, percent change - April 1, 2020 (estimates base) to July 1, 2022, (V2022)
Facts updated for U.S., States, and Puerto Rico on 12/22/22 Population estimates, July 1, 2022, (V2022) Population estimates base, April 1, 2020, (V2022) Population, percent change - April 1, 2020 (estimates base) to July 1, 2022, (V2022)
Fact updated for Counties on 12/15/22 Persons in poverty, percent, 2021
Facts updated for U.S., States, Puerto Rico, Counties, Municipios, Places, Zona Urbanas, Comunidades, and Minor Civil Divisions on 12/8/22 Veterans, 2017-2021 Foreign born persons, percent, 2017-2021 Owner-occupied housing unit rate, 2017-2021 Median value of owner-occupied housing units, 2017-2021 Median selected monthly owner costs -with a mortgage, 2017-2021 Median selected monthly owner costs -without a mortgage, 2017-2021 Median gross rent, 2017-2021 Households, 2017-2021 Persons per household, 2017-2021 Living in same house 1 year ago, percent of persons age 1 year+, 2017-2021 Language other than English spoken at home, percent of persons age 5 years+, 2017-2021 Households with a computer, percent. 2017-2021 Households with a broadband Internet subscription, percent, 2017-2021 High school graduate or higher, percent of persons age 25 years+, 2017-2021 Bachelor's degree or higher, percent of persons age 25 years+, 2017-2021 With a disability, under age 65 years, percent, 2017-2021 In civilian labor force, total, percent of population age 16 years+, 2017-2021 In civilian labor force, female, percent of population age 16 years+, 2017-2021 Mean travel time to work (minutes), workers age 16 years+, 2017-2021 Median household income (in 2019 dollars), 2017-2021 Per capita income in past 12 months (in 2019 dollars), 2017-2021
Facts updated for Municipios, Places, Zona Urbanas, Comunidades, and Minor Civil Divisions on 12/8/22 Persons without health insurance, under age 65 years, percent, 2017-2021 Persons in poverty, percent, 2017-2021
Facts updated for Places, Zona Urbanas, Comunidades, and Minor Civil Divisions on 12/8/22 Persons under 5 years, percent, 2017-2021 Persons under 18 years, percent, 2017-2021 Persons 65 years and over, percent, 2017-2021 Female persons, percent, 2017-2021
Facts updated for Puerto Rico, Municipios, Places, Zona Urbanas, Comunidades, and Minor Civil Divisions on 12/8/22 White alone, percent, 2017-2021 Black or African American alone, percent, 2017-2021 American Indian and Alaska Native alone, percent, 2017-2021 Asian alone, percent, 2017-2021 Native Hawaiian and Other Pacific Islander alone, percent, 2017-2021 Two or More Races, percent, 2017-2021 Hispanic or Latino, percent, 2017-2021 White alone, not Hispanic or Latino, percent, 2017-2021
Facts updated for States and Puerto Rico on 9/15/22 Persons without health insurance, under age 65 years, percent, 2021 Persons in poverty, percent, 2021
Facts updated for the U.S on 9/13/22 Persons without health insurance, under age 65 years, percent, 2021 Persons in poverty, percent, 2021
Fact updated for States and Counties on 8/11/22 Persons without health insurance, under age 65 years, percent, 2020
Facts updated for U.S., States, and Counties (Source: Population Estimates) on 6/30/22 Persons under 5 years, percent, July 1, 2021, (V2021) Persons under 18 years, percent, July 1, 2021, (V2021) Persons 65 years and over, percent, July 1, 2021, (V2021) Female persons, percent, July 1, 2021, (V2021) White alone, percent, July 1, 2021, (V2021) Black or African American alone, percent, July 1, 2021, (V2021) American Indian and Alaska Native alone, percent, July 1, 2021, (V2021) Asian alone, percent, July 1, 2021, (V2021) Native Hawaiian and Other Pacific Islander alone, percent, July 1, 2021, (V2021) Two or More Races, percent, July 1, 2021, (V2021) Hispanic or Latino, percent, July 1, 2021, (V2021) White alone, not Hispanic or Latino, percent, July 1, 2021, (V2021)
Facts updated for Puerto Rico and Municipios (Source: Population Estimates) on 6/30/22 Persons under 5 years, percent, July 1, 2021, (V2021) Persons under 18 years, percent, July 1, 2021, (V2021) Persons 65 years and over, percent, July 1, 2021, (V2021) Female persons, percent, July 1, 2021, (V2021)
Facts updated for U.S., States, and Counties on 6/30/22 Total nonemployer establishments, 2019
Facts updated for U.S., States, Puerto Rico, Counties, Municipios, Places, and Minor Civil Divisions on 6/23/22 Total accommodation and food services sales, 2017 ($1,000) Total health care and social assistance receipts/revenue, 2017 ($1,000) Total transportation and warehousing receipts/revenue, 2017 ($1,000) Total retail sales, 2017 ($1,000) Total retail sales per capita, 2017
Facts updated for U.S., States, Counties, Places, and Minor Civil Divisions on 6/23/22 All employer firms, Reference year 2017 Men-owned employer firms, Reference year 2017 Women-owned employer firms, Reference year 2017 Minority-owned employer firms, Reference year 2017 Nonminority-owned employer firms, Reference year 2017 Veteran-owned employer firms, Reference year 2017 Nonveteran-owned employer firms, Reference year 2017
Facts updated for U.S., States, Puerto Rico, Counties, Municipios, Places, Zona Urbanas, Comunidades, and Minor Civil Divisions on 6/23/22 Population per square miles, 2020 Land area in square miles, 2020
Facts Updated for Places and Minor Civil Divisions on 5/26/22 Population Estimates, July 1, 2021 (V2021) Population Estimates base, April 1, 2020 (V2021) Population, Percent Change - April 1, 2020 (estimates base) to July 1, 2021, (V2021)
Facts Updated for U.S., States, and Counties on 5/26/22 Housing Units, July 1, 2021 (V2021)
Fact updated for U.S., States, and Counties on 5/12/22 Building permits, 2021
Facts updated for U.S., States, Puerto Rico, Counties, and Municipios on 4/28/22 Total employer establishments, 2020 Total employment, 2020 Total annual payroll, 2020 ($1,000) Total employment, percent change, 2019-2020
Facts updated for Counties and Municipios on 3/24/22 Population estimates, July 1, 2021, (V2021) Population estimates base, April 1, 2020, (V2021) Population, percent change - April 1, 2020 (estimates base) to July 1, 2021, (V2021)
Facts updated for U.S., States, Puerto Rico, Counties, Municipios, Places, Zona Urbanas, Comunidades, and Minor Civil Divisions on 3/17/22 Veterans, 2016-2020 Foreign born persons, percent, 2016-2020 Owner-occupied housing unit rate, 2016-2020 Median value of owner-occupied housing units, 2016-2020 Median selected monthly owner costs -with a mortgage, 2016-2020 Median selected monthly owner costs -without a mortgage, 2016-2020 Median gross rent, 2016-2020 Households, 2016-2020 Persons per household, 2016-2020 Living in same house 1 year ago, percent of persons age 1 year+, 2016-2020 Language other than English spoken at home, percent of persons age 5 years+, 2016-2020 Households with a computer, percent. 2016-2020 Households with a broadband Internet subscription, percent, 2016-2020 High school graduate or higher, percent of persons age 25 years+, 2016-2020 Bachelor's degree or higher, percent of persons age 25 years+, 2016-2020 With a disability, under age 65 years, percent, 2016-2020 In civilian labor force, total, percent of population age 16 years+, 2016-2020 In civilian labor force, female, percent of population age 16 years+, 2016-2020 Mean travel time to work (minutes), workers age 16 years+, 2016-2020 Median household income (in 2020 dollars), 2016-2020 Per capita income in past 12 months (in 2020 dollars), 2016-2020
Facts updated for Municipios, Places, Zona Urbanas, Comunidades, and Minor Civil Divisions on 3/17/22 Persons without health insurance, under age 65 years, percent, 2016-2020 Persons in poverty, percent, 2016-2020
Facts updated for Places, Zona Urbanas, Comunidades, and Minor Civil Divisions on 3/17/22 Persons under 5 years, percent, 2016-2020 Persons under 18 years, percent, 2016-2020 Persons 65 years and over, percent, 2016-2020 Female persons, percent, 2016-2020
Facts updated for Puerto Rico, Municipios, Places, Zona Urbanas, Comunidades, and Minor Civil Divisions on 3/17/22 White alone, percent, 2016-2020 Black or African American alone, percent, 2016-2020 American Indian and Alaska Native alone, percent, 2016-2020 Asian alone, percent, 2016-2020 Native Hawaiian and Other Pacific Islander alone, percent, 2016-2020 Two or More Races, percent, 2016-2020 Hispanic or Latino, percent, 2016-2020 White alone, not Hispanic or Latino, percent, 2016-2020
Facts updated for U.S., States, and Puerto Rico on 12/21/21 Population estimates, July 1, 2021, (V2021) Population estimates base, April 1, 2020, (V2021) Population, percent change - April 1, 2020 (estimates base) to July 1, 2021, (V2021)
Fact updated for States and Counties on 12/16/21 Persons in poverty, percent, 2020
Facts updated for the U.S on 9/14/21 Persons without health insurance, under age 65 years, percent, 2020 Persons in poverty, percent, 2020
Facts updated for Counties, Municipios, Places, Zona Urbanas, Comunidades, and Minor Civil Divisions on 8/12/21 Population, Census, April 1, 2020
Fact updated for Counties on 6/24/21 Persons without health insurance, under age 65 years, percent, 2019
Facts updated for U.S., States, and Puerto Rico on 5/18/21 Population, Census, April 1, 2020
Fact updated for U.S., States, and Counties on 5/18/21 Building permits, 2020
Facts updated for U.S., States, Puerto Rico, Counties, and Municipios on 4/22/21 Total employer establishments, 2019 Total employment, 2019 Total annual payroll, 2019 Total employment, percent change, 2018-2019
Why can't I find my ZIP Code?
QuickFacts does not contain data for Postal ZIP Codes. Only States, Counties, Places, and Minor Civil Divisions ( MCDs
) for Puerto Rico and the United States with populations above 5000. When you search via a ZIP code QuickFacts provides a list of near matches for the geographic types contained within the application. These near matches are created from US Census Bureau ZIP Code Tabulation Areas ( ZCTAs )
which are generalized area representations of United States Postal Service (USPS) ZIP Code service areas.
Explore Census Data for ZCTAs data and surveys
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What is QuickFacts?
QuickFacts is an easy to use application that provides tables, maps, and charts of frequently requested statistics from many Census Bureau censuses, surveys, and programs. Profiles are available for the nation, all 50 states plus the District of Columbia and Puerto Rico, and all counties. Cities and towns with a population of 5,000 or more are also included.
What are the recommended browsers?
IE11+, Chrome, Firefox and Safari (Safari on MAC only)
How do I begin?
QuickFacts begins in TABLE view with data shown for the UNITED STATES. You can change to MAP view, CHART view, or the DASHBOARD view, that shows all three views at once.
How do I “Enter state, county, city, town, or ZIP code?”
Begin typing the name of the geography or ZIP code. After the second character, a list of choices will appear on the drop down. Locate and select your area by single-clicking the mouse or by using the up and down arrows and then pressing the Enter/Return key. The Enter/Return key may also be used if only one geography appears or your highlighted selection is at the top of the list. This becomes one of your selected geographies and is added to the TABLE in the first data column, moving UNITED STATES to the second data column.
How do I “SELECT A FACT?”
Simply click on SELECT A FACT to show the dropdown list, which is grouped by topic. Scroll down to highlight the FACT you want and click on the FACT to select it. In addition, you can double click on the row of the FACT in the TABLE.
How do I narrow the results?
In TABLE view, click ALL TOPICS and select the topic you want. The table view will show only facts within that topic. To view all facts again, select ALL TOPICS. In MAP view, you can further narrow results down to counties, county subdivisions, or places by selecting a geography color-coded circle and a small pop-up window appears with further area selections to view. For example, if your selected geography is a city, and you chose a city in that state on the map, you will have the option to Add this geography to your table, view at the United States level or view the counties in that state. In CHART view, you can toggle between all geographies at the same level as your selected area or those you have selected by using the ‘Show selected locations' checkbox. In DASHBOARD view, you can narrow down only what facts are showing by using the ALL TOPICS dropdown, as indicated above.
In TABLE view, how many geographies can I see?
TABLE view allows six geographies in the table. To add additional geographies use the search box. As you add geographies, they are added to the TABLE in the first data column, moving other geographies to the next column to the right. If there are more than one geography present, you may delete any geography by clicking the
icon. An orange circle on the TABLE icon indicates the total number of geographies currently selected. This is visible throughout the application above the data views.
In MAP view, how many geographies can I see? Can I zoom in and see data?
There are 3 additional controls in addition to the zoom in/out and full screen controls: Left Border Slide-out - Allows the user to quickly move to and remove their selected geographies. Switch Control in the upper right corner - Turns on the ability to select geographies across state boundaries. Toggle Button in the upper right corner - Toggles view between Townships and Places.
Clicking on a geography opens an info window. Within the info window you can: Add or remove a geography to your selection. View the current selected fact's value and footnote notations.
The new switch and toggle button are present on the map only when needed. All new controls will be pointed out to the user with a "NEW!" tooltip when first presented to the user. Hovering over the new control will give the user a description of the control's function as well as its current status if applicable.
Changing geography level is accomplished by zooming in/out. The progression as you zoom in is: States, Counties, Places & Townships. When zoomed into Places & Townships level a toggle button will be available within the upper right map controls to swap between the two.
When you select the MAP view icon, you are given a choice from your selected geographies to view one on the map. Once you click on a geography, you will see your selected geography outlined in red and all geographies at the same level. For example, if you selected a county, you will see all the counties in that state.
Geographies with numeric fact values are placed in ascending order and distributed into five groups containing the same number of geographies. The geography groups are then shaded from cyan (lowest values) to dark cyan (highest values). The value range for these groups will depend on the fact and geographies that fall within the group. Geographies with non-numeric fact values and footnotes are shaded with colors other than cyan and assigned to a specific footnote.
When viewing the entire US there are icons for Alaska, Hawaii and Puerto Rico in the corners that allow you to focus the map directly on those locations. When the map focuses on one of these locations their associated icon changes to the 48 contiguous states an allows you to reset the map to view the entire US.
In CHART view, how many geographies can I see? Can I see data?
When you select he CHART view icon, you are given a choice to ‘View Selected Locations' or choose one of the selected geographies. If you chose ‘View Selected Locations', you will see a chart for all selected geographies. If you only have one geography selected, the chart will open with this geography along with all sibling geographies. For example, if you have selected a state, you will see all the states, plus the District of Columbia and Puerto Rico. Hover over or click on each bar in the CHART to see the actual data value.
In DASHBOARD view, how many geographies can I see?
DASHBOARD view is a combination of all three views. When you select the DASHBOARD view icon, you are given a choice to create a dashboard for one of your selected geographies. DASHBOARD's TABLE shows fact data only for one selected geography. On DASHBOARD's TABLE you cannot add a geography. DASHBOARD's CHART shows data for the selected geography and all its siblings, same as the expanded CHART view. You can add and remove a selected geography from the dashboard chart. Selected Locations checkbox is not available on the DASHBOARD's CHART. The DASHBOARD's MAP shows data for the selected geography and places at the same level, just as in the expanded MAP view.
Where can I get data for other levels of geography, like metropolitan areas?
While not available in QuickFacts profiles, there are a number of sources on census.gov
for data about metropolitan areas.
How can I browse more datasets for my selected location?
Whenever you see an orange magnifying glass
, click it for all the detailed links to other datasets.
Can I share data from QuickFacts?
Yes. The MORE menu item opens a popup where you have options to PRINT, download a CSV, EMAIL, EMBED, and post on TWITTER and FACEBOOK.
What do these icons mean and what happens when I click them?
Click for additional information such as Sources, Definitions, and sometimes Margins of Error, or More Information.
Click for all the detailed links to other sets of data about the respective geography.
Click to set the application to its default state. This will remove all selected geographies and begin a new search. Your prior searches and results will not be saved.
Click to open the popup for all the download and share options.
Click this icon to delete a geography.
Click this icon to add a geography.
What are the footnotes at the bottom of all QuickFacts pages?
Value Notes
Estimates are not comparable to other geographic levels due to methodology differences that may exist between different data sources.
Some estimates presented here come from sample data, and thus have sampling errors that may render some apparent differences between geographies statistically indistinguishable. ]
Click the Quick Info
icon to the left of each row in TABLE view to learn about sampling error.
In Vintage 2022, as a result of the formal request from the state, Connecticut transitioned from eight counties to nine planning regions. For more details,
please see the Vintage 2022 release notes available here: Release Notes.
The vintage year (e.g., V2022) refers to the final year of the series (2020 thru 2022). Different vintage years of estimates are not comparable.
Users should exercise caution when comparing 2017-2021 ACS 5-year estimates to other ACS estimates.
For more information, please visit the 2021 5-year ACS Comparison Guidance
page. Fact Notes (a) Includes persons reporting only one race (c) Economic Census - Puerto Rico data are not comparable to U.S. Economic Census data (b) Hispanics may be of any race, so also are included in applicable race categories Value Flags - Either no or too few sample observations were available to compute an estimate, or a ratio of medians cannot be calculated because one or both of the median estimates falls in the lowest or upper interval of an open ended distribution. F Fewer than 25 firms D Suppressed to avoid disclosure of confidential information N Data for this geographic area cannot be displayed because the number of sample cases is too small. FN Footnote on this item in place of data X Not applicable S Suppressed; does not meet publication standards NA Not available Z Value greater than zero but less than half unit of measure shown
QuickFacts data are derived from: Population Estimates, American Community Survey, Census of Population and Housing, Current Population Survey, Small Area Health Insurance Estimates, Small Area Income and Poverty Estimates, State and County Housing Unit Estimates, County Business Patterns, Nonemployer Statistics, Economic Census, Survey of Business Owners, Building Permits. Close Close Please Note! Close
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draft-johansson-netconf-owl-00
NETCONF Configuration Data Modeling using OWL (Internet-Draft, 2008)
Internet Engineering Task Force L. Johansson, Ed.
Internet-Draft Stockholm university
Intended status: Informational March 11, 2008
Expires: September 12, 2008
NETCONF Configuration Data Modeling using OWL
draft-johansson-netconf-owl-00
Status of this Memo
By submitting this Internet-Draft, each author represents that any
applicable patent or other IPR claims of which he or she is aware
have been or will be disclosed, and any of which he or she becomes
aware will be disclosed, in accordance with
Section 6 of BCP 79
.
Internet-Drafts are working documents of the Internet Engineering
Task Force (IETF), its areas, and its working groups. Note that
other groups may also distribute working documents as Internet-
Drafts.
Internet-Drafts are draft documents valid for a maximum of six months
and may be updated, replaced, or obsoleted by other documents at any
time. It is inappropriate to use Internet-Drafts as reference
material or to cite them other than as "work in progress."
The list of current Internet-Drafts can be accessed at
http://www.ietf.org/ietf/1id-abstracts.txt
.
The list of Internet-Draft Shadow Directories can be accessed at
http://www.ietf.org/shadow.html
.
This Internet-Draft will expire on September 12, 2008.
Copyright Notice
Copyright (C) The IETF Trust (2008).
Abstract
This document outlines an approach for a NETCONF data modeling
language based on the W3C Web Ontology Language (OWL).
Johansson Expires September 12, 2008 [Page 1]
Internet-Draft NETCONF OWL March 2008 Table of Contents 1 . Introduction and Basic Terminology . . . . . . . . . . . . . . 3 2 . Information modeling using OWL . . . . . . . . . . . . . . . . 3 3 . Building protocols using OWL and RDF . . . . . . . . . . . . . 6 4 . Advanced concepts . . . . . . . . . . . . . . . . . . . . . . 7 4.1 . Your own RDF serialization . . . . . . . . . . . . . . . . 7 4.2 . Versioning . . . . . . . . . . . . . . . . . . . . . . . . 7 5 . NETCONF using OWL . . . . . . . . . . . . . . . . . . . . . . 8 5.1 . Some of the NETCONF Requirements . . . . . . . . . . . . . 8 6 . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . 10 7 . IANA Considerations . . . . . . . . . . . . . . . . . . . . . 10 8 . Security Considerations . . . . . . . . . . . . . . . . . . . 10 9 . References . . . . . . . . . . . . . . . . . . . . . . . . . . 10 9.1 . Normative References . . . . . . . . . . . . . . . . . . . 10 9.2 . Informative References . . . . . . . . . . . . . . . . . . 10 Author's Address . . . . . . . . . . . . . . . . . . . . . . . . . 11 Intellectual Property and Copyright Statements . . . . . . . . . . 12 Johansson Expires September 12, 2008 [Page 2]
Internet-Draft NETCONF OWL March 2008 1 . Introduction and Basic Terminology The NETCONF working group has identified the need for a configuration
data modeling language . This document outlines an approach to
fulfill these requirements using the Web Ontology Laguage
[ W3C.CR-owl-ref-20030818 ] (OWL). The OWL can be thought of as an
information modeling language with the expressive power of UML but
with a comparatively simple textual representation. 2 . Information modeling using OWL The Web Ontology Language (OWL) is a language for describing
information and models based on the Resource Description Framework
(RDF). Both RDF and OWL are W3C specifications. The OWL can be
thought of as the schema language for RDF-based data in much the same
way as LDAP schema is the modeling language describing LDAP-based
data.
A single OWL model (collection of OWL modeling elements) is called an
"ontology" and can be thought of as an OWL module. The OWL is
inherently extensible and has the expressive power of common modeling
languages like UML but with a much simpler textual representation of
models.
There are several existing implementations of OWL today all of which
support validation of OWL ontologies.
The OWL comes in three variants: OWL-Lite, OWL-DL and OWL-Full. A
complete description of the differences can be found in OWL Web
Ontology Language Guide [ W3C.CR-owl-guide-20030818 ] section 1.1 .
Most information modeling applications use OWL-DL which has enough
expressive power for most modeling needs while remaining relatively
easy to implement in modern programing languages. From the point of
view of a programmer OWL-DL can be viewed as a OO meta-model with
support for multiple inheritance: i.e there is a class concept and a
property (aka class member) concept. Classes have class members.
Class members (properties) has a domain and a range. The domain is a
class. The range is either a primitive type (all XML Schema types
are OWL primitive types) or another class.
The OWL is based on the Resource Description Framework
[ W3C.PR-rdf-primer-20031215 ] (RDF) which provides the data
representation underlying both OWL and OWL class instances. This
means that an OWL schema (a collection of classes and properties) is
expressed as RDF as is any OWL class instance. In other words the
OWL is a "self hosting" extension of RDF. There are several ways to
represent RDF in textual form: N-Triples, N3 or RDF/XML any of which Johansson Expires September 12, 2008 [Page 3]
Internet-Draft NETCONF OWL March 2008 is able to carry the full expressive power of OWL.
Before this gets too abstract we present a small example in the
approximate domain of NETCONF: the switch ontology, this time
represented using RDF/XML for the simple reason that this alternative
is by far the easiest to understand for the layman: Johansson Expires September 12, 2008 [Page 4]
Internet-Draft NETCONF OWL March 2008 <?xml version="1.0" encoding="UTF-8"?>
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
xmlns:rdfs="http://www.w3.org/2000/01/rdf-schema#"
xmlns:owl="http://www.w3.org/2002/07/owl#"
xmlns="http://www.ietf.org/netconf/switch/#"
xml:base="http://www.ietf.org/netconf/switch/#">
<owl:Ontology>
<rdfs:comment>
Example switch ontology
</rdfs:comment>
</owl:Ontology>
<owl:Class rdf:ID="Port"/>
<owl:Class rdf:ID="PortCollection"/>
<owl:Class rdf:ID="Layer2Element"/>
<!-- A Switch a layer2 network element that when viewed
as a collection of ports has at least 1 port -->
<owl:Class rdf:ID="Switch">
<rdfs:subClassOf rdf:resource="#PortCollection"/>
<rdfs:subClassOf rdf:resource="#Layer2Element"/>
<owl:subClassOf>
<owl:Restriction>
<owl:onProprety rdf:resource="port"/>
<owl:minCardinality>1</owl:minCardinality>
</owl:Restriction>
</owl:subClassOf>
</owl:Class>
<owl:DatatypeProperty rdf:ID="speed">
<rdfs:domain rdf:resource="#Switch"/>
<rdfs:range rdf:resource="http://www.w3.org/2001/XMLSchema#integer"/>
</owl:DatatypeProperty>
<owl:DatatypeProperty rdf:ID="connected">
<rdfs:domain rdf:resource="#Switch"/>
<rdfs:range rdf:resource="http://www.w3.org/2001/XMLSchema#boolean"/>
</owl:DatatypeProperty>
<owl:ObjectProperty rdf:ID="port">
<rdfs:domain rdf:resource="#PortCollection"/>
<rdfs:range rdf:resource="#Port"/>
</owl:ObjectProperty>
</rdf:RDF> Johansson Expires September 12, 2008 [Page 5]
Internet-Draft NETCONF OWL March 2008 This example illustrates a few of the notable aspects of OWL as a
modeling tool. We have defined 4 classes - Port, PortCollection,
Layer2Element and Switch. A Switch inherits from both Layer2Element
and PortCollection and an anonymous class which restricts the port
attribute defined on PortCollection to having at least 1 port. In
plain English this means that a Switch is a Layer2Element and a
PortCollection with at least 1 port. In fact this sentence is a
reasonably good "English serialization" of the Switch model element.
This can be made more precise by studying the semantic foundations of
RDF and OWL.
The PortCollection can be thought of as an "abstract" class or
interface whereas the Switch is a concrete class which adds
specification details to both Layer2Element (which is included here
only to illustrate multiple inheritance) and PortCollection. Most
modern OO languages are easily able to build models from OWL meta-
models - i.e transform the meta-model given by an OWL schema into a
native model. This process is especially simple for languages which
natively support multiple inheritance in some form or another: eg
Ruby, Perl or Python but even more restrictive languages like Java
can easily emulate multiple inheritance through the use of the
factory/interface/implementation pattern. 3 . Building protocols using OWL and RDF In the same way that OWL can be used to model information it can be
used to model the representation of operations, if not their
semantics. This is analogous to using ASN.1 to model both protocol
elements and the objects operated upon by the protocol elements. The
result becomes inherently transport-neutral: anything which can send
messages using any of the serialiations of RDF can be used as the
transport of an OWL-based protocol.
The mental model to strive for is that the messages transported by a
"OWL-driven" protocol are RDF graphs - i.e structured data in RDF
form represented using some serialization of RDF (eg N-triples).
This graph may support several ontologies (eg multiple versions of
the sam protocol but we'll get back to that), i.e may express
relationships between individuals of multiple (possibly related) OWL
schema. By selecting (a set of) ontologies it is possible to create
a native object representation of the message. Johansson Expires September 12, 2008 [Page 6]
Internet-Draft NETCONF OWL March 2008 +------------------------------------------+
| Object | Message abstraction |
+------------------------------------------+
| Ontology | Protocol description |
+------------------------------------------+
| RDF Graph | Protocol message |
+------------------------------------------+
This approach lends itself very well to implementation in modern
agile "duck-typed" programming languages but can also be done
(typically by employing code-generation) in strongly typed languages.
Naturally this isn't the first (or probably last) time a formal
language has been used to define information models and protocols
with varying results. One notable difference between OWL and related
efforts (eg ASN.1, XML Schema, Relax-NG, XDR) is that OWL has the
full expressive power of UML which means that there is little nead to
"dumb-down" the wire-representation of the objects modeled in the
application in order to meet the limitations of the interface
description language: i.e the application native information model
can be used more or less straight away as a basis for an OWL/RDF
model for the applications remoting needs. 4 . Advanced concepts 4.1 . Your own RDF serialization Defining a new serialization of RDF is always an option if any of the
existing serializations are found to be lacking in some respects.
For instance it may be a good choice to use RDF/XML as a
serialization for protocol messages but the (lack of) readability of
XML may lead one to define a separate serialization for use when
defining ontologies for a given application.
As long as a full serialization is defined then almost all of the
drawbacks of defining a DSL (Domain Specific Language) are addressed
without adding too much complexity to a protocol definition or
information model. 4.2 . Versioning Managing multiple versions of the same information model can be
challenging. The OWL has a few constructs which helps with this job,
notably (again) multiple inheritance and the fact that an RDF graph
can support multiple ontologies concurrently. There are also owl
constructs such as the owl:equivalentProperty and owl:equivalentClass Johansson Expires September 12, 2008 [Page 7]
Internet-Draft NETCONF OWL March 2008 relationships which allows one (version of) an ontology to be related
to another in a mashine-readable way. 5 . NETCONF using OWL The approach to using OWL as a basis for NETCONF configuration data
modeling would be to define a basic NETCONF ontology containing
concepts which are common to any NETCONF configuration model. Next
define ontologies for NETCONF operations and NETCONF notifications
(as identified in the requirements) and finally agree on standard RDF
serialiations for NETCONF models - eg use RDF/XML always or use RDF/
XML for protocol messages and a custom serialization (to be defined)
for NETCONF models. 5.1 . Some of the NETCONF Requirements This is not an exhaustive treatise of the list of requirements found
in [ NETCONFREQS ] but rather an attempt to single out the requirements
where the choice of OWL has a signifficant impact
3.1.1 - Notification Definitions. By definiting a NETCONF
notification ontology.
3.1.4 - All Base Operations. By defining a NETCONF operations
ontology and related semantics.
3.1.5 - Define new NETCONF Operations. Define another NETCONF
operations ontology extending the base NETCONF operations
ontology.
3.1.5 - Separation of Operations and Payload. Even if OWL is
expressed in RDF and OWL ontologies are by definition valid RDF
this won't cause any confusion, mainly because we have limited
ourselves to OWL-DL where there is a clear separation between
model elements and instances.
3.1.7 - Error Annotation. Multiple inheritance allows one to tie
annontations in any form to any model element simply by making
everything that needs annotation inherit from an annotation class.
3.2.1 - Human Readable. Arguably humans can read RDF. If a
counter-example is produced then a custom RDF serialiation may be
in order.
3.2.4 - Document Information. Ontologies have metadata natively -
RDF is after all a metadata representation mechanism. Johansson Expires September 12, 2008 [Page 8]
Internet-Draft NETCONF OWL March 2008 3.2.5 - Ownership and Change Control. Everything in RDF is
identified using URIs, including the ontologies themselves.
Ownership and Change control is exercised via control over the
namespaces involved.
3.2.6 - Dependency Risk Reduction. The version of OWL and RDF
used in an ontology are referenced explicitly by default.
3.2.8 - Internationaliation and Localization. All RDF literals
are language-tagged by default.
3.3 - Resusability Requirements. OWL by construction is modular.
References between OWL ontologies (modules) are the norm.
3.4.3 - Validation. Validation of RDF against an OWL schema is
readily available. Tools for validation of OWL schema can be
readily found on the Internet.
3.5.1 - Human-Readable Semantics. RDF is based on the notion of
statements of the form subject relation object which can be
spelled out as propostitions of the form "Something has relation X
to Something else". This makes it almost an automatic process to
produce a plain text version of an ontology even if readability
may require extra effort. Apart from that the standard
documentation constructs built into OWL provide means to include
documentation in the ontology.
3.5.2 - Basic Types. All XML Schema types are primitive types of
OWL
3.5.3 - Opaque Data. The owl:Thing class is the superclass of all
classes. Properties with range owl:Thing are essentially defining
opaque data properties of a class.
3.5.4 - Keys. Each object in an RDF graph is uniquely identified
by its URI. The concept of a key is not native to RDF but can be
easily represented in OWL either by using the owl:
InverseFunctionalProperty to declare a property unique or by
defining a class whose properties are the (compound) key of any
superclass of that key-class.
3.5.5 - Relationships. OWL supports all types of relationships
1:1, 1:n, or m:n. Since all relationships in OWL use URIs as
identifiers there is no ambiguity when resolving relationship
identifiers
3.5.8 - Characterize Data. Define two classes - ConfigurtionData,
StatusData with no properties, these classes act as markes on Johansson Expires September 12, 2008 [Page 9]
Internet-Draft NETCONF OWL March 2008 classes allowing an implementation to make the destinction.
3.5.10 - Formal Constraints. Support for most of these
requirements are either native or can be implemented in the model.
3.6.1 - Language extensibility. OWL is versioned and expressed in
terms of RDF it is quite possible to extend both RDF and OWL.
3.6.2 - Model Extensibility. OWL has native constructs which can
be used to express how one model extends, imports and is
compatible with another model. This also applies in part to 3.6.3
3.6.3 - Instance Data Extensibility. Since the ontology URI is
normally part of (as the base URI of) the URIs of the model
elements in the ontology it is easy to include ontology version
informaiton in all types. 6 . Acknowledgements 7 . IANA Considerations This memo includes no request to IANA. 8 . Security Considerations 9 . References 9.1 . Normative References [ RFC2119 ] Bradner, S., "Key words for use in RFCs to Indicate
Requirement Levels", BCP 14 , RFC 2119 , March 1997. 9.2 . Informative References [ NETCONFREQS ]
"Requirements for a Configuration Data Modeling Language",
< http://svn.resiprocate.org/rep/ietf-drafts/rcdml/ draft-presuhn-rcdml-00.html >.
[ W3C.CR-owl-guide-20030818 ]
Smith, M., Welty, C., and D. McGuinness, "OWL Web Ontology
Language Guide", W3C CR CR-owl-guide-20030818,
August 2003. Johansson Expires September 12, 2008 [Page 10]
Internet-Draft NETCONF OWL March 2008 [ W3C.CR-owl-ref-20030818 ]
Dean, M. and G. Schreiber, "OWL Web Ontology Language
Reference", W3C CR CR-owl-ref-20030818, August 2003.
[ W3C.PR-rdf-primer-20031215 ]
Manola, F. and E. Miller, "RDF Primer", W3C PR PR-rdf-
primer-20031215, December 2003.
Author's Address
Leif Johansson (editor)
Stockholm university
Stockholm, SE-10691
Sweden
Phone: +46 8 162000
Email: leifj@it.su.se Johansson Expires September 12, 2008 [Page 11]
Internet-Draft NETCONF OWL March 2008
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Copies of IPR disclosures made to the IETF Secretariat and any
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Innovia Films Ltd v Frito -Lay North America, Inc [2012] EWHC 790 (Pat) (30 March 2012)
England and Wales High Court (Patents Court) Decisions
Neutral Citation Number: [2012] EWHC 790 (Pat) Case Nos: HC11C03841, HC11C04566
IN THE HIGH COURT OF JUSTICE CHANCERY DIVISION PATENTS COURT
Royal Courts of Justice Strand, London, WC2A 2LL 30 March 2012
B e f o r e :
THE HON MR JUSTICE ARNOLD____________________
Between:
INNOVIA FILMS LIMITED Claimant - and - FRITO-LAY NORTH AMERICA, INC. Defendant
____________________
Iain Purvis QC and Hugo Cuddigan (instructed by W P Thompson & Co) for the Claimant Andrew Lykiardopoulos (instructed by Bristows) for the Defendant Hearing dates: 20-21 March 2012____________________
HTML VERSION OF JUDGMENT____________________
Crown Copyright ©
MR JUSTICE ARNOLD :
Contents
Topic Paragraphs Introduction 1-2 Factual background 3-27 The parties 4-6 The disclosures by IFL to Frito-Lay 7-15 The patent applications filed by Frito-Lay 16-25 The 331 family 16-18 The 775 family 19-20 The 500 family 21 The 033 family 22-23 The relationships between the Frito-Lay Applications 24 The European Applications 25 IFL's case on entitlement and breach of confidence 26 Frito-Lay's defence to IFL's claims 27 The proceedings 28-32 Legal context 33-38 European Patent Convention 33-34 Protocol on Recognition 35 Patents Act 1977 36 Brussels I Regulation 37 Rome II Regulation 38 Service out of the jurisdiction: general principles 39-46 Stage 1 41 Stage 2 42-46 Staying proceedings on the ground of forum non conveniens: general principles 47 Issue 1: Does this Court have exclusive jurisdiction with respect to the European Applications? 48-76 Issue 2: What is the consequence of this Court having exclusive jurisdiction over the European Applications? 77-86 Issue 3: Should this Court exercise jurisdiction under section 12 of the 1977 Act in respect of the other Frito-Lay Applications, and in particular the pending US applications? 87-93 Issue 4: Does this Court lose jurisdiction under section 12 if an application proceeds to grant? 94-98 Issue 5: What is the law applicable to IFL's claim for breach of confidence? 99-111 Events prior to 11 January 2009 102-108 Events after 11 January 2009 109-111 Issue 6: Should IFL have permission to serve the breach of confidence claim outside the jurisdiction? 112-121 Serious issue to be tried on merits? 113 Good arguable case as to jurisdictional gateway? 114-120 Is England the appropriate forum? 121 Issue 7: What is the extent of the Texas Court's jurisdiction? 122-126 Issue 8: Which court is the appropriate forum? 127-134 Territorial connections of the parties 128 Factual connections between the events and particular courts 129 Key witnesses 130 Documents 131 Applicable law 132 Risk of irreconcilable judgments 133 Conclusions 134 Issue 9: Should Master Bragge's order be set aside for material non-disclosure? 135 Conclusion 136
Introduction
In these proceedings the Claimant ("IFL") contends that it is the rightful owner of various patent applications filed by the Defendant ("Frito-Lay"), and of any patents granted as a result thereof, and that Frito-Lay has acted in breach of confidence. For the reasons explained below, IFL has commenced two actions before this Court ("3841" and "4566"). On 11 November 2011 Master Bragge granted IFL permission to serve the Claim Form in action 3841 on Frito-Lay outside the jurisdiction. There is no dispute that action 4566 was properly served on Frito-Lay within the jurisdiction by service at the offices of its patent attorneys, being the address for service provided by Frito-Lay under rule 103(1) of the Patents Rules 2007. If the two actions are permitted to proceed, it is likely that they will be consolidated.
There are now two applications by Frito-Lay before the Court:
i) An application in action 3841 (a) to set aside permission to serve the claim out of the jurisdiction, save as in so far it relates to entitlement to the European Applications (as to which, see below), on the grounds that this court either does not have jurisdiction or should not exercise jurisdiction over the claim, alternatively of material non-disclosure, and (b) for a stay of the claim so far as it relates to entitlement to the European Applications pending the determination of a claim brought by Frito-Lay in the US District Court for the Eastern District of Texas Tyler Division ("the Texas Court").
ii) An application in action 4566 that the claim be stayed either permanently on the ground that this court should not exercise jurisdiction over the claim or pending determination of Frito-Lay's claim in the Texas Court.
Factual background
The following account of the factual background is, save where indicated, based on IFL's statements of case and evidence. Frito-Lay denies any wrongdoing, but understandably it has served very little evidence addressing the substantive merits of IFL's case. In those circumstances counsel for Frito-Lay accepted that the court had to consider the present applications upon the assumption that the facts alleged by IFL are true. I should make it clear, however, that it does not necessarily follow that those allegations will be proved at trial.
The parties
IFL is the world's largest manufacturer of cellulose films for food packaging applications. It is the proprietor of the trade mark Cellophane. It has a world-class R&D centre concentrating on the development of innovative film processes and products, based in Wigton, Cumbria. It has extensive knowledge of the development of cellulose/bioplastic material combinations. IFL was the first company to develop cellulose packaging films that were compliant with the global norms for organic recycling methodologies.
IFL is part of the Innovia Group of companies which is wholly owned and controlled by Innovia Films (Holding 3) Ltd ("IFH"). The Innovia Group's US subsidiary is Innovia Films, Inc. ("IFI"), based in Smyrna, Georgia. IFI is also wholly owned and controlled by IFH. I shall refer to IFL and IFI collectively as Innovia.
Frito-Lay is a wholly-owned subsidiary of PepsiCo Inc. It manufactures and markets convenient foods, and in particular chips/crisps. It has premises in Plano, Texas.
The disclosures by IFL to Frito-Lay
Between around 7 and 11 November 2004 Jessica Hammond, a Strategic Account Manager employed by IFI, met representatives of Frito-Lay at Packexpo, a packaging trade exhibition, in Chicago. Ms Hammond told Frito-Lay that IFL was in the business of designing and developing novel configurations of food packaging film, and that these films were manufactured and distributed by IFI in the US. At that time or soon thereafter it was arranged that Innovia and Frito-Lay would meet to discuss whether IFL's proposals for films suitable for snack food packaging might satisfy Frito-Lay's requirements.
On 2 February 2005 there was a meeting between Ms Hammond and Stewart Richards (Technical Account Manager) of IFI and representatives of Frito-Lay including Anthony Knoerzer (Group Manager Packaging), Brad Rodgers (Senior Project Manager) and Steven Callahan (Senior Project Engineer) at Frito-Lay's premises in Plano at which Frito-Lay's requirements were discussed. It was agreed at the meeting that a non-disclosure agreement would be entered into.
Shortly before and on 7 February 2005 Andrew Sweetman (Business Development & Sustainability Manager) of IFL prepared a series of PowerPoint slides setting out his initial thoughts and proposals for multilayer films for packaging snack products for Frito-Lay. Mr Sweetman sent the slides by email to Ms Hammond, who sent them to Mr Knoerzer and Mr Rodgers.
On 1 and 7 March 2005 respectively representatives of IFI and Frito-Lay signed a Confidentiality and Non-Disclosure Agreement for the Mutual Disclosure of Information ("the NDA"). It is common ground that this is retrospective in effect. It provides that "The terms herein shall be governed by and construed in accordance with the laws of the State of Delaware without regard to principles of conflicts of laws". There is no reference in the NDA to IFL.
On 23 March 2005 Mr Sweetman gave a PowerPoint presentation at a meeting at Frito-Lay's premises. The meeting was also attended by Ms Hammond and Mr Richards of IFI and by Mr Knoerzer and Mr Rodgers of Frito-Lay.
On 22 August 2005 David Beeby, Innovia's CEO, attended a meeting with Mr Knoerzer and Mr Rodgers at Frito-Lay's premises at which the project was discussed. During the meeting Mr Beeby disclosed that IFL had succeeded in laminating two types of film together.
On 13 September 2005 there was a telephone conference between Mr Sweetman, Stefan van den Branden (R&D Manager), Jonathan Hewitt (Group Leader, Surface Energy), Simon Read (Senior Project Leader, Surface Engineering) and Paul Watters (Project Leader, Surface Engineering) of IFL, Ms Hammond of IFI, and Mr Knoerzer and Mr Rodgers of Frito-Lay. During the telephone conference IFL's representatives discussed the progress they had made in developing environmentally friendly packaging with improved barrier properties.
Between 13 September and 13 October 2005 Mr Hewitt and Mr Watters worked on proposals for multilayer film structures for Frito-Lay. They prepared a series of PowerPoint slides which Mr Hewitt emailed to Ms Hammond. Ms Hammond printed and bound these to present to Frito-Lay at a meeting scheduled for 18 or 19 October 2005. In the event the meeting was postponed until 9 November 2005, when the presentation was given to Frito-Lay.
IFL contends that during the course of the communications described above it disclosed to Frito-Lay confidential information comprising four categories of invention in circumstances importing an obligation of confidence. It is not necessary for present purposes to describe the precise nature of those inventions. It is important, however, to note the following points about IFL's case:
i) IFL contends that its employees, and not those of IFI, devised the inventions.
ii) IFL contends it disclosed the inventions to Frito-Lay. IFL says that, to the extent that IFI was involved, IFI simply acted as a conduit for the information.
iii) IFL contends that Frito-Lay owed an equitable obligation of confidence to IFL. IFL relies upon the existence of the NDA as one of the factual circumstances giving rise to that equitable obligation, but it does not allege breach of the NDA per se. I shall return to this point below.
The patent applications filed by Frito-Lay
The 331 family. On 14 August 2006 Frito-Lay filed US Patent Application 11/464,331 ("331") entitled "Environmentally-Friendly Multi-Layer Flexible Film Having Barrier Properties" naming Mr Knoerzer and Mr Rodgers as inventors. This was published by the United States Patent and Trade Mark Office ("USPTO") on 14 February 2008. The application was granted on 31 May 2011 as US Patent 7,951,436.
On 7 August 2007 Frito-Lay filed International Patent Application PCT/US2007/075330 (published as WO 2008/021811) claiming priority from 331. This application designates a large number of countries by way of both national (including United Kingdom) and regional (including European) patents. When it entered the regional phase, it was re-published by the European Patent Office ("EPO") as European Patent Application 2 069 146.
Subsequently, Frito-Lay filed US Patent Application 13/091,900, which is a continuation of 331. This was granted on 31 January 2012 as US Patent 8,105,667.
The 775 family. On 31 August 2007 Frito-Lay filed US Patent Application 11/848,775 ("775") entitled "Package and Multi-Layer Flexible Film Having Paper Containing Post Consumer Recycled Fiber" naming Mr Knoerzer and Mr Rodgers as inventors. This was published on 5 March 2009. It has not yet been granted.
On 28 August 2008 Frito-Lay filed International Patent Application PCT/US2008/074623 (published as WO 2009/032748) claiming priority from 775 and 500 (as to which, see below). This application again designates a large number of countries by way of both national (including United Kingdom) and regional (including European) patents. When it entered its regional phase in the EPO, it was re-published as European Patent Application 2 200 821.
The 500 family. On 14 February 2008 Frito-Lay filed US Patent Application 12/031,500 ("500") entitled "Environmentally-Friendly Multi-Layer Flexible Film Having Barrier Properties" naming Mr Knoerzer, Mr Rodgers and Kenneth Laverdure as inventors. This was published on 3 July 2008. It is a continuation in part of both 331 and 775. It was granted on 17 May 2011 as US Patent 7,943,218.
The 033 family. On 14 February 2008 Frito-Lay filed US Patent Application 12/716,033 ("033") entitled "Bio-Based In-Line High Barrier Metalized Film and Process for its Production" naming Mr Knoerzer, Mr Rodgers, Mr Laverdure and Eldridge Mount III as inventors. This was published on 2 September 2010. It is a continuation in part of 500, and hence of 331 and 775.
On 2 March 2011 Frito-Lay filed International Patent Application PCT/US2011/026881 (published as WO 2011/109528) claiming priority from 033. This application again designates a large number of countries by way of both national (including United Kingdom) and regional (including European) patents.
The relationships between the Frito-Lay A pplications . I shall refer to the applications filed by Frito-Lay as described above, including all national and regional applications stemming from the international applications, as "the Frito-Lay Applications". A simplified diagram of how the families interrelate is set out below:
The European Applications. It can be seen from the foregoing that there are presently two European Patent Applications in issue, namely EP A 2 069 146, which forms part of the 331 family, and EP A 2 200 821, which forms part of the 775 and 500 families. I shall refer to these as "the European Applications". When WO 2011/109528 enters the regional phase, there will be a third European Patent Application in issue. It is clear that this will stand in the same position, jurisdictionally speaking, as the other two.
IFL's case on entitlement and breach of confidence
IFL contends that the inventions described and claimed in the Frito-Lay Applications were devised by its employees, in particular Mr Sweetman and Mr Hewitt, and disclosed to Frito-Lay in confidence as described above. Accordingly, IFL contends that its employees were the true inventors of the inventions the subject of the Frito-Lay Applications, and that IFL is the true proprietor of the Frito-Lay Applications and of any patents granted pursuant to those applications. (In the alternative, IFL contends that its employees were co-inventors of those inventions, and accordingly that it is entitled to an interest in the Frito-Lay Applications and patents granted pursuant thereto.) Furthermore, IFL contends that, in filing and prosecuting the Frito-Lay Applications, in causing the Frito-Lay Applications to be published and in procuring the grant of patents pursuant thereto, Frito-Lay has acted in breach of the equitable obligation of confidence it owed IFL. Accordingly, IFL claims that Frito-Lay holds the Frito-Lay Applications and any patents granted pursuant thereto on constructive trust. It also claims an account of profits or an inquiry as to damages.
Frito-Lay's defence to IFL's claims
Since it is disputing this Court's jurisdiction, Frito-Lay has not yet served a Defence in either action. Nor, as mentioned above, has it served much evidence going to the merits of IFL's claims. Frito-Lay has indicated, however, that it will contend that its employees devised the inventions described in the Frito-Lay Applications independently starting before the disclosures relied on by IFL, as Frito-Lay alleges in its Complaint in the Texas Court. Accordingly, Frito-Lay contends that it is the true proprietor of the Frito-Lay Applications and any patents granted pursuant thereto, and Frito-Lay denies any misuse of confidential information.
The proceedings
There are three sets of proceedings between the parties presently pending.
First, on 21 October 2011 IFL filed a reference to the Comptroller-General of Patents, Designs and Trade Marks under section 12 of the Patents Act 1977 in respect of the Frito-Lay Applications. In its Statement of Grounds IFL stated that it intended to issue proceedings against Frito-Lay in this Court for breach of confidence and entitlement to the European Applications pursuant to section 82 of the 1977 Act, undertook to remove the European Applications from the reference upon this court becoming seized of jurisdiction and requested the Comptroller to decline to deal with the reference. On 16 December 2011 the Comptroller decided to decline to deal with the reference. Accordingly, this Court now has jurisdiction in respect of this claim. The Claim Form in action 4566 was issued on 30 December 2011 and served with the Particulars of Claim on 23 February 2012. No claim is made in respect of the European Applications in this action. On 7 March 2012 Frito-Lay acknowledged service stating its intention to contest this Court's jurisdiction. On 15 March 2012 it issued the application referred to in paragraph 2(b) above.
Secondly, on 4 November 2011 IFL's Claim Form in action 3841 was issued in this Court. In this action IFL claims entitlement to the European Applications pursuant to section 82 of the 1977 Act. IFL also claims the wider relief described in paragraph 26 above as a result of Frito-Lay's alleged breaches of confidence. As noted above, Master Bragge granted permission to serve out of the jurisdiction on 11 November 2011. On 19 December 2011 Frito-Lay acknowledged service stating its intention to contest this Court's jurisdiction. On 3 January 2012 it issued the application referred to in paragraph 2(a) above.
Thirdly, on 23 November 2011 Frito-Lay issued proceedings in the Texas Court against Innovia ("the Texas Claim"). In the Texas Claim Frito-Lay claims declarations that it is the rightful owner, and that its employers were the true inventors, of all the Frito-Lay Applications and patents granted pursuant thereto. Furthermore, it seeks declarations that it has not breached the NDA or any implied or express duty of confidence owed to either IFI or IFL. In the Complaint Frito-Lay expressly relies upon IFL's 3841 action and the section 12 reference to the Comptroller as establishing that there is a "real, cognizable, and justiciable controversy" between the parties. On 14 December 2011 Innovia filed a motion to dismiss or in the alternative stay the Texas Claim. I was informed that the motion is expected to be heard either later this month or next month, but that no date has yet been set.
In addition to the proceedings mentioned above, on 9 November 2011 IFL requested the EPO to suspend examination of the European Applications. The EPO granted that request on 18 November 2011.
Legal context
European Patent Convention
As originally adopted in 1973, the European Patent Convention ("the EPC"), of which the United Kingdom is one of the Contracting States, included the following provisions:
" Article 60
Right to a European patent
(1) The right to a European patent shall belong to the inventor or his successor in title. If the inventor is an employee the right to the European patent shall be determined in accordance with the law of the State in which the employee is mainly employed; if the State in which the employee is mainly employed cannot be determined, the law to be applied shall be that of the State in which the employer has his place of business to which the employee is attached.
(2) If two or more persons have made an invention independently of each other, the right to the European patent shall belong to the person whose European patent application has the earliest date of filing; however, this provision shall apply only if this first application has been published under Article 93 and shall only have effect in respect of the Contracting States designated in that application as published.
(3) For the purposes of proceedings before the European Patent Office, the applicant shall be deemed to be entitled to exercise the right to the European patent.
Article 61
European patent applications filed by non-entitled persons
(1) If by a final decision it is adjudged that a person referred to in Article 60, paragraph 1, other than the applicant, is entitled to the grant of a European patent, that person may, within a period of three months after the decision has become final, provided that the European patent has not yet been granted, in respect of those Contracting States designated in the European patent application in which the decision has been taken or recognised, or has to be recognised on the basis of the Protocol on Recognition annexed to this Convention:
(a) prosecute the application as his own application in place of the applicant,
(b) file a new European patent application in respect of the same invention, or
(c) request that the application be refused.
(2) The provisions of Article 76, paragraph 1, shall apply mutatis mutandis to a new application filed under paragraph 1.
(3) The procedure to be followed in carrying out the provisions of paragraph 1, the special conditions applying to a new application filed under paragraph 1 and the time limit for paying the filing, search and designation fees on it are laid down in the Implementing Regulations.
…
Article 167
Reservations
…
(2) Each Contracting State may reserve the right to provide that:
…
(d) it shall not be bound by the Protocol on Recognition.
…"
When the EPC was amended in 2000, Article 167 was deleted. Furthermore, Articles 60 and 61 now provide:
" Article 60
Right to a European patent
(1) The right to a European patent shall belong to the inventor or his successor in title. If the inventor is an employee, the right to a European patent shall be determined in accordance with the law of the State in which the employee is mainly employed; if the State in which the employee is mainly employed cannot be determined, the law to be applied shall be that of the State in which the employer has the place of business to which the employee is attached.
(2) If two or more persons have made an invention independently of each other, the right to a European patent therefor shall belong to the person whose European patent application has the earliest date of filing, provided that this first application has been published.
(3) In proceedings before the European Patent Office, the applicant shall be deemed to be entitled to exercise the right to a European patent.
Article 61
European patent applications filed by non-entitled persons
(1) If by a final decision it is adjudged that a person other than the applicant is entitled to the grant of the European patent, that person may, in accordance with the Implementing Regulations:
(a) prosecute the European patent application as his own application in place of the applicant;
(b) file a new European patent application in respect of the same invention; or
(c) request that the European patent application be refused.
(2) Article 76, paragraph 1, shall apply mutatis mutandis to a new European patent application filed under paragraph 1(b)."
Protocol on Recognition
The Protocol on Jurisdiction and the Recognition of Decisions in respect of the Right to the Grant of a European Patent ("the Protocol on Recognition") annexed to the EPC includes the following provisions:
"Section I
Jurisdiction
Article 1
(1) The courts of the Contracting States shall, in accordance with Articles 2 to 6, have jurisdiction to decide claims, against the applicant, to the right to the grant of a European patent in respect of one or more of the Contracting States designated in the European patent application.
(2) For the purposes of this Protocol, the term "courts" shall include authorities which, under the national law of a Contracting State, have jurisdiction to decide the claims referred to in paragraph 1. Any Contracting State shall notify the European Patent Office of the identity of any authority on which such a jurisdiction is conferred, and the European Patent Office shall inform the other Contracting States accordingly.
(3) For the purposes of this Protocol, the term 'Contracting State' refers to a Contracting State which has not excluded application of this Protocol pursuant to Article 167 of the Convention.
Article 2
Subject to Articles 4 and 5, if an applicant for a European patent has his residence or principal place of business within one of the Contracting States, proceedings shall be brought against him in the courts of that Contracting State.
Article 3
Subject to Articles 4 and 5, if an applicant for a European patent has his residence or principal place of business outside the Contracting States, and if the party claiming the right to the grant of the European patent has his residence or principal place of business within one of the Contracting States, the courts of the latter State shall have exclusive jurisdiction.
Article 4
Subject to Article 5, if the subject-matter of a European patent application is the invention of an employee, the courts of the Contracting State, if any, whose law determines the right to the European patent pursuant to Article 60, paragraph 1, second sentence, of the Convention, shall have exclusive jurisdiction over proceedings between the employee and the employer.
Article 5
(1) If the parties to a dispute concerning the right to the grant of a European patent have concluded an agreement, either in writing or verbally with written confirmation, to the effect that a court or the courts of a particular Contracting State shall decide on such a dispute, the court or courts of that State shall have exclusive jurisdiction.
(2) However, if the parties are an employee and his employer, paragraph 1 shall only apply in so far as the national law governing the contract of employment allows the agreement in question.
Article 6
In cases where neither Articles 2 to 4 nor Article 5, paragraph 1, apply, the courts of the Federal Republic of Germany shall have exclusive jurisdiction.
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Section II
Recognition
Article 9
(1) Subject to the provisions of Article 11, paragraph 2, final decisions given in any Contracting State on the right to the grant of a European patent in respect of one or more of the Contracting States designated in the European patent application shall be recognised without requiring a special procedure in the other Contracting States.
(2) The jurisdiction of the court whose decision is to be recognised and the validity of such decision may not be reviewed.
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Article 11
(1) In relations between any Contracting States the provisions of this Protocol shall prevail over any conflicting provisions of other agreements on jurisdiction or the recognition of judgments.
(2) This Protocol shall not affect the implementation of any agreement between a Contracting State and a State which is not bound by the Protocol."
Patents Act 1977
The 1977 Act includes the following provisions:
" Determination before grant of questions about entitlement to patents, etc.
8.(1) At any time before a patent has been granted for an invention (whether or not an application has been made for it)—
(a) any person may refer to the comptroller the question whether he is entitled to be granted (alone or with any other persons) a patent for that invention or has or would have any right in or under any patent so granted or any application for such a patent; or
(b) any of two or more co-proprietors of an application for a patent for that invention may so refer the question whether any right in or under the application should be transferred or granted to any other person;
and the comptroller shall determine the question and may make such order as he thinks fit to give effect to the determination.
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(7) If it appears to the comptroller on a reference of a question under this section that the question involves matters which would more properly be determined by the court, he may decline to deal with it and, without prejudice to the court's jurisdiction to determine any such question and make a declaration, or any declaratory jurisdiction of the court in Scotland, the court shall have jurisdiction to do so.
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Determination after grant of questions referred before grant
9. If a question with respect to a patent or application is referred by any person to the comptroller under section 8 above, whether before or after the making of an application for the patent, and is not determined before the time when the application is first in order for a grant of a patent in pursuance of the application, that fact shall not prevent the grant of a patent, but on its grant that person shall be treated as having referred to the comptroller under section 37 below any question mentioned in that section which the comptroller thinks appropriate.
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Determination of questions about entitlement to foreign and convention patents, etc
12.(1) At any time before a patent is granted for an invention in pursuance of an application made under the law of any country other than the United Kingdom or under any treaty or international convention (whether or not that application has been made)—
(a) any person may refer to the comptroller the question whether he is entitled to be granted (alone or with any other persons) any such patent for that invention or has or would have any right in or under any such patent or an application for such a patent; or
(b) any of two or more co-proprietors of an application for such a patent for that invention may so refer the question whether any right in or under the application should be transferred or granted to any other person;
and the comptroller shall determine the question so far as he is able to and may make such order as he thinks fit to give effect to the determination.
(2) If it appears to the comptroller on a reference of a question under this section that the question involves matters which would more properly be determined by the court, he may decline to deal with it and, without prejudice to the court's jurisdiction to determine any such question and make a declaration, or any declaratory jurisdiction of the court in Scotland, the court shall have jurisdiction to do so.
(3) Subsection (1) above, in its application to a European patent and an application for any such patent, shall have effect subject to section 82 below.
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(6) In the following cases, that is to say—
(a) where an application for a European patent (UK) is refused or withdrawn, or the designation of the United Kingdom in the application is withdrawn whether before or after publication of the application but before a question relating to the right to the patent has been referred to the comptroller under subsection (1) above or before proceedings relating to that right have begun before the relevant convention court;
(b) where an application has been made for a European patent (UK) and on a reference under subsection (1) above or any such proceedings as are mentioned in paragraph (a) above the comptroller, the court or the relevant convention court determines by a final decision (whether before or after publication of the application) that a person other than the applicant has the right to the patent, but that person requests the European Patent Office that the application for the patent should be refused; or
(c) where an international application for a patent (UK) is withdrawn, or the designation of the United Kingdom in the application is withdrawn, whether before or after the making of any reference under subsection (1) above or the publication of the application;
the comptroller may order that any person (other than the applicant) appearing to him to be entitled to be granted a patent under this Act may within the prescribed period make an application for such a patent for the whole or part of any matter comprised in the earlier application (subject, however, to section 76 below) and that if the application for a patent under this Act is filed, it shall be treated as having been filed on the date of filing the earlier application.
(7) In this section—
(a) references to a patent and an application for a patent include respectively references to protection in respect of an invention and an application which, in accordance with the law of any country other than the United Kingdom or any treaty or international convention, is equivalent to an application for a patent or for such protection; and
(b) a decision shall be taken to be final for the purposes of this section when the time for appealing from it has expired without an appeal being brought or, where an appeal is brought, when it is finally disposed of.
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Determination of right to patent after grant
37.(1) After a patent has been granted for an invention any person having or claiming a proprietary interest in or under the patent may refer to the comptroller the question—
(a) who is or are the true proprietor or proprietors of the patent,
(b) whether the patent should have been granted to the person or persons to whom it was granted, or
(c) whether any right in or under the patent should be transferred or granted to any other person or persons;
and the comptroller shall determine the question and make such order as he thinks fit to give effect to the determination.
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(8) If it appears to the comptroller on a reference under this section that the question referred to him would more properly be determined by the court, he may decline to deal with it and, without prejudice to the court's jurisdiction to determine any such question and make a declaration, or any declaratory jurisdiction of the court in Scotland, the court shall have jurisdiction to do so.
(9) The court shall not in the exercise of any such declaratory jurisdiction determine a question whether a patent was granted to a person not entitled to be granted the patent if the proceedings in which the jurisdiction is invoked were commenced after the end of the period of two years beginning with the date of the grant of the patent, unless it is shown that any person registered as a proprietor of the patent knew at the time of the grant or, as the case may be, of the transfer of the patent to him that he was not entitled to the patent.
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Jurisdiction to determine questions as to right to a patent
82.(1) The court shall not have jurisdiction to determine a question to which this section applies except in accordance with the following provisions of this section.
(2) Section 12 above shall not confer jurisdiction on the comptroller to determine a question to which this section applies except in accordance with the following provisions of this section.
(3) This section applies to a question arising before the grant of a European patent whether a person has a right to be granted a European patent, or a share in any such patent, and in this section 'employer-employee question' means any such question between an employer and an employee, or their successors in title, arising out of an application for a European patent for an invention made by the employee.
(4) The court and the comptroller shall have jurisdiction to determine any question to which this section applies, other than an employer-employee question, if either of the following conditions is satisfied, that is to say—
(a) the applicant has his residence or principal place of business in the United Kingdom; or
(b) the other party claims that the patent should be granted to him and he has his residence or principal place of business in the United Kingdom and the applicant does not have his residence or principal place of business in any of the relevant contracting states;
and also if in either of those cases there is no written evidence that the parties have agreed to submit to the jurisdiction of the competent authority of a relevant contracting state other than the United Kingdom.
(5) The court and the comptroller shall have jurisdiction to determine an employer-employee question if either of the following conditions is satisfied, that is to say—
(a) the employee is mainly employed in the United Kingdom; or
(b) the employee is not mainly employed anywhere or his place of main employment cannot be determined, but the employer has a place of business in the United Kingdom to which the employee is attached (whether or not he is also attached elsewhere);
and also if in either of those cases there is no written evidence that the parties have agreed to submit to the jurisdiction of the competent authority of a relevant contracting state other than the United Kingdom or, where there is such evidence of such an agreement, if the law applicable to the contract of employment does not recognise the validity of the agreement.
(6) Without prejudice to subsections (2) to (5) above, the court and the comptroller shall have jurisdiction to determine any question to which this section applies if there is written evidence that the parties have agreed to submit to the jurisdiction of the court or the comptroller, as the case may be, and, in the case of an employer-employee question, the law applicable to the contract of employment recognises the validity of the agreement.
(7) If, after proceedings to determine a question to which this section applies have been brought before the competent authority of a relevant contracting state other than the United Kingdom, proceedings are begun before the court or a reference is made to the comptroller under section 12 above to determine that question, the court or the comptroller, as the case may be, shall stay or sist the proceedings before the court or the comptroller unless or until the competent authority of that other state either—
(a) determines to decline jurisdiction and no appeal lies from the determination or the time for appealing expires, or
(b) makes a determination which the court or the comptroller refuses to recognise under section 83 below.
(8) References in this section to the determination of a question include respectively references to—
(a) the making of a declaration or the grant of a declarator with respect to that question (in the case of the court); and
(b) the making of an order under section 12 above in relation to that question (in the case of the court or the comptroller).
(9) In this section and section 83 below 'relevant contracting state' means a country which is a party to the European Patent Convention and has not exercised its right under the convention to exclude the application of the protocol to the convention known as the Protocol on Recognition.
Effect of patent decisions of competent authorities of other states
83.(1) A determination of a question to which section 82 above applies by the competent authority of a relevant contracting state other than the United Kingdom shall, if no appeal lies from the determination or the time for appealing has expired, be recognised in the United Kingdom as if it had been made by the court or the comptroller unless the court or he refuses to recognise it under subsection (2) below.
(2) The court or the comptroller may refuse to recognise any such determination that the applicant for a European patent had no right to be granted the patent, or any share in it, if either—
(a) the applicant did not contest the proceedings in question because he was not notified of them at all or in the proper manner or was not notified of them in time for him to contest the proceedings; or
(b) the determination in the proceedings in question conflicts with the determination of the competent authority of any relevant contracting state in proceedings instituted earlier between the same parties as in the proceedings in question.
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Interpretation
130. …
(6) References in this Act to any of the following conventions, that is to say—
(a) The European Patent Convention;
(b) The Community Patent Convention;
(c) The Patent Co-operation Treaty;
are references to that convention or any other international convention or agreement replacing it, as amended or supplemented by any convention or international agreement (including in either case any protocol or annex), or in accordance with the terms of any such convention or agreement, and include references to any instrument made under any such convention or agreement.
(7) Whereas by a resolution made on the signature of the Community Patent Convention the governments of the member states of the European Economic Community resolved to adjust their laws relating to patents so as (among other things) to bring those laws into conformity with the corresponding provisions of the European Patent Convention, the Community Patent Convention and the Patent Co-operation Treaty, it is hereby declared that the following provisions of this Act, that is to say, sections 1(1) to (4), 2 to 6, 14(3), (5) and (6), 37(5), 54, 60, 69, 72(1) and (2), 74(4), 82, 83, 100 and 125, are so framed as to have, as nearly as practicable, the same effects in the United Kingdom as the corresponding provisions of the European Patent Convention, the Community Patent Convention and the Patent Co-operation Treaty have in the territories to which those Conventions apply.
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Brussels I Regulation
Council Regulation 44/2001/EC of 22 December 2000 on jurisdiction and the recognition and enforcement of judgments in civil and commercial matters ("the Brussels I Regulation") includes the following provisions:
" Article 4
1. If the defendant is not domiciled in a Member State, the jurisdiction of the courts of each Member State shall, subject to Articles 22 and 23, be determined by the law of that Member State.
2. As against such a defendant, any person domiciled in a Member State may, whatever his nationality, avail himself in that State of the rules of jurisdiction there in force, and in particular those specified in Annex I, in the same way as the nationals of that State.
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Article 22
The following courts shall have exclusive jurisdiction, regardless of domicile:
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4. in proceedings concerned with the registration or validity of patents, trade marks, designs, or other similar rights required to be deposited or registered, the courts of the Member State in which the deposit or registration has been applied for, has taken place or is under the terms of a Community instrument or an international convention deemed to have taken place.
Without prejudice to the jurisdiction of the European Patent Office under the Convention on the Grant of European Patents, signed at Munich on 5 October 1973, the courts of each Member State shall have exclusive jurisdiction, regardless of domicile, in proceedings concerned with the registration or validity of any European patent granted for that State;
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Article 71
1. This Regulation shall not affect any conventions to which the Member States are parties and which in relation to particular matters, govern jurisdiction or the recognition or enforcement of judgments.
2. With a view to its uniform interpretation, paragraph 1 shall be applied in the following manner:
(a) this Regulation shall not prevent a court of a Member State, which is a party to a convention on a particular matter, from assuming jurisdiction in accordance with that convention, even where the defendant is domiciled in another Member State which is not a party to that convention. The court hearing the action shall, in any event, apply Article 26 of this Regulation;
(b) judgments given in a Member State by a court in the exercise of jurisdiction provided for in a convention on a particular matter shall be recognised and enforced in the other Member States in accordance with this Regulation.
Where a convention on a particular matter to which both the Member State of origin and the Member State addressed are parties lays down conditions for the recognition or enforcement of judgments, those conditions shall apply. In any event, the provisions of this Regulation which concern the procedure for recognition and enforcement of judgments may be applied."
Rome II Regulation
European Parliament and Council Regulation 864/2007/EC of 31 July 2007 on the law applicable to non-contractual regulations ("the Rome II Regulation") includes the following provisions:
" Article 4
General rule
1. Unless otherwise provided for in this Regulation, the law applicable to a non-contractual obligation arising out of a tort/delict shall be the law of the country in which the damage occurs irrespective of the country in which the event giving rise to the damage occurred and irrespective of the country or countries in which the indirect consequences of that event occur.
2. However, where the person claimed to be liable and the person sustaining damage both have their habitual residence in the same country at the time when the damage occurs, the law of that country shall apply.
3. Where it is clear from all the circumstances of the case that the tort/delict is manifestly more closely connected with a country other than that indicated in paragraphs 1 or 2, the law of that other country shall apply. A manifestly closer connection with another country might be based in particular on a pre-existing relationship between the parties, such as a contract, that is closely connected with the tort/delict in question.
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Article 6
Unfair competition and acts restricting free competition
1. The law applicable to a non-contractual obligation arising out of an act of unfair competition shall be the law of the country where competitive relations or the collective interests of consumers are, or are likely to be, affected.
2. Where an act of unfair competition affects exclusively the interests of a specific competitor, Article 4 shall apply.
3. (a) The law applicable to a non-contractual obligation arising out of a restriction of competition shall be the law of the country where the market is, or is likely to be, affected.
(b) When the market is, or is likely to be, affected in more than one country, the person seeking compensation for damage who sues in the court of the domicile of the defendant, may instead choose to base his or her claim on the law of the court seised, provided that the market in that Member State is amongst those directly and substantially affected by the restriction of competition out of which the non-contractual obligation on which the claim is based arises; where the claimant sues, in accordance with the applicable rules on jurisdiction, more than one defendant in that court, he or she can only choose to base his or her claim on the law of that court if the restriction of competition on which the claim against each of these defendants relies directly and substantially affects also the market in the Member State of that court.
4. The law applicable under this Article may not be derogated from by an agreement pursuant to Article 14."
Service out of the jurisdiction: general principles
The general principles governing service out of the jurisdiction were recently re-stated by Lord Collins of Mapesbury LSC delivering the advice of the Privy Council in AK Investment CJSC v Kyrgyz Mobile Tel Ltd [2011] UKPC 7 , [2011] 1 CLC 205 as follows:
"71. On an application for permission to serve a foreign defendant … out of the jurisdiction, the claimant … has to satisfy three requirements: Seaconsar Far East Ltd. v Bank Markazi Jomhouri Islami Iran [1994] 1 AC 438, 453-457. First, the claimant must satisfy the court that in relation to the foreign defendant there is a serious issue to be tried on the merits, i.e. a substantial question of fact or law, or both. The current practice in England is that this is the same test as for summary judgment, namely whether there is a real (as opposed to a fanciful) prospect of success: e.g. Carvill America Inc v Camperdown UK Ltd [2005] EWCA Civ 645 , [2005] 2 Lloyd's Rep 457 , at [24]. Second, the claimant must satisfy the court that there is a good arguable case that the claim falls within one or more classes of case in which permission to serve out may be given. In this context 'good arguable case' connotes that one side has a much better argument than the other: see Canada Trust Co v Stolzenberg (No 2) [1998] 1 WLR 547 , 555-7 per Waller LJ, affd [2002] 1 AC 1 ; Bols Distilleries BV v Superior Yacht Services [2006] UKPC 45 , [2007] 1 WLR 12 , [26]-[28]. Third, the claimant must satisfy the court that in all the circumstances [England] is clearly or distinctly the appropriate forum for the trial of the dispute, and that in all the circumstances the court ought to exercise its discretion to permit service of the proceedings out of the jurisdiction.
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81. A question of law can arise on an application in connection with service out of the jurisdiction, and, if the question of law goes to the existence of jurisdiction, the court will normally decide it, rather than treating it as a question of whether there is a good arguable case: Hutton (EF) & Co (London) Ltd. v Mofarrij [1989] 1 WLR 488, 495 (CA); Chellaram v Chellaram (No 2) [2002] EWHC 632 (Ch) , [2002] 3 All ER 17 , [136].
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88. The principles governing the exercise of discretion set out by Lord Goff of Chieveley in Spiliada Maritime Corp v Cansulex Ltd [1987] AC 460 , at 475-484, are familiar, and it is only necessary to re-state these points: first, in both stay cases and in service out of the jurisdiction cases, the task of the court is to identify the forum in which the case can be suitably tried for the interests of all the parties and for the ends of justice; second, in service out of the jurisdiction cases the burden is on the claimant to persuade the court that England … is clearly the appropriate forum; …"
Lord Goff's speech in Spiliada v Cansulex establishes that the question of forum is to be approached in two stages. The first stage is to ask whether England is clearly and distinctly the natural forum, that is to say, the forum "with which the action has the most real and substantial connection". If England is not the natural forum, the second stage is to ask whether England is nevertheless the appropriate forum, in particular because there is a real risk that the claimant will not obtain substantial justice in the natural forum.
Stage 1 . The factors that may be taken into account in determining which is the natural forum for the action include: (a) the personal connections which the parties have to the countries in question; (b) the factual connections which the events relevant to the claim have with those countries; (c) factors affecting convenience or expense such as the location of the witnesses or documents; and (d) the applicable law.
Stage 2 . The House of Lords made it clear in Amin Rasheed v Kuwait Insurance Co [1984] AC 50 that, in exercising its discretion, it is not normally appropriate for the court to compare the quality of justice obtainable in a foreign forum which adopts a different procedural system (such as that of the civil law) with that obtainable in a similar case conducted in an English court. As Lord Wilberforce said at 72D, "It is not appropriate … to embark upon a comparison of the procedures, or methods, or reputation or standing of the courts of one country as compared with those of another".
Although earlier cases had suggested that it was relevant to enquire whether or not a stay or refusal of permission to serve out would deprive the claimant of a "legitimate personal or juridical advantage", the correct approach to this question was explained by Lord Goff in Spiliada v Cansulex at 482D-F:
"…as Oliver L.J. [1985] 2 Lloyd's Rep. 116, 135, pointed out in his judgment in the present case, an advantage to the plaintiff will ordinarily give rise to a comparable disadvantage to the defendant; and simply to give the plaintiff his advantage at the expense of the defendant is not consistent with the objective approach inherent in Lord Kinnear's statement of principle in Sim v. Robinow , 19 R. 665, 668.
The key to the solution of this problem lies, in my judgment, in the underlying fundamental principle. We have to consider where the case may be tried 'suitably for the interests of all the parties and for the ends of justice.' Let me consider the application of that principle in relation to advantages which the plaintiff may derive from invoking the English jurisdiction. Typical examples are: damages awarded on a higher scale; a more complete procedure of discovery; a power to award interest; a more generous limitation period. Now, as a general rule, I do not think that the court should be deterred from granting a stay of proceedings, or from exercising its discretion against granting leave under R.S.C. Ord. 11, simply because the plaintiff will be deprived of such an advantage, provided that the court is satisfied that substantial justice will be done in the available appropriate forum."
Lord Goff returned to this point in Connelly v R.T.Z. Corporation plc (No 2) [1998] AC 854 at 872G – 873A:
"From the discussion [in Spiliada v Cansulex ], a general principle may be derived, which is that, if a clearly more appropriate forum overseas has been identified, generally speaking the plaintiff will have to take that forum as he finds it, even if it is in certain respects less advantageous to him than the English forum. He may, for example, have to accept lower damages, or do without the more generous English system of discovery. The same must apply to the system of court procedure, including the rules of evidence, applicable in the foreign forum. This may display many features which distinguish it from ours, and which English lawyers might think render it less advantageous to the plaintiff. Such a result may in particular be true of those jurisdictions, of which there are many in the world, which are smaller than our own, and are in consequence lacking in financial resources compared with our own. But that is not of itself enough to refuse a stay. Only if the plaintiff can establish that substantial justice cannot be done in the appropriate forum, will the court refuse to grant a stay …"
Examples of factors that are generally ignored include:
i) the comparative level of disclosure: see Spiliada v Cansulexat 482E-G;
ii) different rules of evidence or provision for cross-examination: see RTZ v Connellyat 873 and Ceskoslovenska Obchodni Banka AS v Nomura International plc[2003] ILPR 20 at [17] (Jonathan Sumption QC sitting as a Deputy High Court Judge, as he then was);
iii) the experience of the foreign court in trying particular types of case: see The Varna (No 2)[1994] 2 Lloyds Rep 41 at 48 (Clarke J, as he then was) and Ceskoslovenska v Nomuraat [15];
iv) the duration of proceedings in the natural forum unless the delay would be excessive: compare The Vishva Ajay[1989] 2 Lloyd's Rep 558 with Radhakrishna Hospitality Service Private Ltd v EIH Ltd[1999] 2 Lloyd's Rep 249, Chellaram v Chellaram (No 2)[2002] EWHC 632 (Ch),[2002] 3 All ER 17and Ceskoslovenska v Nomura;
v) the claimant's prospects of success: see Dicey, Morris & Collins, The Conflict of Laws(14 thed) at §12-033.
On the other hand, the court will have regard to a real risk that the claimant will not obtain substantial justice in the foreign forum, although this will weigh less heavily in the exercise of the court's discretion than evidence that justice "will not" be obtained: see AK Investments v Kyrgyz at [91]-[95] and Pacific International Sports Clubs Ltd v Surkis [2010] EWCA Civ 753 at [31]-[35] (Mummery LJ).
Staying proceedings on the ground of forum non conveniens : general principles
Even where a claim has been properly served within the jurisdiction, this Court may decline to exercise its jurisdiction and grant a stay of the proceedings on the ground of forum non conveniens . Whereas in a service out case the burden is on the claimant to show that England is the appropriate forum, a defendant applying to stay a claim has the burden of showing that an alternative forum is the appropriate forum. Subject to that, the principles laid down in Spiliada v Consulex are equally applicable.
Issue 1: Does this Court have exclusive jurisdiction with respect to the European Applications?
IFL contends that this Court has exclusive jurisdiction to determine entitlement to the European Applications. Frito-Lay accepts that this Court has jurisdiction to determine entitlement to the European Applications, but disputes that it is exclusive of the jurisdiction of the Texas Court. It is common ground that, if IFL is correct on this issue, it has significant consequences with regard to the other issues that fall to be decided on these applications. Accordingly, it is logical to determine this issue first.
It is common ground that section 82(4)(b) of the 1977 Act gives this Court jurisdiction to determine entitlement to the European Applications: Frito-Lay is the applicant and it does not have its residence or principal place of business in any of the EPC Contracting States, while IFL is the party claiming that the patents should be granted to it and it has its residence and principal place of business in the United Kingdom. There is no agreement between the parties to submit to the jurisdiction of any other Contracting State.
On its face, section 82(4)(b) does not say that this Court's jurisdiction is exclusive. Section 82, however, is one of those sections which is declared by section 130(7) to be "so framed as to have, as nearly as practicable, the same effects in the United Kingdom as the corresponding provisions of" the EPC. It is common ground that it follows that section 82(4)(b) must be construed consistently with Article 3 of the Protocol on Recognition, which does say that the courts of the relevant Contracting State shall have exclusive jurisdiction.
The dispute is as to what is meant by "exclusive". IFL contends that this means exclusive of the jurisdiction of any other state whatsoever. Frito-Lay contends that it merely means exclusive of the jurisdiction of any other Contracting State. In my judgment IFL's interpretation is to be preferred. My reasons are as follows.
First, I consider that the natural meaning of the words "shall have exclusive jurisdiction" is exclusive of all other possible jurisdictions. Frito-Lay's construction involves reading in a limitation which is not apparent on the face of Article 3.
Secondly, this is the usual meaning of "exclusive jurisdiction" in European legislation, and in particular in Article 16 of the Brussels Convention on Jurisdiction and the Enforcement of Judgments in Civil and Commercial Matters of 1968, now Article 22 of the Brussels I Regulation. (In passing, it should be noted that entitlement disputes do not fall within Article 22(4) of the Brussels I Regulation: see Case 288/82 Duijnstee v Goderbauer [1983] ECR 3663.)
Thirdly, in the specific context of Article 3 of the Protocol on Recognition, the Article is addressing a situation in which the applicant has his residence or principal place of business outside the Contracting States whereas the party claiming entitlement ("the claimant") has his residence or principal place of business in a Contracting State. It follows that the most likely rival jurisdictions are (a) the non-Contracting state in which the applicant has his residence or principal place of business and (b) the Contracting State in which the claimant has his residence or principal place of business. In providing that state (b) is to have exclusive jurisdiction, the obvious inference is that Article 3 is intended to exclude the jurisdiction of state (a) (as well as any further alternative states). It would very odd if the jurisdiction of state (a) were not excluded, yet that is the effect of Frito-Lay's interpretation.
Fourthly, this interpretation is supported by Article 5(1) of the Protocol on Recognition. That says that if the parties have agreed that a particular Contracting State shall determine the dispute, then that State has exclusive jurisdiction. Again, it would be very odd if that did not exclude the courts of non-Contracting states. Furthermore, it is telling that there is no provision for the parties to agree that the courts of a non-Contracting state shall have jurisdiction even if they both have their residence or principal place of business in that state. For this reason I am unimpressed by the argument of counsel for Frito-Lay that Article 6 of the Protocol on Recognition cannot have been intended to trump such an agreement. As discussed below, there will be no problem if the parties are content to litigate in that state. If the claimant is not, then on its face Article 6 gives Germany exclusive jurisdiction. In any event, even if "exclusive jurisdiction" is to be given a more restricted meaning for the purpose of Article 6, it does not necessarily follow that it must be interpreted in the same way in the context of Article 3.
Fifthly, this interpretation is supported by Article 9 of the Protocol on Recognition, to which section 83 of the 1977 Act gives effect, since it is only the decisions of courts of Contracting States that are required to be recognised. There is no provision for recognition of decisions of courts of non-Contracting states.
Sixthly, this interpretation is supported by consideration of the purpose of the Protocol on Recognition. As counsel for IFL pointed out, the EPC created a unique system which had not previously existed, under which a single application to the EPO could result in multiple patents in the Contracting States. In those circumstances it was clearly necessary to set up a clear system to deal with entitlement disputes. Article 60(3) EPC creates a legal fiction for the purposes of proceedings in the EPO that the applicant is deemed to be entitled, and the EPO has no jurisdiction to determine entitlement. Instead, the Protocol on Recognition creates a scheme under which one, and only one, Contracting State has jurisdiction to determine entitlement, and its determination must then be recognised by the EPO under Article 61 EPC and by all other Contracting States under Article 9 of the Protocol on Recognition. (The only exception to this is provided by Article 11(2) of the Protocol on Recognition, which deals with the situation where there is a conflicting treaty between a Contracting State and a state which is not party to the EPC. It is common ground, however, that there is no such treaty relevant to the present case.) This scheme is plainly intended to ensure legal certainty. IFL's interpretation gives effect to that intention, since it ensures that (save in the exceptional case where Article 11(2) of the Protocol on Recognition applies, which may give rise to a geographical split of entitlement) there is only one state in the world with jurisdiction to determine entitlement to a European patent application. Frito-Lay's interpretation frustrates that intention, since it allows for the possibility of multiple competing jurisdictions.
Seventhly, IFL's interpretation promotes the interests of parties who have their residence or principal place of business in a Contracting State, in that they can be sure that entitlement disputes will be dealt with by the courts of a Contracting State, whereas Frito-Lay's interpretation undermines those interests. As for parties who have their residence or principal place of business in a non-Contracting state, by applying for a European patent, they sign up to the scheme created by the Protocol on Recognition. If they do not like that scheme, they do not have to apply for a European patent. They can apply for national patents in the Contracting States instead.
Eighthly, I consider that IFL's interpretation receives more support from the three EPO authorities to which I was referred than does Frito-Lay's interpretation. I shall take these in chronological order.
In J34/86 Bowles/Divisional application [1988] EPOR 266 a US application and a European application claiming priority therefrom had been filed by a former employee of a United States corporation. The US application had proceeded to grant in the employee's name. In litigation between the corporation and its ex-employee after grant, the Court of Special Appeals of Maryland confirmed a ruling of the Circuit Court that the corporation was entitled to all rights in the invention defined by certain specified claims of the US patent. The ex-employee was ordered to assign those rights to the corporation. An application by the ex-employee to the Court of Appeals of Maryland for review was refused, and no further review by the US Supreme Court was sought. Subsequent to the decision of the Court of Special Appeals, but prior to the refusal of the ex-employee's application for review, the corporation filed the European application in suit under Article 61(1) EPC in respect of the subject-matter to which they had been held entitled in the Maryland litigation. The Receiving Section of the EPO refused to accord this application the filing and priority dates of the ex-employee's application, on the ground that when it was made, the decision of the Maryland Court of Special Appeals had not become final.
The corporation appealed. On the appeal the corporation relied primarily on a subsequent assignment made by the ex-employee pursuant to the orders of the Maryland courts. This assigned "all rights" in the invention defined by the specified claims of the US patent and expressly covered "any divisional applications in any countries", but it did not expressly cover priority rights. The corporation argued that the assignment provided legal basis for treating the application in suit as a divisional in the corporation's name of the application originally filed by the ex-employee.
The Legal Board of Appeal allowed the appeal, holding that the assignment could be regarded as confirmation of the corporation's right to the invention claimed in the proposed divisional application, including the right to priority. The Board also held that it would not be right to ignore the assignment on the ground that to recognise it would be tantamount to enforcing a ruling of a court in a non-Contracting state. It left open the question whether action under Article 61 EPC could be taken on the basis of a decision of such court, but said that giving effect to an assignment was different even if the assignment was executed in compliance with a court order.
As counsel for IFL submitted, this decision does not contradict IFL's interpretation of Article 3 of the Protocol on Recognition. Furthermore, as noted above, it provides at least a partial answer to counsel for Frito-Lay's argument based on Article 6 of the Protocol on Recognition.
In G3/92 Latchways/unlawful applicant [1995] EPOR 141 Latchways Ltd, an English company, had developed a novel rope grip device and disclosed a prototype in confidence to Cleveland Dodge, a US citizen, for the purpose of considering its exploitation in the United States. Mr Dodge filed patent applications in respect of the device in the United States in 1984 and in the EPO in 1985, the latter claiming priority from the US application. The European application was published, but subsequently deemed withdrawn for failure to pay the examination fee.
Latchways developed the device further and filed patent applications in the United Kingdom in 1986 and in the EPO in 1987, the latter claiming priority from the UK application. The European search report transmitted to Latchways in 1988 made Latchways aware for the first time of the 1985 European application by Mr Dodge.
Latchways filed a reference to the Comptroller under section 12 of the 1977 Act and obtained a decision from the Comptroller that it was entitled to the grant of a European patent for the invention the subject of the Mr Dodge's 1985 European application. Latchways accordingly filed a new European application in respect of the subject-matter of the 1985 application under Article 61(1)(b) EPC. The Receiving Section of the EPO held that Latchways was not entitled to do so, since the 1985 application was no longer pending. Latchways appealed, and the Legal Board of Appeal referred the question of law to the Enlarged Board of Appeal.
By a majority decision, the Enlarged Board of Appeal held that, when it has been adjudged by a final decision of a national court that a person other than the applicant is entitled to the grant of a European patent, and that person, in compliance with the requirements of Article 61(1) EPC, files a new European patent application in respect of the same invention under Article 61(1)(b) EPC, it is not a pre-condition for the application to be accepted that the earlier original usurping application is still pending before the EPO at the time the new application is filed.
The decision of the majority includes the following passage which is relevant to the present issue:
"3.1 Article 1(1) Protocol provides that …. In relation to any particular claim by an alleged lawful applicant against an actual applicant for a European patent, the particular Contracting State whose courts have jurisdiction to decide the claim is determined by the system of jurisdiction set out in Articles 2 to 8 Protocol. For any such claim, this system of jurisdiction designates the courts of one (and only one) Contracting State as the proper forum in which the claim must be decided.
After a court in a Contracting State has given a final decision on 'the right to the grant of a European patent in respect of one or more of the Contracting States designated in the European patent application', Article 9(1) Protocol provides that such a decision 'shall be recognised without requiring a special procedure in the other Contracting States'. Furthermore, Article 9(2) Protocol provides that 'The jurisdiction of the court whose decision is to be recognised and the validity of such decision may not be reviewed'.
3.2 Under Article 167(2) EPC, a Contracting State to the EPC may reserve the right to provide that it shall not be bound by the Protocol on Recognition. Under Article 167(3) EPC, such a reservation can only have effect for a limited period of time. Article 1(3) Protocol provides that for the purposes of the Protocol, the term 'Contracting State' refers to a Contracting State which has not excluded application of the Protocol on Recognition under Article 167 EPC.
3.3 Thus, in accordance with the above provisions of the Protocol on Recognition, a claim to the right to the grant of a European patent can only be decided before a court of the appropriate Contracting State; this is the only forum in which a lawful applicant may commence proceedings to establish his right. Furthermore, when such a claim has been decided in a final decision of such a national court in favour of a lawful applicant (B) and against an unlawful applicant (A) for a European patent application, that decision has to be recognised in all the other Contracting States which are bound by the Protocol. Under the Protocol on Recognition, subject to Articles 10 and 11(2) thereof, recognition is automatic and as of right.
3.4 When a national court of the appropriate Contracting State decides an individual case concerning a claim to entitlement to the grant of a European patent under the Protocol on Recognition, it will apply the particular national law which governs determination of the case, which may or may not be its own national law, within the framework of its own legal system. Without the system of jurisdiction and recognition provided by the Protocol on Recognition, an individual case concerning a dispute as to who has the right to apply for a European patent could be the subject of proceedings in more than one national court, and could be decided differently in different national courts. It would then be impossible for the EPO to deal with one applicant (that is, the lawful applicant) in respect of the European application which is the subject of such proceedings
The above provisions of the Protocol on Recognition avoid such difficulties. A claim to the entitlement to the grant of a European patent is decided by a court of just one Contracting State, and whatever the result in that court, its decision is recognised in all the other Contracting States which are bound by the Protocol. This system of jurisdiction set out in the Protocol has its counterpart in Article 61 EPC, by which a dispute concerning the legal right provided by Article 60(1) EPC, having been decided by the appropriate national court, can be implemented and enforced for the purpose of the granting procedure before the EPO. Following the initiation by the lawful applicant (B) of a new procedure before the EPO in accordance with Article 61 EPC, the EPO is required to deal thereafter in such new procedure with the lawful applicant (B) in place of the unlawful applicant (A). "
I recognise that this decision was taken on the basis of Article 61 EPC as originally enacted, and that it has subsequently been amended. Nevertheless, I agree with counsel for IFL that this reasoning supports IFL's interpretation of Article 3 of the Protocol on Recognition.
In J6/03 Heath/Suspension of proceedings (unreported, 29 September 2004) Mr Heath, who was resident in Canada, had filed an application for a European patent. Matrix Service Inc, a Canadian company, and Matrix Service Co, a US company (collectively "Matrix") requested suspension of the proceedings under EPC Rule 13 (which permits suspension where there are entitlement proceedings pending) on the grounds that Matrix had commenced proceedings against Mr Heath before the Canadian Superior Court of Justice of Ontario. In the Canadian proceedings Matrix claimed that it was entitled to the grant of the European patent on the grounds that Mr Heath, who was an ex-employee of Matrix, had acted in breach of various agreements. Matrix sought inter alia an order requiring Mr Heath to assign any and all right, title and interest in the European patent application to Matrix. The Legal Division of the EPO rejected the request for suspension on the ground Rule 13 EPC was to be regarded as an implementing provision to Article 61(1) EPC, which in turn was based on the closed system of jurisdiction and recognition provided for by the Protocol on Recognition. The Legal Division considered that the Canadian court did not have jurisdiction under the Protocol on Recognition. Matrix appealed. The Legal Board of Appeal dismissed the appeal, holding that the proceedings initiated before the Canadian courts did not fulfil the requirements of Rule 13 EPC.
In its decision the Board expressed doubts with regard to the Legal Division's view that Article 61(1) EPC (1973 version) excluded recognition of a decision of a non-Contracting state. The Board said that the first and second possibilities mentioned in Article 61(1) ("decision given in a Contracting State" and "decision recognised in a Contracting State") applied to cases where a Contracting State had a made a reservation under Article 167(2)(d) EPC. The Board pointed out that the third possibility ("has to be recognised on the basis of the Protocol on Recognition") covered the situation where a judgment of a court of a non-Contracting state (such as Canada) was recognised by a Contracting State, which could occur where that Contracting State had made a reservation. As a result, there might be a geographical split of entitlement to the European application. The Board noted, however, that there was no longer any reservations under Article 167(2)(d), and all Contracting States were bound by the Protocol on Recognition. The question, therefore, was whether the Protocol on Recognition excluded recognition of a decision of a non-Contracting State.
At [14] the Board said:
"As no formal exclusion of recognition of decisions of third States is specifically prescribed by the Protocol, such an exclusion could only be established by the interpretation of the jurisdiction established by Articles 2 to 6 of the Protocol as exclusive international jurisdiction not only between the members of the Convention but also with respect to third States. Only in the latter case, the lack of international jurisdiction of a court of a non-European State will be an indispensable issue concerning admissibility in national court proceedings on recognition."
The Board went on to note that Articles 2-5 of the Protocol on Recognition did not apply to the instant case. With regard to Article 6, the Board said:
"18. Article 6 Protocol reads ... The word 'exclusive' may be interpreted in such a way that international jurisdiction of courts of third States shall not be recognised by the Contracting States. However, it is known from national procedural law that such a broad interpretation depends on the connecting factor given in the provision. Article 6 Protocol only provides a residual or auxiliary jurisdiction without any reference to specific connecting factors. Therefore, Article 6 Protocol could be interpreted as a provision which provided for a further jurisdiction in cases where otherwise a general and automatic recognition for all Contracting States could not be achieved but not as one which generally excludes the recognition of international jurisdiction of courts of third States. This opinion is emphatically supported by legal literature (see Stauder, Münchner Gemeinschaftskommentar, Anerkennungsprotokoll, Köln 1984, Article 6, note 4 and Heath, Münchner Gemeinschaftskommentar, Europäisches Patentübereinkommen, Köln 2004, Article 61, note 61).
It seems that the first instance did not consider these opinions and took the view that Article 6 of the Protocol establishes an exclusive jurisdiction which has to be defended in national recognition proceedings with respect to decisions of courts of third States.
19. Even considering the European Convention as a whole and the Historical Documents relating to it ( travaux préparatoires ), the Board finds no clear indication whether or not these implications were recognised when the EPC was drafted and what purpose should prevail in view of the national delegations concerned.
However with respect to the present case, this question need not be finally decided because from the Board's point of view a restrictive application of Rule 13 EPC is required for other reasons."
Despite this, the Board went on to say at [25]:
"When the Protocol was drawn up, it was also agreed that recognition of decisions does not extend to decisions of courts of a third Country recognised in a Contracting State on the basis of a bilateral agreement (see doc. BR/219 d/72, No. 65) and on a proposal from the United Kingdom Article 10(2) [ sic – I think this should be 11(2)] was added to the Protocol. If the Contracting States would have vested any jurisdiction for recognition to the EPO, with respect to decisions of courts of third States, it would have been discussed at this stage of negotiation and the appropriate rules on recognition would have been developed but no mention on this point can be found in the Historical Documentation relating to the European Patent Convention ( travaux préparatoires ) and the Protocol. Thus, the Board considers that the EPO has no jurisdiction to recognise decisions of courts of third States without the basis of an appropriate constitutive provision. This conclusion cannot be disputed on the basis that the EPO has a competence to 'recognise' a transfer of a European patent application under Rule 20(1) EPC after submission of documents proving the legal transfer of the rights concerned, such transfer being based on a voluntary legal action going against the entitlement of the inventor under Article 60(1) EPC as an original right."
As I understand this, the Board concluded that, even if Contracting States could recognise a judgment of a court of a non-Contracting state, as to which the Board expressed no concluded opinion, the EPO itself could not. Accordingly, the Board held that Rule 13 should not be interpreted as applying to proceedings before the courts of non-Contracting states, which could only be given effect to by the EPO if and in so far as the resulting judgment was recognised in one or more Contracting States.
I recognise that this decision provides support for counsel for Frito-Lay's argument as to the interpretation of Article 6 of the Protocol on Recognition. As counsel for IFL pointed out, however, it provides no support for interpreting Article 3 in the manner suggested by Frito-Lay.
Issue 2: What is the consequence of this Court having exclusive jurisdiction over the European Applications?
IFL contends that, as a consequence of this Court having exclusive jurisdiction over entitlement to the European Applications, no stay can be granted of action 3841 so far as it relates to the European Applications on forum non conveniens grounds. Frito-Lay disputes this. In the alternative, Frito-Lay contends that this does not preclude a stay being granted on case management grounds.
It is common ground that the EPC, including the Protocol on Recognition, is a convention falling within Article 71(1) of the Brussels I Regulation. The Court of Justice of the European Union has held that, when jurisdiction is founded under an Article 71 convention, it is to be considered, at least for the purposes of Article 26, as jurisdiction derived from Brussels I: see Case C-148/03 Nürnberger Allgemeine Versicherungs AG v Portbridge Transport International BV [2004] ECR I-10327 at [17] (a case decided under Articles 57 and 20 of the Brussels Convention, which correspond to Article 71 and 26 of the Brussels I Regulation).
IFL contends that, when jurisdiction is mandatory on the basis of the Brussels I Regulation, including by virtue of an Article 71 convention, the doctrine of forum non conveniens has no application. Frito-Lay disputes this.
Counsel for IFL primarily relied in support of this contention on the decision of the CJEU in Case C-281/02 Owusu v Jackson 1005] ECR I-1383. In that case the claimant, who was domiciled in the United Kingdom, had hired a holiday villa in Jamaica which had access to a private beach from the first defendant, who also domiciled in the United Kingdom. The claimant suffered severe injuries while diving from the beach onto a submerged sandbank, and brought an action in England for damages against the first defendant and other defendants, Jamaican companies of which one owned the beach and others had licences in connection with its use. The defendants invited the judge to decline jurisdiction in favour of the courts of Jamaica, on the basis of the doctrine of forum non conveniens , but the judge refused on the grounds that, despite the connecting factors with Jamaica, Article 2 of the Brussels Convention obliged him to assume jurisdiction vis-à-vis the first defendant, and that if the English court did not hear the claims against the other defendants also, there would be a risk of conflicting decisions in different jurisdictions. The Court of Appeal asked the Court of Justice whether, when jurisdiction was founded on Article 2, it was inconsistent with the Brussels Convention for a court of a contracting state to exercise a discretionary power, available under its national law, to decline jurisdiction in favour of the courts of a non-contracting state.
The Court of Justice held that this was inconsistent with the Brussels Convention for the following reasons:
"37. It must be observed, first, that Article 2 of the Brussels Convention is mandatory in nature and that, according to its terms, there can be no derogation from the principle it lays down except in the cases expressly provided for by the Convention (see, as regards the compulsory system of jurisdiction set up by the Brussels Convention, Case C-116/02 Gasser [2003] ECR I-0000, paragraph 72, and Case C-159/02 Turner [2004] ECR I-0000, paragraph 24). It is common ground that no exception on the basis of the forum non conveniens doctrine was provided for by the authors of the Convention, although the question was discussed when the Convention of 9 October 1978 on the Accession of Denmark, Ireland and the United Kingdom was drawn up, as is apparent from the report on that Convention by Professor Schlosser (OJ 1979 C 59, p. 71, paragraphs 77 and 78).
38. Respect for the principle of legal certainty, which is one of the objectives of the Brussels Convention (see, inter alia, Case C-440/97 GIE Groupe Concorde and Others [1999] ECR I-6307 , paragraph 23, and Case C-256/00 Besix [2002] ECR I-1699 , paragraph 24), would not be fully guaranteed if the court having jurisdiction under the Convention had to be allowed to apply the forum non conveniens doctrine.
39. According to its preamble, the Brussels Convention is intended to strengthen in the Community the legal protection of persons established therein, by laying down common rules on jurisdiction to guarantee certainty as to the allocation of jurisdiction among the various national courts before which proceedings in a particular case may be brought ( Besix , paragraph 25).
40. The Court has thus held that the principle of legal certainty requires, in particular, that the jurisdictional rules which derogate from the general rule laid down in Article 2 of the Brussels Convention should be interpreted in such a way as to enable a normally well-informed defendant reasonably to foresee before which courts, other than those of the State in which he is domiciled, he may be sued ( GIE Groupe Concorde and Others , paragraph 24, and Besix , paragraph 26).
41. Application of the forum non conveniens doctrine, which allows the court seised a wide discretion as regards the question whether a foreign court would be a more appropriate forum for the trial of an action, is liable to undermine the predictability of the rules of jurisdiction laid down by the Brussels Convention, in particular that of Article 2, and consequently to undermine the principle of legal certainty, which is the basis of the Convention.
42. The legal protection of persons established in the Community would also be undermined. First, a defendant, who is generally better placed to conduct his defence before the courts of his domicile, would not be able, in circumstances such as those of the main proceedings, reasonably to foresee before which other court he may be sued. Second, where a plea is raised on the basis that a foreign court is a more appropriate forum to try the action, it is for the claimant to establish that he will not be able to obtain justice before that foreign court or, if the court seised decides to allow the plea, that the foreign court has in fact no jurisdiction to try the action or that the claimant does not, in practice, have access to effective justice before that court, irrespective of the cost entailed by the bringing of a fresh action before a court of another State and the prolongation of the procedural time-limits.
43. Moreover, allowing forum non conveniens in the context of the Brussels Convention would be likely to affect the uniform application of the rules of jurisdiction contained therein in so far as that doctrine is recognised only in a limited number of Contracting States, whereas the objective of the Brussels Convention is precisely to lay down common rules to the exclusion of derogating national rules.
44. The defendants in the main proceedings emphasise the negative consequences which would result in practice from the obligation the English courts would then be under to try this case, inter alia as regards the expense of the proceedings, the possibility of recovering their costs in England if the claimant's action is dismissed, the logistical difficulties resulting from the geographical distance, the need to assess the merits of the case according to Jamaican standards, the enforceability in Jamaica of a default judgment and the impossibility of enforcing cross-claims against the other defendants.
45. In that regard, genuine as those difficulties may be, suffice it to observe that such considerations, which are precisely those which may be taken into account when forum non conveniens is considered, are not such as to call into question the mandatory nature of the fundamental rule of jurisdiction contained in Article 2 of the Brussels Convention, for the reasons set out above."
It was been held that the applicability of forum non conveniens is also excluded in cases where there is mandatory jurisdiction under Article 5(6) ( Gomez v Gomez-Manche Vives [2008] EWHC 259 (Ch) at [112]-[116] (Morgan J) reversed on other grounds [2008] EWCA Civ 1065 , [2009] Ch 245 ) and Article 23 of the Brussels I Regulation ( Equitas Ltd v Allstate Insurance Co [2008] EWHC 1671 (Comm) , [2009] Lloyd's Rep IR 227 at [64] (Beatson J), UBS AG v HSH Nordbank AG [2009] EWCA Civ 585 , [2009] Lloyd's Rep 272 at [103] (Collins LJ, as he then was)).
Counsel for Frito-Lay argued that the present case was to be distinguished from Owusu and the authorities referred to in the preceding paragraph on the ground that jurisdiction in the present case was founded on Article 4 of the Brussels I Regulation. Counsel for Frito-Lay submitted, and counsel for IFL did not dispute, that where jurisdiction was founded on Article 4, then the doctrine of forum non conveniens remained applicable: see Dicey, Morris & Collins, The Conflict of Laws (14 th ed) at §12-016.
Counsel for IFL submitted, however, that in the present case jurisdiction was not founded upon Article 4, but upon an Article 71 convention, as discussed above. He did not dispute that, in the absence of Article 71 and the EPC's Protocol on Recognition, Article 4 would have been applicable, but he argued in effect that Article 71 and the EPC's Protocol on Recognition overrode Article 4. I accept that argument. Article 4 is expressly subject to Articles 22 and 23, which provide for exclusive jurisdiction in certain cases. Where Articles 22 or 23 apply, the court cannot decline jurisdiction on forum non conveniens grounds. Where an Article 71 convention provides for exclusive jurisdiction, then it seems to me that the same result should follow. Furthermore, as counsel for IFL submitted, all the reasons given by the Court of Justice in Owusu in the passage quoted above apply with equal force to the Protocol on Recognition.
Accordingly, I conclude that no stay can be granted of action 3841 so far as it relates to the European Applications on forum non conveniens grounds.
I turn next to Frito-Lay's alternative contention that a temporary stay may be granted on case management grounds. Counsel for IFL did not dispute that the Court has jurisdiction to grant such a stay, but pointed out that such stays are only granted in "rare and compelling circumstances": see Reichhold Norway ASA v Goldman Sachs International [2000] 1 WLR 173 at 186 (Lord Bingham of Cornhill CJ). He disputed that such circumstances existed in the present case. I shall return to this point below.
Issue 3: Should this Court exercise jurisdiction under section 12 of the 1977 Act in respect of the other Frito-Lay Applications, and in particular the pending US applications?
It is common ground that this Court has no jurisdiction under section 12 of the 1977 Act to determine entitlement to patents which were granted as at the date of the Claim Form in action 4566 (or possibly the date of the reference to the Comptroller, if that makes any difference), and in particular the two granted US patents referred to in paragraphs 16 and 21 above. (The third granted US patent, referred to in paragraph 18 above, was granted after the date of the Claim Form).
IFL contends that this Court has jurisdiction under section 12 in respect of all the Frito-Lay Applications which were pending as at the date of the Claim Form, including the pending US applications. Frito-Lay does not dispute that, on the face of section 12, the Court appears to have jurisdiction; but it contends that the Court should not exercise it, or at least should decline to exercise it in respect of the pending US applications. IFL accepts that this Court has power to grant a stay of the section 12 proceedings on normal forum non conveniens grounds, which I will consider below. This issue at this stage is whether there is any more fundamental reason as to why this Court should decline to exercise its jurisdiction under section 12. Frito-Lay advances two such reasons, one general and one more specific.
Generally, Frito-Lay contends that the purpose of section 12 is primarily to enable resolution of disputes over international patent applications where the UK is the Receiving Office under the Patent Co-operation Treaty and/or the inventions claim priority from a UK application. This is to ensure that, where there is a dispute about a UK patent application under section 8, it can be resolved together with all the foreign applications which stem from it under section 12. This avoids the need for litigation in multiple fora for all the foreign filings in the same patent family where that family has its base in the UK. Frito-Lay says that it is not the purpose of section 12 to provide some roving international jurisdiction over any foreign patent applications even where the base filings are in a foreign country.
In considering this submission, two points need to be borne in mind. The first is that section 12 confers subject-matter jurisdiction. It does not, in and of itself, confer personal jurisdiction over any particular defendant. The second is that, even where personal jurisdiction can be established, the court can decline to exercise jurisdiction over the dispute on forum non conveniens grounds, which will involve considering the connections of the parties and the dispute with the competing fora. I accept that the fact that the base filings were made in a foreign country may in an appropriate case be a factor pointing away from the court exercising jurisdiction. I do not accept that it is determinative, however. Thus, contrary to the submission of counsel for Frito-Lay, it is not unprecedented for the section 12 jurisdiction to be exercised in respective of international applications claiming priority from a US patent application (see e.g. Ladney and Hendry's International Application [1998] RPC 319) or even US patent applications themselves (see e.g. LIFFE Administration and Management v Pinkava [2007] EWCA Civ 217 , [2007] RPC 30).
More specifically, Frito-Lay contends that this Court is precluded from determining entitlement to pending US applications. It is common ground that, in order to determine which party was entitled to be granted US patents in respect of the disputed inventions, the Court would have to apply US law. It is also common ground, however, that the US Court of Appeals for the Federal Circuit has recently held that there is no private right of action to challenge the inventorship of, and hence entitlement to, pending US applications, as opposed to granted patents, and that such relief can only be granted by the Director of the USPTO under 35 USC §§116 & 135(a): see HIF Bio, Inc. v Yung Shin Pharmaceuticals Industrial Co Ltd 600 F. 3d 1347 (Fed. Cir., 2010).
Counsel for IFL submitted that this was merely a procedural bar, rather than a rule of substantive law, and therefore did not preclude this Court from determining entitlement to pending US applications in the exercise of its section 12 jurisdiction. IFL has served no expert evidence in support of this submission, however, even though it has served expert evidence with respect to US law (as to which, see further below). In the light of the clear statement of Judge Gajarsa giving the opinion of the CAFC in HIF at 1354 that "no private right of action exists", and in the absence of expert evidence to the contrary, it appears to me that the bar is substantive, not procedural.
Accordingly, I conclude that this Court has jurisdiction under section 12 to determine entitlement to pending US applications, but that, applying the applicable substantive law, IFL would have no claim to entitlement to those applications which this Court could uphold. (It should be noted that this problem did not arise in LIFFE v Pinkava because in that case there was no issue as to inventorship, and the dispute was one as to entitlement as between employer and employee, which was governed by section 39 of the 1977 Act.) In this regard, this Court's jurisdiction is neither more extensive, nor less extensive, than that of the Texas Court. Of course, once the pending US applications proceed to grant, this jurisdictional obstacle will cease to apply in either court.
Issue 4: Does this Court lose jurisdiction under section 12 if an application proceeds to grant?
It is probable that, in countries where (unlike in the EPO) IFL cannot obtain a suspension of the prosecution proceedings, a number of the Frito-Lay Applications will proceed to grant between now and the date of any trial of these actions. Frito-Lay contends that, as and when each foreign application is granted, this Court will cease to have jurisdiction to deal with it under section 12. IFL disputes this.
Frito-Lay's contention might be thought to receive support from the absence of any counterpart to section 9 so far as section 12 is concerned and from the fact that section 37 does not apply to foreign patents. As counsel for IFL pointed out, however, in the sequel to the Ladney and Hendry case, Cinpres Gas Injection Ltd v Melea Ltd [2008] EWCA Civ 9 , [2008] RPC 17, Jacob LJ giving the judgment of the Court of Appeal held at [76]:
"So a s. 8 application is transmuted into a s. 37 application upon grant. That can only be because the subject-matter - the cause of action - of the two applications is the same. Although, oddly, there is no similar provision for s.12 (perhaps because s.12 covers not only UK but foreign applications) the logic is the same. In short whether the dispute is about a right to an application or to the patent resulting from an application, the cause of action, entitlement, is about one indivisible thing, ownership."
Counsel for IFL submitted that it followed from this reasoning that what mattered was whether the Court had jurisdiction over the cause of action as at the date of the commencement of the proceedings. If it did, the Court did not lose jurisdiction merely because an application matured into a patent, because the cause of action remained the same.
Counsel for Frito-Lay countered that the Court of Appeal was not considering the issue that is presently before this Court. Furthermore, he pointed out that the statements quoted above were made in the context of a case concerning successive claims to ownership of (i) an international patent application (claiming priority, as noted above, from a US patent application) under section 12 and (ii) a European Patent (UK) under section 37.
I accept that Cinpres v Melea is distinguishable for the reasons given by counsel for Frito-Lay. Nevertheless, I find the logic of counsel for IFL's submission persuasive. I therefore conclude that this Court will not cease to have jurisdiction to deal with the Frito-Lay Applications under section 12 merely because they proceed to grant between now and trial.
Issue 5: What is the law applicable to IFL's claim for breach of confidence?
It is common ground that entitlement to the European Applications must be decided in accordance with Article 60 EPC, entitlement to the US applications and patents must be decided in accordance with US law and entitlement to the national applications stemming from the international applications must be decided in accordance with the relevant national laws. There is a dispute, however, as to the law applicable to IFL's claim for breach of confidence. IFL contends that the applicable law is English law, while Frito-Lay contends that it is Delaware law, or possibly Texas law.
In order to determine this issue, it is first necessary to determine the rule or rules for ascertaining the applicable law, bearing in mind that most of the events giving rise to damage relied on by IFL occurred prior to 11 January 2009, but some occurred after that date (in particular, prosecution of the Frito-Lay Applications, procuring publication of some of the Frito-Lay Applications and procuring the grant of those patents which have been granted). The significance of that date is that in Case C-412/100 Homawoo v GMF Assurances SA [2011] ECR I-0000 the CJEU ruled that:
"Articles 31 and 32 of Regulation (EC) No 864/2007 of the European Parliament and of the Council of 11 July 2007 on the law applicable to non-contractual obligations ('Rome II'), read in conjunction with Article 297 TFEU, must be interpreted as requiring a national court to apply the Regulation only to events giving rise to damage occurring after 11 January 2009 and that the date on which the proceedings seeking compensation for damage were brought or the date on which the applicable law was determined by the court seised have no bearing on determining the scope ratione temporis of the Regulation."
It is important to emphasise that, as noted above, IFL's claim is for breach of an equitable obligation of confidence. Under English law, an equitable obligation of confidence will arise as a result of the acquisition or receipt of confidential information if (but only if) the acquirer or recipient either knows or has notice (objectively assessed by reference to a reasonable person standing in his shoes) that the information is confidential: see Force India Formula One Team Ltd v 1 Malaysia Racing Team Sdn Bhd [2012] EWHC 616 (Ch) at [224] and the authorities cited there.
Events prior to 11 January 2009. In his skeleton argument counsel for Frito-Lay suggested that the applicable law should be determined in accordance with section 11 of the Private International Law (Miscellaneous Provisions) Act 1995. In Kitechnology BV v Unicor GmbH Plastmachinen [1995] FSR 766 at 777-778, however, the Court of Appeal held that claims for breach of an equitable obligation of confidence did not arise in tort as a matter of English law in the context of considering whether they fell within Article 5(3) of the Brussels Convention (now Article 5(3) of the Brussels I Regulation). It follows that the applicable law must be determined in accordance with common law principles of conflicts of law.
Identifying the relevant common law principles is not straightforward, however. As Lord Phillips of Worth Matravers MR stated when delivering the judgment of the Court of Appeal in Douglas v Hello! Ltd (No 3) [2005] EWCA Civ 106 , [2006] QB 125 at [97]:
" Dicey & Morris on the Conflict of Laws , 13th ed (2000), vol 2, at paras 34-029ff, suggest, somewhat tentatively, that a claim for breach of confidence falls to be categorised as a restitutionary claim for unjust enrichment and that the proper law is the law of the country where the enrichment occurred. While we find this reasoning persuasive, it does not solve the problem on the facts of this case…."
In the current (14 th ) edition of Dicey, Morris & Collins, the editors deal with this question as follows (omitting footnotes):
"34–033 Choice of law for equitable obligations and wrongs. The courts have had little occasion to consider the choice of law rules applicable to causes of action which would, as a matter of English domestic law, be seen as being based on or concerned with an equitable obligation or equitable wrong. There is no reason to suppose that the domestic law distinction between equity and the common law is reflected in the rules of characterisation and choice of law in the conflict of laws; there is therefore no need for a choice of law rule for 'equitable obligations'. But many actions which would in English law be seen as equitable (for breach of confidence, or to require a bribe-taker to account for the bribe, or to enforce fiduciary duties against someone who has made an unauthorised profit, for example) and which when arising under a foreign law present problems of characterisation, may well be characterised as being restitutionary in nature. If so, they will fall within the scope of [Rule 230]. Authority is scanty. Though it has been said that, as equity acts in personam, equitable claims are governed by the lex fori, this almost certainly means no more than that a court may order equitable remedies in accordance with its own procedural law over a defendant subject to its personal jurisdiction in respect of rights which have been found to arise under the law identified by its choice of law rules. Given the similarity between equitable wrongs on the one hand, and torts and breaches of contract on the other, it may be appropriate to regard claims which would in domestic law be equitable wrongs as being governed by the choice of law rules applicable to these areas of law, rather than by Rule 230, at least where the measure of recovery is not determined by reference to the enrichment of the defendant.
34–034 Support for the law which governs the relationship between the parties may be derived from the approach of the High Court of Australia in Att-Gen (UK) v Heinemann Publishers Australia Pty Ltd. In upholding the refusal to grant an injunction to restrain the publication of a book said to involve the commission of breaches of the obligation of confidence owed by Peter Wright, a United Kingdom Crown Servant, the High Court considered that it was prevented from granting a remedy by the rule against the enforcement of foreign penal, revenue, or other public laws, or a principle of public international law related to it. It was evidently accepted that the choice of law rule which determined whether the plaintiff had a right capable of being enforced, but whose enforcement was in turn prevented by the rule of international law relied on by the publisher, pointed to English law, even though the author resided (and was presumably paid) in Australia, and though the publication complained of, and hence any presumed enrichment, took place in Australia. The law with which Wright's obligation, and the rights associated with its breach, was most closely connected was English, and was not the law of Australia where the fruits of its breach by publication in Australia, accrued to him.
…
34-037 These cases suggest that equitable claims for compensation fall outside the scope of Rule 230. They also indicate that an English court will not necessarily apply the applicable law of the contract or tort to such equitable claims, even when brought concurrently with actions in contract or tort.
34–038 It is suggested that equitable claims to disgorge the value of the enrichment of the defendant fall within the scope of Rule 230. The question then arises as to how to apply the Rule to such cases. The application of the law of the place of enrichment, without significant modification, has been approved and applied in England and in Singapore, and may be considered the dominant view. But the slenderness of the authority for it has been judicially noticed, and there is some judicial support for an approach, in some cases at least, which accords greater significance to the parallel with other causes of action to which different choice of law rules apply. So, if the nature of the claim is that a wrong has been done which is analogous to a tort, from which the defendant has made a profit, it might be appropriate for the place of the enrichment to be one factor, but not necessarily a dominant factor, in the identification of the proper law of the obligation to make restitution. This would mean that greater emphasis might be placed on the law under which the relationship between the relevant parties was created, or which governed the relationship between them, than on the fact that the enrichment occurred in a particular place.
.…
34–040 Outside the context of such relationships, it is suggested that Rule 230(2)(c) should be applied to equitable claims based upon the enrichment of the defendant, so that the law of the place of enrichment will normally be applied. So, in Douglas v Hello! Ltd (No.3), the Court of Appeal held that a claim for breach of confidence should be classified as restitutionary and subject to what is now Rule 230. This led to the application of the law of the place of enrichment, English law, where magazine publishers had allegedly profited from unauthorised acts of publication. However, the Court of Appeal noted that in deciding whether the information used was unauthorised as a matter of English law, the court would have regard to the law of the place where the photographs in questions were taken, New York, in deciding whether the claimants could reasonably have expected the information to have remained private.
34–041 The conclusion to be drawn from these cases is that an equitable claim which is founded on an allegation of unlawful or knowing receipt, or any other equitable claim to disgorge an unjust enrichment, will fall within the scope of [Rule 230]. But a claim which is founded on an allegation of wrongdoing for which compensation is sought does not do so, even if English domestic law would regard the liability as equitable. They also illustrate that claims for equitable damages which are compensatory in nature will not necessarily be governed by the choice of law rules applicable to contracts or torts when arising concurrently, or in connection with, such claims. …"
Counsel for Frito-Lay relied upon the fact that the NDA stipulates that the applicable law is Delaware law, and argued that that was the law that the parties had chosen to apply to the question of confidentiality. While I see the force of that argument, the problem with it is that, as noted above, IFL does not allege any breach of the NDA. Furthermore, the facts relied upon by IFL in support of its claim for breach of confidence go beyond the NDA.
Counsel for IFL relied upon the following facts (or alleged facts): (a) IFL, an English company acting through its employees, devised the confidential information; (b) IFL did so in England, because its employees were located in England; (c) IFL disclosed the information to Frito-Lay, albeit in some cases through the conduit of IFI; and (d) IFL disclosed the information partly in (or at least from) England and partly in Texas. He argued that these facts supported the application of English law following the approach of the High Court of Australia in Attorney-General v Heinemann Publishers Australia Pty Ltd (1988) 165 CLR 30.
If one approaches the question on the basis that IFL's claim is a restitutionary claim for unjust enrichment, and asks where the enrichment occurred, then, unless one says that the enrichment occurred in Texas because that is where Frito-Lay is based, the problem which arises is that the enrichment occurred virtually worldwide, since Frito-Lay has filed international patent applications covering a large number of countries.
In the circumstances of the present case, I consider that it makes more sense to adopt the approach of the High Court of Australia of identifying the law with which Frito-Lay's obligation to IFL, and the rights associated with its breach, are most closely associated. Given the manner in which IFL's claim is framed, I accept the argument of counsel for IFL that the facts set out in paragraph 106 above point to English law as being that law.
Events after 11 January 2009 . It is common ground that claims for breach of an equitable obligation of confidence fall within Article 6 of the Rome II Directive when read together with Article 39 of Agreement on Trade-related Aspects of Intellectual Property Rights which forms Annex 1C to the Agreement establishing the World Trade Organisation signed in Morocco on 15 April 1994 (commonly known as "TRIPS"), to which the European Union and all its Member States are party. Article 6 of Rome II contains a specific choice of law regime for "a non-contractual obligation arising out of an act of unfair competition", while Article 39 of TRIPS requires WTO Member States to protect undisclosed information "in the course of ensuring effective protection against unfair competition". (Since this is common ground, I do not need to explain why it is necessary to have regard to TRIPS for this purpose.)
In the present case counsel for IFL submitted that Article 6(2) was the applicable rule on the ground that the acts of unfair competition alleged affected the interests of a specific competitor, namely IFL. Since counsel for Frito-Lay did not argue to the contrary, I accept that submission. It follows that Article 4 applies.
Neither counsel relied on Article 4(1). Rather, both relied on Article 4(3). Counsel for Frito-Lay again argued that the NDA gave rise to a closer connection with Delaware than any other state. Counsel for IFL again argued that IFL's claim was more closely connected with England. In my view the claim is more closely connected with England for similar reasons to those given in paragraph 108 above.
Issue 6: Should IFL have permission to serve the breach of confidence claim outside the jurisdiction?
I turn next to consider whether IFL has satisfied the three requirements identified by Lord Collins in AK Investment v Kyrgyz for obtaining permission to serve the breach of confidence claim out of the jurisdiction.
Serious issue to be tried on merits? There is no dispute that IFL has shown that there is serious issue to be tried on the merits.
Good arguable case as to jurisdictional gateway? The jurisdictional gateway relied upon by IFL is that provided by paragraph 3.1(2) of CPR Practice Direction 6B – Service out of the Jurisdiction:
"A claim is made for an injunction ordering the defendant to do or refrain from doing an act within the jurisdiction."
Counsel for Frito-Lay submitted that IFL did not have a good arguable case that it was claiming an injunction ordering Frito-Lay to do or refrain from doing an act within the jurisdiction. In support of this argument he relied upon G.A.F. Corp v Amchem Products Inc [1975] Lloyd's Rep 601. In that case GAF and Amchem were both US companies. Under a contract between them made in the USA GAF was to send Amchem lists of chemicals it wanted Amchem to test as herbicides or plant growth regulators and Amchem was to select those it was prepared to test. GAF was then to send Amchem samples of the selected chemicals for Amchem to test and Amchem was to report the test results to GAF. The contract contained mutual obligations as to confidentiality. In 1966 GAF sent Amchem a particular acid and various esters of it for testing. In 1967 Amchem filed two US patent applications for the use of these chemicals as herbicides and plant growth regulators. In 1967-68 Amchem filed patent applications in various countries, including France, Germany and the UK. A number of these applications, including the UK application, had proceeded to grant. In 1972 the parties concluded a contract under which Amchem was obliged to purchase the acid from GAF.
Not long afterwards, GAF commenced proceedings in France, Germany, England and the USA. In the US proceedings GAF claimed a declaration that Amchem held the various patent applications and any resulting patents on constructive trust for GAF. GAF also claimed various injunctions and an order that Amchem assign the inventions to GAF. In the English proceedings GAF claimed (1) a declaration that it was entitled to the UK patent, (2) an order that Amchem assign the UK patent to GAF alternatively hold it on trust for GAF and (3) an injunction to restrain Amchem from taking any action for the enforcement of, amending, failing to maintain in force or assigning the UK patent. It is pertinent to note that paragraph (3) of the prayer for relief was added by amendment after GAF had obtained permission to serve the English proceedings on Amchem outside the jurisdiction. Amchem applied to set the permission aside.
Megarry J set aside permission. He held that that GAF had failed to establish that the case fell within what was then RSC Order 11 rule 1, but that even if it did the US court was "overwhelmingly" a more appropriate forum than the English court and furthermore GAF had been guilty of material non-disclosure in making its ex parte application to serve out. On the question whether the claim for an injunction satisfied Order 11 rule 1(i) (which corresponds to PD6B para 3.1(2)), he said:
"So far as par. 2 is concerned, I cannot see that it is. If framed as it stands, the order could be complied with by effecting an assignment anywhere in the world, and not merely within the jurisdiction, the Court may be able to cut down its scope so as to convert a prohibition sought against doing some act anywhere within the jurisdiction, so that it will then fall within par. ( i ); see In re De Penny , [1891] 2 Ch 63 ; and see The Tropaioforos ( No. 2 ), [1962] 1 Lloyd's Rep. 410, at p. 421. Such a process converts a more burdensome claim into a less burdensome order. But I do not think the same process can apply to a mandatory order. If a claim to a mandatory order to do some act anywhere were to be converted into a mandatory order to do the act within the jurisdiction, the order would become more burdensome than the claim, and not less burdensome; for instead of being able to comply with the order by doing the act anywhere, the defendant could comply with the order only by doing the act in this particular jurisdiction. In the present case, if the defendants truly are under an obligation to assign the patent to the plaintiffs, why should they be ordered to do this within the jurisdiction instead of in the United States, where they both are? I do not think that par. 2 of the relief claimed falls within par. ( i ) or r. 1.
I turn to par. 3 of the relief claimed. This, as it seems to me, is essentially incidental or ancillary. The real claim is to the declaration of ownership and the order to assign; and once the order has been carried out, par. 3 would of necessity be inoperative. When judgment is given in the action, the injunction under par. 3, if granted at all, would have only a limited operation and a life that in all probability would be short. It is a form of injunction more suited for interlocutory relief. I appreciate that Rosler v Hilber was a very different case, but I think that the principle of that case applies here. At best, the injunction falls within the letter of par. ( i ) and not the spirit. Accordingly I do not think that I need discuss the authorities which consider the precise words in which the standard of proof in these cases should be expressed."
On appeal Russell and Stamp LJJ upheld Megarry J's decision that the USA was the appropriate forum assuming, without deciding, that the case was within Order 11 rule 1.
In the present case IFL seeks the following prohibitory and mandatory injunctive relief in respect of its breach of confidence claim:
i) "An injunction to restrain [Frito-Lay] … from acting so as to prejudice [IFL's] equitable interests in the Applications in Suit and/or the Patents in Suit [as defined in the Particulars of Claim]".
ii) "An order that [Frito-Lay] does take all steps within its power … to assign or procure the assignment to [IFL] of each of the Applications in Suit and/or the Patents in Suit …".
iii) "An order that [Frito-Lay] does take all steps within its power to correct or procure the corrections of the inventorship as recorded on the corresponding registers for each of the Applications in Suit and/or the Patents in Suit … such that Mr Sweetman and Mr Hewitt be mentioned as inventors thereof".
The prohibitory injunction is essentially a generalised form of the injunction which was considered by Megarry J in the second paragraph I have quoted from GAF v Amchem . If the matter were free from authority, I might well have concluded that the injunction fell within PD6B para 3.1(2), but that is not the position. Counsel for IFL submitted that the present case was distinguishable from GAF v Amchem , but it seems to me that Megarry J's reasoning is equally applicable here. I do not feel able to say that that reasoning is wrong, and accordingly I shall follow it. In my judgment the second order is clearly not within PD6B para 3.1(2) for the reasons given by Megarry J in the first paragraph I have quoted from GAF v Amchem . As for the third order, I consider that this is within PD6B para 3.1(2) in so far as it relates to (a) the UK national applications stemming from the international applications and (b) any European Patents (UK) granted pursuant to the European Applications. In my view this is not purely incidental or ancillary: an assignment will not in itself carry with it any right to correct inventorship, and inventorship can be of significance, in particular for the inventors themselves by virtue of section 40 of the 1977 Act (which confers on employee inventors a right to compensation in respect of inventions and patents of outstanding benefit to their employer). I therefore conclude that IFL has a good arguable case that the claim falls within PD6B para 3.1(2).
Is England the appropriate forum? I shall consider this below.
Issue 7: What is the extent of the Texas Court's jurisdiction?
The Texas Court will obviously determine the extent of its own jurisdiction, and whether to exercise or decline that jurisdiction, when disposing of Innovia's motion to dismiss. Nothing I say can, or should be interpreted as an attempt to, pre-empt the Texas Court's conclusions on these matters. Nevertheless, since the parties before me are in dispute as to the extent of the Texas Court's jurisdiction, and since this dispute has a bearing on the forum non conveniens issue, I must assess the position as best I can.
Both sides have served opinions prepared by distinguished retired US judges. IFL relies upon an opinion of the Hon. Joseph J. Farnan, Jr., who was a District Judge for the District of Delaware from 1985 to 2010. Frito-Lay relies upon an opinion of the Hon. Robert M. Parker, who was a District Judge for the Eastern District of Texas from 1979 to 1994 and a Circuit Judge of the Court of Appeals for the Fifth Circuit from 1994 to 2002. I note in passing that neither opinion complied with the formal requirements of CPR r. 35.10, Practice Direction 35 – Experts and Assessors and the Protocol for the Instruction of Experts to Give Evidence in Civil Claims, but in the circumstances I am prepared to overlook this.
Although there is a large measure of agreement between Judge Farnan and Judge Parker, there are two points of difference between them, only one of which is necessary for me to consider. As noted above, it is common ground that the Texas Court has jurisdiction over the granted US patents, but not the pending US applications. It is also common ground that the Texas Court does not have jurisdiction over foreign applications and patents corresponding to the pending US applications. The dispute is as to the Texas Court's jurisdiction over foreign applications and patents corresponding to granted US patents. Judge Farnan is of the opinion that the Texas Court has jurisdiction to consider the inventorship of (and hence entitlement to) a foreign application related to a granted US patent if, but only if, the scope of the claims of the foreign application is the same of the scope of the claims of the US patent. Judge Parker is of the opinion that the Texas Court's jurisdiction is not so limited.
Neither counsel dissented from the approach to conflicts of expert evidence as to foreign law that I set out in VTB Capital plc v Nutritek International Cor p [2011] EWHC 3107 (Ch) at [201]:
"To my surprise, counsel were unable to direct me to any authority as to the correct approach to such conflicts on an application such as the present. Obviously, I cannot resolve the conflicts without cross-examination. … Nevertheless, counsel were, I think, more or less agreed by the end of the hearing that I was both entitled and obliged to consider the quality of the evidence, taking into account factors such as the experience of the experts, the cogency of their reasoning and the materials relied upon to support it."
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Cabo Espichel Natura 2000 SPA Check List · iNaturalist Canada
Cabo Espichel Natura 2000 SPA Check List
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Phallusia fumigata
Last observation: Phallusia fumigata from 2970 Sesimbra, Portugal on March 26, 2023 at 11:28 AM by Ana Santos (View All)
Ascidia mentula
Last observation: Ascidia mentula from Oceano Atlântico Norte, Sesimbra, PT on May 07, 2023 at 10:13 AM by Sílvia Tavares (View All)
Red Sea Squirt ( Halocynthia papillosa )
Last observation: red sea squirt from Oceano Atlântico Norte, Sesimbra, PT on May 07, 2023 at 09:51 AM by Sílvia Tavares (View All)
Microcosmus claudicans
Last observation: Microcosmus claudicans from Nossa Senhora do Cabo, Setubal, Portugal on September 11, 2013 at 11:43 AM by João Pedro Silva (View All)
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Microcosmus polymorphus
Last observation: Microcosmus polymorphus from Cabo Espichel, Portugal on August 14, 2022 at 12:42 PM by Ana Santos (View All)
Stolonica socialis
Last observation: Stolonica socialis from Oceano Atlântico Norte, Sesimbra, PT on April 25, 2022 at 11:03 AM by Sílvia Tavares (View All)
Star Tunicate ( Botryllus schlosseri )
Last observation: Star Tunicate from Portugal on October 24, 2021 at 08:20 AM by Sílvia Tavares (View All)
Polycitor crystallinus
Last observation: Polycitor crystallinus from Oceano Atlântico Norte, Sesimbra, PT on June 12, 2022 at 09:19 AM by Sílvia Tavares (View All)
Bluish Club-shaped Ascidian ( Rhopalaea neapolitana )
Last observation: Bluish club-shaped ascidian from Oceano Atlântico Norte, Sesimbra, PT on June 05, 2022 at 10:33 AM by Sílvia Tavares (View All)
Pycnoclavella communis
Last observation: Pycnoclavella communis from Sesimbra, Portugal on June 10, 2022 at 11:19 AM by Ana Santos (View All)
Pycnoclavella atlantica
Last observation: Pycnoclavella atlantica from Oceano Atlântico Norte, Sesimbra, PT on February 26, 2023 at 11:10 AM by Sílvia Tavares (View All)
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Lightbulb Sea Squirt ( Clavelina lepadiformis )
Last observation: Lightbulb Sea Squirt from Parque Natural da Arrábida, Sesimbra, Setúbal, Portugal on April 18, 2021 at 01:19 PM by Ester Serrao (View All)
Polysyncraton lacazei
Last observation: Polysyncraton lacazei from 2970 Sesimbra, Portugal on March 26, 2023 at 11:13 AM by Ana Santos (View All)
Synoicum blochmanni
Last observation: Synoicum blochmanni from 2970 Sesimbra, Portugal on April 25, 2023 at 11:48 AM by Ana Santos (View All)
Aplidium punctum
Last observation: Aplidium punctum from 2970 Sesimbra, Portugal on April 02, 2023 at 11:22 AM by Ana Santos (View All)
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Pegea confoederata
Pyrosoma atlanticum
Last observation: Pyrosoma atlanticum from Oceano Atlântico Norte, Sesimbra, PT on April 16, 2023 at 10:59 AM by Sílvia Tavares (View All)
Iberian Green Frog ( Pelophylax perezi )
Last observation: Iberian Green Frog from Sesimbra, Portugal on March 29, 2013 at 12:38 PM by claudio_marques (View All)
Fire Salamander ( Salamandra salamandra )
Last observation: Fire Salamander from Castelo, 2970, Portugal on February 26, 2022 at 01:44 PM by Filipa Machado (View All)
Ocellated Lizard ( Timon lepidus )
Last observation: Ocellated lizard from Sesimbra, Portugal on April 23, 2022 at 07:26 PM by André Balças (View All)
Large Psammodromus ( Psammodromus algirus )
Last observation: Large Psammodromus from Sesimbra, Portugal on March 30, 2023 at 06:05 AM by Jim Brighton (View All)
Moorish Gecko ( Tarentola mauritanica )
Last observation: Moorish Gecko from Cabo Espichel, Portugal on August 04, 2018 at 10:34 AM by Antonio Xeira (View All)
Western Montpellier Snake ( Malpolon monspessulanus )
Last observation: Western Montpellier Snake from Cabo Espichel on May 04, 2023 at 04:41 PM by Sara Bravo (View All)
Horseshoe Whip Snake ( Hemorrhois hippocrepis )
Last observation: Horseshoe Whip Snake from Castelo, 2970, Portugal on February 01, 2015 at 08:35 AM by rui_duarte (View All)
Ladder Snake ( Zamenis scalaris )
Last observation: Ladder Snake from Sesimbra, Portugal on April 25, 2017 at 12:17 PM by Tiago Abreu (View All)
Little Owl ( Athene noctua )
Last observation: Little Owl from Castelo, 2970, Portugal on August 10, 2021 at 09:12 AM by Luís Lourenço (View All)
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European Bee-Eater ( Merops apiaster )
Last observation: European Bee-eater from Cabo Espichel, Portugal on June 21, 2019 at 10:51 AM by Raquel Coelho (View All)
Rock Pigeon ( Columba livia )
Last observation: Rock Pigeon from Sesimbra, Portugal on June 02, 2023 at 05:09 PM by Jorge Vítor (View All)
Stock Dove ( Columba oenas )
Last observation: Stock Dove from Sesimbra, Portugal on October 25, 2014 at 08:40 AM by Pedro Ramalho (View All)
Red-legged Partridge ( Alectoris rufa )
Last observation: Red-legged Partridge from Castelo, 2970, Portugal on May 14, 2022 at 08:21 AM by Luís Lourenço (View All)
Yellow-legged Gull ( Larus michahellis )
Last observation: Yellow-legged Gull from Sesimbra, Portugal on February 12, 2023 at 04:31 PM by Tiago Carrapiço (View All)
Eurasian Dotterel ( Charadrius morinellus )
Last observation: Eurasian Dotterel from Castelo, 2970, Portugal on May 22, 2020 at 07:00 PM by Frederico Conceição (View All)
Razorbill ( Alca torda )
Last observation: Razorbill from Oceano Atlântico Norte, Sesimbra, PT on April 28, 2023 at 10:49 AM by martim_zk (View All)
Great Skua ( Stercorarius skua )
Last observation: Great Skua from Parque Natural da Arrábida, Sesimbra, Setúbal, Portugal on September 08, 2021 at 10:58 AM by Helio Batista (View All)
Cory's Shearwater ( Calonectris diomedea )
Last observation: Cory's Shearwater from Parque Natural da Arrábida, Sesimbra, Setúbal, Portugal on September 08, 2021 at 10:55 AM by Helio Batista (View All)
Little Egret ( Egretta garzetta )
Last observation: Little Egret from Sesimbra, Portugal on March 29, 2023 at 10:38 AM by Bruce Taterka (View All)
Peregrine Falcon ( Falco peregrinus )
Last observation: Peregrine Falcon from Sesimbra, Portugal on February 16, 2023 at 01:10 PM by Helio Batista (View All)
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Eurasian Kestrel ( Falco tinnunculus )
Last observation: Eurasian Kestrel from Sesimbra, Portugal on April 07, 2023 at 12:13 PM by Jorge Vítor (View All)
Alpine Swift ( Apus melba )
Last observation: Alpine Swift from Sesimbra, Portugal on May 19, 2020 at 09:22 AM by Daniel Raposo (View All)
Little Swift ( Apus affinis )
Last observation: Little Swift from Castelo, 2970, Portugal on May 19, 2020 at 06:05 PM by Luís Lourenço (View All)
Eurasian Marsh-Harrier ( Circus aeruginosus )
Last observation: Eurasian Marsh-Harrier from Cabo Espichel, Portugal on June 21, 2019 at 10:57 AM by Raquel Coelho (View All)
Common Buzzard ( Buteo buteo )
Last observation: Common Buzzard from Cabo Espichel, Portugal on June 21, 2019 at 10:17 AM by Raquel Coelho (View All)
Black Kite ( Milvus migrans )
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EclipseWise - Partial Solar Eclipse of -0999 Mar 29
This page is part of the EclipseWise.com Website. It contains Predictins, information and links for the Partial Solar Eclipse of -0999 Mar 29 .
Solar Eclipse Prime Page
Partial Solar Eclipse of -0999 Mar 29 (1000 Mar 29 BCE)
Fred Espenak
Introduction
The
Partial Solar Eclipse of -0999 Mar 29 (1000 Mar 29 BCE)
is visible from the geographic regions shown on the map to the right.
Click on the map to enlarge it.
For an explanation of the features appearing in the map,
see
Key to Solar Eclipse Maps
.
The instant of
greatest eclipse
takes place on -0999 Mar 29 at 18:08:26 TD (11:07:19 UT1).
This is 6.8 days after the Moon reaches apogee.
During the eclipse, the Sun is in the constellation
Aries
.
The
synodic month
in which the eclipse takes place has a
Brown Lunation Number
of -36137.
The eclipse belongs to
Saros 52
and is number 22 of 86 eclipses in the series.
All eclipses in this series occur at the Moon’s
descending node
.
The Moon moves northward with respect to the node with each succeeding eclipse in the series and
gamma
increases.
This is a very deep partial eclipse.
It has an
eclipse magnitude
of 0.6893,
while
Gamma
has a value of -1.1647.
The partial solar eclipse of -0999 Mar 29 is preceded two weeks earlier by a total lunar eclipse on
-0999 Mar 14
.
These eclipses all take place during a single
eclipse season
.
The eclipse predictions are given in both
Terrestrial Dynamical Time (TD)
and
Universal Time (UT1)
.
The parameter
ΔT
is used to convert between these two times (i.e.,
UT1 = TD - ΔT
).
ΔT
has a value of
25267.0
seconds for this eclipse.
The
uncertainty in ΔT
is
621.5 seconds corresponding to a standard error in longitude of the eclipse path of ± 2.60°.
The following links provide maps and data for the eclipse.
Orthographic Map: Partial Solar Eclipse of -0999 Mar 29 - global map of eclipse visibility
Google Map: Partial Solar Eclipse of -0999 Mar 29 - interactive map of the eclipse path
Circumstances Table: Partial Solar Eclipse of -0999 Mar 29 - eclipse times for hundreds of cities
Saros 52 Table - data for all eclipses in the Saros series
The tables below contain detailed predictions and additional information on the
Partial Solar Eclipse of -0999 Mar 29
.
Eclipse Data: Partial Solar Eclipse of -0999 Mar 29
Eclipse Characteristics Parameter Value Eclipse Magnitude 0.68934 Eclipse Obscuration 0.60725 Gamma -1.16473
Conjunction Times Event Calendar Date and Time Julian Date Greatest Eclipse -0999 Mar 29 at 18:08:26.2 TD (11:07:19.1 UT1) 1356260.963416 Ecliptic Conjunction -0999 Mar 29 at 18:20:56.7 TD (11:19:49.6 UT1) 1356260.972102 Equatorial Conjunction -0999 Mar 29 at 17:25:32.5 TD (10:24:25.5 UT1) 1356260.933628
Geocentric Coordinates of Sun and Moon -0999 Mar 29 at 18:08:26.2 TD (11:07:19.1 UT1) Coordinate Sun Moon Right Ascension 23h55m45.1s 23h57m08.4s Declination -00°28'05.4" -01°31'01.0" Semi-Diameter 15'49.6" 15'32.7" Eq. Hor. Parallax 08.7" 0°57'03.0"
Geocentric Libration of Moon Angle Value l -4.8° b 1.5° c -25.3°
Prediction Paramaters Paramater Value Ephemerides JPL DE406 ΔT 25267.0 s k (penumbra) 0.2725076 k (umbra) 0.2722810 Saros Series 52 (22/86)
Explanation of Solar Eclipse Data Tables
Penumbral Shadow Contacts and Extremes: Partial Solar Eclipse of -0999 Mar 29
Contacts of Penumbral Shadow with Earth Contact Event Contact Time TD Time UT1 Latitude Longitude First External Contact P1 16:14:45.5 09:13:38.5 67°11.7'S 047°37.5'W Last External Contact P4 20:02:21.4 13:01:14.4 30°33.7'S 076°53.4'E
Extreme Northern and Southern Path Limits of Penumbra Contact Event Contact Time TD Time UT1 Latitude Longitude North Extreme Path Limit 1 N1 16:40:29.7 09:39:22.7 56°23.9'S 053°37.1'W South Extreme Path Limit 1 S1 19:36:37.1 12:35:30.1 19°40.9'S 083°14.7'E
Explanation of Penumbral Shadow Contacts and Extremes Tables
Polynomial Besselian Elements: Partial Solar Eclipse of -0999 Mar 29
Polynomial Besselian Elements -0999 Mar 29 at 18:00:00.0 TD (=t0) n x y d l1 l2 μ 0 0.29382 -1.12960 -0.4677 0.55130 0.00511 88.3335 1 0.51161 0.16920 0.0158 -0.00012 -0.00012 15.0055 2 0.00000 0.00006 -0.0000 -0.00001 -0.00001 0.0000 3 -0.00001 -0.00000 - - - -
Tan ƒ1 0.0046269 Tan ƒ2 0.0046039
At time t1 (decimal hours), each besselian element is evaluated by:x = x0 + x1*t + x2*t 2+ x3*t 3(or x = Σ [xn*t n]; n = 0 to 3)where: t = t1 - t0 (decimal hours) and t0 = 18.000
Explanation of Polynomial Besselian Elements
Links for the Partial Solar Eclipse of -0999 Mar 29 (1000 Mar 29 BCE)
Orthographic Map: Partial Solar Eclipse of -0999 Mar 29 - global map of eclipse visibility
Google Map: Partial Solar Eclipse of -0999 Mar 29 - interactive map of the eclipse path
Circumstances Table: Partial Solar Eclipse of -0999 Mar 29 - eclipse times for hundreds of cities
Saros 52 Table - data for all eclipses in the Saros series
Partial Solar Eclipse of -0999 Mar 29 - Google search for links to this eclipse
Links to Additional Solar Eclipse Information
Home - home page of EclipseWise with predictions for both solar and lunar eclipses
Solar Eclipses - primary page for solar eclipse predictions
Solar Eclipse Links - detailed directory of links
Six Millennium Catalog of Solar Eclipses - covers the years -2999 to +3000 (3000 BCE to 3000 CE)
Saros Catalog of Solar Eclipses - covers Saros series -30 through 190
World Atlas of Solar Eclipse Maps - index page
Solar Eclipse Search Engine - search for solar eclipses from -1999 to +3000
Javascript Solar Eclipse Explorer - calculate all solar eclipses visible from a city
Thousand Year Canon of Solar Eclipses 1501 to 2500 - link to the publication
MrEclipse.com - eclipse resources and tips on photography
Solar Eclipses for Beginners - a primer on solar eclipse basics
MrEclipse Photo Index - an index of solar eclipse photographs
Calendar
The Gregoriancalendar (also called the Western calendar) is internationally the most widely used civil calendar.
It is named for Pope Gregory XIII, who introduced it in 1582.
On this website, the Gregoriancalendar is used for all calendar dates from 1582 Oct 15 onwards.
Before that date, the Juliancalendar is used.
For more information on this topic, seeCalendar Dates.
The Juliancalendar does not include the year 0.
Thus the year 1 BCE is followed by the year 1 CE (See:BCE/CE Dating Conventions).
This is awkward for arithmetic calculations.
Years in this catalog are numbered astronomically and include the year 0.
Historians should note there is a difference of one year between astronomical dates and BCE dates.
Thus, the astronomical year 0 corresponds to 1 BCE, and astronomical year -1 corresponds to 2 BCE, etc..
Eclipse Predictions
Predictions for the
Partial Solar Eclipse of -0999 Mar 29
were generated using theJPL DE406solar and lunar ephemerides.
The lunar coordinates were calculated with respect to the Moon's Center of Mass.
The predictions are given in both Terrestrial Dynamical Time (TD)and Universal Time (UT1).
The parameterΔTis used to convert between these two times (i.e., UT1 = TD - ΔT).ΔThas a value of
25267.0
seconds for this eclipse.
Theuncertainty in ΔTis
621.5 seconds corresponding to a standard error in longitude of the eclipse path of ± 2.60°.
Acknowledgments
Last Updated:
2019 Mar 22
| https://www.eclipsewise.com/solar/SEprime/-0999--0900/SE-0999Mar29Pprime.html |
BJOC - Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium
Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium
Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium
Alphonse Fiebor 1 ,
Richard Tia 2 ,
Banothile C. E. Makhubela 1 and
Henok H. Kinfe 1
2 Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Associate Editor: L. Ackermann Beilstein J. Org. Chem. 2018, 14, 1859–1870. https://doi.org/10.3762/bjoc.14.160 Received 11 May 2018 , Accepted 26 Jun 2018 , Published 23 Jul 2018
Abstract
Unlike their SCS analogues, SNS pincer complexes are poorly studied for their use in coupling reactions. Accordingly, a series of water soluble cationic Pd(II) SNS pincer complexes have been successfully synthesised and investigated in detail for their catalytic activity in Suzuki–Miyaura coupling reactions. By using only 0.5 mol % loading of the complexes, the coupling of inactivated aryl bromides and activated aryl chlorides with various boronic acids in water was achieved in excellent yields and the catalysts were found to be reusable for three cycles without a significant loss of activity. The investigation of the mechanism of the reaction revealed that a Pd(II) to Pd(IV) route is the more likely pathway which was further supported by computational studies.
Keywords: cationic palladium(II) complexes ; Pd(II)/Pd(IV) complexes ; SNS pincer complexes ; Suzuki–Miyaura
Graphical Abstract
Introduction
The Suzuki–Miyaura C–C coupling reaction is a powerful method for the synthesis of ubiquitous biaryls and has been extensively employed in the synthesis of natural products, pharmaceuticals, agrochemicals, and polymers. The reaction usually involves a palladium-catalysed coupling of aryl boronates with aryl halides in organic solvents in the presence of an excess of base[1-3]. With the drive for the development of environmentally friendly and low cost protocols, a number of methodologies for the Suzuki–Miyaura reaction under aqueous conditions or in neat water have been reported[4-6]. This has been achieved via microwave heating[7-15], ultrasonication[16-18], ligand-free methodologies[19-25]and the use of water-soluble palladium pre-catalysts/catalysts[26-30]. The latter is the preferred choice since it allows for the reusability of the catalyst for subsequent reactions after simple phase separation[31]. However, the commonly employed phosphorous and carbene ligand-based palladium(II) complexes are found to be in most cases sensitive to moisture and air limiting the scope of their catalytic application in aqueous reactions[32,33]. This limitation encouraged for the development of organosulfur ligand based palladium(II) complexes by exploiting the strong donor properties of sulfur. Such complexes are found to be resistant to moisture, air and thermal stress/elevated temperatures and have been applied in catalysing Suzuki–Miyaura coupling reactions[32,33]. As it was elegantly reviewed by Singh and co-workers[33], these organosulfur ligands can be classified into pincer type (symmetrical and unsymmetrical), thioethers, thiourea-based ligands, sulfur-substituted NHCs, thiosemicarbazones and sulfated Schiff bases. Of the pincer ligands, there are several examples of SCS-based palladium(II) complexes ( 1–13,Figure 1) which were reported to catalyse the Suzuki–Miyaura coupling reaction but the corresponding easy-to-synthesise SNS pincer complexes are well underrepresented[33].
Figure 1:Examples of reported SCS palladium(II) pincer complexes 1–13.
Figure 1:Examples of reported SCS palladium(II) pincer complexes 1–13.
To the best of our knowledge, the only examples reported in the literature are the water-soluble pincer complexes 14, 15and 16(Figure 2a). While pincer complex 14provided moderate (38–68%) GC yields over 6 h at 75 °C using 2 mol % catalyst loading with inactivated aryl bromides, pincer complex 15was found to be incompatible with both activated and inactivated aryl bromides according to the study conducted by Bai and Hor[34]. Similarly, Kumar et al. studied the catalytic activity of pincer complex 16and reported that the catalyst was compatible with activated aryl bromides to provide reasonable yields over 12 h at 100 °C using 2 mol % catalyst loading; but required stoichiometric amounts of tetra- n-butylammonium bromide (TBAB) to effect the reaction of inactivated aryl bromides[35]. A further limitation of these catalysts is their incapability to catalyse the coupling reaction when either activated or inactivated aryl chlorides are employed as coupling partners. Encouraged by the high hydrophilicity and the potential activity of such complexes, we are interested in the synthesis of cationic palladium(II) SNS pincer complexes of the general structure 17(Figure 2b) having rigid fused cyclic rings imparted by a pyridine backbone; and systematic investigation of their catalytic activity in the aqueous Suzuki–Miyaura coupling reaction. Herein, we report the synthesis of the SNS Pd(II) pincer complexes and their interesting catalytic activities in the Suzuki–Miyaura cross coupling reactions in neat water.
Figure 2:a) Reported SNS palladium(II) pincer complexes 14– 16as catalysts for Suzuki–Miyaura cross coupling[34]; b) Proposed SNS palladium(II) pincer complexes 17.
Figure 2:a) Reported SNS palladium(II) pincer complexes 14– 16as catalysts for Suzuki–Miyaura cross coupling ...
Results and Discussion
Our study commenced with the preparation of the SNS pincer ligand 19ausing literature reported protocols[36]as shown inScheme 1. Treatment of in situ-generated thiophenolate with 2,6-bis(chloromethyl)pyridine ( 18) afforded pincer ligand 19ain 73% yield. Initial attempts for the synthesis of SNS-Pd(II) complex 17a(with Cl −counter ion) were unsuccessful since the reaction of the SNS pincer ligand 19awith PdCl 2(MeCN) 2led to the formation of N,S-Pd(II) 20apresumably due to the weak basicity of the sulfur atom. Gratifyingly, the problem was solved by treatment of the reaction mixture with the halide abstractor AgOTf to provide the desired SNS-Pd(II) complex 17ain quantitative yield (Scheme 1).
Scheme 1:Synthesis of pincer ligands 19a– dand complexes 17a– d.
The structure of the complex was established using NMR spectroscopy and high-resolution mass spectrometry. Among others, the downfield shift of all the protons in the complex, when compared to the corresponding protons of the ligand, by a difference of Δδ H0.5 to 1.3 suggests the deshielding of the nuclei due to coordination with the palladium. The downfield shift of the protons is in accordance with other previously reported palladium(II) complexes[37]. The symmetry of the complex was supported by the appearance of the two protons of the pyridine moiety as a doublet at δ H7.76. Furthermore, the formation of the two fused five-membered rings was confirmed by the appearance of the axial and equatorial protons of the bridging methylene groups as two broad singlets at δ H5.59 and δ H5.16 each integrating for two protons as opposed to the appearance of the corresponding protons in the ligand as a singlet at δ H4.29 integrating for four protons. In a similar fashion, complex 17bwas synthesised and characterised successfully while ligands 19cand 19dpossessing the electron-donating thioether side groups favoured the formation of the corresponding pincer complexes 17cand 17ddirectly without formation of an isolable bidentate intermediate observed during the synthesis of complexes 17aand 17b. Furthermore, the successful synthesis of the pincer complexes was confirmed by X-ray crystallography and the representative X-ray crystal structure of 17dis shown inFigure 3[38].
Figure 3:Molecular structure of 17d. Selected bond distances (Å) and bond angles (°); S(1)–Pd(1)–Cl(1) 93.27(4), S(2)–Pd(1)–Cl(1) 93.34(4), N(1)–Pd(1)–S(1) 86.70(9), N(1)–Pd(1)–S(2) 86.71(9), C(6)–S(1)–C(9) 100.2(2), C(7)–S(2)–C(13) 102.72(2), S(1)–C(6) 1.808(4), S(2)–C(7) 1.816(4), Pd(1)–Cl(1) 2.3044(10).
Figure 3:Molecular structure of 17d. Selected bond distances (Å) and bond angles (°); S(1)–Pd(1)–Cl(1) 93.27...
Single crystals suitable for X-ray analysis of complexes 17dwere obtained by slow evaporation of a mixture of dichloromethane and diethyl ether at about −4 °C. Crystallographic data and structure refinement parameters for 17dare summarised inTable 1. Formation of the tridentate pincer complex was confirmed by the crystal structure of 17d. The structure is accompanied by two lattice water molecules interacting with each other and an uncoordinated chloride ion through hydrogen bonding. The expected square planar geometry of palladium(II) complexes can be observed in the crystal structure of 17dwhere the bond angles around the palladium metal centre are 93.27(4)°, 93.34(4)°, 86.70(9)° and 86.71(9)° for S(1)–Pd(1)–Cl(1), S(2)–Pd(1)–Cl(1), N(1)–Pd(1)–S(1) and N(1)–Pd(1)–S(2), respectively. It is observed that the sec-butyl groups attached to the sulfur atom are pointing away from the plane of the metal centre such that the thioether angles are 100.2(2)° and 102.72(2)° corresponding to C(6)–S(1)–C(9) and C(7)–S(2)–C(13), respectively. The thioether C–S bond lengths obtained are 1.808(4) Å and 1.816(4) Å for S(1)–C(6) and S(2)–C(7), respectively.
Table 1:Crystal data and structure refinement parameters for 17d.
identification code Complex 17d empirical formula C 15 H 24 Cl 2 NPdS 2 , 2(H 2 O) formula weight 124.20 temperature/K 100.01 crystal system triclinic space group P-1 a /Å 7.7438(12) b/ Å 7.8801(12) c /Å 17.140(3) α/° 76.788(2) β/° 89.363(2) γ/° 82.357(2) volume/Å 3 1009.0(3) Z 8 ρ calc g/cm 3 1.635 μ/mm −1 1.398 F(000) 508.0 crystal size/mm 3 0.7 × 0.27 × 0.2 radiation Mo Kα (λ = 0.71073) 2Θ range for data collection/° 4.884 to 52.232 index ranges −9 ≤ h ≤ 9, −9 ≤ k ≤ 9, −21 ≤ l ≤ 21 reflections collected 17514 independent reflections 4019 [R int = 0.0199, R sigma = 0.0159] data/restraints/parameters 4019/0/228 goodness-of-fit on F 2 1.101 final R indexes [I>=2σ (I)] R 1 = 0.0393, wR 2 = 0.0836 final R indexes [all data] R 1 = 0.0410, wR 2 = 0.0845 largest diff. peak/hole / e Å −3 1.83/−1.47
The thioether bond lengths and angles were found to be consistent to the reported data of 1.816 Å and 100.75°, respectively, by Sogukomerogullari et al.[39] .Similarly, the Pd–Cl bond length of 17d(2.3044(10) Å) also corresponds to that of square planar complexes with a chlorine ligand reported in literature[40]. The crystal structure of 17dalso shows a static disorder of a CH 2carbon of one of the sec-butyl groups (C14). The atom site occupancy factors of the two positions of the CH 2carbon atom was refined to 0.571(11) and 0.429(11). This shows that the carbon atom has equal probability of being oriented in the two positions.
With the desired pincer complexes in hand, we then moved on to investigate their potential as catalysts for Suzuki–Miyaura coupling reactions. In our first attempt, the electronically deactivated 4-bromoanisole ( 21a) along with phenylboronic acid ( 22a) as coupling partner and pincer complex 17aas catalyst were selected, in order to identify the optimum catalyst and reaction conditions (Table 2). Carrying out the reaction with equimolar amounts of the coupling partners in water at 140 °C for 4 hours in the presence of 1 mol % pincer complex 17aand K 3PO 4(2 equiv) led to the formation of the biaryl 23ain 92% yield (Table 2, entry 1). The colour of the reaction mixture remained yellow. The use of solvents other than water gave inferior yields (Table 2, entries 2 and 3) which could be attributed to the high hydrophilicity of the pincer complex 17a. Several bases including pyridine, Et 3N, KOH, K 2CO 3and Cs 2CO 3were then evaluated. All except Et 3N provided the expected biaryl 23ain comparable and excellent yields (Table 2, entries 4–8). The poor performance of Et 3N as base in the reaction could be due to its low water solubility. KOH as a common laboratory reagent gave a comparable yield to the other bases. Therefore, we opted to use KOH as our preferred base for the reaction. An improved 93% yield was obtained when the reaction was carried out at 120 °C (Table 2, entry 9). However, lowering the reaction temperature to less than 120 °C resulted in comparatively poorer yields (Table 2, entries 10–12). Monitoring of the reaction at different time intervals under otherwise identical conditions showed slightly progressive increase in the yield of the product formed (Table 2, entries 13–15) with a maximum yield of 93% after 4 hours (Table 2, entry 9). However, stirring the reaction mixture beyond 4 hours did not lead to improved yields. Investigation on the loading of the catalyst indicated that 1 mol % was sufficient to drive the reaction to near completion (93% yield,Table 2, entry 9) considering the minor byproduct formed via homocoupling of the phenylboronic acid coupling partner. Reducing the catalyst loading by half yielded a competitive yield of 86% (a 7% decreased yield,Table 2, entry 16). Catalyst loading of less than 0.5 mol % provided inferior yields (Table 2, entries 17 and 18). In agreement with a literature report[27], the addition of TBAB (0.5 equiv) improved the performance of the reaction (Table 2, entries 14 vs 19 and 16 vs 20) but the colour of the reaction mixture turned black.
Table 2:Optimization of the Suzuki–Miyaura cross coupling reaction of 4-bromoanisole ( 21a) and phenylboronic acid ( 22a).
Entry Base Solvent Cat. Cat. loading Temp. Additive Time (h) Yield (%) a 1 K 3 PO 4 H 2 O 17a 1 140 – 4 92 2 K 3 PO 4 DMF 17a 1 140 – 4 67 3 K 3 PO 4 toluene 17a 1 140 – 4 0 4 Pyr H 2 O 17a 1 140 – 4 90 5 Et 3 N H 2 O 17a 1 140 – 4 51 6 KOH H 2 O 17a 1 140 – 4 90 7 K 2 CO 3 H 2 O 17a 1 140 – 4 95 8 Cs 2 CO 3 H 2 O 17a 1 140 – 4 92 9 KOH H 2 O 17a 1 120 – 4 93 10 KOH H 2 O 17a 1 100 – 4 84 11 KOH H 2 O 17a 1 80 – 4 79 12 KOH H 2 O 17a 1 20 (rt) – 4 41 13 KOH H 2 O 17a 1 120 – 0.5 77 14 KOH H 2 O 17a 1 120 – 1 80 15 KOH H 2 O 17a 1 120 – 2 82 16 KOH H 2 O 17a 0.5 120 – 4 86 17 KOH H 2 O 17a 0.25 120 – 4 46 18 KOH H 2 O 17a 0.06 120 – 4 0 19 KOH H 2 O 17a 1 120 TBAB 1 91 20 KOH H 2 O 17a 0.5 120 TBAB 4 94 21 KOH H 2 O 17a 0.5 120 – 2 80 22 KOH H 2 O 17a 0.5 120 TBAB 2 85 23 KOH H 2 O 17c 0.5 120 – 2 73 24 KOH H 2 O 17c 0.5 120 TBAB 2 90 25 KOH H 2 O 17d 0.5 120 – 2 72 26 KOH H 2 O 17d 0.5 120 TBAB 2 93 27 KOH H 2 O 17b 0.5 120 – 2 75 28 KOH H 2 O 17b 0.5 120 TBAB 2 85 29 KOH H 2 O and Hg 17a 0.5 120 2 72 30 KOH H 2 O and Hg 17a 0.5 120 TBAB 2 92
aGC yield.
Among the set of SNS pincer complexes investigated in this study, pincer complex 17awas found to be the most active catalyst in the absence of TBAB as an additive (Table 2, entry 21 vs 23, 25 and 27). Such an outcome suggests that the sterically less demanding planar phenyl group renders greater access to the metal centre for the substrates than the bulkier side groups (both with electron-donating and electron-withdrawing substituents) and leads to the enhanced catalytic activity observed for 17a, which thus implies that the catalytic activity is influenced by steric as opposed to electronic effects. On the contrary, carrying out the reactions under otherwise identical conditions but with the presence of TBAB, the activity of the catalysts was reversed. The electron rich and sterically demanding tert-butylphenyl and isobutyl thioether possessing SNS pincer complexes resulted in higher yields (Table 2, entry 24 and 26) than the electronically poor and sterically less demanding phenyl group (Table 2, entry 22) as well as the electronically poor but sterically demanding 4-bromophenyl thioether (Table 1, entry 28) possessing SNS pincer complexes. These results suggest that in the presence of TBAB the mechanism of the reaction changes and the catalytic activity seems to be under the influence of electronic as opposed to steric effects. When the reaction mixture turned black in the presence of TBAB, we were under the impression that the reaction could have proceeded via formation of palladium nanoparticles as it is common with most palladium catalysed coupling reactions. However, mercury drop experiments provided comparable yields (Table 2, entry 29 and 30) under the same reaction conditions ruling out the possibility of a coupling reaction catalysed by palladium nanoparticles[37].
The fact that the reaction mixture remained yellowish in the absence of TBAB and the mercury drop experiments did not lead to an appreciable decrease in yield, the reaction was proposed to proceed via a Pd(II) to Pd(IV) mechanism contrary to the previously reported SNS pincer Pd(II) complexes which proceeded via formation of Pd nanoparticles[35](Pd(II) to Pd(0) type of mechanism). Literature suggestions on a Pd(II) to Pd(IV) mechanism are known for biscarbene (CNC), alkylphosphine (PCP) and aminophosphine (PCP) pincer complexes, and in each of these cases, catalysis was unaffected by metallic mercury during the cross-coupling reactions[41-43]. In addition, stable Pd(IV) complexes have been widely prepared and characterised, thus for the catalysis of the pincer complexes in the current study, the Pd(II) to Pd(IV) mechanism was proposed as shown inScheme 2[44].
Scheme 2:Proposed mechanism of the Suzuki–Miyaura coupling reaction using pincer complex 17d.
Scheme 2:Proposed mechanism of the Suzuki–Miyaura coupling reaction using pincer complex 17d.
In order to verify the viability of the Pd(II) to Pd(IV) mechanism proposed, an exploratory computational study using the semi-empirical PM3 method was performed on the oxidative addition stage of the mechanism to determine if the results obtained theoretically could support the experimental results. The oxidative addition stage was selected because it is also the rate-determining step for the catalytic cycle, and thus it can be used to compare the rate of conversions. The PM3 method has been parameterised for transition metal systems and has been found to give geometries, relative energies and activation energy trends in good agreement with high-level density functional theory (DFT) results at a fraction of the computational cost[45,46]. It is therefore adequate for studies in which the prime purpose is to determine or verify preferred reaction pathways.
Oxidative addition of 4-bromoanisole to complex 17dproceeds by the C–Br bond activation to form a weakened Pd···Br bond, of 3.104 Å length in transition state ( TS1), which ultimately results in a new Pd–Br bond, of 2.605 Å length ( IM1) (Figure 4). The Pd–Br distance is calculated to be 2.60 Å and is consistent with similar Pd–Br bond lengths found in the literature for single crystal X-ray structures[47,48]. This oxidative addition step involves a low activation energy barrier of −43.9 kcal/mol. This negative energy implies that there is a stable intermediate between the reactants and the transition state ( TS1). Thus, when the energy of the transition state is lower than the energy of the reactants or intermediates from which the transition state is formed it means there is a stable intermediate between them.
Figure 4:Energy profile for the oxidative addition reaction involving 4-bromoanisole and Pd(II) catalyst precursor 17d. The change in energy for 17dwas calculated by computing it in kcal/mol as a cation at 298.15 K and 1 atm.
Figure 4:Energy profile for the oxidative addition reaction involving 4-bromoanisole and Pd(II) catalyst pre...
Nonetheless, such a relatively low energy barrier indicates that the reaction proceeds at a fast rate in getting to the intermediate ( IM1), thus it is kinetically favoured. The reaction then proceeds via transition state TS2, leading to the cleavage of the C(sp 2)–Br bond and the formation of a new Pd–C(sp 2) bond, to form a cisintermediate of energy −93.0 kcal/mol. The new Pd–C(sp 2) bond distance of 2.00 Å falls within the reported Pd–C(sp 2) bond distances[47,48]. Since the bromo ligand is larger in atomic radius than the chloro ligands the more stable form of the oxidative addition product is the transform. As such, the cisproduct can isomerise to a more stable transintermediate of energy −93.6 kcal/mol having a Pd–C(sp 2) bond length of 1.99 Å.
Next, under the optimal conditions with 17das a catalyst (since it provided the highest yield in the presence of TBAB,Table 2, entry 26), we examined the substrate scope with different substituents on the aromatic rings of the bromobenzene and phenylboronic acid. The results are summarised inTable 3and the scope and yields compare favourably well with reported methods. First, the substrate scope of the phenylboronic acid coupling partner was investigated. Under the optimised reaction conditions, the presence of electron-donating and moderately deactivating groups provided slightly better yields and faster reactions than those possessing strongly deactivating substituents (Table 3, entries 2–4 vs 5). Next, the substrate scope of the aryl bromides was studied. Interestingly, the reaction provided excellent yields with both activated and deactivated aryl bromides, though the presence of a strongly electron-withdrawing substituent gave marginally better yields than those possessing electron-donating groups (Table 3, entries 6–11) without much influence on the rate of the reaction. The slightly lower yield of the reaction in the preparation of 23icould be ascribed to steric encumbrance exerted by the NO 2-substituent located at the ortho-position of the aryl bromide.
Table 3:Results from the Suzuki–Miyaura cross-coupling reactions of various aryl bromides and boronic acids using pincer complex 17das catalyst. a
Entry ArBr ArB(OH) 2 Product Yield (%) Time (h) GC Isolated 1 21a 22a 23a 93 88 2 2 21a 22b 23b 96 90 1.5 3 21a 22c 23c 94 86 2 4 21a 22d 23d 92 86 2 5 21a 22e 23e 87 81 3 6 21b 22a 23f 98 91 2 7 21c 22a 23g 96 82 2 8 21d 22a 23h 96 88 1.5 9 21e 22a 23i 94 81 2 10 21a 22f 23j 96 89 2 11 21a 22g 23k 95 86 2 12 21f 22a 23l 83 77 3 13 21f 22f 23m 89 81 3
aCatalyst loading (0.5 mol %), ArX (1.63 mmol), ArB(OH) 2(2.61 mmol), H 2O (2 mL), KOH (3.26 mmol), 120 °C, 2 h, TBAB (0.5 equiv relative to ArX).
Encouraged by these results, the reactivities of aryl chlorides were investigated under the optimised conditions. While activated aryl chloride 21freacted with boronic acids possessing either electron-donating or electron-withdrawing groups to provide the corresponding biaryls in reasonable yields, to our dismay the reaction of inactivated aryl chlorides led to the recovery of starting materials (Table 3, entries 12 and 13).
Finally, the investigation of the reusability of the catalyst was carried out using the model cross-coupling reaction of 4-bromoanisole ( 21a) and phenylboronic acid ( 22a) under the optimised conditions (Scheme 3andFigure 5). After completion of the reaction, the products were extracted with toluene and to the remaining aqueous layer, which contains the catalyst system, fresh 4-bromoanisole ( 21a) and phenylboronic acid ( 22a) were added for the second and third cycles of the reaction. To our delight, the catalyst could be reused at least three times without significant loss of activity (93%, 80% and 75% for the 1st, 2nd and 3rd run, respectively) considering the fact that some of it could have been extracted along with the product and the results are summarised inFigure 5.
Scheme 3:Investigation on the reusability of the catalyst.
Scheme 3:Investigation on the reusability of the catalyst.
Figure 5:Reusability of pincer complex 17das a catalyst for the Suzuki–Miyaura cross coupling reaction.
Figure 5:Reusability of pincer complex 17das a catalyst for the Suzuki–Miyaura cross coupling reaction.
Since the bidentate complexes 20aand 20bare also potential catalysts in their own right, the catalytic activity of 20awas investigated in the Suzuki–Miyaura coupling reaction of 4-bromoanisole ( 21a) and phenylboronic acid ( 22a) as a proof of concept. As expected, it catalysed the reaction and provided biaryl 23ain moderate yield demonstrating the potential of such complexes in coupling reactions (Scheme 4).
Scheme 4:Suzuki–Miyaura coupling reaction catalysed by the SN-bidentate complex 20a.
Scheme 4:Suzuki–Miyaura coupling reaction catalysed by the SN-bidentate complex 20a.
Conclusion
A series of novel cationic Pd(II) complexes have been successfully synthesised using easy to prepare SNS pincer ligands. A detailed investigation into the application of these complexes in the Suzuki–Miyaura coupling reaction was conducted using various aryl bromides and boronic acids as coupling partners in aqueous medium. All the complexes could catalyse the Suzuki–Miyaura coupling reaction to provide the corresponding biaryls in excellent yields with only 0.5 mol % catalyst loading. Furthermore, unlike the previously reported SNS pincer Pd(II) complexes, the catalysts in the current study were compatible with both electron-donating and electron-withdrawing substituents on the aryl bromides and boronic acid substrates as well as activated aryl chlorides. Depending on the presence or absence of the TBAB additive, the reaction may be fine-tuned to either proceed via steric or electronic control. The advantage of using these water-soluble catalysts for the coupling reaction was their reusability for up to three times without significant loss in activity. Moreover, the mechanism of the coupling reaction was probed by a theoretical study that supported the experimental results. Contrary to the previously reported SNS pincer Pd(II) complexes that were proposed to proceed via a Pd(II) to Pd(0) type of mechanism, on the basis of the study described in this article the coupling reaction is proposed to proceed via a Pd(II) to Pd(IV) mechanism. This suggests the effect of the chain length of the linker and the nature of the backbone on the catalytic activity of the SNS pincer Pd(II) complexes. In the future, efforts to fine tune the electronic and structural features of the thiophenyl and pyridinyl groups will be carried out in order to enable the catalysts to activate aryl chlorides, possessing electron-donating substituents, in the coupling reaction.
Supporting Information
Supporting Information File 1: Experimental part. Format: PDF Size: 383.1 KB Download Supporting Information File 2: NMR spectra. Format: PDF Size: 2.7 MB Download
Acknowledgements
We thank the University of Johannesburg (UJ), the Research Centre for Synthesis and Catalysis of the Department of Chemistry at UJ, Sasol Ltd and the National Research Foundation (NRF) for funding. The use of UJ Spectrum’s NMR facilities is also acknowledged. We would also like to thank Mr. Novisi Oklu for his help in solving of the crystal structure.
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37. Pioquinto-Mendoza, J. R.; Conelly-Espinosa, P.; Reyes-Martínez, R.; Toscano, R. A.; Germán-Acacio, J. M.; Avila-Sorrosa, A.; Baldovino-Pantaleón, O.; Morales-Morales, D. J. Organomet. Chem. 2015, 797, 153–158. doi:10.1016/j.jorganchem.2015.08.024 Go to reference 37
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3D spherical analysis of baryon acoustic oscillations | Astronomy & Astrophysics (A& A)
Astronomy & Astrophysics (A& A) is an international journal which publishes papers on all aspects of astronomy and astrophysics
A&A 540, A115 (2012)
3D spherical analysis of baryon acoustic oscillations
Abstract
Context.Baryon acoustic oscillations (BAOs) are oscillatory features in the galaxy power spectrum which are used as a standard rod to measure the cosmological expansion. These have been studied in Cartesian space (Fourier or real space) or in spherical harmonic space in thin shells.
Aims.Future wide-field surveys will cover both wide and deep regions of the sky and thus require a simultaneous treatment of the spherical sky and of an extended radial coverage. The spherical Fourier-Bessel (SFB) decomposition is a natural basis for the analysis of fields in this geometry and facilitates the combination of BAO surveys with other cosmological probes readily described in this basis. In this paper, we present a new way to analyse BAOs by studying the BAO wiggles from the SFB power spectrum.
Methods.In SFB space, the power spectrum generally has both a radial ( k) and tangential ( ℓ) dependence and so do the BAOs. In the deep survey limit and ignoring evolution, the SFB power spectrum is purely radial and reduces to the Cartesian Fourier power spectrum. In the opposite limit of a thin shell, all the information is contained in the tangential modes described by the 2D spherical harmonic power spectrum.
Results.We find that the radialisation of the SFB power spectrum is still a good approximation even when considering an evolving and biased galaxy field with a finite selection function. This effect can be observed by all-sky surveys with depths comparable to current surveys. We also find that the BAOs radialise more rapidly than the full SFB power spectrum.
Conclusions.Our results suggest the first peak of the BAOs in SFB space becomes radial out to ℓ~ 10 for all-sky surveys with the same depth as SDSS or 2dF, and out to ℓ~ 70 for an all-sky stage IV survey. Subsequent BAO peaks will also become radial, but for shallow surveys these may be in the non-linear regime. For modes that have become radial, measurements at different ℓ’s are useful in practice to reduce measurement errors.
Key words:methods: observational / cosmology: observations / large-scale structure of Universe / methods: statistical / methods: data analysis
© ESO, 2012
1. Introduction
The study of large scale structure (LSS) with galaxy surveys is a promising tool to study the dark universe (Peacock et al. 2006;Albrecht et al. 2006). Baryon acoustic oscillations (BAOs) are a special feature in the galaxy power spectrum present on scales 100 h -1Mpc, which are due to oscillations in the coupled baryon-photon fluid before recombination (Sunyaev & Zeldovich 1970;Peebles & Yu 1970;Eisenstein et al. 2005;Seo & Eisenstein 2003,2007). The BAOs are considered a powerful cosmological tool as the BAO scale acts as a standard ruler with which to probe cosmic expansion both in the radial and tangential directions.
BAOs were first detected byEisenstein et al. (2005)in SDSS data (Adelman-McCarthy et al. 2008) and later with 2dF galaxies (Colless et al. 2003;Cole et al. 2005) and finally with both surveys (Percival et al. 2007b), though others suggest current data cannot currently probe the BAO scale sufficiently (Cabré & Gaztañaga 2011).
Until now, BAOs have been studied in Cartesian space, either in Fourier space (Seo & Eisenstein 2003,2007), or in real space (Eisenstein et al. 2005;Xu et al. 2010;Slosar et al. 2009), and in 2D spherical harmonic space on thin spherical shells (Dolney et al. 2006). These descriptions use different information and therefore have different constraining power for cosmological parameters (Rassat et al. 2008).
Future wide-field BAO surveys will, however, cover both large and deep areas of the sky, and thus require a simultaneous treatment of the spherical sky geometry and of extended radial coverage. The spherical Fourier-Bessel (SFB) decomposition is a natural basis for the analysis of fields in this geometry. The SFB analysis is powerful as it uses a coordinate system in which the radial selection function and physical effects are naturally described. Moreover, this description facilitates the combination of BAO surveys with other cosmological probes which are readily described in the SFB decomposition such as the smooth power spectrum and redshift space distortions (Heavens & Taylor 1995;Fisher et al. 1995b;Percival et al. 2004;Erdoğdu et al. 2006a,b), weak lensing (Heavens 2003;Castro et al. 2005;Kitching et al. 2008), and the integrated Sachs-Wolfe effect (ISW,Shapiro et al. 2011). Studying BAOs from wide-field surveys with an SFB expansion, is therefore natural both for the geometry considered, and for unifying the treatment with the other probes.
In Sect.2we first review the general decomposition of a 3D field in SFB space and introduce the concept of radialisationwhen the field is statistically isotropic and homogeneous. In Sect.3.1, we introduce a new way to consider the BAOs, by studying the baryon wiggles in SFB space, in a similar way as in Fourier space, while in Sect.3.2we discuss the radialisation of BAOs in SFB space in the context of existing and future surveys. In Sect.4we present our conclusions.
2. 3D spherical Fourier-Bessel (SFB) expansion
2.1. Expansion of an homogeneous and isotropic field
Let us consider a field f( r) at time t, where r= ( r,θ,ϕ) in spherical polar coordinates. In practice, this field may represent the galaxy or mass density (or overdensity) in the universe. In a flat geometry, the field can be decomposed in the 3D SFB basis set, which is complete and orthonormal, as (1)where j ℓ( x) are spherical Bessel functions of the first kind, Y ℓm( θ,ϕ) are spherical harmonics, ℓand mare multipole moments and kis the wavenumber. The inverse relation is (2)where we use the same conventions asLeistedt et al. (2012)andCastro et al. (2005)(see alsoHeavens & Taylor 1995;Fisher et al. 1995b, who use a different convention and basis set).
This decomposition can be viewed as the spherical polar coordinate analogue to the Fourier decomposition in Cartesian coordinates given byThe 3D SFB power spectrum C ℓ( k) of the field f( r) is given by the the 2-point function of the SFB coefficients f ℓm( k) which can be written as (5)when the field is statistically isotropic and homogeneous (hereafter, the SIH condition). Similarly and in the same condition, the Fourier power spectrum P( k) is implicitly defined by (6)These two power spectra are related by (see for e.g.,Fisher et al. 1995b;Castro et al. 2005): (7)Thus, the SFB power spectrum C ℓ( k) is independent of the multipole ℓ, and thus only has a radial ( k) dependence. This remarkable yet recondite fact is only true if the field fulfills the SIH condition.
In the following subsections, we discuss the impact of the (partial) violation of this condition in practice and the implication for the measurements of BAO in SFB analysis.
2.2. Finite surveys
2.2.1. Gaussian selection function
As a first example, let us consider a Gaussian selection function defined as (15)where r 0is a radius parameter and the normalisation obeys Eq. (9) (with). In this case, the window function can be integrated analytically (using relation 6.633.2 ofGradshteyn et al. 2000), and Eq. (13) becomes: (16)where I ν( x) is the modified Bessel function of the first kind. This analytical form considerably facilitates the evaluation of Eq. (12) (see Sect.Afor a way to numerically calculate the above equation for large arguments of I ν( x)).
2.2.2. Radial limit
In the case where the radial selection function corresponds to full radial coverage (i.e. φ( r) = 1,∀ r), the window function becomes (17)Inserting this expression into Eq. (12), we recover Eq. (7), namely (18)meaning that the 3D spherical spectrum is only dependent on radial coordinate k, as discussed above.
As we show in AppendixA, this limit can also be obtained by taking the limit r 0→ ∞ for the Gaussian weight function of Eq. (15) and is achieved in practice when the condition (see Eq. (A.4)) (19)is satisfied. We refer to this as the radialisationof the field and discuss this more in Sect.3.
2.2.3. Tangential Limit
In the other extreme case, the radial selection function covers only a thin shell of the field at a distance r ∗ (20)where the normalisation of Eq. (9) was chosen with. Equation (12) then becomes (21)This can be related to the statistics of the 2D projected field (22)whose spherical harmonic decomposition is given byand whose 2D spherical harmonic power spectrumis defined by (25)This power spectrum is related to the 3D Fourier space power spectrum P( k) by: (26)where the 2D window functionis given by (27)Note that due to our choice of normalisation for φ( r) in Eq. (9),has units of volume.
In the case of a thin-shell selection function (Eq. (20)), this reduces to (28)Thus, the SFB power spectrum (Eq. (21)) is simply related to the 2D spherical harmonic power spectrum 1by (29)The term k k′ j ℓ( k r ∗) j ℓ( k′ r ∗) is a geometric factor which does not depend on the field f. Thus, in this case, all the information in the 3D SFB spectrum C ℓ( k, k′) is contained in the 2D power spectrum, i.e. depends solely on ℓ.
Fig. 1Ratioof SFB spectrum with and without the physical effects of baryons in ( ℓ,k) space for a wide and shallow survey ( left, r 0= 100 h -1Mpc) and a wide and deep survey ( right, r 0= 1400 h -1Mpc) using a Gaussian selection function in r. The baryonic wiggles are seen both in the radial ( k) and the tangential ( ℓ) directions, but as r 0is increased, only radial wiggles – with increased amplitude – persist. This radialisationof the information is due to mode-cancelling along the line of sight for deep surveys.
2.3. Evolution and bias
For a realistic galaxy field, the SIH condition will not be met due to the radial evolution of the field from the growth of structure and redshift dependent bias.
For a biased and evolving field in the linear regime, the galaxy power spectrum P evol( k,r) will have an explicit distance dependence: (30)where the term b( r) is the linear bias, assumed to be scale-independent, D( r) is the growth factor and P( k) = P( k,r= 0) is the matter power spectrum at r= z= 0. The linear approximation will hold up to a redshift-dependent scale k max( z). In the standard cosmological model, we find k max( z= 0) ≃ 0.12 hMpc -1(i.e., before the second BAO peak) and k max( z= 2) ≃ 0.25 hMpc -1.
For the realistic galaxy field, an approximation for the spherical 3D power spectrum for the galaxy field is still given by Eq. (12), but the window function will incorporate the linear growth and bias functions as (31)
3. Application to baryon acoustic oscillations
3.1. SFB Analysis of BAOs
The matter power spectrum in Eq. (12) includes the physical effects of baryons, which create oscillations in Fourier space (Sunyaev & Zeldovich 1970;Peebles & Yu 1970;Seo & Eisenstein 2003;Eisenstein et al. 2005;Seo & Eisenstein 2007). These BAOs can be isolated by considering the ratio R P( k) in Fourier space: (32)where P b( k) is the galaxy (or matter) power spectrum including the physical effect of BAOs, and P nob( k) is broad band or “smooth” part of the galaxy (or matter) power spectrum. In linear theory the growth and bias terms cancel out so that Eq. (32) is independent of z. These oscillations can also be probed in 2D spherical harmonic space (Dolney et al. 2006). We are interested here to see if they can similarly be probed in SFB space as well.
In SFB space, we consider the ratiogiven by: (33)where similarly to Fourier space,is the diagonal SFB power spectrum (Eq. (14)) including the physical effects of baryons andis the “smooth” part of the SFB power spectrum. These are calculated by using P b( k) or P nob( k) instead of P( k) in Eq. (12) and then considering Eq. (14). The SFB decomposition suggests that the BAOs can manifest themselves in both kand ℓspace.
In Fig.1, we plotfor two wide-field galaxy surveys with a shallow (left) and deep (right) galaxy Gaussian selection functions with r 0= 100 h -1Mpc, and 1400 h -1Mpc respectively (see Sect.2.2.1). We chose a fiducial concordance cosmology with Ω m= 0.25, Ω DE= 0.75, Ω b= 0.045, w 0= −0.95, w a= 0.0, h= 0.70, σ 8= 0.80, n s= 1 and no running spectral index. We consider both to be “realistic” surveys, i.e. with evolution due to growth taken into account and a linear galaxy bias (taken as), using Eq. (31) for the window function.
Fig. 2Slices in(solid, red) compared to R P( k) (dashed, black) for ℓ= 5,50 ( top, bottom), for a wide and shallow galaxy survey ( left, r 0= 100 h -1Mpc, or z m~ 0.05) and a wide and deep galaxy survey ( right, r 0= 1400 h -1Mpc or z m~ 0.8).
In the LHS of Fig.1(narrow survey), the BAOs depend on both kand ℓmodes, illustrating that the wiggles can be measured simultaneously in the ℓand kdirections, which is the first result of this paper.
However, in the RHS of Fig.1(wide survey), the BAOs appear to have only a radial ( k) dependence, except at very large physical scales ( k< 0.01 hMpc -1), where the dependence is both radial and tangential. This is a practical illustration of Eq. (18) (see also Eq. (A.5)). This can be understood as tangential modes being attenuated due to mode-cancelling along the line of sight – the attenuation becomes important when the selection function spans a wide redshift range. We refer to this effect as the radialisationof the power spectrum, where we have used the baryonic wiggles to probe the radialisation. We discuss the radialisation limit in more detail in Sects.3.2and4.
One of the important results of Fig.1is that the radial limit is still reached even when evolution (growth and bias) of the field are considered. This can only be considered numerically since there is no analytic solution to Eq. (31) due to the inclusion of the growth and bias terms. We test this again with strongly evolving values of the galaxy bias, e.g., where n= −10,2, and find this still has little effect on the radialisation of. The growth values for standard concordance cosmology do not seem to have an effect on reaching the radialisation limit.
3.2. Radialisation limit
We are interested in quantifying the effect of the radialisation on the BAOs themselves. In Fig.2, we consider slices in ℓand kthroughin order to investigate how rapidly the limit in Eq. (18) is reached. The black (dashed) lines in Fig.2correspond to R P( k) (which are independent of ℓand of the survey selection function) and the red (solid) lines correspond tofor different slices in ℓspace and for narrow (LHS) and wide (RHS) selection functions. As the survey selection function is widened, we find that: (34)i.e.tends towards the oscillations in R P( k), not only in phase, but also in amplitude. This is noticeable in Fig.1: the amplitude of the first peak for example is higher for the deep survey ( > 9%) than for the shallow survey ( < 8%). This is another check of Eq. (7).
Fig. 3Radialisation limit as defined by Eq. (19) (diagonal lines) for Gaussian surveys (Eq. (15)) with r 0= 40,70,200,300,1400 h -1Mpc, i.e. roughly corresponding to the following surveys: IRAS ( z mean~ 0.015), 2MRS ( z mean~ 0.03), SDSS ( z mean~ 0.10), 2dF ( z mean~ 0.15), and a stage IV survey ( z mean~ 0.80). Information above the diagonal line is in the radial limit. We overplot the physical scales corresponding to the first three BAO peaks for comparison.
Equation (19) gives us an analytic way to study the limit where we can expect the SFB power spectrum to behave radially. In Fig.3, we plot the lines corresponding to the radial limit in ( k,ℓ) space for different surveys with Gaussian distributions (Eq. (15)) corresponding to r 0= 40,70,200,300,1100 [ h -1Mpc] . We have chosen these values as they correspond roughly to the following surveys (for the chosen fiducial survey): IRAS ( z mean~ 0.015,Fisher et al. 1995a;Strauss et al. 1992), 2MRS (2 MASS All-Sky Redshift Survey, z mean~ 0.03,Huchra et al. 2012), SDSS (Sloan Digital Sky Survey, z mean~ 0.10,Adelman-McCarthy et al. 2008), 2dF (2 degree Field, z mean~ 0.15,Colless et al. 2003) and a Stage IV galaxy survey ( z mean~ 0.80,Albrecht et al. 2006). Note that, in principle, these surveys would have to be all-sky to obey the radialisation limits plotted in Fig.3.
The area above each diagonal line corresponds the radial limit, i.e. where the radialisation has taken place and Eq. (18) holds. We overplot the radial scales corresponding to the first three peaks of the BAOs to show how these will be probed for different survey depths.
By comparing the diagonal lines in Fig.3with the BAO “turnover” (i.e. the ℓ-dependent k-scale at which the BAOs switch from being mostly tangential to mostly radial) in Fig.1, we notice however that the BAOs seem to become radial before the full SFB power spectrum does, especially for large ℓ. This surprising effect, further motivates the use of the SFB analysis for BAOs.
Fig. A.1Window function W ℓ( k, k′) for the Gaussian selection function with for ℓ= 3 and r 0= 100 h -1Mpc ( left) and r 0= 1400 h -1Mpc ( right). As the selection function parameter r 0becomes larger (i.e., increasing the redshift coverage from z med~ 0.05 to z med~ 0.8), the window function tends towardsfor scales where.
4. Conclusion
In this paper, we have presented a new way to study BAOs using a SFB decomposition of a wide-field deep galaxy survey. The BAO signal in SFB space can be studied by considering the ratioof the SFB power spectrum with wigglesto the smooth SFB power spectrum, similarly to what is done in Fourier space. In this decomposition, BAOs can be observed simultaneously in both the radial ( k) and tangential ( ℓ) modes.
For a field which is statistically isotropic and homogeneous (SIH), the SFB power spectrum is purely radial, i.e. independent of tangential modes, and reduces to the Cartesian Fourier power spectrum. In the other extreme limit where the field is in a thin shell, we showed that all the SFB information is contained in the tangential modes and is simply related to the 2D spherical harmonic power spectrum.
Considering the practical case where the field is observed with a radial selection function (thus partially violating the SIH condition), we find that the radial limit can still be reached for selection functions covering a large radial range (see AppendixA), which we refer to as the radialisationof the power spectrum. The radialisation will be limited to a region in ( ℓ,k) space corresponding to, where r 0parameterises the radial selection function. We find that radialisation is a good approximation for these modes even when evolution due to growth and bias are considered, both of which can be considered as a further violation of the SIH condition. To study this limit, we have derived an analytic solution to the window function of a non-evolving, unbiased galaxy field when the radial selection function is a Gaussian in rcentered on the observer (Eq. (16)).
We also find the BAOs considered in SFB space radialise as the survey depth is increased, meaning both the phase and amplitude of the BAOs tend towards the Fourier space ratio R P( k). This means that BAOs for a wide-field shallow survey have smaller amplitude and are spread across the ( ℓ,k) space, while BAOs for a wide-field deep survey have a larger amplitude and are confined to the radial modes (Figs.1and2).
We study the radial limit analytically (Fig.3) and find that it can in principle be observed (for a limited ℓ-range and for small physical scales) with all-sky surveys with current surveys depths or for future stage-IV surveys. This suggest that the first BAO peak becomes radial up to ℓ~ 10 for an all-sky survey with similar depth to SDSS or 2dF, and up to ℓ~ 70 for an all-sky stage IV survey. In practice though, the radialisation might be observable to even higher ℓsince we observe that the BAOs radialise more rapidly than the full SFB power spectrum, especially at large ℓ. Subsequent BAO peaks also become radial for large values of ℓand for shallower surveys, though these may be already be in the non-linear regime. For modes that have become radial, measurements at different ℓ’s are useful in practice, to reduce measurement errors due to cosmic variance and shot noise.
We note that we have ignored redshift-space distortions in our analysis though the prescription for these in SFB space is well known (see for e.g.,Heavens & Taylor 1995). These distortions may affect the radialisation as they will introduce mode-mixing, albeit with a distinct signature and are readily described in the SFB basis. Further ℓ-mode mixing will occur for incomplete sky coverage, which can be corrected for using the mask geometry.
1
Equation (29) is conceptually different from Eq. (B3) inKitching et al. (2011): the former is an exact solution for a thin shell, while the latter uses the Limber approximation.
2
www.icosmo.org
Acknowledgments
The authors are grateful to Pirin Erdoğdu, Alan Heavens, Ofer Lahav, François Lanusse, Boris Leistedt and Adam Amara for useful discussions about SFB decompositions. The SFB calculations use the discrete spherical Bessel transform (DSBT) presented inLanusse et al. (2012)and the authors are grateful to François Lanusse for help implementing this. We extended iCosmo 2software for our calculations (Refregier et al. 2011). This research is in part supported by the Swiss National Science Foundation (SNSF).
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Appendix A: Radial limit for a Gaussian selection function
As shown in Sect.2.2.1, when the galaxy selection is Gaussian, i.e. φ( r) = e − ( r / r 0 ) 2, it is the galaxy selection function (Eq. (13)) reduces to (A.1)where I ν( x) is the modified Bessel function of the first kind. For numerical reasons, it is often useful to evaluate the exponentially scaled modified Bessel function of the first kindinstead of I ν( x), in which case it is useful to re-write the above equation as: (A.2)FigureA.1shows the window function for two values of r 0, ℓ= 3 as a function of k, k′. As r 0becomes large, it can be seen that the window function tends towards a delta function.
To study this limit more precisely, we use the asymptotic form for the modified Bessel functionfor x≫ | α 2− 1/4 | , which gives (A.3)in the limit where, or approximately, (A.4)Using the definition of a Dirac delta function, namely ∫d x h( x) δ( x− x 0) = h( x 0) for an arbitrary function h( x), the window function becomes, in the limit r 0→ ∞, (A.5)in agreement with Eq. (17) for the radial case discussed in Sect.2.2.2. Thus, if the condition of Eq. (A.4) holds, the power spectrumbecomes radial (i.e. independent of ℓ) and equal to C ℓ( k) δ( k− k′) = P( k) δ( k− k′) as in Eq. (18).
All Figures
Fig. 1Ratioof SFB spectrum with and without the physical effects of baryons in ( ℓ,k) space for a wide and shallow survey ( left, r 0= 100 h -1Mpc) and a wide and deep survey ( right, r 0= 1400 h -1Mpc) using a Gaussian selection function in r. The baryonic wiggles are seen both in the radial ( k) and the tangential ( ℓ) directions, but as r 0is increased, only radial wiggles – with increased amplitude – persist. This radialisationof the information is due to mode-cancelling along the line of sight for deep surveys. In the text
Fig. 2Slices in(solid, red) compared to R P( k) (dashed, black) for ℓ= 5,50 ( top, bottom), for a wide and shallow galaxy survey ( left, r 0= 100 h -1Mpc, or z m~ 0.05) and a wide and deep galaxy survey ( right, r 0= 1400 h -1Mpc or z m~ 0.8). In the text
Fig. 3Radialisation limit as defined by Eq. (19) (diagonal lines) for Gaussian surveys (Eq. (15)) with r 0= 40,70,200,300,1400 h -1Mpc, i.e. roughly corresponding to the following surveys: IRAS ( z mean~ 0.015), 2MRS ( z mean~ 0.03), SDSS ( z mean~ 0.10), 2dF ( z mean~ 0.15), and a stage IV survey ( z mean~ 0.80). Information above the diagonal line is in the radial limit. We overplot the physical scales corresponding to the first three BAO peaks for comparison. In the text
Fig. A.1Window function W ℓ( k, k′) for the Gaussian selection function with for ℓ= 3 and r 0= 100 h -1Mpc ( left) and r 0= 1400 h -1Mpc ( right). As the selection function parameter r 0becomes larger (i.e., increasing the redshift coverage from z med~ 0.05 to z med~ 0.8), the window function tends towardsfor scales where. In the text
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COVID-19: Healthy Oregon (Oregon Saludable): Together We Can (Juntos Podemos) - Full Text View - ClinicalTrials.gov
COVID-19: Healthy Oregon (Oregon Saludable): Together We Can (Juntos Podemos) (OSJP)
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ClinicalTrials.gov Identifier: NCT04793464 Recruitment Status :
Completed First Posted : March 11, 2021 Last Update Posted : February 28, 2023
Sponsor:
National Institute on Drug Abuse (NIDA)
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Leslie Leve,, University of Oregon
Study Details
Study Description
Brief Summary:
The global SARS-CoV-2 pandemic that causes the severe respiratory illness COVID-19 is the worst health crisis that the United States has faced in a century. Although this highly contagious virus has infected millions of Americans already, the disease burdens are disproportionately born by historically underserved populations such as Latinx communities. This disparity is notable in Oregon, where the 13% of the population that is Latinx represents approximately 44% of COVID-19 cases. An urgent need exists to reach Oregon's Latinx community to prevent SARS-CoV-2 transmission.
The overall goal of this study is to implement a Promotores de Salud intervention to increase the reach, access, uptake, and impact of testing in Latinx communities in Oregon. This project will fully integrate with the National institutes of Health (NIH) Rapid Acceleration of Diagnostics (RADx) consortium and its Coordination and Data Collection Center (CDCC). With guidance and leadership from the study's Latinx Community and Scientific Advisory Board, 38 testing sites have been established to test the Promotores de Salud intervention. The investigators will test whether the Promotores de Salud intervention will increase testing rates and promote better health behaviors in communities over time. The investigators will test the intervention using a randomized control trial comparing the intervention to county outreach services as usual. Evaluation of the Promotores de Salud intervention held during a testing event (compared to distribution of a pamphlet only) will test whether culturally competent education results in greater use of strategies that reduce transmission of COVID-19 at the community and individual level.
The investigators have designed a working group structure with teams focused on: Community Engagement, Molecular Biology, Data Science, and Implementation Science. These working groups are coordinated by an Administrative Hub and guided by the study's Latinx Community and Scientific Advisory Board.
Over time, this project will help communities institutionalize optimal local testing frameworks supported by University of Oregon laboratory facilities for testing capacity, technical support for testing logistics, and collection of data on health behaviors, testing rates, and sustainability. The resulting structures and systems will be poised for future scale-up to other vulnerable communities and/or for other public health purposes (e.g., vaccination campaigns).
Condition or disease Intervention/treatment Phase Health Behavior Health Care Utilization Behavioral: Promotores de Salud Behavioral: Services as usual Not Applicable
Detailed Description:
To assess the proportion of Latinx community members tested at each site, the investigators will use de-identified health information provided to the study by the University of Oregon's (UO) COVID-19 clinical genomics laboratory, who are processing the tests. To assess health behaviors, a subset of adult participants at each site will be invited to participate in a research survey, administered at baseline and again 30 days later. For both approaches, the study anticipates engaging a greater proportion Latinx community members, relative to overall county demographics. The overall study population is expected to be 85% Hispanic and 15% non-Hispanic, with 84% of individuals identifying as White in both ethnic groups and the remaining 16% identifying as African American, Asian, Pacific Islander, American Indian/Alaska Native, or more than one race. There will be 19 sites per study group (38 total) and up to roughly 3,600 adult individuals in the intervention (n = 1,800) or control conditions (n = 1,800).
This study also leverages data from a patient registry from the University of Oregon's COVID-19 clinical genomics laboratory.
Quality Assurance, Data Checks, Source Data Verification, Data Dictionary, and Standard Operating Procedures: Data and biospecimens will be collected in-person at testing sites, requiring direct interaction with participants. In order to report SARS-CoV-2 infection results back to each participant, name, date of birth, and contact information are collected. To fulfill reporting requirements to the Oregon Health Authority, county of residence and zip code are also collected for each person tested. Data used to evaluate the efficacy of intervention will involve aggregate variables derived from data collected as part of the diagnostic testing procedure and will be aggregated at the level of the testing site (e.g., tests performed, race and ethnicity percentages, etc.).
For the collection of SARS-CoV-2 samples, testing facilitators will guide participants in the self-collection process. For anterior nares, participants are instructed to place the nasal swab about 1cm into their nostril and rotate it, making contact with the nasal membrane for 10 seconds, then repeating the process with the same swab in the other nostril. Parents are instructed to collect the sample for their child if the child is under 10 years old, or if the minor child requests parental assistance. Testing site staff can assist participants who have low dexterity or physical impairments in sample collection. In case of an injury during sample collection, the partnering community organization staff will direct the participant to the appropriate medical resources. Samples will be placed into sterile barcoded vials (1 ml Matrix, barcoded screw-cap tubes) that each contain 500 microliters (μl) of DNA/RNA Shield. Each Matrix tube will then be closed tightly and will be placed in a standard plastic laboratory microcentrifuge tube rack with eight rows and twelve columns (8-by-12 rack with 96 positions). This rack will then be externally decontaminated by brief submersion in accelerated hydrogen peroxide (H202). Each 96-position microcentrifuge tube rack will then be labeled and placed in a sterile temporary container with wet ice at 4Cdegrees. If possible at each site, racks will be periodically transferred either to a refrigerator (4C) or freezer (-20C) for storage. At the end of the day all racks will be transported on wet ice to the COVID-19 clinical genomics Laboratory at UO, ensuring that they will arrive no longer than 48 hours after collection and preferably within 12-24 hours. If the testing site is located too distally for hand transport, tube racks will be secured and shipped by express methods on dry ice.
Each 96 well collection plate will next proceed to molecular processing using the standard, FDA approved Thermo Fisher TaqPath analysis protocol. All steps of this approved protocol will be followed exactly, including the appropriate reagents, volumes, and inclusion of appropriate positive and negative controls. In addition, investigators will employ the software analysis system and parameters exactly as specified. First, RNA will be extracted from each well using the MagMax Viral/Pathogen Nucleic Acid Isolation Kit (ThermoFisher, #100081242) which removes potentially inhibiting contamination and increases the sensitivity and consistency of subsequent qPCR protocols. Depending upon the number of samples to be processed, the RNA extraction will either occur by hand using multichannel pipettors or through the use of the Hamilton Robot. The purified RNA will then be retrotranscribed for analysis using the TaqPath RT-PCR COVID-19 Kit on either 96 well or 384 well QuantStudio5 (QS5) thermocyclers depending upon the number of samples to be processed. If the lab technicians need to process 384 samples, they will use the Hamilton liquid handling robot (Hamilton, Microlab VANTAGE 2.0) to aliquot from each of four-96 well plates into the 384 well plate format for subsequent qPCR amplification. In this RT-PCR process, probes anneal to three unique forward and reverse primers for three SARS-CoV-2 genes: ORF1ab, N Protein and S Protein.
All laboratory and reporting will be automated through the use of barcodes, robotics, 96 and 384 well qPCR machines, and the use of a fully HIPAA and CAP3 compliant Laboratory Information Management System (LIMS) built by L7 informatics (https://l7informatics.com/). These system automations and use of LIMS allow increased throughput (up to several thousand samples per day) and rapid analysis and automated reporting of results through the LIMS. The qPCR data are stored in the LIMS system for analysis using the Applied Biosystems COVID-19 Interpretive Software to allow a qualitative assessment of whether the virus is present in the sample (a 'positive' case), absent, or uncertain. The LIMS system in the COVID-19-MAP lab allows the integration of this analysis software into the appropriate step of the overall sample tracking workflow pipeline, and therefore the immediate result can be linked to the appropriate barcode in the database. Furthermore, the LIMS system is connected and communicates via a local area network (LAN) with all equipment (e.g., robots and qPCR machines) to document each step of the process for CLIA validation. The results for each sample, and associated metadata on the steps during processing, are then associated with each assigned barcode and can then be disseminated, as appropriate, to the Oregon Health Authority, the appropriate county health department, and the individual. Test results will be available within 48 hours and no later than 4 days to the individual and/or the health authority.
After testing occurs, researchers will have access to aggregate, community-level (e.g., counts and prevalence rates), de-identified data prepared by the UO's CLIA clinical genomics laboratory. The data will include four protected health identifiers: site zip code, participant zip code, testing result, and testing date. It will also include demographic data this is not protected health information such as age range, race, and ethnicity. These data will be used to assess outreach activities aimed at increasing participation of Latinx community members in SARS-COV-2 testing. The primary outcome for this aspect of the study is site-level testing rates of Latinx individuals.
Sample Size Assessment, Plan for Missing Data, Statistical Analysis Plan: For the primary efficacy evaluation of the Promotores intervention, the investigators will employ standard normal theory analysis of covariance (ANCOVA) and auto-regressive linear modeling for continuous outcomes such as COVID-19 knowledge; and they will employ pre-post generalized linear modeling for count and ordered categorical outcomes such as proportion of Latinx tested at each geographic site. To address the non-independence of participants in the intervention design, investigators will estimate linear mixed models. Two primary sources of missing data are expected, item non-response and attrition over time. For dropout, investigators will conduct standard attrition analyses to compare baseline characteristics between attriters and completers. They will consider propensity score matching procedures and complier average causal effects models to address substantial differences. For item non-response and scale score development, investigators will require 70% of scale items be present for scoring. They will test whether scale level data are missing completely at random (MCAR) within waves and then across waves. If data are not MCAR, under assumptions of missing at random (MAR, i.e., data are not dependent on missing values of the intervention response variable), investigators will employ one of two recommended approaches for SEM, full information maximum likelihood (FIML) or multiple imputation (MI). Although these approaches can be problematic when data are non-ignorable missing, they are still recommended for handling missingness, particularly with covariates associated with attrition. Both methods provide more efficient standard errors than listwise or pairwise deletion, or mean substitution. Should missing data or attrition be associated with covariates, investigators will include appropriate covariates in hypothesis testing. For the pre-post individual level criterion outcomes, 38 sites with roughly 50 to 100 participants per site plus attrition (n = 2160) an alpha level of .05 and intra-class correlations ranging from .05 to .20 provides power to detect effects ranging from .19 to .32, respectively (small to moderate).
Finally, data will be collected in accordance with Tier 1 "common data elements" from the national Duke Coordination and Data Collection Center (CDCC). The CDCC directly assists each individual RADx-UP project to optimize engagement, outreach, testing strategies, and to facilitate co-learning opportunities between and among RADx-UP projects. Key outcome data and the testing procedures for obtaining the sample, analysis platform, analysis procedures, and test resulting will be collected and represented in a consistent manner for harmonization across the consortium, integrated with test reporting requirements under the Coronavirus Aid, Relief, and Economic Security Act (CARES Act).
Study Design
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for study information Study Type : Interventional
(Clinical Trial) Actual Enrollment : 1626 participants Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single (Outcomes Assessor) Primary Purpose: Prevention Official Title: Scaling Up SARS-CoV-2 Testing to Serve Latinx Communities Actual Study Start Date : February 4, 2021 Actual Primary Completion Date : December 31, 2022 Actual Study Completion Date : December 31, 2022
Resource links provided by the National Library of Medicine
MedlinePlus related topics: COVID-19 (Coronavirus Disease 2019)
U.S. FDA Resources
Arms and Interventions
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Outcome Measures
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Primary Outcome Measures
:
Latinx testing engagement [ Time Frame: One time point only (~15 minute), when a participant engages in COVID-19 testing at a testing site, no longitudinal follow-up ]
Number and proportion of Latinx community members tested at each site, defined by the number and proportion of Latinx tested divided by the total census block frequency of Latinx individuals above the age of 3.
COVID-19 Prevention Health Behaviors [ Time Frame: Change from baseline health behaviors at 30 days ]
From the PhenX toolkit, Protocol - COVID-19 Knowledge, Attitudes, and Avoidant Behaviors, participants are asked to indicate "Which of the following have you done in the last seven days to keep yourself safe from coronavirus? Only consider actions that you took or decisions that you made personally." There are a total of 17 possible items participants rate as a binary, Yes/No, response. The scale will range from 0-17. Participants are also asked "Which of the following have you done in the last five days?" There are 5 items that increase risk for COVID-19, rated on a checklist (check indicates participation in behavior). The scale ranges from 0-5 with 5 indicating greater risk behavior.
COVID-19 Knowledge and Attitudes [ Time Frame: Change from baseline COVID-19 attitudes and knowledge at 30 days ]
Participants are asked, "How can the novel coronavirus be transmitted?" adapted from the PhenX toolkit COVID-19 COMMUNITY RESPONSE SURVEY, KNOWLEDGE & ATTITUDES TOWARDS COVID-19. Participants to indicate using a Yes/No response. The sum of responses indicates overall knowledge of transmission out of a possible score of 2 with 2 indicating greater knowledge.
Participants are also asked: "In your opinion, how effective are the following actions for keeping you safe from COVID-19?" A list of 5 prevention strategies are listed. Participants indicate their response on a scale Very Effective (5) to Not Effective at All. The possible score ranges from 5 to 25.
The are also asked: "How safe or unsafe are the following actions for avoiding exposure to coronavirus?" A list of 11 activities are listed and responses are on scale of 1 (Extremely Unsafe) to 4 (Extremely Safe).
Attitudes Towards COVID-19 Vaccines [ Time Frame: Change from baseline attitudes towards COVID-19 vaccines at 30 days ]
Participants are asked, "How likely are you to get vaccinated for coronavirus once a vaccination is available to the public?" on a 5-item response scale of "Very likely" to "Definitely not". The item will be computed on a scale of 1-5 with 5 indicating greater likelihood of receiving the vaccine and lower vaccine hesitancy.
Secondary Outcome Measures
:
Broadband internalizing symptoms [ Time Frame: Change from baseline symptoms at 30 days ]
Participants respond to the Phenx Toolkit depression (2 items) and anxiety (2 items) subscales regarding how much or how often they have been bothered by each problem during the past 2 weeks. Items are rated on a scale ranging from 0-4, where 0="none/not at all" and 4= "severe/nearly every day". A mean score will be computed from the 4 items, with higher scores indicating more symptoms.
Eligibility Criteria
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Layout table for eligibility information Ages Eligible for Study: 3 Years and older (Child, Adult, Older Adult) Sexes Eligible for Study: All Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:
Proportion Tested: Age 3 or older
Proportion Tested: Received testing at study testing site
Individual Survey: 15 or older
Exclusion Criteria:
• Individual Survey: Unable to understand Spanish or English or another language translated by a qualified translator at a 5th grade level
Contacts and Locations
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04793464
Locations
Layout table for location information United States, Oregon University of Oregon Eugene, Oregon, United States, 97403
Sponsors and Collaborators
University of Oregon
National Institute on Drug Abuse (NIDA)
National Institutes of Health (NIH)
Investigators
Layout table for investigator information Principal Investigator: Leslie D Leve, PhD University of Oregon
Study Documents (Full-Text)
Documents provided by Leslie Leve,, University of Oregon:
Informed Consent Form [PDF] July 21, 2021
Publications of Results:
Searcy JA, Cioffi CC, Tavalire HF, Budd EL, Cresko WA, DeGarmo DS, Leve LD. Reaching Latinx Communities with Algorithmic Optimization for SARS-CoV-2 Testing Locations. Prev Sci. 2023 Jan 9:1-12. doi: 10.1007/s11121-022-01478-x. Online ahead of print.
Anda S, Budd EL, Halvorson S, Mauricio AM, McWhirter EH, Cioffi CC, Garcia JIR, Cresko WA, Leve LD, DeGarmo DS. Effects of a Health Education Intervention for COVID-19 Prevention in Latinx Communities: A Cluster-Randomized Controlled Trial. Am J Public Health. 2022 Nov;112(S9):S923-S927. doi: 10.2105/AJPH.2022.307129.
DeGarmo DS, De Anda S, Cioffi CC, Tavalire HF, Searcy JA, Budd EL, Hawley McWhirter E, Mauricio AM, Halvorson S, Beck EA, Fernandes L, Currey MC, Ramirez Garcia J, Cresko WA, Leve LD. Effectiveness of a COVID-19 Testing Outreach Intervention for Latinx Communities: A Cluster Randomized Trial. JAMA Netw Open. 2022 Jun 1;5(6):e2216796. doi: 10.1001/jamanetworkopen.2022.16796.
Other Publications:
Budd EL, McWhirter EH, De Anda S, Mauricio AM, Mueller MV, Cioffi CC, Nash A, Van Brocklin K, Yarris K, Jackson A, Terral H, Garcia JIR; Juntos Podemos Community and Scientific Advisory Board; Cresko WA, DeGarmo DS, Leve LD. Development and design of a culturally tailored intervention to address COVID-19 disparities among Oregon's Latinx communities: A community case study. Front Public Health. 2022 Sep 23;10:962862. doi: 10.3389/fpubh.2022.962862. eCollection 2022.
Layout table for additonal information Responsible Party: Leslie Leve,, Lorry Lokey Professor, College of Education; Associate Director, Prevention Science Institute, University of Oregon ClinicalTrials.gov Identifier: NCT04793464 History of Changes Other Study ID Numbers: 10032020.002 P50DA048756-02S2 ( U.S. NIH Grant/Contract ) First Posted: March 11, 2021 Key Record Dates Last Update Posted: February 28, 2023 Last Verified: February 2023 Individual Participant Data (IPD) Sharing Statement: Plan to Share IPD: Yes Plan Description: We will share IPD with the RADx-Up CDCC. All Tier 1 data elements required by the CDCC will be shared. Supporting Materials: Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Time Frame: IPD will be shared in accordance with timeframes set by the RADX-UP CDCC Access Criteria: The RADX-UP CDCC will make these determinations URL: https://radx-up.org/about/
Layout table for additional information Studies a U.S. FDA-regulated Drug Product: No Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Leslie Leve,, University of Oregon:
Latinx SARS-CoV-2 COVID-19 Hispanic Testing
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U.S. Department of Health and Human Services
| https://clinicaltrials.gov/show/NCT04793464 |
Hubble watches spun-up asteroid coming apart | EurekAlert! Science News
A small asteroid has been caught in the process of spinning so fast it's throwing off material, according to new data from NASA's Hubble Space Telescope and other observatories.
Hubble watches spun-up asteroid coming apart
NASA/Goddard Space Flight Center
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IMAGE:This Hubble Space Telescope image reveals the gradual self-destruction of an asteroid, whose ejected dusty material has formed two long, thin, comet-like tails. The longer tail stretches more than 500,000...view more
Credit: NASA, ESA, K. Meech and J. Kleyna (University of Hawaii), and O. Hainaut (European Southern Observatory)
A small asteroid has been caught in the process of spinning so fast it's throwing off material, according to new data from NASA's Hubble Space Telescope and other observatories.
Images from Hubble show two narrow, comet-like tails of dusty debris streaming from the asteroid (6478) Gault. Each tail represents an episode in which the asteroid gently shed its material -- key evidence that Gault is beginning to come apart.
Discovered in 1988, the 2.5-mile-wide (4-kilometer-wide) asteroid has been observed repeatedly, but the debris tails are the first evidence of disintegration. Gault is located 214 million miles (344 million kilometers) from the Sun. Of the roughly 800,000 known asteroids between Mars and Jupiter, astronomers estimate that this type of event in the asteroid belt is rare, occurring roughly once a year.
Watching an asteroid become unglued gives astronomers the opportunity to study the makeup of these space rocks without sending a spacecraft to sample them.
"We didn't have to go to Gault," explained Olivier Hainaut of the European Southern Observatory in Germany, a member of the Gault observing team. "We just had to look at the image of the streamers, and we can see all of the dust grains well-sorted by size. All the large grains (about the size of sand particles) are close to the object and the smallest grains (about the size of flour grains) are the farthest away because they are being pushed fastest by pressure from sunlight."
Gault is only the second asteroid whose disintegration has been strongly linked to a process known as a YORP effect. (YORP stands for "Yarkovsky-O'Keefe-Radzievskii-Paddack," the names of four scientists who contributed to the concept.) When sunlight heats an asteroid, infrared radiation escaping from its warmed surface carries off angular momentum as well as heat. This process creates a tiny torque that can cause the asteroid to continually spin faster. When the resulting centrifugal force starts to overcome gravity, the asteroid's surface becomes unstable, and landslides may send dust and rubble drifting into space at a couple miles per hour, or the speed of a strolling human. The researchers estimate that Gault could have been slowly spinning up for more than 100 million years.
Piecing together Gault's recent activity is an astronomical forensics investigation involving telescopes and astronomers around the world. All-sky surveys, ground-based telescopes, and space-based facilities like the Hubble Space Telescope pooled their efforts to make this discovery possible.
The initial clue was the fortuitous detection of the first debris tail, observed on Jan. 5, 2019, by the NASA-funded Asteroid Terrestrial-Impact Last Alert System (ATLAS) telescope in Hawaii. The tail also turned up in archival data from December 2018 from ATLAS and the Panoramic Survey Telescope and Rapid Response System (Pan-STARRS) telescopes in Hawaii. In mid-January, a second shorter tail was spied by the Canada-France-Hawaii Telescope in Hawaii and the Isaac Newton Telescope in Spain, as well as by other observers. An analysis of both tails suggests the two dust events occurred around Oct. 28 and Dec. 30, 2018.
Follow-up observations with the William Herschel Telescope and ESA's (European Space Agency) Optical Ground Station in La Palma and Tenerife, Spain, and the Himalayan Chandra Telescope in India measured a two-hour rotation period for the object, close to the critical speed at which a loose "rubble-pile" asteroid begins to break up.
"Gault is the best 'smoking gun' example of a fast rotator right at the two-hour limit," said team member Jan Kleyna of the University of Hawaii in Honolulu.
An analysis of the asteroid's surrounding environment by Hubble revealed no signs of more widely distributed debris, which rules out the possibility of a collision with another asteroid causing the outbursts.
The asteroid's narrow streamers suggest that the dust was released in short bursts, lasting anywhere from a few hours to a few days. These sudden events puffed away enough debris to make a "dirt ball" approximately 500 feet (150 meters) across if compacted together. The tails will begin fading away in a few months as the dust disperses into interplanetary space.
Based on observations by the Canada-France-Hawaii Telescope, the astronomers estimate that the longer tail stretches over half a million miles (800,000 kilometers) and is roughly 3,000 miles (4,800 kilometers) wide. The shorter tail is about a quarter as long.
Only a couple of dozen active asteroids have been found so far. Astronomers may now have the capability to detect many more of them because of the enhanced survey capabilities of observatories such as Pan-STARRS and ATLAS, which scan the entire sky. "Asteroids such as Gault cannot escape detection anymore," Hainaut said. "That means that all these asteroids that start misbehaving get caught."
The researchers hope to monitor Gault for more dust events.
###
The team's results have been accepted for publication by the Astrophysical Journal Letters.
The Hubble Space Telescope is a project of international cooperation between NASA and ESA (European Space Agency). NASA's Goddard Space Flight Center in Greenbelt, Maryland, manages the telescope. The Space Telescope Science Institute (STScI) in Baltimore, Maryland, conducts Hubble science operations. STScI is operated for NASA by the Association of Universities for Research in Astronomy in Washington, D.C.
http://www.nasa. gov/ goddard
Keywords
Original Source
https:/ / www. nasa. gov/ feature/ goddard/ 2019/ hubble-watches-spun-up-asteroid-coming-apart
| https://archive.eurekalert.org/pub_releases/2019-03/nsfc-hws032819.php |
EWG's Food Scores | Fisher Whole Natural Almonds
Check out the food score for Fisher Whole Natural Almonds from EWG's Food Scores! EWG's Food Scores rates more than 80,000 foods in a simple, searchable online format to empower you to shop smarter and eat healthier.
Fisher Whole Natural Almonds
Lower scores accompany better foods.
Image source: Kwikee
How it compares to other almonds? (Click to Learn)
EWG Overall Score Breakdown
The product score is based on weighted scores for nutrition, ingredient and processing concerns. Generally, nutrition counts most, ingredient concerns next and degree of processing least. The weighted scores are added together to determine the final score.Read more about scores here.
EWG Overall Score Breakdown
EWG scored on three factors: nutrition, ingredient concerns, and the degree of processing.Read the full scoring methodology.
Lower concern
N
I
Higher concern
Lower concern
Higher concern
N Nutrition Concern
P Processing Concern
Nutrition Concern Details
Considers calories, saturated fat, trans fat, sugar, sodium, protein, fiber and fruit, vegetable and nut content to differentiate between healthful and less healthful foods. For more information on nutrition concerns,read our full methodology.
Per gram, high in protein [read more]
Per gram, high in naturally occurring fiber [read more]
Per gram, high in calories [read more]
Per gram, high in calories
The World Health Organization states that "there is convincing evidence that a high intake of energy-dense foods promotes weight gain" (WHO 2002). Foods that are high in calories by weight are also likely to be highly processed, high in sugars, starch or fat and lower in nutrients. Conversely, foods that are low in calories by weight tend to be fruits, vegetables, beans, whole grains and soups that are high in nutrients and promote healthier diets. Studies have shown they also help people to maintain their weight by providing a satisfying amount of food even at lower calorie levels (Rolls 2005).
The nutrition factors used for scoring Fisher Whole Natural Almonds
Positive factors
Fruit, vegetable, bean or nut content
Protein content
Fiber content
Omega-3 fatty acids
Negative factors
Calorie density
Sugar/low-calorie sweetener content
Sodium content
Saturated fat content
Trans fat content
Ingredient Concern Details
Considers food additives, pesticides, hormones, antibiotics and contaminants like mercury and BPA, which can affect human health and the environment. For more information on ingredient concerns,read methodology.
This product is not certified organic [read more]
Processing Concern Details
Estimates how much the food has been processed. Considers many factors, chief among them, modification of individual ingredients from whole foods and number of artificial ingredients. For more information on processing concerns,read our full methodology.
Product has been classified as having no processing concerns
Products with no processing concerns identified are generally whole foods without additives.
EWG's Top Findings
This product is not certified organic [read more]
This product is not certified organic
Products bearing the USDA certified organic seal must contain at least 95 percent organic ingredient, and must be produced without the use of synthetic pesticides and fertilizers and free of genetically engineered ingredients.
Does not contain artificial or industrial ingredients [read more]
Does not contain artificial or industrial ingre...
EWG has not identified any artificial or industrial ingredients in this product.
Per gram, high in protein [read more]
Per gram, high in protein
Protein is a source of amino acids that are required for the proper growth, maintenance and repair of tissues. It also provides the building blocks for important enzymes and hormones. Protein provides calories and if eaten in excess will be stored as fat. Protein is found in high amounts in beans, nuts, eggs, seafood and meat. Protein is essential to health, but eating too much also carries an environmental and health cost. Learn more: http://www.ewg.org/meateatersguide/
Per gram, high in naturally occurring fiber [read more]
Per gram, high in naturally occurring fiber
Fiber is important for overall health and may reduce the risk of cardiovascular disease, obesity and type 2 diabetes. It's also important for healthy bowel function. Fiber may also help to decrease appetite by providing a feeling of fullness. Americans average only 15 grams of fiber a day, much less than the recommended 25 grams for women and 38 grams for men. Good sources of fiber are beans, split peas, fruits, vegetables, whole grains and nuts.
Product has been classified as having no processing concerns
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Ingredient List
From the Package
INGREDIENTS: ALMONDS.
* Older Product
Products remain in the database for two years after their label information is recorded in stores. A product with label information last recorded more than a year ago is marked with an * identifying it as an older product.
* Discontinued Product
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Please note that EWG obtains the displayed images of products from third parties and that the product's manufacturer or packager may change the product's packaging at any point in time. Therefore, EWG assumes no responsibility for the accuracy of images presented.
Other Information
Certified free of genetically engineered ingredients [read more]
Certified free of genetically engineered ingred...
This product is certified or advertises itself to be free of ingredients that were genetically engineered or derived from genetically engineered crops. For more information on the topic visit: http://www.ewg.org/research/shoppers-guide-to-avoiding-ge-food
Note: The presence or absence of genetically engineered ingredients does not affect the score of a product.
Nutrition Facts
16.0 servings per containerServing Size10 z 14.0 g 28.0 g (1x) 42.0 g 56.0 g (2x) 84.0 g (3x) 112.0 g (4x) Amount Per 28 g Calories 160 % Daily Value (based on a 2,000 calorie diet and adult bodyweight) Update the values for someone: -age- 1-3 years 4-8 years 9-13 years 14-18 years 19-30 years 31-50 years 51-70 years over 70 years -gender/life stage- male female pregnant female lactating female goQUICK FACTS: 18.0 18.0 % Total Fat 14 g 2.0 2.0 % Total Carbs 6 g % Protein 6 gAVOID TOO MUCH: 5.0 5.0 % Saturated Fat 1 g Trans Fat 0.0g 0.0 0.0 % Cholesterol 0 mg 0.0 0.0 % Sodium 0 mg Added Sugar Ingredients: none listedNUTRIENTS: 13.0 13.0 % Dietary Fiber 4 g Vitamin D (no value on present label) 6.0 6.0 % Calcium 6.0 6.0 % Iron 4.0 4.0 % Potassium 210 mg† Institute of Medicine. 2010. "Dietary Reference Intakes Tables and Application." Accessed April 8, 2014:link
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Emotional Acumen on the Propensity of Graduating Technology Students to Whistle-Blow About Organizational Cyber Security Breaches: Education Journal Article | IGI Global
Emotional Acumen on the Propensity of Graduating Technology Students to Whistle-Blow About Organizational Cyber Security Breaches: 10.4018/IJSEUS.2018100101: Emotional acumen is relatively a new concept compared to the other decision-making variables in the existing literature. Comprehending the procedure in which
Emotional Acumen on the Propensity of Graduating Technology Students to Whistle-Blow About Organizational Cyber Security Breaches
Nimisha Bhargava, Mani Kumari Madala, Darrell Norman Burrell
Source Title: International Journal of Smart Education and Urban Society (IJSEUS) 9(4)
Copyright: © 2018 |
Pages: 14
DOI: 10.4018/IJSEUS.2018100101
OnDemand: (Individual Articles) Available $29.50
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Abstract Emotional acumen is relatively a new concept compared to the other decision-making variables in the existing literature. Comprehending the procedure in which the individuals captivate themselves in ethical decision-making and the factors stimulating this procedure may be imperative for burgeoning more efficient education for ethics. The U.S. Securities and Exchange Commission issued new guidance calling on public companies to be more forthcoming when disclosing nature and scope of cybersecurity breaches. The statement also warns that corporate insiders must not trade shares when they have information about cybersecurity issues that is not public yet. Understanding the emotional underpinnings is critical to guiding how individuals deal with the complex nature of morally infused predicaments, their awareness of the moral dilemma, judgments about the potential consequences and their intention to act or propensity to whistle-blow related to cybersecurity breaches are significantly affected by the emotional acumen. Article Preview Top IntroductionEmotion is a human existence's alluring facet which articulates delight, adore, love, aggravation, despair, detestation and rage as well. Generally, human beings have hardly any complexity in assessing if someone is articulating cheerfulness, revelation, dread or annoyance just by gazing at an individual's face. Emotions are exclusive to each individual and are generally classified as A) Positive emotions which are filled with yearning for delight, zeal, amusement and unity and as B) Negative emotions are filled with regret, the dread of the unknown and sorrow (Abdullah et al., 2013; Goleman, 2005; Goleman, 2007).The U.S. Securities and Exchange Commission issued new guidance calling on public companies to be more forthcoming when disclosing nature and scope of cybersecurity breaches. The statement also warns that corporate insiders must not trade shares when they have information about cybersecurity issues that is not public yet. This requires that organizations create cultures where employees develop the emotional acumen to act ethically and honestly when it comes to coming forward about wrongdoing or whistleblowing.Developing actionable dexterity in social and emotional intelligence is a critical aspect of developing a high level of emotional and business acumen (Goleman, 2007) The impact of emotional acumen with respect to whistleblowing would be interesting to explore as the emotional acumen is the sharpness or readiness of an individual to perceive a situation. Sharper the ability of a person to perceive a given situation, better will he/she be able to act accordingly, which ultimately means a person becoming smarter about their feelings in a way that is more emotionally and socially intelligent (Rathbone, 2012; Goleman, 2005; Goleman, 2007) Since, the process of whistleblowing involves the ability to thoroughly understand, analyse, decide and accordingly act to any kind of situation which demands justice hence, emotional acumen might play a major role (Burke & Cooper, 2013).Miceli and Near (1992) defined whistleblowing as the disclosure by current or former members of an organization of immoral, illegitimate or illegal practices under the control of the employers, to organizations or persons that might be able to effect action. Some authors have explained whistleblowing is an ethical issue of extreme significance as it protects against the harmful economic, environmental and social impact of multi-national companies entering worldwide markets (Weiss, 2006; Hoffman and Mcnulty, 2010; Courtemanche, 1988). According to Stewart (1996), whistleblowing is considered as a primary instrument for encouraging individual accountability and organizational answerability. Whistleblowing as a phenomenon looks mystifying due to its complex procedure involving personal and organizational factors. Therefore, whistleblowing research is essential for several reasons. The first is because unethical behavior is a continuing problem in a variety of organizations. When individuals. Whistleblowing can have serious consequences, both for the individual whistleblower and for the organization. Whistleblowers often suffer retaliation (Wilde, 2013).
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Energies | Free Full-Text | An Analysis of Circular Economy Literature at the Macro Level, with a Particular Focus on Energy Markets
Sustainability is a strategic approach to develop a more sustainable economy to support the environment and socio-economic development. Literature on sustainability has been concerned mainly with global warming and environmental degradation issues, whereas the Circular Economy (CE) concept has recently been suggested as an alternative solution to support market sustainability and deal with both environmental and socio-economic challenges. In order to tackle these challenges, countries must switch from linear economies that follow the “take-make-dispose” principle to circular and sustainable economies. This study applies a structural and conceptual literature review to elucidate the most decisive determinants in the formation of circular strategies, particularly in the context of the energy sector. This study examines obstacles that hinder CE adoption and formulates drivers and measures to overcome them. The strategic literature review shows that the circular approach is critical in achieving sustainable development. Circularity can be considered a novel and innovative approach to alleviating the contradiction between rapid economic growth and energy and raw materials shortages. The CE structure must be considered as a sustainable foundation to enhance economic growth by avoiding waste, preserving natural capital, managing resource scarcity, recycling materials, maximizing energy efficiency, and recirculating them into the economy. Analysis reveals that the circular system is a key pillar of sustainability, security, and efficiency in the energy sector. The sustainable energy transition requires incorporating the CE principles in the design process. It also revealed that both public and private sectors must move away from the linear paradigm towards circularity to achieve CE implementation.
An Analysis of Circular Economy Literature at the Macro Level, with a Particular Focus on Energy Markets
by Arezoo Ghazanfari
School of Economics, Finance and Marketing, RMIT University, Melbourne, VIC 3000, Australia
Energies 2023 , 16 (4), 1779; https://doi.org/10.3390/en16041779
Received: 22 December 2022 / Revised: 5 February 2023 / Accepted: 8 February 2023 / Published: 10 February 2023
Abstract
Sustainability is a strategic approach to develop a more sustainable economy to support the environment and socio-economic development. Literature on sustainability has been concerned mainly with global warming and environmental degradation issues, whereas the Circular Economy (CE) concept has recently been suggested as an alternative solution to support market sustainability and deal with both environmental and socio-economic challenges. In order to tackle these challenges, countries must switch from linear economies that follow the “take-make-dispose” principle to circular and sustainable economies. This study applies a structural and conceptual literature review to elucidate the most decisive determinants in the formation of circular strategies, particularly in the context of the energy sector. This study examines obstacles that hinder CE adoption and formulates drivers and measures to overcome them. The strategic literature review shows that the circular approach is critical in achieving sustainable development. Circularity can be considered a novel and innovative approach to alleviating the contradiction between rapid economic growth and energy and raw materials shortages. The CE structure must be considered as a sustainable foundation to enhance economic growth by avoiding waste, preserving natural capital, managing resource scarcity, recycling materials, maximizing energy efficiency, and recirculating them into the economy. Analysis reveals that the circular system is a key pillar of sustainability, security, and efficiency in the energy sector. The sustainable energy transition requires incorporating the CE principles in the design process. It also revealed that both public and private sectors must move away from the linear paradigm towards circularity to achieve CE implementation.
Keywords:
circular economy
;
sustainability
;
waste to energy
;
renewable energy
;
energy transition
1. Introduction
Since the 20th century, greenhouse gas emissions have been the primary driver of climate change and global warming, leading to various health and environmental issues. Aside from climate change, air pollution, respiratory diseases, food shortages, and wildfire outbreaks result from climate change caused by greenhouse gases. In light of this, global emissions have caused concern in all economies [ 1 , 2 , 3 ]. Several factors contribute to global emissions, including a sizeable simultaneous surge in population, consumption, and economic growth, which are associated with an increase in resource and land consumption and waste production [ 4 ]. Population growth will increase the demand for natural resources, specifically energy, raw materials, water, and fertile land. Environmental pressure increases dramatically as the demand for these resources grows [ 5 , 6 ]. Humanity’s irreversible effects on the earth could make it impossible for the next generations to enjoy high living standards, primarily due to global warming, biodiversity loss, and land degradation [ 7 ].
Electricity production is one of the sectors contributing significantly to greenhouse gas emissions. Approximately 60% of the world’s electricity is generated from fossil fuels, requiring a gradual shift towards a more secure, sustainable, and accessible energy system. As reported by the International Energy Agency (IEA), over 40% of all energy-related emissions come from electricity generation. Globally, fossil fuels emit approximately 34 billion tonnes of CO 2 annually [ 8 , 9 ].
In order to mitigate environmental threats, countries should adopt green strategies to establish a modern, circular, and sustainable economy. To transition toward a sustainable low-carbon energy system, countries must switch from fossil fuels to renewable energy sources and improve their energy efficiency. Recently, the world has seen an acceleration of ambitions regarding energy transition and decarbonization, particularly in terms of achieving net-zero carbon emission targets. In order to achieve net-zero targets and energy-efficient development, all industries must modify their infrastructures, a process that will require large-scale reconstruction and retrofitting for a very high cost. Energy industries also need to be entirely redesigned and implement new technologies in the process of electricity production or industrial activities (i.e., batteries and solar photovoltaic (PV)). In addition, the linear decarbonization process only focuses on the reduction of emissions from energy production and renewable energy consumption, which are not sufficient to reach net-zero targets. The CE approach is recently on government agendas as an effective means to support sustainability, accelerate decarbonization, and facilitate energy efficiency [
10
]. Therefore, CE approaches are complementary to existing energy and decarbonization policies in enhancing the energy transition toward a clean environment. Creating resources from waste is one of the most effective ways to contribute to sustainable development. To reduce waste and emissions in energy transition policies, policy makers must consider CE principles in their energy transition guidelines.
In terms of energy market perspective and CE strategies, countries have the potential to produce electricity from biomass, biogas, wind, and solar or use energy store systems or portable batteries. New technologies are being developed to generate energy from waste in a circular manner. As traditional technologies and coal-fired power stations are replaced by infrastructures and new technologies, it is essential to apply CE principles to unlock waste’s resource potential and minimize its management challenges. For example, waste-to-energy (WtE) generation technologies have recently emerged and gained increasing attention. WtE technologies utilize waste to generate energy in the form of electricity or heat. Like other power generators that use thermal coal, oil, or solar, WtE plants use waste as a fuel to produce electricity. In these plants, the concept of energy from waste involves converting non-recyclable materials into energy through various methods, including thermal and non-thermal processes (combustion, gasification, landfill gas recovery, and anaerobic digestion). A WtE system contributes to a sustainable and circular economy in various ways. As one of the solutions to increase circularity in the energy sector, we provide an explanation of WtE technologies in this study.
The circular strategy has become one of the most popular research areas from various disciplines and hemispheres in terms of conceptualization, definitions, drivers, metrics, and sustainability. The literature mainly concentrates on specific industries like manufacturing [ 17 , 18 ], construction [ 19 , 20 ], supply chain [ 21 , 22 ], energy [ 23 , 24 ], fashion [ 25 , 26 ], and water industries [ 27 , 28 ]. However, this study goes a step further and examines all aspects of the CE, such as motivations, barriers, technologies, and requirements for switching from a linear to a circular system in the global market and also the energy sector. The aim of this paper is to identify factors that can hamper, encourage, facilitate, or stimulate the transition towards a CE system.
Using a systematic literature review and various perspectives of scientific studies, this paper explains what the circular economy is, why it is essential, what are drivers and barriers, and how it can be accelerated. Unlike the previous literature, which has discussed the background and concept of the CE itself, in this paper we examine current CE progress as well as the steps that need to be taken to accelerate its growth. In the first stage, an in-depth and general analysis is provided of corporate CE approaches and their applicability and transferability to the macroeconomic level across all industries. Then, a particular emphasis is placed on the energy sector to examine the implications of the CE system in the energy sector in terms of decarbonizing electricity generation and utilization, as well as its wider implications. We discuss principal drivers and obstacles to the implementation of CE approaches in a global context as well as in energy markets. We identify how the current scheme of policies could facilitate and incentivize CE measures to complement existing energy policies in order to achieve the full decarbonization target.
This article explores the potential for CE development in all industrial sectors through waste management strategies. Through a combination of literature review and computational models, we identify the main motivations and obstacles to the implementation of CE and propose significant solutions that policymakers and government officials should consider. It is revealed that CE approaches are very critical and effective solutions for economic growth, sustainability, and energy decarbonization, which are beneficial not just for energy markets but also for other industries. It shows that the CE contributes to the reduction of pollution, water acidification, and carbon emissions that ultimately contribute to climate change. Furthermore, this study illustrates how CE strategies can lead to a range of environmental benefits in the energy sector.
It has been discovered that there are many obstacles that have to be addressed in order to establish a circular system that is capable of bringing socio-economic and environmental benefits to the wider economy. There are practical barriers to the CE adoption in economies, including economic and financial obstacles, regulatory policies that are dominantly targeted towards traditional and linear economic models and hence linear decarbonization policies, knowledge barriers, cultural obstacles, and technical limitations. It is interesting to note that obstacles are interconnected. For example, the lack of CE policies reflects a lack of knowledge about the CE concept among regulators and legislators. Alternatively, consumer knowledge and awareness are reflected in regulators’ knowledge. It indicates that all aspects of society can contribute to the adoption and implementation of circular economic systems. Therefore, the first step in the transition from a linear to a circular economy is enhancing social knowledge about the importance and benefits of circularity.
The practical implications of this study can be represented as follows. First, circularity is frequently the subject of research among scientists and professionals. However, CE development requires the involvement of governmental bodies, policymakers, and stakeholders beyond the expert community in order to increase knowledge of CE necessity and its implementation. This paper will stimulate and motivate governmental bodies to invest in circular developments and bio-energy generators to reduce emissions. Second, circularity can be considered as a novel and innovative approach to alleviate the contradiction between rapid economic growth and shortages of energy and raw materials. Third, since eco-circular approaches are developed to enhance efficient resource allocation, CE approaches should remain applicable even once zero-emission targets are achieved. Fourth, we found that waste-to-energy technologies are the best alternative way to generate electricity from waste, which contributes to a sustainable and circular economy in a variety of ways. A waste-to-energy plant can produce electricity, heat, or fuel in the form of renewable and clean energy, resulting in fewer greenhouse gases and a smaller carbon footprint. Fifth, a clear public policy framework should be implemented by evaluating economic strategies, CE perspectives, and decarbonization policies simultaneously.
The remainder of this paper is organized as follows. We discuss the research design and framework of the study in Section 2 . A conceptual analysis of the CE approach is presented in Section 3 . Results are presented and discussed in Section 4 , while the conclusion is summarized in Section 5 .
2. Research Design
This section aims to identify the most relevant studies in the context of the CE. This study is certainly not the first on the topic of circularity, and a great deal of literature has already been published on the transition from a linear to a circular system. Previous studies focused on particular geographic locations or industries. In addition, they only focused on a few of the following concepts: motivations, challenges, technologies, practices, industries, and requirements. However, this study presents a comprehensive overview of all aspects of CE adoption in global markets. Accordingly, this paper aims to delve into the main motivations, obstacles, and requirements in implementing a CE at the macro level, with a particular focus on energy markets.
2.1. Framework of the Literature Review
An integrated systematic review was conducted in this study to evaluate different perspectives of the CE. Systematic reviews help identify trends and changes in a research area and track the evolution of knowledge about a specific topic [ 29 ]. This study is designed to achieve a comprehensive understanding of CE within both the global view and the energy transition concept. Significant objectives of this study are: (1) present a comprehensive review of the CE literature; (2) examine various aspects of circular economies, like advantages/disadvantages, motivations, barriers, and implementations; and (3) provide recommendations and solutions for accreditation of the CE. The framework of the literature review is presented in Figure 1 .
Figure 1. Framework of literature review.
2.2. Literature Review
In the first step, a structured keyword search is conducted across a variety of search engines to improve the reliability of the collected data, including Google Scholar, Science Direct, Willey, JSTOR, Taylor & Francis, PubMed, and IEEE Xplore, Scopus, and Web of Science. It must be noted that Google Scholar is considered the primary web search engine for the literature collection in this study. Other databases are considered for robustness checks to identify all relevant studies. However, Google Scholar provides access to all referenced studies.
Keywords like ‘Circular Economy’, ‘CE’, ‘Circularity’, ‘Circular’, ‘Circular System’, ‘Decarbonization’, ‘Energy’, ‘Renewable Energy’, and ‘Energy Transition’ are investigated. In CE notion, the following keywords are used: ‘Motivation’, ‘Driver’, ‘Advantage’, ‘Disadvantage’, ‘Obstacle’, ‘Barrier’, ‘Practices’, ‘Solution’ and ‘Recommendation’ are jointly found.
Considering the numerous potential benefits of the CE compared with the conventional economy, a large strand of literature has been undertaken to examine various features of the CE across a wide range of contexts. A variety of publications are examined to develop a comprehensive and robust study, including peer-reviewed articles, grey literature, PhD dissertation and books. From 2010 to 2022, more than 900 studies focused on circular economies across different sectors. There has been a particular focus on manufacturing, agriculture, construction, supply chain, energy, fashion, and water industries. These studies mainly focus on some specific areas, which are highlighted in a representative list in
Table 1
, along with some samples of studies. As shown in the table, supply chain, agri-food, energy, fashion, manufacturing, furniture, and water are the main spotlights of CE studies within these sectors.
Table 1. Circular economy literature.
Conducting a systematic literature review commences by determining which publications are worth considering and which should be excluded. More than 349 publications were collected, of which 52 publications are considered relevant to the research objectives since they study different aspects of the CE in the global markets and the energy sector. The division of the studies sheds light on the debate surrounding the CE within the scientific and practitioner communities.
Figure 2
depicts the distribution of studies with a specific focus on circularity from 2010 to 2022. The figure shows that the number of publications in the CE context has increased significantly in the past decade.
Figure 2. Distribution of studies based on publication year, 2010–2022.
Figure 3
presents the main characteristics of the sourced literature, including the most common geographical locations of CE studies and the distribution of literature in the energy sector. The distribution of studies based on geographical locations is presented in
Figure 3
a. As shown, China, European countries, India, Africa, and the United States are the most significant countries considered by scholars. China accounts for the majority of studies; 250 studies have been conducted there (23%).
Figure 3
b displays the contribution of energy studies from 2010 to 2022. Research findings reveal that fewer studies have conceptually examined circularity approaches in energy markets. The number of publications has increased significantly since 2016, indicating a growing interest in CE strategies in the energy sector.
Figure 3. Main characteristics of the literature. Section “ a ” shows the share of studies based on their scope of research, while Section “ b ” shows the number of CE studies in the energy sector.
At the end of the review process, a comprehensive assessment of all collected studies is conducted to find motivations, barriers, and requirements for switching from linearity to the circular economy and presents essential solutions.
3. Conceptual Analysis of Circular Economy
3.1. Global Review of Circular Economy
In the late 1970s, the concept of the CE gained momentum. It was introduced by Kenneth E. Boulding, who first mentioned it as an academic concept in 1966, criticizing linear “cowboy economies” and describing a future “spaceship economy” in which all used resources were redirected back into it [ 13 , 100 ]. The CE, derived from Boulding’s theory, was developed by the environmental economists Pearce and Turner [ 101 ] in which they discuss the lack of markets and prices for environmental goods and emphasize the need to internalize these costs. It is more likely that a transition towards a circular system will occur if these externalities are internalized [ 102 ]. There are several authors, including Andersen [ 103 ], Ghisellini et al. [ 13 ], and Su et al. [ 104 ], who give credit for the introduction of the concept to Pearce and Turner [ 105 ].
Some specific features of CE were introduced by Stahel and Reday [ 106 ], particularly in the field of industrial economics. In their conceptualization, a loop economy is used to describe industrial strategies for preventing waste, creating jobs, efficiently utilizing resources, and dematerializing the industrial system.
As stated by Ghisellini et al. [ 13 ], a circular strategy is an economic structure designed to improve resource efficiency and interaction between the economy, environment, and society. Accordingly, CE can be considered as a novel and innovative approach to alleviating the contradiction between rapid economic growth and shortages of energy and raw materials [ 107 ].
There have been several academic reviews about CE concepts, including those by Andersen [ 103 ], Su et al. [ 104 ], Sassanelli et al. [ 108 ], Kristensen and Mosgaard [ 109 ], De Pascale et al. [ 110 ], and Mhatre et al. [ 111 ]. There has been a particular focus on supply chains, sustainable business models, and circular product design.
The principles of CE are as follows: (1) enhance and preserve natural resources through the management and replenishment of natural capital; (2) make optimal use of materials and resources to maximize value; and (3) eliminate negative externalities from the economic system and lifestyles in order to promote system effectiveness [ 112 , 113 ].
Over the past two decades, the CE has gained momentum among policymakers, influencing national, regional, and local governments, as well as inter-governmental agencies. Germany has been a pioneer in the incorporation of the CE into national laws. In 1996, Germany passed the CE and Waste Management Act (also referred to as the Circular Economy Act or the “KrWG”) that explicitly promoted the concept of CE [ 114 ]. In January 2002, this was followed by Japan, which established a comprehensive legal framework, titled Japan’s 2002 Basic Law, to achieve a recycling-based society [ 104 , 115 , 116 ]. Another country was China, which introduced the “Circular Economy Promotion Law of the People’s Republic of China” in January 2009 [ 117 ]. Figure 4 is a graphical scheme of a cyclical pattern in a circular economy.
Figure 4. Circular economy process.
3.2. Waste to Energy
Millions of tons of waste are constantly produced and dumped in landfills, which adversely affects ecosystems, the environment, and the health of humans and wildlife. New technologies are being developed to generate energy from waste in a circular manner. Waste-to-energy (WtE) is the process that uses waste to generate energy in the form of electricity or heat. Like other power generators that use thermal coal, oil, or solar, WtE plants use waste as a fuel to produce electricity. In these plants, the concept of energy from waste involves converting non-recyclable materials into energy through various methods, including thermal and non-thermal processes (combustion, gasification, landfill gas recovery, and anaerobic digestion). Economies are striving to develop technologies for compressing and disposing of waste while also generating energy from it. The energy that is produced in the form of electricity, heat, or fuel using WTE plants is renewable, clean, and environmentally friendly, producing fewer greenhouse gases and having a limited impact on the environment [
118
,
119
].
Recently, the phenomenon of WtE generation has emerged and gained increasing traction [ 120 , 121 , 122 ]. In developed countries, it is being successfully implemented as a measure of waste management and energy security. Therefore, many countries have started using waste to recover energy [ 123 ]. A WtE system contributes to a sustainable and circular economy in the following ways:
Recovering energy from waste can be significantly beneficial in facilitating energy transition and reaching zero-carbon decarbonization targets;
WtE methods are instrumental to enhance energy security, reduce reliance on fossil fuels, and generate clean and reliable sources of thermal energy, electricity, and fuels;
Implementing a sustainable framework with no contradiction with existing decarbonization measures;
One of the most effective approaches to enhance the efficiency of power generation and energy consumption through waste incineration operations;
Recovery of secondary raw materials from incineration residues;
Delivering a hygienic service to society through municipal waste management and the treatment of combustible non-recyclable waste.
Let us examine how waste to energy is currently applied worldwide. Figure 5 shows the generating capacity of power plants that use renewable energy sources to produce electricity. As presented in Figure 5 , the amount of electricity generated by waste globally increased from 2012 to 2021, with Europe, Asia, and North America generating the most electricity from biogas, bioenergy, renewable municipal waste, and solid biofuels.
Figure 5. Electricity generated by type of waste renewable energy. Source of Data: International Renewable Energy Agency (IRENA) [ 124 ], Figures “ a ”, “ b ”, “ c ” and “ d ” show the generating capacity of power plants using bioenergy, biofuels, renewable waste, and biogas, respectively.
Despite the growing application of renewable energy and waste in electricity generation in the last decade, fossil fuel is still the primary source of energy.
Figure 6
illustrates the level of different types of fuels employed to generate electricity. It is evident that there is a significant difference between renewable energy (including waste energy) and high-carbon fuels. In 2021, nuclear power and renewable energy generated more than one-third (36.7%) of global electricity. As for waste energy, it contributed only 3%, which is a very small percentage. Therefore, countries should pay significant attention to waste resources to generate electricity in order to repurpose waste in a positive way and also diminish coal-fired generator emissions.
Figure 6. Global electricity production by source of fuel. Source of Data: International Renewable Energy Agency (IRENA) [ 124 ].
4. Result and Discussion
4.1. Drivers and Barriers
This study examines opportunities and barriers to implementing a CE to develop research agendas. Following a review of the literature, several factors have contributed to or prevented a CE, ranging from arguably the “hardest” (technical, economic) to the “softest” (social, institutional) factors. The “drivers/opportunities” are aspects that stimulate and facilitate transitions towards the CE system, while “barriers/obstacles” hinder progress.
4.1.1. General Circular Economy Drivers
The first step to examining the drivers of CE implementation is to identify and understand the motivational factors. Table 2 illustrates these drivers. We have categorized these drivers based on their similarities and definition. Motivational factors and drivers are based on a review of previous literature, including studies undertaken by Pitt and Heinemeyer [ 125 ], Ghisellini et al. [ 113 ], Lieder and Rashid [ 117 ], Govindan and Hasanagic [ 6 ], Prieto-Sandoval et al. [ 126 ], Cramer [ 127 ], Ranta et al. [ 128 ], De Jesus and Mendonça [ 129 ], Tura et al. [ 130 ], Salim et al. [ 131 ], Agyemang et al. [ 132 ], Gusmerotti et al. [ 133 ], Jabbour et al. [ 134 ], Dijkstra et al. [ 135 ], Jia et al. [ 136 ], Aloini et al. [ 137 ], Neves and Marques [ 138 ], and Neligan et al. [ 139 ].
Table 2. CE drivers at global market.
4.1.2. Circular Economy Drivers in Energy Sector
The purpose of this section is to present potential drivers of the circular pathway in the energy sector, which are presented below [ 140 , 141 , 142 , 143 , 144 , 145 ]:
Sustainable energy production—WtE systems that convert waste materials into energy contribute to the transition to a circular economy. In addition to producing a sustainable energy market, these technologies can reduce environmental and health risks associated with waste;
Conservation of critical materials—the energy transition will require a shift towards renewable energies by shifting away from fossil fuels towards wind, hydro, solar, and geothermal power or zero-emission technologies supported by batteries. However, the transition to green technologies will lead to a massive demand for minerals like lithium, cobalt, and rare minerals. As IEA [ 146 ] reported, achieving the net-zero target by 2040 will require a six-fold increase in mineral input. There could be requirements of more than a 40-fold increase for some critical metals, such as lithium, and over 20-fold for nickel and cobalt. Extraction and mining are the only ways to obtain these materials, which are hazardous to the environment and human health. Moreover, these metals are discovered in relatively small concentrations that are tough to extract, resulting in a more expensive and time-consuming extraction process than other minerals. Through the transition to a CE, economies are capable of recycling these materials from millions of tons of electronic devices like laptops, hard drives, batteries, and other devices. Therefore, it allows countries to eliminate their dependence on mining metals and extend existing materials’ lifespan using circular pathways;
Economic development—the combination of circular systems and energy production can lead to economic and ecological improvements. In the production of metals, energy, foods, and other types of products, circular production reduces emissions and energy requirements. By doing so, money can be saved, emissions reduced, and energy production and consumption are decreased. Thus, economies will be less dependent on critical materials because they will be able to recycle them. As a result, a circular and efficient energy market can contribute to economic growth;
Environmental drivers—greenhouse gas emissions can be reduced through the use of new technologies and the efficient use of waste materials, such as biogas and biomass;
The efficient use of materials—circular economies and recycling technologies allow countries to recycle and reuse 95% of the critical materials, such as aluminium, steel, glass, copper, etc. Therefore, all metals used in batteries (i.e., lithium, nickel, and cobalt) can be recycled. The result is an increase in battery production and a decrease in coal-fired generation units;
Waste reduction—the waste disposal process includes five steps: waste transfer, landfill, incineration, waste compaction, and composting. It is both highly harmful to the environment and health and extremely expensive. By using waste resources for energy generation, economies can reduce waste disposal costs and generate electricity, which is vital for human life;
Reduction of fossil fuel consumption—WtE facilities instead of coal-fired plants can save over 200,000 barrels of coal per year;
Material efficiency—material efficiency developments could offer a valuable alternative solution to current decarbonization policies along with renewable energy use and energy efficiency. By incorporating CE systems into material production, energy consumption can be reduced, thereby reducing greenhouse gas emissions (GHG);
Battery recycling—for developing technologies and business models, recycling different types of batteries is placed at the top of the pyramid, and extensive research and development is being conducted, leading to a revolution in circular economies.
4.1.3. General Circular Economy Barriers
Implementing a CE would require fundamental changes in industrial practices and consumption patterns, especially in heavy industries and resource production areas, leading to significant obstacles. In recent years, several publications have developed around barriers that have restricted CE implementation. In order to implement a CE system, we must overcome a number of obstacles that can be classified into the following segments: economic and financial obstacles; knowledge barriers; political challenges; technical roadblocks; cultural obstacles; and regulatory barriers. In this section, we provide a general overview of potential barriers to CE adoption in global economies as well as energy markets, which are presented in Table 3 . They are based on studies undertaken by Govindan and Hasanagic [ 6 ]; Bet et al., 2018 [ 7 ]; Grafström and Aasma [ 102 ]; Ranta et al. [ 128 ]; de Jesus and Mendonça [ 129 ]; Cramer [ 127 ]; Salim et al. [ 131 ]; Agyemang et al. [ 132 ]; Geng et al. [ 147 ]; Xue et al. [ 148 ]; Zhu and Geng, 2013 [ 149 ]; Vanner et al. [ 150 ]; Bicket et al. [ 151 ]; Gumley [ 152 ]; Rizos et al. [ 153 ]; Rizos et al. [ 154 ]; Böttcher and Müller [ 155 ]; Ilić and Nikolić [ 156 ]; Pheifer, 2017 [ 157 ]; Mont et al. [ 158 ]; Wildschut [ 159 ]; Hart et al. [ 160 ] and Jabbour et al. [ 161 ].
Table 3. Barriers to the CE implementation in global markets.
4.1.4. Barriers to the CE Acceptance in Energy Industries
The CE strategies are evidently of great importance in the energy market and can have a significant impact on energy transition and decarbonization. While CE creates a variety of benefits and opportunities for the energy market, CE implementation is hampered by a number of practical obstacles that prevent entrepreneurs and policymakers from taking advantage of them. A number of these barriers are outlined below:
Government regulations—the current economic policies and regulations are predominantly based on linear economic models, not circular pathways, in energy markets. As a result, there is less governmental support for the CE adoption in the energy sector;
Consumer behavior—the level of energy embodied in products is significantly impacted by decisions made by consumers in all types of situations (individuals, industries, and governments) and is capable of reducing energy demand. Accordingly, decisions made by consumers play an important role in the development of circular economies. However, a reverse condition exists, and consumer attitudes and demands are major barriers to the CE implementation. Energy efficiency, environmental protection, recycling, and circular systems are not well known by the general public [ 162 , 163 ];
Energy transition—in today’s world, climate change, global warming, and health problems caused by greenhouse gases are the major issues. As a result, political attention has shifted to the green energy transition nationally and internationally. Accordingly, the political, governmental, and energy authorities focus mainly on the green energy transition. There is a struggle among governments to involve the public and businesses in this transition. Therefore, the circular transition receives less attention from the government and entrepreneurs in energy markets;
Emphasis on renewable energy—energy transition refers to the transition from traditional fossil-fuel-based energy production and consumption systems to renewable energy sources. As a result, the primary focus of research is to develop renewable systems, energy sustainable technologies, and renewable generations. Consequently, there is a lack of knowledge and awareness about circular systems in energy markets;
Lack of battery recycling technologies—developing long-life batteries plays a crucial role, specifically in the energy and transportation sectors. A wide range of batteries are designed for energy storage systems and electric vehicles. Lithium-ion batteries are likely to play a major role as they are widely used in electronic devices (i.e., mobile phones, laptops, digital cameras) and electric vehicles (EVs). However, the energy sector faces a new challenge with the development of batteries, which is battery recycling;
Batteries consist of hazardous materials that can be classified as hazardous waste [ 164 ]. Most batteries are composed of toxic materials such as lead, cadmium, mercury, nickel, or copper, which are all hazardous to human health and the environment and pose a threat to water sources and ecosystems if they leach out of landfills [ 165 , 166 ]. However, most batteries are not properly recycled, especially lithium-ion batteries, which are expensive and difficult to recycle. The number of lithium-ion batteries being recycled is still relatively low due to the cost of recycling and the immaturity of recycling processes. These batteries have been designed and manufactured in ways that make it difficult to repair, remanufacture, or recycle them. As a result, two key issues arise here: (1) lack of recycling technologies in battery industries; (2) as material markets fluctuate, it can be difficult to achieve economic efficiency in battery recycling;
Lack of recycling infrastructure for wind energy markets—millions of tons of composite materials have recently been used in the world wind energy sector and construction of wind turbine blades such as glass fiber, composite materials, fiber, resin, wood, foam, adhesives, coatings, copper, and steel. The recycling infrastructure for turbine blade materials is still under development, requiring further research and implementation. For such materials, recycling infrastructures have not yet been established, studies about end-of-life treatment technologies remain in the developmental stage, and there are no secondary markets for recycled materials [ 167 ];
In light of the global transition towards sustainable and green environments, biofuels would be a good step toward a cleaner pathway. Compared with petroleum-based fuels, biofuels come from renewable resources and often produce cleaner emissions than fossil fuels. However, water, land, forests, and fertilizers required for sufficient biofuel production may result in other issues, such as food crisis, water depletion, contamination of lands, deforestation, fertilizer-related pollutants, and other environmental risks [ 168 , 169 ].
4.2. Recommendations and Solutions
By considering the economic and political aspects of CE implementation, various approaches can be taken to address the challenges and promote the solutions outlined in Table 4 .
Table 4. Recommendations and solutions.
To address the lack of framework discussed previously in the barrier section, economic strategies, CE perspectives, and decarbonization policies must be evaluated simultaneously in order to establish a clean energy-based economy that targets economic growth. The recommendations and mentioned policies are imperative solutions for CE adoption and can create a sustainable and essential framework for economies and industries to move from a linear to a circular system.
5. Conclusions
Sustainability is a strategic approach to develop a more sustainable global economy to support the environment and socioeconomic development. Literature on sustainability has been concerned mainly on global warming and environmental degradation issues, whereas a CE concept has recently been suggested as an alternative solution to support market sustainability and deal with both environmental and socioeconomic challenges. To tackle these challenges, countries must switch from linear economies that follow the “take-make-dispose” principle to circular and sustainable economies. The CE approach focuses on the transformation of waste into resources and linking production with consumption activities. In spite of the CE importance in all economies, this area of research has received little attention. The aim of this study is to uncover the most important determinants of circular strategies from a global economic perspective through a structural and conceptual literature review. The study examines barriers to the CE adoption and proposes drivers and measures to overcome them.
In terms of energy, recent years have seen an acceleration of ambitions regarding energy transition and decarbonization, particularly in terms of achieving net-zero carbon emission targets. For net-zero targets and energy efficient development, all sectors, primarily the energy industry, will need to modify their infrastructures, a process that will require extensive reconstruction and retrofitting at high costs. Furthermore, the linear decarbonization process focuses only on reducing emissions from energy production and renewable energy consumption, which are not sufficient to achieve net-zero emissions. Recently, the CE approach has been gaining attention as a means to accelerate decarbonization and facilitate energy efficiency. Therefore, CE approaches are complementary to existing energy and decarbonization policies in promoting energy transitions toward a cleaner environment. Circularity emphasizes the transformation of waste into resources. Nowadays, recycling materials and waste in an efficient manner are imperative to maintain a sustainable environment. Accordingly, this paper aims to analyze various aspects related to implementing the CE approaches at the macro and energy levels.
A systematic literature review indicates that circularity is an essential strategy to attain sustainable development. The CE structure should be considered a sustainable framework to enhance economic growth by reducing waste, protecting natural resources, managing resource scarcity, recycling materials, improving energy efficiency, and recirculating them into the economy. Findings reveal that the circular system is a key pillar of sustainability, security, and efficiency in the energy sector.
In terms of the energy concept, the study concluded that the integration of CE approaches in economies through coherent public policy approaches must be considered as an essential component of existing decarbonization instruments, since they are capable of both increasing efficiency and decarbonizing during the energy transition. Embedding the CE principles into the design process is essential for the sustainable energy transition. It also found that both the public and private sectors need to move away from linear paradigms to achieve CE implementation. From a technological perspective, countries have the potential to produce electricity from biomass, biogas, wind, and solar, or use energy store systems or portable batteries. As traditional technologies and coal-fired power stations are replaced by infrastructures and new technologies, it is essential to apply CE principles to unlock waste’s resource potential and minimize its management challenges. As an example, WtE generation technologies contribute to a sustainable and circular economy in various ways. These technologies utilize waste to generate energy in the form of electricity or heat. A WtE system contributes to a sustainable and circular economy in various ways.
It has been discovered that there are major barriers that need to be overcome in order to create a circular economy that is capable of bringing socio-economic and environmental benefits to the wider economy. There are practical barriers to the CE adoption in economies, including economic and financial obstacles, regulatory policies that are dominantly targeted towards traditional and linear economic models and hence linear decarbonization policies, knowledge barriers, cultural obstacles, and technical limitations. It is interesting to note that obstacles are interconnected. For example, the lack of CE policies reflects a lack of awareness and knowledge about the CE concept among the regulatory authorities. On the other hand, the levels of knowledge and awareness of consumers are reflected in regulators’ knowledge levels. It indicates that all aspects of society can contribute to adopting and implementing circular economic systems. Therefore, the first step in the transition from a linear to a circular economy is enhancing social knowledge of the CE necessity. In addition, economic strategies, CE perspectives, and decarbonization policies must be evaluated simultaneously in order to address obstacles and implement a clear public policy framework.
According to the findings, circularity is frequently the subject of research among scientists and professionals. However, the CE development requires the involvement of governmental bodies, policymakers, and stakeholders beyond the expert community to surge knowledge of the necessity of CE and its accomplishment. Circularity can be considered as a novel and innovative approach in alleviating the contradiction between the rapid economic growth and shortages of energy and raw materials. This paper will stimulate and motivate governmental bodies to invest in circular developments and bio-energy generators to reduce emissions. Moreover, since eco-circular approaches are developed to enhance efficient resource allocation, CE approaches should remain applicable even once zero-emission targets are achieved.
Funding
This research received no external funding.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Framework of literature review.
Figure 2. Distribution of studies based on publication year, 2010–2022.
Figure 3. Main characteristics of the literature. Section “ a ” shows the share of studies based on their scope of research, while Section “ b ” shows the number of CE studies in the energy sector.
Figure 4. Circular economy process.
Figure 6. Global electricity production by source of fuel. Source of Data: International Renewable Energy Agency (IRENA) [ 124 ].
Table 1. Circular economy literature.
Industry Sample of Publications Supply Chain De Angelis et al., 2018 [ 30 ]; Farooque et al., 2019 [ 31 ]; Hussain & Malik, 2020 [ 32 ]; Kumar et al., 2021 [ 33 ] Agri-food Toop et al., 2017 [ 34 ]; Esposito et al., 2020 [ 35 ]; Gkountani et al., 2021 [ 36 ]; Liu et al., 2021 [ 37 ] Energy van Leeuwen et al., 2018 [ 38 ]; Priyadarshini & Abhilash, 2020 [ 39 ]; Holmberg & Ideland, 2021 [ 40 ] Fashion & Textiles de Aguiar et al., 2021 [ 41 ]; Radhakrishnan, 2021 [ 42 ]; Chen et al., 2021 [ 43 ] Manufacturing Paletta et al., 2019 [ 44 ]; Acerbi & Taisch, 2020 [ 45 ]; Badhotiya et al., 2022 [ 46 ] Furniture & Wood Susanty et al., 2020 [ 47 ]; Hartini et al., 2021 [ 48 ]; Paul et al., 2022 [ 49 ] Water Ayçin & Kayapinar Kaya, 2021 [ 50 ]; Liu et al., 2021 [ 51 ]; Salminen et al., 2022 [ 52 ] Plastic Simon, 2019 [ 53 ]; Guyot Phung, 2019 [ 54 ]; Alvarez-Risco et al., 2020 [ 55 ] Public Klein et al., 2020 [ 56 ], Barreiro-Gen & Lozano, 2020 [ 57 ]; Droege et al., 2021 [ 58 ] Automotive Saidani et al., 2018 [ 59 ]; Kayikci et al., 2021 [ 60 ]; Sopha et al., 2022 [ 61 ]; Baldassarre et al., 2022 [ 62 ] Construction Jones and Comfort, 2018 [ 63 ]; Bilal et al., 2020 [ 64 ]; Hjaltadóttir & Hild, 2021 [ 65 ]; Giorgi et al., 2022 [ 66 ] Tourism Brightley, 2017 [ 67 ]; Falcone, 2019 [ 68 ]; Vatansever et al., 2021 [ 69 ]; Kazancoglu et al., 2021 [ 70 ] Mining Kinnunen & Kaksonen, 2019 [ 71 ]; Singh et al., 2020 [ 72 ]; Gedam et al., 2021 [ 73 ]; Luthra et al., 2022 [ 74 ] Electronic Gama et al., 2016 [ 75 ]; O’Connor et al., 2018 [ 76 ]; Curtis et al., 2021 [ 77 ]; Rizos & Bryhn, 2022 [ 78 ] Coffee Van Keulen & Kirchherr, 2021 [ 79 ]; Pires, 2022 [ 80 ] Leather Moktadir et al., 2020 [ 81 ]; Karuppiah et al., 2021 [ 82 ]; Cabrera-Codony et al., 2021 [ 83 ] Logistics Van Buren et al., 2016 [ 84 ]; Dutta et al., 2021 [ 85 ]; Gupta & Singh, 2021 [ 86 ] Finance Hassan et al., 2020 [ 87 ]; Gonçalves et al., 2022 [ 88 ] Medical MacNeill et al., 2020 [ 89 ]; Kandasamy et al., 2022 [ 90 ] Maritime Laso et al., 2018 [ 91 ]; Milios et al., 2019 [ 92 ]; Okumus et al., 2022 [ 93 ] Aerospace Stavileci & Andersson, 2015 [ 94 ]; Brennan & Vecchi, 2020 [ 95 ]; Dias et al., 2022 [ 96 ] Cosmetic Fortunati et al., 2020 [ 97 ]; Lourenço-Lopes et al., 2020 [ 98 ]; Morea et al., 2021 [ 99 ]
Table 2. CE drivers at global market.
Factor Drivers Environmental Developing a circular and sustainable economy is a strategic approach to protecting the environment through waste reduction. CE has the potential to increase the availability and efficiency of resources. Technical New technologies that facilitate resource optimisation, re-manufacturing and re-generation of products. The potential to improve existing operations. Economic-Financial To increase profits and market share, industries would adopt CE initiatives that have the potential to reduce costs, boost efficiency, generate new revenue streams, and improve profitability. Through CE, industries can reduce production waste, that can boost profit margins, enhance customer loyalty, entice new customers, and boost investment return. Increasing the long-term revenue generation by recycling activities. There is potential for entrepreneurship, innovation, business development, and synergistic relationships. CE’s potential for economic development and job creation goes beyond profit margins and cost savings. Institutional-Regulatory Developing regulations and standards associated to recycling and circular economy. Establishing rules and standards by government authorities to support and promote more sustainable production and the use of recycled products. End-of-life management policies to protect resources, safety, health, and environment. Through support funds, credits, and loans, the government can assist enterprises in transitioning from linear to circular pathways. Social-Cultural Creating a country with minimal waste-related health and environmental problems is a desired goal of governments and societies. CE has the potential to alleviate landfill, solid waste, and emissions by performing functions that include reusing, reprocessing, and recycling waste. Increasing global awareness of sustainability that is connected to social awareness, environmental literacy, and shifting consumer preferences (e.g., from ownership of assets to services models). Consumers are empowered to make environmentally responsible decisions. By increasing consumer awareness of the environmental impact of their purchasing decisions, waste can be significantly reduced. Health Traditional economies dump substantial amounts of the waste directly or indirectly into the environment, posing a threat to animal and human health. Shifting from a linear to a circular pathway will provide ample opportunity to improve health. The development of circular products with minimal environmental impacts can reduce greenhouse gas emissions and preserve ecosystems. Supply-chain A reduction in supply dependence and the prevention of high and volatile prices are potential advantages. Resources and capabilities are more readily available due to multidisciplinary. Organizational Potential for differentiation and strengthening the company brand. Enhancing knowledge about the demands of sustainability. The circular strategy is integrated into the company’s strategy and goals. Increasing the level of knowledge, skills and capabilities for the CE.
Table 3. Barriers to the CE implementation in global markets.
Classifications Obstacles Economic & Financial Obstacles Large capital requirements, high initial costs and uncertain return/profit—CE processes are expensive, so they are not widely adopted. Economies must bear significant up-front costs and risks in the short term—e.g., upgrading machinery, relocating, and shifting factories, creating new distribution and logistics systems, recruiting skilled and professional employees, and training staff. Developing a strong business case will be necessary before transforming a country’s economy toward a CE. Lack of financial support and tax incentives—the CE Adoption is hampered by financial barriers, difficulties in funding CE business models, and high up-front investment costs. Knowledge Barriers Lack of knowledge that is necessary as a part of the transition towards a circular economy. In order to switch from linear to circular, it is necessary for us to know how and what the necessary steps are. However, given the novelty, complexity, and disruptive nature of the CE, it appears that people lack the proper knowledge. The lack of awareness of the benefits of circular economies has been identified as a barrier to implementing circularity. Following a review of the literature, knowledge gaps have been determined based on five aspects: relatability, transition, validation, product life-cycle analysis, and awareness. Political Obstacles Lack of knowledge about circularity in the energy sector—due to the political pressure on ending fossil fuel use and raising green energies consumption, researchers are developing more cost-effective methods for generating and distributing renewable energy. However, governmental authorities and political parties face challenges in involving citizens and businesses in the transition toward renewable energy by focusing on the CE in the energy sector. In consequence, the circular transition does not receive much political attention. Technical Barriers Lack of technical support and training about the CE concept. A shortage of qualified and technical labour forces. Lack of data and information. Infrastructure and development models that require many resources—the traditional model relies on massive growth in industry and infrastructure that is resource-intensive. It is clear that emerging economies require a less resource-intensive development model, but there are no ready-made options. Lack of IT-based measures and monitoring systems—even though specific waste detection software exists, it has not reached every business or has not been used because waste stream data are scarce. Moreover, IT systems are essential for a transition from a physical-goods-based economy to a service-based economy and a less resource-intensive immaterial economy. Cultural Barriers Cultural challenges—cultural barriers concern aspects of the social, behavioural, and managerial contexts where the CE needs to develop, including the entrenched nature of the linear economy; ownership and status perspectives; and silo mentality. Lack of consumer interest/awareness—the principles of the CE are not yet well known in society. Lack of interest, knowledge, skills, and engagement throughout the value chain by suppliers, customers, and internal is a core cultural barrier to engage with the CE adoption and collaboration in the value chain. Insufficient demand in the market for recycled, remanufactured, or reused products. Hesitant company culture—lacking policies in support of a CE transition and obstructions in laws and regulations of economies. Regulatory Barriers Lack of regulatory support—the absence of policies in support of the CE transition and obstructions in laws and regulations of economies could pose substantial obstacles to transferring from linearity to circularity in economies. A lack of policies, taxes, and subsidies that support the transition to CE—the government support and financial aid supporting linear production methods pose major obstacles to improving the financial competitiveness of a CE.
Table 4. Recommendations and solutions.
Groups Recommendations Political Policies relating to renewable energies should be sustainable from an environmental perspective. Biofuels must contribute positively to lowering CO 2 emissions, protecting water and land resources from depletion and contamination, and protecting the environment. Subsidies to encourage excessive resource consumption should be eliminated, and all ‘externals’ should be incorporated into energy and resource prices for the market to respond effectively. Governments should prohibit producing biofuels that jeopardise the supply of food and crops essential for animal feed and humans. In addition, importers and exporters of biofuels should be aware of and follow all environmental laws and biofuel standards. Biofuel regulations must be aligned with food security policies that protect poor and food-insecure economies. In particular, there should be a focus on the challenges caused by rising food prices in countries heavily reliant on imported foods, particularly among developing countries and vulnerable rural consumers. Financial The implementation and development of CE programs require financial resources, which means companies need access to a variety of funding options. The most effective way to lead industries towards a CE is through collaboration within the industry value chains as well as establishing financial instruments for investment across all industrial chains at the macro level rather than in a single industry. Consequently, risks and profits can be distributed, and collaboration opportunities can arise to establish a circular economy that is profitable for all sectors. Technology Implement circular design principles to make future energy infrastructure more durable, repairable, and recyclable. Political Governments play a critical role in facilitating the transition towards circularity, and insufficient regulations and policies substantially impact the transition from a linear economy to a circular one. As a result, it can be argued that a progressive legal framework and thoughtful principles could facilitate CE adoption. Implementing transparent, robust, and predictable policy frameworks will encourage investments by industries in CE systems. Governments and policymakers must accelerate the transition to CE approaches while addressing global challenges like climate change and water scarcity. These include legislative measures as well as voluntary actions by stakeholders. In order to optimize the treatment and management of resources and waste streams, policy gaps and market barriers must also be addressed. Economies must refrain from dumping unsuitable technologies in third-world countries and exporting machinery and equipment to countries with inadequate waste-management strategies. Production Resource-efficient manufacturing practices and optimal logistics approaches must be integrated into all industrial policies. Decommissioned equipment can be remanufactured and reused by industries for lower-tier applications. Social A positive public perception of sustainable practices has a large influence on their behavior, which can motivate industries to revise their business models to promote circularity. In spite of this, due to the relative novelty of CE practices and the existence of linear economic systems in most industries, there is a lack of education relating to CE practices. Given that CE is a novel concept, companies tend to avoid high risks by taking small, safe steps rather than undertaking a complete transformation toward circular approaches. In order to embrace both individuals and industries about circular economic system, knowledge and comprehension need to be cultivated. Through education and media coverage, governments can increase public awareness of circular economies. Waste Recycling Implement a waste management plan for end-of-life infrastructure by adopting appropriate processing methods. The number of materials and components that can be recycled should be maximized in order to generate secondary raw materials for new energy infrastructures and other manufacturing sectors.
Chicago/Turabian Style
Ghazanfari, Arezoo. 2023. "An Analysis of Circular Economy Literature at the Macro Level, with a Particular Focus on Energy Markets" Energies16, no. 4: 1779.
https://doi.org/10.3390/en16041779
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here .
Article Metrics
Chicago/Turabian Style
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here .
| https://www.mdpi.com/1996-1073/16/4/1779/html |
TOLSURA Loss of Exclusivity (LOE). When do the patents on TOLSURA expire, and when will TOLSURA go generic?
TOLSURA patent expiration dates, news, international patents, generic entry, and litigation and lawsuits
TOLSURA Drug Patent Profile
Which patents cover Tolsura, and when can generic versions of Tolsura launch?
Tolsurais a drug marketed byMayne Pharmaand is included in one NDA. There are six patents protecting this drug.This drug hasthirty patent family membersin twelve countries.The generic ingredient in TOLSURA is itraconazole. There are fifteendrug master file entriesfor this compound. Twentysuppliersare listed for this compound. Additional details are available on theitraconazoleprofile page.
DrugPatentWatch ® Litigation and Generic Entry Outlook for Tolsura
A generic version of TOLSURA was approved as itraconazoleby SANDOZ on May 28 th, 2004.
Summary for TOLSURA
International Patents: 30 US Patents: 6 Applicants: 1 NDAs: 1 Finished Product Suppliers / Packagers : 1 Clinical Trials : 1 Formulation / Manufacturing : see details Drug Prices : Drug price information for TOLSURA What excipients (inactive ingredients) are in TOLSURA? TOLSURA excipients list DailyMed Link: TOLSURA at DailyMed
Recent Clinical Trials for TOLSURA
Identify potential brand extensions & 505(b)(2) entrants
Sponsor Phase Mayne Pharma International Pty Ltd Phase 2 George R Thompson Phase 2
Pharmacology for TOLSURA
Drug Class Azole Antifungal Mechanism of Action Breast Cancer Resistance Protein Inhibitors Cytochrome P450 3A4 Inhibitors P-Glycoprotein Inhibitors
Anatomical Therapeutic Chemical (ATC) Classes for TOLSURA
J02AC Triazole and tetrazole derivatives J02A ANTIMYCOTICS FOR SYSTEMIC USE J02 ANTIMYCOTICS FOR SYSTEMIC USE J Antiinfectives for systemic use
US Patents and Regulatory Information for TOLSURA
TOLSURA is protected by six US patents.
Patents protecting TOLSURA
Itraconazole compositions and dosage forms, and methods of using the samePatent Number: ⤷ Try a TrialPatent Expiration: ⤷ Try a TrialPatented Use: TREATMENT OF FUNGAL INFECTIONS, INCLUDING BLASTOMYCOSIS, HISTOPLASMOSIS, AND ASPERGILLOSIS
Itraconazole compositions and dosage forms, and methods of using the samePatent Number: ⤷ Try a TrialPatent Expiration: ⤷ Try a Trial
Pharmaceutical compositions for poorly soluble drugsPatent Number: ⤷ Try a TrialPatent Expiration: ⤷ Try a Trial
Itraconazole compositions and dosage forms, and methods of using the samePatent Number: ⤷ Try a TrialPatent Expiration: ⤷ Try a Trial
Itraconazole compositions and dosage forms, and methods of using the samePatent Number: ⤷ Try a TrialPatent Expiration: ⤷ Try a Trial
Itraconazole compositions and dosage forms, and methods of using the samePatent Number: ⤷ Try a TrialPatent Expiration: ⤷ Try a TrialPatented Use: TREATMENT OF FUNGAL INFECTIONS, INCLUDING BLASTOMYCOSIS, HISTOPLASMOSIS, AND ASPERGILLOSIS
Show 10 25 50 100 entries
Applicant Tradename Generic Name Dosage NDA Approval Date TE Type RLD RS Patent No. Patent Expiration Product Substance Delist Req. Exclusivity Expiration Search Applicant Search Tradename Search Generic Name Search Dosage Search NDA Search Approval Date Search TE Search Type Search RLD Search RS Search Patent No. Search Patent Expiration Search Product Search Substance Search Delist Req. Search Exclusivity Expiration Mayne Pharma TOLSURA itraconazole CAPSULE;ORAL 208901-001 Dec 11, 2018 RX Yes Yes ⤷ Try a Trial ⤷ Try a Trial Y ⤷ Try a Trial Mayne Pharma TOLSURA itraconazole CAPSULE;ORAL 208901-001 Dec 11, 2018 RX Yes Yes ⤷ Try a Trial ⤷ Try a Trial Y ⤷ Try a Trial Mayne Pharma TOLSURA itraconazole CAPSULE;ORAL 208901-001 Dec 11, 2018 RX Yes Yes ⤷ Try a Trial ⤷ Try a Trial ⤷ Try a Trial Mayne Pharma TOLSURA itraconazole CAPSULE;ORAL 208901-001 Dec 11, 2018 RX Yes Yes ⤷ Try a Trial ⤷ Try a Trial Y ⤷ Try a Trial Mayne Pharma TOLSURA itraconazole CAPSULE;ORAL 208901-001 Dec 11, 2018 RX Yes Yes ⤷ Try a Trial ⤷ Try a Trial Y ⤷ Try a Trial Mayne Pharma TOLSURA itraconazole CAPSULE;ORAL 208901-001 Dec 11, 2018 RX Yes Yes ⤷ Try a Trial ⤷ Try a Trial Y ⤷ Try a Trial >Applicant >Tradename >Generic Name >Dosage >NDA >Approval Date >TE >Type >RLD >RS >Patent No. >Patent Expiration >Product >Substance >Delist Req. >Exclusivity ExpirationSubscribe to access the full database, orTry a Trial
Showing 1 to 6 of 6 entries
EU/EMA Drug Approvals for TOLSURA
Company Drugname Inn Product Number / Indication Status Generic Biosimilar Orphan Marketing Authorisation Marketing Refusal Search Company Search Drugname Search Inn Search Product Number / Indication Search Status Search Generic Search Biosimilar Search Orphan Search Marketing Authorisation Search Marketing Refusal Avimedical B.V. Fungitraxx itraconazole EMEA/V/C/002722 For the treatment of aspergillosis and candidiasis in companion birds, Authorised no no no 2014-03-12 >Company >Drugname >Inn >Product Number / Indication >Status >Generic >Biosimilar >Orphan >Marketing Authorisation >Marketing RefusalSubscribe to access the full database, orTry a Trial
Showing 1 to 1 of 1 entries
International Patents for TOLSURA
See the table below for patents covering TOLSURA around the world.
Country Patent Number Title Estimated Expiration Search Country Search Patent Number Search Title Search Estimated Expiration Australia 2331801 ⤷ Try a Trial Australia 2020217438 Itraconazole compositions and dosage forms, and methods of using the same ⤷ Try a Trial European Patent Office 1239831 COMPOSITIONS PHARMACEUTIQUES AMELIOREES POUR MEDICAMENTS PEU SOLUBLES (IMPROVED PHARMACEUTICAL COMPOSITIONS FOR POORLY SOLUBLE DRUGS) ⤷ Try a Trial Mexico 366829 COMPOSICIONES Y FORMAS DE DOSIFICACION DE ITRACONAZOL Y METODOS DE USO DE LAS MISMAS. (ITRACONAZOLE COMPOSITIONS AND DOSAGE FORMS, AND METHODS OF USING THE SAME.) ⤷ Try a Trial Spain 2398643 ⤷ Try a Trial World Intellectual Property Organization (WIPO) 2013192566 ⤷ Try a Trial >Country >Patent Number >Title >Estimated ExpirationSubscribe to access the full database, orTry a Trial
Showing 1 to 6 of 6 entries
| https://www.drugpatentwatch.com/p/tradename/TOLSURA/drug-master-files/drug-master-files/drug-master-files/supplier/ITRACONAZOLE/atc-class/J |
Fukushima Technical Discussion Open Thread | Brave New Climate
It was suggested in a comment -- and I agree -- that the previous open threads on the Fukushima Daiichi Nuclear Accident were becoming difficult to read, because they are such a mixture of technical details and philosophical discourse. That is, it's generally a bad idea to cater to two different audiences in one comment…
Fukushima Technical Discussion Open Thread
It wassuggested in a comment— and I agree — that the previous open threads on the Fukushima Daiichi Nuclear Accident were becoming difficult to read, because they are such a mixture of technical details and philosophical discourse. That is, it’s generally a bad idea to cater to two different audiences in one comment thread. So, I will split them up.
Pleaserestrictall discussion here to technical information, analysis, criticisms and questions on FD — no philosophising or excursions into whether nuclear power is ‘good’ or ‘bad’ or the implications of FD for the future of nuclear power (except for new technical developments, e.g. safety standards), etc. You may impart your deep wisdom on how the world should work on the other open thread I’m about to open.
Besides the above guidelines, the other rules of the Open Threadson BNC apply.Read herefor details.
To kick off discussion, below is the latest FEPCstatus report (I’ll update this as new reports come in). You will also be interested in:
— JAIF Updates#35and#36
—NISA Major Parameters 0600 March 29
—NISA Summary Conditions 0600 March 29
—————-
Radiation Levels
At 11:45PM (JST) on March 28, TEPCO announced that plutonium 238, 239 and 240 were detected in the soil sampled on March 21st and 22nd at five spots in Fukushima Daiichi Nuclear Power Station. Concentration of detected plutonium 238, 239 and 240 are the same level of the fallout observed in Japan at the atmospheric nuclear tests in the past and poses no major impact on human health.
At 6:30PM on March 29, radiation level at main gate (approximately 3,281 feet from Unit 2 reactor building) of Fukushima Daiichi Nuclear Power Station: 177 micro Sv/hour.
At 6:30PM on March 29, radiation level at west gate (approximately 3,609 feet from Unit 2 reactor building) of Fukushima Daiichi Nuclear Power Station: 120.2 micro Sv/hour.
Measurement results of environmental radioactivity level around Fukushima Nuclear Power Station announced at 7:00PM on March 29 are shown in the attached PDF file. English version is available at: http://www.mext.go.jp/english/radioactivity_level/detail/1304082.htm
For comparison, a human receives 2,400 micro Sv per year from natural radiation in the form of sunlight, radon, and other sources. One chest CT scan generates 6,900 micro Sv per scan.
Fukushima Daiichi Unit 1 reactor
At 1:00PM on March 29, pressure inside the reactor core: 0.371MPa.
At 1:00PM on March 29, water level inside the reactor core: 1.65 meters below the top of the fuel rods.
At 1:00PM on March 29, pressure inside the primary containment vessel: 0.265MPaabs.
At 1:00PM on March 29, the temperature of the reactor vessel measured at the water supply nozzle: 570.9 degrees Fahrenheit
As of 3:00PM on March 29, transferring the water found at the turbine building to the condenser continues.
As of 4:00PM on March 29, the injection of freshwater into the reactor core continues.
Fukushima Daiichi Unit 2 reactor
At 1:00PM on March 29, the temperature of the spent fuel pool: 114.8 degrees Fahrenheit.
At 1:00PM on March 29, pressure inside the reactor core: -0.025MPa.
At 1:00PM on March 29, water level inside the reactor core: 1.5 meters below the top of the fuel rods.
At 1:00PM on March 29, pressure inside the primary containment vessel: 0.1MPaabs.
As of 4:00PM on March 29, the injection of freshwater into the reactor core continues.
As of 7:00PM on March 29, approximately 96 tons of water in total has been injected into the spent fuel storage pool.
Fukushima Daiichi Unit 3 reactor
At 12:00PM on March 29, pressure inside the reactor core: 0.029MPa.
At 12:00PM on March 29, water level inside the reactor core: 1.85 meters below the top of the fuel rods.
At 12:00PM on March 29, pressure inside the primary containment vessel: 0.1075MPaabs.
At 2:17PM on March 29, TEPCO began to shoot freshwater aimed at the spent fuel pool, with a specialized vehicle normally used for pumping concrete, until 6:18PM (approximately 100 tons in total).
As of 4:00PM on March 29, the injection of freshwater into the reactor core continues.
As of 7:00PM on March 29, approximately 4,697 tons of water in total has been shot to the spent fuel storage pool.
Fukushima Daiichi Unit 4 reactor
At 11:50AM on March 29, lighting was restored in the Central Control Room.
As of 7:00PM on March 29, approximately 960 tons of water in total has been shot to the spent fuel storage pool.
Fukushima Daiichi Unit 5 reactor
At 2:00PM on March 29, the temperature of the spent fuel pool: 101.5 degrees Fahrenheit.
Fukushima Daiichi Unit 6 reactor
At 2:00PM on March 29, the temperature of the spent fuel pool: 70.7 degrees Fahrenheit.
Fukushima Daiichi Common Spent Fuel Pool
At 3:10PM on March 28, the temperature of the spent fuel pool: 95 degrees Fahrenheit.
As of 7:00PM on March 29, approximately 130 tons of water in total has been injected to the spent fuel storage pool.
(1) A complete loss of station power occurs,accompanied by complete loss of emergency corecooling systems. The control rods areautomatically inserted at the beginning of theaccident, terminating the fission reaction.
(2) No active efforts are made by the operators tomitigate the accident.
(3) A short time after the loss of power and corecooling the upper core becomes uncovered.
(3) The control rods melt in a part of the uppercore, probably near to the center and top. Thiscan happen without a simultaneous melting of thefuel rods, if the control rods are made of boroncarbide, since it has a lower melting point thanZircaloy fuel cladding. Control rods are relocatedin this way, out of a part of the upper core,leaving that area with close to normal reactorgeometry, but no control rods. But there is nowater present, only steam; and therefore there isstill no fission reaction.
(4) Just at this point, and before fuel rods inthe upper core begin to melt and relocatedownwards together with the control rods, theelectrical power is suddenly restored to theplant.
(5) The partially damaged core is then flooded bycold fresh water, due to the restarting of theemergency core cooling pumps. Fresh water is themoderator in a BWR. So re-critcality can now occurin that part of the core which has been cleared ofcontrol rods, but still has close to normalreactor geometry.
(6) The fission reaction restarts in part of thedamaged core (re-criticality).
Since the control rods are now gone, the factorsthat will limit the re-initiated fission reactionare the natural ones that always operate in a LWR:namely void formation and Doppler broadening.
That is: as the fission reaction speeds up, itgenerates more heat. The additional heat boilswater, creating steam bubbles in the liquidphase. Steam is less dense than liquid water, soit doesn’t slow neutrons nearly asefficiently. This void formation in turn slows thefission reaction down.
Doppler broadening of the neutron spectrum alsooccurs due to heat generated by the fissionreaction. Neutrons which hit nuclei in the fuel,or in the cladding, or that hit oxygen nuclei inthe water scatter elastically if they aren’tabsorbed and don’t cause fission reactions. Butdue to heat, the nuclei are also movingaround. Such elastically scattered neutrons gainor lose a little energy as they scatter, and thiswill change the overall energy spectrum of theneutrons. The neutrons will gain energy onaverage, as the scattering material heats up. Butthermal neutron induced fission cross-sectionsalso drop significantly with increasing neutronenergies, so the rate of the fission reaction isin turn reduced as temperature increases.
Depending on the rate at which fresh cold water ispumped into the damaged core region, faster beingworse, and also depending on other details, therecan occur a big pulse of reactor power in thesmall fraction of the core that is partiallydamaged. Depending on how big a pulse and how thatenergy is dissipated, the reactor power can eitheroscillate and finally die away, continueoscillating, or possibly die down to some constantlow fraction of the total reactor power.
This is potentially a big problem, if theoperators don’t do anything at all to try tomitigate the situation.
But the whole sequence of events can be avoided,though, if the operators inject borated instead offresh water into the damaged core once power comesback, or as soon as they have the ability to doso. Borated water acts as a neutron poison (likethe control rods) and will prevent re-criticality.
That was actually done in this accident, as Iunderstand it. The operators pumped boratedseawater into the RPVs, over the damaged cores.
I imagine that uncertaintly about the extent ofdamage to the reactor cores and worry about theabove scenario may have been the main reason forinjecting the borated seawater into the cores.
More complete melting of the reactor cores makesrecriticality very much less likely, because thefuel then relocates downward in the RPV togetherwith the melted fuel rods. Moreover, the geometryof completely melted fuel is extremelyunfavourable for forming a critical configurationwith reespect to thermal neutrons: there is noroom to fit the moderator inside a blob of moltenfuel cladding, control rods, and fuel pellets, andany water that gets trapped or sits on top wouldsimply be boiled away by the heat.
A critical configuration with respect to fastneutrons isn’t a realistic possibility, due to thelow enriched fuel that is used in light waterreactors. Critical masses with fast neutrons aresimply too large (even for the optimal sphericalgeometry).
Notice that the above scenario for re-criticalityhas to occur pretty early on in the accident. It’svery hard for me to imagine a scenario in whichre-criticality occurs at late times, or once thefuel has become significantly damaged.
I suppose conceivably, such a thing might occur,for a vey small fraction of the core, if enoughshattered or disintegrated fuel pellets somehowsurvived melting, and found their way into a poolof fresh water, say in the suppression pool. Butsuch a reaction would be limited by the samemechanisms mentioned above, as well as probablyothers, like the ability of such fuel to flow awayfrom the critical region.
If you go to the latest JAIF report (http://www.jaif.or.jp/english/news_images/pdf/ENGNEWS01_1302343542P.pdf), water injection to containment vessel is a reporting item. Status reads : to be confirmed (R1), to be decided (seawater) (R2), and, to be confirmed (R3).
George: I do seem to remember seeing that item about injecting water to containment in some of the earlier JAIF updates, but I wasn’t sure whether injection to containment meant just a slow spray of water into the containment, possibly for cooling purposes, or an actual attempt to flood the containment.
I certainly agree with you that if containment flooding were to be accomplished, then all of the major drainage paths out of the PCV, below the level of the bottom of the RPV would need to be closed off as tightly as possible.
etudiant, on 11 April 2011 at 12:54 AM said:
Given the estimate of a decade long D&D program, these emissions look to remain a factor for some time
There are lot’s of unanswered questions at the moment, but for radiation to get far it needs a transport mechanism. The first job will be to deny a transport mechanism.
[Comment deleted. Violation of citation policy] MODERATORDo not post just a throwaway remark and a link.
Citation policy is this:
BARRY BROOKThe commenting rules are not meant to be confusing, they’re meant to be logical. This is not a forum for cut-and-pasting slabs of text, with no other comment other than a link. Tell people why you think they should be interesting in reading this, and what it means for this discussion. Otherwise, you’re not thinking and not contributing. Simple as that.
Citing literature and other sources: appropriate and interesting citations and links within comments are welcomed, but please DO NOT cite material that you have not yourself read, digested and understood. As a general rule, please introduce any and every link or reference with a short description of the material, your judgement on its quality, and the specific reason you are including it (i.e. how it is relevant to the discussion).
Question: when does TEPCO run out of qualified workers? I mean workers who have both required skills and useful remaining radiation allowance.
I would like to know how fast the existing TEPCO manpower pool is being depleted (I mean their remaining radiological allowances). A week ago WNN reported that 21 out of 370 workers had reached 100 milliseverts [thanks to Hank Roberts 4/11/11 2:01]:
http://www.world-nuclear-news.org/RS_Deaths_confirmed_at_Fukushima_Daiichi_0304111.html
It would help to have an idea what part of the remaining work requires high-skill and high-site-experience vs. just cleanup labour. Is extensive site-experience even a big issue?
The labour supply is defined by the radiological allowance. Is there a consensus on what the worker allowance should be?
Steve Darden, on 12 April 2011 at 8:07 PM said:
Question: when does TEPCO run out of qualified workers? I mean workers who have both required skills and useful remaining radiation allowance>
A fair portion of the maintenance and upgrades that are done at NPP’s is performed during refueling outages. Since refueling only occurs every 18 months or so there is an industry pool of ‘temporary help’.
2011 US Columbia Operating Station budget – includes $10 million for temporary help and overtime during refueling outage.
Click to access Final%202011%20Columbia%20Generating%20Station.pdf
“(3) The control rods melt in a part of the uppercore, probably near to the center and top. Thiscan happen without a simultaneous melting of thefuel rods, if the control rods are made of boroncarbide, since it has a lower melting point thanZircaloy fuel cladding.”
false
The boron carbide has the melting point 2763°C –http://en.wikipedia.org/wiki/Boron_carbide, Zircaloy has melting point much lower – The pure Zirconium itself has 1855°C melting point –http://en.wikipedia.org/wiki/Zirconium, (and is alloyed by Sn – melting point 231°C – and or Niobium – melting point 2477°C – to form Zircaloys) and the Zirconium even at much lower temperatures already violently reacts with any water present. So the described mechanism of the recriticality is a patent nonsense and I don’t wonder that it is again not sourced by any link whatsoever – as was several times called for by the moderater here…
Personally I think the recriticality claims about the Fukushima are red herrings (I was looking into it after there were the weird Te-129 readings which subsequently showed being errors) because even if the whole cores would melt through the cladding and end on the bottom of the RPV’s there’s not the unpoisoned (borated etc.) moderator (crucial, without it the chain reaction is impossible in the low enriched fuel) for it to regain criticality) The same for the spent fuel pools, moreover there are the fuel rods packed in the boron carbide racks.
You’re right: it’s false, at least the way I summarized thescenario.
But, not being an expert, I’ve summarized it wrongly. The meltingof the B4C is said to occur at 1500K, due to a reaction of thecarbide with stainless steel. Possibly stainless steel may be inproximity with control rods in these reactors.
So the described mechanism of the recriticality is a patentnonsense and I don’t wonder that it is again not sourced by anylink whatsoever – as was several times called for by themoderater here…
There are many sources describing the scenario forrecriticality. Here’s a link to the SARA study:
ftp://ftp.cordis.europa.eu/pub/fp5-euratom/docs/09-sara.pdf
Recriticality has been studied for a total loss ofelectric power accident scenario. In a BWR, the B4C control rodswould melt at about 1500K (due to a eutectic reaction between B4Cand stainlesss steel) and relocate from the core before the fuelwould during core uncovery and heat-up. If electrical powerreturns during this time-window, the duration of which ispredicted to be in the range of a few minutes to about 40nminutes, it is likely that the core will be reflooded usingwater from Emergency Core Cooling Systems (ECCS) or feed watersupplies. Since this water is normally unborated, recriticalityis possible …
Here’s a link to a report produced at ORNL:
IDENTIFICATIONOF AND ASSESSMENT OF BWR IN-VESSEL SEVERE ACCIDENT MITIGATION STRATEGIES
which describes the injection of borated water as a strategy toprevent recriticality in a BWR accident with severe core damagewhen
” … control blades have melted and relocated fromthe core.”
(from section 5. of this report)
NUREG/CR5653 documents the conclusion that there is apotentiality for recriticality in BWRs, if core reflood occurs.
See:
http://www.nrc.gov/reading-rm/doc-collections/nuregs/staff/sr0933/sec3/155r2.html
Personally I think the recriticality claims about theFukushima are red herrings (I was looking into it after therewere the weird Te-129 readings which subsequently showed beingerrors) because even if the whole cores would melt through thecladding and end on the bottom of the RPV’s there’s not theunpoisoned (borated etc.) moderator (crucial, without it thechain reaction is impossible in the low enriched fuel) for it toregain criticality) The same for the spent fuel pools, moreoverthere are the fuel rods packed in the boron carbideracks.
I agree with you about all of the late recriticality claims, andI would add that the early recriticality possibility seems torequire a perfect storm. But it has, at least, been considered apossibility.
Thanks David and Jan.
g
Here’s the relevant NRC snippet on recrit. Thanks to David.
ISSUE 155.4: IMPROVE CRITICALITY CALCULATIONS
DESCRIPTION
The Board believed that doubts still remained as to whether the TMI-2 core became critical, or was very close to critical, during the TMI-2 accident and recommended that the NRC establish guidelines that deal with criticality following a severe reactor accident.1362 These guidelines should take into account abnormal geometries and possible core conditions that could result from the accident. The Board believed that the accident scenario developed by the TMI-2 licensee was sufficiently detailed that a series of geometric configurations could be simulated for criticality calculations. Variables that could be estimated reasonably well included the presence of water, oxidation of cladding, melting and movement of fuel, melting of poison rods, and movement of poison.
CONCLUSION
The safety concern was addressed by DSR/RES in SARP Task 4.3: Investigate the Possibility and Consequences of Recriticality in Degraded BWR Cores.1382 The staff’s study was documented in NUREG/CR-56531379 in which it was concluded that there was the potential for recriticality in BWRs, if core reflood occurs after control blade melting has begun but prior to significant fuel rod melting. However, a recriticality event would most likely not generate a pressure pulse significant enough to fail the vessel. Two strategies were identified that would aid in regaining control of the reactor and terminate the recriticality event before containment failure pressures are reached: (1) initiation of boron injection at or before the time of core reflood, if the potential for control blade melting exists; and (2) initiation of RHR suppression pool cooling to remove the heat load generated by the recriticality event and extend the time available for boration.
The issue was not considered to be a major concern for PWRs because of their design that includes a safety injection system for supplying borated water to the core. Furthermore, it was concluded in NUREG/CR-58561417 that, during a severe accident, an unmoderated recriticality of the molten, consolidated portion of a degrading core cannot occur at U235 enrichments characteristic of a PWR. Based on the staff’s efforts in addressing the safety concerns in the SARP, this issue was DROPPED from further pursuit as a new and separate issue. In an RES evaluation,1564 it was concluded that consideration of a 20-year license renewal period did not change the priority of the issue.
Cheers, Gregory :)
harrywr2, on 12 April 2011 at 11:19 PM said
“…industry pool of ‘temporary help’.” Thanks Harry – that’s comforting.
“Sorry I have to spell it out — I thought it would be interesting that the Union of Concerned Scientists stated that nitrogen injection has never been attempted before (to their knowledge) after a reactor has been running.”
Nitrogen in the containment is quite standard feature of the newer BWR designs by default to prevent hydrogen combustion in case of a LOCA accident and yes it must be sometimes injected in the CPV during operation to maintain the pressure.
se e.g. here:
I[Comment deleted. Violation of the citation rule]
@ David Kahana
I’m not much convinced about the mechanism of the recriticality you describe anyway:The B4C-steel eutectic melting would be impossible in cases the RPV would be completely dry, because the Zircaloy rapid oxidation would be impossible in such a case. If it would still not be completely dry as is most likely and Zircaloy starts to burn with steam then even if triggering the control rod eutectic it would have much higher temperature – partly because the exothermic violent reaction with the steam, partly because of the decay heat of the fuel inside, so it would most probably be the fuel rods not the control rods which will loose integrity first.I think the theorizing about this scenatio is based on tests like this:http://cat.inist.fr/?aModele=afficheN&cpsidt=15755028But they have major flaw – no fuel with very high after scram decay heat is involved inside the Zircaloy tubes.
Btw. Only a crazy would flood the RPV with even partially melted core with a fresh unborated water. It would be better to leave the RPV dry and flood the CPV instead – as the document you link suggests.
@ David B. BensonIn the case of the No4 it is quite sure – there was no fuel in the RPV whatsoever.
This is only tangentially related to Fukushima, but it does illustrate the difficulty of doing any kind of sensible risk analysis based on likely tsunami height.
http://en.wikipedia.org/wiki/Megatsunami
I would be interested in a technical discussion on environmental aspects of Fukushima. Has anyone compiled available data into coherent picture? Particularly interested in total Cs deposition as this will be the important one going forward. Sea water more difficult but should be less of an issue due to high salts which should inhibit significant uptake in marine organisms. Fukushima prefecture is starting to look ugly. Depends whether highs are coherent or spot samples. Anyone?
Does anyone know how much spent fuel is stored at Fukushima in casks? I assumed that since there is a separate spent fuel pool that there was no cask storage but this article suggests otherwisehttp://www.technologyreview.com/energy/37388/?nlid=4364&a=f
An 18 March update on radiation levels around Fukushima from the DoE at their blog,http://blog.energy.gov/content/situation-japan/
Although it’s helpful in some ways, I find it a little irritating that they have only given a map of the estimated one-year dose, they have saturated their colour scale rather early at 20mSv, and they have included doses in the month just gone, likely more than half the dose. Is anyone aware of an accessible (less processed) version of current dose rates?
Athttp://www.jaif.or.jp/english/there are occasional, most recently April 19th, PDFs with the titleTrend of Radiation in the Environment around Fukushima Daiichi NPS PDF.
Also similar updates for radioactivity in the nearby sea.
( How fire can be domesticated)
The following is a quote from a WSJ article in this mornings WSJ
“Under its strategic plan unveiled Sunday, Tepco is planning to fill the containment vessels of the plant’s No. 1 and No. 3 reactor units with water and employ heat-exchanging systems that could include an air-cooling solution. Similar plans are in place for the heavily damaged No. 2 reactor unit but must await the repair of leaks that are allowing the escape of highly radioactive water contaminated by the damaged fuel rods.”
The entire article can be found here.http://online.wsj.com/article/SB10001424052748703916004576270643486719236.html
As read from the quote above, Tepco is planning to fill the “containment” vessels.
This must be an error. I think they are just going to cool the water in the PRV by creating a new closed loop cooling system for the RPV and cooling this loop via an air cooled heat exchanger similer to french design. I would assume also that the air cooling would consist of an evap cooling tower.
Can anyone clear up what is going on here??
Thx,GSB
A better description can be found at IEEE:
TEPCO Announces a “Roadmap to Restoration” at Fukushima Dai-1
A link is given there to theTEPCO description of the roadmap.
I don’t detect a mention of filling the containment vessels with water. Mention is made of increasing the level of water to cover the “active fuel”.
1 Maintain Stable Cooling– Nitrogen gas injection– Flooding up to top of active fuel– Examination and implementation ofheat exchange function. 2 (Unit 2) Cool the reactor while controlling the increase of accumulated water until the PCV is sealed.
Sounds more like they want to increase the water levels in the RPVs and for unit 2 to control the additional release of water until they can fix the hole in the suppression pool …
Oops, sorry, spoke too soon. In the second pdf at the TEPCO site:
Current Status [1] (Units 1 to 3) Cooling Achieved by water injection while there is partial damage to fuel pellets.
-Continued injection of fresh water and further cooling measures are required.
Countermeasure [1]: Injecting fresh water into theRPV by pumps.Risk[1]: Possibility of hydrogen explosion due to condensation of steam in the PCV when cooled, leading to increased hydrogen concentration.
Countermeasure [2]: Injecting Nitrogen gas into the PCV (start from unit 1.)
Countermeasure [3]: Consideration of flooding the PCV up to the top of active fuel.
Thx for the response David,
Perhaps they are anticipating a situation where they can not stop the leakage from the PRV in R2. I don’t know how they would repair leaking control rod seals. Pump seals could more easily be fixed. At any rate it is something “under consideration”. I would think that R1 and R2 would be cooled without flooding the CV’s. Set up a new closed loop on the PRV cooling water using an “air cooled” heat exchanger and that this air cooled heat exchanger would use air cooled water towers.
Can anyone agree or disagree??
Oops.
Revise last statement to R1 and R3.
I would think that R1 and R3 would be cooled without flooding the CV’s. Set up a new closed loop on the PRV cooling water using an “air cooled” heat exchanger and that this air cooled heat exchanger would use air cooled water towers.
Chhers, George.
It would seem crazy to flood the PCV of R2 if there is a leak in the torus which is what I though they suspected … that would only make the leak worse.
So maybe they’re thinking about that only for R1 and R3?
For R2, it would seem they’ld have to fix the hole first. And that fix will have to be able to take the hydrostatic pressure, before they could flood it.I also don’t see how they could accomplish that fix with very high radiation levels that may exist near the leak.
It would seem to me to be better to cut the flow rate to the RPV in R2 to the minimum necessary to continue cooling so as to limit the leakage, and like you say, try to set up some kind of air cooling with a closed loop, putting the heat exchanger in a lower radiation area.
I think the other problem is that the CV may not be able to stand another earthquake when said CV is filled w/ water.
So in summary I just don’t see flooding ANY of the CV’s w/ water as a likely route they would take.
Perhaps we will get some video from the Robot. Apparently it gets it’s camera all fogged up w/ steam when they try to go inside the CV of R2.
David,Cyril R posted this in the other thread. We are keeping the CV flooding issue here in this blog.
CyrilR quote:
Cyril R., on 20 April 2011 at 3:34 AM said:
George, the latest JAIF update says ‘to be confirmed’ in the category water injection to containment vessel, for units 1 and 3. For unit 2, it says ‘to be decided (seawater)’.
There is also the AREVA presentation which says they flooded at least 1 unit (unit 1 probably).
George, yes, that’s a very good point aboutthe additional stress on the PCV and thechance of another earthquake.
I did see the Areva presentation, and itcertainly suggested that flooding of R1 PCV hadbeen done. There were also hints that R1 hadhad a LOCA caused by the earthquake before thetsunami hit — it was in a video presentation by a Hitachi engineer. I’ll try to find a link.
I understand why they would want to flood the containment in such a case, but I imagined itwould only be up to the level of the PRV bottomto try to prevent melting through.
About the JAIF updates: I’ve never been quite clearwhat they mean by “water injection to containment.”
Is there a separate water spray system inside the drywell, to be used for cooling to condense steam? Or do they really mean filling the whole thing up?
I’ld really love to see the video from the robot. I hopeit works.
Does anyone know how much spent fuel is stored at Fukushima in casks?
Don’t know how much fuel is stored in casks but Tepco has a picture of a cask and cask mover on their website.
Link with presentation from Dr. Matthias Braun (AREVA) for reference to the statement that PCVs flooding:
It says at least one contaiment (unit 1) flooded.
The JAIF references say ‘to be confirmed’ at containment flooding. Perhaps mistranslation but my definition of ‘to be confirmed’ is ‘we’ve done it but haven’t verified the exact effect’.
Pump seals could more easily be fixed. At any rate it is something “under consideration”. I would think that R1 and R2 would be cooled without flooding the CV’s.
In my simple mind, I think the problem is that the seals that are leaking are located inside the containment vessel which would make the inside of the containment vessel inaccessible.
As far as the cooling system, it appears they are talking about an air cooling heat exchanger…I.E. A large radiator rather then getting the sea water pumps and condensers functioning again.
Thx Cyril for the link, an excellent presentation. I found the reactor core isolation pump/cooling slide especially interesting. The reactor was able to run it’s cooling loop pump off the turbine that used reactor steam as an energy source. No outside source required for the pump, just battery power….pretty ingenious.
Also R1 went the longest w/o cooling.
Perhaps 1 or more of the wet wells ARE flooded as shown in the slide.
Thanks GRLC. Only Iitate is above 2microsieverts/hr of those monitoring stations, and a rough calculation shows that the dose from 15-19 Mar at that location is equivalent to a year at the current dose rate (which will drop further). So for evacuation-lifting purposes, almost all areas should be re-opened unless there is a realistic threat of further releases from Fukushima Daiichi on the same scale as mid March. Certainly people should be allowed back to check on their houses and possessions, where the roads etc. permit.
@George Bower – your PCV/containment flooding questionI confirmed the PCV flooding strategy in my commentson the 18th:
TEPCO’s briefing slides (4) are availablehere. My speculation that they would flood the PCV appears to be correct:
Countermeasure [9]: Flood the PCV up to the top of active fuel.
I agree with David – if they achieve their objectives in 9 months I will be impressed and relieved. My understanding is that TEPCO knows little about the actual state of the machinery inside the buildings. And they have no experience of doing such construction in a hot environment – with or without robots.
The TEPCO plan describes the strategy for R1 and R3 fairly clearly: first fix the leaks, seal the containment, then flood to at least the top of the fuel and recirculate and cool as you outlined. For R2 the torus leaks must first be repaired (the “sticky cement” plan?). The annotated TEPCO diagram was excellent.
I’ve found two well-informed sources of analysis on the Daiichi stabilization plan. KBMAN worked 25 years ago on the same generation BWR/Type I containment. Hislatest on the TEPCO planincludes this
One of the primary steps mentioned in their plan is to flood the containment vessels of units 1 and 3 up to the level of the fuel to guarantee the fuel remains covered and to assist in cooling. They are also looking at building external heat exchangers to be used in conjunction with filtration systems to be able to recycle the water being pumped through the reactors and also cool the water in the containments. This step also helps to provide more effective cooling for the fuel sediment on the bottom of the reactors by conducting heat away from the bottom of the reactor vessel.
They also wish to do this for unit 2 but must first repair the damage to the containment vessel. There is mention of using “sticky cement” to make this repair, I’m not sure exactly what they mean by that. This is presumably the leak caused by the explosion in or near the torus during the first week of the emergency. Meanwhile, the leaks in the containment at unit 2 appear to be flowing directly to the service trench in the turbine building. They pumped thousands of gallons only to have the level rise back up again. They may end up needing to seal up the secondary leaks and treat the entire system – trench and all – as the “reactor vessel”. Stop adding new water and instead process the water from the trench and inject it back into the reactor.
Will Davis offers very timely analysis.His firston the TEPCO announced plan discussed the PCV flooding strategy.
The detailed releases by TEPCO do also indicate the desire to flood the PCV’s or Primary Containment Vessels (dry wells) up to the top of the active fuel region. The few illustrations released so far are not of what you might call a highly technical nature but they seem to indicate at least feed to the plant through the normal feed line and then removal of the water from the suppression pool. There is also one that shows a totally separate closed circuit cooling system that circulates only through the pressure vessel and a heat exchanger. Clearly the plans are in a state of flux and we’ll have to see how this shakes out. To help you understand why some of these considerations are of interest to us, look at the following illustration of an earlier style BWR reactor pressure vessel and internals. You’ve seen this before on this site, but it’s been marked up for this article…
Thanks for your rough calculations and observation that “almost all areas should be re-opened unless there is a realistic threat of further releases”.
The latest DOE dose-map slide I’ve seen was headed First-Year…commencing March 16. So that’s good, it does not sum up the earlier exposures. But as I read the map everything hotter than the blue will continue to be an exclusion zone.
Am I missing something?
Steve, I haven’t seen the future plans of the definition of the evacuation zone anywhere. I doubt they exist in any formal sense. For reference, the actual current evacuation zone is the inner circle on that presentation.
But I don’t understand your “that’s good” remark – the significant impact on these areas was from 15 March onward, so practically all the initial higher-level dose rates are included in the calculation for that map. I’d like to see a map that starts its year from now, or at least from the start of April. It would look very different.
The continuation of an exclusion zone when access would not be harmful is a repeat of the mass psychology mistakes identified after Chernobyl. This land is not blighted or uninhabitable and should not be treated as such.
But I don’t understand your “that’s good” remark – the significant impact on these areas was from 15 March onward, so practically all the initial higher-level dose rates are included in the calculation for that map. I’d like to see a map that starts its year from now, or at least from the start of April. It would look very different.
My bad – I wanted DOE to be doing what you said. That “must be” why I saw March 16 and thought April 16. There are alternative age-related hypotheses for synapse meltdowns like that…
The continuation of an exclusion zone when access would not be harmful is a repeat of the mass psychology mistakes identified after Chernobyl. This land is not blighted or uninhabitable and should not be treated as such.
I agree. I’ve not done my homework to verify what the projected dose would be. My guess is the authorities will continue the currently defined zone until they are confident there will not be any more “excitement” with new releases from NPP1. I.e., they are excluding in fear of new releases rather than based on existing contamination.
Steve Darden,
Article on long term exposure standardhttp://www.asahi.com/english/TKY201104110139.html
2.5 uSv=0.25mRem.The Japanese set the ‘long term’ exposure standard to 20 mSv per year or 2.5 uSv/hr.(using 8,000 hour year)
The DOE Map from April 7th is more informative of current dose rate.http://www.slideshare.net/energy/radiation-monitoring-data-from-fukushima-area-04072011
| https://bravenewclimate.com/2011/03/30/fukushima-technical-discussion-open-thread/?like_comment=123570&_wpnonce=6b6e72aa2e |
Pseudomonas aeruginosa internalization by corneal epithelial cells involves MEK and ERK signal transduction proteins | Request PDF
Request PDF | Pseudomonas aeruginosa internalization by corneal epithelial cells involves MEK and ERK signal transduction proteins | Invasion of epithelial cells represents a potential pathogenic mechanism for Pseudomonas aeruginosa. We explored the role of mitogen-activated... | Find, read and cite all the research you need on ResearchGate
Article
Pseudomonas aeruginosa internalization by corneal epithelial cells involves MEK and ERK signal transduction proteins
August 2002
FEMS Microbiology Letters213(1):73-9
DOI: 10.1111/j.1574-6968.2002.tb11288.x
Source
PubMed
Authors:
<here is a image 64b2d529afc6e443-b97087aade6694e8>
David J Evans
Touro University California United States
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Inna A Maltseva
Inna A Maltseva
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Josephine Wu
Josephine Wu
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe>
Suzanne M Fleiszig
University of California, Berkeley
Abstract
Invasion of epithelial cells represents a potential pathogenic mechanism for Pseudomonas aeruginosa. We explored the role of mitogen-activated protein kinase kinases (MEK 1/2) and the extracellular signal-regulated kinases (ERK 1/2) in P. aeruginosa invasion. Treatment of corneal epithelial cells with MEK inhibitors, PD98059 (20 microM) or UO126 (100 microM), reduced P. aeruginosa invasion by approximately 60% without affecting bacterial association with the cells (P=0.0001). UO124, a negative control for UO126, had no effect on bacterial internalization. Infection of cells with an internalization-defective flhA mutant of P. aeruginosa was associated with less ERK 1/2 tyrosine phosphorylation than infection with wild-type invasive P. aeruginosa. An ERK-2 inhibitor, 5-iodotubercidin (20 microM), reduced P. aeruginosa invasion by approximately 40% (P=0.035). Together, these data suggest that P. aeruginosa internalization by epithelial cells involves a pathway(s) that includes MEK and ERK signaling proteins.
... Examination of P. aeruginosa clinical isolates has shown that some invade and replicate within mammalian cells that are not considered professional phagocytes, e.g. epithelial and endothelial cells [13][14][15][16][17][18][19][20][21]
[22]
. Several host cell factors have been shown to be involved in P. aeruginosa invasion, including, the cystic fibrosis transmembrane conductance regulator protein (CFTR) [17], the surface glycosphingolipid asialo-GM1 [15], the actin cytoskeleton [18], intracellular calcium and calmodulin signaling [19], RhoA [20], Src-family tyrosine kinases [21], and MEK and ERK signal transduction proteins [22]. ...
... epithelial and endothelial cells [13][14][15][16][17][18][19][20][21][22]. Several host cell factors have been shown to be involved in P. aeruginosa invasion, including, the cystic fibrosis transmembrane conductance regulator protein (CFTR) [17], the surface glycosphingolipid asialo-GM1 [15], the actin cytoskeleton [18], intracellular calcium and calmodulin signaling [19], RhoA [20], Src-family tyrosine kinases [21], and MEK and ERK signal transduction proteins
[22]
. Nevertheless, the molecular mechanisms of the bacterial internalization are poorly understood, and the cellular receptors involved are largely unknown. ...
... P. aeruginosa adherence to human respiratory epithelium is thought to be essential in the initiation and maintenance of respiratory infections in cystic fibrosis patients and upon suppression of the immune system [17,
22,
27]. P. aeruginosa internalization by several CFTR-positive and -negative mammalian cell types has been observed both in vivo and in vitro [3,13,22]. ...
Role of αvβ5 integrins and vitronectin in Pseudomonas aeruginosa PAK interaction with A549 respiratory cells
Article
Sep 2004
MICROBES INFECT
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Johanne Leroy-Dudal
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Hélène Di Martino
Elisabeth Cossard
<here is a image 7ee1bc247f87b098-8a0c60a28e5de9e0> Patrick Di Martino
Bacterial adherence to mammalian cells and their internalization are thought to participate in Pseudomonas aeruginosa pathogenicity. In this study, we explored the role of alpha5beta1 and alphavbeta5 integrins and their natural ligands, fibronectin (Fn) and vitronectin (Vn), in P. aeruginosa interaction with epithelial cells by using the PAK reference bacterial strain, A549 respiratory, and SKOV-3 human ovarian cell lines. The host cell cytoskeleton and cellular tyrosine kinases seem to be solicited during the PAK-respiratory cell interaction: cytochalasin D and genistein decreased the bacterial adherence and internalization. Blocking antibodies to alphavbeta5 integrins were the only antibodies tested to have inhibitory activity against PAK adherence to A549 cells. PAK internalization by A549 and SKOV-3 cells was markedly decreased in the presence of blocking antibodies to Vn and alphavbeta5 integrins. Addition of Vn in excess restored PAK invasion of both A549 and SKOV-3 cells in the presence of anti-Vn antibodies. Immunofluorescence experiments revealed that, in the presence of bacteria, the Vn fibrillar network disappeared, and alphavbeta5 staining was concentrated in sites where adherent bacteria were present. Taken together, these findings suggest that alphavbeta5 integrins, and their natural ligand Vn, are involved in PAK entry into human epithelial cells.
... Although the functional role remains to be elucidated for P. falciparum-host interaction, the same authors observed that the recombinant peptide PpMC-179 (corresponding to the minimal endothelial CD36binding domain from P. falciparum erythrocyte membrane protein1 e PfEMP1), in a Src-dependent manner, activated extracellular signal-regulated kinase 1/2 (ERK1/2) [7]. On the other hand, different studies suggest that activation of ERK1/2 is involved in internalization of several bacteria such as Pseudomonas aeruginosa
[8]
, L. monocytogenes [9] and Campylobacter jejuni [10]. Moreover, membrane rafts of host cell, recently defined as small (10e200 nm), highly dynamic and heterogeneous membrane domains which are enriched in cholesterol and sphingolipids [11], seem to be essential for the infection events of some pathogens, such as P. aeruginosa, Shigella flexneri and P. falciparum, leading to modulation of host cell signaling events, and, consequently, to their internalization and intracellular survival (see review ref. [12]). ...
... This activation was slightly dependent on SFK activation, indicating that different kinases, other than SFKs, are activating ERK1/2. Although this present work clearly showed that P. brasiliensis adhesion to A549 cells is membrane raftdependent, enabling also SFKs clustering and activation in these cell domains, and despite host cell ERK1/2 kinases have been related to invasion of some bacteria, such as P. aeruginosa
[8]
and L. monocytogenes [9], we failed to get consistent data when using PP2 and PD98059 as tools to analyze the importance of these kinases in P. brasiliensis adhesion, indicating that other signaling molecules might be more decisive in this event. In fact, activation of SFKs or ERK1/2 kinases seems also to be involved in expression of inflammatory cytokines by epithelial cells [29], and therefore, in this manner, P. brasiliensis could be modulating host immune responses. ...
Interaction of epithelial cell membrane rafts with Paracoccidioides brasiliensis leads to fungal adhesion and Src-family kinase activation
Article
Full-text available
May 2008
MICROBES INFECT
Paloma K. Maza
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Anita Straus
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Marcos Sergio Toledo
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Erika Suzuki
Membrane rafts are cholesterol- and sphingolipid-enriched cell membrane domains, which are ubiquitous in mammals and play an essential role in different cellular functions, including host cell-pathogen interaction. In this work, by using several approaches, we demonstrated the involvement of epithelial cell membrane rafts in adhesion process of the pathogenic fungus Paracoccidioides brasiliensis. This conclusion was supported by the localization of ganglioside GM1, a membrane raft marker, at P. brasiliensis-epithelial cell contact sites, and by the inhibition of this fungus adhesion to host cells pre-treated with cholesterol-extractor (methyl-beta-cyclodextrin, MbetaCD) or -binding (nystatin) agents. In addition, at a very early stage of P. brasiliensis-A549 cell interaction, this fungus promoted activation of Src-family kinases (SFKs) and extracellular signal-regulated kinase 1/2 (ERK1/2) of these epithelial cells. Whereas SFKs were partially responsible for activation of ERK1/2, membrane raft disruption with MbetaCD in A549 cells led to total inhibition of SFK activation. Taking together, these data indicate for the first time that epithelial cell membrane rafts are essential for P. brasiliensis adhesion and activation of cell signaling molecules.
... These data we confirmed in vivo. ERK involvement in PA pathogenicity has already been reported previously as an internalization pathway for the bacteria
(31
(Figures 3C,D). The important gap between the percentage of IFN-γ-positive NK cells among PBMC and sorted NK cells (Figures 1A and 3B,D) underscores the key role of the microenvironment to initiate inflammatory response after PA infection. ...
Exoenzyme T Plays a Pivotal Role in the IFN-γ Production after Pseudomonas Challenge in IL-12 Primed Natural Killer Cells
Article
Full-text available
Oct 2017
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mickael Vourc'H
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Antoine Roquilly
<here is a image e3040bcba3ee4939-dc0fcda489f7ac7e> Alexis Broquet
Karim Asehnoune
Pseudomonas aeruginosa (PA) expresses the type III secretion system (T3SS) and effector exoenzymes that interfere with intracellular pathways. Natural killer (NK) cells play a key role in antibacterial immunity and their activation is highly dependent on IL-12 produced by myeloid cells. We studied PA and NK cell interactions and the role of IL-12 using human peripheral blood mononuclear cells, sorted human NK cells, and a human NK cell line (NK92). We used a wild-type (WT) strain of PA (PAO1) or isogenic PA-deleted strains to delineate the role of T3SS and exoenzymes. Our hypotheses were tested in vivo in a PA-pneumonia mouse model. Human NK cells or NK92 cell line produced low levels of IFN-γ in response to PA without IL-12 stimulation, whereas PA significantly increased IFN-γ after IL-12 priming. The modulation of IFN-γ production by PA required bacteria-to-cell contact. Among T3SS effectors, exoenzyme T (ExoT) upregulates IFN-γ production and control ERK activation. In vivo, ExoT also increases IFN-γ levels and the percentage of IFN-γ+ NK cells in lungs during PA pneumonia, confirming in vitro data. In conclusion, our results suggest that T3SS could modulate the production of IFN-γ by NK cells after PA infection through ERK activation.
... Different studies have shown that P. aeruginosa internalization requires interaction with host cell targets such as lipid rafts [48,49], caveolin-1 [50] and -2 [51] or CFTR [50,52]. Also, it has been shown that entry involves the actin [53,54] and microtubules [55] cytoskeleton as well as host cell signaling proteins such as Src family of tyrosine kinases [56,57], MER-ERK
[58]
and Abl tyrosine kinase [59]. Whether these factors are specifically involved in other routes of P. aeruginosa internalization or they are also part of the entry mechanism described in this work, will need to be tested by future research. ...
Elimination of Pseudomonas aeruginosa through Efferocytosis upon Binding to Apoptotic Cells
Darío Capasso
<here is a image 2c2b642519d7d86b-4080bb16482937a4> María Victoria Pepe
<here is a image a0400e1685e174a2-cba4236a12dc3e9b> Jéssica Rossello
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Arlinet Kierbel
For opportunistic pathogens such as Pseudomonas aeruginosa, the mucosal barrier represents a formidable challenge. Infections develop only in patients with altered epithelial barriers. Here, we showed that P. aeruginosa interacts with a polarized epithelium, adhering almost exclusively at sites of multi-cellular junctions. In these sites, numerous bacteria attach to an extruded apoptotic cell or apoptotic body. This dead cell tropism is independent of the type of cell death, as P. aeruginosa also binds to necrotic cells. We further showed that P. aeruginosa is internalized through efferocytosis, a process in which surrounding epithelial cells engulf and dispose of extruded apoptotic cells. Intracellularly, along with apoptotic cell debris, P. aeruginosa inhabits an efferocytic phagosome that acquires lysosomal features, and is finally killed. We propose that elimination of P. aeruginosa through efferocytosis is part of a host defense mechanism. Our findings could be relevant for the study of cystic fibrosis, which is characterized by an exacerbated number of apoptotic cells and ineffective efferocytosis.
... Of note, flagellin and T3SS components are not the only P.a PAMPs involved in that process: indeed, P.a pili has been shown to activate the inflammasome, independently of NLRC4, through an unknown mechanism (Arlehamn and Evans, 2011). Importantly, Burkholderia cepacia, another important bacterial pathogen often present in cystic fibrosis patients, which can survive intra-cellularly in macrophages and epithelial cells (Martin and Mohr, 2000;
Evans et al., 2002)
, has been described to induce particularly strong pro-inflammatory responses in myeloid cells and has also been shown to activate the inflammasome, through a T6SS-dependent mechanism. This was shown to be mediated through the activation of the host cell pyrin, a component of the NLRP inflammasome (Gavrilin et al., 2012). ...
Pseudomonas aeruginosa elastase LasB modulates CFTR expression and innate immune responses in airway epithelial cells
Conference Paper
<here is a image 624b7583a944da2b-6d113a5988f2bd76> Vinciane Saint-Criq
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Fabien Bastaert
<here is a image d632ebd8eafb086d-2de18517ed7be045> Aurélie Hatton
<here is a image 7ee3111d8cfb4769-5992dc967ccb3472> Jean-Michel Sallenave
Introduction
Pseudomonas aeruginosa (P.a.) is an opportunistic pathogen that is responsible for nocosomial infections and is the major bacterium found in the cystic fibrosis (CF) lungs. Our group has shown that host endogenous proteases such as neutrophil elastase are able to cleave and inactivate CFTR in the airways [1]. Here we hypothesize that the P.a. virulence factor elastase LasB could modulate CFTR expression and innate immune responses in airway epithelial cells.
Methods
The effect of recombinant LasB and secretomes from P.a. strains (WT and ΔLasB PAO1, referred as WT-SEC and ΔLasB-SEC) on CFTR integrity was evaluated in the alveolar epithelial cell line A549 infected with the adenovirus Ad GFP-WT-CFTR and in the Calu-3 cell line grown on semi-permeable supports. The P.a. elastase and secretomes were used to treat the corrected CF cell line CFBE41o-WT-CFTR for ion transport experiments in Ussing chambers and the NCI-H292 and the polarized Calu-3 cell lines for the measurement of secreted cytokines and that of elafin, an important mucosal anti-microbial molecule.
Results
SDS-PAGE analysis of the secretomes showed that LasB is the main secreted protein by WT PAO1. Recombinant LasB (10 nM) and the WT-SEC (10%) but not the ΔLasB-SEC, induced a slight decrease in CFTR expression in our CFTR overexpressing model. The recombinant elastase did not show any effect on the activity of ENaC or CFTR in Ussing chamber experiments. However, WT-SEC (10%) seemed to decrease CFTR activity as reported by the measurement of forskolin/ibmx induced short-circuit current (ΔIsc) and CFTR(Inh-172)-sensitive ΔIsc, when compared to the effect of the ΔLasB-SEC or the LB medium alone. Finally, recombinant LasB, as well as the WT-SEC but not ΔLasB-SEC decreased IL-6 and elafin secretion whereas it had no effect on IL-8 secretion.
Conclusion
Taken together, our results show that LasB, the major type 2 secretion system virulence factor, is able to modulate the expression of CFTR and its activity when used in the P.a. secretome. Moreover, it targets the immune response by regulating the expression of cytokines and anti-microbial peptides and we are currently investigating the molecular mechanisms and signalling pathways underlying these processes.
... cytokines (e.g., IL-12) may be instrumental in the inability of these patients to clear semi-facultative intra-cellular pathogens in the lung, such as P.a., B.c. and NTHI, as suggested recently by a variety of animal and human studies
Evans et al., 2002;
Moser et al., 2002;Martin and Mohr, 2000;Moser et al., 1997). ...
Modulation of dendritic cells by human neutrophil elastase and its inhibitors in pulmonary inflammation
Dendritic cells (DC) are sentinels of the immune system that display an extraordinary capacity to present antigen to naïve T cells and initiate immune responses. DCs are distributed throughout the lungs in the conducting airways of the tracheobronchial tree and in the parenchymal lung, and play a pivotal role in controlling the immune response to inhaled antigens. The respiratory surface is continually exposed to potentially injurious particulates and pathogenic organisms, to which tightly regulated innate and adaptive immunological responses are made. The airways are usually sterile in healthy individuals. However, patients with chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) have increased susceptibility to microbial infections and increased neutrophil elastase (NE) in lung secretions.
This thesis was designed to test the hypotheses that; (i) excess NE may result in a dysregulation of lung DCs function in pulmonary chronic diseases, and (ii) the natural NE inhibitors in the respiratory system are able to rescue the NE-mediated dysregulation of DCs and potentially enhance their antigen presenting activity.
The data in this thesis demonstrate that purified human NE down-regulated murine bone marrow (BM)-derived DC co-stimulatory molecules (CSM; CD40, CD80 and CD86), which was due to its proteolytic activity. NE-treated LPS-matured DCs were less efficient at presenting ovalbumin (OVA) peptide to naïve OVAspecific transgenic (D011.10) T cells. In addition, immature DCs (iDC) simultaneously treated with LPS and NE failed to mature fully and produced significantly less IL-12 and TNF-α than DCs matured in the presence of LPS alone. Similarly, treatment of mature DC (mDC) with pooled and individual COPD and CF sputum samples caused a reduction in CD80 and CD86 levels (but not CD40) which positively correlated with the NE concentration present in the samples.
The demonstration that NE could adversely affect DC phenotype and function suggested that augmentation of NE inhibitors could reverse this process and preserve DC function in inflammatory microenvironments. Over-expression of an NE specific inhibitor (elafin) in the lungs of mice (using either replication-deficient adenovirus [Ad] or elafin transgenic [eTg] mice) increased the number (immunofluorescence) and activation status (flow cytometric measurement) of CD11c+/MHCII+ lung DCs in in vivo models. Replication-deficient Ad vectors encoding NE inhibitors, namely elafin, secretory leukocyte protease inhibitor (SLPI) and α1-protease inhibitor (α1-PI), were also used to infect DCs in vitro, to further study the effect of these NE-inhibitors on DCs in isolation.
These findings suggest that purified NE and NE-containing lung inflammatory secretions are powerful down-regulators of DC maturation, resulting in reduced capacity of these potent APCs to efficiently present antigens; whereas, NE inhibitors could boost immunity by increasing the activation state and/or number of DCs.
... Of note, flagellin and T3SS components are not the only P.a PAMPs involved in that process: indeed, P.a pili has been shown to activate the inflammasome, independently of NLRC4, through an unknown mechanism (Arlehamn and Evans, 2011). Importantly, Burkholderia cepacia, another important bacterial pathogen often present in cystic fibrosis patients, which can survive intra-cellularly in macrophages and epithelial cells (Martin and Mohr, 2000;
Evans et al., 2002)
, has been described to induce particularly strong pro-inflammatory responses in myeloid cells and has also been shown to activate the inflammasome, through a T6SS-dependent mechanism. This was shown to be mediated through the activation of the host cell pyrin, a component of the NLRP inflammasome (Gavrilin et al., 2012). ...
Phagocytic and signaling innate immune receptors: Are they dysregulated in cystic fibrosis in the fight against Pseudomonas aeruginosa?
<here is a image 7ee3111d8cfb4769-5992dc967ccb3472> Jean-Michel Sallenave
Cystic fibrosis (CF) is a genetic disease that affects mainly the lung and the digestive system, causing progressive disability and organ failure. The most prevalent CFTR mutation dF508 (which constitutes 70% of all mutations) results in an incorrect targeting of the CFTR molecule to the membrane. It is now a well accepted concept that mucosal innate immune responses are dysregulated in cystic fibrosis through a cycle of infectious and inflammatory episodes. However, although much work has focused on the late consequences of chronic lung inflammation in CF, very little is known on the early events leading to infection and colonisation, such as that of Pseudomonas aeruginosa (P.a).
We review here the involvement of a range of innate phagocytic/signalling receptors in the control of this pathogen (mannose receptor, complement receptor-3, toll-like receptors) and evaluate the possibility that the activity of some of these receptors may be dysregulated in cystic fibrosis, potentially explaining the florid infections encountered in this disease
... While Erk 1/2 and p38 have also been shown to be necessary for invasion of Shigella, Chlamydia, and Salmonella spp. [39]
[40]
[41], the molecular mechanism by which Erk 1/2 and p38 promote bacterial invasion of intestinal cells is not known. It may be that the activation of Erk 1/2 and p38 alter gene transcription and the synthesis of proteins necessary for bacterial uptake or that Erk 1/2 and p38 activate other cellular proteins involved in bacterial invasion. ...
The Campylobacter jejuni CiaD effector protein activates MAP kinase signaling pathways and is required for the development of disease
<here is a image ab58b296e1564a83-0f3bddf77a7dfc37> Derrick R Samuelson
<here is a image 14ff76e1ab9e5338-5b813d554222dd7b> Tyson P Eucker
Julia A. Bell
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mike Konkel
Enteric pathogens utilize a distinct set of proteins to modulate host cell signaling events that promote host cell invasion, induction of the inflammatory response, and intracellular survival. Human infection with Campylobacter jejuni, the causative agent of campylobacteriosis, is characterized by diarrhea containing blood and leukocytes. The clinical presentation of acute disease, which is consistent with cellular invasion, requires the delivery of the Campylobacter invasion antigens (Cia) to the cytosol of host cells via a flagellar Type III Secretion System (T3SS). We identified a novel T3SS effector protein, which we termed CiaD that is exported from the C. jejuni flagellum and delivered to the cytosol of host cells.
We show that the host cell kinases p38 and Erk 1/2 are activated by CiaD, resulting in the secretion of interleukin-8 (IL-8) from host cells. Additional experiments revealed that CiaD-mediated activation of p38 and Erk 1/2 are required for maximal invasion of host cells by C. jejuni. CiaD contributes to disease, as evidenced by infection of IL-10 knockout mice. Noteworthy is that CiaD contains a Mitogen-activated protein (MAP) kinase-docking site that is found within effector proteins produced by other enteric pathogens. These findings indicate that C. jejuni activates the MAP kinase signaling pathways Erk 1/2 and p38 to promote cellular invasion and the release of the IL-8 pro-inflammatory chemokine.
The identification of a novel T3SS effector protein from C. jejuni significantly expands the knowledge of virulence proteins associated with C. jejuni pathogenesis and provides greater insight into the mechanism utilized by C. jejuni to invade host cells.
... However, when infected with P. aeruginosa, the primary HPCEC with siRNA-reduced levels of caveolin-1 failed to increase MAPK phosphorylation, suggesting that during infection the composition of caveolin-1-enriched "signaling hubs" changes to transmit an outside-in MAPK activation signal. These observations are intriguing, given that P. aeruginosa invasive strains such as 6294 utilize MAPK p42/p44 to gain entry into the epithelial host and suggest that caveolin-rich platforms are facilitating p42/p44 activation
(47)
. Unlike infection with the 6294, infection with the cytotoxic PA14 strain yielded milder changes of the caveolin-1 enrichment, suggesting that MIF-dependent regulation may impact the pathogenesis of those strains differently. ...
Homotrimeric Macrophage Migration Inhibitory Factor (MIF) Drives Inflammatory Responses in the Corneal Epithelium by Promoting Caveolin-rich Platform Assembly in Response to Infection
<here is a image 715e371f0008d8a1-83bb05a44dad8e4f> Thomas Reidy
Alexander Rittenberg
Markryan Dwyer
<here is a image bdee1358df5f7fd1-a75278fb1e803c88> Mihaela Gadjeva
Acute inflammation that arises during Pseudomonas aeruginosa-induced ocular infection can trigger tissue damage resulting in long term impairment of visual function, suggesting that
the appropriate treatment strategy should include the use of anti-inflammatory agents in addition to antibiotics. We recently
identified a potential target for modulation during ocular infection, macrophage migration inhibitory factor (MIF). MIF deficiency
protected mice from inflammatory-mediated corneal damage resulting from acute bacterial keratitis. To gain a better understanding
of the molecular mechanisms of MIF activity, we analyzed the oligomeric states and functional properties of MIF during infection.
We found that in human primary corneal cells infected with P. aeruginosa, MIF is primarily in a homotrimeric state. Homotrimeric MIF levels correlated with the severity of infection in the corneas
of infected mice, suggesting that the MIF homotrimers were the functionally active form of MIF. During infection, human primary
corneal cells released more IL-8 when treated with recombinant, locked MIF trimers than when treated with lower MIF oligomers.
MIF promoted P. aeruginosa–induced IL-8 responses via the formation of caveolin-1-rich “signaling hubs” in the corneal cells that led to elevated MAPK
p42/p44 activation and sustained inflammatory signaling. These findings suggest that inhibiting homotrimerization of MIF or
the functional activities of MIF homotrimers could have therapeutic benefits during ocular inflammation.
... Src and PI 3-kinase has been implicated in the regulation of events involved in the alteration of the actin cytoskeleton [28,29] and the roles in bacterial invasion of host cells have been reported [30,31]. Recent studies have identified MEK and ERK signaling proteins play very important role in the invasion of bacteria, such as P. aeruginosa, Staphylococcus aureus and Listeria monocytogenes [27,
32,
33]. Our reports proved that K. pneumonia induced ERK1/2 activation in T24 cells. ...
High-mobility group protein N2 (HMGN2) inhibited the internalization of Klebsiella pneumoniae into cultured bladder epithelial cells
ACTA BIOCH BIOPH SIN
<here is a image ba0059a3d1d9a406-f830946120af7c1b> Bo Fan
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ning Huang
Since bacterial invasion into host cells is an important step in the infection process, using the agents to interfere with
bacterial internalization is an attractive approach to block the infection process. In this work, we describe a new, previously
unrecognized role of the human cationic host defense peptide HMGN2 during Klebsiella pneumoniae infections. Our results revealed that the internalization of K. pneumoniae strain 03183 into cultured bladder epithelial cells (T24) was significantly reduced at HMGN2 concentrations that were unable
to produce any bacteriostatic or bactericidal effect. Using microarrays and follow-up studies, we demonstrated that HMGN2
affected the internalization of K. pneumoniae strain 03183 by inhibiting the attachment of bacteria, and then decreasing bacteria-induced ERK1/2 activation and actin polymerization,
which might contribute to bacterial internalization into T24 cells. This disruption of bacterial internalization implied that
HMGN2 could provide protection against K. pneumoniae infections.
... For example, MEK and ERK activity are increased in cells infected with S. typhimurium [71]. Moreover, pretreatment of cells with the MEK inhibitor PD98059 curtails invasion in some cell types by several organisms, including L. monocytogenes [54], S. typhimurium [55], Chlamydia pneumonia [72] and P. aeruginosa
[73]
. Importantly, IQGAP1 is a scaffold in the MAPK pathway. ...
IQGAP1 in microbial pathogenesis: Targeting the actin cytoskeleton
FEBS LETT
Hugh Kim
Colin D White
<here is a image 18750a9fc9564e7d-f828bc31d76d2826> David B Sacks
Microbial pathogens cause widespread morbidity and mortality. Central to the pathogens' virulence is manipulation of the host cell's cytoskeleton, which facilitates microbial invasion, multiplication, and avoidance of the innate immune response. IQGAP1 is a ubiquitously expressed scaffold protein that integrates diverse signaling cascades. Research has shown that IQGAP1 binds to and modulates the activity of multiple proteins that participate in bacterial invasion. Here, we review data that support a role for IQGAP1 in infectious disease via its ability to regulate the actin cytoskeleton. In addition, we explore other mechanisms by which IQGAP1 may be exploited by microbial pathogens.
... The pathway of P. aeruginosa internalization is sensitive to cytochalasin D, an actin-depolymerizing agent, is inhibited by the tyrosine kinase inhibitors herbimicin and genistein, and may involve the tyrosine kinase src, suggesting that protein phosphorylation events accompany internalization (Fleiszig et al., 1995; Evans et al., 2002a). The components of this signal transduction cascade have not been identified, although recent evidence suggests that mitogen-activated protein kinase kinase and extracellular signal-regulated kinase kinases may be involved (
Evans et al., 2002b
). Some strains of P. aeruginosa trigger the activation of the acid sphingomyelinase and the release of ceramide in sphingolipid-rich rafts. ...
Epithelial Cell Polarity Alters Rho-GTPase Responses to Pseudomonas aeruginosa
<here is a image 45f452e604098cfa-2ed9c44cc00af249> Barbara Kazmierczak
Keith Mostov
<here is a image 209503c121e459cb-a4fe3be1d8f8612d> Joanne N Engel
Pseudomonas aeruginosa is an opportunistic human pathogen that preferentially infects damaged epithelial tissues. Previous studies have failed to distinguish whether the increased susceptibility of injured epithelium results from the loss of cell polarity or increased access to the basolateral surface. We have used confluent monolayers of Madin-Darby canine kidney (MDCK) cells cultured on porous filter supports for 1-3 d as a model system to investigate whether the differentiation state of a polarized model epithelium affected the response of epithelial cells to this pathogen. Confluent incompletely polarized MDCK cell monolayers (day 1) efficiently internalized apically applied P. aeruginosa via a pathway that required actin polymerization and activation of Rho-family GTPases and was accompanied by an increase in the amount of activated RhoA. In contrast, P. aeruginosa entry into highly polarized MDCK monolayers (day 3) was 10- to 100-fold less efficient and was insensitive to inhibitors of actin polymerization or of Rho-family GTPase activation. There was no activation of RhoA; instead, Cdc42-GTP levels increased significantly. Basolateral infection of highly polarized MDCK monolayers was less efficient and insensitive to Clostridium difficile Toxin B, whereas basolateral infection of incompletely polarized MDCK monolayers was more efficient and required activation of Rho-family GTPases. Together, our findings suggest that as epithelial barrier differentiates and becomes highly polarized, it becomes resistant to P. aeruginosa infection. Nevertheless, polarized epithelial cells still sense the presence of apically infecting P. aeruginosa, but they may do so through a different group of surface proteins and/or downstream signaling pathways than do incompletely polarized cells.
... the most rapidly devastating bacterial infection of the cornea. 14 -20 The virulence of P. aeruginosa for the cornea has been correlated with a variety of factors, [21][22][23][24][25][26][27]
[28]
[29] including the production of the extracellular enzyme protease IV. Production of this enzyme has been shown in several animal models to correlate with tissue damage during keratitis. ...
Pseudomonas keratitis: protease IV gene conservation, distribution, and production relative to virulence and other Pseudomonas proteases
INVEST OPHTH VIS SCI
Armando R Caballero
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Brett Thibodeaux
<here is a image d7a68594d95ba0e0-490bc24b2f633223> Mary Marquart
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Richard O'Callaghan
To determine the distribution of the protease IV gene, the production of this and other proteases by multiple strains of Pseudomonas, and the virulence of a mutant specifically deficient in protease IV.
The protease IV gene was cloned, its sequence analyzed, and its chromosomal location determined by pulse-field gel electrophoresis. Three PCR reactions were used to detect the protease IV gene in 30 Pseudomonas isolates and protease production was determined by Western blot analysis, colorimetric assay, and zymography. An allelic replacement mutant deficient in the protease IV gene was analyzed for enzyme production, corneal growth, and corneal virulence.
The protease IV gene was identified in all P. aeruginosa, but none of the non-aeruginosa strains tested. The protease IV genes of strains PA103-29 and PAO1 were in a common chromosomal site and had 98.5% sequence identity with variations occurring mainly in the promoter region. The protease IV activity of the 23 wild-type P. aeruginosa strains tested varied from 2.3 to 221.5 x 10(-3) U/mg protein in the culture supernatant. Protease IV was produced by all P. aeruginosa wild-type strains. A protease IV-deficient mutant derived from strain PA103-29 had reduced virulence compared with its parent strain and unexpectedly produced alkaline protease.
The protease IV gene and its product are common to P. aeruginosa, but not to other Pseudomonas species. Protease IV activity varies among P. aeruginosa strains, and a mutant specifically deficient in this activity produced alkaline protease and had reduced corneal virulence.
... By using specific monoclonal antibodies directed against integrins and ECM proteins, the involvement of a 5 b 1 and a v b 5 integrins and their respective natural ligands fibronectin and vitronectin in P. aeruginosa adherence and invasion has been demonstrated (Leroy-Dudal et al., 2004). Src-family PTKs, MAP kinases and ERK are involved in P. aeruginosa internalisation by mammalian cells, and inhibition of Src-like tyrosine kinases resulted in a complete blockade of bacterial internalisation (Esen et al., 2001;
Evans et al., 2002)
. ...
Engagement of integrins as a cellular route of invasion by bacterial pathogens
VET J
Antonio Scibelli
Sante Roperto
<here is a image d87708fada50ac6c-1060dfbb51ec1323> Laura Manna
Norma Staiano
Integrins are heterodimeric receptors that mediate important cell functions, including cell adhesion, migration and tissue organisation. These transmembrane receptors regulate the direct association of cells with each other and with extracellular matrix proteins. However, by binding their ligands, integrins provide a transmembrane link for the bidirectional transmission of mechanical forces and biochemical signals across the plasma membrane. Interestingly, several of this family of receptors are exploited by pathogens to establish contact with the host cells. Hence, microbes subvert normal eukaryotic cell processes to create a specialised niche which allows their survival. This review highlights the fundamental role of integrins in bacterial pathogenesis.
... Although the in vivo effects of these changes remain to be investigated, the reduced Th1 cytokine levels induced by NE treatment of DCs may, in part, explain the reported Th2 imbalance in the lung immune response to bacteria in patients with CF (45,46) and the reported loss of IFN-␥-secreting cells in patients with COPD (47). This local Th2-biased phenotype may be instrumental in the inability of these patients to clear semifacultative intracellular pathogens in the lung, such as P. aeruginosa, B. cepacia, and H. influenzae, as suggested recently by a variety of animal and human studies (48)(49)
(50)
(51)(52)(53)(54)(55)(56)(57). In that context, our strategy of overexpression of the elastase inhibitor, elafin, could be dually advantageous by inhibiting NE and, as shown recently, by providing a Th1-biasing signal in the lungs (58). ...
Inflammatory Lung Secretions Inhibit Dendritic Cell Maturation and Function via Neutrophil Elastase
Ali Roghanian
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ellen Drost
William MacNee
<here is a image ff4a8f7b8c895bdb-ce4f9424fa6d1875> Jean-Michel Sallenave
Continuous episodes of infection are a feature of lung diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). Lung antigen-presenting dendritic cells (DCs) sample inhaled antigen to initiate immune responses. Therefore, we hypothesized that inflammatory mediators, such as neutrophil elastase (NE) released into the lung, may be able to modulate their activity.
To determine whether sputum (from patients with COPD and those with CF) or NE can alter DC phenotype and function. Method: NE and sputum samples were incubated with immature or mature murine DCs (mDCs). DC phenotype and function were studied by fluorescence-activated cell sorter and Western Blot analysis, assessing their expression of costimulatory molecules and their ability to induce T cell proliferation.
COPD/CF sputum samples and human NE downregulated the expression of CD40, CD80, and CD86 (but not major histocompatibility complex II) on DCs and inhibited LPS-induced DC maturation. This effect was partially (sputa) to significantly (NE) reversed by addition of recombinant secretory leukocyte protease inhibitor. Western Blot analysis showed that purified NE degraded CD86 in mDC lysates in a time- and dose-dependent fashion, and caused shedding of CD86 into the supernatants of mDC cultures. NE treatment also inhibited the antigen-presenting ability of mDCs, as measured by their ability to induce ovalbumin-specific D011.10-transgenic T-cell proliferation.
Our data indicate that NE in lung inflammatory secretions of patients with COPD/CF may disable DCs and prevent them from mounting an adequate immune response. This may have implications for the infection-driven generation of disease exacerbations in these two pathologies.
... Activation of MAP kinase family members precedes transcription factor's activation and regulates the inflammatory response to a diverse number of pathogens. A number of studies have shown activation of MAP kinases in response to different constituents ⁄ products of P. aeruginosa especially in epithelial cells [18,22,
[35]
[36][37]. Our study reports that viable P. aeruginosa bacteria cause rapid phoshorylation of all MAP kinase family members (p38, ERK1 ⁄ 2 and JNK) in fresh human monocytes, the main source of TNF-a production. ...
TNF-alpha Induction by Pseudomonas aeruginosa Lipopolysaccharide or Slime-glycolipoprotein in Human Monocytes is Regulated at the Level of Mitogen-activated Protein Kinase Activity: A Distinct Role of Toll-like Receptor 2 and 4
SCAND J IMMUNOL
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> George Lagoumintzis
<here is a image 19adb95780905e24-862749c430386da2> Panagiota Xaplanteri
G Dimitracopoulos
<here is a image cba2b35d6910d253-4807bd53c6f5a290> Fotini Paliogianni
TNF-alpha production has a central role in the development and progression of Pseudomonas aeruginosa septic shock. We have previously shown that P. aeruginosa slime-glycolipoprotein (slime-GLP) is the most potent stimulant compared to P. aeruginosa lipopolysaccharide (LPS), for TNF-alpha production and NF-kB activation in human monocytes. Herein, we show that secretion of TNF-alpha by fresh human monocytes, induced by P. aeruginosa slime-GLP, LPS or viable bacteria, was paralleled by phosphorylation and/or activation of Mitogen-activated Protein Kinases (MAPKs) ERK1/2, p38 as well as c-Jun NH(2)-terminal kinase. TNF-alpha levels were significantly reduced by ERK1/2 inhibitor (PD98059), or p38 inhibitor (SB203580). Combination of both inhibitors almost abolished TNF-alpha induction. Pseudomonas aeruginosa slime-GLP differed from the P. aeruginosa-LPS only regarding the strength of p38 and ERK1/2 activation, with slime-GLP leading to a stronger activation of p38 and ERK1/2. Involvement of TLR2 and TLR4 for phosphorylation of p38 and ERK1/2 was shown using specific blocking anti-TLR2 and anti-TLR4 antibodies. Activation of both p38 and ERK1/2 induced by P. aeruginosa slime-GLP was dramatically reduced in the presence of anti-TLR2 and to a lesser degree in the presence of anti-TLR4, whereas the P. aeruginosa-LPS-induced stimulation was inhibited only in the presence of anti-TLR4. Our data show that P. aeruginosa viable bacteria, through slime-GLP, stimulate specific members of the MAPKs more efficiently than the P. aeruginosa-LPS, involving mainly TLR2.
... These targets interact with bacterial invasion ligands, including lipopolysaccharide (LPS), flagellin, and pili (10,22,69). Invasion also involves numerous host cell intracellular signaling proteins, including Src-family tyrosine kinases (15,17,18,34), calcium-calmodulin (17), MEK-ERK
(19)
, Akt (36,37), and the actin cytoskeleton (35,43,44,57). However, little is known of the intracellular fate of P. aeruginosa after internalization or of the bacterial or host cell factors involved in intracellular survival/replication, with the exception that a complete LPS core is required (16,69). ...
Pseudomonas aeruginosa Induces Membrane Blebs in Epithelial Cells, Which Are Utilized as a Niche for Intracellular Replication and Motility
Article
Full-text available
Jun 2008
INFECT IMMUN
<here is a image 029f627a154605ba-51ad6eed9537c1f2> Annette Angus
Amanda Ackerman Lee
<here is a image 919d3e739cfbb78f-1af045ec6f29e2fb> Danielle Augustin
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Suzanne M Fleiszig
Pseudomonas aeruginosa is known to invade epithelial cells during infection and in vitro. However, little is known of bacterial or epithelial factors
modulating P. aeruginosa intracellular survival or replication after invasion, except that it requires a complete lipopolysaccharide core. In this
study, real-time video microscopy revealed that invasive P. aeruginosa isolates induced the formation of membrane blebs in multiple epithelial cell types and that these were then exploited for
intracellular replication and rapid real-time motility. Further studies revealed that the type three secretion system (T3SS)
of P. aeruginosa was required for blebbing. Mutants lacking either the entire T3SS or specific T3SS components were instead localized to intracellular
perinuclear vacuoles. Most T3SS mutants that trafficked to perinuclear vacuoles gradually lost intracellular viability, and
vacuoles containing those bacteria were labeled by the late endosomal marker lysosome-associated marker protein 3 (LAMP-3).
Interestingly, mutants deficient only in the T3SS translocon structure survived and replicated within the vacuoles that did
not label with LAMP-3. Taken together, these data suggest two novel roles of the P. aeruginosa T3SS in enabling bacterial intracellular survival: translocon-dependent formation of membrane blebs, which form a host cell
niche for bacterial growth and motility, and effector-dependent bacterial survival and replication within intracellular perinuclear
vacuoles.
Contact lens-related corneal infection: Intrinsic resistance and its compromise
Article
Nov 2019
PROG RETIN EYE RES
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Suzanne M Fleiszig
Abby R. Kroken
Vincent Nieto
<here is a image 64b2d529afc6e443-b97087aade6694e8> David J Evans
Contact lenses represent a widely utilized form of vision correction with more than 140 million wearers worldwide. Although generally well-tolerated, contact lenses can cause corneal infection (microbial keratitis), with an approximate annualized incidence ranging from ∼2 to ∼20 cases per 10,000 wearers, and sometimes resulting in permanent vision loss. Research suggests that the pathogenesis of contact lens-associated microbial keratitis is complex and multifactorial, likely requiring multiple conspiring factors that compromise the intrinsic resistance of a healthy cornea to infection. Here, we outline our perspective of the mechanisms by which contact lens wear sometimes renders the cornea susceptible to infection, focusing primarily on our own research efforts during the past three decades. This has included studies of host factors underlying the constitutive barrier function of the healthy cornea, its response to bacterial challenge when intrinsic resistance is not compromised, pathogen virulence mechanisms, and the effects of contact lens wear that alter the outcome of host-microbe interactions. For almost all of this work, we have utilized the bacterium Pseudomonas aeruginosa because it is the leading cause of lens-related microbial keratitis. While not yet common among corneal isolates, clinical isolates of P. aeruginosa have emerged that are resistant to virtually all currently available antibiotics, leading the United States CDC (Centers for Disease Control) to add P. aeruginosa to its list of most serious threats. Compounding this concern, the development of advanced contact lenses for biosensing and augmented reality, together with the escalating incidence of myopia, could portent an epidemic of vision-threatening corneal infections in the future. Thankfully, technological advances in genomics, proteomics, metabolomics and imaging combined with emerging models of contact lens-associated P. aeruginosa infection hold promise for solving the problem - and possibly life-threatening infections impacting other tissues.
Differential expression of antimicrobial peptides in corneal infection and regulation of antimicrobial peptides and reactive oxygen species by type III secretion system of Pseudomonas aeruginosa
Article
Full-text available
Jan 2018
<here is a image 885cd099501d7936-d40eaa1cd2f95c8b> Prerana Sharma
<here is a image 3af917f6163c7e94-eb6a4a6ef6d97efb> Sanjukta Guha
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Prashant Garg
<here is a image 9db7f9ade1c32a85-4d540a82676ae7d3> Sanhita Roy
Pseudomonas aeruginosa is an opportunistic pathogen and is the major cause of corneal infection worldwide that secret several virulent toxins through its type III secretion system (T3SS). In defense against pathogenic insults, epithelial cells and macrophages express antimicrobial peptides (AMPs) that are essential components of host immune response. In this study, we have determined the expression of several AMPs in patients with P. aeruginosa corneal infection. We also used an in vitro model of infection using human corneal epithelial cells and macrophages to determine the gene expression of AMPs and cellular response to wild-type and T3SS mutant P. aeruginosa. We found differential expression of several AMPs in patient samples and also found that P. aeruginosa repress AMP expression in both epithelial cells and macrophages by its T3SS in vitro. It dampens AMP expression by causing delay in NF-κB, p38 and ERK activation and inhibits reactive oxygen species generation in these cells by its T3SS. Our study show the profile of AMPs expressed during P. aeruginosa keratitis and suggest the pivotal role of the T3SS in epithelial cells and macrophages during P. aeruginosa infection.
Pseudomonas aeruginosa Interactions with Host Cells
Chapter
Jan 2004
<here is a image 6f8d23a70ddc74cb-bf022e5939c309cf> Gerald B Pier
Joanna B. Goldberg
The opportunistic nature of many different Pseudomonas aeruginosa infections leaves patients withcompromised immune systems highlysusceptible to infection. Common forms of immunesuppression leading to P. aeruginosa infectionincludeburn and traumawounds, diseasessuch as AIDS, or chemotherapeutic treatments that affect leukocyte numbers and functions. Cystic fibrosis (CF) patients develop chronic life-threatening lung infections with P. aeruginosa and can be considered to have defective innate and acquired immunity to this organism. Althoughrare, peoplewhouse extended-wear soft contact lenses are at an increasedrisk for acute ulcerative keratitis.
Pseudomonas Keratitis: Protease IV Gene Conservation, Distribution, and Production Relative to Virulence and Other Pseudomonas Proteases
Article
Feb 2004
INVEST OPHTH VIS SCI
Armando R Caballero
purpose. To determine the distribution of the protease IV gene, the production of this and other proteases by multiple strains of Pseudomonas, and the virulence of a mutant specifically deficient in protease IV.
methods. The protease IV gene was cloned, its sequence analyzed, and its chromosomal location determined by pulse-field gel electrophoresis. Three PCR reactions were used to detect the protease IV gene in 30 Pseudomonas isolates and protease production was determined by Western blot analysis, colorimetric assay, and zymography. An allelic replacement mutant deficient in the protease IV gene was analyzed for enzyme production, corneal growth, and corneal virulence.
results. The protease IV gene was identified in all P. aeruginosa, but none of the non-aeruginosa strains tested. The protease IV genes of strains PA103-29 and PAO1 were in a common chromosomal site and had 98.5% sequence identity with variations occurring mainly in the promoter region. The protease IV activity of the 23 wild-type P. aeruginosa strains tested varied from 2.3 to 221.5 × 10⁻³ U/mg protein in the culture supernatant. Protease IV was produced by all P. aeruginosa wild-type strains. A protease IV–deficient mutant derived from strain PA103-29 had reduced virulence compared with its parent strain and unexpectedly produced alkaline protease.
conclusions. The protease IV gene and its product are common to P. aeruginosa, but not to other Pseudomonas species. Protease IV activity varies among P. aeruginosa strains, and a mutant specifically deficient in this activity produced alkaline protease and had reduced corneal virulence.
Alpha(V)Beta(5) integrins mediates Pseudomonas fluorescens interaction with A549 cells
Article
Full-text available
Jan 2014
FRONT BIOSCI
<here is a image 5c1706bfddb7d08c-cb5672200b5da9bb> Elisabetta Buommino
<here is a image 4eddc7482667a34e-82de5efe0ea2026b> Marina Di Domenico
Iole Paoletti
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Giovanna Donnarumma
Interaction of pathogenic bacteria with human cells is usually an essential step in the infection process. The bacterial invasion is stimulated by microbial binding to mammalian extracellular matrix proteins such as vitronectin, fibronectin or integrins. We have recently shown that some strains isolated from a clinical environment are able to grow at/or above 37°C. In particular, we demonstrated that P. fluorescens AF181 binds specifically to the surface of A549 human respiratory epithelial cells and that adhesiveness modulates the inflammatory response. In this study, the involvement of AlphaᵥBeta₅ integrins and its respective natural ligand vitronectin (VN) in P. fluorescens AF181 adherence and invasion was examined. The host cell cytoskeleton and cellular tyrosine kinases seem to be solicited during the P. fluorescens-respiratory cell interaction; consequently, cytochalasin D and genistein decreased the bacterial adherence and internalization. Gene silencing of αᵥ, β₅ integrins and vitronectin reduced P. fluorescens adherence and internalization to A549 cells. Taken together, these findings suggest that AlphaᵥBeta₅ integrins and their natural ligand VN are involved in P. fluorescens adherence and invasion in human epithelial cells.
Contribution of Lethal Toxin and Edema Toxin to the Pathogenesis of Anthrax Meningitis
Article
Full-text available
Jul 2011
INFECT IMMUN
Celia M Ebrahimi
Tamsin R Sheen
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Christian Renken
<here is a image 9848c92f2da4e359-b1ebe3f53a822d07> Kelly Doran
Bacillus anthracis is a Gram-positive spore-forming bacterium that causes anthrax disease in humans and animals. Systemic infection is characterized by septicemia, toxemia, and meningitis, the main neurological complication associated with high mortality. We have shown previously that B. anthracis Sterne is capable of blood-brain barrier (BBB) penetration, establishing the classic signs of meningitis, and that infection is dependent on the expression of both major anthrax toxins, lethal toxin (LT) and edema toxin (ET). Here we further investigate the contribution of the individual toxins to BBB disruption using isogenic toxin mutants deficient in lethal factor, ΔLF, and edema factor, ΔEF. Acute infection with B. anthracis Sterne and the ΔLF mutant resulted in disruption of human brain microvascular endothelial cell (hBMEC) monolayer integrity and tight junction protein zona occludens-1, while the result for cells infected with the ΔEF mutant was similar to that for the noninfected control. A significant decrease in bacterial invasion of BBB endothelium in vitro was observed during infection with the ΔLF strain, suggesting a prominent role for LT in promoting BBB interaction. Further, treatment of hBMECs with purified LT or chemicals that mimic LT action on host signaling pathways rescued the hypoinvasive phenotype of the ΔLF mutant and resulted in increased bacterial uptake. We also observed that toxin expression reduced bacterial intracellular survival by inducing the bulk degradative autophagy pathway in host cells. Finally, in a murine model of anthrax meningitis, mice infected with the ΔLF mutant exhibited no mortality, brain bacterial load, or evidence of meningitis compared to mice infected with the parental or ΔEF strains.
Vitronectin in bacterial pathogenesis: A host protein used in complement escape and cellular invasion
Article
Nov 2010
MOL MICROBIOL
<here is a image 54bfc99aab596525-e4f3c4e4f27ef625> Birendra Singh
<here is a image e55ad0853a9d28c9-49360cda057e68c0> Yu-Ching Su
<here is a image 3bfb0e0932f7b844-6ac3c65619d8d59f> Kristian Riesbeck
The multifunctional human glycoprotein vitronectin (Vn) plays a significant role in cell migration, tissue repair and regulation of membrane attack complex (MAC) formation. It also promotes neutrophil infiltration and, thus, enhances the inflammatory process during infection. In the host, a balanced homeostasis is maintained by Vn due to neutralization of the self-reactivity of the MAC. On the other hand, Vn bound to the bacterial surface protects from MAC-mediated lysis and enhances adhesion. Gram-negative bacterial pathogens including Moraxella catarrhalis, Haemophilus influenzae and Neisseria gonorrhoeae use Vn recruitment to prevent MAC deposition at their surface. Moreover, Gram-positive bacterial pathogens such as Streptococcus pneumoniae and S. pyogenes utilize Vn for effective adhesion to host cells and subsequent internalization. Vitronectin has an Arg-Gly-Asp (RGD) sequence for binding the host cell integrin receptors and a separate bacterial-binding domain for pathogens, and thus more likely functions to cross-link bacteria and epithelial cells. Once bacteria are attached to the vitronectin-integrin complex, various host cell-signalling events are activated and promote internalization. In this review, we focus on the important roles of vitronectin in bacterial pathogenesis and describe different strategies used by pathogens to evade the host response by the help of this intriguing molecule.
Annexin II is a novel receptor for Pseudomonas aeruginosa
Article
Mar 2005
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Susanne Kirschnek
Constantin Adams
<here is a image 118b2caac9b8a13d-ec49358e948eda0c> Erich Gulbins
Infections with Pseudomonas aeruginosa (P. aeruginosa) are critical in ventilated and poly-traumatized patients. Most important, these bacteria cause frequent and chronic pulmonary infections in patients with cystic fibrosis. Therefore, identification of molecular mechanisms that mediate the infection of mammalian cells with P. aeruginosa is urgently required. Here, we aimed to identify novel receptors that are involved in internalization of P. aeruginosa into mammalian epithelial cells. Employing SDS-PAGE purification and mass spectrometry we demonstrate that annexin II specifically binds to P. aeruginosa. The significance of the interaction of annexin II with P. aeruginosa for the infection of mammalian cells is indicated by the finding that neutralization of the ligands on P. aeruginosa by incubation of the bacteria with recombinant, soluble annexin II prevents internalization of P. aeruginosa into human epithelial cells.
| https://www.researchgate.net/publication/11251217_Pseudomonas_aeruginosa_internalization_by_corneal_epithelial_cells_involves_MEK_and_ERK_signal_transduction_proteins |
Epidermal RAF prevents allergic skin disease | eLife
In keratinocytes, the BRAF and RAF1 proteins work independently to balance the activity of mitogenic and stress kinase cascades and uphold the mechanical and immunological barrier functions of the epidermis.
Epidermal RAF prevents allergic skin disease
Max F. Perutz Laboratories, University of Vienna, Austria ;
https://doi.org/10.7554/eLife.14012
Version of Record
Accepted for publication after peer review and revision.
Josipa Raguz
Ines Jeric
Joanna Daniela Nowacka
Sanya Eduarda Kuzet
Christian Rupp
Irmgard Fischer
Silvia Biggi
Tiziana Borsello
Manuela Baccarini
(2016)
Epidermal RAF prevents allergic skin disease
eLife 5 :e14012.
https://doi.org/10.7554/eLife.14012
July 19, 2016 (Go to version)
Accepted
June 13, 2016
Received
December 23, 2015
Of interest
Human DUX4 and mouse Dux interact with STAT1 and broadly inhibit interferon-stimulated gene induction
Amy E Spens, Nicholas A Sutliff ... Stephen J Tapscott
Josipa Raguz
Ines Jeric
Theodora Niault
Joanna Daniela Nowacka
Sanya Eduarda Kuzet
Christian Rupp
Irmgard Fischer
Silvia Biggi
Tiziana Borsello
Manuela Baccarini
(2016)
Epidermal RAF prevents allergic skin disease
eLife 5 :e14012.
https://doi.org/10.7554/eLife.14012
Abstract
The RAS pathway is central to epidermal homeostasis, and its activation in tumors or in Rasopathies correlates with hyperproliferation. Downstream of RAS, RAF kinases are actionable targets regulating keratinocyte turnover; however, chemical RAF inhibitors paradoxically activate the pathway, promoting epidermal proliferation. We generated mice with compound epidermis-restricted BRAF/RAF1 ablation. In these animals, transient barrier defects and production of chemokines and Th2-type cytokines by keratinocytes cause a disease akin to human atopic dermatitis, characterized by IgE responses and local and systemic inflammation. Mechanistically, BRAF and RAF1 operate independently to balance MAPK signaling: BRAF promotes ERK activation, while RAF1 dims stress kinase activation. In vivo, JNK inhibition prevents disease onset, while MEK/ERK inhibition in mice lacking epidermal RAF1 phenocopies it. These results support a primary role of keratinocytes in the pathogenesis of atopic dermatitis, and the animals lacking BRAF and RAF1 in the epidermis represent a useful model for this disease.
https://doi.org/10.7554/eLife.14012.001
eLife digest
The skin is the largest organ of the body and shields it from damage. It is also home to cells of the immune system, which protect the body from infections. To maintain its role as a barrier, the skin regenerates throughout life, constantly producing new cells to replace the old ones. If this process goes wrong and the skin regenerates too much, the skin may produce tumors. Likewise, disrupting the immune barrier can lead to autoimmune or allergic skin diseases such as psoriasis or atopic dermatitis (also known as eczema).
The outer layer of the skin is called the epidermis, and is made up of cells known as keratinocytes. A family of proteins called RAF plays an important role in controlling how keratinocytes behave. These proteins are part of a signaling pathway that controls the production of new cells and is disrupted in skin tumors. Therapies that inhibit RAF are effective treatments for these tumors but have side effects that can affect the skin so severely that the treatment must be interrupted.
Keratinocytes also play a role in the development of allergic skin diseases. However, it is not known whether they do so by triggering the disease themselves, or by responding to stimuli produced by immune cells.
Raguz et al. investigated what would happen if RAF proteins were removed from keratinocytes in the epidermis of mice. This caused the mice to develop an allergic disease similar to human atopic dermatitis. This was an unexpected effect and different from the side effects caused by drugs that inhibit RAF proteins. By analyzing the signaling pathway that RAF is part of, Raguz et al. discovered that removing RAF from the epidermis reduces the pathway’s ability to prevent excessive stress signals being sent throughout the skin. Under these conditions, the keratinocytes bring about inflammation and allergy by activating the immune cells in the skin and elsewhere.
Overall, the results presented by Raguz et al. indicate that allergic dermatitis can be triggered by defects in keratinocytes rather than in immune cells. Furthermore, RAF in the epidermis appears to prevent allergic skin diseases. Future studies could use mice that lack RAF in their epidermis to further understand atopic dermatitis and to investigate the way in which drugs that target RAF can damage the skin.
https://doi.org/10.7554/eLife.14012.002
Introduction
The largest organ of the body, the skin, allows exchange with the environment while shielding the organism from insults of mechanical, chemical, and infectious nature. In the skin, the epidermis acts as a mechanical barrier which prevents water loss and the entry of potentially harmful chemicals; in addition, through the interplay between keratinocytes in the epidermis and immune cells based mainly in the underlying dermis, the skin works as an immunological barrier actively defending the body from pathogens (Pasparakis et al., 2014;Nestle et al., 2009). Maintaining these barrier functions throughout life requires continuous regeneration of the epidermis and appropriately balanced immune responses. Dysregulation of the regenerative process can lead to a wide range of defects, from epidermal thickening to malignancies; and an imbalance in the skin’s immune reactions can lead to recurrent infections, or inflammatory/allergic diseases such as psoriasis or atopic dermatitis.
The RAF/MEK/ERK signaling pathway plays an essential role in the epidermis. Downstream of the EGFR and RAS, it acts in hair follicle development and wound healing; its mild activation in Rasopathies, genetic diseases caused by activating mutations in the pathway, results in skin phenotypes ranging from thickening of palms and soles to the development of papillomas; and strong activation in keratinocytes results in tumorigenesis (Kern et al., 2011;Ratushny et al., 2012). In animal models, epidermis-restricted inducible activation of RAF or MEK causes massive cutaneous hyperplasia and reduced differentiation (Khavari and Rinn, 2007). Consistently, RAF1 (also known as CRAF) and BRAF are essential for the development and progression of RAS-induced tumors although they fulfil different roles, with RAF1 preventing keratinocyte differentiation (Ehrenreiter et al., 2009) and BRAF promoting proliferation through MEK/ERK activation (Kern et al., 2013). The requirement for MEK/ERK in epidermal proliferation has been independently assessed (Khavari and Rinn, 2007;Dumesic et al., 2009;Scholl et al., 2009;Scholl et al., 2009).
In line with their prominent roles in cell proliferation and tumorigenesis in a number of tissues, the components of the EGFR/RAS/RAF/MEK/ERK pathway are attractive targets for molecule-based therapy. Many inhibitory compounds have been developed that are currently in clinical trials or have reached the clinic. Reflecting the function of the pathway in skin, cutaneous toxicities are one of the main adverse effects of these therapies; they can be severe and lead to an interruption of the therapy or to its termination (Belum et al., 2013;Curry et al., 2014;Dy and Adjei, 2013). These adverse effects can be roughly classified as inflammatory reactions, elicited chiefly by blocking EGFR or MEK; and proliferative events, caused by multikinase inhibitors such as sorafenib or by more specific RAF inhibitors (vemurafenib, dabrafenib). Cutaneous inflammation induced by agents blocking EGFR (erlotinib or cetuximab) and by MEK inhibitors (selumetinib and trametinib) is characterized by papulopustular rash, pruritus, and suppurative folliculitis in ≥80% of the patients (Curry et al., 2014). The effects of erlotinib and cetuximab are on-target, as recently demonstrated by two studies showing similar inflammatory phenotypes in mice with epidermis-restricted EGFR ablation (Mascia et al., 2013;Lichtenberger et al., 2013).
Skin rashes and pruritus are also observed in patients treated with inhibitors targeting RAF. Up to half of the cutaneous reactions induced by these compounds, however, consist of anomalous epidermal proliferation events ranging from different forms of keratosis to the development of drug-induced papillomas, keratoacanthomas, and squamous cell carcinomas (4–30% depending on the study and the inhibitors used) (Anforth et al., 2013). These side effects are mechanism-based and rely on the paradoxical activation of MEK/ERK promoted by the inhibitors in cultured cells, animal models, and patients (Samatar and Poulikakos, 2014;Holderfield et al., 2014). Consistent with this, combination treatment (RAF plus MEK inhibitors) reduces cutaneous toxicity (Flaherty et al., 2012;Mattei et al., 2013).
In contrast to RAF inhibitor treatment, inducible epidermis-restricted ablation of BRAF and RAF1 causes the rapid regression of RAS-driven tumors without apparent cutaneous toxicity (Kern et al., 2013). Here, we systematically test the effect of compound BRAF/RAF1 ablation in epidermis and show that it gives rise to a progressive disease strongly resembling human atopic dermatitis. Mechanistically, the disease relies on the combination of reduced ERK and increased stress kinase activation, leading to chemokine/cytokine overproduction and chronic, systemic inflammation.
Results
Epidermal BRAF and RAF1 are essential to prevent local and systemic inflammation
BRAF and RAF1 were ablated in the epidermis by introducing the Krt5-Cretransgene (Tarutani et al., 1997) into a Braf f/f ; Raf1 f/fbackground (Kern et al., 2013) (Figure 1A). The mice (heretofore referred to as Δ/Δep2) were born at Mendelian ratio but with their eyes open (Figure 1B), probably as a result of the migration defects of RAF1-deficient keratinocytes (Ehrenreiter et al., 2005). With time, however, they started to show symptoms of a progressive skin disease. These included intense itching and scratching resulting in partial alopecia and self-inflicted wounds (Figure 1B). Histological examination of the non-affected areas revealed thickening of the epidermis correlated with increased proliferation and expansion of both the basal and suprabasal keratinocytes but not with keratinocyte apoptosis (Figure 1CandFigure 1—figure supplement 1A). Filaggrin (FLG) expression was similar to that of the controls (Figure 1—figure supplement 1A). We also observed a rich dermal infiltrate comprised of activated (β1 Tryptase+) mast cells, granulocytes, dendritic cells and, less abundant, T cells and macrophages (Figure 1C–DandFigure 1—figure supplement 1B). In line with the dermal inflammatory reaction, Δ/Δep2 epidermis was characterized by the robust expression of the keratinocyte activation marker K6, of the cell adhesion molecule ICAM1, and by the sporadic expression of MHC class II molecules (Figure 1E), all upregulated in inflammatory conditions including atopic dermatitis (Freedberg et al., 2001;Fan et al., 2003;Caughman et al., 1992). Consistent with this, Δ/Δep2 epidermal lysates enriched in K5/K10-positive keratinocytes (Doma et al., 2013) contained increased amounts of the cytokine TSLP, associated with skin allergic disorders (Ziegler et al., 2013) (Figure 1F), as well as of other chemokines and cytokines, with CCL7, IL18, IL5 and IL13 levels significantly higher than controls (Figure 1G).
Figure 1 with 1 supplement see all
Compound deletion of BRAF and RAF1 in the epidermis leads to severe skin inflammation in adult mice.
( A) BRAF and RAF1 are efficiently deleted in epidermal cells as shown by PCR analysis of tail tissue and immunoblotting of epidermal lysates isolated from 3 weeks old F/F2 and Δ/Δep2 (n = 4). ACTB … see more
https://doi.org/10.7554/eLife.14012.003
Epidermal ablation of BRAF and RAF1 had profound systemic effects. The mice failed to thrive (Figure 2A) and presented with enlarged spleens and lymph nodes. The splenomegaly could largely be attributed to increased numbers of Mac1+Gr1+ cells (Figure 2B), a cell type found both in the spleen of a mouse model of FITC contact hypersensitivity/ S. aureusinfection and in the blood and skin infiltrates of atopic dermatitis patients (Skabytska et al., 2014). The lymph nodes contained elevated numbers of activated T, B, and dendritic cells (Figure 2C). In the blood, we observed leukocytosis and increased amounts of the chemokines CCL2 and CCL7, as well as of GCSF; in addition, serum IgEs were elevated in Δ/Δep2 mice (Figure 2D). Thus, the phenotype of adult Δ/Δep2 mice resembled a skin-specific allergic disease.
Figure 2
Inflammatory response in adult Δ/Δep2 animals.
( A) The body weight of Δ/Δep2 mice is significantly reduced compared to their littermates (n = 5). The data was analyzed by two-way analysis of variance (ANOVA) test. ( B) Increased spleen/body … see more
https://doi.org/10.7554/eLife.14012.005
To determine whether the systemic phenotype was secondary to the severe skin inflammation observed in adult animals, we examined Δ/Δep2 mice at weaning (3 weeks of age), at which stage they did not groom more than control littermates nor showed any signs of skin rash, except a mild eyelid irritation (Figure 3—figure supplement 1A). Skin architecture and keratinocyte proliferation were not altered at this stage (Figure 3—figure supplement 1A). In terms of dermal infiltrate, a 2-fold increase in mast cells could already be observed, but these cells were not activated (Figure 3AandFigure 3—figure supplement 1A). Granulocytes and dendritic cell numbers were indistinguishable in 3 weeks old F/F2 and Δ/Δep2 littermates (Figure 3—figure supplement 1A). In the epidermis, ICAM1 expression was slightly upregulated, while K6 and MHC II expression could not be detected (Figure 3AandFigure 3—figure supplement 1B). TSLP, CCL2, CCL7, and a number of cytokines (GMCSF, IL6, 4, 5, 13, 2) were already significantly elevated in the epidermal lysates, while only a trend could be observed for others (Figure 3BandFigure 3—figure supplement 1C). Systemically, enlarged lymph nodes contained increased amounts of activated T, B, and dendritic cells, while the spleen was normal both in size and cell composition (Figure 3CandFigure 3—figure supplement 1D). In the blood, the number of monocytes and granulocytes was increased, as were the levels of CCL2, CCL7, and GCSF. However, no significant difference in serum IgEs could be observed at this point (Figure 3D). The increase in T, B, and dendritic cells in lymph nodes and the granulocytosis could be traced as far back as 10 days of age, at which time point GCSF was the only cytokine elevated in the serum of Δ/Δep2 mice (Figure 3E–F). Thus, ablation of both Brafand Raf1in mouse epidermis does not directly disturb skin architecture but rather affects the cross-talk between keratinocytes and the innate and adaptive immune system.
Figure 3 with 1 supplement see all
Local and systemic inflammatory phenotype in young Δ/Δep2 animals.
( A) Local inflammation in 3 weeks old Δ/Δep2 animals. Total mast cells (toluidine blue staining, TB; quantified in the plot, n = 4–5) and ICAM1 staining. Scale bars, 25 µm. ( B) Inflammatory … see more
https://doi.org/10.7554/eLife.14012.006
Lack of epidermal BRAF and RAF1 causes transient inside-out barrier defects
Inflammatory skin conditions often involve impaired skin barrier function. Δ/Δep2 embryos performed normally in an outside-in dye penetration assay, indicating that stratum corneum permeability was not affected (Figure 4A). We next monitored the weight of E18.5 embryos of different genotypes for 9 hr after birth as a proxy for transepidermal water loss and thus for the barrier function of tight junctions. Δ/Δep2 embryos lost three-fold the weight of littermate controls (Figure 4B). Molecularly, reduced expression of E-cadherin (CDH1), an adherens junction protein known to regulate tight junctions (Tunggal et al., 2005), and of the tight junction protein claudin 1 (CLDN1), which is crucial for the maintenance of the inside-outside barrier (Furuse et al., 2002) and has been found downregulated in atopic dermatitis patients (De Benedetto et al., 2011) was still evident at P3 in Δ/Δep2 epidermis, while occludin expression was normal (OCLN) (Figure 4C). The architecture of P3 Δ/Δep2 skin was indistinguishable from that of controls (Figure 4—figure supplement 1A); P3 epidermal lysates contained highly variable amounts of chemokines and cytokines, predominantly CCL2, IL6 and IL18. All were increased in the Δ/Δep2 epidermal lysates, albeit not significantly (Figure 4—figure supplement 1B). The E-cadherin and claudin 1 downregulation was transient and was no longer detectable in 3 weeks old Δ/Δep2 mice (Figure 4D). Single deletion of RAF1 (RAF1Δ/Δep) and BRAF (BRAFΔ/Δep) did not lead to increased body weight loss in E18.5 embryos; consistently, the expression levels of tight junction proteins were normal in P3 epidermis (Figure 4—figure supplement 1C–D).
Figure 4 with 1 supplement see all
Transient inside-outside barrier defects in Δ/Δep2 animals.
( A) Intact outside-in barrier function (determined by toluidine blue penetration of the stratum corneum) in E19.5-day-old Δ/Δep2 embryos compared to controls (n = 6). Representative pictures; two … see more
https://doi.org/10.7554/eLife.14012.008
To assess the relevance of the transient perinatal barrier defect of Δ/Δep2 mice, we deleted Brafand Raf1in 3 weeks old mice using tamoxifen-inducible Krt5-Cre (Indra et al., 1999). These animals, termed Δ/Δep2 TX, showed conversion of both F to Δ alleles and strongly reduced expression of BRAF and RAF1 proteins in tail tissue (Figure 5A). Δ/Δep2 TXmice developed a milder disease than the Δ/Δep2 mice, characterized by much slower kinetics (8 months between ablation and overt symptoms), moderate keratinocyte hyperproliferation (assessed as increased epidermal thickness) and activation (as determined by K6 and ICAM1 expression), as well as by a modest increase in activated mast cells and granulocytes in the dermis (Figure 5B). At the systemic level, we observed mild splenomegaly with an increase in Mac1+Gr1+ cells (Figure 5C) as well as enlarged lymph nodes containing activated lymphocytes and dendritic cells (Figure 5DandFigure 5—figure supplement 1). Increased numbers of lymphocytes and granulocytes were found in the blood, while IgE levels were comparable to controls (Figure 5E). Thus, circumventing the transient barrier defect of the Δ/Δep2 animals postponed and attenuated the clinical manifestation of the disease.
Figure 5 with 1 supplement see all
Local and systemic inflammation in Δ/Δep2 TX mice.
( A) PCR analysis of tail tissue (left) and immunoblot analysis of epidermal lysates obtained from Δ/Δep2 TXanimals. ( B) Macroscopic appearance of Δ/Δep2 TXmice and histological analysis of H&E … see more
https://doi.org/10.7554/eLife.14012.010
Increased JNK and reduced ERK activation in Δ/Δep2 epidermis and cells
To gain insight in the molecular correlates of the phenotype, we analyzed MAPK signaling in the epidermis. We observed decreased activation of ERK and increased activation of JNK, assessed by the phosphorylation of both MAPK and their respective downstream targets pRSK and pJUN, in non-lesional epidermis of adult Δ/Δep2 and Δ/Δep2 TXmice; in contrast, phosphorylation of the p38 target MAPKAPK2 was not affected (Figure 6A and B). A more detailed analysis of 3 weeks old animals confirmed low ERK activation and increased phosphorylation of JNK (and, to a lower degree, p38) in Δ/Δep2 epidermal lysates (Figure 6C). Consistent with this phosphorylation pattern, the levels of the dual specificity phosphatase DUSP1 and DUSP10, negative regulators of the stress kinases (Patterson et al., 2009), were low in the Δ/Δep2 lysates. BRAFΔep lysates were characterized by reduced ERK phosphorylation only, while RAF1Δep lysates showed increased phosphorylation of all three MAPK. The expression of ICAM1 as marker of inflammation was detected only in the Δ/Δep2 lysates, leading to the hypothesis that the combination of high JNK, low ERK activation is at the basis of the inflammatory phenotype of Δ/Δep2 animals (Figure 6C).
Figure 6
Molecular consequences of BRAF/RAF1 deletion in primary keratinocytes and epidermis.
( A, B) Immunohistochemical analysis of pERK and pJNK, their downstream targets pRSK and pJUN, and the p38 downstream target pMAPKAPK2 in adult F/F2 and Δ/Δep2 ( A), and F/F2 TXΔ/Δep2 TXepidermis ( B). … see more
https://doi.org/10.7554/eLife.14012.012
Inhibition of ERK activation induces inflammatory skin disease in RAF1Δep mice
We tested this hypothesis by treating 6 weeks old RAF1Δep animals with a MEK inhibitor (MEKi; trametinib, in clinical use; daily by gavage for 32 days) to decrease ERK activation and determine whether this would phenocopy the Δ/Δep2 disease. MEKi efficiently reduced ERK phosphorylation and slightly increased JNK phosphorylation in both control and RAF1Δep epidermal lysates, but increased p38 phosphorylation was only observed in the RAF1Δep (Figure 7A). Consistently, MEKi reduced the expression of the phosphatases DUSP1 and 10 and of CLDN1 in RAF1Δep epidermis only (Figure 7A). Within a month, the RAF1Δep animals developed an inflammatory skin disease characterized by K6 and ICAM1 expression in the epidermis, by the presence of activated dermal mast cells and by an increase in TSLP (Figure 7B). In control animals, inhibitor treatment did not affect, or reduced chemo- or cytokine amounts; GMCSF, IL5, IL2 and CCL4 were reduced significantly, and a trend could be observed for IL4, IL17, IL27, and CXCL1. In contrast, a comparison between inhibitor-treated RAF1F/F and RAF1Δep lysates revealed a significant upregulation of CCL2, GMCSF, IL18, IL5, IL13, IL2, IL17 and CCL4 (Figure 7CandFigure 7—figure supplement 1). This correlated with increased Mac1+Gr1+ cells in the spleen and activated T, B, and dendritic cells in the lymph nodes (Figure 7D) as well as with increased circulating IgEs and granulocytosis (Figure 7E). Thus, inhibiting ERK in the RAF1Δep animals recreates the immunological environment necessary to bring about a disease very similar to that observed in Δ/Δep2 mice.
MEK/ERK inhibition in RAF1Δep animals phenocopies the Δ/Δep2 phenotype.
RAF1Δep animals were treated with a MEK inhibitor (MEKi; trametinib, daily by gavage for 32 days). ( A) Immunoblot of epidermal lysates showing the effect of MEKi on the phosphorylation and … see more
https://doi.org/10.7554/eLife.14012.013
The inflammatory skin disease of Δ/Δep2 mice can be prevented by JNK inhibition but not by MyD88, TNF or caspase 1/11 ablation
Collectively, the data above suggest that JNK activation was responsible for the inflammatory skin phenotype. To assess whether this was the case in vivo, we treated Δ/Δep2 animals with the specific peptide inhibitor D-JNKI1. D-JNKI1 efficiently blocked JUN phosphorylation, increased ERK and RSK phosphorylation (Figure 8A), and prevented the development of the disease as determined by ICAM1 and TSLP expression in the epidermis as well as by eyelid inflammation and mast cells accumulation in the dermis (Figure 8A–B). Consistent with the data inFigure 3—figure supplement 1B, K6 expression could not be observed in the interfollicular epidermis in any of the experimental groups (Figure 8—figure supplement 1A). Compared to untreated 3 weeks old animals, vehicle (TAT-peptide) alone had minor effects on the level of some chemokines and cytokines; the increase in IL17 and IL18 in TAT-peptide-treated Δ/Δep2 vs F/F2 animals became significant; the opposite was observed for CCL7, IL13 and IL4 (compareFigures 3Band8C; andFigure 3—figure supplement 1withFigure 8—figure supplement 1B). Treatment with D-JNKI1 reduced chemo- and cytokines in epidermal lysates of Δ/Δep2 animals to levels indistinguishable from, or lower than (CCL2, CCL4, GMCSF and IL4), those of F/F2 controls. Exceptions were IL6, which was significantly reduced in Δ/Δep2, but not in F/F2 epidermal lysates; and IL5, which was not affected by the inhibitor in either genotype (Figure 8CandFigure 8—figure supplement 1B). At the systemic level, D-JNKI1 normalized the numbers of activated B and dendritic cells in lymph nodes, while the numbers of activated T cells where reduced in both F/F2 and Δ/Δep2 lymph nodes (Figure 8D). Thus, JNK activation and the resulting chemo- and cytokine accumulation in the epidermis are required for disease development.
Figure 8 with 2 supplements see all
D-JNKI1 treatment rescues inflammation in Δ/Δep2 mice.
Mice were treated with D-JNKI1 or TAT peptide (22 mg/kg i.p. at 10 days of age) and analyzed after 12 days ( A) D-JNKI1 treatment prevents disease onset in Δ/Δep2 mice. Immunoblot of epidermal … see more
https://doi.org/10.7554/eLife.14012.015
To determine whether the increased JNK activation observed in the Δ/Δep2 animals was due to a specific signal, we mated them to MyD88 knockout animals (Adachi et al., 1998), to block both TLR (with the exception of TLR3) and IL1 signaling (Janssens and Beyaert, 2002). We also used TNFA knockout mice to prevent TNF signaling (Kuprash et al., 2005), and caspase 1/11 knockout mice to ablate IL1 and IL18 production (Smith et al., 1997). None of these knockouts altered the progression (onset around 2 months of age) or severity of the Δ/Δep2 skin disease (Figure 8—figure supplement 2). The Myd88 knockout, however, reduced the splenomegaly observed in the Δ/Δep2 mice. This specific phenotype is caused by an increase in Mac1+/Gr1+ splenocytes (Figure 2B), and its selective rescue in the compound Δ/Δep2;MyD88 knockout animals is likely due to the crucial role of MyD88 in the generation of these cells (Arora et al., 2010;Delano et al., 2007).
Interfering with the JNK pathway decreases the production of proinflammatory molecules in primary Δ/Δep2 keratinocytes and RAF knockdown HaCat cells
A concomitant increase in JNK activation and decrease in ERK activation is the basis of the skin disease of Δ/Δep2 animals. To test whether this molecular phenotype was cell-autonomous and to gain some insight in the molecular mechanisms underlying JNK activation, we established and analyzed primary keratinocytes cultures. Δ/Δep2 keratinocytes were “primed” for inflammation: they constitutively expressed ICAM1 (Figure 9A) and, upon stimulation, significantly increased amounts of chemokines (CCL2, CCL7) and cytokines (IL6, IL18, TSLP, IL13,Figure 9B; IL4 was not detected under these conditions). In addition, Δ/Δep2 keratinocytes showed decreased ERK activation in response to EGF and a strong increase in pJNK when co-treated with proinflammatory stimuli (Figure 9A). Treatment with D-JNKI1, a cell-penetrating, protease-resistant peptide that prevents JNK interaction with its JBD-dependent targets (Borsello and Forloni, 2007), reduced the expression of the inflammatory proteins ICAM1, TSLP, CCL2 and CCL7, but did not have any major effect on ERK activation and on the stress kinase phosphatases DUSP1 and DUSP10, expressed at lower levels in Δ/Δep2 keratinocytes (Figure 9C–D).
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Increased stress kinase signaling and JNK pathway-dependent cytokine and chemokine production by primary keratinocytes lacking BRAF and RAF1.
( A) Reduced ERK phosphorylation and increased JNK/p38 activation in primary Δ/Δep2 keratinocytes stimulated with EGF and/or TNFα and IL1β for 15 min. ( B) Increased cytokine and chemokine production … see more
https://doi.org/10.7554/eLife.14012.018
To ensure that the effects observed in the Δ/Δep2 cells and tissue could be reproduced by acute ablation, we performed knockdown experiments in the human keratinocyte cell line HaCat. Concomitant silencing of BRAFand RAF1(double knockdown, KD2) abolished basal ERK phosphorylation, decreased ERK activation and increased JNK activation by a combination of EGF and proinflammatory stimuli (Figure 9—figure supplement 1A). Constitutive ICAM1 expression was not observed in KD2 cells, but they expressed higher levels of this molecule when treated with TNFα. ICAM1 expression was reduced by D-JNKI1 in KD2 cells and increased by MEKi in RAF1KD cells (Figure 9—figure supplement 1B–C). CCL2mRNA accumulation, which depends on concomitant stress kinase activation and ERK inhibition, was also elevated in a JNK-dependent manner in KD2 cells (Figure 9—figure supplement 1B); MEK inhibition strongly increased CCL2mRNA in WT cells (Pastore et al., 2005) and even more so in RAF1KD cells (Figure 9—figure supplement 1C).
Mixed lineage kinase 3 (MLK3) activates the JNK pathway (Gallo and Johnson, 2002) and can function both as a positive regulator of ERK signaling, via kinase-independent mechanisms (Chadee and Kyriakis, 2004;Chadee et al., 2006) and as a negative regulator of ERK, via JNK-dependent mechanisms (Shen et al., 2003). Importantly, MLK3 binds to JIP1 (Whitmarsh et al., 1998), and signal flow from this upstream kinase would be interrupted by D-JKNI1. We thus determined whether MLK3 was implicated in the imbalance in ERK/JNK signaling observed in Δ/Δep2 primary keratinocytes and in KD2 HaCat cells. MLK3 downregulation by two independent shRNAs strongly reduced both ERK and JNK phosphorylation in F/F2 cells treated with EGF and proinflammatory stimuli; however, in Δ/Δep2 cells, only JNK phosphorylation was reduced (Figure 9E). Consistently, MLK3 downregulation reduced ICAM1 upregulation and the induction of Ccl2and TslpmRNA (Figure 9F). Essentially the same results were obtained by downregulating MLK3 in WT and KD2 HaCat cells (Figure 9—figure supplement 1D). Thus, MLK3 is responsible for JNK activation and the induction of inflammatory molecules in Δ/Δep2 keratinocytes and HaCat cells.
Discussion
BRAF and RAF1 prevent keratinocyte-driven allergic inflammation
Keratinocytes have long been known to contribute to the pathogenesis of skin inflammatory disorders, but whether they do so by reacting to stimuli produced by immune cells or by initiating the cascade leading to the disease is still a matter of debate. We describe an essential role of BRAF and RAF1 in keratinocytes in the control of allergic inflammation. Mice lacking BRAF/RAF1 in keratinocytes develop a disease clinically very similar to human atopic dermatitis (Bieber, 2010). It starts with a barrier defect accompanied by the reduced expression of crucial tight junction proteins and by a marginally increased expression of chemokines and cytokines, particularly CCL2, IL6 and IL18. It then progresses to a stage in which the skin appears unaffected, yet both local (mast cell infiltration, chemokine and cytokine production) and systemic (T and B cell activation, increased amounts of circulating leukocytes and chemokines) anomalies become evident while TSLP and IgE levels are only slightly increased. This is reminiscent of the early phase of atopic dermatitis in children, prior to IgE sensitization (Bieber, 2010). Unlike the majority of atopic dermatitis patients (De Benedetto et al., 2012), however, the Δ/Δep2 animals don’t have a stratum corneum defect, which may help explain the lack of symptoms at this stage. Adult mice present with a full-fledged disease characterized by rich dermal infiltrates, increased cytokine production, clearly elevated IgEs and mast cell activation, in good correlation with the intense pruritus causing extensive scratching and self-inflicted wounds. The initial barrier defect contributes to full-fledged disease, since ablation of BRAF/RAF1 after the third week causes a less severe condition lacking IgE sensitization and mast cell activation, yet recapitulating the systemic symptoms of the disease. This could be likened to late-onset, IgE-sensitization-independent dermatitis (Bieber, 2010). Thus, BRAF and RAF1 act together to ensure the timely establishment of the inside-out barrier of the epidermis and to prevent allergic inflammation. The data support the hypothesis that the keratinocytes play a primary role in the pathogenesis of atopic dermatitis, and the Δ/Δep2 animals may be useful as a model for this disease (Figure 10).
Figure 10
Molecular and physiological defects in mice lacking BRAF and RAF1 in the epidermis.
Compound BRAF/RAF1 ablation in keratinocytes induces an imbalance in MAPK signaling, resulting in low ERK, high JNK activation. This causes early inside-outside barrier defects accompanied by … see more
https://doi.org/10.7554/eLife.14012.020
A set of chemokines and Th2 cytokines underlies Δ/Δep2 allergic inflammation
In this respect, our experiments provide information about the minimal set of keratinocyte-derived factors required for the establishment of allergic, atopic dermatitis-like inflammation.
In the phase before IgE sensitization and mast cell activation, we detected significantly higher levels of TSLP, CCL2, CCL7, GMCSF, IL2, IL5, IL6, and IL13 in Δ/Δep2 epidermal lysates; most chemokines and cytokines in the Δ/Δep2 animals were sensitive to D-JNKI1 inhibitor treatment, which brought Δ/Δep2 and F/F2 epidermal lysates down to indistinguishable levels. Conversely, the set of cytokines (TSLP, IL5, IL13, IL18, borderline IL2 and IL17) observed in adult, diseased Δ/Δep2 mice was similar to that promoting symptomatic disease in RAF1Δep animals treated with trametinib, which showed an increase in TSLP, IL2, IL5, IL13, as well as in IL18. These data can be interpreted to mean that ERK signaling negatively regulates the production of allergy-promoting factors. However, it is important to note that trametinib treatment reduced IL2 and IL5 as well as GMCSF in the F/F2 epidermis, indicating that sensitivity to ERK inhibition must be seen in the context of altered cell-autonomous signaling (increased JNK activation in RAF1Δep epidermis) and/or tissue milieu. Along the same lines, Δ/Δep2 keratinocytes treated with inflammatory stimuli were significantly more efficient than F/F2 in producing CCL2, CCL7, IL6, IL18, TSLP and IL13, but not IL2 or IL5, resembling, but not fully reproducing, the spectrum observed in epidermal lysates. At this stage, it is impossible to determine whether these discrepancies might be due to the presence of cell types other than keratinocytes in the epidermal lysates or whether the culture and stimulation conditions used did not recapitulate the situation in vivo.
Be that as it may, the range of chemokines and cytokines overrepresented in the Δ/Δep2 mice and in the trametinib-treated RAF1Δep mice is consistent with allergic inflammation. In this respect, strong expression of CCL2 has been reported in the basal keratinocytes of atopic dermatitis patients (Giustizieri et al., 2001), and expression of CCL7, which can attract basophils, eosinophils, mast cells and Th2 cells, can be induced by allergens in atopic skin (Ying et al., 1995).
TSLP, the signature cytokine of allergic disease, promotes the functions of these same cell types (Ziegler et al., 2013), and is responsible for the extreme itching accompanying atopic dermatitis (Wilson et al., 2013). High levels of TSLP (Liu, 2006), but also of IL5 and IL13 have been reported in the skin of atopic dermatitis patients, particularly in those with elevated IgEs (Jeong et al., 2003). In mice, it could be shown that the expression of TSLP (Liu, 2006), IL4, IL5 and IL13 induces atopic dermatitis as well as asthma (Lee and Flavell, 2004), and IL5 knockout mice exposed to allergens are less prone than wild-type to develop skin eosinophilia and epidermal thickening (Spergel et al., 1999). Finally, expression of IL13 in keratinocytes is sufficient to induce a disease mimicking atopic dermatitis (Zheng et al., 2009). Thus, these cytokines appear instrumental for the development of atopic dermatitis with IgE sensitization. IL18, on the other hand, can stimulate both Th1 and Th2 responses (Nakanishi et al., 2001), and appears to be causally involved in a different type of atopic dermatitis. IL18 is essential for the induction of dermatitis by the epidermis-restricted expression of caspase 1, the enzyme that generates active IL18 from its precursor. In addition, expression of IL18 in keratinocytes induces a late-onset dermatitis associated with mastocytosis, but independent of IgE production (Konishi et al., 2002). More recently, IL18 knockout mice were shown to be resistant to infection-associated atopic dermatitis, in a mouse model generated by perturbing the stratum corneum with detergent prior to topical application of S. aureusprotein A (Terada et al., 2006). However, stratum corneum defects could not be observed in Δ/Δep2 mice, and caspase 1 ablation does not modify the course of the Δ/Δep2 disease. Thus, IL18 is not a determining factor in the context of the Δ/Δep2 dermatitis, which rather resembles a Th2/IgE-driven disease.
An imbalance in MAPK signaling underlies skin inflammation in Δ/Δep2 mice
Ablation of BRAF and RAF1 in the epidermis has non-redundant functions converging on MAPK cascades. Decreased ERK and increased JNK activation are observed in Δ/Δep2 epidermis in vivo independently of the severity of the disease as well as in Δ/Δep2 keratinocytes and BRAF/RAF1 knockdown HaCat cells. Thus, the imbalance in MAPK signaling represents an intrinsic defect of cells and tissues lacking BRAF/RAF1. While BRAF ablation, as in many other tissues/organs, is responsible for reduced ERK activation (Desideri et al., 2015), RAF1 ablation correlates with a previously unnoticed increase in stress kinase activation. Consistent with this, we have observed a reduction in the expression of two DUSPs involved in the inactivation of stress kinases, which is strongest in the Δ/Δep2 epidermis. This is in line with the reported positive role of p38 in the induction of DUSP expression and of ERK in its attenuation at multiple levels (Caunt and Keyse, 2013;Taxman et al., 2011), which would predict that decreased ERK signaling would be needed to reduce DUSP expression and stabilize JNK phosphorylation when p38 is active. Importantly, both DUSPs have been implicated in the production of cytokines by immunocompetent cells and in murine models of inflammatory and autoimmune disease (Lang et al., 2006).
We could further identify MLK3 as the kinase responsible for JNK activation as well as for the expression of inflammatory molecules in primary Δ/Δep2 keratinocytes and BRAF/RAF1 knockdown HaCat cells costimulated with EGF, TNFα and IL1β (as a proxy for the alterations observed in the Δ/Δep2 animals). The lack of basal JNK activation in unstimulated cells suggests a cross-talk at the level of BRAF/RAF1 and MLK3 rather than direct MLK3 activation by BRAF/RAF1 ablation. Such a cross-talk was previously reported to occur in the context of ERK signaling, which is positively regulated by MLK3 via the stabilization of the RAF dimer (Chadee and Kyriakis, 2004;Chadee et al., 2006). It is possible that in turn, BRAF and RAF1 would restrict the involvement of MLK3 in the JNK pathway, at the same time promoting ERK and reducing JNK activation in stimulated cells (Figure 10).
While the mechanistic details remain to be fully elucidated, the relevance of the imbalance in MAPK signaling for the development of the atopic dermatitis-like disease in Δ/Δep2 animals was shown in vivo in two complementary ways: 1) by preventing disease onset with the specific peptide inhibitor D-JNKI1; and 2) by inducing disease in healthy RAF1Δep animals with a MEK inhibitor (Figure 10). The second set of experiments also clearly shows that the function of BRAF and RAF1 in the epidermis is not redundant. Finally, the combined RAF knockout and inhibitor data help explain why in patients the cutaneous toxicity of RAF inhibitors, which increase ERK activation, is mostly related to hyperproliferation (Anforth et al., 2013), while inhibitors of ERK activation promote the onset or exacerbate the course of cutaneous inflammatory reactions involving stress kinase activation (Curry et al., 2014).
Materials and methods
Animal studies and inhibitor treatment
All strains were maintained on a Sv/129 background. Krt5-CreBraf f/f ;Raf1 f/fmice were generated for this study by mating Krt5-Cre;Braf f/f :: Krt5-Cre;Raf1 f/fanimals. These strains, the Krt5-CreER(TX);Braf f/f ;Raf1 f/fmice as well as their genotyping and the tamoxifen-induced deletion of the RAFalleles have been previously described (Kern et al., 2013;Ehrenreiter et al., 2005). Inducible RAF deletion was performed at the age of three weeks.
Krt5-CreBraf f/f ;Raf1 f/fwere mated with MyD88 (Adachi et al., 1998), TNF (Kuprash et al., 2005), and caspase 1/11 (Smith et al., 1997) knockout mice, all maintained on a C57BL/6 background, to test the contribution of the respective signaling pathways to the Krt5-CreBraf f/f ;Raf1 f/fphenotype.
In selected experiments, the MEK inhibitor GSK1120212 (trametinib, Selleckchem, Germany) was applied daily by gavage for 32 days (Doma et al., 2013). The peptide inhibitor D-JNKI1 was synthesized at the Istituto di Ricerche Farmacologiche 'Mario Negri' (Milano, Italy), as previously described (Borsello et al., 2003). Ten days old animals were injected once i.p. (22 mg/kg) with D-JNKI1 or TAT peptide control ((D-Pro1,2) retro-(D-HIV-TAT (aa 48-57), Enzo Life Sciences, NY, USA, BML-El384-0001). Animal experiments were authorized by the Austrian Ministry of Science, Research and Economy.
Histology and immunohistochemistry
H&E staining, TUNEL, BrdU incorporation and immunohistochemistry were carried out as described (Ehrenreiter et al., 2009) on paraffin or cryostat sections. The following antibodies were used: β1 Tryptase (AF1937) and ICAM1 (AF796) from R&D Systems (Minneapolis, MN); CD11c (14–0114) and MHC II (14–5321) from Affymetrix eBioscience (Santa Clara, CA); K6 (905701), K5 (905501), K10 (905401) and Involucrin (924401) from BioLegend (San Diego, CA); F4/80 (AbDSerotec, UK, MCAP497); CD4 (550280) and CD8 (550281) from BD Biosciences (San Jose, CA); Filaggrin (ab24584), pRSK (ab32413) and pJNK (ab4821) from Abcam (UK); pJUN (9164) and pERK (4376) from Cell Signaling Technology (Danvers, MA). Granulocytes were visualized using the Naphthol AS-D Chloroacetate (specific esterase) kit (Sigma, 91C-1KT) according to the manufacturer's instruction. Toluidine blue staining for mast cells was carried out as described (Mascia et al., 2013). Histology images were acquired with a ZEISS microscope Imager M1 (20x/0.5 or 10x/0.3 Plan-NeoFluar objectives) equipped with ZEISS AxioCamMRc5. Data were analyzed with ZEISS Axiovision Release 4.8.1 software (Carl Zeiss, Germany). Fluorescent images were acquired with ZEISS Axioplan2 microscope (40x objective, Zeiss Plan – NEOFLUAR; Num: ap. 1.3) equipped with Spot Pursuit Camera (Visitron Systems, Germany) and analyzed with VisiView software (Visitron Systems).
Blood analysis and FACS
Peripheral blood cell counts were acquired using V-Sight (Menarini Diagnostics, Italy). Spleen and lymph node cells were stained with antibodies against CD11c (550261), CD4 (553051), MHC II (557000), CD69 (557392), CD80 (553768), CD8 (553032), B220 (553090), Mac1 (553310) and Gr1 (553128) all from BD Bioscience and analyzed by FACSCalibur (BD Bioscience) and FlowJo V10 software (Ashland, OR).
FlowCytomix analyte assay and ELISA
Cytokines and chemokines were detected in cell supernatants, serum samples and epidermal tissue lysates using the Affymetrix eBioscience bead-based multiplex immunoassay. Data were analyzed with FlowCytomix Pro2.4 software. GCSF (R&D Systems, DY414), TSLP (R&D Systems, DY555) and IgEs (Bethyl Laboratories, E90-115) in serum samples were detected by ELISA according to the manufacturer's protocol.
Barrier function assays
Water loss assay and toluidine blue dye staining of embryos were carried out as described (Tunggal et al., 2005).
Cell culture
HaCaT cells obtained from the DKFZ and mouse keratinocytes were maintained as described (Doma et al, 2013). BRAF (L-003460-00), MLK3 (L-003577-00) and RAF1 (L-003601-00) were silenced using ON-TARGETplus SMARTpool siRNAs (Thermo Fisher Scientific, Waltham, MA). Nontargeting pool (D-001810-10-20) was used as control. In accordance with the supplier's protocol, 5×10 5cells were transfected with 25 nM of the previously mentioned oligos. Cells were treated with EGF (2 ng/ml, R&D Systems, 2028-EG) and/or with TNFα (2.5 ng/ml, Millipore, Billerica, MA, 654245) and IL1β (2.5 ng/ml, R&D Systems, 401-ML/CF) as indicated. For cytokine/chemokine assays supernatants were collected 24 hr later. In selected experiments, cells were pretreated for 1 hr with medium containing DMSO (for trametinib) or TAT peptide only (for D-JNKI1) or with the following inhibitors: D-JNKI1 (2µM) or trametinib (5µM).
Lentiviral vectors, cloning and transduction procedure
Request a detailed protocol
Two independent shRNAs against mouse MLK3 (shRNA1, binding site 2266–2285 and shRNA2, binding site 2383–2402) were designed as 97-bp oligomers containing a 20bp targeting sequence embedded in a shRNAmir stem, amplified and cloned into Xho and EcoRI sites of the miRE lentiviral recipient vector pRRL.SFFV.GFP.miRE.PGK.Puro (SGEP) (Fellmann et al., 2013). The SGEP plasmid containing Renilla shRNA served as a control. Lentiviral vectors were transfected in 293T cells. Viral supernatants were collected after 24 and 48 hr and passed through a 0.45-μm filter (Sarstedt, Germany). Each fresh viral supernatant was used for primary keratinocyte spinfection (1500 g, 30 min). Primary keratinocyte cultures were harvested 72 hr after first transduction.
Immunoblotting
Cell and epidermal lysates prepared as previously described (Doma et al., 2013) were immunoblotted using the following primary antibodies (1:1000): TUBA (T9206,) from Sigma; pERK1/2 (9101), ERK1/2 (9102), JNK1/2 (9258), pJNK 1/2 (9251), pJUN (9164), pMAPKAPK2 (3041), pp38 (9211), p38 (9212) and ICAM1 (4915) from Cell Signaling Technology; ACTB (sc-1616), 14-3-3 (sc-1657), BRAF (sc-5284), RAF1 (sc-133) and MLK3 (sc-166639 and sc-536) from Santa Cruz Biotechnology (Dallas, TX); CDH1 (610181) from BD Biosciences; OCLN (ab31721), pRSK (ab32413), TSLP (ab188766) and DUSP10 (ab140123) from Abcam; GAPDH (ABS16) and DUSP1 (07–535) from Millipore; ICAM1 (AF796, R&D Systems) and CLDN1 (374900, Invitrogen, Karlsbad, CA).
Quantitative PCR
RNA was isolated using Nucleospin RNA II kit (Macherey-Nagel, Germany). cDNA was prepared using Oligo(dT) 18primer, dNTPs, and RevertAidReverse Transcriptase (Thermo Fisher Scientific). qPCR was performed using Go Taq qPCR Master mix (A6002, Promega, Madison, WI). Relative expression was calculated by the ΔΔCT method using ACTBas housekeeping gene. Human CCL2primers used: for 5`-CAGCCAGATGCAATCAATGC-3´ and rev 5´-GCACTGAGATCTTCCTATTGGTGAA-3´, human ACTBfor 5`-AGAGCTACGAGCTGCCTGAC-3´ and rev 5´-AGCACTGTGTTGGCGTACAG-3´. Mouse Ccl2primers used: for 5`-CCCAATGAGTAGGCTGGAGA-3´ and 5`-AAAATGGATCCACACCTTGC-3´; mouse Tslpfor 5`-CGACAGCATGGTTCTTCTCA-3´ and 5`-CGATTTGCTCGAACTTAGCC-3´, mouse ActBfor 5`-CCTCTATGCCAACACAGTGC-3´ and 5`-GTACTCCTGCTTGCTGATCC-3´.
Statistical analysis
Histological samples from at least three animals per condition and genotype were analyzed by counting or measuring at least 3–5 microscopic field/section and analyzed by ImageJ software. Values are expressed as mean (±SEM). The number of biological replicates and, where applicable, technical replicates are indicated in the figure legends. p values were calculated using the two-tailed Student's t test, hetero- or homoskedastic as determined by a previous F-test of equality of variances or, when indicated, by two-way analysis of variance (ANOVA) test. A p value ≤ 0.05 is considered statistically significant.
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Decision letter
Roger J Davis
Reviewing Editor; University of Massachusetts Medical School, United States
In the interests of transparency, eLife includes the editorial decision letter and accompanying author responses. A lightly edited version of the letter sent to the authors after peer review is shown, indicating the most substantive concerns; minor comments are not usually included.
Thank you for submitting your work entitled "Epidermal RAF prevents allergic skin disease" for consideration by eLife. Your article has been favorably evaluated by Tony Hunter (Senior editor) and four reviewers, one of whom is a member of our Board of Reviewing Editors.
The reviewers have discussed the reviews with one another and the Reviewing Editor has drafted a list of experiments and changes that we feel must be completed before this work could be published in eLife. At this point, it would help us to have a response from you concerning the list of requirements and the time it would take to complete these task before we make a final recommendation.
Summary:
The manuscript addresses the role of the RAF kinases BRAF and RAF1 in keratinocytes. Mice with combined loss of expression of these kinases in the epidermis exhibit skin defects similar to the human disease, atopic dermatitis (AD). There is local and systemic inflammation, including increased production of chemokines and TH2-type cytokines. The authors show that BRAF is required for ERK activation and that RAF1 suppresses the activation of the stress-activated MAP kinases JNK and p38. Inhibition of JNK in mice prevents the skin defects while inhibition of MEK in mice lacking epidermal RAF1 promotes these.
The authors conclude that RAF enzymes play a key role in the pathogenesis of the atopic dermatitis-like disease in mice and suggest that this may represent a relevant model for studying the disease. Overall the study is interesting. It builds on previous work addressing the complex interplay between the RAF enzymes and the observations that inhibitors targeting RAF can result in inflammatory skin conditions.
Essential revisions:
1) TSLP is a key cytokine for AD-like disease, thus an increase in TSLP levels is very relevant for the conclusions of this study. However, TSLP staining in the epidermis does not look specific, as it should be localized to the cytoplasm, not to the nucleus. The authors should determine the levels of TSLP by RNA and protein (WB or ELISA) in epidermal extracts in all Figures.
2) It is well accepted that IL-4/IL-13 cytokines play important roles in the development of AD. It is necessary to include analyses of both cytokines in all experiments.
3) The IHC analysis is difficult to interpret; some examples includeFigure 3Awhere the panels are too small; Figure 6—figure supplement 1 where the changes in staining between F/F2 and ∆/∆ep2 are unclear; inFigure 8B: please use the same magnification that is used for TSLP staining in all panels to make staining more visible; and in regards to ICAM staining use, a better example that clearly shows the epidermis is needed. In general, the quality of all IHC images should be improved and quantifications should be included.
4) The data on MLK3 expression in HaCat cells are not convincing. Is MLK3 activated by loss of Raf1/Braf? JNK inhibition in KD2 cells inFigure 9Dis not clear either, and thus these results should be repeated in ∆/∆ep2 keratinocytes in vitro.
5) There is a large body of evidence presented in the manuscript as data not shown that relates to the investigation of increased JNK activation, such as mating the ∆/∆ep2 mice to MyD88, TNFα and caspase 1/11 knock-out mice. These data should be included in the paper, as these results are relevant to the conclusions of the manuscript.
6) The use of SP600125 is not recommended because it is a relatively non-selective kinase inhibitor. Any experiment where SP600125 was used should be replaced with a more selective inhibitor.
7) The RNAi studies are poorly designed – phenotypes should be confirmed with two independent single oligonucleotides and rescued by expression of an RNAi-resistant cDNA.
8) The authors show that BRAF/RAF1 deletion causes an "inside out" barrier defect (Figure 4). Comparing mice with combined BRAF/RAF1 deletion, with mice presenting single deletion for BRAF or RAF1, would be important. Some studies have shown that RAF1 is implicated in disrupting tight junctions (Oncogene. 2007 26(8):1222-30 PMID: 16924233; J Cell Biol. 2000 148(4):791-800.PMID: 10684259).
9) The transient barrier defect conclusion in E18.5 embryos is unclear. At the end of the subsection “Lack of epidermal BRAF and RAF1 causes transient inside-out barrier defects” it is proposed that this defect affects the progression of the disease. This is partly based on the fact that deletion of Braf/Raf1 at 3 weeks produces a more modest phenotype. This may be one possible explanation. The milder phenotype may be a reflection of less robust gene deletion in the K5CreER(TX) mice. An immunoblot of epidermal lysates for BRAF and RAF1 should be included inFigure 5A.
10)Figure 6: First, there appears to be specific activation of one ERK isoform (which one?) based on the pERK immunoblot inFigure 6A, whilst inFigure 6Cboth isoforms are phosphorylated. Second,Figure 6B– significance value for IL-13 missing. Third,Figure 6D– what is the explanation for why D-JNKi specifically suppresses CCL2 and CCL7 levels in the Δ/Δep2 mice, while the JNK/p38 inhibitors reduce levels in both F/F2 and knock-out mice?
11)Figure 7A: D-JNKi appears to suppress pERK in F/F2 epidermis to similar levels as found in Δ/Δep2. Is there an explanation for this?
12) Overall the outline of the paper is not very logical and it should be improved for clarity. For example, the analysis of the inflammation markers is often inconsistent, and the cytokines/chemokines shown inFigure 1Fshould also be shown in the subsequent figures such asFigure 2D.
https://doi.org/10.7554/eLife.14012.021
Author response
Essential revisions:
1) TSLP is a key cytokine for AD-like disease, thus an increase in TSLP levels is very relevant for the conclusions of this study. However, TSLP staining in the epidermis does not look specific, as it should be localized to the cytoplasm, not to the nucleus. The authors should determine the levels of TSLP by RNA and protein (WB or ELISA) in epidermal extracts in all Figures.
The level of TSLP determined by immunoblotting have been found elevated in adult animals (Figure 1F), and in 3 weeks old mice (Figure 3B); in addition, TSLP levels are decreased in D-JNKI1-treated ∆/∆ep2 mice (Figure 8A) and increased in RAF1∆/∆ep mice treated with MEKi (Figure 7C). TSLP amounts, determined by ELISA, are significantly increased in the supernatant of primary Δ/Δep2 keratinocytes; treatment with a D-JNKI1 abolishes this increase (Figure 9B and D); Tslp mRNA levels are also increased in Δ/Δep2 keratinocytes; this increase is abolished by MLK3 silencing (Figure 9F). Collectively, the data show that TSLP is elevated in a JNK pathway-dependent manner in Δ/Δep2 tissues and cells.
2) It is well accepted that IL-4/IL-13 cytokines play important roles in the development of AD. It is necessary to include analyses of both cytokines in all experiments.
These data were already included in the manuscript, either in the main Figures (original 1F, adult mice – nowFigure 1G;Figure 3B, 3-weeks old mice; originalFigure 7C, andFigure 7—figure supplement 1A,D-JNKI1 – nowFigure 8CandFigure 8—figure supplement 1A; originalFigure 8andFigure 8—figure supplement 1, trametinib – nowFigure 7CandFigure 7—figure supplement 1; originalFigure 6B– nowFigure 9B, keratinocytes). IL-4 was not detected, this is stated in the first paragraph of the subsection “Interfering with the JNK pathway decreases the production of proinflammatory molecules in primary Δ/Δep2 keratinocytes and RAF knockdown HaCat cells”..
3) The IHC analysis is difficult to interpret; some examples include Figure 3A where the panels are too small; Figure 6—figure supplement 1 where the changes in staining between F/F2 and ∆/∆ep2 are unclear; in Figure 8B : please use the same magnification that is used for TSLP staining in all panels to make staining more visible; and in regards to ICAM staining use, a better example that clearly shows the epidermis is needed. In general, the quality of all IHC images should be improved and quantifications should be included.
We used low magnification to show a larger portion of the epidermis; however, we agree with the reviewers that some of the immunostainings are less clear in this magnification. The revised manuscript includes higher magnifications inFigure 3A,Figure 3—figure supplement 1, Figure 6—figure supplement 1 (original manuscript; nowFigure 6A); inFigure 8B(nowFigure 7B), the same magnification originally used for the TSLP panel has been used for K6 and ICAM1; however, the original lower magnification is still shown for the panels showing changes in the dermis, i.e.: H&E, β1-tryptase, and toluidine blue. Quantifications of the IHC analysis are shown wherever they are possible.
4) The data on MLK3 expression in HaCat cells are not convincing. Is MLK3 activated by loss of Raf1/Braf? JNK inhibition in KD2 cells in Figure 9D is not clear either, and thus these results should be repeated in ∆/∆ep2 keratinocytes in vitro.
We have succeeded in performing this experiment (JNK inhibition by MLK3 silencing) in ∆/∆ep2 keratinocytes, even if knockdown experiments in primary cells are notoriously difficult. The lentiviral vectors used to knockdown MLK3 in keratinocytes were constructed by Joanna Nowacka in the lab. The authors’ list has been revised to reflect her contribution. The new experiment is shown in revisedFigure 9E–F, while the original experiment in HaCat cells is now shown inFigure 9—figure supplement 1). Concerning MLK3 activation, we have now tried several different phosphospecific antibodies against the autophosphorylation sites, all of which gave a very high background but no reliable signal. However, the lack of JNK activation in unstimulated Δ/Δep2 keratinocytes suggests a cross-talk at the level of BRAF/RAF1 and MLK3 rather than direct MLK3 activation by BRAF/RAF1 ablation. A sentence to this effect has been added to the Discussion (subsection “An imbalance in MAPK signaling underlies skin inflammation in Δ/Δep2 mice”, second paragraph).
5) There is a large body of evidence presented in the manuscript as data not shown that relates to the investigation of increased JNK activation, such as mating the ∆/∆ep2 mice to MyD88, TNFα and caspase 1/11 knock-out mice. These data should be included in the paper, as these results are relevant to the conclusions of the manuscript.
The revised manuscript includes representative pictures of the animals and of their lymphoid organs (Figure 8—figure supplement 2) as well as information on the number of animals monitored (Legend toFigure 8—figure supplement 2) and on the time of disease onset. The paragraph read as follows:
“None of these knockouts altered the progression (onset around 2 months of age) or severity of the Δ/Δep2 skin disease (Figure 8—figure supplement 2). The Myd88 KO, however, reduced the splenomegaly observed in the Δ/Δep2 mice. This specific phenotype is due to an increase in Mac1+/Gr1+ splenocytes (Figure 2B), and its selective rescue in the compound Δ/Δep2;MyD88 KO animals is likely due to the crucial role of MyD88 in the generation of these cells (Arora et al., 2010; Delano et al., 2007).”
6) The use of SP600125 is not recommended because it is a relatively non-selective kinase inhibitor. Any experiment where SP600125 was used should be replaced with a more selective inhibitor.
All experiments involving SP600125 have been replaced with experiments in which JNK activation was inhibited by D-JNKI1. In addition, the experiment in revisedFigure 9Cnow clearly shows that D-JNKI1 reduces ICAM1 expression in ∆/∆ep2 primary keratinocytes.
7) The RNAi studies are poorly designed – phenotypes should be confirmed with two independent single oligonucleotides and rescued by expression of an RNAi-resistant cDNA.
The RNAi studies involving knockdown of Raf1 and BRaf are backed up by all the experiments performed in knockout mice and cells, making off-target effects more than unlikely. Therefore, we have attempted to perform the requested experiments/controls only for MLK3 knockdown in Δ/Δep2 keratinocytes (see also response to point 4). Knockdown/re-expression experiments in primary mouse keratinocytes are notoriously difficult; we have succeeded in targeting MLK3 with two separate hairpins encoded by a lentiviral vector, but the reconstitution experiments using a single vector expressing both the hairpin and WT or shRNA-resistant MLK3 have failed because the infection efficiency with these large constructs went from 60-90% to less than 20%. This is a problem because keratinocytes cannot be FACS-sorted – they will not reattach and in fact will die after sorting. Irrespective of this, we now show that MLK3 knockdown by two distinct shRNAs in primary keratinocytes (revisedFigure 9E–Fand Figure legend toFigure 9; discussed in the last paragraph of the subsection “Interfering with the JNK pathway decreases the production of proinflammatory molecules in primary Δ/Δep2 keratinocytes and RAF knockdown HaCat cells”) has the same effect as MLK3 knockdown by a pool of siRNAs targeting distinct sites in HaCat cells (Figure 9—figure supplement 1of the revised version). We are therefore confident that the effects of MLK3 silencing are specific.
8) The authors show that BRAF/RAF1 deletion causes an "inside out" barrier defect ( Figure 4 ). Comparing mice with combined BRAF/RAF1 deletion, with mice presenting single deletion for BRAF or RAF1, would be important. Some studies have shown that RAF1 is implicated in disrupting tight junctions (Oncogene. 2007 26(8):1222-30 PMID: 16924233; J Cell Biol. 2000 148(4):791-800.PMID: 10684259).
This experiment has been included in the revised manuscript (Figure 4—figure supplement 1C–D; discussed in the first paragraph of the subsection “Lack of epidermal BRAF and RAF1 causes transient inside-out barrier defects”). The figure shows that neither single knockout shows inside-out barrier defects or reduced tight junction proteins expression.
9) The transient barrier defect conclusion in E18.5 embryos is unclear. At the end of the subsection “Lack of epidermal BRAF and RAF1 causes transient inside-out barrier defects” it is proposed that this defect affects the progression of the disease. This is partly based on the fact that deletion of Braf/Raf1 at 3 weeks produces a more modest phenotype. This may be one possible explanation. The milder phenotype may be a reflection of less robust gene deletion in the K5CreER(TX) mice. An immunoblot of epidermal lysates for BRAF and RAF1 should be included in Figure 5A .
This experiment has been included inFigure 5A. As described in the second paragraph of the subsection “Lack of epidermal BRAF and RAF1 causes transient inside-out barrier defects” and shows nearly complete deletion of both proteins in epidermal lysates.
10) Figure 6 : First, there appears to be specific activation of one ERK isoform (which one?) based on the pERK immunoblot in Figure 6A , whilst in Figure 6C both isoforms are phosphorylated. Second, Figure 6B – significance value for IL-13 missing. Third, Figure 6D – what is the explanation for why D-JNKi specifically suppresses CCL2 and CCL7 levels in the Δ/Δep2 mice, while the JNK/p38 inhibitors reduce levels in both F/F2 and knock-out mice?
In the revised version of the manuscript,Figure 6C(now 9C) has been replaced by a new figure showing the effect of the specific JNK inhibitor D-JNKI1. We agree with the reviewer, however, that there is some preference for the phosphorylation of one isoform, and this is ERK2. This can also be observed in epidermal lysates throughout the paper and in HaCat cells. The reason for this preference is not known, but unequal phosphorylation of ERK isoforms has been frequently observed in many different tissues and cells.Figure 6B(now 9B), we stand corrected; this value has been inserted in the revised Figure.Figure 6D(now removed), the explanation is likely that SP600125+SB203580 have a stronger impact and more off target effects than the specific D-JNKI1. In fact we have been requested to remove the experiments in which SP600125 was used for exactly this reason.
11) Figure 7A : D-JNKi appears to suppress pERK in F/F2 epidermis to similar levels as found in Δ/Δep2. Is there an explanation for this?
There is no obvious or easy explanation for this result; however, it should be noted that gradual differences in intensity observed in IHC may be difficult to interpret. We have therefore performed immunoblot analysis of epidermal lysates, which has given us a more quantitative measure of the differences observed inFigure 7A(Figure 8Ain the revised version) and does not show a significant reduction in pERK or in the downstream target pRSK in F/F2 epidermal lysates.
12) Overall the outline of the paper is not very logical and it should be improved for clarity. For example, the analysis of the inflammation markers is often inconsistent, and the cytokines/chemokines shown in Figure 1F should also be shown in the subsequent figures such as Figure 2D .
We have done our best to improve the manuscript’s clarity, describing all the in vivo studies first and moving the experiments with cultured cells, now restricted to keratinocytes, to the end of the results. We have also inverted the order ofFigures 7and8; in the current version of the manuscript, the in vivo experiments using D-JNKI1 directly precede the experiments in primary keratinocytes, which also explore the impact of the JNK pathway on the phenotype in culture. Concerning inflammation markers, we have added K6 as an inflammation marker in addition to ICAM1 in all experiments. The cytokines/chemokines shown inFigure 1Gare shown for each experiment, but in the Figure supplements rather than in the main Figures, which are already extremely crowded.
https://doi.org/10.7554/eLife.14012.022
Article and author information
Author details
Josipa Raguz
Department of Microbiology, Immunology and Genetics, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
Contribution
JR, Conception and design of experiments, Acquisition, analysis and interpretation of data, Preparation of data for publication, Drafting or revising the article
Competing interests
The authors declare that no competing interests exist.
Ines Jeric
Department of Microbiology, Immunology and Genetics, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
Contribution
IJ, Acquisition of data, Analysis and interpretation of data, Drafting and revising the article
Competing interests
The authors declare that no competing interests exist.
Theodora Niault
Department of Microbiology, Immunology and Genetics, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
Contribution
TN, Conception and design of experiments, Acquisition of data, Analysis and interpretation of data
Competing interests
The authors declare that no competing interests exist.
Joanna Daniela Nowacka
Department of Microbiology, Immunology and Genetics, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
Contribution
JDN, Conception and design of the shRNA vectors, Acquisition of data, Analysis and interpretation of data
Competing interests
The authors declare that no competing interests exist.
Sanya Eduarda Kuzet
Department of Microbiology, Immunology and Genetics, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
Contribution
SEK, Acquisition of data, Analysis and interpretation of data, Drafting the article
Competing interests
The authors declare that no competing interests exist.
Christian Rupp
Department of Microbiology, Immunology and Genetics, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
Contribution
CR, Conception and design of inhibitor experiments, Acquisition of data, Analysis and interpretation of data
Competing interests
The authors declare that no competing interests exist.
Irmgard Fischer
Department of Microbiology, Immunology and Genetics, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
Contribution
IF, Acquisition of data, Analysis and interpretation of data, Drafting and revising the article
Competing interests
The authors declare that no competing interests exist.
Silvia Biggi
Department of Neuroscience, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy
Contribution
SB, Synthesized and contributed D-JNKI1, Analysis and interpretation of the D-JNKI1 data, Drafting and revising the article
Competing interests
The authors declare that no competing interests exist.
Tiziana Borsello
Department of Neuroscience, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy
Contribution
TB, Analysis and interpretation of D-JNKI1 data, Drafting and revising the article, Contributed unpublished essential data or reagents
Competing interests
Manuela Baccarini
Department of Microbiology, Immunology and Genetics, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
Contribution
MB, Conception, design and supervision of the project, Analysis and interpretation of data, Drafting and revising the article
For correspondence
manuela.baccarini@univie.ac.at
Competing interests
The authors declare that no competing interests exist.
"This ORCID iD identifies the author of this article:" 0000-0002-3033-391X
Funding
Austrian Science Fund (W1220-B09)
Manuela Baccarini
European Commission (INFLA-CARE FP7_HEALTH 223151)
Manuela Baccarini
Austrian Science Fund (P 19530)
Manuela Baccarini
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Acknowledgements
We thank Karin Ehrenreiter, Clemens Bogner, Eszter Doma, Jana Strouhalová, Gijs Versteeg, Sandra Vidak and the animal facility for assistance. We thank Mareike Roth and Johannes Zuber (IMP, Vienna) for their help with the shRNA experiments. The work was supported by grants W1220-B09 and P 19530 (FWF), and INFLA-CARE (European Community), all to MB.
Ethics
Animal experimentation: The study was performed in accordance with the National Austrian legislation (Law of Animal Experiments 2012 ("TVG-Tierversuchsgesetz"; Federal Law regulating the "Experimentation on living animals" BGBI. I Nr.114/2012) and the overriding EU and international legislation and codes of conduct. Animals were bred and housed in the MFPL facility, which follows the "Charter of Fundamental Rights of the European Union", the opinion of the "European Group on Ethics in Science", and the "Protocol on the Protection and Welfare of Animals". Care of mice is performed by licensed animal caretakers according to FELASA recommendations. Animal experiments involving genetic manipulations are governed by the "Gentechnikgetsetz" (GTG, 12.07.1994). All experiments described in the manuscript were authorized by the Austrian Ministry of Science, Research and Economy (GZ: BMWF-66.006/0030-II/3b/2013 and BMWF-66.006/0012-II/10b/2010).
Reviewing Editor
Publication history
Received: December 23, 2015
Accepted: June 13, 2016
Version of Record published: July 19, 2016 (version 1)
Version of Record updated: September 8, 2016 (version 2)
Version of Record updated: September 13, 2016 (version 3)
Copyright
© 2016, Raguz et al.
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Categories and tags
Research Article
Immunology and Inflammation
mechanisms of disease
allergy
atopic dermatitis
RAF
MAPK
Research organism
Mouse
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February 2023
Frontiers in Pediatrics11
DOI: 10.3389/fped.2023.1111088
License
CC BY 4.0
Authors:
<here is a image 58551997d0ee5a5c-9b56631fb9357267>
Fabien Beaufils
Centre Hospitalier Universitaire de Bordeaux
<here is a image abf19429255496c4-a4ae58944cc248a0>
Raphaël Enaud
Centre Hospitalier Universitaire de Bordeaux
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
François Gallode
François Gallode
This person is not on ResearchGate, or hasn't claimed this research yet.
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Grégory Boucher
Grégory Boucher
This person is not on ResearchGate, or hasn't claimed this research yet.
Abstract and Figures
Introduction
Forced spirometry is the gold standard to assess lung function, but its accessibility may be limited. By contrast, home spirometry telemonitoring allows a multi-weekly lung function follow-up but its real-life adherence, reliability, and variability according to age have been poorly studied in patients with CF (PwCF). We aimed to compare real-life adherence, reliability and variability of home spirometry between children, teenagers and adults with CF.
Methods
This real-life observational study included PwCF followed for six months in whom lung function ( i.e , forced expiratory volume maximum in 1 s (FEV1), forced vital capacity (FVC), forced mid-expiratory flow (FEF) and FEV1/FVC ratio) was monitored by both conventional and home spirometry between July 2015 and December 2021. The adherence, reliability and variability of home spirometry was assessed in all PwCF and compared between children (<12years old), teenagers (12–18 years old) and adults.
Results
174 PwCF were included (74 children, 43 teenagers and 57 adults). Home spirometry was used at least one time per week by 64.1 ± 4.9% PwCF, more frequently in children and teenagers than in adults (79.4 ± 2.9%, 69.2 ± 5.5% and 40.4 ± 11.5% respectively). The reliability to conventional lung function testing was good for all assessed parameters ( e.g. , FEV1: r = 0.91, p < 0.01) and the variability over the 6 months of observation was low (FEV1 coefficient of variation = 11.5%). For each parameter, reliability was better, and the variability was lower in adults than in teenagers than in children
Conclusion
Home spirometry telemonitoring appears to be a reliable tool for multi-weekly lung function follow-up of PwCF.
<here is a image 8c468519864cc56b-9ee6dbfd17a0ee93>
Adherence of home spirometry in the three age groups. Adherence was analysed from home spirometry transmitted data. Comparison between children (6–11 years old; “C”), teenagers (12–17 years old; “T”) and adults (>18 years old; “A”) were performed for the time to early interruption of home spirometry use (A), the average test-to-test delay (B), the absolute number of tests per patient during the follow-up period (C) and the absolute number of tests per patient per week (D), the absolute number of tests per patient during the follow-up period normalized by the recommended objective (i.e.; 3 per week for children/teenagers and 1 per week for adults corresponding to 78 and 26 tests for children/teenagers and adults respectively during the whole follow-up period) (E), the absolute number of tests per patient per week during the follow-up period normalized by the recommended objective (F), the percentage of patients with low (achieved <30% of the objective), medium (30%–50%), good (50%–80%) and excellent (>80%) adherence during the follow-up period (G) or month-by-month (H). Comparisons were performed using Kaplan-Meyer curves and Log-rank test (A) or Kruskal-Wallis tests with Dunn post-test for quantitative variables (B,C,E) or two-way ANOVA with Bonferroni post-test (D–F), Chi square and Fisher exact tests (G,H). A p value < 0.05 was considered significant. …
<here is a image e08b978d79f9ed29-0d6819d4e2c6a365>
Agreement between conventional and home spirometry results. Agreement between conventional (conv) and its closest home spirometry (Home Mes 1) were assessed using correlation test [the coefficient of correlation r and the intraclass correlation (ICC) are presented] (A–D), and Bland-Altman test (E–H) for the forced expiratory volume in one second (FEV1) (A,E), the forced vital capacity (FVC) (B,F), the forced expiratory flow between 25 and 75% of FVC (FEF25-75) (C,G) or the FEV1/FVC ratio (D,H). A p value < 0.05 was considered significant. …
<here is a image ad61efa76f9de6a6-4ef93d4760605450>
Agreements between lung function testing results assessed by both conventional spirometry and home spirometry. …
Figures - available via license: Creative Commons Attribution 4.0 International
EDITEDBY
GaryJamesConnett,
UniversityHospitalSouthamptonNHS
FoundationTrust,UnitedKingdom
REVIEWEDBY
KelvinDMacDonald,
OregonHealthandScienceUniversity,United
States
VikasGoyal,
Children ’ sHealthQueensland,Australia
* CORRESPONDENCE
FabienBeau fils
fabien.beau fils@chu-bordeaux.fr
SPECIALTYSECTION
ThisarticlewassubmittedtoPediatric
Pulmonology,asectionofthejournalFrontiers
inPediatrics
RECEIVED 29November2022
ACCEPTED 06February2023
PUBLISHED 23February2023
CITATION
Beau fi lsF,EnaudR,GallodeF,BoucherG,
MaceyJ,BergerP,FayonMandBuiS(2023)
Adherence,reliability,andvariabilityofhome
spirometrytelemonitoringincystic fibrosis.
Front.Pediatr.11:1111088.
doi:10.3389/fped.2023.1111088
COPYRIGHT
©2023Beau fi ls,Enaud,Gallode,Boucher,
Macey,Berger,FayonandBui.Thisisanopen-
accessarticledistributedunderthetermsofthe
CreativeCommonsAttributionLicense(CCBY) .
Theuse,distributionorreproductioninother
forumsispermitted,providedtheoriginal
author(s)andthecopyrightowner(s)are
creditedandthattheoriginalpublicationinthis
journaliscited,inaccordancewithaccepted
academicpractice.Nouse,distributionor
reproductionispermittedwhichdoesnot
complywiththeseterms.
Adherence,reliability,and
variabilityofhomespirometry
telemonitoringincystic fi brosis
FabienBeau fi ls 1,2,3 * ,RaphaëlEnaud 1,2,3 ,FrançoisGallode 2,
GrégoryBoucher 2 ,JulieMacey 2 ,PatrickBerger 1,2,3,
MichaelFayon 1,2,3 andStéphanieBui 2,3
1
Univ.Bordeaux,CentredeRechercheCardio-ThoraciquedeBordeaux,INSERMU1045,Bordeaux
ImagingCenter,Bordeaux,France,
2
CHUBordeaux,DépartementdePédiatrie,CIC-P1401,Service
d ’ Anatomopathologie,Serviced ’ ExplorationFonctionnelleRespiratoire,Bordeaux,France,
3
INSERM,
CentredeRechercheCardio-ThoraciquedeBordeaux,U1045,Centred ’ InvestigationClinique
(CIC-P1401),Bordeaux,France
Introduction: Forcedspirometryisthegoldstandardtoassesslungfunction,but
itsaccessibilitymaybelimited.Bycontrast,homespirometrytelemonitoring
allowsamulti-weeklylungfunctionfollow-upbutitsreal-lifeadherence,
reliability,andvariabilityaccordingtoagehavebeenpoorlystudiedinpatients
withCF(PwCF).Weaimedtocomparereal-lifeadherence,reliabilityand
variabilityofhomespirometrybetweenchildren,teenagersandadultswithCF.
Methods: Thisreal-lifeobservationalstudyincludedPwCFfollowedforsixmonths
inwhomlungfunction( i.e ,forcedexpiratoryvolumemaximumin1s(FEV1),
forcedvitalcapacity(FVC),forcedmid-expiratory fl ow(FEF)andFEV1/FVCratio)
wasmonitoredbybothconventionalandhomespirometrybetweenJuly2015
andDecember2021.Theadherence,reliabilityandvariabilityofhome
spirometrywasassessedinallPwCFandcomparedbetweenchildren(<12years
old),teenagers(12 – 18yearsold)andadults.
Results: 174PwCFwereincluded(74children,43teenagersand57adults).Home
spirometrywasusedatleastonetimeperweekby64.1±4.9%PwCF,more
frequentlyinchildrenandteenagersthaninadults(79.4±2.9%,69.2±5.5%and
40.4±11.5%respectively).Thereliabilitytoconventionallungfunctiontesting
wasgoodforallassessedparameters( e.g. ,FEV1:r=0.91, p <0.01)andthe
variabilityoverthe6monthsofobservationwaslow(FEV1coef fi cientof
variation=11.5%).Foreachparameter,reliabilitywasbetter,andthevariability
waslowerinadultsthaninteenagersthaninchildren
Conclusion: Homespirometrytelemonitoringappearstobeareliabletoolfor
multi-weeklylungfunctionfollow-upofPwCF.
KEYWORDS
cystic fi brosis,telemonitoring,spirometry,reliability,adherence-compliance-persistance
Introduction
Cystic fi brosis(CF)isoneofthemostcommonsevereautosomalrecessivedisease( 1).
CFisrelatedtomutationsinthe cystic fi brosistransmembraneconductanceregulator(CFTR)
gene,whichencodestheCFTRepithelialionchannelinvolvedinchlorideandbicarbonate
transport,leadingtoimpairedmucushydrationandclearance( 2).
Inthelung,CFTRdysfunctionincreasestheriskofpulmonaryexacerbation,chronic
pulmonaryinfectionsandin fl ammationresultinginincreasedlungfunctiondecline( 3 – 5)
anddecreasedsurvival( 6 ).Respiratorydiseaseremainstheleadingcauseofdeathin
TYPE OriginalResearch
PUBLISHED 23February2023
|
DOI 10.3389/fped.2023.1111088
Frontiersin Pediatrics 01frontiersin.org
patientswithCF(PwCF)despiteCFTRfunctionimprovementby
theCFTRmodulatorsdevelopedinthelastdecade( 7 – 10 ).Thus,
properlungfunctionmonitoringremainsamajorgoalinthe
follow-upofPwCF.
Forcedspirometryisthegoldstandardtesttofollowlung
function( 11 )bymeasuringtheforcedexpiratoryvolumeinone
second(FEV1),theforcedvitalcapacity(FVC),theforced
expiratory fl owbetween25%and75%ofFVC(FEF25-75),and
theFEV1/FVCratio.Previousstudiesdemonstratedanincreased
lungfunctiondeclineinpatientswithcystic fi brosis( 4 ),the
changeandthefailuretorecoverthebaselineFEV1after
pulmonaryexacerbation( 3 , 5 ).However,forcedspirometry
performedinpulmonaryfunctionlaboratoriesrequiresatrained
techniciananditsaccessibilitycanbelimited( 12).
Inrecentyears,theriseoftelemedicineandthedevelopmentof
homespirometrytelemonitoring,particularlyduringCOVID-19
pandemic,resultedinmonitoringofthepatient ’ slungfunction
severaltimesaweekathome.However,theusefulnessofthese
devicesrequiresbothgoodpatientcomplianceandreliableand
reproducibleresultscomparedtoconventionalspirometry.Home
spirometrytelemonitoringdeviceshavealreadydemonstrateda
goodqualityofperformedspirometry( 13 ),adherence( 14 )anda
goodreliabilityofhomespirometryresultscomparedtolung
functionresultsobtainedinadedicatedlaboratoryinasmall
groupofCFpatients( 14 – 16 ).However,mostofthestudies
involvinghomespirometryincludedmainlyteenagers(12 –18
yearsold)and/oradults(>18yearsold)( 13 , 16 – 18).The
differencesinadherence,reliabilityandvariabilityofhome
spirometrybetweenchildren,teenagersandadultswithCFhave
neverbeenassessedpreviously.
AtBordeauxUniversityHospital,homespirometry
telemonitoringusingtheBluetooth-enabledMIR-Spirobank
®
Smartdevicehasbeenincludedinthepatientfollow-upsince
2015, fi rstinchildrenandteenagersandtheninadults.Weaimed
toassessandcompareadherence,reliabilityandvariabilityof
homespirometrybetweenchildren,teenagersandadultswithCF.
Materialsandmethods
Studydesign
Thisobservational,real-lifestudywasconductedatthe
BordeauxUniversityHospital,France.Thestudywasconducted
inaccordancewiththeDeclarationofHelsinkiprinciplesand
approvedbytheSouth-WestandOverseasProtectionCommittee
(CPP)III.AccordingtothelawinforceinFrance,thenon-
oppositionofthepatientand/orhislegalrepresentativesfor
patientsunder18yearsofagewasobtainedfortheuseof
clinicaldataandlungfunctiontestingresultswhichdidnot
requirethepatients ’ informedconsent.
Thestudyincludedpatientswithcon fi rmedCF(sweatchloride
>60mmol/Land/orCFTRgenemutations)followedatthe
paediatricoradultCFcentresolderthan5yearsold,ableto
performforcedspirometryandusinghomespirometryinroutine
carebetweenJuly2015andJune2021.Patientswereincludedat
the firstuseoftheSpirobanksmart
®
andwerefollowedupfor6
months.Atthebeginningofthefollow-upwiththeSpirobank
smart
®
,patientswereadvisedtoperformatleast3measurements
perweekforchildren(6 – 12years)andteenagers(12 – 18years),
andatleastoneweeklymeasurementforadults.Theadvised
numberofmeasurementswaschosento fi twiththenumberof
respiratoryphysiotherapysessionsperweekperformedbypatients
(i.e.,atleast3timesaweekforchildrenandatleastoncefor
adults).Childrenwerealsoadvisedtobehelpedbytheirparents
toperformedhomespirometry.Thephysiotherapistswere
encouragedtoremindand/ortohelppatientstousethedevice
duringrespiratoryphysiotherapysessions.
Datacollected
Atinclusion,wecollectedcli nicaldatafromthepatient ’ smedical
fi lesincludingtheage,gender,bodymassindex(BMI),CFTR
mutations,comorbidities[pancreaticinsuf fi ciency,cystic fi brosis
relateddiabetes(CFRD)],chroniccolonizationstatusfor
pseudomonasaeruginosa(PA)andmethicillinsusceptible
staphylococcusaureus(MSSA),treatments(inhaledbronchodilator,
inhaledcorticosteroid,CFTRmodulators)andresultsofthelast
lungfunctiontesting(LFT)performedinadedicatedlaboratoryat
thephysiologydepartmentoftheUniversityHospitalofBordeaux
( i.e .,FEV1,FVC,FEF25-75,andFEV1/FVC).
Duringthefollow-upperiod,wealsocollectedLFTresultsfrom
boththe fi rstlungfunctiontestingperformedinourlabafter
inclusion(namedthereafterFEV1
conv
,FVC
conv
,andFEF25-
75
conv
,FEV1/FVC
conv
)andresultsfromforcedspirometry
measurementsperformedathomewithSpirobanksmart
®
.Of
note,resultsfromforcedspirometryperformedwiththe
Spirobanksmart
®
areautomaticallyrecordedinthededicated
smartphoneapplicationbyBluethooth
®
ateachuse.Data
recordedbytheapplication(Pneumotel
®
)arethenanonymously
transmittedbythepatientinrealtimetothePneumotel
®
platformDataarethencollectedbyAquiRespi,anotherplatform
dedicatedtothecoordinationofrespiratorycareintheNew
Aquitaineregion(France)whichisincontactwiththepatients ’
practitioners.Foreachpatient,alldatafromhomespirometry
collectedbyAquiRespiduringthe6monthsafterinclusionwere
collectedbytheinvestigators(FB,GB).Wespeci fi callyidenti fied
theresultsofthehomespirometryclosesttotheconventional
LFTasFEV1
homeM1
,FVC
homeM1
,andFEF25-75
homeM1
,FEV1/
FVC
homeM1,
andthoseofthesecondclosesthomespirometryto
conventionalLFTasFEV1
homeM2
,FVC
homeM2
,andFEF25-
75
homeM2
,FEV1/FVC
homeM2
.Patientparticipationinthestudy
wasdiscontinuedifthelastrecordedmeasureoccurredbefore
theendoftheobservationperiod(hereaftercalledearlystoppers).
Statisticalanalyses
TheanalyseswereperformedusingGraphpadPrism5.1
software(GraphPadSoftware,LaJolla,CA).Resultsarepresented
asabsolutevalueswithpercentage[ n / N (%)]forcategorial
Beau fi lsetal.10.3389/fped.2023.1111088
Frontiersin Pediatrics 02frontiersin.org
| https://www.researchgate.net/publication/368771870_Adherence_reliability_and_variability_of_home_spirometry_telemonitoring_in_cystic_fibrosis |
Chen v. Chen - Pennsylvania - Case Law - VLEX 887513975
0: [object Object]. 1: [object Object]. 2: [object Object]. 3: [object Object]. 4: [object Object]
Chen v. Chen
<table><tbody><tr><td> Court</td><td> Superior Court of Pennsylvania</td></tr><tr><td> Writing for the Court</td><td> FORD ELLIOTT, KLEIN, and MONTEMURO, JJ.</td></tr><tr><td> Citation</td><td> 840 A.2d 355</td></tr><tr><td> Parties</td><td> Wheamei Jenq CHEN
v.
Richard CHEN
v.
Theresa Chen.
Appeal of Richard Chen, Appellant</td></tr><tr><td> Decision Date</td><td> 19 December 2003</td></tr></tbody></table>
840 A.2d 355
Wheamei Jenq CHEN
v.
Richard CHEN
v.
Theresa Chen.
Appeal of Richard Chen, Appellant
Superior Court of Pennsylvania.
Argued February 25, 2003.
Filed December 19, 2003.
840 A.2d 356
Charles A. Banta, Easton, for appellant
Donald F. Spry, III, Bethlehem, for Theresa Chen, appellee.
Before: FORD ELLIOTT, KLEIN, and MONTEMURO, 1JJ.
840 A.2d 357
OPINION BY FORD ELLIOTT, J
¶ 1 Richard Chen ("Husband") appeals the order entered June 28, 2002 in the Court of Common Pleas of Northampton County directing him to pay $59,292 in arrearages in accordance with a property settlement agreement entered into on June 27, 1983.We affirm.
¶ 2 Husband and Wheamei Jenq Chen ("Wife") had two children during the course of their six-year marriage. Robert Chen was born on May 16, 1978, and Theresa Chen was born on February 5, 1982. This case concerns only Theresa. The parties divorced on June 27, 1983 and entered into a property settlement agreement ("agreement").
¶ 3 The provision of the agreement that addressed Husband's child support obligation provided as follows:
9. Child Support
The Husband agrees and contracts to pay to Wife the sum of $25.00 per week as child support for the support of the child, Theresea, (sic) who will be in the custody of Wife. The Husband further agrees that upon obtaining regular employment or upon any increase in salary the aforementioned support award will be increased in accordance with the Northampton County Domestic Relations Guidelines. Husband hereby waives, releases and renounces any and all claims to child support for Robert.
¶ 4 On June 27, 1983, a support order was entered in the amount of $25 per week. Husband deposited $25 into a bank account set up in Illinois every week as required. (Notes of testimony, 1/24/02 at 28, 58.) At no time did Wife seek an increase in the support amount. 2Following the divorce, Robert lived with his father while Theresa lived with her mother.( Id.at 20-21, 26.) In 1985, Husband moved to Michigan where he continues to reside.( Id.at 65, 68-69). Since the divorce, Wife lived in Illinois, Taiwan, Philadelphia, Pennsylvania, and Tampa, Florida.( Id.at 22-24.)
¶ 5 On April 27, 2000, Wife filed a petition for special relief, enforcement of the property settlement agreement, and contempt of court. Wife sought to enforce the child support provision in the agreement and collect arrearages. After turning 18, Theresa filed a petition to intervene on May 25, 2000, as a party to her mother's action. In her petition, Theresa alleged that she was a third party beneficiary to the agreement. On November 27, 2000, the trial court found that Theresa was a third party beneficiary to the agreement and granted her petition.
¶ 6 On January 28, 2002, a non-jury trial was held. Shortly before trial, Wife withdrew her petition. The case proceeded to trial on Theresa's petition. On June 28, 2002, the trial court entered an order in favor of Theresa and against her father in the amount of $59,292.80.
¶ 7 Husband raises the following issues for our review:
I. DID THE COURT ERR IN FINDING THAT THE INTERVENER IS A THIRD PARTY BENEFICIARY OF THE PROPERTY SETTLEMENT AGREEMENT ENTERED INTO BETWEEN HER PARENTS?
II. DID THE COURT ERR IN FINDING THAT THE PROPERTY SETTLEMENT AGREEMENT
840 A.2d 358
OF THE PARTIES IMPOSED A POSITIVE DUTY ON [HUSBAND] TO PURSUE AN INCREASE IN SUPPORT
III. DID THE COURT ERR IN ACCEPTING THE OPINION TESTIMONY OF A WITNESS WITHOUT PROPERLY QUALIFYING THAT WITNESS AS AN EXPERT?
Husband's brief at vi.
¶ 8 Husband first argues the trial court erred in finding that Theresa, the intervener, is a third party beneficiary of the agreement. In Guy v. Liederbach,501 Pa. 47,459 A.2d 744(1983), our supreme court adopted the Restatement (Second) of Contracts § 302 (1979) as the law of this Commonwealth concerning third party beneficiary rights.Section 302 states:
Intended and Incidental Beneficiaries
(1) Unless otherwise agreed between promisor and promisee, a beneficiary of a promise is an intended beneficiary if recognition of a right to performance in the beneficiary is appropriate to effectuate the intention of the parties and either
(a) the performance of the promise will satisfy an obligation of the promisee to pay money to the beneficiary; or
(b) the circumstances indicate that the promisee intends to give the beneficiary the benefit of the promised performance.
(2) An incidental beneficiary is a beneficiary who is not an intended beneficiary.
Restatement (Second) of Contracts § 302 (1979); see also Scarpitti v. Weborg,530 Pa. 366,609 A.2d 147(1992).
¶ 9 Consequently, the Guycourt concluded:
There is thus a two part test for determining whether one is an intended third party beneficiary: (1) the recognition of the beneficiary's right must be `appropriate to effectuate the intention of the parties,' and (2) the performance must `satisfy an obligation of the promisee to pay money to the beneficiary' or `the circumstances indicate that the promisee intends to give the beneficiary the benefit of the promised performance.'
Id.at 60, 459 A.2d at 751.
¶ 10 The first prong of the test sets forth a standing requirement which empowers the trial court to determine, in its discretion, whether third party beneficiary status is appropriate in a particular case. Clifton v. Suburban Cable TV Co., Inc.,434 Pa.Super. 139,642 A.2d 512, 514 (1994). The second prong defines the two types of claimants who may be intended as third party beneficiaries. Id.
¶ 11 Instantly, applying the test set out above, we conclude that the trial court correctly determined that the intervener was a third party beneficiary of her parent's agreement. The primary intent of the parties in paragraph 9 of the agreement was to help Theresa by providing for her financial support. Wife was asked if she used the money she received from Husband for the support of Theresa. (Notes of testimony, 1/24/02 at 26.)Wife responded: "Yes, it's not enough, but, yes, of course, I had to. I wish I could provide her more, so in the event—certain events I would like her to join, but I couldn't."( Id.) Clearly, Wife intended to give Theresa the benefit of the child support payments. As a...
6 practice notes
Chen v. Chen United States United States State Supreme Court of Pennsylvania March 20, 2006 ...for her benefit based on her parents' property settlement agreement was an issue of first impression in the Commonwealth. Chen v. Chen, 840 A.2d 355, 359 (Pa.Super. 2003). To determine whether Daughter could enforce the provision as an intended beneficiary, the court applied the two-part te......
Com. v. Kopicz United States Superior Court of Pennsylvania December 19, 2003 ...compelled, self-incriminating testimony, and the core of the guarantee against compelled self-incrimination is the exclusion of 840 A.2d 355any such evidence."). by allowing the Board to requisition as evidence for the prosecution all statements made by Appellant when he was institutionali......
Stalloy Metals, Inc. v. Kennametal, Inc., No. 2012–G–3054. United States United States Court of Appeals (Ohio) December 3, 2012 ...interpretation is a question of law, this Court is not bound by the trial court's interpretation.” Chen v. Chen, 2003 Pa.Super. 497, 840 A.2d 355, 360 (2003). “Our standard of review over questions of law is de novo * * *.” Kripp v. Kripp, 578 Pa. 82, 91 n. 5, 849 A.2d 1159 (2004). When a w......
Stamerro v. Stamerro United States Superior Court of Pennsylvania December 21, 2005 ...the sole determiner of facts and absent an abuse of discretion, we will not usurp the trial court's fact-finding function." Chen v. Chen, 840 A.2d 355, 360 (Pa.Super.2003), appeal granted in part, 578 Pa. 433, 853 A.2d 1011 (2004).1 On appeal from an order interpreting a marital settlement ......
6 cases
Chen v. Chen United States United States State Supreme Court of Pennsylvania March 20, 2006 ...for her benefit based on her parents' property settlement agreement was an issue of first impression in the Commonwealth. Chen v. Chen, 840 A.2d 355, 359 (Pa.Super. 2003). To determine whether Daughter could enforce the provision as an intended beneficiary, the court applied the two-part te......
Com. v. Kopicz United States Superior Court of Pennsylvania December 19, 2003 ...compelled, self-incriminating testimony, and the core of the guarantee against compelled self-incrimination is the exclusion of 840 A.2d 355any such evidence."). by allowing the Board to requisition as evidence for the prosecution all statements made by Appellant when he was institutionali......
Stalloy Metals, Inc. v. Kennametal, Inc., No. 2012–G–3054. United States United States Court of Appeals (Ohio) December 3, 2012 ...interpretation is a question of law, this Court is not bound by the trial court's interpretation.” Chen v. Chen, 2003 Pa.Super. 497, 840 A.2d 355, 360 (2003). “Our standard of review over questions of law is de novo * * *.” Kripp v. Kripp, 578 Pa. 82, 91 n. 5, 849 A.2d 1159 (2004). When a w......
Stamerro v. Stamerro United States Superior Court of Pennsylvania December 21, 2005 ...the sole determiner of facts and absent an abuse of discretion, we will not usurp the trial court's fact-finding function." Chen v. Chen, 840 A.2d 355, 360 (Pa.Super.2003), appeal granted in part, 578 Pa. 433, 853 A.2d 1011 (2004).1 On appeal from an order interpreting a marital settlement ......
| https://case-law.vlex.com/vid/chen-v-chen-887513975 |
Shikonin as an inhibitor of the LPS-induced epithelial-to-mesenchymal transition in human breast cancer cells
Shikonin as an inhibitor of the LPS-induced epithelial-to-mesenchymal transition in human breast cancer cells
Authors:
Darong Hong
Soon Young Jang
Eun Hyang Jang
Bom Jung
In-Hye Cho
Min-Ju Park
Seo Young Jeong
Jong-Ho Kim
Affiliations: Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, Dongdaemun-gu, Seoul 130-701, Republic of Korea, Department of Pharmacy, Graduate School, Kyung Hee University, Dongdaemun-gu, Seoul 130-701, Republic of Korea
Published online on: October 13, 2015 https://doi.org/10.3892/ijmm.2015.2373
Pages: 1601-1606
Abstract
Shikonin (SK), a natural naphthoquinone isolated from the Chinese medicinal herb, has been known to suppress the proliferation of several cancer cells. However, its role in the epithelial mesenchymal transition (EMT) has yet to be demonstrated. The aim of the present study was to examine the effects of SK on EMT. Lipopolysaccharide (LPS) induced EMT-like phenotypic changes, enhancing cell migration and invasion. SK markedly reduced the expression of the LPS-induced EMT markers, including N-cadherin in MDA-MB‑231 cells, and increased the expression of E-cadherin in MCF-7 cells. SK also inhibited cell migration and invasion in vitro. The effects of SK on the LPS-induced EMT were mediated by the inactivation of the NF-κB-Snail signaling pathway. The results provided new evidence that SK suppresses breast cancer cell invasion and migration by inhibiting the EMT. Therefore, SK is a potentially effective anticancer agent for breast tumors, by inhibiting metastasis.
Introduction
Breast cancer ranks among the most common malignant
tumors afflicting women worldwide (
1
,
2
).
Cancer metastasis is the leading cause of mortality in patients
with breast cancer, with breast cancer survival rates having
decreased from 90% for localized to 20% for metastatic disease
(
3
). The prognosis of patients
with advanced cancer is associated with the degree of aggressive
metastasis (
4
,
5
). Thus, elucidation of the mechanisms
involved in the metastasis of cancer is imperative as there are
limited effective therapies once the cancer has spread. The process
of cancer metastasis appears to be regulated by a variety of gene
products; however, the precise mechanisms of tumor cell
dissemination are poorly understood (
6
–
8
).
The epithelial-mesenchymal transition (EMT), which has been
recognized for several decades as a fundamental process of
embryogenesis, may be involved in numerous pathological processes,
particularly cancer progression (
9
). During the EMT of cancer cells
in
situ
, epithelial cell layers lose their polarity and their
cell-cell contacts, and then undergo significant remodeling of the
cytoskeleton. The expression of proteins such as E-cadherins which
promote cell-cell contact may be lost, and the cells may acquire
N-cadherin which enhances their capacity for cell migration and
invasion, and are pivotal events in the initial step of metastasis
(
10
,
11
). Therefore, investigators have
focused on inhibiting the EMT of cancer cells as a new therapeutic
strategy to prevent cancer metastasis.
Shikonin (SK) is an active naphthoquinone compound
extract derived from the Chinese medicinal herb,
Litho-spermum
erythrorhizon Sieb et Zucc
. SK has been reported to exert
anti-proliferative and pro-apoptotic effects against various cancer
cells via several mechanisms such as inhibition of topoisomerase-I,
the regulation of phosphorylation-dependent activities of
extracellular-regulated protein kinase, suppression of tumor
necrosis factor receptor-associated protein 1 expression, and
activation caspases (
12
–
16
). In addition, it was previously
reported that SK induces the suppression of migration and invasion
through the modulation of MMP-9 in human breast cancer cells
(
17
). As previously mentioned,
the migration and invasion of cells are associated with EMT for
metastasis. In the present study, we hypothesized that SK is an
effective inhibitor of EMT during cancer progression, and may
therefore be used as an agent for breast tumors. The results showed
that, SK significantly inhibited the invasion and migration of
MCF-7 and MD-MB231 human breast cancer cells during LPS-induced EMT
by downregulating the NF-κB-Snail signaling pathway. Thus, SK is an
excellent candidate agent for use against breast tumors as it
inhibits metastasis.
Materials and methods
Cell culture and reagents
MDA-MB-231 and MCF-7 cells [all purchased from the
American Type Cell Collection (ATCC), Manassas, VA, USA] were
maintained in Dulbecco's modified Eagle's medium (DMEM; Gibco,
Grand Island, NY, USA) supplemented with 10% fetal bovine serum
(FBS; Gibco) and 1% penicillin/stereptomycin antibiotics. Shikonin
(SK) was purchased from Sigma-Aldrich (St. Louis, MO, USA). The
antibodies NF-κB p65 subunit and β-actin were purchased from Santa
Cruz Biotechnology, Inc. (Santa Cruz, CA, USA), Snail was purchased
from Cell Signalling Technology (Beverly, MA, USA), and N- and
E-cadherin were purchased from BD Biosciences (San Jose, CA,
USA).
Cell proliferation assay
Proliferation assays were based on the
3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT)
method. Cells were seeded at a density of 1×10
4
cells
per well in a 96-well plate. After overnight culture, SK (0.2, 0.5,
1, 2, 5, 10, 20 and 50
µ
M) was added to the cells and
cultured for 24 h. The medium was removed and DMSO (Sigma-Aldrich)
was added to the MTT solubilization solution. Absorbance was
measured at 550 nm. For the colony-forming assay, single-cell
suspensions of 5×10
3
cells were seeded in a 6-well plate
and allowed to adhere for 24 h at 37°C in culture medium. The cells
were subsequently treated with 5 or 50
µ
M SK. After 10 days,
the colonies were fixed with 100% methanol for 10 min at room
temperature and stained with 0.1% crystal violet. The plates were
washed with PBS (Gibco) and images were captured.
Cell migration assay
Migration was assessed using a wound-healing assay.
The cells were seeded at 2×10
4
MDA-MB-231 and MCF-7
cells per well and cultured for 24 h. After scraping the cell
monolayer with a sterile micropipette tip (Axygen, Union City, CA,
USA), the wells were washed with PBS, and treated with LPS (5
µ
g/ml) or co-treated with LPS (5
µ
g/ml) and SK (5
µ
M). The first image of each scratch was obtained at time
zero. At 24 h, each scratch was examined and captured at the same
location and the healed area was measured.
Transwell invasion assay
The invasion of tumor cells was assessed in
Transwell chambers equipped with 8
µ
m pore size, 6.5-mm
diameter polyvinylpyrrolidone-free polycarbonated membranes
(Corning Costar Inc., Corning, NY, USA) that were coated with 1
mg/ml fibronectin. The cells were seeded onto the upper wells at a
concentration of 1×10
5
MDA-MB-231 and MCF-7 cells/well
and were cultured for 24 h following treatment with LPS (5
µ
g/ml) or co-treatment with LPS (5
µ
g/ml) and SK (5
µ
M). The bottom chambers of the Transwell were filled with
conditioned medium. After incubation for 24 h, the cells were fixed
with 100% methanol for 10 min at room temperature, stained with
0.1% crystal violet and counted under a light microscope.
Western blotting
MDA-MB-231 and MCF-7 cells were treated with with
LPS (5
µ
g/ml) or co-treated with LPS (5
µ
g/ml) and SK
(5
µ
M) for 24 h. After lysing cells with RIPA buffer, the
proteins were resolved by SDS-PAGE and immuno blotted using primary
antibodies such as mouse monoclonal anti-human-N-cadherin, mouse
monoclonal anti-human-E-cadherin, rabbit polyclonal
anti-human-NF-κB p65 subunit, mouse monoclonal anti-human-Snail,
and mouse polyclonal anti-human-β-actin antibody (dilution ratio
1:1,000). Subsequent to treatment with the secondary antibodies
(rabbit anti-mouse IgG and goat anti-rabbit IgG; dilution ratio
1:5,000), the immunoreactive bands were visualized using the
standard ECL method.
Immunofluorescent staining
MDA-MB-231 and MCF-7 cells were grown in 4-chamber
slides in serum-free media, and were treated with LPS (5
µ
g/ml) or co-treated with LPS (5
µ
g/ml) and SK (100
µ
M). After 24-h incubation, the cells were fixed with 4%
paraformaldehyde at 4°C. The cells were washed with PBS containing
0.1% BSA and incubated with anti-N-cadherin or anti-E-cadherin
antibody for 1 h followed by 1-h incubation with
fluorescence-tagged secondary antibody, then counter-stained with
DAPI for 5 min. Cell images were captured at x200 magnification on
a Leica fluorescence microscope (Leica, Buffalo Grove, IL,
USA).
Statistical analysis
The results are presented as mean ± SE. Statistical
comparisons between groups were carried out using one-way ANOVA
followed by the Student's t-test. A P-value <0.05 was considered
statistically significant.
Results
Effect of SK on the growth of human
breast cancer cells in vitro
We initially examined the effect of SK on the
proliferation of the MCF-7 and MDA-MB-231 human breast cancer cell
lines. The cells were treated for 24 h with predetermined
concentrations of SK as previously mentioned, and cell viability
was measured using the MTT assay. As shown in
Fig. 1A
, cell proliferation was inhibited
by SK in a dose-dependent manner, although a different
IC
50
(the drug concentration that causes 50% growth
inhibition) was observed for each cell line (12.2±0.7
µ
M for
MDA-MB-231 and 17.1±0.4
µ
M for MCF-7). The long-term effects
of SK were determined by culturing MCF-7 and MDA-MB-231 cells with
or without SK for 10–15 days, and then performing colony-forming
assays. At a concentration of 5
µ
M, SK did not show any
significant effect, whereas 50
µ
M SK almost completely
inhibited colony formation (
Fig.
1B
). Therefore, we considered 5
µ
M SK a suitable dose
for subsequent experiments.
<table><tbody><tr><td>
<here is a image 1c1aae1e9fde3147-7c5b436da34ec617>
</td><td> Figure 1Shikonin (SK) inhibits the growth of
human cancer cells. (A) MDA-MB-231 and MCF-7 cells were seeded in a
96-well plate and treated with different concentrations of SK after
24 h. Cell proliferation was determined using the MTT assay. Data
are presented as the percentage of proliferation relative to that
in the medium-treated controls. The results are expressed as the
means ± SD of three replicate measurements from a single
experiment, and are representative of three separate experiments.
(B) MDA-MB-231 and MCF-7 cells were seeded in a 6-well plate and
treated with 0, 5 and 50 µM SK for 15 days. Colonies were
fixed with 100% methanol for 10 min at rom temperature and stained
with 0.1% crystal violet. Representative photographs demonstrating
colony formation are shown.</td></tr></tbody></table>
Effect of SK on the LPS-induced migration
of human breast cancer cells
LPS (5
µ
g/ml) may act as an independent
factor to trigger the EMT process, as has previously been reported
by Chen and colleagues (
13
). We
investigated the effects of SK on cell migration to verify that SK
inhibits the LPS-induced EMT as EMT is associated with enhanced
tumor progression. The cancer cell lines were treated with LPS
alone, LPS plus SK (5
µ
M), or SK alone (5
µ
M), and
wound-healing assays were performed. The LPS-treated cancer cells
exhibited a ≥1.7-fold increase in migration, whereas treatment with
5
µ
M SK inhibited this LPS-induced migration by 70 and 40%
for MDA-MB-231 and MCF-7, respectively (
Fig. 2A and B
). The inhibition of
migration was also observed in the SK alone treatment group, where
SK decreased the migration by 60 and 30% for MDA-MB-231 and MCF-7,
respectively, compared to the untreated control group. These
results showed that SK decreased the migration of cancer cells
during EMT by LPS.
<table><tbody><tr><td>
<here is a image c7017feeeac11ea0-77d2470fcce0922d>
</td><td> Figure 2Shikonin (SK) inhibits the LPS-induced
cell migration of MDA-MB-231 and MCF-7 cells. (A) MDA-MB-231 and
(B) MCF-7 cells were wounded by scratching with a pipette tip and
were then incubated with or without 5 µg/ml LPS and SK (5
µM). Representative images of wound healing were captured at
the time of scratching and 24 h thereafter. Cell migration into the
wounded area was quantified as the fold ratio of wound healing
(n=5). *P<0.05, **P<0.01 vs.
LPS-treated cells.</td></tr></tbody></table>
Effect of SK on the LPS-induced invasion
of human breast cancer cells
We examined whether SK inhibits the LPS-induced
invasiveness of cancer cells. Following treatment with LPS alone,
the number of invasive cells significantly increased compared with
the untreated cells. However, the number of invasive cells was
significantly reduced in the cells treated with the combination of
LPS plus SK (
Fig. 3A
). The
quantitative analysis is shown in
Fig. 3B
, and the results revealed that SK
significantly inhibited the LPS-induced invasion of cancer by 60
and 40% for MDA-MB-231 and MCF-7, respectively, compared to the
untreated control group. These results suggested that SK inhibits
the effect of LPS, whereby it increases the invasiveness of human
cancer cells, as occurs at the EMT.
<table><tbody><tr><td>
<here is a image bb38a0a6df7d10a7-d4cae220ebe256b7>
</td><td> Figure 3Shikonin (SK) inhibits the cell
invasion stimulated by LPS. (A) MDA-MB-231 and MCF-7 cells treated
with the SK (5 mM), with or without 5 µg/ml LPS, for 24 h,
and invasion was determined by Transwell assays. Representative
photomicrographs of membrane-associated cells stained with crystal
violet. (B) Cell invasion values were quantified as the fold ratio
of invaded cells (n=5). *P<0.05,
**P<0.01 vs. LPS-treated cells.</td></tr></tbody></table>
Effect of SK on the expression of
EMT-associated proteins
To investigate the effect of SK on LPS-induced EMT,
we monitored the expression of the EMT-associated proteins, E- and
N-cadherin by western blotting (
Fig.
4A
). The expression of N-cadherin was significantly upregulated
in MDA-MB-231, whereas that of E-cadherin was downregulated in the
LPS-treated group compared with their expression in the controls.
However, SK reversed the LPS-induced EMT by inhibiting the
expression of N-cadherin, and reinducing E-cadherin expression. We
also examined N- and E-cadherin expression in cancer cells by
immunofluorescence (
Fig. 4B
).
Consistent with the western blotting results, in MDA-MB-231 cells,
N-cadherin was highly expressed after LPS treatment, but
significantly decreased by the co-treatment with SK. In MCF-7
cells, E-cadherin was seldom expressed after LPS treatment, but
significantly recovered by the co-treatment with SK. Taken
together, the western blotting and fluorescence imaging results
suggested that SK exerts an inhibitory effect on EMT.
<table><tbody><tr><td>
<here is a image 8be68d254b26c749-ce2caad7db433914>
</td><td> Figure 4Shikonin (SK) regulates the expression
of EMT-associated proteins and inhibits the activation of
NF-κB-Snail signaling. (A) Expression of E-cadherin, β-catenin,
N-cadherin, and vimentin proteins in MDA-MB-231 and MCF-7 cells was
determined with western blotting. (B) MDA-MB-231 cells were
immunostained with anti-N-cadherin antibody and MCF-7 cells were
incubated with anti-E-cadherin antibody, and the nuclei were
counterstained with 4′,6-diamidino-2-phenylindole (DAPI) after SK
treatment. (C) Western blot analysis of the expression of the NF-κB
p65 subunit and Snail protein in MDA-MB-231 and MCF-7 cells after
treatment with SK for 24 h.</td></tr></tbody></table>
NF-κB-Snail signaling pathway for
reversal of LPS-induced EMT marker expression
It has been previously reported that many drugs may
inhibit the invasion and migration of cancer cells by suppressing
NF-κB activation and Snail induction, suggesting that the NF-κB
signaling pathway is critically involved in the acquisition of EMT
through its downstream target, the transcription factor Snail
(
18
). We investigated the
expression of the NF-κB p65 subunit and Snail protein with western
blotting to determine whether the effect of PCAE described above is
associated with the inhibition of the NF-κB-Snail pathway. As shown
in
Fig. 4C
, LPS significantly
upregulated the expression of NF-κB p65 and Snail protein, which
reduced the expression of E-cadherin and increased the expression
of N-cadherin. These effects were blunted by SK, suggesting that SK
suppresses LPS-triggered EMT by counteracting NF-κB p65 activation
and Snail induction by LPS.
Discussion
The EMT is the best-known example of the changes
that occur in the patterns and functions of cancer cells (
19
). Epithelial cells acquire
mesenchymal fibroblast-like phenotypes, with reduced cell-cell
adhesion, loss of polarity, and increased migration and
invasiveness (
20
). The profound
changes in cytoskeletal architecture that occur during EMT,
together with a reduction in intercellular adhesion and an increase
in motility, are fundamental to the metastatic process, enabling
these cells to break through the basal membrane and migrate over
long distances (
21
). The EMT is
considered to be a significant step in the invasive cascade,
facilitating the migration of tumor cells from their site of origin
and their dissemination to distant tissues (
22
). EMT is a complex, stepwise
phenomenon that is involved in embryonic development, as well as
other physiological and pathological conditions, playing a role in
enhancing the invasive and metastatic behavior of cancer cells.
Therefore, inhibition of EMT is an attractive therapeutic approach
that may have a significant effect on disease outcome.
As previously reported, LPS induces EMT in breast
cancer cells, increasing their invasion and migration and resulting
in enhanced lung metastasis (
23
). In the present study, we have shown
that breast cancer cells can be induced by LPS to undergo a
stimulated EMT, increasing N-cadherin expression in MDA-MB-231, and
reducing E-cadherin expression in MCF-7. SK inhibits the action of
LPS in inducing the EMT, reversing the altered expression of
proteins associated with cell invasion and migration. We also found
that NF-κB-SNAIL signaling is required for the LPS-induced EMT in
breast cancer cells, which clarifies the mechanism by which SK
inhibits cancer cell metastasis.
SK, an active naphthoquinone isolated from the
Chinese medicinal herb,
Lithospermum erythrorhizon Sieb et
Zucc
, showed anticancer activity in previous studies (
24
). Recent findings have shown that SK
induces apoptosis, and suppresses cancer cell proliferation
(
25
). However, SK has not been
associated with cancer metastasis via the EMT, although its strong
antitumor effects have been reported. To the best of our knowledge,
this is the first study to demonstrate that the antimetastatic
effects of SK are associated with the EMT in cultured human breast
cancer cells. Therefore, our results suggest a new chemopreventive
role for SK in inhibiting the progression of cancer metastasis.
In the present study, we have shown that SK inhibits
the LPS-induced EMT, and thus cell migration and invasion, which
result from the dysregulation of cell-cell adhesion proteins and
the expression of EMT-associated proteins, such as E- and
N-cadherin. Cadherins are transmembrane glycoproteins that mediate
Ca
2+
-dependent cell-cell adhesion (
26
). E-cadherin is expressed by most
epithelial tissues and facilitates tight cell-cell adhesion and
suppresses the dissociation of epithelial cells from their
locations. The loss of E-cadherin expression correlates with the
invasiveness and undifferentiated phenotype of many
epithelium-derived cancer cells (
27
). However, N-cadherin is associated
with the heightened invasive potential of cancer cells. N-cadherin
is typically expressed by mesenchymal cells, is overexpressed in
some cancer cells, and correlates with cell invasiveness (
28
). Therefore, the loss of E-cadherin
expression and the gain of N-cadherin expression in cancer cells
have functional significance in cancer progression and metastasis
(
29
).
The results of the present study have also
demonstrated that the mechanism of action of SK may involve the
suppression of NF-κB-Snail signaling. NF-κB is a structurally
conserved family of dimeric transcription factors that plays
pivotal roles in maintaining an invasive phenotype as well as
promoting carcinogenesis (
30
).
It also plays a central role in EMT through direct activation of
the transcription of Snail, which has been established as a
critical mediator of EMT (
31
).
The expression of Snail mRNA at the EMT may be reversed by the
inhibition of NF-κB, which is the upstream regulator of SNAIL
expression at the EMT (
32
). Our
results support these previous findings and provide a mechanistic
basis for the inhibition of tumor progression by SK.
In conclusion, we have demonstrated that SK
inhibition of tumor invasion and migration is associated with the
EMT process during tumor progression, and is possibly mediated by
suppressing NF-κB-Snail signaling and regulating the expression of
N- and E-cadherin, which are important downstream EMT markers.
Although further
in vivo
studies are required to establish
the potential of SK as an anticancer therapeutic agent, we suggest
that SK is an effective anticancer agent with antimetastatic
activity against breast tumors.
Acknowledgments
This study was supported by the Traditional Korean
Medicine R&D program funded by the Ministry of Health and
Welfare through the Korea Health Industry Development Institute
(HI14C05830000).
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NATO - Opinion: Opening speech by NATO Secretary General Jens Stoltenberg at the High-Level Dialogue on Climate and Security, NATO Public Forum , 28-Jun.-2022
(As delivered)
Opening speech
by NATO Secretary General Jens Stoltenberg at the High-Level Dialogue on Climate and Security, NATO Public Forum
(As delivered)
Your Excellencies, Ladies and Gentlemen, it is really great to see you all, and it is good to be here today, just before we start the NATO Summit.
At this Summit, we will address all the issues that affect our security.Russia’s war in Ukraine, cyber, terrorism, disruptive technologies and many other threats and challenges.But we also know that climate change poses a serious risk to us all.Therefore I am very pleased to be with you today.At the first High-Level Dialogue on Climate Change and Security, bringing together NATO Allies with partner nations and other stakeholders from around the world.I thank you all for being here today.
***From the High North to the Sahel, Climate change is a crisis multiplier.More extreme weather devastates communities, and fuels tensions and conflicts.Climate change matters for our security,so it matters for NATO.
That is why NATO is determined to set the gold standard on addressing the security implications of climate change.
Here in Madrid, leaders will endorse a new Strategic Concept, the Madrid Strategic Concept. It will state that climate change is a defining challenge of our time.
For NATO, this means three things.Increasing our understanding, adapting our Alliance, and reducing our own emissions.
First, increasing our understanding.Today, I am releasing our first-ever assessment of how climate change affects our security, our military assets, installations and activities, as well as our resilience and civilian preparedness.
Climate change deeply affects the environment in which our women and men operate.From extreme heat in our training mission in Iraq, to melting ice in the Arctic.And from rising sea levels and storms that threaten our naval bases, to hurricanes that disable our airfields.The list is long. There are many ways climate change affects our security.
So second, we must adapt.Providing our armed forces with the equipment they need to operate in extreme heat and extreme cold.Training them to assist in disaster relief.Reinforcing our coastal facilities against rising water levels.And addressing the security implications of more economic and military activity in High North.
We have identified the initial steps in our adaptation.We now take account of climate change when planning our operations and missions.And when developing new capabilities.This way, we make sure we remain effective in increasingly harsh environments.
And third, we must reduce the impact of our military activities on the climate.We cannot compromise our military effectiveness.NATO is about preserving peace through a credible deterrence and defence.Nothing is more important.If we fail to preserve peace, we will also fail to fight climate change.
At the same time, we also have a responsibility to reduce emissions.To this end, we have developed the first methodology for measuring NATO’s greenhouse gas emissions, civilian and military. It sets out what to count and how to count it, and it will be made available to all Allies to help them reduce their own military emissions.
This is vital, because what gets measured, can get cut.
Based on this new methodology, I can announce today the first emissions targets for NATO as an organization.By 2030, we will reduce emissions by at least 45%, reducing to net zero by 2050.
We have conducted a thorough analysis of how to do this.It will not be easy. But it can be done.
A big part of this will be our transition away from fossil fuels.All Allies are committed to reducing their greenhouse gas emissions as part of the Paris Agreement.Adapting their militaries will contribute to this.Including more green-tech such as renewables, climate-friendly synthetic fuels and more energy-efficient solutions.
There is a technological revolution happening right now.A green energy revolution.One that can be of huge benefit for our militaries.Already today, the best new cars are actual electric cars.
And I believe that in the future, the most advanced military vehicles, and the most resilient armed forces, will be those that do not rely on fossil fuels.
By making our equipment more efficient,and by taking full advantage of new technologies, we can improve our militaries and strengthen our security, as well as help tackle climate change.It will also increase our resilience.
The war in Ukraine shows the danger of being too dependent on commodities from authoritarian regimes.The way Russia is using energy as a weapon of coercion highlights the need to quickly wean ourselves off Russian oil and gas.
At the same time, we must not swap one dependency for another.Lots of new, green technologies and the rare earth minerals they require come from China.So we must diversify our energy sources and our suppliers.
Instead, we should work together ,to ensure that national policies enhance our collective military strength and NATO is the ideal platform for Allies to coordinate our efforts.By setting shared benchmarks and standards we can innovate together while maintaining our operational effectiveness.Therefore I will ask NATO civilian and military authorities to develop a new “Energy Transition By Design” initiative, and present it at the next High Level Dialogue Meeting next year.
These High-Level Meetings will be held annually, establishing NATO at the nexus between climate and security.
Climate change is not a threat that exists far beyond the horizon, or long into the future.We see its impact on our security right now.
We now have a plan with concrete actions to address the security risks of climate change.To ensure our Alliance adapts to the challenge, and to protect NATO’s one billion citizens.
Thank you so much
Moderator Hadley Gamble (CNBC): Secretary General, once again welcome and thank you so much for those remarks. It's fantastic to be here with you all today. My name is Hadley Gamble, I'm the senior correspondent for CNBC News covering politics and energy markets and how often they come together.
Secretary General, in those remarks, essentially you were saying that energy security equals national security. It's a conversation that we've been having again and again, the two of us, for a long time now, even prior to the invasion of Ukraine. And you mentioned that working together between NATO Allies is essential in terms of tackling climate change, in terms of coordinating efforts. I want to float something with you. Over the last several days, we've heard the idea of an oil cap floated amongst G7 members, what that might look like. When you think about that a little bit more broadly, could NATO lead that conversation? Because essentially, you've got to negotiate with the rest of the world here. And a lot of the rest of the world blames the West and blames NATO for inflation, high energy prices and the idea that we could at some point in the near future be talking about a food scarcity problem that could eventually lead to famine. So in terms of that oil cap, how do you think that that's actually going to get done and will NATO lead the way?
NATO Secretary General Jens Stoltenberg: So first of all, I think that, you now mentioned many challenges and we have to understand that all of those challenges are related to the war in Ukraine, which is a brutal war of aggression by President Putin against the independent sovereign nation in Europe. And the reason for…, the consequences which impact global energy markets, global food markets, the responsibility for that is President Putin’s. You have to understand that… the easiest way to end all these problems is just to end the war and for President Putin to withdraw its forces and end attacking a sovereign independent nation.
Then, I think we also have to remember that the reason why we have the challenges with, for instance, food prices and the problems of getting grain out of Ukraine is not because of our economic sanctions. There are no sanctions from NATO Allies against exports of grain. So the reason why it's hard to get grain out of Ukraine, food out of Ukraine is the war, is the Russian blockade.
Then I, of course, recognize that our economic sanctions, for instance, on parts of Russian industry, on the financial sectors, also have global ramification, also for the energy markets. And therefore Europeans, NATO Allies, the United States, partners, they pay a price. There's no way to deny that. But that price is much lower than the price we will pay if Putin gets his way by using military force against an independent nation. It is about the price we have to pay for freedom, for upholding the rules-based international order and ensure that the lesson President Putin learns from this war is [not] that he will be rewarded by using this kind of a brutal military force. So I'm not in a way suggesting that there's zero consequences for us, economically as NATO Allies and partners, by the sanctions we are imposing on Russia. But I’m saying that the most severe are direct consequences of the war itself, grain. And second that the fact that we are paying a price is actually a price worth paying to support the brave Ukrainian people in upholding the right for self-defence.
Then, on that specific issue of oil cap. Well, the message from this high-level meeting and also in the assessment I delivered today was to look at the direct link between military activities, climate change and our security. And therefore, NATO will not be the forum to address something which is more directly related to the economic consequences of higher oil prices. So we'll leave it to the…and I think it was good that the G7 and other Allies are engaging in those issues. We will focus on climate change and of course on all the other core tasks of NATO, but the discussions on how to, as I said, deal with a high energy crisis… I think there are other platforms that are more suitable than NATO.
Moderator:Secretary General, just as a follow-on to that, you mentioned in your comments authoritarian regimes. Were you referring to China, Russia, and perhaps OPEC members like Saudi Arabia, and the UAE?
NATO Secretary General:I referred to the fact that I have always believed in free trade. I still believe in free trade. I think that free trade actually fuels prosperity, growth. It's good for our economies. And division of labour has been key for economic development over centuries. At the same time, I think we need to realize that too heavy dependence on some specific commodities can create vulnerabilities for our free and open societies.
And therefore, it's not as if free trade always promotes freedom. Actually, sometimes we have to be careful. And one example is too heavy dependence on gas from Russia. That was not obvious for everyone before Ukraine. But now it’s obvious for everyone that the high dependence by European Allies on imports of gas from Russia has made them vulnerable in a way they should never have been in the situation and now with the brutal invasion of Ukraine.
Second, I also believe that of course we should trade with China. China is the biggest, soon the biggest economy in the world. Trade with China has been important for many other companies for prosperity…and it will be also the future. But we have to be aware of the same risks of too heavy dependence for instance, on rare earth minerals, which are key for many different technologies, including green technologies. We have to be aware of the risk of China controlling critical infrastructure. Not so many years ago, two, three years ago, there was a big discussion on whether we should be concerned about China's control of 5G networks. Now, I think everyone realizes that that is something that matters for our security. So we should not… in a way in the shadow of the idea of free trade, open up, and make our infrastructure vulnerable to Chinese control when we, for instance, speak about 5G networks.
And then lastly, we should also realize the danger of too much naive free trade if that leads to that we are sharing key technologies we are developing with authoritarian powers. So, I'm not against trading with authoritarian countries. That will be the case, has been and will be the case in the future. But we need to be aware of the risks, the vulnerabilities. And therefore the work we now do in NATO to improve resilience, to increase awareness on these issues. And then, in dialogue with Allies in different ways, also ensure that we…well, we continue to be in favour of free trade. But we also have to have some limits and some guidelines on how to not create new vulnerabilities as we have seen, for instance, with our dependence on imports of Russian gas.
Moderator:Secretary General, when you think about this within the context of the current situation with regards to climate change and the energy transition, I just want to read you a couple of comments that we've heard in recent days as quoted to CNBC. The CEO of Exxon discussing the current energy situation and saying that society is going to pay a very high price if governments and industries abandoned fossil fuels too soon. The CEO of BP essentially saying that the world needs to back those who deliver the energy, that the world needs today as well as tomorrow. When you think about that within the context of where we are now, there is deep concern that consumers across the West and elsewhere are gonna basically face a cost of living crisis in the coming months as a direct result of the situation that we're seeing today in Ukraine. What is your message to the oil and gas community at this point? Are you willing as NATO Allies to work with them through this transition? Should we be investing more money now? And not just renewables, but also fossil fuels today?
NATO Secretary General:So first of all, many NATO Allies are of course working very closely with the industry, also the energy industry, and also those parts of the energy industry that are investing in fossil fuels. And what we see is that many of these companies, they're actually now also key in the transition away from fossil fuels. So I think a lot of the technology, the capital, the competence these companies have, will be key for the transition away from fossil fuels.
Moderator:So demonizing them isn't the way forward?
NATO Secretary General: No, no, that's never the answer. Because the issue, the question is not whether we have to move away from fossil fuels. There's no way we can achieve the goals we have set to reduce emissions of greenhouse gases, either by moving away from fossil fuels and/or by developing technologies for carbon capture. And I think we have to do both.
Then, of course, the high prices we see now, they are a big problem for ordinary households throughout the world. And again, poor people are more vulnerable than rich people because they're more able to pay for it and higher energy prices, those who don't have so much… for them, this is really, really a serious problem.
I think the answer is to increase supply. And of course, what we have seen is that the high prices on oil and gas, and also the cut in supply, has to some extent lead to that some countries are moving back to coal. That is bad for climate, but of course it reflects the desperate situation they are in.
Hopefully, and I think that also will happen, and it's happening, and that is that increased prices on oil and gas will also then incentivize investments in more energy efficient solutions. Because you can reduce emissions just by finding more energy efficient solutions even though you continue to use different types of fossil fuels. By investing in new types of energy, everything from biofuels to clean synthetic fuels, to also hydrogen, and other green and clean energy sources.
And then, I am a man that believes in the idea of carbon capture. We have seen several big projects, and I think that with increasing carbon prices, and increasing awareness of the need to reduce carbon emissions, there will be big carbon capture projects that will help us to provide both energy and reduce emissions at the same time.
Moderator:You mentioned the backlash there. It's something that the UN Secretary General has also talked about, the risk of backlash because of the higher living costs. Essentially, power prices can take three to five years to fall back to lower levels, according to the CEO of Germany's largest power producer. There's a lot of speculation at this point about a time in the near future, potentially as we move into the winter months, that you're going to lose the support of the public. What is NATO's strategy to ensure that that doesn't happen?NATO Secretary General:To convey how important this fight is and to convey how important it is that we support Ukraine.Of course, there is no way to deny that we pay a price, as I said. But you have to remember that by far the highest price is paid by the Ukrainian people and Ukrainian Armed Forces. They are actually fighting every day. We see casualties. We see attacks on cities, on civilian infrastructure, on hospitals, on schools. So I, of course, I recognize that also people in NATO allied countries and partners see the consequences of the war because of higher energy prices. And I share those concerns. And as political leaders throughout the Alliance they are addressing that in different ways. But that's a very different situation than the situation people experience in Ukraine, where they actually are killed, and where we see atrocities, and where people are afraid of their lives. So we have to put things in perspective.
Second, and this is about the kind of moral and political obligation to Ukraine. But second, it is in our interest to support Ukraine. We support Ukraine partly because they are a close partner. We have worked with them for many years, but also because it will be our world, the world of NATO Allies will be more insecure if Putin wins this war.
So it's in our security interest to make sure that Ukraine prevails as a sovereign, independent nation. And therefore, we need to provide support as long as it takes. And…has a much higher price than to pay price now to ensure that Ukraine prevails.
Moderator:Secretary General walk us through how this looks from a hardware perspective. Are we going to see electric F-35s? Where are we today in those types of prototypes?
NATO Secretary General: I'm very careful predicting exactly what kind of electric vehicles or whatever. It may be not electric, it may be hydrogen there may be fuel cells that are different types of energy solutions. I will not be specific exactly on what will be the winning technology.
What we see now, at least when it comes to vehicles, cars, is that electric is really on the offensive. And maybe other technologies for more heavy vehicles, for instance, hydrogen. The experts have different views. I think the most important we can do is to support research, development and price emissions. Because if we support the open new technologies, if we put a price on carbon emission, it will become profitable to develop clean technologies. And then, actually, it will leave to the industry to innovate and to find out exactly what is the best solution to this specific task, either to …big battleships or to… smaller cars or whatever that is. That is not for politicians, but that's for the industry to decide and then offer those solutions to the military.
What I'm absolutely certain about, is that if there's a technological revolution taking place in the civilian sector, which is now the case, with less and less dependence on fossil fuels, and more and more new green technologies for all energy solutions in the civilian sector, from electric cars to carbon capture, to fuel cells, to hydrogen in the civilian sector, it will not be good for the military if we end up as the only fossil fuel sector left in the world some decades from now. That will weaken our military capabilities. So if we want to maintain the technological edge and have the best cars, the best planes, the best technologies, then we need to be green. Not only because we care about climate change, but because we care about having the best technologies in our armed forces.
So in the short term, there may be a contradiction between green and military effectiveness. In the long run, green and military effectiveness is the same.
Moderator:Secretary General, we only have a few minutes left and I have to ask you one of the burning questions ahead of the next couple of days. And that of course is Sweden and Finland and…joining the Alliance. Where are we today with that question?
NATO Secretary General: The decisions by Finland and Sweden to apply for membership they are historic. And that will strengthen the security of Finland and Sweden, of NATO and be important for the whole transatlantic alliance. At the same time, we need to ensure that when new Allies or new countries joined the Alliance, we have to take into account the security interests of all Allies. And Türkiye has expressed some serious concerns on issues like terrorism, and we all know that no NATO Ally has suffered more terrorist attacks than Türkiye. Thousands of people have been killed. And PKK and other groups they are responsible for these terrorist attacks. And PKK is a terrorist organization. That is something which is… not only many NATO Allies proscribe PKK as a terrorist organisation, but the European Union, Finland and Sweden. So of course, to sit down then and discuss with Türkiye how can we step up, do more together and fighting terrorism which is a threat to our security, is an issue that is absolutely legitimate and important as part of the accession process… and dialogue we now have with Finland and Sweden.
I will not promise anything. I can only tell you that I have spoken several times with President Erdoğan, with the Finnish President and with the Swedish Prime Minister. We will meet later on today. President Erdoğan, President Niinistö and Prime Minister Andersson. And I hope that we can make some progress, but let's meet first and then I can update you afterwards.
Moderator:Secretary General, all my friends in the press corps are going to be jealous of that. When you think about this a bit more broadly, Sir, billions of dollars of weapons and aid going to Ukraine, unprecedented economic sanctions on Russia, the Russian ruble currently stable, those sanctions and undoubtedly we'll see more effectiveness as time goes on.
But there is a big portion of the world, part of the world I live in - the Middle East. And looking out to the Sahel, as you mentioned in your speech earlier, to Africa, elsewhere, they are very worried about food security issues, they are very worried about famine, they're worried about higher energy costs, and frankly, civil and social unrest. What is NATO's leverage there in convincing countries like China, like India to pay a cap for Russian oil or to leave Russian energy supplies altogether?
NATO Secretary General: Well, first of all, again, the food prices. I fully understand that people all over the world, including in the Middle East and in Africa, are extremely concerned. But the reason for increased food prices is not NATO, is not sanctions. It is Russia's brutal war against Ukraine. Full stop. And if President Putin was willing to stop the war, or at least allow ships to sail with grain out of Ukraine, it would help to reduce the food prices. I welcome the fact that NATO Allies in different ways, but actually in particular Türkiye and President Erdoğan are engaged in different initiatives to try to find a way to get grain out by… on ships over the Black Sea. But there are also some initiatives to try to at least increase, to some extent, the amount of food we're getting out on land, over NATO and EU territory in Europe. There are some serious logistical challenges with that, but at least it can help perhaps to increase somewhat the amount we're getting out.
Then, on China. One of the messages we have is that we don't regard China as an adversary. And China, of course, is soon the biggest economy in the world. We need to engage with China, for instance on issues like climate change. It matters for the whole energy market.
But we are disappointed by the fact that China has not been able to condemn the Russian invasion of Ukraine, that China is spreading many of the false narratives about NATO, the West. And also that China and Russia are more close now than they've ever been before. We saw that in the joint statement by China and Russia, President Xi and President Putin in the beginning of February where they said that the partnership was limitless, I think was the language, but at least they stated very clearly, both China and Russia that they were against any NATO enlargement. And that's the first time China so explicitly had a strong opinion directed against NATO and NATO enlargement.
Moderator:And doesn't that worry you that there is a situation where you can see NATO versus the rest of the world?
NATO Secretary General: We cannot stop supporting Ukraine because not all countries all over the world support us. Then, we had the vote in the UN where 141 nations condemned the invasion. We have a responsibility to support Ukraine. Partly by providing support, military support, economic support, humanitarian support. NATO Allies have supported Ukraine since 2014. We didn't wake up in February 2022. Actually, I've been in Yavoriv and other places in Ukraine, where I’ve seen Canadian, US, UK and also NATO personnel training, helping equipping the Ukrainian Armed Forces. The Ukrainian Armed Forces are much better equipped, much better trained, much larger, much better commanded in 2022 than in 2014. Not least because of the support, the training, the equipment they have received for many years from the NATO allied countries. It's first and foremost the bravery, the courage of Ukrainians that have enabled to stand up against the brutal Russian invasion. But the support they have achieved from 2014 and onwards has of course, also been key. Now our responsibility is to step up, to do more and be ready to stand for long haul because this this may last.
Then, so if the issue is that we should not do this because it may create the impression that we have some responsibility for some of the problems in the world economy, the answer is absolutely no. We have to continue to support Ukraine, including imposing a price on Russia by imposing sanctions.
And then, we have to engage in dialogue, in public communications, to explain that the core problem is not the way we support Ukraine. The core problem is the unprovoked, unjustified war by President Putin against Ukraine. That's the problem.
Moderator:Secretary General thank you so much for joining us.
NATO Secretary General: Thank you.
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NATO Secretary General opening speech at the NATO Public Forum 28 Jun. 2022
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NATO Secretary General says that Climate Change matters for NATO 28 Jun. 2022
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Publications - Global Disability Innovation Hub
The GDI Hub brings together academic excellence, innovative practice and co-creation; harnessing the power of technology for good.
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COVID-19 as social disability: the opportunity of social empathy for empowerment
Ikenna D Ebueny, Emma M Smith,
Catherine Holloway
, Rune Jensen, Lucía D'Arino, Malcolm MacLachlan
Social empathy is ‘the ability to more deeply understand people by perceiving or experiencing their life situations and as a result gain insight into structural inequalities and disparities’. Social empathy comprises three elements: individual empathy, contextual understanding and social responsibility. COVID-19 has created a population-wide experience of exclusion that is only usually experienced by subgroups of the general population. Notably, persons with disability, in their everyday lives, commonly experience many of the phenomena that have only recently been experienced by members of the general population. COVID-19 has conferred new experiential knowledge
on all of us. We have a rare opportunity to understand and better the lives of persons with disabilities for whom some aspects of the COVID- 19 experience are enduring. This allows us greater understanding of the importance of implementing in full a social and human rights model of disability, as outlined in the UNCRPD.
BMJ Global Health; 2020
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Abstract
COVID-19 as social disability: the opportunity of social empathy for empowerment COVID-19 has conferred new experiential knowledge on society and a rare opportunity to better understand the social model of disability and to improve the lives of persons with disabilities. The COVID-19 experience may offer contextual knowledge of the prepandemic lives of persons with disabilities and foster greater social awareness, responsibility and opportunities for change towards a more inclusive society. Information, family and social relationships, health protection and healthcare, education, transport and employment should be accessible for all groups of the population. The means must be developed and deployed to ensure equity – the deployment of resources so that people with different types of needs have the same opportunities for living good lives in inclusive communities. We have learnt from COVID-19 that inclusive healthcare and universal access should be the new normal, that its provision as a social good is both unifying and empowering for society as a whole.
Cite
COVID-19 as social disability: the opportunity of social empathy for empowerment
Ebuenyi ID, Smith EM, Holloway C , et al
COVID-19 as social disability: the opportunity of social empathy for empowerment BMJ Global Health
2020; 5:
e003039.
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COVID-19 as social disability: the opportunity of social empathy for empowerment
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Developing inclusive and resilient systems: COVID-19 and assistive technology
Emma M. Smith, Malcolm MacLachlan, Ikenna D. Ebuenyi, Catherine Holloway
& Victoria Austin
While the inadequacies of our existing assistive technology systems, policies, and services have been highlighted by the acute and rapidly changing nature of the COVID-19 pandemic, these failures are also present and important during non-crisis times. Each of these actions, taken together, will not only address needs for more robust and resilient systems for future crises, but also the day-to-day needs of all assistive technology users. We have a responsibility as a global community, and within our respective countries, to address these inadequacies now to ensure an inclusive future.
Disability & Society; 2020
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Abstract
Developing inclusive and resilient systems: COVID-19 and assistive technology
Assistive technology is a critical component of maintaining health, wellbeing, and the realization of rights for persons with disabilities. Assistive technologies, and their associated services, are also paramount to ensuring individuals with functional limitations have access to important health and social service information, particularly during a pandemic where they may be at higher risk than the general population. Social isolation and physical distancing have further marginalized many within this population. We have an opportunity to learn from the COVID-19response to develop more inclusive and resilient systems that will serve people with disabilities more effectively in the future. In this Current Issues piece, we present a starting point for discussion, based on our experiences working to promote access to assistive technologies through inclusive and sustainable systems and policies.
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Developing inclusive and resilient systems: COVID-19 and assistive technology
Emma M. Smith, Malcolm MacLachlan, Ikenna D. Ebuenyi, Catherine Holloway & Victoria Austin (2021) Developing inclusive and resilient systems: COVID-19 and assistive technology, Disability & Society, 36:1, 151-154, DOI: 10.1080/09687599.2020.1829558
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Developing inclusive and resilient systems: COVID-19 and assistive technology
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Assistive Technology (AT), for What?
Vicki Austin , Catherine Holloway
This year (2022) has seen the publication of the World’s first Global Report on Assistive Technology (GReAT) [ 1
]. This completes almost a decade of work to ensure assistive technology (AT) access is a core development issue. The lack of access to assistive products (APs), such as wheelchairs, hearing aids, and eyeglasses, as well as less well-referenced products such as incontinence pads, mobile phone applications, or walking sticks, affects as many as 2.5 billion people globally. Furthermore, the provision of APs would reap a 1:9 return on investment [
2
]. This could result in a family in need netting (or living without) over GBP 100,000 in their lifetime [ 2
] or more, if we count dynamic overspills in the economy such as employment of assistive technology services and manufacturing of devices [ 3
].
Societies; 2021
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Abstract
Assistive Technology (AT), for What?
Amartya Sen’s seminal Tanner lecture: Equality of What?
began a contestation on social justice and human wellbeing that saw a new human development paradigm emerge—the capability approach (CA)—which has been influential ever since. Following interviews with leading global assistive technology (AT) stakeholders, and users, this paper takes inspiration from Sen’s core question and posits, AT for what?
arguing that AT should be understood as a mechanism to achieve the things that AT users’ value. Significantly, our research found no commonly agreed operational global framework for (disability) justice within which leading AT stakeholders were operating. Instead, actors were loosely aligned through funding priorities and the CRPD. We suggest that this raises the possibility for (welcome and needed) incoming actors to diverge from efficiently designed collective action, due to perverse incentives enabled by unanchored interventions. The Global Report on Assistive Technology (GReAT) helps, greatly! However, we find there are still vital gaps in coordination; as technology advances, and AT proliferates, no longer can the device-plus-service approach suffice. Rather, those of us interested in human flourishing might explore locating AT access within an operational global framework for disability justice, which recognizes AT as a mechanism to achieve broader aims, linked to people’s capabilities to choose what they can do and be.
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Assistive Technology (AT), for What?
Austin, V.; Holloway, C. Assistive Technology (AT), for What? Societies 2022
, 12
, 169. https://doi.org/10.3390/soc120...
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Assistive Technology (AT), for What?
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Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution
Sahan Bulathwela, María Pérez-Ortiz,
Catherine Holloway
, John Shawe-Taylor
This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies.
Workshop on Machine Learning for the Developing World (ML4D) at the Conference on Neural Information Processing Systems 2021; 2021
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Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution
Artificial Intelligence (AI) in Education has been said to have the potential for building more personalised curricula, as well as democratising education worldwide and creating a Renaissance of new ways of teaching and learning. Millions of students are already starting to benefit from the use of these technologies, but millions more around the world are not. If this trend continues, the first delivery of AI in Education could be greater educational inequality, along with a global misallocation of educational resources motivated by the current technological determinism narrative. In this paper, we focus on speculating and posing questions around the future of AI in Education, with the aim of starting the pressing conversation that would set the right foundations for the new generation of education that is permeated by technology. This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies. Finally, we ask what would it take for this educational revolution to provide egalitarian and empowering access to education, beyond any political, cultural, language, geographical and learning ability barriers.
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Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution
Type
Workshop
Themes
Assistive & Accessible Technology
Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts
Tabish Ahmed, Sahan Bulathwela
The informational needs of people are highly contextual and can depend on many different factors such as their current knowledge state, interests and goals [1, 2, 3]. However, an effective information retrieval companion should minimise the human effort required in i) expressing a human information need and ii) navigating a lengthy result set. Using topical representations of the user history (e.g. [4]) can immensely help formulating zero shot queries and refining short user queries that enable proactive information retrieval (IR). While the world has digital textual information in abundance, it can often be noisy (e.g. extracted through Automatic Speech Recognition (ASR), PDF text extraction etc.), leading to state-of-the-art neural models being highly sensitive to the noise producing sub-optimal results [5]. This demands denoising steps to refine both query and document representation. In this paper, we argue that Wikipedia, an openly available encyclopedia, can be a humanly intuitive knowledge base [6] that has the potential to provide the world view many noisy information Retrieval systems need.
Published at the First Workshop on Proactive and Agent-Supported Information Retrieval at CIKM 2022; 2022
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Abstract
Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts
Extracting useful information from the user history to clearly understand informational needs is a crucial feature of a proactive information retrieval system. Regarding understanding information and relevance, Wikipedia can provide the background knowledge that an intelligent system needs. This work explores how exploiting the context of a query using Wikipedia concepts can improve proactive information retrieval on noisy text. We formulate two models that use entity linking to associate Wikipedia topics with the relevance model. Our experiments around a podcast segment retrieval task demonstrate that there is a clear signal of relevance in Wikipedia concepts while a ranking model can improve precision by incorporating them. We also find Wikifying the background context of a query can help disambiguate the meaning of the query, further helping proactive information retrieval.
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Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts
Type
Article
Themes
Assistive & Accessible Technology
These tools help visually impaired scientists read data and journals
Alla Katsnelson
This article was featured in Nature and discusses tools that help visually impaired scientists read data and Journals. Innovation Manager, Daniel Hajas, was interviewed as part of this piece and highlights the need for an ecosystem approach, and access to data / visualisations for blind members of the research and science community.
Nature; 2023
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These tools help visually impaired scientists read data and journals
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A Randomized Cluster Trial to Evaluate a Mobile Mammography Unit in Breast Cancer Screening in France (Mammobile) - Full Text View - ClinicalTrials.gov
A Randomized Cluster Trial to Evaluate a Mobile Mammography Unit in Breast Cancer Screening in France (Mammobile) (Mammobile)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT05164874 Recruitment Status :
Enrolling by invitation First Posted : December 21, 2021 Last Update Posted : December 21, 2021
Sponsor:
Université de Caen Normandie
Collaborators:
National Cancer Institute, France
Regional health agency, Normandy France
Pink ribbon (Ruban Rose, France)
Normandy regional cancer screening coordination center
Departmental councils
Information provided by (Responsible Party):
Élodie Guillaume, Université de Caen Normandie
Study Details
Study Description
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
Organized breast cancer screening (OBCS) has been implemented nationwide since 2004 inFrance, but the participation rate remains low (51%) and inequities in participation were reported. Strategies as mobile mammography units could be effective to increase participation in OBCS and reduce inequities, especially in underserved areas in regard to this screening. Our main objective is to evaluate this device and to identify how to incorporate a mobile unit in the OBCS with a view to tackle territorial inequities in OBCS participation. The project will be conducted as a randomized controlled cluster trial in 2022-2024, in remote areas of 4 French departments. The main intervention is to propose an appointment at the mobile unit in complement to the current OBCS in these remote areas. In addition, few weeks before this intervention, local actors will carry out actions to promote OBCS with mobile unit specific information tools. This randomized controlled trial will provide a high level of evidence in assessing the mobile unit effects on participation and inequities.
Condition or disease Intervention/treatment Phase Breast Cancer Device: Mobile Mammography Unit Not Applicable
Detailed Description:
Context In most EU member states, breast cancer screening is organised with a mammography screening. However, there are still differences in the way screening programmes are implemented. In France, the organized breast cancer screening (OBCS) has been conducted, nationwide since 2004. A screening mammography is offered every two years to women aged 50 to 74 at average risk for this cancer. They receive from management structures in charge of this screening (SMS), an invitation to visit an accredited radiologist's office. A radiological imaging of the breast with two views plus a clinical breast examination is realized. Two different radiologists assure readings. In the last three year, the national participation rate remains stable around 51%. In addition, studies, using ecological indices of deprivation, highlight social and territorial inequalities: women living in disadvantaged area or far from a radiologist's office less participate. Different strategies can be implemented to increase participation to breast cancer screening, especially in populations with low-income or in rural areas, who have less access to screening. Among these strategies, mobile mammography units (MMU) seem effective. Therefore, in the French context, there is very little evidence on how to intervene to reduce health socio-territorial inequalities in screening, so public health decision-makers are unable to base proposals on evidence.
Intervention The main intervention will be a proposition for an appointment at the MMU in complement to the current OBCS. This complementary mode of screening offers the possibility for women furthest away from the radiologist's office to undergo screening in the MMU. All women eligible for OBCS and living in the zone selected for the intervention will be invited to participate either in a radiologist's office or in the MMU, keeping the choice of their place of screening. The breast screening in the MMU will follow the same protocol as screening at the radiologist's office according to national recommendations, so that the quality level of screening proposed in the MMU will the same as in any radiologist office. The MMU will be equipped with a latest-generation digital scenographer as well as an ultrasound system according to the compliance rules of the specifications published by the National Institute of Cancer. The quality of the mammographic radiographic equipment will also be certified by the Nuclear Safety Agency.
About two weeks before the MMU is parked, local actors, will carry out actions to inform women on the organized breast cancer screening and on the MMU. Women will receive the timetable of these actions with the invitation to participate in screening.
An algorithm was developed to constitute clusters integrating some constraints in a regional scenario.
Aggregation of IRIS was done according to the travel time to the radiology centres, the most distant IRIS has been selected and then merged with neighbouring IRIS, still by distance run, until reaching areas of the expected population size. This except size is around 100 women. Expecting a 40% participation to the MMU, 32 to 48 mammograms daily should be performed.
This algorithm was applied to all IRIS according to distance rank, until no more aggregation was possible. 91,982 women (95.6%) and 1,067 IRIS (94.3%) were selected in the final population in 356 clusters (with 258 created by the algorithm).
All the women constituting the target population is geolocated and geocoded. Thus, for each woman, history of screening, the current date of screening invitation, IRIS of residence, level of social deprivation according to an ecological deprivation index (the European Deprivation Index) and the distance between the woman's house and the nearest approved radiologist's office are known.
A randomization in parallel group have been perform to constitute the intervention arm (n=178 clusters) and the control arm (n=178 clusters), corresponding to 45275 in intervention arm vs 46707 in control arm.
Evaluations The overall objectives of the study are to evaluate the intervention's ability a) to reduce the socio-territorial inequalities of participation in breast cancer screening in a regional area (Normandy) in setting remote from radiologist's office b) to increase participation rate and c) understand how intervention interact with contextual factors and which causal mechanisms leading to these results in order to identify the optimal modalities for extending the MMU at the national level.
Concerning the first two objectives, the main evaluation criterion will be participation in screening, measured and compared between the "intervention" and "control" arm, at the aggregate level (cluster) and individual level in intent to treat. At the aggregate level, the comparison of screening participation will allow us to measure the raw and age-standardized increase in participation due to the intervention. At the individual level, multilevel logistic regressions, taking into account cluster data, allow to assess the increase in the probability of participating in screening after adjustment of the social deprivation, age and other available individual characteristics.
Although the calculation of the number of subjects in the study came from a pragmatic approach, the intraclass correlation factor was estimated at 0.0083, which with an average area size of 318.6 women gives a design effect equal to 3.63. Thus, the minimum significant difference in participation that can be proven will be 1.5%.
Actors information action, will be prospectively registered in a dedicated database and will be include in the global model analysis.
To furthermore explore contextual effect and to provide elements of knowledge on the causal mechanisms contributing to the effectiveness of the intervention the quantitative analyses will be completed by a qualitative approach inspired by the combined approaches that have emerged in realistic randomised controlled trials, using a theory that goes beyond logic models to describe contextual mechanisms and contingencies. An intervention theory was developed and three auto questionnaires will respectively explore, the informed choice, satisfaction to realized the mammography in the mammobile and the ComB Model construct implied in the screening behaviour.
Study Design
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for study information Study Type : Interventional
(Clinical Trial) Estimated Enrollment : 91982 participants Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: This intervention will be conducted as a prospective randomized controlled cluster trial.The cluster of the study is an aggregation of géographical areas. It was done according to the travel time to the radiology centres, the most distant areas has been selected and then merged with neighbouring areas, still by distance run, until reaching areas of the expected population size. This except size is around 100 women. Expecting a 40% participation to the mobile unit, we will achieve 32 to 48 mammograms daily. A randomization in parallel group have been perform to constitute the intervention arm and the control arm. Masking: Single (Participant) Primary Purpose: Prevention Official Title: Evaluation of a Mobile Mammography Unit. A Randomized Cluster Trial Protocol of a Population Health Intervention Research to Reduce Breast Cancer Screening Disparities in Normandy, France (Mammobile) Estimated Study Start Date : February 14, 2022 Estimated Primary Completion Date : February 2024 Estimated Study Completion Date : September 2024
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics: Breast cancer
MedlinePlus related topics: Breast Cancer Mammography
U.S. FDA Resources
Arms and Interventions
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Arm Intervention/treatment Experimental: InterventionWomen will receive a proposition for an appointment at the MMU in complement to the current screening invitation, keeping the choice of their place of screening.Women will also receive the timetable of prevention actions with the invitation to participate in screening. Device: Mobile Mammography Unit The main intervention will be a proposition for an appointment at the MMU in complement to the current OBCS No Intervention: Control No change from the usual breast cancer screening organization
Outcome Measures
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Primary Outcome Measures
:
Aggregated breast cancer screening participation rate 3 months after the last invitation [ Time Frame: 3 months after the last invitation at the end of the two years of the intervention ]
Participation rate will be measure at area level and compare between intervention and control arm.
Individual breast cancer screening participation rate 3 months after the last invitation [ Time Frame: 3 months after the last invitation at the end of the two years of the intervention ]
It will also be assessed at indivdual level with multilevel logistic regression
Impact of the mobile unit on social inequalities in screening participation [ Time Frame: 3 months after the last invitation at the end of the two years of the intervention ]
Impact of the mobile mammography unit on social inequalities will be assessed by comparing intervention and control arm. Social statut is measure with an ecological deprivation index
Impact of the mobile unit on territorial inequalities in screening participation [ Time Frame: 3 months after the last invitation at the end of the two years of the intervention ]
impact of the mobile mammography unit territorial inequalities will be assessed by comparing intervention and control arm. The distance to the radiologiste center will be used as territorial mesure
Secondary Outcome Measures
:
Informed choice to breast cancer screening for participating women [ Time Frame: through study completion, an average of 3 month ]
An autoquestionnaire adressed to control and intervention arm will compare the informed choice
Informed choice to breast cancer screening for non-participating women [ Time Frame: Women will be considered as "non participating" 18 month after the invitation ]
An autoquestionnaire adressed to control and intervention arm will compare the informed choice
Satisfaction to mammography [ Time Frame: through study completion, an average of 3 month ]
An autoquestionnaire adressed to control and intervention arm will adressed the satisfaction to the mammography screening
Com-B Model Evaluation for participating women [ Time Frame: through study completion, an average of 3 month ]
An autoquestionnaire adressed to control and intervention arm will assessed if the mobile mammography unit and the prevention action have been facilitators to opportunity, motivation or capacity, to participate to breast cancer screening
Com-B Model Evaluation for non-participating women [ Time Frame: Women will be considered as "non participating" 18 month after the invitation ]
An autoquestionnaire adressed to control and intervention arm will assessed if the mobile mammography unit and the prevention action have been facilitators to opportunity, motivation or capacity, to participate to breast cancer screening
Eligibility Criteria
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Layout table for eligibility information Ages Eligible for Study: 50 Years to 74 Years (Adult, Older Adult) Sexes Eligible for Study: Female Accepts Healthy Volunteers: Yes
Criteria
Inclusion Criteria:
women eligible to breast cancer screening campaign : aged 50 to 74 years, and with the only risk of breast cancer being age. The previous screening mammography dating from 22 months
Exclusion Criteria:
outside the ages
with specific risk of breast cancer
Contacts and Locations
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05164874
Locations
Layout table for location information France Normandy Caen, Normandy, France, 14000
Sponsors and Collaborators
Université de Caen Normandie
National Cancer Institute, France
Regional health agency, Normandy France
Pink ribbon (Ruban Rose, France)
Normandy regional cancer screening coordination center
Departmental councils
Investigators
Layout table for investigator information Principal Investigator: Elodie Guillaume, PhD Université de Caen Normandie
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Guillaume E, Rollet Q, Launay L, Beuriot S, Dejardin O, Notari A, Crevel E, Benhammouda A, Verzaux L, Quertier MC, Launoy G. Evaluation of a mobile mammography unit: concepts and randomized cluster trial protocol of a population health intervention research to reduce breast cancer screening inequalities. Trials. 2022 Jul 8;23(1):562. doi: 10.1186/s13063-022-06480-w.
Layout table for additonal information Responsible Party: Élodie Guillaume, PhD in Epidemiology and Public Health, Université de Caen Normandie ClinicalTrials.gov Identifier: NCT05164874 History of Changes Other Study ID Numbers: UCaenNormandie First Posted: December 21, 2021 Key Record Dates Last Update Posted: December 21, 2021 Last Verified: November 2021 Individual Participant Data (IPD) Sharing Statement: Plan to Share IPD: Yes Plan Description: Individual data is collected as part of the usual organization of organized breast cancer screening. It is the authorized structure that manages these data. Time Frame: Data concerning participation, place of participation, date, distance and socioeconomic status will be anonimously analysed after the two years.
Layout table for additional information Studies a U.S. FDA-regulated Drug Product: No Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Élodie Guillaume, Université de Caen Normandie:
breast cancer screening mobile mammography unit social and territorial inequalities randomized cluster trial
U.S. National Institutes of Health
| https://clinicaltrials.gov/ct2/show/NCT05164874 |
Novel disubstituted chrysene as a potent agent against colon cancer
Novel disubstituted chrysene as a potent agent against colon cancer
Authors:
Bimal B. Banik
Manas K. Basu
Published online on: September 8, 2010 https://doi.org/10.3892/ol.2010.167
Pages: 1033-1036
Metrics:
Abstract
Research on polycyclic aromatic hydrocarbons and their derivatives has received significant attention from the scientific community. The present study involved the synthesis of several novel 6,12-disubstituted chrysene derivatives. Nitration of chrysene with nitric acid produced 6,12-dinitrochrysene which when reduced yielded 6,12-diaminochrysene. A coupling reaction of 6,12-diaminochrysene with an acid in the presence of isobutylchloroformate produced amide. The reduction of amide produced an amine. The amino was converted to a hydrochloride salt. The new compounds were characterized through different types of analytical data. One of these compounds demonstrated marked activity in vivo against a colon cancer cell line. Inhibition of the growth of this tumor was best noted at day 20 when each treatment regimen inhibited the average tumor volume by 50%. In a number of in vivo tests in various regimens, the hydrochloride salt demonstrated consistent inhibition of the growth of the cancer HT-29 cell line. Despite the research progress in polycyclic aromatic compounds, the use of these types of molecules as anticancer agents has not been reported systematically.
Introduction
Research on polycyclic aromatic hydrocarbons and
their derivatives has received significant attention from chemists,
biologists and medical investigators (
1
). However the use of these molecules as
anticancer agents has yet to be investigated systematically. Bair
et al
reported the effectiveness of polyaromatic compounds
against tumor cell lines (
2
3
–
6
).
To extend a previously published investigation
involving biologically active aromatic compounds, this study
describes the synthesis of several novel 6,12-disubstituted
chrysene derivatives. Notably, one of these compounds demonstrated
marked activity
in vivo
against a colon cancer cell
line.
Materials and methods
Materials
Chrysene, nitric acid, hydrazine hydrate,
isobutylcholoformate, lithium aluminum hydride, tetrahydrofuran,
hydrochloric acid, and the colon cancer HT-29 cell line were used
in the study.
Synthesis
Chrysene 1 on nitration with nitric acid
produced 6,12-dinitrochrysene 2 and this compound was then
reduced by hydrazine hydrate/Pd-C to yield 6,12-diaminochrysene
3. 6,12-Diaminochrysene 3 was then condensed with
acid 5 in the presence of isobutylchloroformate to yield
amide 6. Amide 6 on reduction yielded amine 7.
Amine 7b was converted to its salt 8 (
7
–
12
).
Experiment
N,
N-(6,12-chrysenyl)-bis-(4-(4N-methylpipera-zinyl)-butane-1,4-diamine
(
8
): mp 166–168°C; IR (film): 3383,
2932, 2849, 2798, 1594, 1524, 1452, 1357, 1277, 1225, 1162, 1113,
1048, 1012; cm
−1
): δ1.6 (m, 8H),
2.3 (s, 6H), 2.5 (m, 20H), 3.5 (t, 4H), 7.6 (m, 6H), 8.0 (d, 2H,
J
= 8 Hz), 8.6 (d, 2H,
J
= 8 Hz); UV: 370, 286, 234
with a mass of 567, 531, 313, 304, 284, 263, 230, 216, 206, 154 and
130 was used. The analysis was calculated for
C
36
H
50
N
6
: C, 76.3, H, 8.9, N,
14.8. The result obtained was: C, 76.61, H, 8.88, N, 14.67.
Preparation of salt 8
The hydrochloride salt 8 of the amine
7 was prepared by mixing it with an excess hydrochloric acid
solution in ether for 1 h and filtering the residue (100% yield).
The salt was characterized after regenerating the parent amine by
the basification-extraction procedure.
In vivo results
Compound 8 activity against the
human colon cancer HT-29 cell line
Table Ishows a
typical in vivoexperiment.
Table I Compound 8 activity against the
colon cancer HT-29 cell line in vivo.
Table I
Compound 8 activity against the
colon cancer HT-29 cell line in vivo.
Tumor
volume/mouse Day 11 13 17 20 25 27 Controls (17) 85.9
mm 3 240.8
mm 3 285.8
mm 3 404.1
mm 3 450.0
mm 3 8/17 13 (10) 35 mg/kg
a.m. 25 mg/kg p.m i.p. x 5 50.1
mm 3 91.4
mm 3 129.3
mm 3 204.0
mm 3 276.0
mm 3 1/10 13 (5) 35 mg/kg a.m.
i.p. x 5 10 mg/kg 6 h later i.p. x 5 15 mg/kg 12 h later i.p. x 5 43.2
mm 3 92.0
mm 3 97.7
mm 3 201.3
mm 3 216.6
mm 3 1/5
[i]Tumor-bearing
mice were sacrificed when their tumors reached an estimated 1
cm 3. Measurements were in 2 dimensions, and tumor volume
was calculated by the formula: TV= (LxW) 2/2. Numbers in
parentheses indicate the effective no. of mice. The no. of mice
sacrificed when the tumors reached 1 cm 3over the
effective number of mice at 27 days is shown. i.p.,
intraperitoneally.
cells, tumor growth was evident in the majority of mice at day 11,
with a rapid increase in the average tumor volume at day 25. Growth
of this tumor in the control mice was consistently between 85 and
100%. When tumors achieved a volume of 1 cm
3
the animals
were sacrificed. As shown in
Table
I
, 47% of the control mice were sacrificed by day 27, and this
result was quite typical of many runs. When treated with 8
either BID (twice daily) or TID (three times a day), inhibition of
the growth of tumors in terms of tumor growth was consistently
evident. Subsequently, on day 27 only 10% of the 8 BID and 20% of
the 8 TID mice were sacrificed. Another indication of the
inhibition of growth of this tumor was best evidenced at day 20
when each regimen inhibited the average tumor volume by 50%.
In a number of
in vivo
tests compound
8 in various regimens demonstrated consistent inhibition of
the growth of HT-29 cells. Although we did not achieve 100%
inhibition of the tumor growth it should be noted that there are no
agents in clinical use against this tumor that are curative.
Discussion
The
in vivo
results demonstrated that
compound 8 was active against the colon cancer HT-29 cell
line. Notably, this compound is a hydrochloride salt and is soluble
in water. We are also encouraged by the finding that in repeated
in vitro
testing by the NCI Program, additional human colon
cancers demonstrated even greater sensitivity to this agent.
Acknowledgements
We gratefully acknowledge the financial support for
this project from NIH/NCI (B.K.B.) and the Golden Family Fund
(F.F.B.); as well as the shared resources of the pharmacology core
facility of the University of Texas M.D. Anderson Cancer
Center.
References
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Applied Sciences | Free Full-Text | Investigating Quantum Coherence by Negative Excursions of the Wigner Quasi-Distribution
Quantum information and quantum communication are both strongly based on concepts of quantum superposition and entanglement. Entanglement allows distinct bodies, that share a common origin or that have interacted in the past, to continue to be described by the same wave function until evolution is coherent. So, there is an equivalence between coherence and entanglement. In this paper, we show the relation between quantum coherence and quantum interference and the negative parts of the Wigner quasi-distribution, using the Wigner signed-particle formulation. A simple physical problem consisting of electrons in a nanowire interacting with the potential of a repulsive dopant placed in the center of it creates a quasi two-slit electron system that separates the wave function into two entangled branches. The analysis of the Wigner quasi-distribution of this problem establishes that its negative part is principally concentrated in the region after the dopant between the two entangled branches, maintaining the coherence between them. Moreover, quantum interference is shown in this region both in the positive and in the negative part of the Wigner function and is produced by the superposition of Wigner functions evaluated at points of the momentum space that are symmetric with respect to the initial momentum of the injected electrons.
Investigating Quantum Coherence by Negative Excursions of the Wigner Quasi-Distribution
by Mauro Ballicchia 1,2 , David K. Ferry 3 , Mihail Nedjalkov 2 and Josef Weinbub 4,*
Department of Information Engineering, Università Politecnica delle Marche, 60131 Ancona, Italy
Institute for Microelectronics, TU Wien, 1040 Wien, Austria
Christian Doppler Laboratory for High Performance TCAD, Institute for Microelectronics, TU Wien, 1040 Wien, Austria
*
Author to whom correspondence should be addressed.
Appl. Sci. 2019 , 9 (7), 1344; https://doi.org/10.3390/app9071344
Received: 23 January 2019 / Revised: 25 March 2019 / Accepted: 27 March 2019 / Published: 30 March 2019
Abstract
:
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Modeling and simulation of quantum entanglement in physical systems.
Abstract
Quantum information and quantum communication are both strongly based on concepts of quantum superposition and entanglement. Entanglement allows distinct bodies, that share a common origin or that have interacted in the past, to continue to be described by the same wave function until evolution is coherent. So, there is an equivalence between coherence and entanglement. In this paper, we show the relation between quantum coherence and quantum interference and the negative parts of the Wigner quasi-distribution, using the Wigner signed-particle formulation. A simple physical problem consisting of electrons in a nanowire interacting with the potential of a repulsive dopant placed in the center of it creates a quasi two-slit electron system that separates the wave function into two entangled branches. The analysis of the Wigner quasi-distribution of this problem establishes that its negative part is principally concentrated in the region after the dopant between the two entangled branches, maintaining the coherence between them. Moreover, quantum interference is shown in this region both in the positive and in the negative part of the Wigner function and is produced by the superposition of Wigner functions evaluated at points of the momentum space that are symmetric with respect to the initial momentum of the injected electrons.
Keywords:
coherence
;
entanglement
;
quasi-distribution
;
non-diagonal Wigner states
;
signed-particles
;
nanowire
1. Quantum Information and The Wigner Function
When we extend the classical idea of informatics, or even the idea of physically-based informatics to the quantum world, we uncover two basic threads: (1) quantum computing, and (2) quantum information as a description of quantum communications. The idea of using quantum mechanics to provide more computing power than classical computers seems to have begun around 1981-2 [ 1 ], but Deutsch put the ideas on a more firm basis a few years later [ 2 ]. Deutsch reformulated the Turing argument [ 3 ] with an assertion that every finite realizable physical system could be simulated in a perfect manner by a universal model computing machine of finite size, and even by a quantum mechanical version of this universal machine. The fact that the quantum computer can be far more efficient than a classical version relies upon the concept of entanglement, or quantum superposition [ 4 ]. Information in such a quantum computer is naturally quantum information, but we tend to use this term more for the transmission of information in a manner in which it cannot be intercepted. Naturally, the ideas of transmitting bits using quantum-based encryption grew along with the ideas of quantum computing, so the two together become quantum information processing [ 5 , 6 ].
Important to each of these applications of quantum mechanics is the use of entanglement. When two bodies interact in a quantum manner they become entangled, which implies that they are now described by a single wave function and are no longer two distinct bodies. Even after they have ceased to interact and have moved some distance away, they remain entangled until some decoherence process acts upon them [ 7 ]. However, in experiments, one must face the fact that entanglement is difficult to measure. There is no physical variable whose eigenvalue yields the entanglement. Hence, people have worked for years to devise measures of entanglement [ 8 ]. Most of these, however, do not provide a clear visualization of the entanglement. But, it has been demonstrated that the Wigner function does provide a clear visualization of entanglement [ 7 ]. And, experimentalists have devised methods of reconstructing the Wigner function from output data of the experiments, particularly in optics (for a review on recent advances see [ 9 ]). One such approach involves the study of entanglement in the Jaynes-Cummings model [ 10 ]. This model studies the interaction between a cavity mode, treated as a harmonic oscillator, and a two-level atom. When the field in the cavity is in a coherent state, the atom is prepared in an excited state. It is found that the atomic and field states become rapidly entangled, and then subsequently disentangle at one-half the so-called revival time [ 11 ]. Thus, the maximum entanglement occurs when the atom Rabi oscillations are at maximum amplitude. It was subsequently demonstrated that the Wigner function can be written as a shifted expectation value of the optical parity operator [ 12 ]. Other optical experiments have shown that it is possible to measure directly a significant fraction of the Wigner function, when a spontaneous parametric down conversion of a photon produces a pair of entangled photons [ 13 ]. In some implementations of superconducting qubits, the entanglement can be used to follow the evolution of the Wigner function of the reduced density matrix of the qubits [ 14 ]. Indeed, it is now clear that the Wigner function can be used to exhibit directly the non-classical behavior through its non-Gaussian and negative excursions [ 15 ].
1.1. The Wigner Function
The remarkable similarities between the classical mechanics and the Wigner formulation of quantum mechanics offers a very convenient, and necessary, way to analyze coherence, entanglement, tunneling, and other characteristic effects of the quantum evolution. Indeed, both theories use phase space, defined by the position
x
and momentum
p
, the physical observables are associated with the same functions
A
(
x, p
) and importantly, the averaged physical quantities 〈
A
〉 are obtained by the same integrals
〈
A
〉
=
∫
d
x
d
p
A
(
x
,
p
)
F
(
x
,
p
)
,
where
F
is either the classical distribution function
f ≥
0, or the Wigner function
f w
. This establishes a unique correspondence between these functions and associates the name ”quasi-distribution” to
f w
. The basic difference is that the latter is still a real function, but allows negative values. This already suggests that these values are manifest of the quantum behavior and provide the kernel of the quantum information. The development of negative values of the Wigner function over phase space dimensions larger than
h
are quantum features and the main focus of this work. As discussed above, these negative features can be associated with a rigorous quantification theory [
16
], developed in analogy with the corresponding theory of entanglement.
1.2. Entanglement in the Wigner Function
Coherence and entanglement are based on the superposition principle, however, they represent conceptually different ideas. The former reflects the wave nature of states to interfere: States with a fixed phase relationship superimpose to represent another state of the physical system. Thus, coherence can be represented in single quantum systems and it is always with respect to a particular basis. In turn, entanglement implicates the (tensor product of) states of two correlated systems in such a way, that a destruction of one of the states in the first system results in a change of the states in the second system.
Notably, the two concepts are quantitatively equivalent, that is, any nonzero amount of coherence in a system can be converted into an equal amount of entanglement between that system and another initially incoherent one [
17
]. This means that the two concepts which describe very different physical notions have a common mathematical foundation and thus can encrypt and carry the same information. The resources theory of coherence, which has been developed in terms of Hilbert space operator mechanics, designates a basis |
a i
〉 and identifies a set of states
I
with a label incoherent. These concepts can be reformulated in phase space terms, moreover the entire theory can be formulated in the phase space. There is a variety of measures of coherence in complex systems, based on the correlations between the subsystems [
18
,
19
].
A principal postulate in the development of a phase space quantum mechanics is the establishment of the correspondence between operators and functions. The problem is that different ordering of the position and momentum operators gives rise to different operators corresponding to one and the same observable, which is a function of the phase space coordinates. There are different rules for ordering the operators such as all momentum operators to the left or to the right, or a fully symmetric ordering. The Wigner theory is developed around the latter with the help of the Weyl map
A
(
x,p
) ↔
W
(
Â
):
W
(
A
^
)
=
∫
d
s
d
q
h
T
r
(
A
^
e
i
ℏ
(
s
x
^
+
q
p
^
)
)
e
−
i
ℏ
(
s
x
+
q
p
)
(1)
The map establishes a one-to one correspondence between operators and functions, or more precisely an isomorphism from the algebra of operators
Â
(
x
^
p
^
) with a product and a commutator [,] to the algebra of phase space functions
A
(
x, p
) with a non-commutative star (∗)-product
A
∗
B
=
W
(
Â
·
B
^
) and a Moyal bracket
i
ℏ[
A, B
]
M
=
W
(
[
A
^
,
B
^
]
)
. Recently, the algebraic notions used to derive the quantifying theory of coherence have been reformulated in terms of the Wigner theory [
20
].
In particular the nondiagonal eigenvector Wigner function
f ij
(
x
,
p
) is introduced in correspondence to the eigenvectors |
a i
〉 of the operator
Â
of a given physical observable:
f
i
j
(
x
,
p
)
=
(2)
The Weyl map allows the transfer of the concepts of the information theory of coherence to the Wigner phase space picture. We may then define coherence in terms of a fixed basis |
a i
〉 in which one has to use (2) for the set of eigenvector Wigner functions
f ij
to define the incoherent states as
σ
^
=
∑
i
P
i
|
a
i
〉
〈
a
i
|
↔
,
σ
=
∑
i
P
i
f
i
i
,
(3)
where
P i
are probabilities. The set of such states are denoted by
I
. Any other state which cannot be presented as in Equation (3) in this way is a coherent state [
21
]. Then the measure for coherence in phase space is C(
f w
) = min
(
f w
,
f w,σ
), where
f w,σ
∈
I
is introduced from the measure for distance
D
[
16
,
17
]. The latter can be based on the von Neumann entropy or trace distance [
16
], which can be equivalently defined in both operator and phase spaces. We conclude that incoherent states involve only diagonal elements
f ii
: From Equation (2) it follows that coherence is directly related to the existence of nondiagonal elements
f ij
in the state representation of
f w
.
The above formal mathematical analysis developed in [
20
] can be directly linked to the negativity of the Wigner function and actually has a transparent physical background in terms of positive and negative particles. Indeed, if we choose
Â
to be the momentum operator
Â
=
p
^
with a basis e
i pj x/ℏ
, the corresponding Wigner basis becomes
f
i
j
(
x
,
p
)
=
e
(
p
i
−
p
j
)
δ
p
i
p
j
)
±
,
(4)
which, due to the exponential prefactor, has the ability to form interference patterns and, in particular, to exhibit negative values. In contrast, for diagonal Wigner basis states, this prefactor becomes unity and (4) reduces to
δ
(
p i
±
p
). Thus, according to Equation (3), incoherent states
f w,σ
have non-negative values. The associated physical picture is of classical particles with a distribution function
f
(
p
) = ∑
i P i δ
(
p i
±
p
). Here each particle “carries” a weight given by the probability
P i
. In this way the Wigner picture reveals that the concept for incoherent states is deeply rooted in classical mechanics. In particular, the evolution of an initial particle distribution, subject to the action of a quadratic potential, is entirely classical: The Wigner potential reduces to a force, which governs particles over classical Newtonian trajectories. We can extend this picture to coherent Wigner states. The latter contain off-diagonal basis states, thus according to Equation (4) the weight of such particles should have complex values. Furthermore, we know that the Wigner function is a real quantity, thus after the cancellation of all imaginary values in the corresponding decomposition of the chosen coherent state, only positive and negative values remain. In this way, we come to two important conclusions:
Quantum coherence is characterized by negative values of the Wigner function;
In a virtual particle picture, coherent states are distinguished from classical states by the existence of particles with a negative weight.
These considerations are independent from the complexity of the system: The existence of subsystems is accounted for by a simple increase of the involved phase space coordinates.
An alternative approach uses the negativity of the Wigner function to define a parameter which measures the non-classicality of a given state based on the distance from a family of coherent states [ 22 ]. The parameter is given by the doubled volume of the integrated (in the whole phase space) negative part of the Wigner function. This definition can be regarded as a projection of the function onto the set of the real numbers between zero and unity. Here, we show that other ways of projection can provide useful information about the quantum evolution.
In the next section, we describe how entanglement can be observed in a simple physical problem, that of electron two-slit propagation around an impurity potential in a quantum nanowire (waveguide). The simulation experiment is very similar to the one already used in [
23
] to analyze coherence effects by comparing classical and quantum density or current density. In contrast, here, we reconstruct the Wigner function in the phase space in order to investigate how the negative excursions, not existing in the classical case, bear information about the involved quantum effects. We show that Wigner-quantum transport can be represented by the evolution of positive and negative particles: The so-called signed-particles. We then turn to the actual simulation and results in the following section.
2. A Simple Example Problem and Methods
2.1. A Quasi-Two-Slit Electron Problem
The aim of this paper is to illustrate how information on entanglement and coherence can be observed by means of the Wigner function of a physical system. The physical system that we consider consists of a portion of a nanowire with a repulsive dopant in the center of it, see Figure 1 . The dopant potential creates a barrier in the center of the nanowire that causes the wave to break into two separate parts passing on either side of the barrier, much like two slits. Electrons that flow along the waveguide, interacting with the repulsive dopant, go through one slit or the other, generating a “ Y-branch ” path.
The lateral boundaries of the experimental setup are considered to be absorbing in order to avoid reflections of the two electron branches from the lateral sides of the nanowire. Minimum uncertainty non-interacting wave packets are injected from the bottom of the nanowire with a temporal spacing of 1 fs. The only source of quantum effects is the presence of the dopant potential that, having a spatial dependence of 1/
r
, presents derivatives of all orders.
The simulation set-up is very similar to that already used in [
23
]: The extent of the simulation domain is of 20 × 30 nm
2
, with the dopant centered at (
x d
,
y d
) = (10 nm, 15 nm). The Wigner pure states are injected from (
x
0
,
y
0
) = (10 nm, 0 nm) in the +y direction with an initial kinetic energy of 0.141 eV. The standard deviation of the minimum uncertainty wave packets is 3 nm in both spatial directions. The electron evolution has been simulated for 400 fs; this time is sufficient for the system to reach steady state. At the end of the simulation the Wigner function is analyzed, specifically to determine those regions of phase space where the quasi-distribution becomes negative.
2.2. Signed-Particles
Historically, the basic similarities between the concepts and notions of classical mechanics and quantum mechanics in phase space motivated the development of particle methods for solving the Wigner equation almost three decades ago [ 24 ]. Different particle approaches have been developed since then [ 25 , 26 , 27 ], which focus mainly on the electrostatic problem in a scalar potential gauge. In particular, the concept of signed-particles, which has matured for 15 years [ 28 ], is based on the application of stochastic approaches to solving integral equations by converting them to different integral forms of the Wigner equation. The concept is not a single, unique particle model, but comprises a set of particle attributes which can be combined and modified to develop suitable algorithms, specific for the physical aspects of the particular problem. Some of these attributes are, however, fundamental and give rise to a heuristic picture of quantum mechanics in terms of particles [ 29 ]. Basic attributes are particle sign, particle generation, and particle annihilation. In a signed-particle approach, point-like particles are enabled with classical features, such as drift over Newtonian (field-less) trajectories but carry the quantum information by their positive or negative sign. The mean value of a generic physical quantity A , represented by a phase space function, is evaluated by the ∑ n sign( n ) A n for all particles n in a desired region, where sign( n ) is the sign of the n -th particle and A n the corresponding value of the physical quantity. During the evolution, each particle generates couples of one positive and one negative particle, according to rules dictated by the Wigner potential, and propagate in space by distinct but fixed momentum (no acceleration). Particles with opposite sign which meet in the phase space annihilate each-other since they have a common probabilistic future but opposite contribution to the physical averages. Proof of concept simulations, showing that Newton’s second law can be reproduced by generation/annihilation of un-accelerated signed-particles [ 29 ], have been conducted, and also for two- and three-dimensional problems [ 30 ]. This allows to prove that annihilation is able to reproduce classical ballistic behavior in the quantum case, where the applied electric field shows constant or linear behavior. Also, there aren’t abrupt variations of the electric potential, like the one introduced by the dopant, that (exceeding quadratic dependence) generate quantum behavior.
3. Results
The Wigner function for a two-dimensional scenario, as the one illustrated in
Section 2.1
, is a function of four variables,
f w
(
x
,
y
,
k x
,
k
y
) and thus needs a five-dimensional space to be visualized. However, useful information can be retrieved from the analysis of the projection of the function onto a two-dimensional space. From a mathematical point of view there are numerous ways to establish such a projection. Two of the variables, called variables of interest, remain active, while the remaining three must be restrained according to some criteria, usually introduced by physical considerations. For example, the value of the Wigner function and of one position and one momentum component can be fixed, or restricted in some limits, or integration on the latter within selected intervals can be performed.
As a first experiment we consider a separation of the negative and the positive part of the Wigner function:
f
w
−
=
f
w
θ
(
−
f
w
)
and
f
w
+
=
f
w
θ
(
f
w
)
. Then both quantities are integrated in the whole momentum space to obtain the spatial distribution of both the negative and the positive parts:
f
w
x
y
−
(
x
,
y
)
=
∬
f
w
−
(
x
,
y
,
k
x
k
y
)
d
k
x
d
k
y
;
f
w
x
y
+
(
x
,
y
)
=
∬
f
w
+
(
x
,
y
,
k
x
k
y
)
d
k
x
d
k
y
(5)
We consider as a reference frame the classical (Boltzmann) distribution, characterized by:
f
B
x
y
−
(
x
,
y
)
=
0
and
f
B
x
y
+
(
x
,
y
)
=
n
(
x
,
y
)
where
n
is the classical density.
Figure 2
a,b show respectively
f
w
x
y
−
and
f
w
x
y
+
. The quantum density, represented by the sum
f
w
x
y
+
+
f
w
x
y
−
, is shown in
Figure 3
a. These quantities reflect the following evolution process. In the region below the dopant, denoted by the green 0.15 eV isoline, the electron flux splits into two entangled parts. These maintain the coherence in the region after the dopant, as no dissipation processes are involved. This results in the interference fringes well visible in the upper parts after the dopant of both figures. Remarkably,
f
w
x
y
−
exhibits firmly negative values in a wide region around the dopant. However, their pattern does not reflect the symmetry of the potential and thus they can’t be associated to the nonlocality of the quantum action. The most pronounced negative values are placed after the dopant, in the region of evolution of the two entangled parts. Now, one can connect this negative region with the fact that, quantum mechanically, the scattering process requires a “collision duration” [
31
]. Quantum mechanically, the wave must first build up a correlation with the impurity, and this is then broken up when the collision is completed. The fact that the entanglement exists beyond the impurity is recognition that the event takes a non-zero amount of time to complete. This is true for the impurities as well as for phonons [
32
]. A similar push of the effect of the impurity potential to the anterior region can be caused by nonlinear screening due to dopants in the contacts [
33
], although no such screening is used here. In contrast, such behavior is entirely missing in
Figure 3
b, where the classical density
n
is reported: The corresponding region is entirely empty! This shows that the negative excursions of the Wigner function provide a direct indicator for interference effects.
It is interesting to see if such analysis can be carried out on other types of projections or is specific to the presented one, where we intentionally separated the negative values of the Wigner function. As a second experiment we consider the Wigner function for two specific points in the momentum space that are (
k
x1
k
y1
) = (−0.26 nm
−1
, 0.89 nm
−1
) and (
k
x2
k
y2
) = (0.26 nm
−1
, 0.89 nm
−1
). The choice of these two points is related to the fact that they are near to the mean momentum along the
y
-direction (0.84 nm
−1
) and symmetrically placed around the initial momentum in the
x
-direction. Classical particles with such momentum coordinates exit near the upper corners of the simulation domain, thus entering well in the region of interest above the dopant, where we expect entanglement and interference effects in the quantum evolution. This can be seen in
Figure 4
b,
Figure 5
b and
Figure 6
b presenting the classical distributions
f
B
(
x
,
k
x
1
,
k
y
1
)
,
f
B
(
x
,
y
,
k
x
2
,
k
)
, and their sum, respectively. The choice of two specific symmetric points with respect to the initial momentum does not limit the analysis, since the evolution of the system is symmetric with respect to the initial momentum, and the choice of all the couples of symmetric points will give a full recovery of the Wigner function. For convenience the viewpoint in
Figure 4
,
Figure 5
and
Figure 6
is now rotated, so that the exit (formerly upper) part of the simulation domain is now the closest one. The corresponding quantum function
f
w
(
x
,
y
,
k
x
1
,
k
y
shown in
Figure 4
a reveals a well-pronounced negative part, which begins around the dopant and is extended until the boundary. The same holds for the function
f
w
(
x
,
y
,
k
x
2
,
k
y
2
)
,
Figure 5
a. We note that in both cases the negative parts are ”internally” placed in the region of correlations between the left and right parts. In
Figure 6
a we report the distribution obtained by the sum
f
w
(
x
,
y
,
k
x
1
,
k
y
1
)
+
f
w
(
x
,
y
,
k
x
2
,
k
y
2
)
. The quantum distribution presents a negative part in front of the dopant between the two branches and a kind of ”interference” behavior appearing due to the summation of the two components in that region. None of this can be seen in the corresponding classical evolution where the distribution between the two branches is zero.
In this way, the information available in the first experiment can be directly retrieved from the second kind of projection, consistently providing a correlation between “negativity” and entanglement/interference.
4. Discussion and Conclusions
The paper illustrates, by exploiting the definition of Wigner non-diagonal basis, the relation between the coherence and the negative part of the Wigner function. In particular, in the signed-particle formulation, quantum coherent states are distinguished from classical ones by the fact that the negative particles bring negative values. This shows that a Wigner signed-particle approach is a convenient way to analyze coherence and entanglement as it allows one to directly reconstruct the Wigner quasi-distribution. In order to show the validity of these considerations a simple physical problem of the electron evolution in a nanowire with a repulsive dopant placed in the center was considered. As observed, the active region of interaction around the dopant is characterized by negative values of the Wigner function, which can be associated to quantum nonlocality. However, the Wigner function values in the region after the dopant, characterized by the coherent evolution of the two entangled electron beams are considerably negative. This manifests the close link between coherent evolution and negative excursion of the Wigner function. In order to better show the link between coherence and negative excursion we have considered points in the momentum space, which are symmetric with respect to the initial momentum and are scattered by the dopant in two separated branches in the classical case. This enables to highlight that the corresponding quantum Wigner quasi-distribution presents a negative excursion in the inner part of these two branches and the superposition of these two negative excursions creates a pattern of interference between the two branches.
Author Contributions
Conceptualization, D.K.F. and J.W.; methodology, M.B. and M.N.; software, M.B.; validation, M.B., M.N., D.K.F., and J.W.; formal analysis, M.B., M.N., D.K.F., and J.W.; investigation, M.B., M.N., D.K.F., and J.W.; resources, M.N. and J.W.; data curation, M.B.; writing—original draft preparation, M.B.; writing—review and editing, M.N., D.K.F. and J.W.; visualization, M.B.; supervision, M.N., D.K.F. and J.W.; project administration, J.W.; funding acquisition, M.N. and J.W.
Funding
The financial support by the Austrian Science Fund (FWF): FWF-P29406-N30, the Austrian Federal Ministry for Digital and Economic Affairs, and the National Foundation for Research, Technology and Development is gratefully acknowledged.
Acknowledgments
The computational results presented have been achieved using the Vienna Scientific Cluster (VSC).
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. The two-slit electron problem: simulation setup.
Figure 1. The two-slit electron problem: simulation setup.
Figure 2.
Spatial distribution of (
a
) the negative part
f
w
x
y
−
(
x
,
y
)
and (
b
) the positive part
f
w
x
y
+
(
x
,
y
)
.
Figure 2.
Spatial distribution of (
a
) the negative part
f
w
x
y
−
(
x
,
y
)
and (
b
) the positive part
f
w
x
y
+
(
x
,
y
)
.
Figure 3.
Comparison between quantum and classical distribution: (
a
) quantum distribution
n
(
x
,
y
)
=
f
w
x
y
+
(
x
,
y
)
+
f
w
x
y
−
(
x
,
y
)
, (
b
) classical distribution
n
(
x
,
y
)
=
f
w
x
y
+
(
x
,
y
)
.
Figure 3.
Comparison between quantum and classical distribution: (
a
) quantum distribution
n
(
x
,
y
)
=
f
w
x
y
+
(
x
,
y
)
+
f
w
x
y
−
(
x
,
y
)
, (
b
) classical distribution
n
(
x
,
y
)
=
f
w
x
y
+
(
x
,
y
)
.
Figure 4. Comparison between quantum and classical phase-space distribution in the point ( k x1, k y1 ) = (−0.26 nm −1 , 0.89 nm −1 ): ( a ) quantum Wigner distribution, ( b ) corresponding classical Boltzmann distribution.
Figure 4. Comparison between quantum and classical phase-space distribution in the point ( k x1, k y1 ) = (−0.26 nm −1 , 0.89 nm −1 ): ( a ) quantum Wigner distribution, ( b ) corresponding classical Boltzmann distribution.
Figure 5. Comparison between quantum and classical phase-space distribution in the point ( k x2 , k y2 ) = (0.26 nm −1 , 0.89 nm −1 ): ( a ) quantum Wigner distribution, ( b ) classical Boltzmann distribution.
Figure 5. Comparison between quantum and classical phase-space distribution in the point ( k x2 , k y2 ) = (0.26 nm −1 , 0.89 nm −1 ): ( a ) quantum Wigner distribution, ( b ) classical Boltzmann distribution.
Figure 6. Comparison between quantum and classical sum of the phase-space distributions in the points ( k x1, k y1 ) = (−0.26 nm −1 , 0.89 nm −1 ) and ( k x2 , k y2 ) = (0.26 nm −1 , 0.89 nm −1 ): ( a ) quantum Wigner distribution, ( b ) classical Boltzmann distribution.
Figure 6. Comparison between quantum and classical sum of the phase-space distributions in the points ( k x1, k y1 ) = (−0.26 nm −1 , 0.89 nm −1 ) and ( k x2 , k y2 ) = (0.26 nm −1 , 0.89 nm −1 ): ( a ) quantum Wigner distribution, ( b ) classical Boltzmann distribution.
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Difference between revisions of "Philip Astley" - Circopedia
Difference between revisions of "Philip Astley"
Revision as of 02:29, 19 February 2016 ( view source ) Djando ( Talk | contribs ) ( → Astley vs. the Royal Circus ) ← Older edit Revision as of 02:29, 19 February 2016 ( view source ) Djando ( Talk | contribs ) ( → Astley vs. the Royal Circus ) Newer edit → Line 43: Line 43: [[Image:Astley's_London_Map.jpg|thumb|right|300px|Astley's Amphitheatre location]]In 1781, Astley's old nemesis, [[Charles Hughes]], returned to London after an eight-year tour of Europe. Hughes partnered with [[Charles Dibdin]], a prolific songwriter and librettist. With the help of a syndicate of London backers, the two men began building a brand-new amphitheatre, this time in stone, on a piece of land located at the crossroads of the three thoroughfares leading to the three bridges serving London (Westminster, Blackfriars, and London Bridge). The place, known as St. George's Circus, had in its center an obelisk that was a well-known landmark. Again, Hughes had moved his operation into the vicinity of Astley's Amphitheatre. [[Image:Astley's_London_Map.jpg|thumb|right|300px|Astley's Amphitheatre location]]In 1781, Astley's old nemesis, [[Charles Hughes]], returned to London after an eight-year tour of Europe. Hughes partnered with [[Charles Dibdin]], a prolific songwriter and librettist. With the help of a syndicate of London backers, the two men began building a brand-new amphitheatre, this time in stone, on a piece of land located at the crossroads of the three thoroughfares leading to the three bridges serving London (Westminster, Blackfriars, and London Bridge). The place, known as St. George's Circus, had in its center an obelisk that was a well-known landmark. Again, Hughes had moved his operation into the vicinity of Astley's Amphitheatre. − The ''Royal Circus, Equestrian and Philharmonic Academy''—as it was pompously named (it would later be known simply as "Hughes' [[Royal Circus]]")—opened November 4, 1782. The first modern amphitheatre to bear the title "circus," it was an elegant structure whose ornate house included a fully equipped theater stage and a circus ring 36'6" in diameter (about 11.15 meters). The idea, in the words of Dibdin, was that "the business of the ring and the stage might be united." The configuration provided a way to give a more prominent place to pantomimes (Dibdin's specialty), but with the addition of an equestrian element that would eventually lead to the development of circus "hippodramas." The stage and ring arrangement devised by Dibdin and Hughes became the standard for practically all circus buildings until the second half of the nineteenth century. + The ''Royal Circus, Equestrian and Philharmonic Academy''—as it was pompously named (it would later be known simply as "Hughes' [[ Royal Circus (London)| Royal Circus]]")—opened November 4, 1782. The first modern amphitheatre to bear the title "circus," it was an elegant structure whose ornate house included a fully equipped theater stage and a circus ring 36'6" in diameter (about 11.15 meters). The idea, in the words of Dibdin, was that "the business of the ring and the stage might be united." The configuration provided a way to give a more prominent place to pantomimes (Dibdin's specialty), but with the addition of an equestrian element that would eventually lead to the development of circus "hippodramas." The stage and ring arrangement devised by Dibdin and Hughes became the standard for practically all circus buildings until the second half of the nineteenth century. With the success of Hughes' Royal Circus, Astley lost his monopoly. Thereafter, he had to contend with serious competition. Luckily for him, neither Dibdin nor Hughes were fiscally competent, and the group formed by the two directors, the circus's shareholders, and their landowners—the West family—proved to be incredibly dysfunctional. Hughes died at the end of 1797. By then the West family had repossessed the Royal Circus and, in 1794, leased it to [[James Jones]] and George Jones, whose company had included for a while [[John Bill Ricketts]], a talented pupil of Charles Hughes who was to open the first American circus. Between 1781 and 1794, the Royal Circus had been racked by ceaseless internal feuds (Dibdin was forced out in 1785), plagued by licensing problems and near-bankruptcies, and gradually fell into a state of disrepair. In 1804, a fire badly damaged the building. After extensive renovations, the Royal Circus focused mostly on theatrical offerings. In 1810, it was converted into a full-fledged theatre. With the success of Hughes' Royal Circus, Astley lost his monopoly. Thereafter, he had to contend with serious competition. Luckily for him, neither Dibdin nor Hughes were fiscally competent, and the group formed by the two directors, the circus's shareholders, and their landowners—the West family—proved to be incredibly dysfunctional. Hughes died at the end of 1797. By then the West family had repossessed the Royal Circus and, in 1794, leased it to [[James Jones]] and George Jones, whose company had included for a while [[John Bill Ricketts]], a talented pupil of Charles Hughes who was to open the first American circus. Between 1781 and 1794, the Royal Circus had been racked by ceaseless internal feuds (Dibdin was forced out in 1785), plagued by licensing problems and near-bankruptcies, and gradually fell into a state of disrepair. In 1804, a fire badly damaged the building. After extensive renovations, the Royal Circus focused mostly on theatrical offerings. In 1810, it was converted into a full-fledged theatre.
Revision as of 02:29, 19 February 2016
Contents
1 Circus Owner, Equestrian
1.1 From The Military To Show Business
1.2 The Birth of the Circus
1.3 Astley's Success
1.4 Astley vs. the Royal Circus
1.5 Astley Expands
1.6 Astley's New Amphitheatre of the Arts and the Olympic Pavilion
2 Suggested Reading
3 Image Gallery
Circus Owner, Equestrian
By Dominique Jando
Philip Astley (c.1800)
Philip Astley (1742-1814) is considered the creator of the modern circus. He was born January 8, 1742 in Newcastle-under-Lyme, in the West Midlands, England, the son of Edward Astley, a veneer-cutter and cabinet-maker. Edward had a short-fuse and a passion for horses, traits he passed on to his son. At age 17, Philip left home after one of many disputes with his father and enrolled in the 15th Light Dragons, a cavalry regiment newly formed by Colonel Granville Elliott.
From The Military To Show Business
Six feet tall and endowed with a stentorian voice, Philip Astley was a giant for his time and didn't easily blend into crowds, even when in uniform. A gifted equestrian, he was put in charge of breaking new horses for his regiment. He was also noticed by the celebrated riding and fencing master, Domenico Angelo, who took him under his tutelage and taught him a new method aimed at improving the use of the cavalry broadsword in battle—an expertise Astley would later display in his shows.
In 1761, Astley and his regiment embarked for the Continent to fight alongside King Frederick II of Prussia in the Seven Years' War (1756-63), known as the French and Indian War in America. Corporal Astley fought gallantly: he captured an enemy standard in battle; rescued the Duke of Brunswick, who had fallen behind enemy lines; and returned to England with the rank of Sergeant Major. He obtained his discharge on June 21, 1766 at Derby, and Elliott, now General, presented him with a white charger named Gibraltar. Astley married around this time. In 1769, his wife (of whom little is known) presented him with a son,
John Philip Conway Astley
(1767-1821).
Trick-riding exhibitions were very popular in the second half of the eighteenth century. England had become a constitutional monarchy in 1688, and the spending power of the nobility had been curbed considerably. Private regiments were disappearing. Lavish equestrian court entertainments (such as carrousels) had ceased to be affordable. Private manèges staffed with riding instructors didn't fare much better. Still, riding masters, most of them coming from the military, could make a good living as
trick Any specific exercise in a circus act.
-riding performers. Thus, following in the footsteps of many great British equestrians (notably Jacob Bates, whose fame stretched from America to Russia), Philip Astley became a showman.
By 1768, he had secured a piece of land known as Glover's Halfpenny Hatch in Surrey County, south of London, between Blackfriars and Westminster bridges, where he had opened in the spring a riding school—a crude roofless enclosure where he taught horsemanship in the morning and performed in the afternoon during the summer season. He presented his "feats on horsemanship" on Gibraltar, and exhibited "The Little Military Horse"—a small horse he had trained to add and subtract numbers (or pretend to do so), feign death, fire a pistol, and perform "mind-reading" tricks. Like most
trick Any specific exercise in a circus act.
riders of his time, Astley performed in a circular arena: for the audience, it was easier to watch an equestrian circling in a well-defined area than to watch him dashing back and forth in a vast open space. For the riders, the centrifugal force generated by galloping in circles made it easier to stand on the back of their mounts. (Contrary to what is often said, however, Philip Astley did not "invent" the circus ring.)
The following year, in 1769, Astley secured a lease on a neighboring lot at the foot of Westminster Bridge, on the corner of Stangate Street and Westminster Bridge Road. Albeit roofless, the new
Astley's Riding House
was a more permanent wooden structure, and the audience at least was protected from the notorious London weather. The Riding House's arena (called either the "circle" or the "circus") had originally a diameter of 65 feet (about 19.5 meters). There, to the sound of fifes and drums, in good military fashion, Astley and some of his pupils offered afternoon performances of an exclusively equestrian nature. By the end of his first summer in the new location, Astley had reason to celebrate: His first two London seasons had been very successful. Yet he knew that if he wanted to establish a permanent place of performance that could attract London audiences over the long haul—especially the much-needed popular audience—he had to change the format of his show.
The Birth of the Circus
Astley's Riding School (1777)
Following the disappearance of court entertainments, London had seen the development of a purely commercial theater, subsidized not by the nobility but by ticket sales. Whatever their specialty, theaters couldn't survive only on a handful of faithful patrons; they had to attract as large an audience as possible. Therefore, they had to please a diversity of tastes. With that in mind, Astley turned to the successful theaters of London (legit houses such as Drury Lane, Covent Garden, and the Haymarket Opera House, but also "secondary" houses such as Sadler's Wells) to find out what attracted the all-important popular section of their audiences.
All of them, he discovered, relied on visual acts (performances by jugglers, ropedancers, "posturers," as acrobats were then called, et al.), which, in the legit houses, were interspersed between the various theatrical offerings. (In the eighteenth century, performing arts were not yet segregated; actors, musicians, dancers, acrobats, and even equestrians all belonged to the same community of entertainers.) Additionally, theater performances were usually capped with "after-pieces," in most cases pantomimes, which, in England, were farcical spectacles with stage tricks and special effects and were the realm of Clown and Harlequin, the
pantomime A circus play, not necessarily mute, with a dramatic story-line (a regular feature in 18th and 19th century circus performances).
's principal stock characters.
Therefore, the show Philip Astley offered at his Riding School for his 1770 London season was a mixture of equestrian and acrobatic acts, followed by a
pantomime A circus play, not necessarily mute, with a dramatic story-line (a regular feature in 18th and 19th century circus performances).
. He had a crude stage erected in the ring for the visual acts and the
pantomime A circus play, not necessarily mute, with a dramatic story-line (a regular feature in 18th and 19th century circus performances).
, and if the stage tricks were certainly limited, the farcical work of the
clown Generic term for all clowns and augustes. '''Specific:''' In Europe, the elegant, whiteface character who plays the role of the straight man to the Auguste in a clown team.
, originally a theatrical character, was a welcome addition to the performance. As Astley had expected, his new formula enjoyed immediate success. With that, a new form of entertainment had been created: the circus as we know it was born.
As in the theater, the extracurricular additions to Astley's show were just that, additions, and the performances at Astley's Riding School remained principally of an equestrian nature. But the great British actor and manager, David Garrick, who, as Astley was rising to fame, was at the eve of his brilliant theatrical career, had already planted the seeds of secession between the theater and other performing arts. To Garrick, whose work had been essential in bringing Shakespeare's plays back to the forefront of the British theatrical tradition, the exhibition of visual entertainers on a theater stage was a sacrilege: "nothing but downright starving would induce me to bring such defilement and abomination to the house of William Shakespeare." Eventually banned from the legit stage, visual entertainers would find in the circus a welcome and ideal refuge.
When not performing in London during the spring and summer seasons, Astley traveled. The success of his exhibitions led him to construct wooden amphitheaters all around the United Kingdom—which soon won him the nickname "Amphi-Philip." The first of these amphitheaters was erected in 1773 in Dublin, Ireland. The following year, Astley's son, John, had his first "
benefit Special performance whose entire profit went to a performer; the number of benefits a performer was offered (usually one, but sometimes more for a star performer during a long engagement) was stipulated in his contract. Benefits disappeared in the early twentieth century.
" there as an equestrian—at age seven. (A "
benefit Special performance whose entire profit went to a performer; the number of benefits a performer was offered (usually one, but sometimes more for a star performer during a long engagement) was stipulated in his contract. Benefits disappeared in the early twentieth century.
" was a gala performance whose entire profit was given to a performer; a
benefit Special performance whose entire profit went to a performer; the number of benefits a performer was offered (usually one, but sometimes more for a star performer during a long engagement) was stipulated in his contract. Benefits disappeared in the early twentieth century.
was often included in a star performer's contract)
Astley's Success
Inevitably, success brought competition. In 1772, one of Astley's former equestrians, the ambitious and talented
Charles Hughes
, opened his own
Hughes' Riding School
not far from Astley's, on Blackfriars Road. Hughes's show was practically a carbon copy of Astley's, and the competition became fierce, generating widespread interest and, consequently, good business. It also caught the attention of the Magistrates of Surrey County, who closed both shows in July 1773 because neither had secured the proper license to perform. Hughes then embarked on a long European tour, but Astley, who had just purchased his piece of land, secured a license for the next season and resumed his British tours. At the time, licensing issues constantly plagued theater entrepreneurs who lacked a Royal Patent–which was the vast majoruty of them. The patented theatres (Covent Garden, Drury Lane, and the Haymarket) made sure it remained so.
In 1774, Philip Astley performed his "feats of horsemanship" for the first time in Paris, at the Manège de Razade, rue des Vieilles Tuileries. The event is of some importance, since in the years to come Paris would become Astley's second home.
In the winter 1778-79, Astley added a roof to his amphitheatre, which allowed him to perform in the winter season and to give evening performances—to the annoyance of the London patentees, with whom he was now in direct competition. He reopened the house in January 1779 under a new name,
Astley's Amphitheatre Riding House
. The show offered the usual fare of equestrian and acrobatic acts, clowns and pantomimes, but Philip Astley didn't appear on the bill in his "feats of horsemanship." At age 38, he had retired from performing as a bareback rider, but remained with the show as its Equestrian Director, or, in modern terminology, its Ringmaster—a function he created for himself.
Astley vs. the Royal Circus
Astley's Amphitheatre location
In 1781, Astley's old nemesis,
Charles Hughes
, returned to London after an eight-year tour of Europe. Hughes partnered with
Charles Dibdin
, a prolific songwriter and librettist. With the help of a syndicate of London backers, the two men began building a brand-new amphitheatre, this time in stone, on a piece of land located at the crossroads of the three thoroughfares leading to the three bridges serving London (Westminster, Blackfriars, and London Bridge). The place, known as St. George's Circus, had in its center an obelisk that was a well-known landmark. Again, Hughes had moved his operation into the vicinity of Astley's Amphitheatre.
The
Royal Circus, Equestrian and Philharmonic Academy
—as it was pompously named (it would later be known simply as "Hughes'
Royal Circus
")—opened November 4, 1782. The first modern amphitheatre to bear the title "circus," it was an elegant structure whose ornate house included a fully equipped theater stage and a circus ring 36'6" in diameter (about 11.15 meters). The idea, in the words of Dibdin, was that "the business of the ring and the stage might be united." The configuration provided a way to give a more prominent place to pantomimes (Dibdin's specialty), but with the addition of an equestrian element that would eventually lead to the development of circus "hippodramas." The stage and ring arrangement devised by Dibdin and Hughes became the standard for practically all circus buildings until the second half of the nineteenth century.
With the success of Hughes' Royal Circus, Astley lost his monopoly. Thereafter, he had to contend with serious competition. Luckily for him, neither Dibdin nor Hughes were fiscally competent, and the group formed by the two directors, the circus's shareholders, and their landowners—the West family—proved to be incredibly dysfunctional. Hughes died at the end of 1797. By then the West family had repossessed the Royal Circus and, in 1794, leased it to
James Jones
and George Jones, whose company had included for a while
John Bill Ricketts
, a talented pupil of Charles Hughes who was to open the first American circus. Between 1781 and 1794, the Royal Circus had been racked by ceaseless internal feuds (Dibdin was forced out in 1785), plagued by licensing problems and near-bankruptcies, and gradually fell into a state of disrepair. In 1804, a fire badly damaged the building. After extensive renovations, the Royal Circus focused mostly on theatrical offerings. In 1810, it was converted into a full-fledged theatre.
Astley Expands
Throughout this period, Astley had no difficulty retaining his supremacy in the nascent circus business. On July 5, 1782, he opened the
Manège Anglois
(the old French spelling for "anglais"), a roofless enclosure on the Boulevard du Temple in Paris. He left Paris at the end of August, having met with considerable success—thanks in large part to his son, John, who had become the true star of the show. Astley returned to the same location the following summer, and John Astley was commanded to perform at the court of Queen Marie-Antoinette at Versailles. The performance resulted in the issuance of a Royal Privilege enabling Philip Astley to open a permanent amphitheatre in Paris. He purchased the lot where he had performed for two summers and there built a wooden amphitheatre, with an address at 16 rue du Faubourg du Temple, practically at the corner of the Boulevard. The
Amphithéâtre Anglais des Sieurs Astley, père et fils
opened its doors on October 16, 1783.
Philip Astley was now running simultaneously, with the help of his son, two permanent amphitheatres in two different capitals—and he would soon obtain a Royal Patent for a third ampitheatre, this one in Dublin, Ireland, which he erected on Peter Street. It opened in 1789. That same year, the French Revolution forced him to vacate his Parisian amphitheatre, which he leased to various theater companies and, starting in 1791, to
Antonio Franconi
, the Italian "father" of the French circus. Despite the permanent performance spaces, Astley's circus company still regularly toured the United Kingdom, laying in temporary wooden structures, which sometimes became semi-permanent provincial bases.
Astley's New Amphitheatre of the Arts and the Olympic Pavilion
Astley's Amphitheatre in 1807
When the war between the United Kingdom and revolutionary France broke out in 1793, Philip Astley, who was 51 years old, reenlisted in the 15th Light Dragons, "acting as a horse-master, celebrity morale-booster and war correspondent in one." On August 16, 1794, while he was serving abroad, Astley's London amphitheatre burned to the ground. It had been refurbished in 1786, with a proper stage (albeit far from the size of the Royal Circus's true theater stage) and the sylvan decoration, replete with false foliage, that Astley had already used in his Parisian amphitheatre. The revamped building had been christened
Astley's Royal Grove
.
The Royal Grove was no more. Astley quickly obtained his discharge from the military and returned to London to rebuild it. This was done in record time:
Astley's New Amphitheatre of the Arts
was ready for the 1795 season, which commenced, as usual, on Easter Monday.
In 1802, after the Peace of Amiens, Astley returned to Paris and regained possession of his amphitheatre on Rue du Faubourg du Temple. The following year, his new London amphitheatre was again consumed by a fire. This was unfortunately the fate of many theatres at the time. Mostly built of wood, with stage areas doubling as storage space for hifghly flammable wood-and- painted canvas scenery, props and even fireworks, the buildings were lit by open flames. Perhaps it is more surprising that they survived at all than that they burned down so frequently.
The Amphitheatre was rebuilt again in 1803, this time following the now-classic model of Hughes's Royal Circus, with a house lavishly decorated by the famous Scottish scene painter John Henderson Grieve, and a full theatre stage, which was said to be the largest in London. That same year, Philip Astley, who had practically reached the status of living legend, was commissioned to design a fireworks display on the Thames for King George III's birthday.
Astley was now more than ever in royal favor. In 1805, he obtained a license to build yet another circus, this time in London proper, at the corner of Newcastle and Wych Streets, in the Strand. The
Olympic Pavilion
opened on September 18, 1806. It was a substantial building, equipped with an equestrian ring reportedly wider than those of Astley's or the Royal Circus, and a full theater stage. But Astley's new circus never took off. It changed name, look, it became a theatre—nothing helped. Astley lost a considerable amount of money in this last venture. He sold the Pavilion in 1813.
On November 1, 2015, a statue of Philip Astley was unveiled at the Newcastle-under-Lyme College's Performing Arts Centre in Newcastle-under-Lyme, Astley's birthplace, to celebrate the "father of the Modern Circus"—a long overdue tribute to a major pioneer of the Performing Arts.
Philip Astley died from stomach ailments in his Parisian home, Rue du Faubourg du Temple, on October 20, 1814. He was seventy-two years old. He was buried at the Père Lachaise cemetery, in Paris, where his grave, unfortunately, is no longer visible. His will asked that all his Parisian properties be sold and for the proceeds to go to his son, John, who also inherited the amphitheatre at Stangate Street. John Philip Conway Astley survived his father by only seven years.
On November 1, 2015, a life-size statue of Philip Astley by the sculptor Andrew Edwards and the members of the Royal Doulton School of Sculpture was unveiled at the Newcastle-under-Lyme College's Performing Arts Centre in Newcastle-under-Lyme, Astley's birthplace—a long overdue tribut to a major figure in the history of Performing Arts.
(London, Sherwood, Jones & Co., 1824)
Maurice Willson Disher,
Greatest Show On Earth
(London, G. Bell and Sons, Ltd., 1937)
Mike Rendell,
Astley's Circus — The story of an English Hussar
(CreateSpace Independent Publishing Platform, 2014) —
ISBN 978-1490496887
Image Gallery
Astley's Riding School (1777)
Philip Astley, c.1800.
Silhouette of Philip Astley (1801)
1802 London Map showing Astley's Amphitheatre
Astley's training method (1804)
Façade of Astley's Amphitheatre, c.1807
Astley's Amphitheatre in 1807
Astley's Amphitheatre (c.1840)
Astley's statue in Newcastle-under-Lyme (2015)
| http://www.circopedia.org/index.php?diff=next&oldid=23883&title=Philip_Astley |
A Conflict Could Be Brewing in the Eastern Mediterranean. Here’s How to Stop It. - Carnegie Europe - Carnegie Endowment for International Peace
Sinan Ülgen
, Asli Aydintasbas
September 17, 2020
Washington Post
Source: Getty
Summary:
The discovery of hydrocarbons in the Eastern Mediterranean has raised tensions in the region. Europe must act to to prevent an actual war from breaking out between Greece and Turkey.
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On Sunday, Turkey pulled back its seismic exploration vessel
, Oruc Reis, from the contested areas of the eastern Mediterranean to pave the path for the beginning of negotiations with Greece. Just as well. Tensions in “the East Med” — the shorthand for a corner of the Mediterranean with rich gas reserves and contested maritime boundaries — run so high that no one is ruling out an actual war between Turkey and Greece.
Turkey, Greece and Cyprus are at loggerheads about how to allocate zones to explore the newly discovered hydrocarbon resources in the area — with
France throwing its weight
behind the Greek position and the
United Arab Emirates sending warplanes
to Crete. The specter of a confrontation between NATO allies could spiral into a conflict that draws in much of Europe. And with Turkey’s involvement in the Libyan war and a bitter Turkish-UAE feud running in the background, Europe risks being sucked into a wider Middle East conflict.
Sinan Ülgen
Sinan Ülgen is a senior fellow at Carnegie Europe in Brussels, where his research focuses on Turkish foreign policy, nuclear policy, cyberpolicy, and transatlantic relations.
More >
@sinanulgen1
At the heart of the matter are two conflicts: the old Cyprus problem — it was partitioned since 1974 into Greek and Turkish zones by U.N. peacekeeping forces — and an even more ancient disagreement between Greece and Turkey about how the maritime boundaries of Greek islands adjacent to Turkey are to be drawn. Greeks say that
under international maritime law
, Greece’s islands should be granted an extensive maritime economic zone. Turks argue that with its long shores, the Anatolian mainland generates its own continental shelf, limiting the scope of the Greek islands.
Asli Aydintasbas
Aydintasbas is a senior fellow at the European Council on Foreign Relations.
Europe is torn
. France, Cyprus and Greece want sanctions to contain what they see as a resurgent Turkey, but remain somewhat isolated. While wanting to show solidarity with Cyprus and Greece, many European countries feel it is a bad idea to alienate Turkey — and that Ankara’s concerns about being frozen out of the eastern Mediterranean are not unwarranted. While paying lip service to European Union solidarity, they are reluctant to support crippling sanctions.
The only way out of this deadlock is to get Turkey and Greece to sit and talk — which is what Germany has been trying to do. Chancellor Angela Merkel is playing the role that U.S. presidents traditionally play, periodically calling
Turkish President Recep Tayyip Erdogan and Greek Prime Minister
Kyriakos Mitsotakis
separately.
Europeans need to recognize that recent conflict in the East Med cannot be addressed in isolation from broader issues that involve Turkey’s involvement in Libya, its regional isolation, the long-standing Cyprus dispute and the overlapping claims on the Aegean. These issues are now interwoven. For example, Turkish troop deployment to Libya in January in support of the Tripoli-based Government of National Accord, and its subsequent maritime deal with the GNA, was out of a desire to stake its claim in the East Med.
Legally and politically, this is not a black-and-white case. The E.U. has called for an
emergency session on Sept. 24
to discuss sanctions on Turkey, but those would only add oil to the fire.
Instead, the E.U. should press Greece and Turkey to return to “ exploratory” talks
, suspended since 2016
, which cover the gamut of legal and political disputes — from maritime boundaries to overhead flights. With simultaneous announcements in Ankara and Athens, the new round of talks should start immediately and also cover the East Med. Turkey and Greece (and perhaps later Turkish and Greek Cypriots) should be encouraged to explore the possibility of joint ventures for the exploration of undersea resources in the disputed maritime geographies. Alternatively, the talks could also eventually lead to an agreement on a joint framework for international adjudication.
Europe and Turkey need one another on a wide range of issues, from migration to security. Ankara needs to tone down the “conquest” rhetoric. But in the absence of U.S. leadership, it is up to Europeans to develop a set of policy options to create a positive agenda and a new bargain with Turkey. Convening a wider conference on the East Med could be a start. Another option could be to give Turkey access to the East Med Gas Forum, a planned pipeline to run across the region, with the purpose of creating an axis that excludes Turkey. The pipeline, a brainchild of the Trump administration, triggered a siege mentality in Ankara, eventually contributing to Turkey’s entry into the Libyan war.
Europeans should also appoint an East Med envoy who can engage in shuttle diplomacy among the different parties for the goals of conflict mitigation and settlement.
And finally, NATO should get involved to prevent a confrontation. The organization can develop a deconflict mechanism between Turkey and Greece, possibly including France, with a view to preempt naval accidents that could lead to war.
In a world so interconnected, there can be no clear winners in a confrontation in the East Med. Best to sit and talk — and share.
This article originally appeared on the Washington Post .
End of document
Carnegie does not take institutional positions on public policy issues; the views represented herein are those of the author(s) and do not necessarily reflect the views of Carnegie, its staff, or its trustees.
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Learn More | https://carnegieeurope.eu/2020/09/17/conflict-could-be-brewing-in-eastern-mediterranean.-here-s-how-to-stop-it-pub-82759 |
Restorative Justice and Earned Redemption
Download Citation | Restorative Justice and Earned Redemption | The author provides a comprehensive discussion of the roots of the new reintegrative and restorative justice theories as well as the success of... | Find, read and cite all the research you need on ResearchGate
March 1998 American Behavioral Scientist
41(6):768-813
DOI: 10.1177/0002764298041006003
Authors:
GORDON BAZEMORE
GORDON BAZEMORE
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References (26)
Abstract
The author provides a comprehensive discussion of the roots of the new reintegrative and restorative justice theories as well as the success of current, preliminary applications of these theories. Arguing that the traditional and opposing theories of the retributive paradigm and the treatment model offer only a simplistic choice between helping or hurting offenders, the author contends that these systems fail to address adequately the needs of communities and victims. In place of these two paradigms, he suggests a new model that he terms reintegrative or restorative justice. This new theory, based on specific cultural approaches to crime found in New Zealand, Japan, and elsewhere, seeks to address the needs of communities and victims through apology and reparation, a process that hopefully leads to the reintegration of offenders into society.
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... For example, the result of punishing behaviour towards free riders is enhanced cooperation within the social system (Fehr and Gächter 2000). Thus, restorative justice should not only benefit the victim and/or the community but also the offender through moral rehabilitation
(Bazemore 1998)
. Nevertheless, there is scant evidence of how restorative justice can work as a control mechanism in service ecosystems. ...
... At a micro level restorative justice comes into play when due to such or similar events, for example, both rider and driver are penalised by Uber located at meso level. For the drivers and depending on the severity of the transgression (service failure vs serious offence), Uber can either have them retrained and hence can also provide a benefit to the offender
(Bazemore 1998)
or exclude them permanently from driving for Uber. Uber can employ this top down restorative justice approach to remove potential disequilibrium between riders and drivers. ...
Infusing tribal reciprocity into service research: towards an integrated and dynamic view of repayment, retaliation and restorative justice for regenerative service ecosystem wellbeing Article Full-text available
Dec 2021
Jörg Finsterwalder Alastair Tombs
Service exchange among actors and the notion of reciprocity have gained momentum in service research. However, reciprocity’s underlying facets and nature have been neglected. Drawing on a tribal notion of dynamic reciprocity facilitates the understanding of contemporary service interactions in service ecosystems. We explore reciprocity’s tribal elements of repayment, retaliation and restorative justice. This tribal view of reciprocity is also linked to relational and regenerative wellbeing. We derive a conceptual framework for service ecosystems research and practice. An expanded view of reciprocity for service exchanges within and across system levels is required to facilitate regenerative service ecosystem wellbeing.
View Show abstract
... No. 28 ISSN: 2363-9849 (Bazemore, 1999)
. The 'earned redemption' narrative can signify a sustained stage of desistance (King, 2013), because it 'allows offenders to 'make amends' to those they have harmed in order to earn their way back into the trust of the community' (Bazemore, 1999: 4). ...
... This ownership over their past identity also reflects their expectation towards society since they do not expect redemption simply by renouncing their past beliefs. Hence their main motivation can be traced back to the notion of 'earned redemption' (Bazemore, 1999)
, which suggests an advanced stage of cognitive transformation given the social and psychological contingencies for successful desistance (King, 2013). In a similar vein, the all-out rejection of their formerly held extremist beliefs suggests that their P/CVE involvement is not constrained by any incomplete deradicalisation. ...
When Healing Turns to Activism: Formers and Family Members' Motivation to Engage in P/CVE. Article Full-text available
Sep 2021
Jonatan Schewe Daniel Koehler
The involvement of former extremists or family members of terrorists in measures aimed at preventing and countering violent extremism (P/CVE) has recently gained more attention in research and practice. However, little is yet known about the motivations of these individuals as to why they chose to engage in P/CVE activities. Understanding what drives such engagement could provide a better appreciation of the potential impact of such deployment, whether beneficial or detrimental to both the individuals involved and their respective P/CVE-target audience – and contribute to the evolving discourse regarding the effectiveness and potential risks of such P/CVE interventions. This article draws on eight biographical-narrative interviews with four former right-wing extremists and with four relatives of jihadist foreign fighters, all of whom are currently engaged in P/CVE work. Through qualitative reconstructive methods, a combination of narrative and thematic approaches was used to reconstruct the action-relevant orientations for the interviewees' activism. Results indicate that family members are motivated by coping mechanisms for traumatic stress, by social relatedness derived from a ‘positive marginality’, and in response to situational demands. Motivations of former extremists include finding their way back into society, having their new identity mirrored back to them, or maintaining a sense of self-continuity through ‘role residuals’. The results show that, in the case of family members, motivation is affected by exposure to traumatic stress. They also suggest that a locus of control among former extremists can signify different stages of deradicalisation in some forms of exit pathways and thus help to identify different risks depending on a former’s P/CVE role.
View Show abstract
... An alternative approach that may circumvent the problems arising from differences between students' and teachers' perspectives concerning rather punitive reactions to misbehavior (as examined in the present research) follows the principles of restorative justice
(Bazemore, 1998;
Braithwaite, 1998). This philosophy of dealing with misbehavior considers the perspectives of victims, offenders, and the community in which the offense occurred to assign a punishment. ...
Comparing Teachers’ and Students’ Perspectives on the Treatment of Student Misbehavior Article Full-text available
Sep 2022 Soc Justice Res
Mathias Twardawski Benjamin E Hilbig
The treatment of student misbehavior is both a major challenge for teachers and a potential source of students’ perceptions of injustice in school. By implication, it is vital to understand teachers’ treatment of student misbehavior vis-à-vis students’ perceptions. One key dimension of punishment behavior reflects the underlying motives and goals of the punishment. In the present research, we investigated the perspectives of both teachers and students concerning the purposes of punishment. Specifically, we were interested in the extent to which teachers and students show preferences for either retribution (i.e., evening out the harm caused), special prevention (i.e., preventing recidivism of the offender), or general prevention (i.e., preventing imitation of others) as punishment goals. Therefore, teachers ( N = 260) and school students around the age of 10 ( N = 238) were provided with a scenario depicting a specific student misbehavior. Participants were asked to indicate their endorsement of the three goals as well as to evaluate different punishment practices that were perceived (in pretests) to primarily achieve one specific goal but not the other two. Results show that teachers largely prefer general prevention, whereas students rather prefer special prevention and retribution. This discrepancy was particularly large in participants’ evaluation of specific punishment practices, whereas differences between teachers’ and students’ direct endorsement of punishment goals were relatively small. Overall, the present research may contribute to the development of classroom intervention strategies that reduce conflicts in student–teacher-interactions.
View Show abstract
... In recent decades, restorative justice (RJ) has become one of the major initiatives in world-wide criminal justice systems (Braithwaite, 1999;Gavrielides, 2016;Menkel-Meadow, 2007). It is regarded as philosophically distinct from other justice schemes ("retributive" and "rehabilitative" models), viewing crime as a violation of people and relationships rather than merely as a violation of a law
(Bazemore, 1998;
Zehr, 1990). In the RJ model, offenders and victims are empowered to communicate how to make reparation in the aftermath of crimes or harmful events (Johnstone, 2013;Zehr, 1990). ...
Can Restorative Justice Reduce Incarceration? A Story From China
Article Full-text available
Jul 2021 JUSTICE Q
Yan Zhang Yiwei Xia
This paper attempts to investigate the capacity of restorative justice (RJ) to reduce incarceration in China. It utilizes a “top-down” approach to explore how macro transitions in Chinese politics and criminal justice translate into micro implementation of RJ, which ultimately affects incarceration. Interviews with Chinese police, prosecutors, and judges revealed how minor injury cases were diverted by RJ throughout the criminal justice system. In addition, 172,731 judicial judgments were coded to estimate RJ’s effect on sentencing lengths and the probability of probation for offenders. The findings suggest that the Chinese approach to implementing RJ does liberate numerous offenders from harsher incarceration. Yet, Chinese RJ reforms remain a thin version without deep roots in civil society, in “bottom-up” social movement excellence, or thorough foundations in restorative Confucianism with roots in ancient Chinese society. RJ is still a marginalized part of a Titanic that resists turning away from the punitive “Strike-Hard” ideology.
View Show abstract
... This perspective leads directly to restorative approaches, a third type of intervention for addressing juvenile crime (Development Services Group, 2010). The goals of restorative justice are to bring together the offender, victim and community members to repair harms resulting from juvenile crime (Bazemore, 1998;
Bergseth & Bouffard, 2007). From this point of view, juvenile crime is more than an act against the state, it is an offense against another person in the perpetrator's community. ...
Strategies for Enhancing Programming in Local Juvenile Courts: Logic Models and Quality Assurance Procedures Article
Jan 2021
David A Julian Keli Bussell Ryan Kapa
Melissa Ross
The authors provide a case-study related to a recent project using program logic models as a primary component in the implementation of a formal quality assurance process in a local juvenile court. Program logic models illustrate the evolution of court personnel’s thoughts about how best to conceptualize programming. Juvenile court officials are developing and implementing formal “quality assurance” procedures to allow for ongoing planning and program development. The authors argue that quality assurance procedures hold great promise for assuring that juvenile court programming is efficient and effective and serves the needs of local communities.
View Show abstract
... These elements are somewhat reminiscent of the restorative justice approach involving an encounter between the parties involved in and affected by an offense, designed to cope with it and its consequences (Marshall, 1999). To initiate the process, the offender must acknowledge the offense and apologize, whereas the victim needs to accept the acknowledgement and convey the message that the offender is good and acceptable (Bazemore, 1998)
. The teshuva process provides both content and theoretical rationale to the restorative justice process. ...
Intervention and rehabilitation methods with offenders—from the Jewish scriptures to the criminological field Article
Oct 2020
Yitzhak Ben Yair
The ancient scriptures of world religions and spiritual traditions offer a treasure of knowledge, much of which is designed to guide the individual to a normative lifestyle through worldviews and practices that reduce antisocial behavior and promote prosocial behavior. Contemporary scholars tend to ignore that knowledge and its ability to contribute to social-scientific discourse and practice, despite the fact that most of the world’s population lives by it, at least to some extent. The present article addresses intervention and rehabilitation with offenders as part of a broader research project examining the ability of the Jewish scriptures to offer an alternative, universal criminological theory—spiritual Jewish criminology. The theory and its basic premises will be presented briefly as a theoretical foundation informing correctional rehabilitation practices, such as the repentance model, Jewish bibliotherapy, and humility as a counterbalance to criminal behavior. Although these practices are already implemented successfully in religious rehabilitation programs in Israel, further study is required in order to assess their effectiveness among other populations that are not Jewish or religious.
View Show abstract
... The community plays a vital role in the process as the former combatants work to remodel themselves and gain acceptance (Bazemore, 1998;
Lopez, Andreouli, & Howarth, 2015). To combat challenges presented by reintegration there is a growing trend for the process to run as a bottom-up approach based on the community's requirements and needs (Specker, 2008). ...
Disarmament, Demobilization, and Reintegration in Nepal
Preprint Full-text available
Jun 2020
Emily Rothstein
When successful, the processes of security sector reform and disarmament, demobilization, and reintegration of former combatants address the needs of both former combatants and their receiving communities. These are aided through the application of transitional justice, efforts for reconciliation, and intentional community-based reintegration programs with assistance from involved international partners and implementing government bodies. In Nepal, the disarmament, demobilization, and reintegration processes were led by the leading political parties using the framework outlined in the 2006 Comprehensive Peace Agreement with support from the United Nations Mission in Nepal. As a result, the process was top-down and did not reflect the needs of the communities or the challenges faced by the former combatants. While the political and economic integration of the former combatants was successful, their social reintegration varied across the country. Additionally, while the Nepali government created transitional justice and reconciliation bodies they have not been used to their full potential.
View Show abstract
... A restorative approach to reintegration means engaging with these wider needs and obligations.
Bazemore (1998)
describes this process as 'earned redemption': those who have done wrong should make amends, and those who have made amends should be supported back into society. RJ can help do this through engaging with the micro communities relevant to individuals, such as family and friends, who can participate in constructive dialogue and become part of the process of reintegration. ...
Restorative justice informed criminal justice social work and probation services Article
Oct 2019
Steve Kirkwood Rania Hamad
Despite the growth of restorative justice (RJ) research, theory and practice, little work has explored its implications for criminal justice social work (CJSW) and probation services. Our analysis demonstrates that an RJ ‘lens’ transforms the view of CJSW, enlarging the scope to help people make amends for harm, magnifying the role for victims of crime, refocusing on the meaningfulness of reparative acts and clarifying the role of communities in reintegration. Our vision of RJ informed CJSW and probation services offers a way of shifting practice to help people repair harm, make good and move on with their lives.
View Show abstract
... Third, moral rehabilitation allows individuals to "earn" their redemption by paying something back to society (McNeill, 2012; see also
Bazemore, 1998)
. From research on desisting formerly incarcerated persons (e.g., Maruna, 2001;Petrich, 2017;Petrich & Morrison, 2015) and substanceabusers (e.g., Pagano, Post & Johnson, 2011;White, 2000), it is evident that many people once considered "deviants" fulfill these needs by taking on the role of a "wounded healer" for others entrenched in antisocial lifestyles (Maruna & LeBel, 2015). ...
Hiring and retaining formerly incarcerated persons: An employer-based perspective Article
Mar 2019
Jerry Goodstein Damon M. Petrich
In this article we adopt an employer-based perspective on the reintegration of formerly incarcerated persons. Specifically, insights from interviews with 26 employers speak to their direct experiences in hiring and retaining formerly incarcerated persons. This article contributes to the literature on employment of formerly incarcerated persons by examining employers’ motivations, perceived benefits (as well as challenges once hired), and factors critical to the successful hiring and retention of formerly incarcerated persons. We also identify ways in which employers may provide a means for the psychological, legal, moral, and social rehabilitation (McNeill, 2012 McNeill, F. (2012). Four forms of ‘offender’ rehabilitation: Towards an interdisciplinary perspective. Legal and Criminological Psychology, 17(1), 18–36. doi:10.1111/j.2044-8333.2011.02039.x[Crossref], [Web of Science ®] , [Google Scholar]) of formerly incarcerated persons.
View Show abstract
... It is suggested that restorative justice practices have been around since the existence of mankind and grounded in ancient codes of conduct. Zehr (2002) stated that some of that evidence can be found in a wide range of sources such as the Code of Hammurabi, the Laws of Ethelbert, and Homer's Iliad
(Bazemore, 1998)
. According to popular origin myths of the restorative justice movement, contemporary restorative justice began in Canada in the late 1970s when a parole officer from Kitchener, Ontario introduced a process for victims and offenders to meet face-to-face (Peacher, 1989). ...
Zero Tolerance, Zero Justice: Teacher Perceptions of Using Restorative Justice
Article
Jun 2018
Ajayi Monell
While many schools are spending millions on instructional programming, new technology, and colorful chart paper for data walls, an area that often takes a back seat to improving achievement is the social and emotional learning of students (SEL). Until the education community starts focusing on the well-being of our students, closing the achievement gap will continue to be a nice catch phrase and not a reality. The purpose of this study was to investigate the perceptions of K-8 teachers to determine how they felt about the use of Restorative Justice, with a focus on Peace Circles. This study explored this alternative approach to discipline and how social and emotional learning can be used to improve school culture and school safety while addressing the clear racial disparities in punitive consequences given to Black males. The participants in this study included nine classroom teachers, one ENCORE teacher, and a support staff member. This study aimed to answer two questions: To what extent do professional development workshops influence teachers’ knowledge and perceptions of restorative justice for discipline? What are teachers’ early experiences using Peace Circles in their classrooms? Ultimately, the need to care for the whole child needs to be at the forefront of decision making when disciplinary choices are made in schools. By putting the human back in humanity when dealing with students, especially our Black males, the education community can truly help all students succeed.
View Show abstract
... Community is a central, yet problematic, concept in the realm of restorative justice because community transcends geographical space by describing a set of interpersonal relationships. The term 'communities of care' has gained attention within restorative justice literature, referring to family, friends and other supporters, joined by relationships rooted in trust and respect (Bazemore, 1998;
Boyes-Watson, 2000). The notion of communities of care is central to understanding community in relation to narrow, explanatory theories of restorative justice. ...
Bridging police and communities through relationship: the importance of a theoretical foundation for restorative policing Article
May 2017
Krystal Glowatski Nicholas A Jones R. Nicholas Carleton
Various models of policing have been studied in the past, but have primarily focused on practice. The current paper applies Llewellyn’s integration of relational theory and restorative justice to the notion of restorative policing. The paper explores how several demographic factors, police organisational support and theoretical constructs associated with relational theory influence the willingness of police officers (n = 296) to engage in practices associated with a restorative approach to policing. The current analytic results evidence relational theory as providing a previously absent and untested theoretical foundation within the discussion of restorative policing.
View Show abstract
... Early theorists tended to talk about restorative justice as a different or new lens through which to view justice (Zehr 1995), or as a third way to do justice
(Bazemore 1998
). This invoked a perception of restorative justice as an alternative to the more conventional models of criminal justice based on rehabilitation or retribution. ...
Sexual Violence and Substantive Equality: Can Restorative Justice Deliver? Article Full-text available
Jun 2017
Shirley Julich Natalie Thorburn
The effects of sexual crimes upon victims and the wider community are pervasive and far-reaching, yet conventional attempts to address offending and seek justice for victims have not succeeded; rather, they have left victims without a sense of justice and often magnified the adverse impacts of the initial victimization. The applicability and appropriateness of restorative justice to such gendered categories of crime has been long debated, but emerging evidence suggests that it may offer victims greater satisfaction by way of recognition of the need for substantive over procedural equality, and consequent privileging of victims’ needs and experiences. This focus on substantive equality and its implications for justice also aligns with international covenants, which recognize the inadequacy of formal equality and traditional approaches to justice when addressing crimes where perpetration is dependent on the manifestation of power and control. The article therefore sets out the case for restorative justice in accordance with these imperatives for substantive equality, and discusses the challenges inherent in providing safe restorative practices.
View Show abstract
The views of victim/survivors of sexual violence about perpetrator post-release measures Article
May 2023
Kelly Richards Jodi Death Carol Ronken
View
Bibliography
Article
Aug 2017
Timothy Longman
Following times of great conflict and tragedy, many countries implement programs and policies of transitional justice, none more extensive than in post-genocide Rwanda. Placing Rwanda's transitional justice initiatives in their historical and political context, this book examines the project undertaken by the post-genocide government to shape the collective memory of the Rwandan population, both through political and judicial reforms but also in public commemorations and memorials. Drawing on over two decades of field research in Rwanda, Longman uses surveys and comparative local case studies to explore Rwanda's response both at a governmental and local level. He argues that despite good intentions and important innovations, Rwanda's authoritarian political context has hindered the ability of transnational justice to bring the radical social and political transformations that its advocates hoped. Moreover, it continues to heighten the political and economic inequalities that underline ethnic divisions and are an important ongoing barrier to reconciliation.
View Show abstract
Looking-at-Community-Based-ADRS-in-India-Through-a-Restorative-Justice-Perspective Chapter
Oct 2022
Swikar Lama
Restorative justice is a type of alternative dispute resolution, but not all ADR (Alternative Dispute Resolution) procedures constitute restorative justice. This chapter examines community-based alternative dispute resolution systems, attempting to distinguish the similarities and differences between ADRS (Alternative Dispute Resolution Systems) and restorative justice procedures. It examines whether these community-based ADRs adhere to restorative justice principles such as victim empowerment, deliberate effort by those involved in decision-making to reduce stigmatization and punishment of the offender, emphasis on strengthening or repairing interpersonal relationships, and so on. It also looks into whether formal restorative justice processes could imbibe some of the good features of these community-based ADRs.
View Show abstract
Third-Party Reactions to Workplace Aggression
Chapter
Feb 2017
Manuela Priesemuth Marie Mitchell
Robert Folger
Workplace aggression is a serious problem for workers and their employers. As such, an improved scientific understanding of workplace aggression has important implications. This volume, which includes chapters written by leading workplace aggression scholars, addresses three primary topics: the measurement, predictors and consequences of workplace aggression; the social context of workplace aggression; and the prevention of workplace aggression. Of note, the book encompasses the various labels used by researchers to refer to workplace aggression, such as 'abusive supervision', 'bullying', 'incivility' and 'interpersonal conflict'. This approach differs from those of previous books on the topic in that it does not focus on a particular type of workplace aggression, but covers an intentionally broad conceptualization of workplace aggression - specifically, it considers aggression from both the aggressors' and the targets' perspectives and includes behaviors enacted by several types of perpetrators, including supervisors, coworkers and customers.
View Show abstract
Forgiving Sin
Chapter
Jan 2022
David Konstan
The modern idea of forgiveness has its roots in the Biblical conception of sin, which may be forgiven by God on condition of confession and repentance. Repentance represents a profound change of heart and rejection of one’s sinful self. Classical Greek and Roman texts record various forms of reconciliation, for example the payment of reparations, but apologies take the form of excusing the offense as in some sense involuntary. One may appeal to external agencies such as the gods or madness, or internal forces such as passion; but this is represented as a lapse rather than as the sign of a moral deficiency. The secularization of Biblical forgiveness, treated as interpersonal rather than in relation to God, has given rise to complex problems in psychotherapy, restorative justice, truth and reconciliation commissions, domestic violence, and more. The sincerity of an apology may be questioned, and the offended party may insist on extreme conditions before granting forgiveness. The role of forgiveness, with its Biblical echoes, is illustrated across several domains.
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On the incompatibility of ‘Western’ and Aboriginal views of Restorative Justice in Canada: a claim based on an understanding of the Cree justice Article
Dec 2021 Contemp Justice Rev
Reza Barmaki
‘Restorative justice’ (RJ) has been a popular notion in Canada. A common belief has been that ‘‘western approaches’ to RJ are compatible with that of Canada’s Aboriginals. I hold a different position. I argue that the religious beliefs of Canada’s Aboriginals are basic to their understanding of RJ. As such, their view of RJ is essentially incompatible with western approaches, which are secular. Any similarity between the two is only an apparent one produced by the indiscriminate uses of similar terms such as ‘holistic’, ‘healing’ or ‘restoration’. I support my argument by providing an account of Canada’s largest Aboriginal group’s view of RJ: the Cree. I demonstrate that it is based on certain religious principles that are absent from western approaches to RJ. As such, it is fundamentally incompatible with secular western approaches to RJ in Canada. These religious principles, basically and broadly speaking, are shared by all Aboriginal groups in Canada.
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Desistance from Sexual Offending: The Role of Circles of Support and Accountability Book
Nov 2021
Kelly Richards
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A Person-Centered Approach to Understanding Endorsement of Restorative Justice in Response to Workplace Mistreatment Article Full-text available
Sep 2021 Soc Justice Res
Tyler Okimoto Udo Konradt Sabrina Krys Niamh Dawson
There is growing body of research investigating endorsement of restorative justice as a response to interpersonal transgressions, but a limited understanding of how endorsement varies across different individuals—for whom is restorative justice seen as an appropriate response? The current research seeks to address this limitation by identifying natural heterogeneity in endorsement of restorative justice. We employ a policy-capturing within-subject design to examine restorative justice endorsement following workplace mistreatment by a supervisor at different levels of severity. Latent growth curve analyses indicated support for restorative justice increased with more unfair treatment, but following a concave, curvilinear slope. Latent class analysis suggested heterogeneity in endorsement patterns. Class 1 (66%) comprised individuals with a low initial level of restorative endorsement and a curvilinear growth trajectory as offense severity increased, while Class 2 (33%) comprised individuals with a medium initial level and a linear growth trajectory. We also examined victim-focused justice sensitivity as a predictor of class membership; but in line with past research, we did not find a significant relationship between victim sensitivity and restorative justice endorsement. These findings identify previously unrecognized heterogeneity in patterns of restorative justice endorsement, pointing to differences in the lay understanding of the when and where restorative processes should be applied. More broadly, this research illustrates how we can utilize person-centered approaches to shed new light on established justice research and theory.
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Homelessness, Mental Health Afflictions, Problematic Substance Use, and Associated Criminality: A Transformative Justice Resolution Chapter
Jan 2021
Jayesh D'Souza
Homelessness and related community ailments have plagued society for a number of years, and governments have found it difficult to get these under control. The sheer number of homeless with mental health afflictions and problematic substance use problems leaves no doubt about the need for a stronger, more urgent government response. Community ailments such as these have led to increased crime rates and incarcerations and overcrowded prisons without a lasting solution in sight. This chapter uses the transformative justice model, with the expectation it produces better results than current models, by examining the source of homelessness, mental health afflictions, and problematic substance use and their bi-directional relationship with crime. This inter-jurisdictional study compares the current situations in the state of California and the province of Ontario, which have a high percent of homeless populations. It proves that special attention to vulnerable populations such as racialized groups, the socioeconomically disadvantaged, and youth is warranted.
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Conclusion
Chapter
Nov 2020
Stephanie Kewley Sarah Pemberton
Mohammed Rahman
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Second Acts and Second Chances: The Bumpy Road to Redemption
Article
Feb 2021 J MANAGE INQUIRY
Robert J Bies Thomas M. Tripp
Laurie J Barclay
Throughout history, there are numerous examples of business and government leaders who have fallen from grace only to rise again, and have a “second act” and a “second chance” as a legitimate social actor or leader—that is, they achieved redemption. We explore “the road to redemption” of leaders—when and why it occurs, and what “bumps” prevent it. In our analysis, we conceptualize redemption as a process with three elements—remorse, rehabilitation, and restoration—and as an outcome (the restoration of legitimacy). We argue that achieving redemption is not a product of chance; rather, it is a social construction process of narrative creation and identity construction involving many parties. Also, the road to redemption is shaped by cultural-specific factors—and it is temporally dependent. From this framework, we identify new directions for the theory and practice of leadership.
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The Role of Proneness to Guilt and Shame Among People in Custody in Promoting Restorative Justice Processes Article
Dec 2020 CRIM JUSTICE BEHAV
Inbal Peleg-Koriat Dana Weimann saks
This research examined the role of guilt and shame proneness among people in custody in shaping attitudes toward restorative justice (RJ) and in predicting the effectiveness of RJ practices. Study 1 ( n = 110) examined the correlation between participant guilt and shame proneness and willingness to participate in an RJ process. It revealed that proneness to guilt, but not to shame, was correlated with willingness to participate in an RJ process. Mediational modeling showed that guilt proneness predicted willingness to participate in an RJ process via its strong correlation with regret and remorse. Study 2 ( n = 133) examined whether shame and guilt proneness affects the effectiveness of an RJ practice. It revealed that high guilt proneness predicted high willingness to participate in RJ, whereas shame proneness moderated the effectiveness of an RJ practice. These results can help practitioners and researchers develop interventions to promote the effectiveness of RJ programs.
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Values-Based Social Work: Case Study on the Particularities of Probation in Romania Chapter
Jan 2018
Antonio Sandu
The purpose of the research is to identify the ethical and axiological perspectives that underlie the process of social construction of the probation practice, and also aim at the ways in which the theoretical perspectives that underlie practice become constituents of the discourse of probation counsellors. The probation practice in Romania derived from social work practice with deviant groups. In the probation practice a large amount of case management instruments are still connected with social work practices. The results lead to the construction of a model of probation that integrates restorative elements with the restitutive ones, but also with elements of utilitarian justice, or centred on humanistic values. The ethical values identified as being constitutive for this model are co-responsibility, dignity and justice.
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Beyond the eternal criminal record: Public support for expungement
Article Full-text available
Sep 2020 Criminol Publ Pol
Alexander L. Burton Francis T. Cullen
Justin T. Pickett Angela Thielo
Research Summary:
In The Eternal Criminal Record, James Jacobs detailed how it has become increasingly difficult for ex-offenders to escape the mark of their criminal record. One way to “wipe the slate clean” is through the official expungement of criminal records. We assess public views toward this policy using a national sample of American adults (N = 1,000). Public support for expungement is high for persons convicted of property and substance-related offenses, who stay crime free for 7 to 10 years, and who “signal” their reform through stable employment and completion of a rehabilitation program. Members of the public are also concerned about unfettered public access to criminal records and want to ensure that any available criminal record information is accurate. The strongest predictor of support for expungement is a belief in redeemability.
Policy Implications:
There is a growing movement in the United States that seeks to curtail the effects of criminal records through their expungement. In recent years, most states have enacted bills creating, expanding, or streamlining criminal record relief. Public opinion is important in this context, because it can motivate or constrain reform efforts. Our findings show that, when the risk to public safety appears low, the American public favors providing second chances by using expungement to wipe clean the record of a criminal offense committed years previously. Further, knowledge about the public’s belief in redeemability may be key to understanding and promoting reform efforts that seek to include rather than exclude offenders back into society.
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The indecent demands of accountability: trauma, marginalisation, and moral agency in youth restorative conferencing Article Full-text available
Sep 2020
William R. Wood
In this article I explore the concept of accountability for young people in youth restorative conferencing. Definitions of accountability in research and programme literature demonstrate significant variation between expectations of young people to admit harms, make amends, address the causes of their offending, and desist from future offending. Such variation is problematic in terms of aligning conferenc-ing goals with accountability expectations. I first draw from research that suggests appeals to normative frameworks such as accountability may not be useful for some young people with significant histories of victimisation, abuse, neglect, and trauma. I then examine problems in accountability for young people that are highly marginalised or 'redundant' in terms of systemic exclusion from economic and social forms of capital. These two issues-trauma on the micro level and social marginalisation on the macro level-suggest problems of getting to accountability for some young people. I also argue trauma and social marginalisation present specific problems for thinking about young offenders as 'moral subjects' and conferenc-ing as an effective mechanism of moralising social control. I conclude by suggesting a clear distinction between accountability and responsibility is necessary to disentangle the conflation of misdeeds from the acute social, psychological, and developmental needs of some young offenders.
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Police Discretion and Restorative Justice in China: Stories from the Street-level Police Article Full-text available
Feb 2021 INT J OFFENDER THER
Yan Zhang
Based on ethnographic data collected from one local police station in China, this article attempts to examine the use of discretion by Chinese police in three different restorative justice (RJ) programs. With reference to Wilson’s organizational style of policing, the hybridity of watch-man, legalistic and service style in Chinese policing is identified, which can help conceptualize how police decision over mediation work has been institutionally co-shaped. This article also deploys Lipsky’s street-level bureaucracy with specific focuses on how the police select cases and facilitate an agreement between stakeholders. Coping strategies defined by Lipsky are found to be employed by the police to confront their huge workload and complicated cases. Overall, RJ in China is primarily promoted as universal top-down national reforms; meanwhile, police discretion, catalyzed by bureaucratic rationalities and the political imperative of social order and stability, is conducive to both the divergence and convergence between RJ in law-books and in action.
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Promoting Inmates’ Positive Attitudes toward Participating in a Restorative Justice Process: The Effects of a Victim Awareness Process Article
Apr 2020 PRISON J
Dana Weimann saks Inbal Peleg-Koriat
In the present study, we conducted an empirical experiment to examine whether exposure to a victim awareness procedure would affect inmates’ attitudes toward participating in a restorative-justice process. In addition, the study sought to evaluate whether there are differences between inmates serving their sentences in prisons with different therapeutic orientations. The findings indicate that participants who were exposed to a victim awareness procedure were more aware of the harm caused to the victim and showed a higher level of positive attitudes toward participating in restorative-justice process than those who were not. Contrary to our hypothesis, no differences were found between the prisons.
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Offenders’ understandings of forgiveness
Article Full-text available
Dec 2019
Tamera Jenkins
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Restorative justice at the crossroads: politics, power, and language
Article
Jul 2019 Contemp Justice Rev
Thalia González Annalise J. Buth
In ‘Reimagining Restorative Justice,’ Schiff and Hooker create analytic space aimed at developing a greater understanding of how ‘restorative justice’ language hinders or supports achieving right and equitable relationships. Despite what appears to be a more narrowly tailored focus on linguistic constructions, their desire to grapple with the practical and imaginative limits of language establishes a broad container from which to explore multivariate tensions within the field. As such, ‘Reimagining Restorative Justice,’ places restorative justice – as a movement, project, theory, or practice – at a crossroads. This article enters into the crossroads in the following conceptual manner. First, it contends that prior to (or at least concurrently with) the re-languaging of restorative justice there must be an interrogation of the framing, transmission, and institutionalization of restorative justice values and ideas. Second, it posits that such examination will expand the possibilities of ‘restorative justice’ language by underscoring the need to shift away from defining it relative to systems. By introducing these ideas, this article seeks to enrich the conventional restorative justice literature by highlighting new lines of theoretical and empirical analysis, which may in turn expand the lexicon of restorative justice itself.
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Revocation of citizenship: how punitive theories and restorative justice principles apply to acts of disloyalty toward the state Article Full-text available
Sep 2019 CRIME LAW SOCIAL CH
Shay Keinan Golan Luzon
Several countries have recently amended or attempted to amend their laws to make it easier for the state to revoke citizenship. Such laws suggest that citizenship is tied to loyalty to the nation state, and can therefore be taken away if it is deemed to have been breached. This paper focuses on possible justifications for applying the punishment of citizenship revocation to acts that are ‘contrary to the interests of the state’ or manifest ‘disloyalty’ to the nation. The paper compares such acts with other criminal acts, and analyses them according to a conventional punitive model of criminal law that includes also a restorative justice perspective. The paper argues that revocation of citizenship as punishment for acts of disloyalty can be justified by several theories of punishment, such as retribution, deterrence, denunciation, rehabilitation, and prevention. When it comes to carrying out the revocation of citizenship, however, several problems may arise. As a possible solution, the paper suggests applying a restorative justice approach to minor or moderate acts of disloyalty.
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Beyond personal reform: Adolescent drug-law offenders and the desistance process Article
Oct 2018
Thomas Anton Sandøy
While much research on desistance addresses processes of change for repeat offenders during and after imprisonment, this article applies insights from desistance studies to novice offenders outside the traditional justice system. In Norway, increasing numbers of adolescent drug-law offenders have been diverted to alternative justice systems over the last decade. Based on in-depth interviews with youth enrolled in programmes to help them refrain from drug use, the article seeks to identify how the early-stage desistance process is understood by would-be desisters. Rather than ascribing the rehabilitative programmes’ direct impact on their behaviour and thinking, the adolescents emphasised the importance of restoring relationships with parents and overcoming legal barriers. Accordingly, the analysis shows how concerns with personal reform were outweighed by (i) social and (ii) legal concerns. While the precedence of external concerns over personal reform may reflect the participants’ age and level of criminal involvement, it also reflects a particular culture of intervention.
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Difference in Perception of Injustice, Negative Emotion, and Rumination by Justice Types Article
Sep 2014
신재은 Ji Sun Park HyunMyoungHo
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Restorative Justice: Reflections and the Retributive Impulse
Chapter
Jun 2018
Alana Saulnier Diane Sivasubramaniam
Formal criminal justice systems worldwide have been increasingly incorporating restorative justice. As such, it is important to consider the state of knowledge on restorative justice, reflecting on that which is known and that which remains largely unknown. This chapter provides an overview of the academic literature associated with restorative justice to date, including: how restorative procedures differ from court-based justice responses; empirical research assessing restorative interventions; and theoretical explanations of the effects of restorative justice relative to court-based models. The latter part of the chapter is dedicated to the importance of better understanding public perceptions of appropriate justice. We draw attention to the discrepancy between legal and lay notions of justice; specifically, that legal notions of justice revolve around deliberative information processing, whereas lay notions of justice often stem from intuitive responses leading to retributive impulses. We argue that laypersons’ retributive motivations present a challenge to restorative justice, but that psychological research devoted to better understanding lay decision-making and justice heuristics offers a means to advance the long-term viability of restorative procedures. We conclude by suggesting more focused research directions that would progress the current state of knowledge, highlighting the value of experimental methods in this area of research.
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A Systems Perspective on Forgiveness in Organizations
Article
Jan 2016
Robert J Bies Laurie J Barclay
Thomas M. Tripp Karl Aquino
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Through the Looking Glass: Taking Stock of Offender Reentry
Article
Feb 2018 J Contemp Crim Justice
Melinda Schlager Arnold
Offender reentry has been part of the fabric of the criminal justice system since the first prison opened its doors and people who went in the front door were, at some point, released. Traditionally, the research on offender reentry has either supported best practice by determining what specific individual-level programming “works” or “doesn’t work” or it has assessed the success of programs in terms of their ability to reduce recidivism. And while we may have moved the dial in the last 50 years with respect to what we know about individual-level offender reentry attributes, there is no effective overarching narrative to explain the offender reentry phenomenon. Overwhelmingly, practitioners and academics in the criminal justice system operate within a paradigm that assesses and evaluates everything using risk. Unfortunately, a risk- or deficit-focused approach to viewing offender reentry severely limits our ability to think differently about the problem. However, if we employ a paradigm for offender reentry that focuses less on problems and more on strengths, different outcomes are possible. Work done in social work that promotes “strengths-based, solution-focused, capacity building, asset creating, motivation enhancing” empowerment models that accentuate the positive serves as an exemplar for us to use in criminal justice when discussing offender reentry. The three strengths-based principles adapted to offender reentry and discussed here are as follows: Officer–offender relationships that emphasize collaboration will promote law-abiding, prosocial behavior; offenders who are empowered will be more likely to seek to change; and cooperation from the community is key to successful offender reentry. Fiscal, political, and common sense reasons for using a strengths-based approach to offender reentry are discussed.
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Structural Quality Standards for Work to Intervene with and Counter Violent Extremism Technical Report Full-text available
Jan 2017
Daniel Koehler
This report provides detailed structural integrity quality standards for designing, evaluating and improving CVE programs. It contains a structural integrity checklist for such programs.
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Immature offenders . A critical history of the representations of the offender in restorative justice Article
Dec 2017 Contemp Justice Rev
Giuseppe Maglione
This paper reconstructs and discusses how the ‘offender’ is represented within policy documents, legal statutes and scholarly literature on restorative justice, published and circulated in England and Wales over the last thirty years. The research first outlines the most wide-ranging and recurrent images and implicit assumptions of the offender in restorative justice. A set of specific offender’s features will be singled out, and the ‘ideal offender’ of restorative justice will be profiled. The final step of this work consists of mapping out the cultural context within which this ideal has emerged, in a historical perspective. The overall goal is to shed light on some taken-for-granted images surrounding the offender in restorative justice, and on the cultural context within which they have developed. In this way, it is possible to contribute toward the critical re-assessment of restorative justice whilst considering implications beyond the British context.
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When My Community Met the Other: Competing Concepts of “Community” in Restorative Justice Article
Nov 2017
Won Kyung Chang
In restorative justice theory, the concept of “community” looms large, since it is the locus of the very restoration to which this form of justice aspires. The questions that then raise themselves are: what is this “community” and how is this community rebuilt through the more relational and dialogical process of restorative justice? In investigating one restorative justice panel program in the United States, it becomes clear that “community” means different things to different individuals. Questioning the possibility of a locally-sanctioned version of justice, this study suggests that the starting point of including “community” in restorative justice should be re-thought.
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Victims’ Attitudes Toward Sex Offenders and Sex Offender Legislation
Article Full-text available
Nov 2017
Susanne Spoo Leah Kaylor Sarah Schaaf Elizabeth L Jeglic
It is commonly assumed that victims of sexual abuse feel more negatively toward sex offenders and advocate for harsher punishments than individuals who have not been victimized. This belief was examined by comparing attitudes toward sex offenders and their treatment, support of registration, notification, and residence restriction policies, as well as general knowledge about sex offenders between a sample of 129 individuals who reported sexual victimization and a sample of 841 individuals who did not report sexual victimization. Overall, we found that victims of sexual abuse reported more positive attitudes toward sex offenders and were more supportive of mandated treatment compared with nonvictims. However, while victims showed decreased support for the community notification laws, there were no differences in support of residence restrictions laws compared with those who reported no victimization. Finally, knowledge about sex offenders predicted attitudes regardless of victim status. These findings are discussed as they pertain to sex offender treatment and legislation.
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The decision to participate in mediation and individual factors: the role of moral foundations and their relation to restorative and retributive orientations Article
May 2017
Ana Pereira
The present study explores people’s willingness to participate in victim–offender mediation and the role played by moral foundations and the retributive and restorative justice orientations in this decision. Participants were exposed to a burglary victimisation hypothetical scenario in order to capture the decision to participate in victim–offender mediation. Based upon our interpretation of the positive association found between the retributive and restorative orientations, our analysis revealed two clear patterns of association between, on the one hand, the fairness/reciprocity moral foundation and the restorative orientation and, on the other hand, the authority/respect moral foundation and the retributive orientation. The ingroup/loyalty moral foundation directly and negatively predicted the decision to participate in mediation, while the fairness/reciprocity moral foundation had an indirect effect on the decision, through the restorative orientation.
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The International Criminal Court and restorative justice: victims, participation and the processes of justice Article
May 2017
Claire Garbett
Until recently, the International Criminal Court (ICC) described its legal practices as offering a balance between retributive and restorative justice. It was held that restorative justice was progressed through its framework of victim participation in legal proceedings. However, there is little research into how, or whether, the Court metes out restorative justice. This article first considers the key pillars of restorative justice as ‘encounter’, ‘amends’ and ‘reintegration’, and the form of victim participation within these practices. It then examines how the ICC aligns to the direct participation of victims prioritised by restorative justice, and shows that victims do not hold such participatory possibilities. Instead, legal professionals take on direct participation in dialogue and decision-making processes. Using Bourdieu’s framing of the juridical field, the article identifies key reasons for the absence of direct victim participation and argues that the ICC primarily functions as a retributive approach to the resolution of conflict.
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Understanding of Business Ethics by Leaders Based in Singapore: A Restorative Justice Perspective Chapter Full-text available
Jun 2017
Razwana Begum Abdul Rahim
The debate between ethical business practices and leadership has been growing and gaining momentum since the global financial crisis in 2008. Though various steps and measures were created to plug the gaps in the area of compliance and corporate governance, there is also an increasing demand for leaders to focus on business ethics. Ethics in business has become a critical topic for business leaders. Similarly, business leaders in Singapore emphasize on business ethics. In Singapore, being a small state relying mainly on commercial organizations for growth and economic development, the government has put in place various measures to ensure transparency and business continuity. These rules and regulations are often translated by the leader. To understand the leaders’ perception of ethical business principles and practices, a research study was carried out in Singapore in 2010 and 2011 with five business leaders. Analysis supports the view that leaders in commercial organizations based in Singapore perceive business ethics as important. Their understanding of business ethics, however, reflected a combination of the individual leaders’ ethical values and the government’s regulatory practices. The research study also indicated the potential of restorative justice in commercial organizations based in Singapore. The leaders’ management style in ensuring conformance by their employees to business ethics highlighted the principles, values and practices of restorative justice.
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Altruistic Prison Programmes in America: A Platform for Transformation
Chapter
Jan 2017
Barbara Cooke
Correctional programmes with elements of altruism or ‘giving back’ have grown increasingly popular over the last 20 years across the United States and other Western countries. This type of programming includes dog training, food bank, and Habitat for Humanity programmes, all of which provide a service to the community. The limited, but growing, literature on these programmes suggests that they promote desistance and have a restorative effect, which theorists have suggested can go hand-in-hand. Supporting the potential mechanisms of change suggested by this literature, correctional and desistance theorists have noted avenues for transformation embedded in altruistic acts. This chapter will expand on the current literature by examining the findings from an evaluation of dog-training programmes. Theoretical mechanisms underlying how altruism programmes can promote desistance are examined. Finally, this chapter will examine the potential future of altruism programmes in American corrections and worldwide.
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A restorative justice approach to legalising unauthorised immigrants
Article
Jan 2017
Michael Sullivan
In this paper, the author argues for a restorative justice approach towards regularising the status of long-term residents who entered a country without authorisation or overstayed their visas. Citizens have an interest in enforcing their immigration laws. However, the author questions the benefit of incarcerating and deporting long-term unauthorised immigrant residents who are willing to make amends for their immigration offences. Here, the author examines two possible applications of restorative justice processes as alternatives to deportation for immigration offences: victim–offender mediation where there is an individual victim who is directly harmed by an unauthorised immigrant’s use of false documents; and community reparative boards to address the more diffuse harms arising from entering and remaining in a country without authorisation. As alternatives to detention and deportation, these processes may provide unauthorised immigrants an opportunity to make amends for immigration offences and...
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Imaging victims, offenders and communities. An investigation into the representations of the crime stakeholders within restorative justice and their cultural context Article
Mar 2017 INT J LAW CRIME JUST
Giuseppe Maglione
This work is a critical analysis of how the main crime stakeholders (victim, offender and community) are represented within policy and legal statutes on restorative justice. The paper starts by sketching out the legal and policy archive of restorative justice, focussing on the most recurrent normative representations of the victim, offender and community, and unearthing their theoretical underpinnings. The goal is to identify a range of typified features and to assemble them together by profiling the ‘ideal stakeholders’ of restorative justice. The research includes a comparison between the ‘ideal’ victim, offender and community, pinpointing any overlaps and differences. Finally, it interrogates the cultural context within which these representations have emerged historically, influencing policy and laws. By way of reconstructing and discussing what is taken for granted in restorative justice and its background, the aim of the work is to foster critical reflection on the normative dimension of a popular development of western penal policies.
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Desistance and restorative justice: learning from success stories of Northern Ireland’s Youth Justice Agency Article
Sep 2016
Brendan Marsh Shadd Maruna
Although individual ‘success stories’ are often dismissed as anecdotal evidence in evaluating the work of criminal justice agencies, such individuals may have a great deal to teach those interested in improving justice interventions. This research explores the self-narratives of 24 young people who were formerly involved in restorative conferencing with the youth justice system in Northern Ireland (UK) to better understand the role that this work had (or did not have) on their efforts to desist from crime. These data suggest that the conferences that had the longest lasting impact were those in which the individual was confronted by a direct victim of personal violence. Conferences that did not involve direct victim input involved lecturing by police officers or that were conducted whilst the young person was intoxicated were largely dismissed by participants as lacking impact. Other aspects of restorative practice beyond conferencing, including reparation plans that involved drug-addiction treatment and other forms of counselling, were discussed more frequently as being central to the desistance process for interviewees. The most impactful aspects of youth justice involvement for interviewees were the human connections made with agency staff.
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An analysis of restorative justice and intimate partner violence policy and practice: Professionals' perspectives and perceptions Thesis Full-text available
Jun 2016
Melissa Garber
This qualitative research project endeavoured to open up the conversation around RJ and IPV and highlight gaps in policy in order to give voice to an area in the RJ process that has, up to this point, been virtually silent. There were two overarching aims. The first was to identify the underlying practice assumptions and values evident in the New Zealand Ministry of Justice (MOJ) restorative justice (RJ) standards for family violence (FV) cases (MOJ, 2013). These would be viewed from the perspective of working with intimate partner violence (IPV) cases in particular. The intention was to compare these assumptions and values with RJ and IPV international theory and New Zealand practice. The second aim was to clarify the processes and criteria used to determine/assess IPV offender suitability and readiness for RJ, ascertain the ways in which these practices were theoretically justified, and to compare the implementation of practice to the explicit and implicit guidelines present in New Zealand policy. To these ends, a collection of 30 criminal justice professionals (judges, lawyers, police officers) and restorative justice facilitators involved in the referral and assessment process of IPV offenders participated in interviews in person, over the phone, or via Skype, which were recorded, transcribed verbatim, and then subject to analysis in order to create a conceptual framework. The analysis identified 18 main themes that were grouped into four main categories: RJ IPV conceptualization, effective RJ IPV assessor qualities, IPV offender assessment for RJ suitability/readiness, and RJ IPV practice issues. These results were compared with policy and with the international literature in order to identify consistencies and inconsistencies and to discover where gaps in policy may become clarified. Results showed that a great deal of the policy was supported by the international literature, however there were several gaps and inconsistencies. Several issues were of interest – namely the lack of clarity in the framework of RJ for IPV (i.e. where does it sit in relation to the traditional criminal justice system, intervention vs. pathway vs. overarching framework), the timing of RJ assessment in terms of treatment and interventions, siloing of agencies, and funding/resourcing issues. A final question that arose for me during analysis was regarding the purpose and value of assessment in these cases. Rather than making a decision regarding suitability in order to exclude an IPV case from the RJ process, if the process was truly restorative, perhaps the outcome of an assessment of IPV offender/case suitability should, instead, be to determine what resources are necessary in order to support any IPV case through the RJ process.
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Täter-Opfer-Ausgleich
Chapter
May 2016
Eduard Matt Frank Winter
In dem Beitrag werden die Grundannahmen des Täter-Opfer-Ausgleiches (TOA) sowie der gegenwärtige Stand und die Rahmenbedingungen seiner Umsetzung in Deutschland beschrieben. Dabei benennen die Autoren als Ziele des TOA (i. S. eines Mediationsverfahrens) die Konfliktbearbeitung und die Wiederherstellung eines sozialen Friedens, also die ‚Heilung‘ der jeweiligen Konflikte. In diesem Zusammenhang wird deutlich, dass der TOA nicht als Sanktionsmaßnahme im Sinne des Strafrechts gedeutet werden sollte, sondern als ein alternativer Umgang mit Konflikten. Diesen Gedanken weiterführend, leuchten die Autoren die Entwicklungspotentiale des TOA in Richtung einer ‚Sozialen Mediation‘ aus und beschreiben erste Entwicklungen, die in diese Richtung weisen.
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Deviance and Deviants Why Adolescent Substance Use Prevention Programs Do Not Work Article Full-text available Oct 1993 EVALUATION REV Joel Brown Jordan Horowitz This article examines the social-historical lineages of adolescent alcohol and other drug (AOD) use prevention programs. It shows how risk factor research evolved from assumptions of deviance regarding the mentally ill and examines patterns in prevention research that have inhibited advancement in the field. These patterns take shape as a general assumption of the target population as deviant, over- or misinterpretation of research results, and evidence that researchers and program managers or administrators shift or initiate programs with no causative basis. For the field to move ahead, researchers, program specialists, and policymakers must reconsider these patterns in light of protective factor and harm reduction approaches. View Show abstract Rethinking the Sanctioning Function in Juvenile Court: Retributive or Restorative Response to Youth Crime Article Full-text available Jul 1995 CRIME DELINQUENCY Gordon Bazemore Mark S. Umbreit Although juvenile courts have always administered punishment to youthful offenders, parens patriae and the individual treatment mission have historically assigned an ambivalent role to sanctioning. In the absence of a coherent sanctioning framework, a punitive model has recently gained dominance over dispositional decision making in juvenile court. This article examines the limitations of sanctioning choices presented by both the individual treatment mission and what some have referred to as a “retributive justice” paradigm. We then consider the implications of an alternative model—restorative justice—as a framework for a new approach to sanctioning consistent with a revitalized juvenile justice mandate. View Show abstract Taking Fear of Crime Seriously: The Tasmanian Approach to Community Crime Prevention Article Full-text available Jul 1996 CRIME DELINQUENCY Mark Brown Kenneth Polk Despite having little serious crime in the form of homicide or sexual assault, the state of Tasmania in Australia has enough crime in terms of assault, burglary, and public order offenses to generate a reasonably high level of fear of crime. The Tasmanian government has embarked upon a novel attempt to address simultaneously both crime and fear of crime through a strategy of crime prevention that focuses on a combination of restorative justice and community enhancement. This positive, developmental approach to crime prevention is fundamentally integrative and stands in sharp contrast to the punishment-oriented policies currently popular in many American jurisdictions. Unlike the Tasmanian proposals, approaches such as “three strikes and you're out” leave the fear of crime problem unresolved, leading to a continuous upward spiral of punitiveness. View Show abstract Conditions of Successful Reintegration Ceremonies: Dealing with Juvenile Offenders Article Full-text available Mar 1994 BRIT J CRIMINOL John Braithwaite Stephen Mugford Shifting criminal justice practices away from sligmalization and toward rcintegration is no small challenge. The innovation of community conferences in New Zealand and Australia has two structural features that are conducive to reinlegralive shaming: (a) selection of the people who respect and care most about the offender as conference participants (conducing to rcintegration) ; and (b) confrontation with victims (conducing to shaming). Observation of some failures and successes of these conferences in reintegrating both offenders and victims is used to hypothesize 14 conditions of successful reinlegration ceremonies. View Show abstract Classification for Effective Rehabilitation: Rediscovering Psychology Article Full-text available Mar 1990 CRIM JUSTICE BEHAV D. A. Andrews James Bonta Robert D. Hoge Reviews 4 principles of classification for rehabilitation: risk, need, responsivity, and professional override in the context of basic research and theory in the psychology of criminal conduct. Risk, need, and responsivity considerations in the psychology of criminal conduct may better reflect knowledge and opinion regarding discretionary services for purposes of rehabilitation than does the discounting of knowledge so characteristic of major portions of mainstream criminology. (PsycINFO Database Record (c) 2012 APA, all rights reserved) View Show abstract Research in Criminology Book Jan 1990 Anne L. Schneider View Crime, Shame and Reintegration Book Mar 1989 John Braithwaite http://johnbraithwaite.com/monographs/ View Show abstract The Truly Disadvantaged: The Inner City, The Underclass, and Public Policy Book Jan 1987 William Julius. Wilson "The Truly Disadvantagedshould spur critical thinking in many quarters about the causes and possible remedies for inner city poverty. As policy makers grapple with the problems of an enlarged underclass they—as well as community leaders and all concerned Americans of all races—would be advised to examine Mr. Wilson's incisive analysis."—Robert Greenstein,New York Times Book Review "'Must reading' for civil-rights leaders, leaders of advocacy organizations for the poor, and for elected officials in our major urban centers."—Bernard C. Watson,Journal of Negro Education "Required reading for anyone, presidential candidate or private citizen, who really wants to address the growing plight of the black urban underclass."—David J. Garrow,Washington Post Book World Selected by the editors of theNew York Times Book Reviewas one of the sixteen best books of 1987. Winner of the 1988 C. Wright Mills Award of the Society for the Study of Social Problems. View Show abstract Community Justice/Restorative Justice: Prospects for a New Social Ecology for Community Corrections Article Sep 1996 Gordon Bazemore Martha Schiff Community corrections policies and programs have lacked a framework which articulates strategies for engaging community groups and defines roles for citizens in the corrections process. In this paper we critique both traditional approaches to community corrections based on an individual treatment model and the new “get tough” approaches which emphasize punitive sanctions and surveillance. We outline a restorative justice model as an alternative to both of these one‐dimensional, case‐driven approaches. The restorative model targets victims, communities, and offenders for intervention and attempts to engage each of these correctional clients in an effort to repair harm, strengthen communities, and reintegrate offenders following appropriate sanctioning. Obstacles to implementation and threats to cooptation and dilution of a restorative agenda are discussed. View Show abstract The Punitive Juvenile Court and the Quality of Procedural Justice: Disjunctions Between Rhetoric and Reality Article Oct 1990 CRIME DELINQUENCY Barry C. Feld The quality of procedural justice is especially relevant to recent changes in juvenile courts' sentencing policies. Punitiveness is reflected in (a) changes in juvenile code purpose clauses and court decisions endorsing punishment; (b) juvenile sentencing statutes and correctional guidelines that employ proportional, determinate, or mandatory sentences; and (c) evaluations of dispositional decision making and conditions of institutional confinement. The shift from treatment to punishment raises basic issues of procedural justice, especially the delivery of legal services. As juvenile courts' sentencing practices resemble increasingly those of their criminal counterparts, does any reason remain to maintain a separate court whose sole distinguishing characteristic is its persisting procedural deficiencies? View Show abstract Toward Community-Oriented Policing: Potential, Basic Requirements, and Threshold Questions Article Jan 1987 CRIME DELINQUENCY Herman Goldstein Recent research that has questioned the value of traditional policing methods has led to experiments with new forms of policing. With increasing frequency, these experiments place greater dependence, for police effectiveness, upon redefining the relationship that the police develop with the community. Out of these efforts, a concept of community-oriented policing is beginning to evolve that—when fully developed—could provide the dominant framework to which all future improvement efforts in policing are linked. A number of minimum requirements for moving in this direction are already identifiable. Most important, among these, is the need to assure that the police engage more directly in dealing with the substantive problems of concern to the communities they serve. Full development of community-oriented policing will require that a number of tough questions first be addressed. Four of these are identified and explored in the article. View Show abstract The Severity of Official Punishment for Delinquency and Change in Interpersonal Relations in Chinese Society Article Nov 1994 J RES CRIME DELINQ Lening Zhang Steven F. Messner This study examines the effects of severity of official punishment for delinquency on the probability of estrangement from four types of significant others—parents, relatives, friends, and neighbors—for a sample of youths in Tianjin, China. Drawing on the labeling perspective, we hypothesize that more severe punishments tend to increase the likelihood that youths experience interpersonal estrangement. We further hypothesize that the strength of the effects of punishment severity on estrangement will vary across types of interpersonal relations. Given the preeminent role of the family in Chinese society, the effect of severity of punishment is expected to be weakest for estrangement from parents and strongest for estrangement from neighbors. The results are generally consistent with expectations, revealing nonsignificant effects of severity of official punishment for delinquency on estrangement from parents and relatives and significant effects only for estrangement from friends and neighbors. In addition, the observed patterns of estrangement in China differ in certain respects from those previously reported in the United States, which suggests that the consequences of labeling for juvenile delinquency are conditioned by the larger sociocultural context. View Show abstract Juvenile Arbitration: Net Widening and Other Unintended Consequences Article Nov 1989 J RES CRIME DELINQ Mark Ezell This study seeks to determine whether a juvenile arbitration program can alter the reach of the court in a unique fashion. Using an interrupted time-series design with a comparison group, it shows that the preprogram trend of increasing rates of judicial handling shifted to a decreasing pattern but that the rates of judicial supervision continued to climb. In addition, there were changes in the court's decision making relating to probation and commitment to residential programs associated with the implementation of the arbitration program. The author concludes that this new style of diversion, one that is sanction oriented, results in larger numbers of youth being in the system longer, subject to system requirements and control. View Show abstract Conditions of Successful Degradation Ceremonies Article Mar 1956 Harold Garfinkel The abstract for this document is available on CSA Illumina.To view the Abstract, click the Abstract button above the document title. View Show abstract Is Incarceration Really Worse? Analysis of Offenders' Preferences for Prison Over Probation Article Mar 1993 Ben M. Crouch Recent correctional reforms have ameliorated the deprivations of prison and indirectly have caused states to toughen probation because many offenders must be diverted from incarceration to meet court-defined limits on prison crowding. These changes raise the possibility that offenders increasingly may view prison as easier or less punitive than probation. Using interview data from newly incarcerated Texas offenders, this analysis examines the extent to which offenders prefer incarceration when presented with choices between paired prison and probation sentences. Though a number of demographic and experiential variables are examined, multivariate analysis reveals that being African-American is the strongest predictor of a preference for prison. Implications of these results are discussed. View Show abstract Delinquent Reform and the Labeling Perspective Article Jun 1985 CRIM JUSTICE BEHAV Gordon Bazemore This article examines the utility of the labeling perspective in the explanation of reform among delinquents. In the labeling view, juvenile court labeling is expected to increase the probability that offending will be extended into the adult years. Further, change in delinquent identity, or the internalization of the delinquent label, is argued to mediate the labeling/reform relationship. Using data on a cohort of delinquents followed for 15 years, an empirical test of this labeling interpretation is presented. This test is replicated in the case of “positive” labeling where the effects on reform of labeling by the school are expected to be mediated by positive self-esteem. A common alternative explanation of the posited relationship between labeling and subsequent offending focused on individual variation in delinquent involvement is also examined using these data. Findings challenge the traditional labeling view that changes in self-esteem or delinquent identity (i.e., “acceptance” of the label) are required intervening processes in the relationship between labeling and future offending or reform. The alternative explanation of the labeling/reform relationship is also not supported in these data. An organizational level interpretation and new research directions are suggested. View Show abstract Improving Policing: A Problem-Oriented Approach Article Apr 1979 CRIME DELINQUENCY Herman Goldstein The police have been particularly susceptible to the "means over ends" syndrome, placing more emphasis in their improvement efforts on organization and operating methods than on the substantive outcome of their work. This condition has been fed by the professional movement within the police field, with its concentration on the staffing, management, and organization of police agencies. More and more persons are questioning the widely held assumption that improvements in the internal man agement of police departments will enable the police to deal more effectively with the problems they are called upon to handle. If the police are to realize a greater return on the investment made in improving their oper ations, and if they are to mature as a profession, they must concern them selves more directly with the end product of their efforts. View Show abstract The New Marginal Youth Article Jul 1984 CRIME DELINQUENCY Kenneth Polk This discussion emphasizes the centrality of the school in considering policy for delinquency prevention and control. Several general processes are suggested whereby schooling itself contributes to youth alienation. A major problem identified is an apparent growth in the number of marginal youth resulting when less successful students are confronted with not only an unpleasant school experience, but a future of limited hope in terms of an occupational career. This situation is seen as having its origins in the rapid changes occurring in the world of work, whereby limited opportunities for long-term work careers are available to those without higher education and technical credentials. As a counter to the resultant alienation, forms of youth action are proposed that both engage young persons in useful and paid work, and integrate marginal youth into the mainstream of school and community life. View Show abstract What Do Alternative Sanctions Mean? Article Mar 1996 U CHICAGO LAW REV Dan M. Kahan American jurisdictions have traditionally resisted fines and community service as alternatives to imprisonment, notwithstanding strong support for these sanctions among academics and reformers. Why? The answer, this article contends, is that these forms of punishment are expressively inferior to incarceration. The public expects punishment not only to deter crime and to impose deserved suffering, but also to make accurate statements about what the community values. Imprisonment has been and continues to be Americans' punishment of choice for serious offenses because of the resonance of liberty deprivation as a symbol of condemnation in our culture. Fines and community service either don't express condemnation as unambiguously as imprisonment, or express other valuations that Americans reject as false. The article also uses expressive theory to explain why the American public has consistently rejected proposals to restore corporal punishment, a form of discipline that offends egalitarian moral sensibilities; and why the public is now growing increasingly receptive to shaming punishments, which unlike conventional alternative sanctions signal condemnation unambiguously. View Show abstract What's “New” About the Balanced Approach? Article Feb 1997 JUVENILE FAM COURT J Gordon Bazemore Over the past decade, many juvenile justice professionals became familiar with the “Balanced Approach as a new mission for juvenile probation. In recent months, a number of jurisdictions have adopted the Balanced Approach, by statute or policy, as the mission for their juvenile courts and juvenile justice systems. However, a great deal of misunderstanding persists about the meaning and practical differences between the Balanced Approach and other intervention models. While both quality and consistency of implementation of “balanced” policy and practice vary widely, some juvenile justice managers are using this new mission as a tool or “roadmap” for comprehensive re-structuring of juvenile justice systems and agencies. This paper argues that when viewed as a guide to systemic, rather than programmatic, reform, the Balanced Approach can be clearly distinguished from both the traditional individual treatment and the new retributive/punitive juvenile justice missions. Six critical differences between the Balanced Approach and these missions are described. View Show abstract Reintegrative Shaming and Regulatory Compliance Article Aug 1994 CRIMINOLOGY T. Makkai John Braithwaite Australian nursing home inspection teams are partitioned into those with an enforcement ideology supportive of reintegrative shaming, those who believe in being tolerant and understanding when confronted with noncompliance with the law, and those with a more stigmatizing ideology toward noncompliers. Nursing homes visited by teams with a reintegrative shaming ideology display significantly improved compliance in the period following the inspection. Nursing homes visited by inspection teams with a more stigmatizing attitude toward noncompliance display an approximately equal drop in compliance. The performance of homes visited by tolerant and understanding inspection teams falls between these two extremes. A more specific test of the theory shows that when interdependency exists between the nursing home and the inspection team, reintegrative shaming has a stronger positive effect on improving compliance. In nursing homes with no link between the home and the inspection team, reintegrative shaming has no effect on compliance levels. These effects demonstrate both the importance and the limitations of reintegrative shaming as a theoretical concept worthy of further empirical investigation. View Show abstract The Impact of Mediating Victim Offender Conflict: An Analysis of Programs in Three States Article Feb 1992 JUVENILE FAM COURT J Mark S. Umbreit Robert B. Coates This article presents the findings of an analysis of victim offender mediation programs working with the juvenile courts in Albuquerque (NM), Minneapolis (MN) and Oakland (CA). The study is based upon 868 interviews with crime victims and offenders, including pre- and post-mediation interviews and two different comparison groups.
The data that emerged from this study indicates that the vast majority of both victims and young offenders experience the mediation process and outcome (restitution agreement) as fair and are satisfied with the program. The mediation process used by the programs in Albuquerque, Minneapolis and Oakland results in greater satisfaction, greater perception of fairness and higher restitution completion rates than found in a matched sample of victims and offenders who were not referred to mediation. View Show abstract New Wine and Old Wineskins: Four Challenges of Restorative Justice Article Jun 1993 Daniel W. Van Ness Dissatisfaction with the current paradigm of criminal justice is leading to new programs with different visions. Some, such as restitution, can be incorporated into existing structures. Others, such as victim-offender reconciliation, point to a possible new approach to criminal justice—restorative justice. In some ways, restorative justice is simply a new application of an ancient vision. It is new wine from old vines. But those of us who celebrate the harvest are advised to remember the parable of new wine and old wineskins. Before we begin to pour—before we insert restorative features into familiar responses to crime—we would do well to reflect on what the consequences may be.
This article has considered four likely consequences: the challenge to abolish criminal law, the challenge to rank multiple goals, the challenge to determine harm rationally, and the challenge to structure community-government cooperation. Although each challenge is significant, I have argued that all can be effectively addressed. Indeed, they must be if criminal justice is to become—using Justice John Kelly's image—a means of healing the wounds of crime. View Show abstract Community Structure and Crime: Testing Social-Disorganization Theory Article Jan 1989 W. Byron Groves Robert J. Sampson Shaw and McKay's influential theory of community social disorganization has never been directly tested. To address this, a community-level theory that builds on Shaw and McKay's original model is formulated and tested. The general hypothesis is that low economic status, ethnic heterogeneity, residential mobility, and family disruption lead to community social disorganization, which, in turn, increases crime and delinquency rates. A community's level of social organization is measure in terms of local friendship networks, control of street-corner teenage peer groups, and prevalence of organizational participation. The model is first tested by analyzing data for 238 localities in Great Britain constructed from a 1982 national survey of 10,905 residents. The model is then replicated on an independent national sample of 11,030 residents of 300 British localities in 1984. Results from both surveys support the theory and show that between-community variations in social disorganization transmit much of the effect of community structural characteristics on rates of both criminal victimization and criminal offending. Sociology View Show abstract Punishment and Modern Society: A Study in Social Theory Article Nov 1991 CONTEMP SOCIOL David Garland In this path-breaking book, David Garland argues that punishment is a complex social institution that affects both social relations and cultural meanings. Drawing on theorists from Durkheim to Foucault, he insightfully critiques the entire spectrum of social thought concerning punishment, and reworks it into a new interpretive synthesis. "Punishment and Modern Society is an outstanding delineation of the sociology of punishment. At last the process that is surely the heart and soul of criminology, and perhaps of sociology as wellâpunishmentâhas been rescued from the fringes of these 'disciplines'. . . . This book is a first-class piece of scholarship."âGraeme Newman, Contemporary Sociology "Garland's treatment of the theorists he draws upon is erudite, faithful and constructive. . . . Punishment and Modern Society is a magnificent example of working social theory."âJohn R. Sutton, American Journal of Sociology "Punishment and Modern Society lifts contemporary penal issues from the mundane and narrow contours within which they are so often discussed and relocates them at the forefront of public policy. . . . This book will become a landmark study."âAndrew Rutherford, Legal Studies "This is a superbly intelligent study. Its comprehensive coverage makes it a genuine review of the field. Its scholarship and incisiveness of judgment will make it a constant reference work for the initiated, and its concluding theoretical synthesis will make it a challenge and inspiration for those undertaking research and writing on the subject. As a state-of-the-art account it is unlikely to be bettered for many a year."âRod Morgan, British Journal of Criminology Winner of both the Outstanding Scholarship Award of the Crime and Delinquency Division of the Society for the Study of Social Problems and the Distinguished Scholar Award from the American Sociological Association's Crime, Law, and Deviance Section View Show abstract Resilience in the Face of Adversity: Protective Factors and Resistance to Psychiatric Disorder Article Jan 1986 Michael. Rutter Almost since the beginnings of psychiatric practice, there has been a recognition that negative life experiences and stressful happenings may serve to precipitate mental disorders (Garmezy & Rutter, 1985). Nearly 200 years ago, Pinel wrote about the psychiatric risks associated with unexpected reverses or adverse circumstances, and it is reported that his initial question to newly admitted psychiatric patients was: “Have you suffered vexation, grief or reverse of fortune?” Nevertheless, although an appreciation that a variety of stressors may play a role in the genesis of psychiatric disorder has a long history, the systematic study of such effects is much more recent. View Show abstract
Recommended publications Discover more
Article
Restorative Justice and Earned RedemptionCommunities, Victims, and Offender Reintegration
March 1998
· American Behavioral Scientist
Gordon Bazemore
The author provides a comprehensive discussion of the roots of the new reintegrative and restorative justice theories as well as the success of current, preliminary applications of these theories. Arguing that the traditional and opposing theories of the retributive paradigm and the treatment model offer only a simplistic choice between helping or hurting offenders, the author contends that these
... [Show full abstract]
systems fail to address adequately the needs of communities and victims. In place of these two paradigms, he suggests a new model that he terms reintegrative or restorative justice. This new theory, based on specific cultural approaches to crime found in New Zealand, Japan, and elsewhere, seeks to address the needs of communities and victims through apology and reparation, a process that hopefully leads to the reintegration of offenders into society
Read more
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Recruiting | https://www.researchgate.net/publication/247751700_Restorative_Justice_and_Earned_Redemption |
Size thresholds for small companies | Download Table
Download Table | Size thresholds for small companies from publication: Financial reporting by small companies in the UK: the demand for abbreviated accounts | The aim of the study is to provide generalisble evidence of the utility of the statutory financial statements of small companies to the directors. It took the form of a postal questionnaire survey of the directors of a tranche of 385 companies meeting the EC size criteria for... | Financial Reporting, Demand and Finance | ResearchGate, the professional network for scientists.
Table 1
Size thresholds for small companies
Source publication
Financial reporting by small companies in the UK: the demand for abbreviated accounts
Conference Paper
Full-text available
Contexts in source publication
Context 1
... the Companies Act 1985 a company may qualify as small if it satisfies certain size tests and meets other qualification criteria (banking companies, insurance companies and authorised persons under the Financial Services Act 1986 are excluded on the grounds of public interest). As far as size is concerned, the qualifying conditions are met by a company if it does not exceed two or more of the criteria shown for the UK
Table 1
in relation to the financial year concerned and the preceding year. The table also shows the EC maxima in force in 1999 (when the study was conducted) and the most recent EC thresholds which the government proposes are adopted by the UK (DTI, 1999a). ...
Context 2
... major recommendation is that the format and contents of small company accounts should be simplified and small companies should no longer be able to file what are referred to as "uninformative" abbreviated accounts. The Review also recommends that the size thresholds for companies able to use the small company accounting regime should be raised to the maximum allowed under EU law (see
Table 1
). Thresholds for exemption from the audit should be raised in the same way. ...
Context 3
... first logistic regression model was developed to test the hypothesis that the likelihood of the directors choosing to file abbreviated accounts increases inversely with the size of the company as measured by turnover and number of employees respectively (H1). The results are shown in panels A and B in
Table 1
0. The final model tests the hypothesis that the likelihood of the directors choosing to file abbreviated accounts increases with their belief that there are cost benefits in doing so (H3). ...
Context 4
... final model tests the hypothesis that the likelihood of the directors choosing to file abbreviated accounts increases with their belief that there are cost benefits in doing so (H3). The results of this test are shown in panels C of
Table 1
0. Interpreting the table, the probability statistics in panels A and B show that TOVER is significant whereas EMPLS is not. ...
Determinants of Audit Opinion after the Scandals of Enron: Empirical Validation in the French Context
p>This study examines the effect of regulatory changes on audit quality in the French context. The evaluation of the risks and the anomalies carried out by the auditors brings them control relating to the financial statements of the company in order to express an opinion on the effectiveness, the regularity, the sincerity and the faithful image of...
The Environmental balance sheet of nations: reflections on global climate change scenarios
Citations
Does Size Influence the Suitability of the IFRS for SMEs? Empirical Evidence for Germany
This study is set within the context of the IASB's initiative to develop an IFRS for small and medium-sized entities (SMEs). It is based on a questionnaire survey of small and medium-sized entities in Germany exploring the suitability of the IASB's proposed SME standard for entities of different size classes. Quantitative size criteria are used in many national jurisdictions to differentiate financial reporting requirements between entities. However, there is very little empirical evidence on the question whether the economic size of an entity has an impact on the economic issues that should be regulated by accounting rules and on management's preferences for specific accounting methods. This paper addresses these deficiencies by exploring to what extend an entity's economic size has an impact on its international exposure, the relevance of specific accounting issues and preparers’ perceptions on costs and benefits associated with the application of selected accounting methods. Our findings are ambiguous. Size effects are revealed with regard to the structure of entities, their international exposure and to a large extent to the relevance of particular accounting issues. Cost and benefit assessments of accounting methods also differ within and between the size clusters investigated, albeit a generalisation of size as a factor determining the cost-benefit considerations of firms with regard to particular accounting treatments and methods is not supported by the study's results.
| https://www.researchgate.net/figure/Size-thresholds-for-small-companies_tbl1_38176058 |
So, What’s a LIFESTYLE BLOG Anyway ? The New #REASONStoTRAVEL Linkup for Travel and Non-travel Bloggers! - Paperblog
Ever pick up a fashion magazine and notice how there are often articles dedicated to luxury destinations and getaways? That’s because the Editors of fashion magazines know that people need to be able to dream of themselves
So, What’s a LIFESTYLE BLOG Anyway ? The New #REASONStoTRAVEL Linkup for Travel and Non-travel Bloggers!
Ever pick up a fashion magazine and notice how there are often articles dedicated to luxury destinations and getaways? That’s because the Editors of fashion magazines know that people need to be able to dream of themselves WEARING the clothes in order to actually buy them!
Can you imagine how popular fashion magazines would be if they showed you pictures of your already cramped closet, or the dress you bought in 2013 with the tags STILL attached because you’ve never worn it?
This is the connection between fashion and travel and this is why LIFESTYLE BLOGS exist!
Fashion shoots are always in interesting and evocative locations to inspire their readers to want to live a certain lifestyle, a glamorous one, that is conjured up in the pages of Vogue. Along comes the internet and Lifestyle Blogs and you have a totally different perspective an alternative to the imaginary life….REAL ONES.
Lifestyle Blogs are about not presenting a made up life, created solely for the purpose of a magazine, but about sharing real inspiration, recipes, outfits and destinations. Of course not *all* lifestyle blogs include travel, or fashion, but they are two categories that will often go hand in hand.
Don’t get me wrong, as much as I’ve been “inspired” by Vogue’s incredibly perfect and stunning photography, models and clothes ….they always remain out of my reach and can get boring.
Bloggers. know them – trust them – follow them
I get a lot of different emails from my loyal readers asking very specific questions about my expat mom life in Modena! Questions like:
How do you find the courage to dress up and look pretty as a stay at home mom?
Can I travel alone in Italy with kids?
Do you regret moving so far from your family?
I need to go to 5 weddings and a baptism this summer and I’m on a budget, what should I wear?
Where should I go in Bologna for a nice evening?
Sometimes I’ve never heard from these readers before and their emails come out of left field, but they make me SO HAPPY! I guess you don’t really realize that people are reading until they start to ask questions! THANK YOU!
When I get emails that say “my husband and I were going to avoid Italy because he is Celiac, but thanks to your posts on gluten free eating we’re planning a trip!” , or “I usually live in my pjs but you’ve inspired me to make more effort with my style”, it is a reminder that blogging is useful! As useful as journalism, or fiction, or documentary film making or any other medium that shares, informs and inspires.
I bought a copy of Vogue the other day. I’ve been so used to the “amateur” photography of blogs that I had forgotten what a *real* photoshoot looked like. Each page was more beautiful than the next, perfection. But perfect is not what I’m into these days. I’m into real life, so I read blogs likeDiary of an Urban Housewifewho takes me through the stunningtulips of the Netherlandswith her family and Pretty Thing and Co., another expat living in Rome and blogging about everyday life. Ever noticed wild poppies growing in Rome? She has and they are stunning.
I also love reading Ashley’s blogComo Perderse en Espagna. She’s a Canadian expat living in Spain and teaching English, who writes detailed articles to help anyone prepare for amove there.Malaysian Meandershas taken me all through Malaysia and back again, and I’ve been planning all the things I’ll dowith my son in Penangthanks to her blog! Kelly from A Lovely Life Indeed kicks my butt into working out while also taking me through the beautiful streets of Galicia. Then there’s Angele fromThe European Malteserwho shares her style but also wonderful evenings inBrusselsand murder mystery dinners with friends (jealous!!)
I also love reading other moms who blog about life like Zaz fromMama and More. A while back she did a whole series on London and it was great to get an insider’s view of the city not from a guide book, but from another mom, who I’ve grown to trust and like because of her blog. When she reviews and suggests a restaurant or market I just know I’ll like it. Recently Hannah from Mums Days decided to take her son Reuben (who is around the same age as my son) to all of the castles in the Northumberland region. I didn’t even know there were that many castles out there and have loved following along, especially the Dally Castle!
Zaz from Mama and More
Madaline from Pretty Thing & Co
Marta from Sweaters, Stripes and Sweets
Angela from the European Malteser
One of the blogs I read almost daily is Becoming a Stay at Home Mom. I never find time to comment but she is my first read in the morning, usually at 4:30am as I’m getting out of bed. Her little Monkey is the same age as my son and she stays home with him and her new baby. We’ve never met, but we have so much in common! She takes him out on wonderful local adventures in Leeds and her son goes through ALL the same phases as mine! I also loveHonest Mumand herluxury getawayseven with young kids! As an expat I’m physically disconnected from Toronto, but through blogs I can stay up to date on what’s happening in the city like the new Aquarium, thanks to Toronto bloggers like Marta from Sweaters, Stripes and Sweets, Susan fromAva Grace’s Closetand Jane from Toronto Shopaholic.
This is what inspires me.
Mytwo weeks in Copenhagenwere planned almost entirely through blogs. I found thisawesome indoor play spacefor in the area where we were renting our apartment through the blogRookie Mom! She’s not a travel blogger but I’m so glad she blogged all about her trip to Copenhagen with her kids. She has SO MANY great tips to offer if you are visiting the city, and although her post is from 2010, ALL of it was still helpful and relevant. I’m grateful she took the time to blog so many great suggestions that no one EVER writes about because they may not seemimportant. Even though the REMISEN playspace isn’t a tourist destination, it helped me plan a fantastic day. We took our son there all morning, he got tired out and after lunch he slept while we enjoyed three (UNDISTURBED) HOURS of museum going as a couplewith our friends! Best Vacation Day Ever!
Notice a theme? Writing about your travels, even if you don’t have a strict travel blog is a great way to help others plan their trip!
EXPO2015 in Milan – Come with me!
Tomorrow is May 1st and so begins the International EXPO 2015 held in Milan, Italy. I’m an EXPO OPTIMIST Blogger and will be sharing with you throughout the EXPO, follow the hashtag #expottimisti! I’m so excited about what I will do, eat and of course….wear!
In order to celebrate this I thought it was finally time I gave more space on my LIFESTYLE BLOG to my other passion….travel!
So beginning tomorrow you’ll have the chance to linkup any and all of your travel posts on the #REASONStoTRAVEL linkup, a new linkup dedicated to travel bloggers and non travel bloggers who want to share their local and international adventures.
This opens on the 1st of every month and is open for THE WHOLE MONTH. You will find a dedicated page on my blog with the most recent linkup and I would LOVE FOR YOU TO DISCOVER NEW BLOGS AND INSPIRATION through this linkup.
This linkup is being supported and co-hosted by 4 other incredible travel bloggers who will also have the linked up present on their blogs!! We will also be retweeting tweets with the #REASONStoTRAVEL hashtag, and I hope you will share our enthusiasm and share what you love!
These are the rules and I hope to see you tomorrow!
#REASONStoTRAVEL
A place for everyone to share their travels.
You don’t have to be a travel blogger to want to share your favorite local spots or tips on international travel.
#REASONStoTRAVEL is a new linkup, open for the whole monthwhere you can share, discover and explore travel!
SHARE YOUR POST ON TWITTER with the hashtag #REASONStoTRAVEL & you’ll get a retweet from your co-hosts:
REASONS TO DRESS– An Italian Lifestyle Blog About Travel, Fashion and Life in Italy
TWITTER / FACEBOOK / INSTAGRAM /PINTEREST/BLOGLOVIN’
CHASING THE DONKEY– Travel Croatia Like a Local, People, Places, Food and Culture
TWITTER/FACEBOOK/ INSTAGRAM /PINTEREST/BLOGLOVIN’
THE CROWDED PLANET– A Nature and Adventure Travel Blog
TWITTER/FACEBOOK/ INSTAGRAM /PINTEREST/ BLOGLOVIN’
UNLOCKING KIKI- A Travel Blog From An American Expat in Iceland
TWITTER/FACEBOOK/ INSTAGRAM / PINTEREST / BLOGLOVIN’
IN SEARCH OF– A Travel Blog From An American Expat in Vilnius, Lithuania
TWITTER / FACEBOOK / INSTAGRAM / PINTEREST / BLOGLOVIN’
Rules:
Linkup your TRAVEL related posts, new and old!
Add the badge or a link back to ANY of the co-hosts
Follow each co-host on at least 1 social network , we’re friendly, social and generally over-sharers!
Tweet your link with the hashtag #REASONStoTRAVEL for a retweet!
Please be social and visit a post that interests you. Don’t forget to use the #REASONStoTRAVEL hashtag to let people know how you found them!
Happy Travels!
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Identification of an Amygdala–Thalamic Circuit That Acts as a Central Gain Mechanism in Taste Perceptions | Journal of Neuroscience
Research Articles, Behavioral/Cognitive
Identification of an Amygdala–Thalamic Circuit That Acts as a Central Gain Mechanism in Taste Perceptions
Maria G. Veldhuizen , Michael C. Farruggia , Xiao Gao , Yuko Nakamura , Barry G. Green and Dana M. Small
Maria G. Veldhuizen
7 Department of Anatomy, Faculty of Medicine, Mersin University, Ciftlikkoy Campus, 33343, Mersin, Turkey
Michael C. Farruggia
1 Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511 2 Modern Diet and Physiology Research Laboratory, Yale School of Medicine, New Haven, Connecticut 06519 3 Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut 06510
Xiao Gao
8 Faculty of Psychology, Southwest University, Chongqing, 400715, China 9 Key Laboratory of Cognition and Personality, Southwest University, Chongqing, China
Yuko Nakamura
10 The UTokyo Center for Integrative Science of Human Behavior, Tokyo, Japan
Barry G. Green
5 The John B. Pierce Laboratory, New Haven, Connecticut 06519 6 Department of Surgery (Otolaryngology), Yale School of Medicine, New Haven, Connecticut 06510
Abstract
Peripheral sources of individual variation in taste intensity perception have been well described. The existence of a central source has been proposed but remains unexplored. Here we used functional magnetic resonance imaging in healthy human participants (20 women, 8 men) to evaluate the hypothesis that the amygdala exerts an inhibitory influence that affects the “gain” of the gustatory system during tasting. Consistent with the existence of a central gain mechanism (CGM), we found that central amygdala response was correlated with mean intensity ratings across multiple tastants. In addition, psychophysiological and dynamic causal modeling analyses revealed that the connection strength between inhibitory outputs from amygdala to medial dorsal and ventral posterior medial thalamus predicted individual differences in responsiveness to taste stimulation. These results imply that inhibitory inputs from the amygdala to the thalamus act as a CGM that influences taste intensity perception.
SIGNIFICANCE STATEMENTWhether central circuits contribute to individual variation in taste intensity perception is unknown. Here we used functional magnetic resonance imaging in healthy human participants to identify an amygdala–thalamic circuit where network dynamics and connectivity strengths during tasting predict individual variation in taste intensity ratings. This finding implies that individual differences in taste intensity perception do not arise solely from variation in peripheral gustatory factors.
amygdala
fMRI
gustation
perception
taste intensity
thalamus
Introduction
Taste acts as a gatekeeper to our internal milieu, with taste quality tuned to identify potentially nutritive or harmful substances (Breslin, 2013) and taste intensity reflecting concentration, and hence quantity, of these substances. Notably, there are considerable individual differences in taste intensity perception that investigators have endeavored to link with food preferences, diet, and risk for obesity and alcohol consumption (Duffy and Bartoshuk, 2000;Pepino and Mennella, 2007;Hayes et al., 2011;Allen et al., 2014;Thibodeau et al., 2017). Investigations into the source of this variance have ocused primarily on possible peripheral mechanisms, such as allelic variation in the TAS2R38 bitter taste receptor gene or the number of taste papillae, but the evidence for such mechanisms in humans is not strong (for review, seeFeeney and Hayes, 2014). Less well explored is the possible influence of central mechanisms. However, there is evidence that such a mechanism may exist. Studies of the phenomenon of thermal taste, in which some individuals perceive taste sensations from temperature alone (Cruz and Green, 2000), has shown that the ability to perceive thermal taste is significantly correlated with ratings of the perceived intensity of chemical tastes and the sweet odorant vanillin (Green and George, 2004;Green et al., 2005;Lim et al., 2008). Importantly, the same studies also showed that the individuals who perceived thermal taste did not rate oral somatosensory sensations of creaminess, spiciness, and astringency or thermal sensations produced on the lip and hand any higher than individuals who did not perceive thermal taste. The specificity of these correlations to taste and olfactory stimuli rules out a cognitive bias or differences in scale usage as significant factors in the individual differences. Furthermore, because taste, olfaction, and somesthetic stimulation (temperature, creaminess, and chemical irritation) are all transduced by different peripheral receptors and cranial nerves, these data suggest that the correlations are driven primarily by a central neural mechanism that is common to taste and smell but not to somesthesis (Green and George, 2004;Green et al., 2005).
The neurobiology of such a “central gain mechanism” (CGM) is unexplored. However, early evidence of taste perception in patients who had undergone surgical resection of the anterior medial temporal lobe for the treatment of pharmacologically intractable epilepsy suggests amygdala involvement. Specifically, resections involving the amygdala, particularly from the right hemisphere, result in reduced sour taste detection thresholds (i.e., increased sensitivity;Small et al., 1997) and stronger ratings of the perceived intensity of suprathreshold taste stimuli (Small et al., 2001a,b). These paradoxical observations have been interpreted as evidence for an inhibitory influence from the amygdala to either the gustatory cortex in the insula, or to earlier taste relays (Small et al., 2001b). Blood oxygenation level-dependent (BOLD) responses in the central nucleus are sensitive to modulation of intensity perception (Small et al., 2003), and there are reciprocal connections between the amygdala and the insular taste cortex (Wang et al., 2018), the gustatory thalamus [ventral posterior medial nucleus (VPM);Krettek and Price, 1977], and brainstem [rostral nucleus of the solitary tract (NST);Norgren, 1976] relays. In addition, the amygdala has previously been described as conferring gain during directed attention by biasing signals to modulate early sensory cortex, assigning greater “weights” to emotionally relevant or salient sensory events (Vuilleumier, 2015).
The current study was designed to test the hypothesis that individual variation in taste intensity perception is associated with inhibitory projections from the amygdala to gustatory regions. Our approach was to assess BOLD response to sweet, sour, salty, and bitter tastants in 28 healthy participants using regression, psychophysiological measurement, and dynamic causal modeling (DCM) analyses to determine whether (1) amygdala response to the tastants covaried with the mean intensity rating across tastants; (2) the responsive region of the amygdala was functionally coupled to gustatory regions including brainstem, thalamus, and insula; and (3) using Bayesian model estimation, whether inhibitory influences from the amygdala to gustatory regions (i.e., effective connectivity;Friston et al., 2011) characterize gustatory network dynamics associated with intensity perception.
Materials and Methods
Participants
Thirty right-handed, nonsmoking participants [21 women, 9 men; mean age, 27.53 ± 4.99 years; age range, 18–38 years; mean body mass index (BMI), 21.67 ± 2.88 kg/m 2; BMI range, 16.08–26.93 kg/m 2], with a mean Edinburgh Handedness Inventory (Oldfield, 1971) score of 90.17 ± 11.41, participated in the current study. They were recruited through advertisements around Yale University and the city of New Haven. The Yale School of Medicine Human Investigation Committee approved the informed consent form, which was subsequently obtained from all study participants. All participants reported having no known taste, smell, neurologic, psychiatric, or other pathologic disorders. Two (of the original 30) participants were excluded because one participant's average taste intensity rating was <2 SDs from the sample mean and another participant's head movements during scanning exceeded a predetermined limit of 1 mm of movement in any direction. The remaining 28 participants (20 women and 8 men) were a mean age of 27.14 ± 4.75 years with an age range of 18–37 years, and had a mean BMI of 21.58 ± 2.96 kg/m 2with a range of 16.08–26.93 kg/m 2.
Taste stimuli and delivery
The taste stimuli consisted of a sweet [0.32 msucrose (Su), Sigma-Aldrich], sour (5.6 × 10 −3 mcitric acid (CA)], salty [0.14 msodium chloride (NaCl)], bitter [3.2 × 10 −5 mquinine sulfate (Qu)], and a “tasteless” solution designed to mimic the ionic components of saliva (O'Doherty et al., 2001). We used the tasteless solution as the control stimulus because water activates taste cortex (Frey and Petrides, 1999;Zald and Pardo, 2000) and is sometimes reported to have a taste (Bartoshuk et al., 1964). The tasteless solution was mixed to the following five different concentrations: 18.75 m mKCl/1.875 m mNaHCO3 in distilled water, and its 75%, 50%, 25%, and 12.5% dilutions. Liquids were delivered to the participants through a portable gustometer system as 0.5 ml of solution infused into the mouth over 4 s. Detailed description of the gustometer system can be found in previous publications (Veldhuizen et al., 2007,2011b).
Experimental procedures
Participants took part in one training and taste psychophysics session, and one fMRI scanning session. Sessions were conducted on separate days.
Training and taste psychophysics session.
This session served to select an appropriate tasteless solution for each participant; assess reliable intensity ratings of four tastants representing sweet, sour, salty, and bitter qualities; familiarize participants with the fMRI task' and identify those who found it uncomfortable to perform the task in a simulated fMRI environment. Participants were instructed to refrain from eating or drinking anything other than water for at least an hour before the session. Upon arrival, they received a detailed explanation of the study. After participants read and signed the consent form, anthropometric measurements were taken. Body weight was measured to the nearest 0.1 kg using a calibrated Seca mBCA 514 medical Body Composition Analyzer (Itin Scale Company) with light clothes on only, and height was measured to the nearest 0.1 cm using a calibrated Seca Digital stationary stadiometer (Itin Scale Company). Body mass index (BMI) was calculated as weight (in kilograms) divided by the squared height (in meters) of the participant (BMI = kg/m 2). Participants were then presented with the five versions of the tasteless solution and selected the one that “tastes most like nothing” in a sequential pairwise choice procedure.
Next, training on how to use the general labeled magnitude scale (gLMS) was provided. The gLMS is an experimentally derived scale validated for use in describing the breadth of intensities an individual can experience in daily life, from sights and sounds to tastes and pains (Green et al., 1993,1996;Bartoshuk et al., 2004). The scale consists of a vertical line bounded by the labels “no sensation” at the bottom and “strongest imaginable sensation” at the top, with the intensity labels “barely detectable,” “weak,” “moderate,” “strong,” and “very strong” spaced quasi-logarithmically along the scale (Green et al., 1993). We then asked participants to use the gLMS, which was presented via computer, to rate the intensity of imagined stimuli, such as the sweetness of milk and the bitterness of fresh spring water as well as actual pure taste stimuli and taste stimuli in mixtures.
Following gLMS training, participants were brought to the fMRI simulator and outfitted with the taste delivery system. Participants lay supine within the simulated bore and were asked to rate the intensity of their feelings of hunger, fullness, thirst, anxiety, and need to urinate. Next, participants used the gLMS to rate the perceived intensity of the four taste stimuli and the tasteless solution they had selected. Each taste stimulus and tasteless solution was delivered eight times, resulting in 40 trials in total. The order of stimulus delivery was randomized across participants. In each trial (Fig. 1 A), the participant was instructed to swallow immediately after receiving each liquid and then rate the intensity of the specific taste quality of that tastant (sweetness, saltiness, sourness, bitterness;Fig. 1 B). When they received the tasteless solution, they were asked to rate overall intensity, since there is no specific taste quality associated with this stimulus. Participants then made a second set of internal states. Liking was measured using a labeled hedonic scale (Lim et al., 2008) consisting of a vertical line scale with the labels “most disliked sensation imaginable” at the lower anchor point, “most liked sensation imaginable” at the upper anchor point, “neutral” in the middle, and “(dis)like slightly,” “(dis)like moderately,” “(dis)like very much,” and “(dis)like extremely” spaced quasi-logarithmically along the scale. Familiarity and wanting were rated using two different visual analog scales. For wanting, “How much do you want to eat more of this?” (“I would never want to eat this” on the left anchor, “Neutral” in the middle, “I would want to eat this more than anything” on the right anchor); for familiarity, “How familiar is this taste?” (“Not familiar at all” on the left anchor, “Neutral” in the middle, “Very familiar” on the right anchor). All of the ratings were conducted in the bore of the simulator using a mouse on a computer monitor viewed via backprojection on a headcoil-mounted mirror. Finally, participants underwent a simulation of a single scanner run, described in detail below.
fMRI scanning session.
The fMRI scanning session took place on a separate day after the training and taste intensity rating session. Participants provided internal state ratings as well as perceptual ratings of the stimuli before and after scanning. Four taste runs were completed during this session. Each run was 9 min and 40 s long, and consisted of the uncued delivery of five different types of stimuli in eight blocks. Blocks had four, six, or eight repeats of the same stimulus. Each run consisted of one block for each of the four taste qualities [throughout this article referred to as taste(Su), taste(CA), taste(NaCl), and taste(Qu)] and four tasteless blocks. A tasteless block was coded as the tasteless control for the tastant that, within a given run, had the same number of repeats in a block [referred to as tasteless(Su), tasteless(CA), tasteless(NaCl), and tasteless(Qu)]. In a block, a repeat of a stimulus presentation consisted of an “on” period of 3 s, during which we presented 0.5 ml of liquid, which was followed by a 6 s interval during which the subject is instructed to swallow (Fig. 1 C). Following each block, there is a 1 ml rinse with water followed by a 10 s rest. The participants were instructed to swallow after receiving each liquid and to keep their eyes closed during the entire run. The order of four taste stimuli blocks and four tasteless blocks within each run was counterbalanced, and the order of the runs was counterbalanced across participants. The number of repeats across taste blocks in this protocol was designed for collapsing across taste qualities and to provide balanced presentation of taste and tasteless blocks. Block design was chosen to improve power within participants and is favored for DCM analyses (Daunizeau et al., 2011).
fMRI scanner.
Images were acquired on a Siemens TIM Trio 3T MRI Scanner equipped with a 32-channel head coil. Echoplanar imaging (EPI) was used to measure the BOLD signal as an indication of cerebral brain activation. A susceptibility-weighted echoplanar method with multiband acceleration factor 4 and GRAPPA (generalized, autocalibrating, partially parallel acquisitions) factor 2 was used to image the regional distribution of the BOLD signal with the following parameters: TR, 1000 ms; TE, 30 ms; flip angle, 60°; FOV, 220 mm; matrix, 64 × 64; slice thickness, 2.5 mm; number of slices, 60. Slices were acquired in an interleaved mode, to reduce the cross talk of the slice selection pulse, and in coronal orientation, to cover the medulla oblongata of the brainstem, where the nucleus of the solitary tract is located. In total, 2376 volumes (594 volumes per run) were acquired. At the beginning of each functional run, the MR signal was allowed to equilibrate over two scans (“dummy images”) for a total of 2 s, which were then excluded from analysis. Anatomical scans were acquired with T1-weighted MPRAGE (magnetization-prepared rapid gradient-echo sequence; TR/TE, 1900/2.52 ms; flip angle, 9°; FOV, 256; matrix, 256 × 256; slice thickness, 1 mm; number of slices, 176). EPI-based field maps were also acquired to correct for susceptibility-induced geometric distortions.
Figure 1.
Overview of task design. A, Chronological events and their duration in a trial during the taste psychophysics session. Each trial commenced with a taste delivery of.5 ml over 2 s. The participant was instructed to swallow immediately after receiving each liquid and then rate the intensity of taste. The intensity scale disappeared from the screen after ∼7 s or as soon as the rating was submitted by clicking a mouse button, whichever occurred first. Then a water rinse of 1 ml was presented over 4 s, followed by a rest period of 10 s before the next trial started, except after the tasteless stimulus, which was immediately followed by the next trial. B, The gLMS that was used for measuring perceived taste intensity. The specific taste quality to be rated (e.g., “sweetness” for sucrose and “saltiness” for sodium chloride) was indicated above the scale. When a participant received the tasteless solution the label was “overall intensity,” since no specific taste quality is associated with this stimulus. Participants used a scanner-compatible handheld trackball mouse to make ratings. The horizontal red cursor tracks up and down the scale with vertical mouse position, and clicking the left mouse button submitted the rating. A new gLMS then appeared on the screen to rate the next taste stimulus. C, Chronological events during a run in the fMRI session. Each block consisted of four, six, of eight repeats of a taste stimulus. Each repeat consists of a taste stimulus presentation over 2 s (0.5 ml), followed by a 7 s interval for swallowing. At the end of each block, a water rinse is presented over 4 s (1 ml), followed by a 15 s rest period before the start of the next block. Tasteless blocks are identical except that there is no water rinse before the 15 s rest period. Each run contained four taste blocks (one for each taste quality) and four tasteless blocks. No intensity ratings were made during the fMRI run.
Data analysis
Behavior.
Taste intensity ratings made on the gLMS for each trial and each participant were first log 10transformed before statistical analysis. Eight intensity ratings for each of the tastants and the tasteless solution were then averaged within each participant, respectively. We ran a one-way repeated-measures ANOVA with GraphPad Prism version 7.01 for Windows to test for differences in average perceived intensity differences between the different stimuli. We performed paired ttests with Bonferroni correction for 15 possible multiple comparisons. For each pair of different taste solutions (i.e., sweet–sour, sweet–salty sweet–bitter, sour–salty, sour–bitter, and salty–bitter) we then calculated the Pearson product-moment correlation of log-mean intensity ratings across participants. We performed one-tailed significance tests due to the strong a priori prediction of positive correlations between the intensities of the taste solutions and the absence of any rationale for a negative correlation. We then corrected for multiple comparisons using a Bonferroni correction for a total of six tests, leading to an α of 0.0167. We averaged across the taste solutions that showed significant correlations in intensity to calculate a grand average score for each participant's taste intensity ratings. This included sweet, sour, and salty tastants, and excluded quinine as a tastant (see Taste psychophysics in the Results section). We used principal component analysis in R studio to confirm the existence of more than a single component in the variance across participants. We calculated a grand taste intensity score for each participant by averaging ratings for sweet, sour, and salty tastants, referred to hereafter as the mean logintensity μ(Su CA NaCl)to be used in subsequent data analyses. Data visualizations were created with GraphPad Prism (scatterplots) and ggplot2 package for RStudio.
fMRI analysis.
Data were analyzed on Linux workstations using MATLAB R2011a (MathWorks) and SPM12 (Wellcome Trust Center for Neuroimaging, London, UK). All functional images from each participant were corrected for geometric distortions caused by susceptibility-induced field inhomogeneities. A combined approach was used that corrects for both static distortions and changes in these distortions attributable to head motion (Andersson et al., 2001;Hutton et al., 2002). The static distortions were calculated for each participant by acquiring a field map and processing it using the FieldMap toolbox implemented in SPM12 (Hutton et al., 2004). The images were then realigned, unwarped, and coregistered to the participant's own anatomic T1 image. The anatomic T1 image was processed using a unified segmentation procedure combining segmentation, bias correction, and spatial normalization (Ashburner and Friston, 2005); the same normalization parameters were then used to normalize the functional images. Then, all functional images were detrended using a method for removing any linear components matching the global signal at each voxel (Macey et al., 2004). Finally, functional images were smoothed with a 6 mm FWHM isotropic Gaussian kernel.
For the time-series analysis on all participants, a high-pass filter (300s) was included in the filtering matrix (adjusted from the convention in SPM12 to reflect the maximal period between two blocks of tasteless) to remove low-frequency noise and slow drifts in the signal. Condition-specific effects at each voxel were estimated using the general linear model (Friston et al., 1995;Worsley and Friston, 1995). The response to events was modeled using a canonical hemodynamic response function included in SPM12. The temporal derivative of the hemodynamic response function was also included as part of the basis set to account for up to 1 s shifts in the timing of the events (Henson et al., 2002). There were two events of interest: “taste” and “tasteless.” For taste, taste blocks taste(Su), taste(CA), and taste(NaCl) were collapsed into a single event “taste(μ Su CA NaCl),” referring to the mean response to these tastants, parallel to the averaging of the ratings in the analysis for psychophysics. The corresponding tasteless blocks were also collapsed into a single event, “tasteless.” Rinses, taste(Qu), and tasteless(Qu) blocks were each modeled as a nuisance effect. The Artifact Detection Tools (ART) toolbox (https://www.nitrc.org/projects/artifact_detect/) for MATLAB was used to detect global mean and motion outliers in the functional data. Motion parameters were included as regressors in the design matrix at the single-subject level. In addition, image volumes in which the z-normalized global brain activation exceeded 3 SDs from the mean of the run or showed 1 mm of composite (linear plus rotational) movement were flagged as outliers and deweighted during SPM estimation. We additionally calculated a composite movement estimate for each participant, frame-to-frame displacement. Frame-to-frame displacement was calculated by taking the Euclidean distance between the center of gravity of an image and the next image (Satterthwaite et al., 2013). We summed frame-to-frame displacement for all images within a run and subsequently averaged them across runs.
To assess group-level main effects of versus Tasteless independent of differences in individual sensitivity, the parameter estimate images for each participant were entered into a one-sample ttest using individual contrasts of taste(μ Su CA NaCl)-tasteless. We also included all individual grand average scores of taste intensity ratings and composite movement estimates. To test the hypothesis that response in the amygdala would correlate with overall subjective taste intensity perception, we regressed individual grand average scores of taste intensity against BOLD response to taste(μ Su CA NaCl)-tasteless across all 28 participants using a small volume correction (sphere with 6 mm radius, containing 123 voxels) defined from a region of amygdala that we have previously shown codes taste intensity perception (at coordinate [(–) 24 −6 −21]) [30]. The tmap threshold was set at p uncorrected< 0.001 and a cluster size at a minimum of 5 contiguous voxels. Unpredicted clusters were considered significant at p< 0.05, false discovery rate corrected across the whole brain.
Psychophysiological interaction (PPI) analysis (Friston et al., 1997) was used to identify functional connectivity between the area of the amygdala sensitive to taste intensity perception and earlier gustatory relays (insular cortex, thalamus, and brainstem) using small volume corrections (sphere with 6 mm radius, containing 123 voxels) defined by centroids from two prior meta-analyses (at coordinates: [(−)8 −26 8, and (−)10 −14 −8];Veldhuizen et al., 2011a;Yeung et al., 2017). We used two meta-analyses because the first only reported thalamic responses in the mediodorsal (md) thalamus, and we wished to include the gustatory thalamus. Peaks were corrected for multiple comparison across the voxels within the small volumes and then corrected for the number of regions included (insula, thalamus, and brainstem). Regions that showed a main effect of taste(μ Su CA NaCl)-tasteless at the group level or a relation with individual grand average scores were used as seed regions. The first eigenvariate of the time-series data were extracted from a 6 mm sphere with a centroid on the coordinate of the amygdala cluster. The eigenvariate was then deconvolved (Gitelman et al., 2003), multiplied with the psychological variable (taste(μ Su CA NaCl)-tasteless), and reconvolved with a hemodynamic response function to form the PPI term. For each participant, we computed new parameter estimate images with the PPI as a regressor of interest and the time-series eigenvariate and psychological variable as nuisance regressors. In order to examine which areas display increased or decreased connectivity with the seed regions associated with intensity perception, we then regressed individual grand average scores of taste intensity ratings against PPI parameter estimate images across all 28 participants.
DCM was used to characterize associations between individual sensitivity to taste and neural circuitry in a network of regions responding to taste(μ Su CA NaCl)-tasteless. We selected the seed and target regions that resulted from using the central amygdala PPI analysis. We specified a single fully connected and driven DCM between these regions. The DCM specified driving inputs (taste and tasteless regressors) into the network at all five regions. The DCM also specified a complete connectivity matrix for intrinsic, steady-state, bidirectional connections among the five regions. No modulatory effects on the connections between regions were specified, as they are not obligatory (Friston et al., 2003) and the design included no within-participant variables qualifying for modulation in the DCM. We first estimated the full DCM for each individual participant. We then used the second-level parametric empirical Bayes framework (Friston et al., 2016) pruning approach to reduce the model to a configuration of parameters to best explain the data observed in the regions. We used the pruning approach separately for the driving inputs and connectivity matrix (Zeidman et al., 2019a). We created a second-level general linear model with a design matrix that includes a constant factor, a regressor-of-interest for the individual grand average scores of taste intensity, and composite movement estimates as a nuisance variable. This results in a (Bayesian) hierarchical model, with estimates for connection strengths (positive or negative) between regions and their uncertainty (i.e., posterior probability;Zeidman et al., 2019b). There are two sets of estimates, as follows: (1) for a model that describes the average neural circuitry across participants, independent of individual sensitivity to taste; and (2) for a model that describes the neural circuitry associated with individual grand average scores of taste intensity. We display any parameters that showed a probability of >0.90. We used all connectivity parameters to predict individual grand average scores of taste intensity, using a leave-one-out cross-validation (LOOCV) framework. In this regression procedure, a model is fitted to data from all but one participant and a prediction of the score is made for that participant, which is repeated in turn for all participants. This results in a Pearson's correlation between predicted and empirical intensity scores. We used an α of 0.05 to determine significance for this correlation.
Data visualizations were created with GraphPad Prism (GraphPad Software) for scatterplots, ggplot2 for boxplots (R-studio), Mango by Research Imaging Institute, UTHSCSA (for SPMs overlaid on brain sections of the BigBrain (Amunts et al., 2013), and Illustrator for DCM models (Adobe).
Data availability
Raw fMRI data are available upon request. Contact dana.small{at}yale.edu.
Statistical maps of the human brain are available on NeuroVault repository:https://identifiers.org/neurovault.collection:7635.
Results
Taste psychophysics
We first set out to determine whether prior findings of high cross-correlations between taste intensity ratings were replicated (Green and George, 2004;Lim et al., 2008). The four taste solutions were all rated as stronger in intensity than tasteless (Fig. 2; main effect of taste stimulus: F (1,135)= 69.14, p< 0.001; sweet-tasteless: t (27)= 9.83, p< 0.001; sour-tasteless: t (27)= 8.94, p< 0.001; salty-tasteless: r= t (27)= 9.94, p< 0.001; bitter-tasteless: t (27)= 8.51, p< 0.001), while the taste solutions were not rated significantly different in intensity from each other (all corrected pvalues >0.826). Pearson correlation analysis showed that intensity ratings of the four taste qualities positively correlated with each other (sweet-sour, r= 0.776; sweet-salty, r= 0.855; sweet-bitter, r= 0.373; sour-salty, r= 0.807; sour-bitter, r= 0.387; and salty-bitter, r= 0.417;Fig. 2); however, the correlation between quinine and the other taste solutions did not survive correction for multiple comparisons. The latter result is consistent with significant individual differences that have been found even among the sensitivities to different bitter compounds (Yokomukai et al., 1993;Delwiche et al., 2001), which has been proposed to result from differences in receptor expression among the 25 bitter taste receptors in humans (Meyerhof et al., 2010). Given these differences, a lower correlation between bitter and other tastes is not unexpected. A principal component analysis confirmed the existence of two components underlying the variance across participants, the first component accounted for 72% of the variance and received loadings from sweet, sour, and salty intensity, and the second component accounted for 19% of the variance and received a loading from quinine. Note also that the tasteless solution showed no significant correlation with any of the four prototypical tastes (sweet-tasteless, r= 0.061; sour-tasteless, r= −0.109; salty-tasteless, r= 0.119; bitter-tasteless, r= 0.041). Thus, we calculated grand intensity scores for each participant's taste intensity ratings by averaging ratings for sweet, sour, and salty tastants, referred to hereafter as the mean logintensity μ(Su CA NaCl). The Pearson correlation matrix between grand intensity scores and the intensity scores of the four taste solutions are shown inFigure 2, including all rvalues (effect size) and pvalues (corrected for multiple comparisons).
Figure 2.
Taste intensity ratings. Below the diagonal: scatterplots of log-transformed intensity ratings on the gLMS for all tastant pairs and each tastant with the average of the three significantly correlated tastants (from top to bottom: citric acid, sodium chloride, quinine, and mean logintensity μ(Su CA NaCl); from left to right sucrose, citric acid, sodium chloride, quinine). Each datapoint represents one participant. Above the diagonal, The boxplots indicate central tendencies and spread of the log-transformed intensity rating ( y-axis on far right), as follows: average (represented by a cross symbol), median (middle bar in box), first and third quartiles (lower and upper hinge), 1.5 × the interquartile range (top and bottom whiskers) and outlying points (separate dots outside the whiskers). We overlaid individual data points (one for each participant) on the boxplots with within-participant SEM of the average of eight ratings they gave for each tastant represented as horizontal error bars. From left to right, the boxplots represent the following: sucrose, citric acid, sodium chloride, quinine, and mean logintensity μ(Su CA NaCl). For interpretation, gLMS label placement is given on the y-axis on the far right.
fMRI data
Main effect of taste versus tasteless
Consistent with previous studies, a main effect of taste(μ Su NA NaCl)-tasteless was observed in bilateral md and anterior-ventral insula, and extending into overlying operculum, bilateral pre- and post-central gyrus, left amygdala, dorsal anterior cingulate cortex, and left putamen (Fig. 3,Table 1).
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Table 1.
Significant clusters of BOLD response to taste(μ Su CA NaCl)-tasteless
Figure 3.
Neural response to taste(μ Su CA NaCl)-tasteless in insula, pre- and post-central gyrus, amygdala, and anterior cingulate cortex (ACC; key: r, right; l, left; MI, middle insula; VI, ventral insula; PG, pre- and post-central gyrus; AM, amygdala; ACC, anterior cingulate cortex). Sections (slice location indicated in MNI coordinates) show canonical anatomic template with SPM T-map overlaid, thresholded at p uncorrected< 0.005, and a minimum of five contiguous voxels. The color gradient scale depicts suprathreshold tvalues. Boxplot graphs show median (center line), mean (diamond), first and third quartiles (lower and upper hinge), 1.5 × the interquartile range (top and bottom whiskers), and outlying points (separate dots outside the whiskers). We plotted parameter estimate of the peak voxels within a significant cluster for the average of taste(μ Su CA NaCl)-tasteless. We overlaid individual data points on the boxplots and connected the dots of an individual participant between the taste and tasteless bars to make it easier to inspect the difference within a single participant.
Regression of BOLD response with mean log intensity μ(Su CA NaCl)
To identify regions sensitive to overall gustatory system sensitivity, we used the mean logintensity μ(Su CA NaCl)as the independent variable in a regression analysis with the BOLD response to taste(μ Su CA NaCl)-tasteless. As predicted, the BOLD response in the left central amygdala was significantly associated with mean logintensity μ(Su CA NaCl). We also observed significant associations with response in the cuneus (Fig. 4,Table 2). Notably, response in insular cortex did not correlate with the mean intensity rating. We also note that neither swallowing estimates ( r (22)= −0.051, p= 0.819; see Extended Data Materials) nor composite movement estimates ( r (27)= −0.124, p= 0.531) correlate with the mean intensity ratings.
Table 2.
Significant clusters of correlation between logintensity μ(S u CA N a C l )and BOLD response to taste(μ Su CA NaCl)-tasteless
Figure 4.
Neural response to taste(μ Su CA NaCl)-tasteless correlated with mean logintensity μ(Su CA NaCl)in A, left amygdala (AM), and B, bilateral cuneus. Brain slices are as described inFigure 3. Scatterplots show each participant's values, with mean logintensity μ(Su CA NaCl)on the x-axis and parameter estimate on the y-axis for the peak voxel within a significant cluster. Regression line with regression coefficient and 95% confidence interval bands are overlaid for illustrative purposes. Positive associations are shown in blue, and negative associations are shown in red.
Functional connectivity of the CGM
Next, to identify regions of the brain where functional connectivity with the amygdala is influenced by taste sensitivity, we first performed a PPI analysis (Friston et al., 1997) and then regressed the responses of areas displaying significant functional connectivity with the mean logintensity μ(Su CA NaCl). The presence of functional connectivity indicates that the connected regions display temporal correlation beyond that accounted for by the task and suggests that the regions form a functional network. The subsequent regression then determines which of these network associations are influenced by taste sensitivity. This analysis revealed amygdala functional connectivity with the md and ventral posterior medial/pulvinar (vpm/pul) thalamus (Fig. 5 A,Table 3). We observed unpredicted functional connectivity in the mid-temporal gyrus (Table 3). No other significant effects were observed.
Table 3.
Significant clusters of correlation between logintensity μ(S u CA N a C l )and psychophysical interactions using peaks from correlation between logintensity μ(S u CA N a C l )(seeTable 2)
Figure 5.
Connectivity correlated with mean logintensity μ(Su CA NaCl). A, Connectivity parameter estimates from PPI analysis between seed region in left amygdala (am) and regions in thalamus (md and vpm/pul) that correlated with logmean intensity μ(Su CA NaCl). Brain sections are as described inFigure 3, and scatterplots are as described inFigure 4. B, Connectivity Bayesian estimates in the DCM of the amygdala and thalamus areas. The gradient of arrows indicates the estimates for connection strengths (positive in orange or negative in blue) between regions for any connections with a posterior probability of p> 0.95. The scatterplot shows each participant's values from the multivariate LOOCV regression, with mean logintensity μ(Su CA NaCl)on the x-axis and connectivity parameter estimate of the multivariate linear DCM model on the y-axis. The regression line with regression coefficient and 95% confidence interval bands is overlaid for illustrative purposes. Asterisks in the model indicate the connection that survived univariate LOOCV regression.
Effective connectivity of the CGM
Whereas PPI identifies correlations between regions, DCM can be used to establish effective connectivity, enabling inferences to be made about the influence that one neuronal system exerts over another (Friston et al., 2011). Based on the PPI and our hypothesized CGM, we predicted the existence of inhibitory modulatory influences from the amygdala to the thalamic nuclei, where the strength of the connection is associated with taste sensitivity. We therefore specified a DCM with five regions (left amygdala, bilateral md/thalamus, and bilateral vpm/pul) to examine the ensemble of connectivity parameters in relation to logintensity μ(Su CA NaCl)and subjected this to Bayesian model estimation. The architecture of the selected model conformed to our prediction, as follows: inhibitory connections were identified from the amygdala to the four thalamic peaks (Fig. 5 B). We also identified a positive bidirectional connection between right md and right vpm/pul. When we entered the connectivity parameters into a multivariate LOOCV regression, we found a significant association between predicted and observed mean logintensity μ(Su CA NaCl( r (27)= 0.37, p= 0.027;Fig. 5 B). To determine which of these connections contributed most to this predictive model, we used a univariate LOOCV approach, which revealed that the connections from amygdala to left vpm/pul and right md survived, as well as the positive connection from right vpm/pul to right md.
Discussion
Significant individual differences exist in taste intensity perception. Some of these differences can be explained by peripheral mechanisms, such as genetic variation in taste receptor expression and biology. However, as noted in the Introduction, while peripheral mechanisms can play a significant role in individual differences in the perceived intensity of individual taste qualities or even specific tastants (e.g., PROP), they are not able to account for overall differences in gustatory system sensitivity, such as the high within-subject cross-correlations among intensity ratings of different taste qualities (Green and George, 2004;Green et al., 2005;Lim et al., 2008). These observations are suggestive of a central mechanism that affects the responsiveness to all taste stimulation. Here we used fMRI and taste psychophysics to identify a region of amygdala where the response to a series of tastants is correlated with overall gustatory system sensitivity and drives inhibitory outputs to the gustatory and limbic nuclei of the thalamus. We further show that the dynamics and strength of these inhibitory connections are able to predict individual variation in taste intensity ratings.
Our primary hypothesis for a CGM focused on the amygdala for several reasons. First, patients with amygdala removal for the treatment of epilepsy show enhanced taste, but not visual, intensity ratings (Small et al., 1997,2001a,b). This enhanced perception suggests the existence of an inhibitory influence from the amygdala to the gustatory network, which when removed releases the target regions from inhibition to enhance the taste signal. Second, our prediction aligns with the known anatomy and physiology of the amygdala. The amygdala can be broadly subdivided into the basolateral complex, which receives sensory inputs, and a central medial division that produces the primary efferent information. Central nucleus efferent projections tend to be inhibitory and play an important role in regulating innate emotional responses and their associated autonomic outflow via connections to brainstem nuclei and md thalamus (Aggleton and Mishkin, 1984;Swanson and Petrovich, 1998;Barbas, 2000;Fadok et al., 2018). Accordingly, and in line with our prediction, we observed a correlation between the response to taste in the central medial nucleus of the amygdala and the mean log intensity ratings to sweet, sour, and salty tastants. Further, our connectivity analyses revealed inhibitory influences from this region to the md and gustatory (i.e., VPM) thalamic nuclei.
In primates, including humans, taste information ascends from the periphery to the rostral NST (Beckstead and Norgren, 1979). In rodents, after an obligatory synapse in the parabrachial pons, the gustatory pathway bifurcates at this point with one projection targeting the amygdala and hypothalamus and a second projection targeting the VPM gustatory thalamus, which subsequently projects to insular taste cortex (Norgren and Leonard, 1971;Norgren, 1976,1984,1990;Kosar et al., 1986). In primates, there is no bifurcation and only a single projection from NST to VPM and finally insular taste cortex (Beckstead et al., 1980;Pritchard et al., 1986,2000). Given this significant interspecies difference, we formed our prediction from the anatomic work in nonhuman primates and reasoned that the target for the inhibitory signal from the amygdala could be NST, thalamus, or insula (and not pons). However, the results from the PPI, which evaluated functional connectivity between the amygdala and the rest of the voxels in the brain, identified selective bilateral connectivity with two thalamic nuclei, highlighting these nuclei as the primary targets for inhibitory modulation.
The md thalamus is not part of the canonical taste pathway. However, it does receive gustatory and olfactory input (Price and Slotnick, 1983;Shi and Cassell, 1998;Cavada et al., 2000), and, although amygdala–thalamic connectivity is understudied, there is some evidence for a direct projection from the central nucleus of the amygdala to the md thalamus (Aggleton and Mishkin, 1984). By contrast, reciprocal connections do not appear to exist (Aggleton et al., 1980), which is consistent with the lack of reciprocal connections revealed here in the DCM analysis. While activation of the md thalamus is frequently found in gustatory fMRI studies, little is understood about its role in gustation. Work in nonhuman primates shows that it projects to the posterior orbitofrontal cortex, which is a site of convergence for taste and smell information (De Araujo et al., 2003;Small et al., 2004) and is proposed to form a tripartite circuit to convey information about emotional (and presumably physiological) significance to afferent sensory information (Timbie and Barbas, 2015). Accordingly, in rodents c-Fos expression is greater for familiar tastes and taste odor mixtures, suggesting sensitivity to flavor nutrient conditioning and therefore physiological significance (Fredericksen et al., 2019).
The second thalamic activation was further posterior and closely corresponded to the thalamic region previously associated with taste intensity perception (Small et al., 2003;Yeung et al., 2016). However, the activation extended into pulvinar, which is of relevance because it is often coactivated with amygdala in response to salient but nongustatory stimuli (Morris et al., 1997,1999). Importantly, the entire human thalamus is only ∼30 × 20 × 20 mm, with the VPM occupying less than one-tenth of this volume (Herrero et al., 2002). Given our 2 mm 3voxel size and 6 mm smoothing kernel, the taste thalamus, which is the parvicellular division of the VPM, is beyond the limits of our spatial resolution. It is therefore likely that the cluster of response we have observed overlaps the taste nucleus. The VPM is the target of gustatory afferents and projects to the insular taste cortex. However, no known direct connections exist between central medial amygdala and VPM (Kaskan et al., 2019). How the inhibitory influences from the central medial amygdala reach the VPM thalamus to regulate perception is therefore unknown and an important topic for future work. A related issue is whether this circuit operates independently from the known basolateral amygdala influence on taste cortex, which has been shown to enhance detection of expected taste stimuli in rodents (Samuelsen et al., 2012). Here we observed no associations between overall intensity perception and basolateral amygdala response or connectivity. Another consideration is the well known role the amygdala plays in orienting to salient stimuli (Cunningham and Brosch, 2012), even when presentation is implicit (Morris et al., 1999). Since the primary function of taste sensation is to guide feeding decisions, amygdala “gating” of taste information could be part of a larger system devoted to the identification of salient stimuli and attentional allocation.
However, whereas amygdala lesions impair taste recognition (Small et al., 1997) similarly to the effects observed with other salient stimuli, such as fearful faces (Adolphs et al., 1994;Calder, 1996), opposing effects are seen with sensitivity. Specifically, sensitivity to taste is enhanced while sensitivity to visual and auditory stimuli that should evoke fear is severely blunted (Adolphs et al., 1994;Calder, 1996). Interestingly, taste identification is likely encoded in parallel with taste detection (Wallroth and Ohla, 2018), with evidence that taste intensity is computed at the perceptual (Veldhuizen et al., 2010) and neural (Katz et al., 2002) levels before identity and hedonic significance. These observations suggest that the CGM may operate on the earliest stages of gustatory processing. Accordingly, the CGM may function to modulate taste and olfactory stimulation to increase the saliency of significant flavor stimuli in the service of selective attention or in the course of associative learning. Indeed, CGMs have been proposed and studied as a mechanism of selective attention in vision and hearing (Connor et al., 1996;Hillyard et al., 1998;Kauramäki et al., 2007;Womelsdorf and Fries, 2007;Jacobs et al., 2012). In this view, individual differences in the perceived intensity of tastes and odors would be attributable in part to differences in the baseline “gain” of such a system. The alternative explanation is that the amygdala response reflects a downstream effect of an earlier modulatory mechanism. However, while the correlational nature of fMRI data means that it is not possible to rule this possibility out, it is unlikely to account for our findings. First, a peripheral mechanism cannot account for the across-tastant and across-modal (olfactory) nature of the effect (Green and George, 2004;Green et al., 2005) and, second, neither can the insular cortex response, which reflects the first cortical relay, because it was not correlated with mean intensity ratings.
Relatedly, there is evidence for opposing responses in gustatory and visual streams of processing, especially regarding allocation of attentional resources. For example, breaches of taste expectation that occur when an individual expects to sense one tastant (e.g., sweet) but receives another (e.g., tasteless) are associated with enhanced response in gustatory, attentional, and error signaling regions coupled with decreased response in visual cortex (Veldhuizen et al., 2011b). Likewise, here we observed positive functional connectivity between the amygdala and the thalamic targets and negative functional connectivity between the amygdala and visual cortex. This suggests that the amygdala may play a role in coordinating the allocation of resources to visual (or distal) versus gustatory (or proximal/visceral) sensory systems, depending on the behavioral context or state of the organism.
We scanned with a multiband sequence to increase spatial coverage and spatial and temporal resolution. Slice leakage artifacts may result from multiband sequences and lead to false positive results (Todd et al., 2016). Here we used a combination of acceleration parameters that are at an intermediate level of signal-to-noise ratio and have an intermediate probability of obtaining a false-positive result. This was aimed to strike a good balance between higher signal-to-noise ratio and avoiding false positive results.
Finally, we note that although we excluded bitter taste from our analyses, we do not suggest that bitter tastants are unaffected by the CGM. Rather, it is likely that central factors are harder to detect because of the significant genetic variation in bitter taste receptors (Kim et al., 2004;Drayna, 2005), causing bitter taste perception to be more strongly influenced by peripheral mechanisms (Meyerhof et al., 2010;Hayes et al., 2015).
Here we identify a region of amygdala where the response to a series of tastants is correlated with overall gustatory system responsiveness and drives inhibitory outputs to the gustatory and limbic nuclei of the thalamus. Since the dynamics and strength of these inhibitory connections are able to predict individual variation in taste intensity ratings, we suggest that this circuit acts to create gain in the gustatory system to regulate taste intensity perception, and that the magnitudeof the gain contributes to individual differences in taste perception.
Footnotes
Received November 4, 2019.
Revision received February 10, 2020.
Accepted March 19, 2020.
The authors declare no competing financial interests.
This work was supported by National Institutes of Health Training Grant T32-NS-041228 (M.C.F.); the Yale Medical School Fellowship (M.C.F.); and National Institutes of Health Grant R01-DC-006706 (D.M.S.).
Correspondence should be addressed to Maria G. Veldhuizen at margaveldhuizen{at}gmail.com or Dana M. Small at dana.small{at}yale.edu
Copyright © 2020 the authors
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Fasting serum insulin and lipid levels in men with epilepsy | Request PDF
Request PDF | Fasting serum insulin and lipid levels in men with epilepsy | Previous studies suggest that obese women taking valproate (VPA) for epilepsy are insulin resistant. To assess the effects of antiepileptic drugs... | Find, read and cite all the research you need on ResearchGate
Fasting serum insulin and lipid levels in men with epilepsy
Neurology60(4):571-4
DOI: 10.1212/01.WNL.0000048209.07526.86
Authors:
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
V Pylvänen
V Pylvänen
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe>
Mikael Knip
University of Helsinki
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
AJ Pakarinen
AJ Pakarinen
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
J Turkka
J Turkka
Abstract
Previous studies suggest that obese women taking valproate (VPA) for epilepsy are insulin resistant.
To assess the effects of antiepileptic drugs on serum insulin and lipid levels in men with epilepsy.
Body mass index (BMI) and fasting serum concentrations of insulin and lipids were measured in 102 men with epilepsy who were treated with VPA, carbamazepine (CBZ), or oxcarbazepine (OXC) monotherapy. Thirty-two healthy men served as control subjects.
Obesity was not more common among VPA-treated men than among other men with epilepsy or the control subjects. However, the obese VPA-treated men had higher serum insulin levels (p < 0.001) than the obese control subjects despite similar BMI. CBZ and OXC did not have any significant effect on any of the measurements. Fasting serum insulin concentrations above the normal range were observed in seven obese VPA-treated patients (35%) but in only one obese control subject (5%). Five obese VPA-treated patients (25%) and one obese control subject (5%) had serum triglyceride levels above the normal range, and a low high-density lipoprotein/total cholesterol ratio was observed in two obese VPA-treated patients (10%).
Obese valproate-treated men have high serum insulin levels, indicating insulin resistance. Moreover, some of the valproate-treated men cluster cardiovascular risk factors such as obesity, hyperinsulinemia, and elevated serum triglyceride concentrations. CBZ and OXC do not seem to have any significant effects on serum insulin or lipid levels in men with epilepsy.
<here is a image 175d1bd4b7439d95-754927124da715c1>
... An increase in the number of adipocytes can also cause alterations in the levels of leptin [8]. VPA therapy is also associated with an elevation of triglycerides (TG) as well as diminished HDL-C levels
[9]
. Inflammation is involved in both the onset as well as progression in the severity of epilepsy [10]. ...
... While VPA treatment causing insulin resistance has been confirmed in several studies; there is contradiction regarding its effect on lipid profile. Some of the investigators found no impact of VPA treatment on lipid profile
[9,
18]. Mohamed et al. found that VPA-treated children had lower serum TC, TG, LDL-C, VLDL-C, and higher HDL-C when compared to untreated and healthy controls [3]. ...
... These differences in lipid profile reported could be attributed to the differences in the study population as well as differences in the duration of treatment. The differences in the study populations with reference to variations in age and gender could explain the differences in the lipid profile reported [3,
9,
[17][18][19]. ...
Biochemical derangements related to metabolic syndrome in epileptic patients on treatment with valproic acid
Article
Full-text available
Jun 2018
SEIZURE-EUR J EPILEP
<here is a image 56b8100749e05597-8e65242d901d5933> Yadav Nisha
Zachariah Bobby
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Vaibhav Wadwekar
Purpose:
Evaluation of biochemical derangements related to metabolic syndrome in epileptic patients on treatment with Valproic acid.
Methods:
This study consisted of two groups of 42 patients. Group I - Newly diagnosed patients with epileptic seizures untreated with any Anti-epileptic drugs (AEDs). Group II - Patients on treatment with Valproic acid for more than one year. Age and gender matched patients of 18-40 years were recruited. Patients who were diabetic, hypertensive, smokers, alcoholics, with persistent infection, head injuries, pregnancy and lactation were excluded from the study. Biochemical parameters, fasting blood glucose, lipid profile, Malondialdehyde (MDA), Total Antioxidant Status (TAS), MDA/TAS ratio, leptin, adiponectin, fasting insulin, high sensitive c-reactive protein (hsCRP), Homeostatic model assessment of insulin resistance (HOMA-IR) and leptin/adiponectin ratio were estimated.
Results:
There was a decrease in Total cholesterol and Low Density Lipoprotein- cholesterol levels among the VPA-treated epileptic patients in comparison to newly diagnosed patients. BMI did not differ between the untreated and treated patients. There were no significant difference in the levels of hsCRP, leptin and TAS between the newly diagnosed and VPA-treated patients. Increased insulin as well as HOMA-IR levels and decreased adiponectin levels were found in VPA treated subjects when compared to the newly diagnosed patients. Oxidative stress parameters (MDA, MDA/TAS ratio) were elevated in VPA treated subjects when compared to newly diagnosed patients.
Conclusion:
VPA treatment increased the risk factors for the development of metabolic syndrome such as hyperinsulinemia, insulin resistance and oxidative stress. However VPA treatment corrected the dyslipidemia of epileptic patients.
... We chose carbamazepine (CBZ) for comparison due to its lower side effect on insulin, lipid levels, and weight gain.
[27,
4] As different studies reported controversial results and also there was not any definite survey in our population, we decided to investigate the IR in two groups of epileptic patients treated with sodium valproate (VPA) and CBZ. By determining the association between VPA and hyperinsulinemia, we could decrease related mortalities and morbidities by modifying this side effect. ...
... Despite the majority of previous studies that have mentioned obesity as a common complication of VPA, [4][5][6][7][8][11][12][13][14][15][16][17][18][19] we have found a few articles without this effect.
[27,
29] In our study, 16.6% (5 cases) of VPA-treated patients and 3.3% (one case) of CBZ-treated were obese. Forty percent (12 cases) of main groups and 23.3% (7 cases) of controls were overweight. ...
... Statistically significant results for TG and HDL are related to BMI just the same as several previous studies. [8,16,33] Different from the majority of previous surveys [6,9,16,
27,
33] and similar to a few of them [53][54][55] in our study not only FBS, serum insulin, and HOMA-IR did not show any statistically significant difference between two groups, but also all measurements were in normal range [ Table 2]. Finally, IR did not happen in any of our patients. ...
The Investigation of Insulin Resistance in Two Groups of Epileptic Patients Treated with Sodium Valproate and Carbamazepine
Article
Full-text available
Mar 2017
Mohammadreza Najafi
Bahareh Bazooyar
<here is a image 33ffe171ec097a53-d09f5660c6ed0559> Mohammad Zare
<here is a image 9f4f8972f3c3807a-9a402fe416a76087> Maseumeh Dashti
Background
Valproic acid (VPA) is a widely used broad-spectrum antiepileptic drug for therapy of generalized and focal epilepsies. Cross-sectional studies have suggested that valproate treatment may be associated with hyperinsulinemia. We decided to investigate hyperinsulinemia as a health-threatening side effect of VPA in Iranian epileptic patients.
Materials and Methods
Body mass index (BMI), lipid profile, fasting serum insulin, fasting blood glucose (FBS), and homeostatic model assessment-insulin resistance (HOMA-IR) were measured in 30 VPA-treated epileptic patients and 30 controls (CBZ-treated). The Chi-square test, t-test, and Pearson correlation test were used.
Results
BMI was higher in VPA group than in control group (25.7 ± 3.5 > 21.7 ± 4.1) (0.000 < 0.05). Prevalence of obesity was 16.6% in VPA group that was almost the same and even lower than general Iranian population. Serum triglyceride (TG) (150 ± 77.2) was higher than CBZ group (114 ± 35.2) (P = 0.023 < 0.05). However, serum high-density lipoprotein level was lower in VPA group than controls (45.2 ± 11.7 < 54.4 ± 13.9) (P = 0.008 < 0.05). Serum insulin, FBS, HOMA-IR, cholesterol, and low-density lipoprotein did not demonstrate statistically significant differences between the two groups (P > 0.05).
Conclusion
Despite the majority of previous studies that are against VPA and according to our study, VPA could be prescribed safely and it may not cause IR and its complications.
... Valproic acid (VPA) is a first line antiepileptic drug (AED) for generalized and absence seizures (Perucca, 2002). The most common side-effects of VPA therapy are weight gain (Biton et al., 2001;Luef et al., 2002) and increased insulin resistance (IR) (Isojarvi et al., 1998;
Pylvanen et al., 2003;
Verrotti et al., 2002) associated with various metabolic and endocrine abnormalities (Isojarvi et al., 1996;Pylvanen et al., 2002). As a general consensus, abnormal glucose tolerance, hyperinsulinaemia, dyslipidaemia and hypertension are the classical symptoms of IR, summarized as the metabolic syndrome (MS) (Reaven, 2002). ...
... Of note, the serum levels of VPA and CBZ were within the normal range excluding a toxic drug effect. The present results are in line with previously published studies concerning weight gain and altered adipocytokine concentrations in VPA treated patients (El-Khatib et al., 2007;Isojarvi et al., 1998;
Pylvanen et al., 2003;
Rauchenzauner et al., 2008a,b;Verrotti et al., 2002). Furthermore and according to prior studies, greatest TC, LDL-C and yGT concentrations were found in the CBZ group (Yilmaz et al., 2001). ...
... Interestingly, serum fasting glucose, serum fasting insulin as well as the HOMA-IR did not differ between groups. There are several possible explanations for this finding: First, a wide range of alterations of serum lipids, apo-lipoproteins and adipocytokines (leptin, adiponectin, visfatin) have been reported during VPA treatment possibly involved in metabolic derangement in these patients (El-Khatib et al., 2007;Isojarvi et al., 1998;
Pylvanen et al., 2003;
Rauchenzauner et al., 2008a,b;Verrotti et al., 2002). Since adipocytokines and their receptor system have recently been suggested as a link between body fat and glucose metabolism (Rauchenzauner et al., 2008c), disturbances in glucose homeostasis might be rather a consequence than a cause in patients treated with VPA. ...
Non-alcoholic fatty liver disease (NAFLD), insulin resistance and lipid profile in antiepileptic drug treatment
Article
<here is a image fb7e60b022e000a8-21ef0d27326d9a65> Gerhard Luef
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Markus Rauchenzauner
Patients undergoing long-term treatment with valproic acid (VPA) are prone to develop different features of the metabolic syndrome (MS). The aim of the present study was to evaluate the occurrence of non-alcoholic fatty liver disease (NAFLD), insulin resistance (IR) and a pro-atherogenic lipid profile in patients undergoing VPA, carbamazepine (CBZ) and lamotrigine (LTG) monotherapy compared to healthy controls.
Abdominal ultrasound as well as measurement of serum fasting insulin and glucose, serum lipids and liver function parameters were performed in VPA (n=23), CBZ (n=22) and LTG (n=23) treated non-diabetic and non-obese epileptic patients compared to healthy controls (n=16).
Ultrasound measurement demonstrated characteristics of fatty liver disease in 60.9% of VPA, in 22.7% of CBZ, in 8.7% of LTG treated patients and in 12.5% of the healthy controls, with highest level of steatosis seen in VPA treated patients. In addition, patients on VPA monotherapy showed a higher body-mass index (BMI) when compared to LTG treated patients and controls (p<or=0.049). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and gamma-glutamyltransferase (gammaGT) were greatest in the CBZ group (p<or=0.043). Interestingly, serum fasting glucose, serum fasting insulin as well as the HOMA-IR did not differ significantly between groups.
In conclusion, VPA (and moderately CBZ) therapy is related to increased risk for ultrasonographic signs of fatty liver disease, emphasizing the importance of regular ultrasound measurements as well as monitoring of serum lipids and BMI during enzyme-modulating AED treatment.
... [8,9] Some of the antiepileptic drugs (AED) can also cause weight gain and subsequent metabolic disturbances and considerable changes in plasma lipids and hormonal levels.
[10]
[11][12] Obesity and MetS are not only affecting the physical fitness and quality of life of these patients but medication compliance and seizure control have also been affected. Few studies have suggested that a patient's body mass index (BMI) may also predict AED response in PWE and drug-resistant epilepsy (DRE). ...
... [38] Studies in both men and women revealed hyperinsulinemia and weight gain in those PWE who were treated with VPA, while CBZ and oxcarbazine (OXC) do not seem to have any significant effects on serum insulin or lipid levels in men with epilepsy.
[10,
11,27,39] VPA induces obesity, which could be related to the serum values of leptin and adiponectin. ...
Obesity and metabolic syndrome in patients with epilepsy, their relation with epilepsy control
Article
Jan 2023
Ann Afr Med
<here is a image ed6f4847c456af03-5c55fe46a5d8e707> Saima Nazish
Obesity and metabolic syndrome (MetS) are commonly observed in patients with epilepsy (PWE). Obesity and MetS are not only affecting the physical fitness and quality of life of these patients, rather antiepileptic drugs (AEDs) compliance and seizure control have also been affected. The objective of this review is to search the published literature regarding the prevalence of obesity and MetS in PWE and their relation to the response to AEDs. A comprehensive search using PubMed, Cochrane Databases, and Google Scholar was performed. A supplementary citation search was also conducted by analyzing the reference lists of identified sources. The initial search revealed 364 articles of potential relevance. The studies were analyzed in detail to obtain clinical information relevant to the objectives of the review. Many observational, case control studies, randomized control trials and few review articles were included for critical appraisal and review writing. Epilepsy is associated with MetS and obesity in all age groups. AEDs and lack of exercise are the chief causes while metabolic disturbances such as adiponectin, mitochondrial dysfunction, valproic acid (VPA)-associated insulin resistance, leptin deficiency, and endocrine dysfunction are also addressable factors. Although the risk of drug-resistant epilepsy (DRE) is also higher among obese PWE, the interaction between, MetS, and its components with DRE remain to be fully investigated. Further research is required to elucidate their interplay. Appropriate and careful selection of AEDs without compromising therapeutic efficacy supplemented by lifestyle counseling for exercise and diet should be practiced to avoid weight gain and potential DRE.
... Lipid metabolism findings in VPA-treated patients have been inconsistent. Some studies have associated VPA treatment with decreased HDL-C [4] and increased TG [4,19,22] levels, whereas others have found no effect of VPA treatment on lipid metabolism [13,
26]
. One possible explanation is that VPA has no direct influence on TG or HDL-C metabolism, in contrast to its effect on insulin. ...
... Previous studies using the HOMA-IR index have reported the presence of IR in patients receiving VPA treatment [3,13,22,23,
26]
. However, an increased HOMA-IR index in these patients most likely reflects hyperinsulinemia, which can occur in obese and normal-weight patients. ...
Comparison of the Metabolic Syndrome Risk in Valproate-Treated Patients with Epilepsy and the General Population in Estonia
Article
Full-text available
Jul 2014
PLOS ONE
<here is a image 5de823a3f2226eb9-f5f4111ce9269dfb> Aleksei Rakitin
<here is a image 1fb6ced6e467eb4a-49803dd48c1adfb9> Triin Eglit
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Sulev Kõks
Sulev Haldre
Background
No study has explored the risk of metabolic syndrome (MS) in patients with epilepsy treated with valproate (VPA) at the population level. The aim of this study was to compare the risk of MS in VPA-treated patients in Estonia to the risk in the general population.
Methods
This study involved 118 patients with epilepsy (63 men, 55 women) who received VPA monotherapy. MS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Data were compared with the results of a population-based study of the prevalence of MS in the same geographic region (N = 493; 213 men, 280 women).
Results
In the multiple logistic regression analysis, after adjustment for age and sex, the risk of MS in VPA-treated patients was not increased compared to the control subjects (odds ratio [OR] = 1.00; 95% confidence interval [CI], 0.59–1.68). VPA-treated patients had higher serum insulin concentrations than control subjects, independent of body mass index (BMI). A positive association was found between MS development and BMI (OR = 1.47; 95% CI, 1.25–1.73) in VPA-treated patients, but there were no associations with the VPA dosage or the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index. In control subjects, BMI and HOMA-IR had similar predictive abilities for MS occurrence. In VPA-treated patients, the predictive ability of the HOMA-IR index was significantly lower than that of BMI, with areas under the receiver operating characteristic curves of 0.808 and 0.897 (P = 0.05), respectively.
Conclusions
The risk of MS is not increased among VPA-treated patients with epilepsy in Estonia compared to the general population. The HOMA-IR index likely has a lower predictive ability for MS in VPA-treated patients compared to its predictive ability in the general population.
... However, findings have been generally inconsistent. 9,[11][12]
[13]
The term ''metabolic syndrome'' (MetS) refers to a cluster of metabolic conditions, such as dysglycemia, dyslipidemia, and hypertension, which are known precursors of cardiovascular and cerebrovascular diseases. Recent studies have revealed that MetS represents an enormous economic burden and is considered a serious public health problem. ...
... Earlier studies have reported lower HDL-C and higher TG concentrations in populations that use VPA, 9,25 whereas others have found that VPA has no effect on changes in lipids.
13
Some articles have even suggested that VPA is associated with increased lipid metabolism, which leads to more favorable lipid profiles, thereby possibly contributing to a protective effect. 26 Although our results cannot completely elucidate the protective effect of VPA against atherogenesis, the lower proportion of abnormal HDL-C in the patient group strengthened the latter opinion. ...
Metabolic syndrome among Chinese obese patients with epilepsy on sodium valproate
Jiajia Fang
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Sihan Chen
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Nanwei Tong
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Dong Zhou
Many publications have addressed the problem of weight gain and endocrine abnormalities in patients treated with sodium valproate (VPA). However, the presence of metabolic syndrome (MetS) among obese patients with epilepsy on VPA has received little attention.
Thirty-six patients receiving VPA monotherapy were included in this study to evaluate the presence of MetS. All patients were interviewed and clinically examined. Blood samples were obtained after an overnight fast, and an oral glucose-tolerance test was performed. Twenty-eight subjects who were obese but had no epilepsy and were otherwise well were collected as controls ("simple obesity" group).
The two study groups were well matched in terms of age, gender and body mass index. Insulin resistance measured via homeostasis model assessment (HOMA) index was more severe among the VPA-treated group (4.91±2.91 vs. 2.00±1.72, P=0.007). The frequency of the MetS was slightly higher in the patients with epilepsy compared to controls (47.2% vs. 32.1%, respectively), but this difference was not statistically significant (P=0.223). Multivariate analysis with stepwise logistic regression revealed low positive correlations between MetS development, HOMA index (P=0.029; r=0.361) and valproic acid dose (P=0.049; r=0.323). These correlations were independent of other clinical parameters.
Our preliminary study suggests that obese patients with epilepsy treated with VPA are at higher risk of MetS than individuals who are "simply obese" but otherwise well. Therefore, the HOMA index should be monitored in obese patients who receive VPA therapy, rather than monitoring body weight alone.
... [4][5][6][7][8] For example, a range of AEDs have been linked to increased levels of homocysteine, 3,4,7,8 treatment with liver enzyme-inducing AEDs can increase levels of cholesterol and atherogenic lipoproteins, 4 carbamazepine can decrease thyroid hormone concentrations, 5,6 and valproate has been associated with weight gain, insulin resistance, and the metabolic sundrome. 4,
9
Investigations of the risk of ischemic heart disease and stroke associated with individual AEDs are therefore warranted and may have important consequences for optimal cardiovascular (CV) risk control in these patients. We therefore conducted a nationwide study, aiming to investigate the effect of epilepsy on myocardial infarction (MI), stroke, CV death, and all-cause death in patients with or without previous stroke. ...
... 27 On the other hand, limited clinical evidence has indicated that valproate may adversely influence the CV risk profile (e.g., by negative microcapillary effects and induction of insulin resistance). 8,
9,
23 Irrespective of mechanisms involved, our findings are suggestive of a net protective effect of valproate on the CV risk profile, as compared with patients treated with carbamazepine. Indeed, the finding that patients with epilepsy and baseline valproate treatment also had a decreased risk of MI compared with individuals without epilepsy and no baseline AED treatment is in alignment with previous findings. ...
Effects of epilepsy and selected antiepileptic drugs on risk of myocardial infarction, stroke, and death in patients with or without previous stroke: A nationwide cohort study
Article
Jul 2011
PHARMACOEPIDEM DR S
Jesper Erdal
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Jonas Olesen
<here is a image 539a2a369e01303d-20190b059c6cde62> Steen Z Abildstrøm
<here is a image f049894c687c0a65-ccf2043b42a3c326> Peter Riis Hansen
Patients with epilepsy have increased morbidity and mortality. We evaluated the risk of myocardial infarction (MI), stroke, and death associated with epilepsy and examined if this risk was modified by treatment with antiepileptic drugs (AEDs).
A cohort consisting of the Danish population was followed from January 1997 to December 2006. The risk of MI, stroke, cardiovascular death, and all-cause death associated with epilepsy was estimated by multivariable Cox proportional hazard models stratified for occurrence of previous stroke. AED use was determined at baseline, and risks associated with exposure to individual AEDs were examined in patients with epilepsy.
In patients without previous stroke, AED-treated epilepsy was associated with an increased risk of MI (hazard ratio [HR], 1.09; 95%CI, 1.00-1.19), stroke (HR, 2.22; 95%CI, 2.09-2.36), cardiovascular death (HR, 1.64; 95%CI, 1.57-1.72), and all-cause death (HR, 1.92; 95%CI, 1.86-1.97). Compared with carbamazepine monotherapy, valproate was associated with a decreased risk of MI (HR, 0.72; 95%CI, 0.59-0.87) and stroke (HR, 0.86; 95%CI, 0.76-0.96), oxcarbazepine and phenobarbital with increased risk of cardiovascular death (HR, 1.10; 95%CI, 1.02-1.19 and HR, 1.08; 95%CI, 1.00-1.17, respectively) and all-cause death (HR, 1.11; 95%CI, 1.05-1.18 and HR, 1.18; 95%CI, 1.12-1.25, respectively), and oxcarbazepine with increased risk of stroke (HR, 1.21; 95%CI, 1.10-1.34), in patients with epilepsy.
Patients with epilepsy exhibit increased risk of MI, stroke, cardiovascular death, and all-cause death. Compared with carbamazepine monotherapy, valproate may decrease, and oxcarbazepine and phenobarbital may increase, the risk of adverse cardiovascular events in these patients.
... We demonstrated that after 1 year of VPA treatment, only obese VPA-treated patients had higher levels of leptin, while non-obese VPAtreated patients continued to show normal leptin levels (18). Finally, some studies have failed to demonstrate a significant correlation between BMI and leptin levels in epileptic patients (4,
9,
11,18). However, it is also possible that VPA causes direct secretion of leptin from adipocytes or alters leptin signalling and decreases negative feedback. ...
... Furthermore, we showed that insulin resistance was more severe in VPA-related obesity than in obesity in general (22). In the same period, Pylvänen et al.
(9)
founded that both obese and lean patients taking VPA had hyperinsulinaemia, suggesting a development of insulin resistance as the leading factor to weight gain during VPA treatment. It is difficult to explain the presence of hyperinsulinaemia in lean patients. ...
Weight gain following treatment with valproic acid: Pathogenetic mechanisms and clinical implications
Article
Sep 2010
OBES REV
Claudia D'Egidio
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mohn Angelika
<here is a image d02e2e5c82a16c55-108bcedc7d6c9492> Alberto Verrotti
<here is a image 4e7019c41dce100a-9ea5bde931ca5a75> Francesco Chiarelli
In the last years, a growing body of literature indicates an association between valproic acid therapy and weight gain. Weight gain during valproate treatment can be observed within the first 3 months of therapy and women seem to be more susceptible than men. The mechanism through which valproic acid may induce a weight gain is still controversial. The scope of this paper is to investigate the possible causal link between treatment and weight gain in epileptic patients. Systematic review of published epidemiological studies has been done in order to evaluate the real extent of this side effect of valproic acid and its clinical implications, such as an increased risk of insulin resistance and other secondary metabolic abnormalities. The knowledge of the potential of valproic acid to cause significant changes in body weight will help in appropriate selection and modification of antiepileptic therapy to minimize the risk for weight abnormalities. Measurements of body weight before initiation of valproic acid therapy should be done as part of the monitoring of patients with epilepsy to detect changes before there are serious adverse consequences; an increase of 2 kg of body weight after 1 month of treatment should imply considerations to change antiepileptic drug therapy.
... The treatment with some AEDs can increase levels of cholesterol, such as carbamazepine, and lead to MI [5,36]. VPA may cause weight gain, insulin resistance, and metabolic syndrome [5,
37]
and increase the risk for MI [38], although, in comparison with carbamazepine, VPA had a reduced risk of MI [39]. In the present study, we provide some evidence the SDS scores of inadequately compensated myocardial ischemia differed between patients treated with enzyme-inducers and patients treated with VPA. ...
Myocardial perfusion imaging single photon emission computed tomography may detect silent myocardial ischemia in patient with epilepsy
Article
Full-text available
Aug 2022
Nucl Med Rev Cent E Eur
<here is a image 0cf9425a6cfc3c08-59a5ccc1f81a5f52> Sofia Markoula
Afroditi Tsoumani
Chainti Antonella Votti
<here is a image 2a85f1f797a8161e-fe07b02a51f03874> Chrissa Sioka
Background:
The aim of the present study was to compare the myocardial perfusion imaging (MPI) with [99mTc]tetrofosmin stress - rest single-photon emission computer tomography (SPECT) of patients with epilepsy with matched control individuals.
Material and methods:
All 29 adult epileptic patients were receiving antiepileptic drugs (AEDs) for epilepsy. Thirty-two individuals matched for gender and age consisted of the control group. MPIs SPECT were performed, and myocardial summed scores were obtained during stress (SSS) and rest (SRS) images. Abnormal MPI was considered when SSS was ≥ 4. In addition, the difference (SDS) between SSS and SRS was also assessed, which represents a rate of reversibility after stress.
Results:
Twenty of 29 (68.97%) patients with epilepsy had abnormal MPI and 14/32 (43.75%) of the controls (p = 0.04). Among males, 18/23 patients and 11/25 controls had abnormal MPI (p = 0.01), with quite a significant difference for mean SSS between male patients and controls (p = 0.002). Furthermore, SDS comparison showed that irreversible abnormalities were more common in patients than in control individuals. A difference of inadequately compensated myocardial ischemia between patients treated with enzyme inducing AEDs and patients treated with valproic acid was also detected.
Conclusions:
Single-photon emission computer tomography (SPECT) may detect increased risk for coronary artery disease and further cardiovascular events in patients with epilepsy. Our findings favor the conclusion that SPECT could be used for the early identification of cardiovascular comorbidity in epilepsy.
... Вальпроаты вызывают гиперинсулинемию -фактор риска сахарного диабета и сердечно-сосудистых заболеваний
[569]
. ...
Epilepsy. Guide for doctors
Book
Full-text available
Jul 2022
<here is a image 7e5d87948fe869e9-97106edcea600290> Alexey Kotov
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Konstantin Vladimirovich Firsov
The monograph presents methods for diagnosing and treating epilepsy in adults. Every effort has been made by the authors and the publisher to ensure the accuracy of the indications, adverse reactions, and recommended doses of medications given in this book. However, this information is subject to change. The information contained in the book is intended for physicians. Carefully read the manufacturer's instructions for use of medicinal products. For neurologists, doctors of other specialties and medical students.
... Indeed, it seems that insulin resistance development might be one of the factors that at least in part has been implicated in weight gain resulting from valproic acid therapy [27,[29][30][31]. In support of this hypothesis, Pylvänen et al., in their study, showed that both obese and lean patients on valproic acid treatment had hyperinsulinemia that indicates valproic acid-associated weight gain resulting from the insulin resistance development [32,
33]
. It is speculated that valproic acid, through several mechanisms, including impairing insulin metabolism, increasing serum levels of free fatty acids, stimulating pancreatic β-cells insulin secretion, decreasing sympathetic activity, impairing insulin signal transduction pathway, and inducing oxidative stress condition may cause hyperinsulinemia and a state of insulin resistance [18]. ...
Evaluation of serum levels of asprosin and other metabolic profiles in patients with idiopathic tonic–clonic generalized epilepsy on treatment with valproic acid
Article
Full-text available
Mar 2022
EUR J CLIN PHARMACOL
Amir-mohammad Yaryari
Mehrdokht Mazdeh
<here is a image c437d79f46f96a7f-c36e16abaa8483aa> Mojdeh Mohammadi
Maryam Mehrpooya
Background
This cross-sectional research was undertaken to determine the serum levels of asprosin, a novel white adipose tissue-derived glucogenic adipokine, in epileptic patients on valproic acid treatment.
Methods
Sixty-six patients diagnosed with idiopathic tonic–clonic generalized epilepsy were divided into three groups: those treated with valproic acid (n = 22), those treated with lamotrigine (n = 22), and twenty-two newly diagnosed or untreated patients. A control group was twenty-two, healthy volunteers with a similar distribution of gender and age. Body mass index (BMI) and fasting serum levels of asprosin, glucose, glycohemoglobin (HbA1c), insulin, and lipid profile were measured for both patients and control groups. Additionally, homeostasis model assessment for insulin resistance (HOMA-IR) was also calculated for the investigated groups.
Results
The mean BMI values and fasting serum levels of glucose, HbA1c, insulin, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride were much higher in subjects treated with valproic acid than those in the other study groups. Furthermore, a higher number of participants in the valproic acid group fulfilled the insulin resistance criterion (defined as HOMA-IR > 2.5) compared with those in other study groups. The mean fasting serum asprosin concentration was also significantly higher in the valproic acid group than in other study groups. This was while the values of the study parameters were comparable in the healthy, un-treated, and lamotrigine groups.
Conclusions
Our finding suggested that elevated asprosin level might be one of the pathological mechanisms involved in the development of obesity, insulin resistance, and metabolic disturbances related to valproic acid treatment.
... There are contradictory results about the nding of lipid metabolism in VPA-treated patients. Some studies have reported no effect of VPA treatment on lipid metabolism
[43,
44] and, whereas others have found increased TG [16,42,45], decrease in HDL level in VPA group [46].we found that, raised TG level acts as a main risk factor for MetS development based on two criteria and decrease in HDL was represented signi cantly for MetS risk based on NCEP index. ...
Frequency of metabolic syndrome and insulin resistance in epileptic patients treated with sodium valproate or carbamazepine monotherapy: A Case-Control Study
Preprint
Full-text available
Dec 2020
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mahnaz Bayat
Nasrin Jalali
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Maryam Poursadeghfard
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Nahid Ashjazadeh
Background
Metabolic syndrome (MetS) represents a collection of metabolic risk factors such as obesity, dyslipidemia, hyperglycemia, and hypertension. Medications can increase the incidence rate of MetS and insulin resistance (IR).
Objective
This study aims to evaluate the effects of Carbamazepine (CBZ) or Valproate (VPA) as monotherapy on the development of MetS and IR in the adult Iranian epileptic patients.
Methods
In this observational analytic case-control study, 80 epileptic patients were treated with VPA (40 patients) or CBZ (40 patients) monotherapies for more than 6 months and 45 age and sex matched controls were included. MetS was assessed based on International Diabetes Federation (IDF) and National Cholesterol Education Program (NCEP) criteria.
Results
In the multiple regression analysis, in VPA-treated patients the risk of MetS (by IDF criteria) was increased 19 times higher than controls (OR = 19.20; 95% CI = 2.62-140.23, P = 0. 004) and risk of IR (by HOMA and QUICKI) was increased 15 and 9 times more than controls (OR = 14.83; 95% CI = 3.03–72.56, P = 0.001) and (OR = 9.13; 95% CI = 2.55–32.65, P = 0.001) respectively. Increase in waist, DBP, and insulin level were also showed as important factors in risk of MetS. In CBZ therapy, the risk of MetS (by IDF) depressed by 17% less than controls and the risk of IR (by HOMA) increased 7 times more than controls.
Conclusion
Treatment with VPA can increase the likelihood of developing MetS and IR while, CBZ therapy could decrease the risk of MetS and increase risk of IR in the epileptic patients in Iran compared to the general population.
... In a patient with a comorbid binge-eating disorder and BD, it was associated with reduced hemoglobin A1c levels (Yamamoto et al., 2013). Oxcarbazepine was shown to be neutral for body weight, serum levels of glucose, insulin, insulin growth factorbinding proteins-1 and 3, and ghrelin in children with epilepsy (Cansu et al., 2011;Rättyä et al., 1999), and did not affect the fasting insulin serum levels in adult men with epilepsy
(Pylvänen et al., 2003)
. With regard to bupropion, the data support its weight-neutral properties (Serretti and Mandelli, 2010) and beneficial role in the management of obesity, glucose, and lipid metabolism disturbances (Anderson et al., 2002;Hollander et al., 2013). ...
Diabetes mellitus risk for 102 drugs and drug combinations used in patients with bipolar disorder
Article
Full-text available
Nov 2019
PSYCHONEUROENDOCRINO
<here is a image 5a97a65b98828a96-b0a4d20c5f7b1b1e> Anastasiya Nestsiarovich
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Berit Kerner
Aurélien J Mazurie
<here is a image ecb66cf93595a2cd-ec910e25546d8ecb> Christophe Gerard Lambert
Objective:
To compare the largest set of bipolar disorder pharmacotherapies to date (102 drugs and drug combinations) for risk of diabetes mellitus (DM).
Methods:
The IBM MarketScan® database was used to retrospectively analyze data on 565,253 adults with bipolar disorder without prior glucose metabolism-related diagnoses. The pharmacotherapies compared were lithium, mood-stabilizing anticonvulsants, antipsychotics, and antidepressants (monotherapy and multi-class polypharmacy). Cox regression modeling included fixed pre-treatment covariates and time-varying drug exposure covariates to estimate the hazard ratio (HR) of each treatment versus "No drug".
Results:
The annual incidence of new-onset diabetes during the exposure period was 3.09 % (22,951 patients). The HR of drug-dependent DM ranged from 0.79 to 2.37. One-third of the studied pharmacotherapies, including most of the antipsychotic-containing regimens, had a significantly higher risk of DM compared to "No drug". A significantly lower DM risk was associated with lithium, lamotrigine, oxcarbazepine and bupropion monotherapies, selective serotonin reuptake inhibitors (SSRI) mono-class therapy and several drug combinations containing bupropion and an SSRI. As additional drugs were combined in more complex polypharmacy, higher HRs were consistently observed.
Conclusions:
There is an increased risk of diabetes mellitus associated with antipsychotic and psychotropic polypharmacy use in bipolar disorder. The evidence of a lower-than-baseline risk of DM with lamotrigine, oxcarbazepine, lithium, and bupropion monotherapy should be further investigated.
... In children, valproate was found to increase leptin levels independent of age, weight, or lipid profile (Hamed et al., 2009). Total cholesterol and triglyceride have also been suggested as being significantly higher in people on valproate than in people on other AEDs or healthy controls even after adjustment for obesity
(Pylvänen et al., 2003)
. Another study found that 43% of people who developed obesity on valproate had metabolic syndrome (Verrotti et al., 2010b). ...
Somatic co‐morbidities in epilepsy
Thesis
Jan 2015
Jan Novy
People with epilepsy seem to have more concomitant medical conditions than the general population. The burden of somatic co‐morbidities plays an important role in the premature mortality in epilepsy. I sought to explore the relation between somatic co‐morbidities and epilepsy, attempting to avoid biases in previous studies. In a first study, I collected clinical, demographic and somatic co‐morbidity data in 2016 consecutive people with epilepsy referred for assessment at a tertiary centre and in 1297 people with epilepsy in the community. In a second study, I analysed the lifelong course of epilepsy of an historical cohort of 235 people who were in residential care at the Chalfont Centre for Epilepsy: 122 had comprehensive post‐mortem examination. Confounders (causes or consequences of epilepsy/ its treatment) were distinguished from co‐morbidities. In the first study, somatic co‐morbidities were significantly more frequent in the referral centre than in the community (49% vs 37%). Consistent risk factors were found in both cohorts. When adjusting for age, epilepsy duration, and absence of underlying brain lesion were independently associated with an increased burden of somatic conditions. In the second study, age at death showed an early peak of mortality between 45‐50 years old. High seizure frequency was an independent predictor of early death due to co‐morbidities. Those who survived increasingly went into spontaneous remission lasting until death; older age and presence of neuropathologically‐confirmed degenerative changes were independent predictors of terminal remission. Somatic co‐morbidities do not occur randomly in relation with epilepsy. Greater epilepsy severity seems to be a risk factor; several other consistent predictors were identified. Epilepsy may cause premature death indirectly through co‐morbid conditions. Ageing and degenerative changes could improve epilepsy drug responsiveness.
... VPA in particular has well-established, common metabolic side-effects including weight gain 130 and increased insulin resistance.
131
VPA, and to a lesser degree CBZ, have been associated with increased risk for ultrasonographic signs of fatty liver disease. 132 CBZ-induced steatosis/steatohepatitis may be idiosyncratic; while hepatotoxicity associated with CBZ is well described in the literature, typically causing hepatitis, 133,134 steatosis/steatohepatitis is rare. ...
Drug-induced fatty liver disease: An overview of pathogenesis and management
Article
Full-text available
Sep 2015
ANN HEPATOL
<here is a image 9c02746d5f11f660-47b8c1b4eff30c87> Sanjaya Satapathy
Vanessa Kuwajima
Jeffrey Nadelson
Arun J. Sanyal
Over the past decades, many drugs have been identified, that can potentially induce steatohepatitis in the predisposed individual. Classically this has been incriminated to amiodarone, perhexiline, and 4,4'-diethylaminoethoxyhexestrol (DH), all of which have been found to independently induce the histologic picture of non-alcoholic steatohepatitis (NASH). Pathogenetic mechanisms of hepatotoxicity although still evolving, demonstrate that mitochondrial dysfunction, deranged ATP production and fatty acid catabolism likely play an important role. Drugs like steroid hormones can exacerbate the pathogenetic mechanisms that lead to NASH, and other drugs like tamoxifen, cisplatin and irenotecan have been shown to precipitate latent fatty liver as well. Further research aiming to elucidate the pathogenesis of drug-induced steatosis and steatohepatitis is needed in order to better design therapeutic targets.
... ya da çal›flmam›za benzer flekilde etkisinin olmad›¤›(19,25,
26,
28,30) bildirilmifltir. Bu durum valproik asidin enzim indüksiyonu yapmamas› ile iliflkili olabilir. ...
Antiepileptik İlaçların Lipit Profili ve Karaciğer Enzimleri Üzerine Etkisi
Article
Full-text available
Sep 2011
<here is a image cc3a7f9e2acc8c57-f7576fa6aea51de5> Dr Nermin Bölükbaşı
Ferda Akar
Sinan Bir
... The present study showed only a non-significant increase in total cholesterol in those receiving combination therapies while those on monotherapy did not show such increase. There are studies supporting this observation
[6]
[7][8][9][10]. ...
Studies on adverse metabolic effects of antiepileptics and their correlation with blood components
Article
Full-text available
Oct 2010
<here is a image d91fb46fc5e6f576-e48fd263d576ce43> Manisha Naithani
Sunny Chopra
<here is a image 7a76a14fcc9f4ccf-480cea3492ee6853> Babu Somani
R K Singh
Epilepsy is a neurological disorder knowing no geographical or social boundaries. Majority of patients can be treated with conventional drugs like phenytoin, phenobarbitone and car-bamazepine. The present study was planned to correlate the metabolic side effects with the serum drug levels to bridge the existing gap between clinical and biochemical evaluation. Correlation of serum concentration of antiepileptics with thyroid profile, lipid profile, liver enzymes and electrolytes was carried out in 130 known patients of epilepsy on monotherapy or combination therapy. Phenytoin, carbamazepine and phenobarbitone estimation was done using High Pressure Liquid Chromatography. All the groups showed an increase in mean alkaline phosphatase and thyroid-stimulating hormone concentration as compared to healthy age and sex matched individuals. Significant positive correlation was found between serum carbamazepine and serum aspartate transaminase and alanine transaminase concen-tration (p<0.005). It was concluded that metabolic alterations are mostly mild and clinically insignificant and do not justify routine testing, except in those known to have a coexisting or recently developed hepatic abnormality.
... The men on VPA had significantly higher insulin and C-peptide levels than both the controls and the CBZ treated patients. This is in concurrence with the study by
Pylva¨nen et al. (2003)
where the discussion of increased risk of cardiovascular disease is raised, and in which significantly higher serum insulin values were found in the obese VPA treated men compared with obese controls with similar BMI. Stephen et al. (2001) also found higher insulin concentrations in men on VPA monotherapy. ...
Overnight Response to Infliximab in Neurosarcoidosis: A Case Report and Review of Infliximab Treatment Practice
Article
Sep 2014
CLIN NEUROPHARMACOL
<here is a image 4d5611792f3207e4-50f386cfa8af99b3> Anastasia Orlova Lorentzen
<here is a image 3ee7ff5b527b191e-1bfb71b0cf34d564> Line Sveberg
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Oyvind Midtvedt
<here is a image 94a9ca00ab32dbc7-0ca27233c6a8969d> Kjell Heuser
Objectives:
Central nervous system manifestations of sarcoidosis occur in approximately 5% of patients with sarcoidosis, often lead to substantial morbidity, and therefore require immediate treatment. Spinal cord involvement is exceptionally rare. The tumor necrosis factor-α inhibitor infliximab seems to be an effective alternative in severe cases, refractory to other therapies, but a standard concept of treatment is lacking.
Methods:
We presented a case of severe corticosteroid-refractory spinal cord sarcoidosis with immediate and dramatic response to infliximab. In addition, we reviewed the literature on infliximab therapy in neurosarcoidosis and drew parallels to other medical fields in order to have a basis for decision making in the initiation and discontinuation of treatment.
Results:
We identified a total of 34 case reports on effective infliximab treatment of therapy-resistant neurosarcoidosis through PubMed search. Nineteen of the 34 cases reported the duration until treatment response. In accordance with our patient, 14 of the 34 case reports showed improvement between first and third infusion. Eight of the 34 cases reported sustained remission after cessation of infliximab. No definite treatment regimen was used.
Conclusions:
Infliximab seems to be a fast-acting and effective drug for severe neurosarcoidosis. No systematic treatment strategy is available because of lack of controlled trials. Until then, therapy regimens may be adapted to those used in other medical fields where infliximab treatment is well established.
... SV was associated with a decreased risk of both stroke and myocardial infarction (MI) compared with carbamazepine. 6,7 This finding is consistent with HDAC inhibition reducing stroke risk, but data are only available from this one study, and other studies have suggested that SV treatment may adversely affect cardiovascular risk factor profile.
8
For this reason, more data are required. ...
Is Sodium Valproate, an HDAC inhibitor, associated with reduced risk of stroke and myocardial infarction? A nested case-control study
Article
Full-text available
Jul 2014
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Alex Dregan
Judith Charlton
<here is a image a8dffb03021f7f3e-cb7de6ef29d49806> Charles Wolfe
Hugh S. Markus
Background
This study aimed to evaluate whether treatment with sodium valproate (SV) was associated with reduced risk of stroke or myocardial infarction (MI).
Methods
Electronic health records data were extracted from Clinical Practice Research Database for participants ever diagnosed with epilepsy and prescribed antiepileptic drugs. A nested case–control study was implemented with cases diagnosed with incident non-haemorrhagic stroke and controls matched for sex, year of birth, and study start date (ratio of 1:6). A second nested study was implemented with MI as outcome. The main exposure variable was SV therapy assessed as: ever prescribed, pre-stroke year treatment, number of SV prescriptions, and cumulative time on SV drug therapy. Odds ratios were estimated using conditional logistic regression.
Results
Data were analysed for 2002 stroke cases and 13 098 controls. MI analyses included 1153 cases and 7109 controls. Pre-year stroke SV treatment (28%) was associated with increased stroke risk (odds ratio 1.22, 95% confidence interval (CI): 1.09 to 1.38, p < 0.001). No association was observed between ever being prescribed SV with ischemic stroke (OR = 1.01, 95% CI: 0.91 to 1.12, p = 0.875). A significant association was observed between ever being prescribed SV with MI (OR = 0.78, 95% CI: 0.67 to 0.90, p < 0.001). Patients in the highest quarter of SV treatment duration had lower odds of ischemic stroke (OR = 0.57, 95% CI: 0.44 to 0.72, p < 0.001) and MI (OR = 0.29, 95% CI: 0.20 to 0.44, p < 0.001).
Conclusion
Sodium valproate exposure was associated with the risk of MI, but not ischemic stroke. However, longer exposure to SV was associated with lower odds of stroke, but this might be explained by survivor bias.
... On the other hand, Isojärvi et al. firstly found that the development of hyperinsulinemia and IR in long-term VPA therapy may be among multiple factors leading to weight gain in some patients. This observation is in agreement with data of successive studies that have suggested that hyperinsulinaemia in obese patients taking VPA is not merely a consequence of IR induced by weight gain but the development of IR may be one of the factors leading to weight gain in some patients (Pylvänen et al., 2002;Verrotti et al., 2002;
Pylvänen et al., 2003;
Lihn et al., 2005;Pylvänen et al., 2006). This is supported by the observation that weight gain during VPA treatment is related to increase in insulin concurrent with decrease in glucose level, which can stimulate appetite and may cause weight gain (Demir and Aysun, 2000). ...
Metabolic and endocrine effects of valproic acid chronic treatment
Article
Sep 2013
<here is a image f8238b14a1e59b30-6a5abf79608a15c5> Vincenzo Belcastro
<here is a image ae8d54168e68577e-d0b7493456697bba> Pasquale Striano
Claudia D'Egidio
<here is a image d02e2e5c82a16c55-108bcedc7d6c9492> Alberto Verrotti
Treatment of epileptic patients with valproic acid (VPA) may be associated with substantial weight changes that may increase morbidity and impair adherence to the treatment regimen. VPA-induced weight gain seems to be associated with many metabolic disturbances; the most frequent are hyperinsulinemia and insulin resistance, hyperleptinemia and leptin resistance. Patients who gain weight during VPA therapy can develop dyslipidemia and metabolic syndrome that are associated with long-term vascular complications such as hypertension and atherosclerosis. Moreover, an elevation in the levels of uric acid and homocysteine, together with oxidative stress, may contribute to atherosclerotic risk in patients under long-term therapy with VPA. The aim of this review is to discuss the metabolic and endocrine effects of VPA chronic treatment in patients with epilepsy.
... A recent prospective study in children who were followed for at least 2 years on VPA found that 40% developed obesity, and of those, 43% developed the metabolic syndrome, whereas non-obese patients did not [46]. Although this evidence supports the notion that drug-induced weight gain drives the development of the metabolic syndrome, Pylvanen and colleagues
[47]
found that obese VPA-treated patients had higher insulin than obese controls, suggesting that obesity may not be solely responsible for the metabolic syndrome in VPA-treated patients. It is not known whether these adverse metabolic effects contribute to increased vascular risk in VPA-treated patients over the long term. ...
Antiepileptic Drugs and Markers of Vascular Risk
Article
Jul 2010
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Carla LoPinto-khoury
Scott Mintzer
Opinion statement:
The most-used treatments for epilepsy worldwide are older-generation drugs such as phenytoin, carbamazepine, phenobarbital, and valproic acid, which have prominent enzymatic effects. Our sense of comfort with these treatments is starting to fade, however, as more and more potential long-term consequences of these drugs come to light. Epidemiologic studies demonstrate that ischemic disease of the heart and brain is more common among patients with epilepsy. Enzyme-inducing drugs are associated with elevations in a host of surrogate markers of vascular risk, suggesting that they could be responsible for increased rates of cardiovascular and cerebrovascular disease. The enzyme-inhibiting drug valproate may have adverse consequences of its own pertaining to glucose and lipid metabolism. These effects stand in addition to those well established in the literature regarding bone metabolism, hormonal abnormalities, and drug-drug interactions. Because patients with epilepsy require medication for years, and often for life, it is difficult to justify the long-term use of these agents when there are capable alternatives. Many of the adverse effects of the older drugs appear to be rapidly reversible, prompting consideration of whether patients who are currently treated with these agents should be switched to alternative therapies, even in the absence of obvious side effects. Newer medications without effects on hepatic enzymes likely do not have these chronic metabolic consequences, and we recommend their use over older-generation drugs whenever possible.
... Others have similarly reported improvement in the clinical features of PCOS after switching from valproate to lamotrigine (138), although further prospective studies are needed to confirm the reversibility of valproate-related PCOS (137). Increased rates of hyperinsulinaemia and lipid and reproductive hormone abnormalities have also been found in men treated with valproate
(139)
(140)(141). ...
The International Society for Bipolar Disorders (ISBD) consensus guidelines for the safety monitoring of bipolar disorder treatments
Article
Oct 2009
BIPOLAR DISORD
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ingeborg Wilting
<here is a image c76f819abd6a6b7f-00337c543a277622> Michael Berk
Safety monitoring is an important aspect of bipolar disorder treatment, as mood-stabilising medications have potentially serious side effects, some of which may also aggravate existing medical comorbidities. This paper sets out the International Society for Bipolar Disorders (ISBD) guidelines for the safety monitoring of widely used agents in the treatment of bipolar disorder. These guidelines aim to provide recommendations that take into consideration the balance between safety and cost-effectiveness, to highlight iatrogenic and preventive clinical issues, and to facilitate the broad implementation of therapeutic safety monitoring as a standard component of treatment for bipolar disorder.
These guidelines were developed by an ISBD workgroup, headed by the senior author (MB), through an iterative process of serial consensus-based revisions. After this, feedback from a multidisciplinary group of health professionals on the applicability of these guidelines was sought to develop the final recommendations.
General safety monitoring recommendations for all bipolar disorder patients receiving treatment and specific monitoring recommendations for individual agents are outlined.
These guidelines are derived from evolving and often indirect data, with minimal empirical cost-effectiveness data available to provide guidance. These guidelines will therefore need to be modified to adapt to different clinical settings and health resources. Clinical acumen and vigilance remain critical ingredients for safe treatment practice.
... For instance it is well known side effects of valproic acid (VPA) in patients include obesity and insulin resistance [136,337
338
339340341342. However, it must also be noted that in a study on the effects of HDAC inhibitors in adipocytes which included trichostatin A (TSA) and valproic acid (VPA) it was found that VPA reduced Leptin mRNA levels while TSA did not, suggesting that VPA therapy may be associated with altered leptin homeostasis contributing to weight gain in vivo, and therefore other HDAC inhibitors may not cause similar effects in relation to obesity and insulin resistance [343]. ...
Targeting Histone Deacetylases for the Treatment of Immune, Endocrine & Metabolic Disorders
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Matthew W Lawless
<here is a image eaa1281ee20f7114-ade0df8a25f870df> Suzanne Norris
<here is a image 9c4c051e24f9543a-b0871b87f094f7cc> Kenneth J O Byrne
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Steven G Gray
The 'histone code' is a well-established hypothesis describing the idea that specific patterns of post-translational modifications to histones act like a molecular "code" recognised and used by non-histone proteins to regulate specific chromatin functions. One modification which has received significant attention is that of histone acetylation. The enzymes which regulate this modification are described as histone acetyltransferases or HATs, and histone deacetylases or HDACs [1]. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. The pro-inflammatory environment is increasingly being recognised as a critical element for both degenerative diseases and cancer. The present review will discuss the current knowledge surrounding the clinical potential & current development of histone deacetylases for the treatment of diseases for which a proinflammatory environment plays important roles, and the molecular mechanisms by which such inhibitors may play important functions in modulating the proinflammatory environment.
... Despite the evidence strongly suggesting that HDi may have an important therapeutic role in the treatment of obesity and diabetes nevertheless there are some caveats that temper this notion. One of the caveats concerns the use of VPA in the treatment of diabetes in that known side effects of this drug in patients are in fact, obesity and insulin resistance [305]
[306]
[307][308][309][310][311]. However, it must also be noted that in a study on the effects of HDAC inhibitors in adipocytes which included TSA and VPA it was found that VPA reduced leptin mRNA levels while TSA did not, suggesting that VPA therapy may be associated with altered leptin homeostasis contributing to weight gain in vivo, and therefore other HDAC inhibitors may not cause similar effects in relation to obesity and insulin resistance [312]. ...
Targeting histone deacetylases for the treatment of disease
<here is a image 9c4c051e24f9543a-b0871b87f094f7cc> Kenneth J O Byrne
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Steven G Gray
The 'histone code' is a well-established hypothesis describing the idea that specific patterns of post-translational modifications to histones act like a molecular 'code' recognized and used by non-histone proteins to regulate specific chromatin functions. One modification, which has received significant attention, is that of histone acetylation. The enzymes that regulate this modification are described as lysine acetyltransferases or KATs, and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. The pro-inflammatory environment is increasingly being recognized as a critical element for both degenerative diseases and cancer. The present review will discuss the current knowledge surrounding the clinical potential and current development of histone deacetylases for the treatment of diseases for which a pro-inflammatory environment plays important roles, and the molecular mechanisms by which such inhibitors may play important functions in modulating the pro-inflammatory environment.
... A one-way ANOVA and Scheffe post hoc tests were used for this evaluation. Based on results from a study by Pylvanen et al.
[16]
, 21 subjects were needed in each cell of BMI category for a power of 0.804 with sensitivity of one standard deviation (S). Correlation coefficients were used to determine the relationships among the BMI, TC, HDL-C, LDL-C, and triacylglycerol variables. ...
Relationships and CHD risks of BMI, lipoproteins, lipids, and blood pressure in African-American men and women
Body mass index (BMI) is believed to be associated with coronary heart disease (CHD) risks. A major question is whether each BMI category provides independent risk information and whether the BMI categories provide similar results for African-American (AA) men and women relative to lipid, lipoproteins, and blood pressure.
A descriptive research design was used to evaluate the effects of BMI categories on lipoproteins, lipids, and blood pressure, and to determine if similar CHD risks related to these variables were observed in AA men and women. The 358 (108 men and 250 women; 40-70 year of age) participants were recruited from churches in a southeastern metropolitan area.
The results indicate that BMI is positively associated with lipoproteins, lipids, and blood pressure in both AA men and women. Relative risks for CHD were higher for obese (BMI > 30 kg/m(2)) men and women, but the overweight (OW) category provided the same information as the normal weight (NW) category for men, but not for women.
This suggests that the same BMI standards provide different CHD risk information for AA men than for AA women and that gender-specific BMI standards may be warranted for more effective CHD risk stratification in AA adults.
The effects of valproate on serum leptin, insulin, and lipid levels in epileptic children
<here is a image 15d6adaee885b39f-7acb844b1dcdd7e7> Huseyin Kilic
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Atalay Demirel
<here is a image 309f89ef3dc08e47-5da4cbf6aa350865> Serap Uysal
Background:
Weight gain is an important adverse effect of valproate (VPA) therapy. Number of mechanisms have been proposed for its pathophysiology. The aim of the present study is evaluation of biochemical derangements in epileptic children on treatment with VPA.
Methods:
Thirty epileptic children treated with VPA and 20 age-sex-matched healthy children were enrolled in this study. Blood samples were received and body mass index were calculated from all of the subjects. Serum insulin, leptin and lipid levels have been compared between two groups.
Results:
Leptin levels were significantly higher in patient group (p=0.009) whereas BMI values were comparable. There was a positive correlation between leptin and BMI among both patient and control groups (r=0.464, p=0.01, r=0.734, p=0.0001 respectively). Total cholesterol and LDL cholesterol levels were lower in VPA-treated epileptic children in comparison to control group (p=0.008; p=0.003 respectively). No significant difference was determined in insulin levels between two groups. A negative correlation was observed between plasma VPA level and TC and LDL-C levels in patients group (r = -0.380, p=0.03, r = -0.474, p=0.008, respectively).
Conclusion:
This study demonstrated that higher leptin levels in patient group despite similar BMI values. Hence, it seems likely that VPA causes a leptin resistance. Unlike other antiepileptics, VPA does not produce an increase in serum cholesterol levels. On the contrary, lower levels of total and low-density lipoprotein (LDL) cholesterol levels in VPA receiving patients have been observed in our study.
Impact of enzyme-inducing anti-epilepsy drugs on lipid levels in elderly patients with epilepsy
It has been speculated that patients with epilepsy in elderly is increasing. The effect of enzyme-inducing antiepileptic drugs (EIAED) on lipid metabolism is well known. However, the study in elderly subjects has been rarely conducted. Furthermore, it has not been directly assessed whether EIAED use causes the change of lipid levels from normal range to abnormal range. Adult patients with epilepsy (235 on EIAED, 213 on non-EIAED) were divided by age (20−64, 65−74 and 75 over years old). Longitudinal change (before starting AED, in 3 and 6 months after starting AED) of serum total cholesterol (TC), triglyceride (TRIG), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C) and non-HDL cholesterol (non-HDL-C) were retrospectively analyzed using mixed models. The risk of change of lipid levels from normal range to abnormal range was also assessed by logistic regression analysis.
Comparison between patients with EIAED use (EIAED group) and patients with non-EIAED use (non-EIAED group) revealed significant differences. non-EIAED group was set as reference. Differences in least square mean (LSM), 95 % confidence interval (CI) and P value in analysis of LDL-C and non-HDL-C levels (1 × 10⁻²) were as follows: 0.23 (0.10 ∼ 0.36), P < 0.001, 0.22 (0.09 ∼ 0.33), P = 0.001 in patients with age 65-74. In patients of age over 75, those were 0.08 (0.01 ∼ 0.15), P = 0.038, 0.17 (0.07 ∼ 0.26), P < 0.001, respectively. In patients with age 65–74, odds ratios (ORs) (95 % CI) in change of TC, LDL and non-HDL-C level from normal range to abnormal range were 32.28 (1.83–567.05), 48.43 (2.69–869.05), 12.04 (1.29–111.88), respectively. In patients with age 75 over, odds ratios (ORs) (95 % CI) in change of TC, LDL and non-HDL-C level from normal range to abnormal range were 46.02 (2.77–762.89), 5.53 (1.27–23.94), 2.38 (1.01–10.76), respectively.
EIAED use had significant impact on changes in lipid levels in elderly patients.
Furthermore, we could assess the impact of switching AED from EIAED to levetiracetam (LEV) in 36 patients including elderly. Switching AED from EIAED to LEV had significant impact in reducing TC, TRIG, LDL-C and non-HDL-C in both younger adult and elderly patients.
Evaluate the Effects of long-term valproic acid treatment on metabolic profiles in newly diagnosed or untreated female epileptic patients: a prospective study
Purpose:
Excessive weight gain associated with sodium valproate (VPA) may predispose patients with epilepsy to other health problems such as insulin resistance. We prospectively evaluated the long-term impact of VPA monotherapy compared with lamotrigine (LTG) monotherapy on anthropometric and metabolic parameters in women with epilepsy. Our primary objective is to understand the underlying mechanism responsible for VPA-induced obesity.
Methods:
Sixty-six female patients with newly diagnosed or untreated epilepsy were included in the study. Thirty-four patients with VPA and thirty-two patients with LTG were treated for a period of one year in our center. Anthropometric and clinical data were collected at 5 time points: before, at 6th week, 3rd month, 6th month, 9th month and 12th month (last visit). Biochemical and hormonal data were collected 2 time points: before and last visit.
Results:
Subjects in the VPA group had significantly higher body weight than LTG-treated subjects (64.88?3.25 vs. 58.28?2.43, P<0.001). HOMA-IR level was significantly increased (2.76 vs. 1.35, P<0.05), and adiponectin levels were significantly lower in the VPA group (3.46 vs. 6.22, P<0.05). Triglycerides levels were significantly increased (118 vs. 96, P<0.05), and HDL-C levels were significantly lower in the VPA group. Both the VPA-treated group and the LTG-treated group showed no significant difference in term of total cholesterol, LDL-C, fasting blood glucose and serum leptin levels.
Conclusions:
Based on the findings of this study, we proposed that VPA induced hypoadiponectinemia which correlates significantly with insulin resistance. These two factors may be responsible for weight gain, possible by stimulating appetite. Valproic acid appears to be use cautionally in obese females with epilepsy.
Changes of serum lipid levels after antiepileptic medication in epileptic patients after brain infarction
Dyslipidemia is a well-known cardio- and cerebro-vascular risk factor. Older antiepileptic drugs (AEDs), including carbamazepine (CBZ), phenytoin (PHT) and phenobarbital, induce the hepatic cytochrome P450 (CYP) system that is extensively involved in the synthesis and metabolism of cholesterols. Those AEDs can increase the potential of dyslipidemia development. The present study sought to examine the changes of serum lipid levels after the single administration of valproate (VA), CBZ, PHT, zonisamide (ZNS), levetiracetam (LEV) or lamotrigine (LTG) for 3 months in epileptic patients after cerebral infarction. CBZ or PHT monotherapy increased the serum TC and LDL-C levels significantly. The serum levels of TC and LDL-C did not differ significantly after the administration of VA, ZNS, LEV, or LTG. Serum HDL-C and TG levels did not differ after treatment with any AEDs significantly. Thus, we should pay more attention to serum lipid levels in post-stroke epileptic patients treated with CYP-induced AEDs. For the secondary prevention of brain infarction, switching to non-CYP-induced AEDs might be considered in patients who CYP-induced AEDs increased serum LDL-C levels.
Influence of antiepileptic drugs on serum lipid levels in adult epilepsy patients
| https://www.researchgate.net/publication/10887764_Fasting_serum_insulin_and_lipid_levels_in_men_with_epilepsy |
Implementation of an Experimental Setup Based on the Three-Omega Method for Thermal Conductivity Measurements of Molten Salts (Conference) | OSTI.GOV
The U.S. Department of Energy's Office of Scientific and Technical Information
Title:
Implementation of an Experimental Setup Based on the Three-Omega Method for Thermal Conductivity Measurements of Molten Salts
Full Record Other Related Research
Abstract
Molten salt reactors (MSRs) are one of the most promising next-generation nuclear reactor designs which use molten salts as the fuel and coolant. To design, model, predict, license, and operate MSRs, the behavior of the fuel and coolant must be understood as a function of temperature and irradiation, i.e., burnup. Of particular importance and complexity is the reliable and reproducible measurement of thermal conductivity of molten salts at high temperatures (> 500 °C). Thermal conductivity provides information on the rate at which heat passes through a specified material and is dependent on chemical composition. Currently, in the national laboratory complex, several methods for measuring thermal conductivity on molten salt systems are under development, however, to date, consistent data have not been produced. Typically, thermal conductivity measurements of high-temperature melts have been conducted by using the Transient Hot Wire (THW) method where thermal conductivity is determined by the change in temperature over time at a certain distance from a heating wire. Another time-dependent technique is the laser flash method, commonly used for solid samples. Laser flash requires prior measurements of density and heat capacity to calculate the thermal conductivity of the sample, introducing additional measurement errors. Steady state and time-dependent measurements more »
such as THW and laser flash have errors from convection and ambient temperature fluctuations (heat radiation). In order to produce high fidelity thermal conductivity data, a measurement technique needs to be developed that will reduce the effect of convection at high temperatures by measuring in a very fast time window. In addition, to measure on actinide and irradiated salts the sample size should be small. Therefore, this project aims to develop a frequency-domain technique based on the three-omega (3?) method, previously proven to work on solids, nanofluids and low temperature solar salts (25 to 250 °C). If the 3?-device can be designed with materials that can withstand high temperatures (>500 °C) and can be configured to reduce errors due to convection, then it would prove to be a valuable technique for ensuring thermal conductivity on molten salt systems needed for MSR development. For this proposal, the 3? instrument will be designed, assembled, and tested on non-radioactive salts before being used on actinide bearing salts. In addition, a thermal model will be developed to determine the thermal conductivity of the sample from the measured thermal oscillation of the sensor. Because 3? is a direct method that requires a small volume of sample and works in a very fast time window, it will aid in suppressing the interference due to convection which is ideal when working with high temperature liquid samples. « less
Authors:
Rocio Rodriguez Laguna, Maria Del [1]
+ Show Author Affiliations
Idaho National Laboratory
Publication Date:
2021-12-02
Research Org.:
Idaho National Lab. (INL), Idaho Falls, ID (United States)
Sponsoring Org.:
INL Laboratory Directed Research & Development (LDRD) program (DOE-Idaho operations office); USDOE Office of Nuclear Energy (NE)
OSTI Identifier:
1836837
Report Number(s):
INL/CON-21-65124-Rev000
DOE Contract Number:
DE-AC07-05ID14517
Resource Type:
Conference
Resource Relation:
Conference: Workshop on Molten Salt Thermal Properties - 2021, Online, 11/15/2021 - 11/17/2021
Country of Publication:
United States
Language:
English
Subject:
36 - MATERIALS SCIENCE ; 11 - NUCLEAR FUEL CYCLE AND FUEL MATERIALS ; 47 - OTHER INSTRUMENTATION ; Thermal conductiviy ; Molten salt reactor ; Three-omega technique ; Thermophysical properties
Citation Formats MLA APA Chicago BibTeX Rocio Rodriguez Laguna, Maria Del. Implementation of an Experimental Setup Based on the Three-Omega Method for Thermal Conductivity Measurements of Molten Salts . United States: N. p., 2021.
Web. Copy to clipboard Rocio Rodriguez Laguna, Maria Del. Implementation of an Experimental Setup Based on the Three-Omega Method for Thermal Conductivity Measurements of Molten Salts . United States. Copy to clipboard Rocio Rodriguez Laguna, Maria Del. 2021.
"Implementation of an Experimental Setup Based on the Three-Omega Method for Thermal Conductivity Measurements of Molten Salts". United States. https://www.osti.gov/servlets/purl/1836837. Copy to clipboard @article{osti_1836837, title = {Implementation of an Experimental Setup Based on the Three-Omega Method for Thermal Conductivity Measurements of Molten Salts}, author = {Rocio Rodriguez Laguna, Maria Del}, abstractNote = {Molten salt reactors (MSRs) are one of the most promising next-generation nuclear reactor designs which use molten salts as the fuel and coolant. To design, model, predict, license, and operate MSRs, the behavior of the fuel and coolant must be understood as a function of temperature and irradiation, i.e., burnup. Of particular importance and complexity is the reliable and reproducible measurement of thermal conductivity of molten salts at high temperatures (> 500 °C). Thermal conductivity provides information on the rate at which heat passes through a specified material and is dependent on chemical composition. Currently, in the national laboratory complex, several methods for measuring thermal conductivity on molten salt systems are under development, however, to date, consistent data have not been produced. Typically, thermal conductivity measurements of high-temperature melts have been conducted by using the Transient Hot Wire (THW) method where thermal conductivity is determined by the change in temperature over time at a certain distance from a heating wire. Another time-dependent technique is the laser flash method, commonly used for solid samples. Laser flash requires prior measurements of density and heat capacity to calculate the thermal conductivity of the sample, introducing additional measurement errors. Steady state and time-dependent measurements such as THW and laser flash have errors from convection and ambient temperature fluctuations (heat radiation). In order to produce high fidelity thermal conductivity data, a measurement technique needs to be developed that will reduce the effect of convection at high temperatures by measuring in a very fast time window. In addition, to measure on actinide and irradiated salts the sample size should be small. Therefore, this project aims to develop a frequency-domain technique based on the three-omega (3?) method, previously proven to work on solids, nanofluids and low temperature solar salts (25 to 250 °C). If the 3?-device can be designed with materials that can withstand high temperatures (>500 °C) and can be configured to reduce errors due to convection, then it would prove to be a valuable technique for ensuring thermal conductivity on molten salt systems needed for MSR development. For this proposal, the 3? instrument will be designed, assembled, and tested on non-radioactive salts before being used on actinide bearing salts. In addition, a thermal model will be developed to determine the thermal conductivity of the sample from the measured thermal oscillation of the sensor. Because 3? is a direct method that requires a small volume of sample and works in a very fast time window, it will aid in suppressing the interference due to convection which is ideal when working with high temperature liquid samples.}, doi = {}, url = {https://www.osti.gov/biblio/1836837},
journal = {}, number = , volume = , place = {United States}, year = {2021}, month = {12} } Copy to clipboard
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Similar records in OSTI.GOV collections: Review of thermophysical property methods applied to fueled and un-fueled molten salts Journal Article Magnusson, Jared ; Memmott, Matthew ; Munro, Troy - Annals of Nuclear Energy
Recent investigation into designs of molten salt reactors (MSR) requires accurate data of candidate salts. Review of the literature shows lacking thermophysical (TP) property data for coolants and fuel-bearing salts of Advanced High Temperature Reactors (AHTR). Measurement uncertainties of current data are even more deficient, and this affects ongoing research where MSR modeling and testing are being performed. Melting temperature, viscosity, density, specific heat capacity, and thermal and electrical conductivity measurements are often not arranged together or discussed in great detail, especially for fuel-bearing salts. Raw data from key findings spanning over 70 years for LiF, LiF-BeF 2
, LiF-NaF-KF, KCl-MgCl 2
, KF-ZrF 4
, more » and NaF-KF-MgF 2 have been organized and presented here. Brief description of methods used to obtain these results, in addition to the TP data of some of these salts as fuel carriers, has also been discussed. Thermal conductivity data are particularly weak due to older, high-error measurement techniques. More recent measurement systems to evaluate salt thermal conductivity show promise for obtaining consistent absolute values. This work concludes that measurement systems such as transient hot-wire method, forced Rayleigh scattering, and laser flash analysis provide the most promise to fill these data gaps and reduce current uncertainty in thermal conductivity measurements of both fueled and un-fueled molten salts. « less https://doi.org/10.1016/j.anucene.2020.107608 Full Text Available Development of High-Temperature Emissivity Measurement Capabilities for Molten Salts at PNNL Technical Report Lonergan, Jason ; Lonergan, Charmayne
In this study, an emissivity measurement system for a liquid molten salt was developed on the bases on the Stefan Boltzmann Law. A prototype device operating in ambient atmosphere was constructed an initial result compared well with available literature. The diffuse emissivity of NaCl-KCl system (NaCl, 51mol% NaCl – 49mol% KCl and KCl) was measured from 550 to 850 °C at a wavelength of 1.3 µm. The system appears to be relatively invariant with composition but a clear trend of decreasing emissivity values from ~0.9 at 550 °C to 0.75 at 850 °C was observed. A schematic for an enclosed more » system for inert atmosphere and actinide salts was drafted. Several of the components for fabrication of this device, improved laser system, furnace, nickel for capsule construction, have been purchased and are ready for assembly. The new laser system will have an improved measurement range of 275-1000 °C. The clam shell furnace has a maximum temperature of 1200 °C and will support the hermetically sealed inert encapsulation vessels. Nickel plate and tubing will create a relatively corrosion resistance capsule for testing that can withstand temperature up to 1000 °C. Emissivity measurements are important for a larger effort to understand radiative heat transfer within molten salts at elevated temperatures (600-1000 °C). Literature review of optical salt properties and radiative heat transfer models indicated that systems within elevated temperature regimes could see upwards of 20% or more of their total heat transferred through photonic mechanisms. Ultimately, future work will measure the total thermal conductivity and break down the molecular and radiative portions. Thermal conductivity, along with other thermal properties of molten salts, both coolant and fuel, are fundamental to modeling and simulations that support MSR design. The results presented here and ongoing work at PNNL will be useful in selecting optimal salt compositions, designing reactor systems, and optimizing heat transfer within a MSR power plant. « less https://doi.org/10.2172/1984700 Full Text Available Radiative Heat Transport and Optical Characterization of High Temperature Molten Salts Other Anderson, Mark ; Scarlat, Raluca ; Kats, Mikhail A. ; ...
The goal of this project was to advance the field of molten fluoride radiative heat transfer (RHT), through optical property measurements, heat transfer loop construction and operation, and computational fluid dynamics simulations. The following outcomes have been accomplished. A comprehensive review has been conducted to compile all available RHT-relevant optical absorption data for molten fluorides. The various measurement methods have also been compiled and critiqued. Thermal emission measurement methods have been refined and documented. A unique thermal emissivity measurement facility has been constructed and used to measure the emissivity of flowing FLiBe-exposed SS316 samples. A slight increase has been observed more » in the emissivity compared to unexposed SS316. A dual reflectance-emission setup was partially demonstrated for the purpose of molten fluoride absorption measurement. Preliminary infrared edge data for FLiNaK was obtained. A visible near-infrared (NIR) measurement setup has been constructed and will be used to measure absorption of corrosion products in FLiBe. A new multi-band thermal radiation method using blackbody-weighted spectral bands for the absorption-coefficient was deployed to investigate the thermal performance of the UW Natural Circulation FLiBe Loop under various power levels and operating conditions. The results showed an increasing and decreasing trend in the overall heat transfer with optical thickness with a maximum at optical thickness τ D ≈Ο(1). A forced convection FLiBe loop was constructed for the purpose of studying corrosion and thermal hydraulic phenomena. A vertical cantilever pump is used to achieve up to 5 gpm and 5 m/s flow velocity in hot and cold test sections. A methodology has been established for modeling radiative heat transfer (RHT) in molten salt coolants for the purpose of quantifying the contribution of thermal radiation in conditions relevant to FHR or MSR systems. The comparison between the results obtained for forced and mixed convection showed that in the studied ranges of optical thickness, the maximum effect of RHT on overall heat transfer was 60% improvement observed at z/D = 250 for forced convection; whereas for mixed convection, that value was higher at 170% observed at z/D = 30. The highest effect of RHT on the overall energy distribution was observed at τ D ≈3.4. Negligible effect (<20%) was observed above τ D =18 and below τ D ≈0.002. A CFD code-to-code comparison was conducted using COMSOL Multiphysics at UW-Madison and STAR-CCM at MIT, for a forced and mixed convection laminar flow for a grey medium in a vertical heated using both COMSOL Multiphysics at UW-Madison and STAR-CCM at MIT. The relative error was the largest at τ D =40 for the radiative heat flux, bulk temperature, and Nusselt number. On the other hand, the relative error was the least at τ D =0.002 for the conductive heat flux, bulk temperature, and Nusselt number. « less Full Text Available Integrated Approach to Fluoride High Temperature Reactor Technology and Licensing Challenges (FHR-IRP) Technical Report Zhang, Dingkang ; Rahnema, Farzad
This document constitutes progress made on this project by the Georgia Tech led Integrated Approach to Fluoride High Temperature Reactor Technology and Licensing Challenges (FHR-IRP). This is the first draft of the project final report. Chapter 3 is focused on Tritium management. Tritium management in Fluoride-salt High-temperature Reactors (FHRs) presents a major operational concern and a significant challenge. Tritium is generated via multiple pathways including various interactions in fuel and structural materials, as well as coolant (primarily interaction with lithium and beryllium), leading to a complex evolution and spatial distribution of tritium generation rate. FHR generates orders of magnitude more more » tritium than in LWRs, and has potential for a significant release, via permeation through structural materials (due to high temperature), and through heat exchanger(s). Therefore, accurate estimate is necessary. For that purpose relevant tritium production pathways were identified. A methodology to obtain space-time dependent tritium generation rate was developed and implemented, employing SCALE and MCNP codes. Detailed models of the reference Advanced High Temperature Reactor (AHTR) design were developed. A multi-parametric metrics was introduced to capture relevant tritium production indicators, including the instantaneous tritium production rate, total tritium production (neglecting subsequent decay), and accumulated tritium production (accounting for the decay). The obtained results will inform tritium management, including the sizing of the components, and to gain insight on the impact of the core design parameters on tritium generation rates.Research effort on Liquid Salt Impurity Removal, Redox and Corrosion Control is discussed in Chapter 4. Section 4.1 is an introduction chapter. Based on the current available knowledge and operation experience on previous MSRs and other types of nuclear reactors, the report identifies the major impurities that are related to either material compatibility, salt properties or radioactive source terms, and the potential contamination sources of these impurities, their transport in the primary coolant loop and available cleanup methodologies for a particular group of impurity. In section 4.2, the available purification methods were discussed, including the liquid/liquid extraction using liquid Bi-Li which has been applied in MSBR and electrochemical purification which is developed based on Pyroprocessing. In this section, the new multi-stage and multi-salt-component was developed and discussed. Section 4.3 discussed the redox potential control for salt chemistry and corrosion mitigation, including the control theory and the soluble/soluble buffer control method. The section also developed method on how to analyze soluble/soluble redox reaction in a molten salt system and designed an electrochemical sensor for redox potential control. Corrosion models were also reported in this section. Section 4.4 focused on how to measure the fundamental properties in a molten salt. As an example, the section focused on La fluoride in the molten salt. The section developed methods on how analyze electrochemical measurement data to obtain the fundamental properties including the redox potential, diffusion coefficient and exchange current density. All these fundamental information is important for salt purification system development. Section 4.5 focused on measurements of corrosion products in the salts. Because of the different behaviors between Cr and La in the salt, new analysis method for Cr fluorides in the salt was developed. Some results for Fe fluoride in the salt and corrosion measurements were also reported. Section 4.6 demonstrated the separation of oxide from the salt. This section also measured the solubility of La 2 O 3 in the salt as function of temperature. Section 4.7 focused on the separation of La and Ce from the molten salt. These two elements were selected because La was found to be separated by using inert electrode, while for separation of Ce, reactive electrode must be selected. Section 4.8 demonstrated the separation iodine ions from the molten salt. Two kinds of working electrode materials (metal W and graphite) were investigated. Section 4.9 focused on the fundamental data of fission products and actinides in liquid Bi. The chapter reviewed the available data, then based a CALPHAD model, the available data were broadened to the concentration-dependent cases. « less https://doi.org/10.2172/1505504 Full Text Available Generation IV Reactors Integrated Materials Technology Program Plan: Focus on Very High Temperature Reactor Materials Technical Report Corwin, William ; Burchell, Timothy ; Katoh, Yutai ; ...
Since 2002, the Department of Energy's (DOE's) Generation IV Nuclear Energy Systems (Gen IV) Program has addressed the research and development (R&D) necessary to support next-generation nuclear energy systems. The six most promising systems identified for next-generation nuclear energy are described within this roadmap. Two employ a thermal neutron spectrum with coolants and temperatures that enable hydrogen or electricity production with high efficiency (the Supercritical Water Reactor-SCWR and the Very High Temperature Reactor-VHTR). Three employ a fast neutron spectrum to enable more effective management of actinides through recycling of most components in the discharged fuel (the Gas-cooled Fast Reactor-GFR, the more » Lead-cooled Fast Reactor-LFR, and the Sodium-cooled Fast Reactor-SFR). The Molten Salt Reactor (MSR) employs a circulating liquid fuel mixture that offers considerable flexibility for recycling actinides and may provide an alternative to accelerator-driven systems. At the inception of DOE's Gen IV program, it was decided to significantly pursue five of the six concepts identified in the Gen IV roadmap to determine which of them was most appropriate to meet the needs of future U.S. nuclear power generation. In particular, evaluation of the highly efficient thermal SCWR and VHTR reactors was initiated primarily for energy production, and evaluation of the three fast reactor concepts, SFR, LFR, and GFR, was begun to assess viability for both energy production and their potential contribution to closing the fuel cycle. Within the Gen IV Program itself, only the VHTR class of reactors was selected for continued development. Hence, this document will address the multiple activities under the Gen IV program that contribute to the development of the VHTR. A few major technologies have been recognized by DOE as necessary to enable the deployment of the next generation of advanced nuclear reactors, including the development and qualification of the structural materials needed to ensure their safe and reliable operation. The focus of this document will be the overall range of DOE's structural materials research activities being conducted to support VHTR development. By far, the largest portion of material's R&D supporting VHTR development is that being performed directly as part of the Next-Generation Nuclear Plant (NGNP) Project. Supplementary VHTR materials R&D being performed in the DOE program, including university and international research programs and that being performed under direct contracts with the American Society for Mechanical Engineers (ASME) Boiler and Pressure Vessel Code, will also be described. Specific areas of high-priority materials research that will be needed to deploy the NGNP and provide a basis for subsequent VHTRs are described, including the following: (1) Graphite: (a) Extensive unirradiated materials characterization and assessment of irradiation effects on properties must be performed to qualify new grades of graphite for nuclear service, including thermo-physical and mechanical properties and their changes, statistical variations from billot-to-billot and lot-to-lot, creep, and especially, irradiation creep. (b) Predictive models, as well as codification of the requirements and design methods for graphite core supports, must be developed to provide a basis for licensing. (2) Ceramics: Both fibrous and load-bearing ceramics must be qualified for environmental and radiation service as insulating materials. (3) Ceramic Composites: Carbon-carbon and SiC-SiC composites must be qualified for specialized usage in selected high-temperature components, such as core stabilizers, control rods, and insulating covers and ducting. This will require development of component-specific designs and fabrication processes, materials characterization, assessment of environmental and irradiation effects, and establishment of codes and standards for materials testing and design requirements. (4) Pressure Vessel Steels: (a) Qualification of short-term, high-temperature properties of light water reactor steels for anticipated VHTR off-normal conditions must be determined, as well as the effects of aging on tensile, creep, and toughness properties, and on thermal emissivity. (b) Large-scale fabrication process for higher temperature alloys, such as 9Cr-1MoV, including ensuring thick-section and weldment integrity must be developed, as well as improved definitions of creep-fatigue and negligible creep behavior. (5) High-Temperature Alloys: (a) Qualification and codification of materials for the intermediate heat exchanger, such as Alloys 617 or 230, for long-term very high-temperature creep, creep-fatigue, and environmental aging degradation must be done, especially in thin sections for compact designs, for both base metal and weldments. (b) Constitutive models and an improved methodology for high-temperature design must be developed. « less https://doi.org/10.2172/951084 Full Text Available Similar Records | https://www.osti.gov/biblio/1836837 |
The Pattern and Effectiveness of Forager Allocation Among Flower Patches by Honey Bee Colonies | Request PDF
Request PDF | The Pattern and Effectiveness of Forager Allocation Among Flower Patches by Honey Bee Colonies | To gather its food efficiently, a colony of honey bees must allocate its foragers among flower patches in accordance with their profitabilities.... | Find, read and cite all the research you need on ResearchGate
Bees
Article
The Pattern and Effectiveness of Forager Allocation Among Flower Patches by Honey Bee Colonies
January 1993
Journal of Theoretical Biology160(1):23–40
DOI: 10.1006/jtbi.1993.1002
Authors:
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
John J. Bartholdi III
John J. Bartholdi III
<here is a image 4ab6ac4296129357-4a699ebf09d211d0>
Thomas Seeley
Cornell University
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe>
Craig A. Tovey
Georgia Institute of Technology
<here is a image d4a4921722d24ce7-528c6853da3d4fb4>
John H. Vande Vate
Georgia Institute of Technology
Abstract
To gather its food efficiently, a colony of honey bees must allocate its foragers among flower patches in accordance with their profitabilities. Previous empirical studies have revealed the mechanisms of the allocation process, but tell us neither the allocation pattern that results nor its effectiveness. To investigate these topics, we develop a system of differential equations that models the allocation process in a hypothetical colony of bees whose behavior closely approximates the observed behavior of real bees. We find that our hypothetical colony tends toward a specific allocation of foragers among flower patches, one in which each forager experiences the same rate of "value" accumulation regardless of which patch she is visiting (the equal value rate allocation). Moreover, we show that no allocation brings value to the hypothetical colony's hive more than twice as quickly as the equal value rate allocation. To test the accuracy of our model and its predictions about the allocation patterns of honey bee colonies, we use the model to generate predictions about the patterns of dancing and other variables for different flower patches that should be observed in real colonies. The results of one empirical test confirm the model's prediction that at equilibrium the foragers from different patches will experience equal rates of value accumulation.
... 133 качестве которых выбираются результаты функционирования семьи, будет давать необходимое решение (как, например, известная теорема предельной полезности [15,14]). Однако такой подход на колониальном уровне практически не пригоден, поскольку: 1) формальные критерии оптимальности семьи точно не известны, 2) не учитываются биологические механизмы реализации цели, которые могут занижать реальную результативность семей по сравнению с идеальной
[16,
14]. ...
... 1), основанный на эмпирической закономерности, что семья направляет своих фуражиров на «наиболее качественные» источники корма [9][10]. Есть основание считать, что эта стратегия фактически и реализует состояние, близкое к оптимальному с точки зрения максимизации приноса корма
[16,
14]. Однако при попытке моделирования возникает фундаментальная проблема: какие источники следует считать наиболее «качественными»? ...
... Моделирование фуражировки при равномерном стационарном распределении фуражиров по массиву нектароносных растений показало значительное уменьшение эффективности нектаросбора, т.е. ее невыгодность для семей [5], что действительно не реализуется в природе [9,
16,
19]. ...
Modeling of Productivity of Nectar Productive (Agro)Ecosystems
Article
May 2007
А.В. Кудряков
A.V. Kudryakov
... Lorsqu'une abeille découvre une parcelle de fleurs intéressantes, elle recrute ses congénères pour butiner celles-ci (Winston, 1993). Ce système assure une grande efficacité pour la colonie tout entière car la majorité des butineuses sont dirigées vers les endroits les plus rentables, et ce à des distances dépassant parfois 10 km
(Bartholdi et al., 1993)
et avec une rapidité permettant l'exploitation de ressources éphémères (Waddington et al., 1994). La distance de butinage d'une colonie dépend de la structure du paysage, de la saison et de la colonie ellemême (Buchmann et Shipman, 1991 ;Steffan-Dewenter et Kuhn, 2003). ...
... Certains prédisent la dynamique comportementale des butineuses, validée au moyen d'expériences sur des ressources alimentaires artificielles Seeley et al., 1991 ;de Vries et Biesmeijer, 1998). D'autres modélisent l'efficience énergétique d'une ruche en relation avec un nombre élevé de sources théoriques de nourriture dont les gains et pertes énergétiques varient
(Bartholdi et al., 1993 ;
Dukas et Edelstein-Keshet, 1998). D'autres encore étudient l'évolution du nombre d'abeilles présentes dans une colonie en fonction de la durée de leurs vols de butinage et de besoins énergétiques variables (Beauchamp, 1992). ...
... Les taux de recrutement des abeilles pour une source de butinage diminue linéairement si la distance entre cette source et la ruche augmente (Menzel et Mercer, 1987). En conséquence, l'attractivité d'un secteur fut supposée diminuant si la distance de butinage augmente, jusqu'à s'annuler pour une distance maximale de 10 000 m, calculée par
Bartholdi et al. (1993)
. Enfin, Guerriat (1999) évalua l'attractivité d'un secteur en portant le taux de recouvrement des espèces mellifères présentes sur ce secteur au carré, de manière à favoriser les espèces les mieux représentées. ...
Prévision des potentialités de production de miel à l’échelle d’un rucher au moyen d’un système d’information géographique
Full-text available
May 2006
Xavier Janssens
<here is a image f2afb638714335f1-1cdd63225b753aa2> Étienne Bruneau
Philippe Lebrun
... In a second category of functions governing a colony's estimates of success, s i is a monotonically increasing function of ∂n i f i /∂n i , the marginal rate of return from task i, and a monotonically decreasing function of n i , the number of ants presently performing task i. In view of the optimum described by
(5)
, this functional relationship implies that the colony's measure of success reflects the actual fitness value of tasks to the colony as a whole. How could individual ants achieve such an estimate of the value of each task? ...
... If ants are able to estimate the returns from a task (the first rule for assessing success), then the colony equalizes returns across all tasks. This results in an ideal free distribution, which can be different from the distribution defined by (5), but is generally not far off
[5]
. However, if individuals are able to estimate marginal value by assessing both returns and the density of ants in a task (the second rule for assessing success), then the colony fulfills the marginal value theorem, achieving the optimal distribution of individuals. ...
... (Whether this surprising asymmetry in the intensity of exploitation is an adaptation that reduces the number of lost ants [13,43], the risk of predation, or the threat of competing ants [9,36], or is instead an incidental characteristic of the colony's dynamics, is not yet clear.) In certain circumstances, the recruitment dynamics described by equation set (6) result in dramatic deviation from the foraging behavior that would maximize the colony's rate of energy gain and would be considered optimal under the marginal value theorem
(5)
. When a colony is presented first with a low-quality food source, and then with a second source of higher quality, it fails to redirect its foraging efforts to the richer source [6,7]. ...
Distributed problem solving in social insects
Oct 2001
<here is a image 4f8e7954d64a5a53-adb54d646513cb0c> Aaron Hirsh
<here is a image 30a5c4662b909f13-2f8e1dc8ef12184b> Deborah M. Gordon
In a social insect colony, large numbers of individuals all follow the same set of behavioral rules. Without centralized control,
these individuals' interactions with each other and with their environment result in the allocation of individuals to various
tasks, and in the distribution of foragers among available food sources. We review this highly parallel and distributed form
of information processing, discussing its potential sophistication, its actual performance in various groups of social insects,
its general strengths and liabilities, and finally, the adaptations that compensate for these liabilities.
... Second, we compare ants that maximize the seed collection rate at the individual level with those that use information about the whole colony to maximize at the colony level. The former strategy is suboptimal but simple to achieve by equalizing seed collection rate across foragers
(Bartholdi et al. 1993;
Pacala et al. 1996;Dukas and Edelstein-Keshet 1998). ...
... 2c). Although the individual-level strategy is not optimal, it uses no global information, is robust in changing environments, and reduces colony intake rate only slightly
(Bartholdi et al. 1993;
Pacala et al. 1996;Seeley 1997). ...
... Our models do not specify the mechanism by which ants achieve a given allocation. Some communication is required
(Bartholdi et al. 1993;
Pacala et al. 1996;Seeley 1997), which could be indirect through pheromones or direct through contact. Decisions could also include components of individual memory or fidelity (Fewell 1990;Crist and MacMahon 1991;Haefner and Crist 1994;Brown and Gordon 2000). ...
Optimization, Conflict, and Nonoverlapping Foraging Ranges in Ants
Dec 2003
<here is a image fb43e5e9d502f090-25de46d6f595baca> Frederick R. Adler
<here is a image 30a5c4662b909f13-2f8e1dc8ef12184b> Deborah M. Gordon
An organism's foraging range depends on the behavior of neighbors, the dynamics of resources, and the availability of information. We use a well-studied population of the red harvester ant Pogonomyrmex barbatus to develop and independently parameterize models that include these three factors. The models solve for an allocation of foraging ants in the area around the nest in response to other colonies. We compare formulations that optimize at the colony or individual level and those that do or do not include costs of conflict. Model predictions were compared with data collected on ant time budgets and ant density. The strategy that optimizes at the colony level but neglects costs of conflict predicts unrealistic levels of overlap. In contrast, the strategy that optimizes at the individual level predicts realistic foraging ranges with or without inclusion of conflict costs. Both the individual model and the colony model that includes conflict costs show good quantitative agreement with data. Thus, an optimal foraging response to a combination of exploitation and interference competition can largely explain how individual foraging behavior creates the foraging range of a colony. Deviations between model predictions and data indicate that colonies might allocate a larger than optimal number of foragers to areas near boundaries between foraging ranges.
... In both of these cases, it is thought that communication about high-quality resources creates a feedback loop: each new forager recruited may in turn recruit more, until overexploitation reduces the rate at which rewards can be collected [8,9]. This feedback loop leads to a preferential buildup of foragers at higher quality resources [10]
[11]
[12]. Although the results of this dynamic process have not been well quantified in nature, it is thought that for many trail-laying ants the result is a collective decision to exploit only the best resource, while honey bees are able to maintain some level of foraging effort even on lower-quality resources [12][13][14][15][16]. ...
... This begs the question: when is dance communication useful, and why did it evolve? Theoretical and empirical studies have suggested that one important function of dancing is to improve the group's foraging efficiency by focusing foraging effort on the most rewarding resources [10,
11,
44]. Therefore, communication might be particularly useful in environments with many resource types that vary in quality [23,45,46]. ...
Dance Communication Affects Consistency, but Not Breadth, of Resource Use in Pollen-Foraging Honey Bees
Oct 2014
PLOS ONE
<here is a image c4cbd11193de11f2-e1456273e93f290f> Matina C. Donaldson-Matasci
<here is a image 05e979201eb567be-578f87aeffcb6306> Anna Dornhaus
In groups of cooperatively foraging individuals, communication may improve the group's performance by directing foraging effort to where it is most useful. Honey bees (Apis mellifera) use a specialized dance to communicate the location of floral resources. Because honey bees dance longer for more rewarding resources, communication may shift the colony's foraging effort towards higher quality resources, and thus narrow the spectrum of resource types used. To test the hypothesis that dance communication changes how much honey bee colonies specialize on particular resources, we manipulated their ability to communicate location, and assessed the relative abundance of different pollen taxa they collected. This was repeated across five natural habitats that differed in floral species richness and spatial distribution. Contrary to expectation, impairing communication did not change the number or diversity of pollen (resource) types used by individual colonies per day. However, colonies with intact dance communication were more consistent in their resource use, while those with impaired communication were more likely to collect rare, novel pollen types. This suggests that communication plays an important role in shaping how much colonies invest in exploring new resources versus exploiting known ones. Furthermore, colonies that did more exploration also tended to collect less pollen overall, but only in environments with greater floral abundance per patch. In such environments, the ability to effectively exploit highly rewarding resources may be especially important-and dance communication may help colonies do just that. This could help explain how communication benefits honey bee colonies, and also why it does so only under certain environmental conditions.
... The resulting self-organized proportionate allocation pattern, derived from multiple and proportionate feedback on goodness of food sources, is described by Seeley et al. (1991) and validated by experimental study on a real honey bee colony. The model given by
Bartholdi, Seeley, Tovey, and Vande Vate (1993)
predicts a steady-state pattern of forager allocation where rate of value accumulation equalizes among forage sites being exploited, i.e., self-organizing allocation results in equal average nectar return where f i (x i ) denotes the value returned from x i foragers collecting nectar at the ith forage site. ...
... Intriguingly, this allocation pattern is not optimal (unlike the famed hexagonal comb structure), although
Bartholdi et al. (1993)
prove that no allocation is more than twice as efficient. Why would a sub-optimal foraging allocation mechanism evolve in honey bee colonies? ...
On Honey Bees and Dynamic Server Allocation in Internet Hosting Centers
Full-text available
Dec 2004
ADAPT BEHAV
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Sunil Nakrani
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Craig A. Tovey
Internet centers host services for e-banks, e-auctions and other clients. Hosting centers then must allocate servers among clients to maximize revenue. The limited number of servers, costs of reallocating servers, and unpredictability of requests make server allocation optimization difficult
Based on the many similarities between server and honey bee colony forager allocation, we pro pose a new decentralized honey bee algorithm which dynamically allocates servers to satisfy request loads. We compare it against an omniscient optimality algorithm, a conventional greedy algorithm, and an algorithm that computes omnisciently the optimal static allocation. We evaluate performance on simulated request streams and commercial trace data
Our algorithm performs better than static or greedy for highly variable request loads, but greedy can outperform it under low variability. Honey bee forager allocation, though suboptimal for static food sources, may possess a counterbalancing responsiveness to food source variability.
... A comparative study [1] showed the similarities and differences between ant foraging and honeybee foraging. Detailed studies of recruitment mechanisms and their effect on forager group sizes, foraging decisions, and resource throughput were performed by means of mathematical topdown modeling
[2]
[3][4]. In addition, bottom-up (individualbased, agent-based) models were frequently used to predict how well local cues can serve as a source of information for individual foragers [5][6][7][8]. ...
... The individuality of foragers regarding the duration of the waggle dance (see Fig. 5) is implemented by a individual value, represented by g
(2)
in Eq. 4, as described in detail in Thenius et al. [27]. Other parameters, like the probability to leave the colony for scouting, the probability to forget a source or the probability to start foraging were (uniformly) distributed randomly around ±30% around the mean values. ...
Swarm-intelligent foraging in honeybees: Benefits and costs of task-partitioning and environmental fluctuations
Mar 2012
NEURAL COMPUT APPL
<here is a image a39339ebcdf10b10-2bed569994f0bd36> Thomas Schmickl
<here is a image 27186b31e24ed648-f45c83dfe3be69ea> Ronald Thenius
<here is a image d1bf001e38e85818-cefb688dfc1b9642> Karl Crailsheim
For honeybee colonies, it is crucial to collect nectar in an efficient way. Empiric experiments showed that the process of decision making, which allows the colony to select the optimal nectar source, is based on individual decisions. These decisions are made by returning nectar foragers, which alter their dancing behaviours based on the nectar source's quality and based on the experienced search time for a receiver bee. Nectar receivers , which represent a shared limited resource for foragers, can modulate the foraging decisions performed by the colony. We investigated the interplay between foragers and receivers by using a multi-agent simulation. Therefore, we implemented agents which are capable of a limited set of behaviours and which spend energy according to their behaviour. In simulation experiments, we tested colonies with various receiver-to-forager ratios and measured colony level results like the emerging foraging patterns and the colony's net honey gain. We show that the number of receivers prominently regulates the foraging workforce. All tested environmental fluctuations are predicted to cause energetic costs for the colony. Task-partitioning additionally influences the colony's decision-making concerning the question whether or not the colony sticks to a nectar source after environmental fluctuations.
... of the other models and additional characteristics, and like others rely on the work in (T. Seeley et al. 1991; Camazine and Sneyd 1991). Moreover, Cox and Myerscough (2003) include polyandry-induced individual bee differences and use simulations to show that a heterogeneous colony can reduce the variance in the average amount of nectar collected.
Bartholdi et al. (1993)
study the pattern of forager allocation and the optimality of it. In related work, Dukas and Edelstein-Keshet (1998) study the spatial distribution of solitary and social food provisioners under different currency assumptions. The work in (Bartholdi et al. 1993) and (Dukas and Edelstein-Keshet 1998) identify connections to the concept o ...
... In related work, Dukas and Edelstein-Keshet (1998) study the spatial distribution of solitary and social food provisioners under different currency assumptions. The work in (
Bartholdi et al. 1993
) and (Dukas and Edelstein-Keshet 1998) identify connections to the concept of the " ideal free distribution " (IFD) (Fretwell and Lucas 1970). The work in (de Vries and Biesmeijer 2002) studies conditions under which their EHD (see above) is reached and discuss the impact of currency and relations to the IFD. ...
Social foraging by honey bees: Mechanisms, dynamics and adaptation
Kevin M. Passino
There are two main components of social foraging by honey bees. First, there is a continuous adjustment of the number of bees dedicated to exploitation of forage sites and wide-area exploration for new forage options. Second, there is a persistent reallocation of the proportions of the foraging workforce dedicated to exploiting each site in order to match unpredictably changing relative forage site profitabilities. In this paper we develop a model of bees' foraging for nectar that can represent individual-level sensing, decision-making, and communication mechanisms, along with known restrictions on information flow in the hive. Our model also represents that as additional bees forage at a site its profitability generally degrades due to exploitation competition; hence, we can study the intimate coupling between the dynamics of forage site profitability and the hive's reallocation of foragers. To illustrate these dynamics, we first show how in spite of the fact that no bee can know the profitability of all sites, the hive achieves an approximate "ideal free distribution" (IFD) of foragers with an allocation of foragers proportional to relative site profitability. We identify the mechanisms underlying the achievement of the emergent distribution and the hive's ability to completely ignore forage sites of relatively inferior quality. We explain how the mechanisms lead to fast reallocations when there are sudden and significant site profitability changes or new site discoveries. Next, we show that natural selection seems to have settled on values of the behavioral parameters representing the dance strength determination rule that balance the desire to maximize nectar intake, yet minimize the time-energy investments in dancing. We show that achievement of this balance allows for individual-level forage site profitability assessment er-rors since the foraging process effectively filters such errors at the colony level. Finally, we identify the close relationships between the dynamics of social foraging and nest-site selection by honey bees since it provides an excellent example of how changing a single individual-level behavioral rule can result in dramatically different emergent group behavior. Building on these relationships we briefly discuss how social foraging can be viewed as a group cognition process.
... We refer to this as the equal harvest-rate distribution. This investigation was inspired by a paper by
Bartholdi et al. (1993)
, who presented a system of differential equations that models the allocation process in a hypothetical colony of bees, whose behaviour closely approximates the observed behaviour of real bees. The allocation pattern they found was one in which each forager experiences the same rate of " value " accumulation regardless of which patch she is visiting. ...
... An EHD emerges only if individuals used gain rate as currency and if lost recruits were incorporated in our calculations of the per capita harvest rate. The processes through which an EHD is reached include indirect interference at the food source (as was suggested by
Bartholdi et al. 1993
), which subsequently determines a nectar forager's abandoning probability and its probability of waggle dancing and, thus, the relative intensity of recruitment to the various food patches. For an EHD to emerge, food patches should not be too large and the number of foragers should be high enough, such that foragers interfere with each other indirectly at the source. ...
Self-organization in collective honeybee foraging: Emergence of symmetry breaking, cross inhibition and equal harvest-rate distribution
May 2002
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Han De Vries
<here is a image 24dd565fea8b22a4-604cdb086fa3eadb> Jacobus C Biesmeijer
De Vries and Biesmeijer described in 1998 an individual-oriented model that simulates the collective foraging behaviour of a colony of honeybees. Here we report how this model has been expanded and show how, through self-organization, three colony-level phenomena can emerge: symmetry breaking, cross inhibition and the equal harvest-rate distribution. Symmetry breaking is the phenomenon that the numbers of foragers visiting two equally profitable food sources will diverge after some time. Cross inhibition is the phenomenon that, by increasing the profitability of one of two equal food sources, the number of foragers visiting the other source will decrease. In some circumstances, the bees foraging on two sources of different profitabilities will be distributed between these sources such that the two average energy harvest rates are equal. We will refer to this phenomenon as the equal harvest-rate distribution. For each of these three phenomena, we show what the necessary behavioural rules to be followed by the individual forager bees are, and what the necessary circumstances are (that is, what values the model parameters should take) in order for these phenomena to arise. It seems that patch size and forager group size largely determine when each of these phenomena will arise. Experimenting with two types of currency, net gain rate and net gain efficiency, revealed that only gain rate may result in an equal harvest-rate distribution of foragers visiting different food sources.
... More recently, in [17] the authors expanded and improved the model in [16] (e.g., taking into account the findings in [18] and by studying an equal harvest rate forager allocation distribution). The work in
[19]
studies the pattern of forager allocation and the optimality of it. The authors in [20] study the spatial distribution of solitary and social food provisioners under different currency assumptions. ...
... The authors in [20] study the spatial distribution of solitary and social food provisioners under different currency assumptions. The work in [17],
[19]
, [20] identifies connections to the concept of the " ideal free distribution " (IFD) [21]. Here, we do not use a detailed characterization of bee and nectar energetics and currency since there is not enough experimental evidence to justify whether or when a gathering rate or efficiency-based currency is used [11]; instead, we develop a generic measure of forage site profitability. ...
Honey Bee Social Foraging Algorithms for Resource Allocation: Theory And Application
Sep 2010
ENG APPL ARTIF INTEL
<here is a image d640d3b4fa5cb42c-395701347fed0380> Nicanor Quijano
Kevin M. Passino
A model of honey bee social foraging is introduced to create an algorithm that solves a class of dynamic resource allocation problems. We prove that if several such algorithms (“hives”) compete in the same problem domain, the strategy they use is a Nash equilibrium and an evolutionarily stable strategy. Moreover, for a single or multiple hives we prove that the allocation strategy is globally optimal. To illustrate the practical utility of the theoretical results and algorithm we show how it can solve a dynamic voltage allocation problem to achieve a maximum uniformly elevated temperature in an interconnected grid of temperature zones.
... These models mainly deal with the situation o f a colony choosing between several nectar sources. There are quite a few models developed to analyse the food source selection process of honey bee colonies (Camazine and Sneyd, 1991;
Bartholdi et al., 1993)
. Camazine et al., (1991) and Camazine et al., (2001) presented a differential equations model to analyse the food-source selection process of honey-bees. ...
The Bees Algorithm: Theory, Improvements and Applications
Mar 2010
<here is a image b7603e16f98050a0-d97b5ea62abb114c> Ebubekir Koç
In this thesis, a new population-based search algorithm called the Bees Algorithm (BA) is presented. The algorithm mimics the food foraging behaviour of swarms of honey bees. In its basic version, the algorithm performs a kind of neighbourhood search combined with random search and can be used for both combinatorial and functional optimisation. In the context of this thesis both domains are considered. Following a description of the algorithm, the thesis gives the results obtained for a number of complex problems demonstrating the efficiency and robustness of the new algorithm. Enhancements of the Bees Algorithm are also presented. Several additional features are considered to improve the efficiency of the algorithm. Dynamic recruitment, proportional shrinking and site abandonment strategies are presented. An additional feature is an evaluation of several different functions and of the performance of the algorithm compared with some other well-known algorithms, including genetic algorithms and simulated annealing. The Bees Algorithm can be applied to many complex optimisations problems including multi-layer perceptrons, neural networks training for statistical process control and the identification of wood defects in wood veneer sheets. Also, the algorithm can be used to design 2D electronic recursive filters, to show its potential in electronics applications. A new structure is proposed so that the algorithm can work in combinatorial domains. In addition, several applications are presented to show the robustness of the algorithm in various conditions. Also, some minor modifications are proposed for representations of the problems since it was originally developed for continuous domains. In the final part, a new algorithm is introduced as a successor to the original algorithm. A new neighbourhood structure called Gaussian patch is proposed to reduce the complexity of the algorithm as well as increasing its efficiency. The performance of the algorithm is tested by use on several multi-model complex optimisation problems and this is compared to the performance of some well-known algorithms.
Please kindly refer to http://orca.cf.ac.uk/id/eprint/55027 for full access at Cardiff University Library.
... Besides the pollen foraging, nectar foraging and inactive foragers, we omitted other tasks that are also regulated in honeybee colonies [62]. This decision was made not only for the sake of staying focused but also because of the fact that these aspects of colony integration were already extensively modeled in the past [52,55,56,59,[63][64]
[65]
[66][67][68][69]. The regulation of pollen storing and nectar foraging workforce, which we addressed here, is less known than the regulatory role of dances, but these regulations also have serious consequences for colony survival and success [12]. ...
Resilience of honeybee colonies via common stomach: A model of self-regulation of foraging
Nov 2017
PLOS ONE
<here is a image a39339ebcdf10b10-2bed569994f0bd36> Thomas Schmickl
<here is a image e6e7443e328127bf-2ebfbc80aeeb5d94> Istvan Karsai
We propose a new regulation mechanism based on the idea of the “common stomach” to explain several aspects of the resilience and homeostatic regulation of honeybee colonies.
This mechanism exploits shared pools of substances (pollen, nectar, workers, brood) that modulate recruitment, abandonment and allocation patterns at the colony-level and enable bees to perform several survival strategies to cope with difficult circumstances: Lack of proteins leads to reduced feeding of young brood, to early capping of old brood and to regaining of already spent proteins through brood cannibalism. We modeled this system by linear interaction terms and mass-action law. To test the predictive power of the model of this regulatory mechanism we compared our model predictions to experimental data of several studies. These comparisons show that the proposed regulation mechanism can explain a variety of colony level behaviors. Detailed analysis of the model revealed that these mechanisms could explain the resilience, stability and self-regulation observed in honeybee colonies. We found that manipulation of material flow and applying sudden perturbations to colony stocks are quickly compensated by a resulting counter-acting shift in task selection. Selective analysis of feedback loops allowed us to discriminate the importance of different feedback loops in self-regulation of honeybee colonies. We stress that a network of simple proximate mechanisms can explain significant colony-level abilities that can also be seen as ultimate reasoning of the evolutionary trajectory of honeybees.
... But in most cases, the colony has to optimize its energy gain within a very limited window of opportunity. Thus, it is potentially hugely misleading to confine the study of the properties of a model only to the steady state of the recruitment process, as is often done in theoretical studies of social insects (Johnson et al. 1987;
Bartholdi et al. 1993;
Anderson 2001). By investigating recruitment strategies dynamically, we have been able to take into account not only energetic costs, but also time costs and 'inertia' at the beginning of the recruitment process. ...
dechaume-moncharmont 05 hidden 548319
Data
May 2015
François-Xavier Dechaume-Moncharmont
<here is a image 05e979201eb567be-578f87aeffcb6306> Anna Dornhaus
Alasdair I. Houston
<here is a image 75e7c4027d1b3a39-7d70e7fc04454c6a> Nigel R Franks
... Differential equation models are by far the most commonly used models in biology (Jones & Sleeman, 2003), due to their ability to characterise the temporal dynamics of systems. Differential equations provide a promising tool for analysing the underlying mechanisms of biological systems, and they have frequently been applied to foraging patterns of insect societies (for example Goss et al., 1989;Deneubourg et al. 1990;
Bartholdi et al. 1993;
Bonabeau et al. 1997;Nicolis & Deneubourg 1999). The power of these models lies in their simple mathematical formalism for describing how populations change through time. ...
Modelling Changes in Foraging and Defensive Behaviour of Ant Colony Members as a Result of Inter-Colony Interactions
Thesis
Full-text available
Jan 2006
<here is a image 526857735b57b071-bea6f54d5e1b0a02> Tom Diethe
Abstract Ithas been observed that the colonies of certain species of ants, for example Pogonomyrmex barbatus, exhibit changes in behaviour as the colonies grow older, despite nearly all of the individual ants in the colony being replaced each year (Gordon 1991, 2000). The behaviour of older colonies is more stable, and they are more,likely to avoid,intraspecific conflict (Gordon & Kulig 1996). Gordon hypothesised,that the reason,for this may,be due,to colony,growth,- a 3-4 year- old colony is in the steepest part of its growth curve, i.e. the 4000 workers of the
... Not only do they allocate forager force according to the nature, quality, and distance of sources, but they also respond to changes in internal variables such as feed needs and storage levels of nectar, pollen, and water (see for example Dreller, Jr., and Fondrk (1999)). Contributions such as de Vries and Biesmeijer (1998),
Bartholdi et al. (1993)
, and others have developed agent-based models that use behavioral rules of individual bees in order to replicate the observed allocation of foraging efforts of hives. They find that the foraging efficiency resulting from the heuristic behavior of colonies is comparable in magnitude to that of a theoretically optimal allocation. ...
The foraging economics of honey bees in almonds
Jan 2011
<here is a image 7850c2483ff79fd3-a7688d0e280abd59> Antoine Champetier
We develop a model of honey bee foraging behavior that can be used to simulate crop yields as functions of honey bee densities. These yield functions help us understand the economic behavior of growers who rely on bees for pollination. One important simulation result for the case of almonds is that the production function facing growers is close to one of fixed proportion in pollination input. Accordingly, the modeling of the foraging behavior of bees provides an explanation for the observed lack of variation in pollinator use and shows how the behavior of bees and growers are connected.
... Also relevant to the present study are the many models developed to analyze the food-source selection process of honeybee colonies (Camazine et al. 1990;Camazine and Sneyd 1991;Camazine 1991;Jenkins et al. 1992;
Bartholdi et al. 1993;
de Vries and Biesmeijer 1998;Biesmeijer and de Vries 2001;Cox and Myerscough 2003;Schmickl and Crailsheim 2003). While the models of Cox andMyerscough 2003 andSchmickl andCrailsheim (2003) may be the most comprehensive, we have benefited most in building a model of the nest-site selection process from the way Camazine and Sneyd (1991) modeled the dance floor in a hive and from the arguments of de Vries and Biesmeijer (1998) on why an "individual-oriented" model (i.e., one that represents some of the behaviors of individual bees) is useful in tracing the connections between individual actions and emergent group behavior. ...
Modeling and analysis of nest-site selection by honeybee swarms: The speed and accuracy trade-off
Oct 2005
<here is a image 4ab6ac4296129357-4a699ebf09d211d0> Thomas Seeley
Kevin M. Passino
Nest-site selection in honeybees is a process of social decision making in which the scout bees in a swarm locate several
potential nest sites, evaluate them, and select the best one by means of competitive signaling. We develop a model of this
process and validate that the model possesses the key features of the bees' decision-making process, as revealed by prior
empirical studies. Next, we use the model to study the “design” of the nest-site selection process, with a focus on how certain
behavioral parameters have been tuned by natural selection to achieve a balance between speed and accuracy. First, we study
the effects of the quorum threshold and the dance decay rate. We show that evolution seems to have settled on values for these
two parameters that seek a balance between speed and accuracy of decision making by minimizing the time needed to achieve
a consensus and maximizing the probability that the best site is chosen. Second, we study the adaptive tuning of the tendency
of bees to explore for vs be recruited to a site. We show that this tendency appears to be tuned to regulate the positive
feedback process of recruitment to ensure both a reasonably rapid choice and a low probability of a poor choice. Finally we
show that the probability of choosing the best site is proportional to its quality, but that this proportionality depends
on its quality relative to other discovered sites.
... Although we labeled the bees ''inspectors,'' they can also be viewed as foragers altering their foraging tempo and rate of recruitment. A forager bee controls 3 aspects of the foraging process: tempo, retirement rate, and recruitment
(Bartholdi et al. 1993;
Seeley 1995 ). The inspector bees can thus be thought of as foragers that make visits to the food sources at a lower rate and tune their recruitment rates to zero for the duration of inspection. ...
How dancing honey bees keep track of changes: The role of inspector bees
Boris Granovskiy
<here is a image b94c68520ec0c59d-912a9fafd308c445> Tanya Latty
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Michael Duncan
<here is a image 16c14097a4ae74d3-4819ea31233a237f> Madeleine Beekman
How do honey bees track changes in their foraging environment? Previously, 2 complementary mechanisms have been identified
by which bees can effectively switch between food sources when their relative quality changes. First, an increase in profitability
of a food source elicits an increase in waggle dances (the bees' recruitment mechanism) for that source. Second, bees that
have retired from foraging at a food source make occasional inspection visits to that food source and resume foraging if its
quality improves. Here, we investigate, using both field experiments and a mathematical model, the relative importance of
these 2 mechanisms. By manipulating dance information available to the bees, we find that when food sources change quality
frequently, inspector bees provide a rapid response to changes, whereas the waggle dance contributes to a response over a
longer time period. The bees' ability to switch feeders without dance language information was found to be robust with respect
to the spatial configuration of the feeders. Our results show that individual memory, in the form of inspector bees, and collective
communication can interact to allow an insect colony to adapt to changes on both short and long timescales.
... For example, individual honeybee foragers follow only a small number of the waggle dances advertising flower patches, and the colony can focus its foraging efforts on the most profitable patches (Seeley, 1995). Many researchers have attempted to better understand collective foraging, especially in social insects
(Bartholdi et al., 1993;
Beckers et al., 1993;Beekman et al., 2001;Nicolis and Deneubourg, 1999). These efforts have revealed many aspects of collective foraging in different species, but they are mostly limited to terrestrial organisms because it is technically difficult to directly observe the foraging galleries of subterranean animals (Su, 2001). ...
Simulation study on the tunnel networks of subterranean termites and the foraging behavior
<here is a image 8e562ed2f5b95968-0b8c808ee5d54baf> Nan-Yao Su
Most subterranean termites forage for food by creating tunnel galleries underground. These tunnel networks reflect a compromise between foraging efficiency and other environmental constraints, such as soil hardness and moisture content. Thus, understanding tunnel networks is important for understanding foraging behavior. Due to the difficulties in direct observation of tunneling patterns in the field, we used a theoretical approach for this analysis. We first constructed a lattice model to simulate the tunnel networks of Coptotermes formosanus Shiraki and Reticulitermes flavipes (Kollar) on the basis of the experimental data provided by Su et al. (Su, N.-Y., Stith, B.M., Puche, H., Bardunias, P., 2004. Characterization of tunneling geometry of subterranean termites (Isoptera: Rhinotermitidae) by computer simulation. Sociobiology 44 (3), 471–483.). Using this model and two of its modified versions, we explored the relationship between the food encounter rate and food distributions and analyzed how this relationship is influenced by changes in the tunnel characteristic constituents, such as the branching tunnel length and frequency. Additionally, we investigated the effects of landscape heterogeneity on the foraging efficiency. In the discussion, we briefly introduced our novel individual-based model comprising individual termites and their surroundings, and we addressed the necessity of this model in the functioning of the network and the formation of the network in relation to foraging behavior.
... These behaviors shown by collective foragers have made theoretical approaches difficult because of its complexity and emergent nature. Nevertheless, there have been attempts to explain collective foraging by insect societies
(Bartholdi et al., 1993;
Beckers et al., 1993;Beekman et al., 2001;Nicolis and Deneubourg, 1999). These models can explain some aspects of foraging behavior in a variety of species, but they are mostly limited to terrestrial organisms. ...
Two strategies for optimizing the food encounter rate of termite tunnels simulated by a lattice model
ECOL MODEL
S.-H. Lee
Paul Bardunias
<here is a image 8e562ed2f5b95968-0b8c808ee5d54baf> Nan-Yao Su
The tunneling structure of the Formosan subterranean termite, Coptotermes formosanus Shiraki, was simulated using a lattice model in order to explore a foraging strategy that optimizes food encounter rate. A tunnel was mimicked by algorithms derived from experimental data that determined the movement of a discrete unit of excavation performed by a cadre of termite workers, the tunnel vector cell (TVC). To be consistent with real tunneling behavior, tunnel propagation was terminated when TVCs did not encounter food particles within a given threshold length L1 (primary tunnel) and L2 (secondary tunnel). The simulations revealed that the length ratio between primary and secondary tunnels, γ (=L2/L1), produced a bimodal distribution of food encounter rates. The encounter rate was optimized at two values of γ because of either a searching distance effect (SDE), characterized by long primary tunnels with short branches, or a searching area effect (SAE), that balances tunnel length with branch length to cover a broad area. These two strategies reflect tunnel geometries that subterranean termites may employ in excavating tunnel patterns that optimize the rate of encountering food sources.
... En situation de compétition, cette règle de décision, qui apparaît facilement applicable puisqu'elle repose sur les gains effectivement perçus par le prédateur et non sur une estimation des taux de renouvellement des ressources des différentes zones, permet d'attein dre l'état d'équilibre propre à la distribution libre idéale. Cela indique que la connaissance nécessaire à une répartition optimale des compétiteurs dans l'envi ronnement peut être obtenue à partir de mécanismes simples d'apprentissage (ou de recrutement dans le cas d'espèces eusociales ; voir par exemple
Bartholdi et al., 1993)
. Ainsi, la répartition d'individus ayant les mêmes capacités compétitives et utilisant un mécanisme d'apprentissage à opérateur linéaire alors qu' ils sont en situation de compétition par interférence dans un environnement formé de nombreuses zones d'alimentation atteint rapidement l'équilibre propre à la distribution libre idéale lorsque les ressources sont renouvelées en continu, que le temps moyen nécessaire pour changer de zone reste faible et que la profitabilité des zones qu'un compétiteur visite successivement varie de manière imprévisible (Bernstein et al., , 1991. ...
Les stratégies optimales d'approvisionnement
REV ECOL-TERRE VIE
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Frank Cézilly
Compte tenu de leur importance majeure dans la survie et donc finalement dans le succès reproducteur de la plupart des animaux, il ne fait aucun doute que les stratégies d’approvisionnement ont été soumises au cours de l’évolution à un processus d’optimisation par la sélection naturelle. Même dans le cas où les ressources alimentaires ne constituent pas en elles-mêmes un facteur limitant, un animal a encore intérêt à optimiser son comportement d’approvisionnement, ne serait-ce que pour minimiser le temps consacré à cette activité, et pouvoir ainsi s’investir davantage dans d’autres activités. Nous présentons ici une revue de question très générale des modèles qui formalisent les stratégies optimales d’approvisionnement. Il faut entendre par là l’ensemble des règles de décision qui permettent à un animal, dans un contexte énergétique bien défini et compte tenu des contraintes spécifiques et environnementales auxquelles il est soumis, de maximiser le taux net d’acquisition d’énergie, ou de minimiser la probabilité de mourir d’inanition. Les différents modèles qui ont été développés dans ce cadre forment ce que l’on appelle la théorie de l’approvisionnement optimal. Le champ d’investigation de cette théorie concerne essentiellement la composition du régime alimentaire et la répartition spatio-temporelle de l’effort de recherche dans un environnement stochastique hétérogène, qu’il soit discret (c’est-à-dire formé de zones d’alimentation bien définies) ou continu (c’est-à-dire formé de zones d’alimentation définies seulement de manière statistique). On a également considéré le cas particulier d’un animal qui exploite son environnement à partir d’un lieu central où il retourne régulièrement. On a aussi largement abordé les effets liés à la compétition interindividuelle que subissent les animaux s’approvisionnant en groupe. La stratégie optimale d’approvisionnement que formalise tel ou tel modèle correspond à un idéal théorique auquel pourront être confrontées les résultats obtenus sur le comportement d’approvisionnement réel d’un animal en conditions expérimentales ou naturelles. Bien que ces conditions soient souvent bien plus complexes que celles qui ont été initialement introduites dans les modèles, il existe généralement une assez bonne adéquation entre les prédictions théoriques et les résultats observés, parce que les animaux utilisent des règles de décision simples mais robustes qui leur permettent de s’adapter remarquablement bien à la plupart des situations qu’ils rencontrent dans leur environnement naturel.
... For example, bee colonies collect food from flowers, whose abundance varies strongly in space and time. Finding these resources requires considerable search effort [2] and effective foraging by the colony depends on an appropriate allocation of bee workers to exploration versus exploitation (collection of food from known resources)
[3]
. ...
The Common Stomach as a Center of Information Sharing for Nest Construction
<here is a image e6e7443e328127bf-2ebfbc80aeeb5d94> Istvan Karsai
Construction of wasp nests is a self organized process that requires building materials, pulp and water foragers, and builders
to cooperate. In this paper we study how the society of agents use a social crop, or common stomach, to store water that also
provides a mechanism for worker connectivity, which in turn regulates building. Our model predicts that via the common stomach
usage, medium sized colonies enjoy the benefit of having highly effective foragers and this in turn means that the colonies
need only endanger a few foragers to ensure steady construction. When pulp foraging becomes more costly than water foraging,
the colonies adjust via recruiting more pulp foragers and less water foragers, but keep high numbers of common stomach wasps
on the nest. The common stomach provides an adaptable platform for indirect worker connectivity and a buffer for water storage.
... But in most cases, the colony has to optimize its energy gain within a very limited window of opportunity. Thus, it is potentially hugely misleading to confine the study of the properties of a model only to the steady state of the recruitment process, as is often done in theoretical studies of social insects (Johnson et al. 1987;
Bartholdi et al. 1993;
Anderson 2001). By investigating recruitment strategies dynamically, we have been able to take into account not only energetic costs, but also time costs and 'inertia' at the beginning of the recruitment process. ...
The hidden cost of information in collective foraging
Many animals nest or roost colonially. At the start of a potential foraging period, they may set out independently or await information from returning foragers. When should such individuals act independently and when should they wait for information? In a social insect colony, for example, information transfer may greatly increase a recruit's probability of finding food, and it is commonly assumed that this will always increase the colony's net energy gain. We test this assumption with a mathematical model. Energy gain by a colony is a function both of the probability of finding food sources and of the duration of their availability. A key factor is the ratio of pro-active foragers to re-active foragers. When leaving the nest, pro-active foragers search for food independently, whereas re-active foragers rely on information from successful foragers to find food. Under certain conditions, the optimum strategy is totally independent (pro-active) foraging because potentially valuable information that re-active foragers may gain from successful foragers is not worth waiting for. This counter-intuitive outcome is remarkably robust over a wide range of parameters. It occurs because food sources are only available for a limited period. Our study emphasizes the importance of time constraints and the analysis of dynamics, not just steady states, to understand social insect foraging.
... Passino's rigorous engineering view trumps an all-too-common view in biomimetic optimization and in artificial intelligence that unconventional methods need only be compared amongst themselves. In this respect, the text is missing a reference to the first stability analysis in the foraging literature
[6]
. ...
Biomimicry for Optimization, Control, and Automation [Book Review]
Not Available
| https://www.researchgate.net/publication/256802738_The_Pattern_and_Effectiveness_of_Forager_Allocation_Among_Flower_Patches_by_Honey_Bee_Colonies |
France: protests against new labour law | libcom.org
France: protests against new labour law
In France, sizable protests agianst a new labour law that threatens to make it easier to lay off workers en evade the 35-hour day. A few mainstream news articles I found through Labourstart (I saw news articees on a Dutch news site as well)
http://economictimes.indiatimes.com/news/international/world-news/hundreds-of-thousands-protest-over-french-jobs-reform/articleshow/51337712.cms
http://www.independent.co.uk/news/world/europe/france-protest-35-hour-working-week-march-demonstration-changes-a6920786.html
Seems quite big. And in a Dutch news site, the labour law that was defeated through the big protests of 2006 was mentioned by way of historical context.
Hadn't heard anything about
Hadn't heard anything about this, according to Le Monde it's a student strike. 70-150 thousand demonstrating in Paris. It might explain the noise at school on Tuesday. (Last week's day of action got 220000 out)115 establishments blockaded since yesterday. Scuffles with Police in Paris, Nantes, Rouen and MArseille.
http://www.lemonde.fr/politique/portfolio/2016/03/17/loi-travail-les-defiles-ponctues-par-des-incidents_4885226_823448.html
It will make it easier to fire people. In terms of the 35 hour week it will cut obligatory bonuses for overtime and make it easier to force overtime.
In other news there has been a 1.2% pay increase for civil servants whose pay has been frozen since 2010, widely seen as a cynical move by Holande ahead of the election. Personally I don't understand it, it isn't enough to bribe anyone and he's almost certainly going to lose if he stands.
Policie beats up student;
Policie beats up student; angry students attack police offices.http://www.thelocal.fr/20160325/pupils-attack-police-stations-after-paris-students-beatingThere must be more on all this, there seems to be an almost complete news black out outside France itself on this.
It's not getting much
It's not getting much publicity here, the student protests on successive thursdays haven't really made the news, I didn' even know that there had been protests at the school I work at.The attacks on the police stations were widely reported and attacked in the media as the work of out of control youth / the work of instigators etc.
Supposedly the demonstrators has been throwing eggs at the riot police before one cops decided to punch a kid who was being lifted up by him and another cop.
https://www.youtube.com/watch?v=CBuzy2-B-T4
The 'ransacking'of a supermarket was, as far as I can tell beoynd the hyperbole, a bit of shoplifting en masse and the students mostly took food to give to the homeless and refugees. I've watched the video of the attack on the police station in the 19th, they threw a traffic cone from twenty feet away and a few tiles were thrown, didn't appear to be any damage, I think the police station in the 10th took more damage. It was also the last day before easter weekend.
The recent strikes have frequently been led, and mostly participated in, by students in seconde, so they're 16ish and haven't chosen their path for the bac (16-18) from the little I have seen and heard.
The French love a protest:
The French love a protest: 266 planned marches against labour reforms todayhttps://t.co/iaPB7ofKeV#greve31marspic.twitter.com/SHz2Lc3thz
— The Local France (@TheLocalFrance)March 31, 2016
18 Parisian secondary schools
18 Parisian secondary schools have closed. In some cases this means that they have suspended lessons, but teachers are still expected to come in. It's very unclear, numbers have been creeping up.Le Monde says 250 schools countrywide blockaded according to unions, 176 according to the government.
Protesting dock workers had also blocked roads around the northern towns of Rouen and Le Havre as well as the Pont de Normandie.
Clashes in St Nazaire (5500) Nantes (12-30000), Rennes (10000) MArseille (120000) and around the Gare de Lyon in Paris. Police firing tear gas
SNCF 24,2% of personnel on strike. 1/2 TGV in the north, normal in the east, 3 / 4 for the rest 1/2 eurostar. 4 trains Intercity in 10, aucun de nuit, local trains 1/2.
Video showing cops hitting
Video showing cops hitting people who are not dispersing quickly enoughhttps://youtu.be/JFXIuIYY6nYVery frustratingly shot video from another angle showing cops just wandering around smacking people with truncheons. Students have widely reported being attacked, especially those who were filming.https://youtu.be/P6nlZLVU81g
https://pbs.twimg.com/media/C
https://pbs.twimg.com/media/Ce35je1WEAAxWS1.jpg
Strikers from schools and universities across the parisian region have been arriving at Place d'Italie for the last hour or so, the second march was supposed to start there at 13H30.It's been raining most of the day.
Caen (2000) Toulouse (20000) Rouen (6000) Grenoble 7000) Clermont-Ferrand (5000) and other cities have strikes, marches and protests. Totals 250k accoridng to the Police 450k according to the unions
PAris metro 3/4
650km of tailbacks due to blockades of roads and bridges by dockers in Le HAvre and Rouen
Socialist Party offices
Socialist Party offices paintbombed in Rouen:
This seems to be the gist of the state response to the movement:
20 odd arrests in Paris
11 in
20 odd arrests in Paris11 in Lyon
Be interesting to see the schools tomorrow.
According to Libération there were about 500 but they started leaving at 4-5 am mainly because they knew the police would come again and when they did at 6 there were only about 100 left. Most were forced into the metro and 20 or so who tried a sit-in were moved by force. Those in the station didn't try to do anything much but they did sing the Marseillaise.About fifty stayed all night on Thursday.
http://danactu-resistance.over-blog.com/2016/03/jeudi-apres-les-manifs-on-occupe-des-places-nuit-debout.htmlThis is a call-out which also has a callout pdf attached. It's more generally anti-capitalist.
Callout for Caen and Saillans here:http://www.racailles.info/2016/03/racailles-appelle-une-nuit-debout-le-31.htmlhttp://latelier.in/nuit-debout-jeudi-31-mars-saillans-des-14h00/Can't find anything suggesting that anything happened although the Caen one claimed to have lots of stuff organised.
Supposedly the nuit debout, where people stay out all night and occupy a square has been going on for a week and has spread to half a dozen cities. One of the key thing is to hold AG (assemblée générale - general meeting) at an AG people discuss what is happening and talk about what to do and then vote on it. AG are usually held in oragnisations / establishments etc and are generally considered binding. For example an AG that votes for a strike can then blockade etc. Student strikes are often called after AG. Strikers are often denounced for calling AG without warning/ packing the room/ deliberate miscounting of votes to force a strike. AG for Nuit Debout are going to be a little different and probably more about actions and immediate strategy. Blocking roads etc seems to be a major one.
300 place du Bouffay, NantesRennes, près de 200 esplanade Charles-de-Gaulleapprently they had picnic blankets, picnics and musical intrsuments500 place du Capitole à Toulouse.Lyon, heavy polie presence blocking access to place Mazagran where the callout was, so 300 met up under the pont de la Guillotière
#NuitDebout if you can be bothered someone is live tweeting.
200 people marching in Paris between 3-4am last night, broke into smaller groups and 50 or so got kettled for a few hours after blocking a road, the cops ended up escorting them to Place de la Republique.
Last night there were hundreds of people in the square in the evening and large groups blocked a main street calling on police to release people who'd been arrested.
There was a strike day yesterday too.In Rennes there was a march and they blocked the station.Long article on 31/01 in Renneshttps://nantes.indymedia.org/articles/34026
Arrests in Nantes during the protests, one person has got six months for being in an 'armed group' and 'covering his face' (So the cops should be getting how long a sentence...)And another two months for throwing something. The trials are being held in camera and very quickly.
A collective statement will be released very soon. Meanwhile I wanted to write this testimony about what we experienced during the day of action on May 1st against the Labour Law in order to make it rapidly public.
The event was, from my point of view, one of the most violently repressed since the beginning of the movement. However, it is also on that day that I was able to participate in the practice of group solidarity, on a scale and a strength I had never known before.
As StreetMedic, we had to give medical help to medically help, reassure, and take care of countless injured. …We have seen and treated serious injuries, caused by flash balls, tear gas, disencirclement grenades. Shots on faces, eyes, hands, limbs, all over the body. We saw fingers severed in half, burnt skin, people in shock, terrified.In general, the wounded come to us in spurts. The first time was in a large trap before reaching Nation: 4 serious injuries, many others with lighter ones. We had to improvise a triage [a way of sorting the wounded depending on the degree of urgency to decide the order of treatment] in a care outpost despite the nearby fighting.
There I saw the protesters protect us, making a barrage using their bodies to block the CRS charges when they came upon us. Lots of people stayed there, putting themselves in danger, taking the risk of being arrested, clubbed, shot. Out of solidarity. And it was this attitude which continued to impress me throughout the day.
Later, at Nation, we took care of a person whose artery had been severed at the ankle through a direct hit by the police. It was a haemorrhage of the pulse, which, in order to maintain a pressure point, made her unmovable. So we stayed with her, to treat her in the centre of the square, while the tear gas rained everywhere and direct hits whistled. Soon other injured people were brought to us.
A security perimeter formed by thirty people stood around us. We waved a large StreetMedic flag in the hope that the police would not charge and would keep out of our reach until we’d rescued…the heaviest injured to be evacuated.
But a continuous shower of tear gas began to rain on our little area. We were almost the last in the square. I was blinded and asphyxiated. One hand compressing the artery of the injured, the other protecting her head from the shooting. But even with the two hands immobilised, seeing nothing and unable to breathe, I knew someone was protecting me.
All these people, StreetMedics, demonstrators, strangers remained around us and kept the line. Some placed their bodies above us to block the cannisters of burning teargas falling on us like rain. One of them saw her bag start to go up in flames. But they all stayed until the end.
I do not want to make a martyrish apology here, and I think we will have a lot of questions to ask ourselves about how we had to put ourselves in danger physically, us protesters, especially the StreetMedics.
But at the end of the day, I wanted to say how I was touched by the massive collective solidarity I witnessed, and this, throughout the day. I saw protesters from very different tendencies take care of each other. Individually, in groups or en masse. Despite an intense and sustained degree of repression.
From my point of view as a StreetMedic, this day was a bloodbath. Our interventions are increasingly that of wartime medical help. But paradoxically, the strongest feeling, the most present for me at the end of the day, is gratitude, a strong sense of cohesion, of solidarity, of strength, of convergence and of determination. The proof-in-acts that we – students, workers, unemployed, precarious – can be stronger in the face of the bosses, of the state, of its police.
Solidarity is an invaluable weapon.
From here:http://dialectical-delinquents.com/france-a-reader/
It's symptomatic of the complete absence of any contribution to the subversion of this world that this movement, the most explosive in Europe for probably 5 years, has received very little interest on this site. Before putting this up, this thread here had its last post almost 4 weeks ago, and this: https://libcom.org/forums/organise/nuis-debout-13042016 had just 9 posts. Compare this with the interest in the current presidential circus in the States ( http://libcom.org/forums/north-america/2016-us-presidential-election-05032016 ) or with the Michael Schmidt thread (almost 1000 posts) - http://libcom.org/forums/general/ak-press-says-michael-schmidt-fascist-25092015 , and you get some idea of what utter disinterest there is in the actually existing class struggle on this site for sore eyes.
Rest in Peace.
https://nantes.indymedia.org/articles/34302
Red Marriott
Red Marriott said:
Quote:
[...] Rest in Peace.
Then that makes your repeated visits here to say this a form of necrophilia
Not that I really care one way or another, but the metaphor doesnt seem to be right; Boris seems to be pissing on the gravestones rather than fucking the dead. Those who like this site might be more easily compared with necrophiliacs if you accept Boris rather vague "Rest In Peace" as meaning the site is a corpse.Or perhaps Coprophiliacs would be more appropriate, considering the admins past..
On police violence against
On police violence against demonstrators, and on poilce efforts to launch a PR counteroffensive:
French police hit back at 'anti-cop hatred' after protest violence
At demonstrations against the labour reform bill outside parliament this week, protesters chanted what has now become a regular slogan: “Everyone hates the police.”
Some skirmishes in the social
Some skirmishes in the social war in France:
Latest direct action news from France
And an analysis, from a Trotskyost background, containing interesting information on the attitude of the trade unions:
April 28, another step towards confrontation with the government
I'm bi lingual and have some
I'm bi lingual and have some spare time at the moment, so if anyone has any French txts that you need translating, I'm happy to help out.
Quote:
Not that I really care
Not that I really care one way or another, but the metaphor doesnt seem to be right; Boris seems to be pissing on the gravestones rather than fucking the dead. Those who like this site might be more easily compared with necrophiliacs if you accept Boris rather vague "Rest In Peace" as meaning the site is a corpse.
Boris's hostility is more passionate and committed than the liking of most users; he is its most loyal opposition. This site, corpse or not, clearly has an ironic enduring attraction for Boris in his incarnation(s), however we metaphorically interpret it.
I'm bi lingual and have some spare time at the moment, so if anyone has any French txts that you need translating, I'm happy to help out.
Cool. There are a few ideas here, honestly it will take as much time as you're willing to put into it. There's so much info out there,it's just scanning, sorting, summarising etc.
There are a few links below. If any lazy journos use them then at least put the article on here too.
Timeline of the nuits debout.
http://www.liberation.fr/france/2016/04/30/du-30-au-60-mars-un-mois-de-nuit-debout_1449387
These are the home pages on this subject for some of the main newspapers:
http://www.lemonde.fr/nuit-debout/
http://www.liberation.fr/nuit-debout,100606
http://www.humanite.fr/etiquettes/nuit-debout
http://www.humanite.fr/etiquettes/loi-travail-el-khomri
http://www.ouest-france.fr/economie/emploi/loi-travail/
Indymedia:
https://lille.indymedia.org/
https://nantes.indymedia.org/
Cool. There are a few ideas here, honestly it will take as much time as you're willing to put into it. There's so much info out there,it's just scanning, sorting, summarising etc.
There are a few links below. If any lazy journos use them then at least put the article on here too.
Timeline of the nuits debout.
http://www.liberation.fr/france/2016/04/30/du-30-au-60-mars-un-mois-de-nuit-debout_1449387
These are the home pages on this subject for some of the main newspapers:
http://www.lemonde.fr/nuit-debout/
http://www.liberation.fr/nuit-debout,100606
http://www.humanite.fr/etiquettes/nuit-debout
http://www.humanite.fr/etiquettes/loi-travail-el-khomri
http://www.ouest-france.fr/economie/emploi/loi-travail/
Indymedia:
https://lille.indymedia.org/
https://nantes.indymedia.org/
Nice one, thanks for the links. I've ended up pretty out of the loop of goings on in France since I cut facebook out of my life 18 months or so ago, as I used to get most of my links to French language sites/txts off mates on there. I'll have a start on it over the weekend.
bedfordtk
I'm bi lingual and have some spare time at the moment, so if anyone has any French txts that you need translating, I'm happy to help out.
Students have widely reported
The government forced through
http://www.theguardian.com/world/2016/may/10/francois-hollande-pushes-through-labour-bill-with-special-decree
France’s Socialist government has taken the risky and controversial decision to bypass parliament and use a special decree to force through a contested labour reform bill by its president, François Hollande, that has brought hundreds of thousands of protesters on to the streets.
The defiant move by the government came as it faces growing pressure from its own rebel MPs and an ongoing street protest movement that has seen violent clashes. The government opted to use a heavy-handed and rare constitutional tactic which allows policies to be pushed through without a parliamentary debate after it failed to win over its own group of rebels.
Re post #39:
Re post #39: https://libcom.org/forums/news/france-protests-against-new-labour-law-17032016?page=1#comment-576902
-jef costellooffers (for translation)bedfordtkonly 4 very mainstream bourgeois, 2 mainstream Stalinist - ie l'humanite - sites (well-known for its consistent sabotage of all forms of class struggle for about 100 years), plus a couple of indymedia sites renowned for information and analysis that never differentiates between dire and diamond. It´s not that such sites are useless, but by ignoring more clearly radical sites, you give the impression that there´s nothing but dominant bullshit out there. In fact, the following anarchist sites are a lot more consistent at least, and yet JC, who I doubt is unaware of them, doesn't suggest them as a source for translation:
http://www.non-fides.fr/http://attaque.noblogs.org/http://lechatnoiremeutier.noblogs.org/http://exploitesenerves.noblogs.org/http://cettesemaine.info/breves/
As for Red Marriotts post ( https://libcom.org/forums/news/france-protests-against-new-labour-law-17032016?page=1#comment-576894 ):
Not that I really care one way or another, but the metaphor doesnt seem to be right; Boris seems to be pissing on the gravestones rather than fucking the dead. Those who like this site might be more easily compared with necrophiliacs if you accept Boris rather vague "Rest In Peace" as meaning the site is a corpse.
Boris's hostility is more passionate and committed than the liking of most users; he is its most loyal opposition. This site, corpse or not, clearly has an ironic enduring attraction for Boris in his incarnation(s), however we metaphorically interpret it.
... "When the wise man points at the moon, the fool looks at his finger."Or to put it another way: when the messenger points out something, the fool ignores what he's pointing out and shoots the messenger for pointing it out. The fact that RM says nothing about the movements in France (nor in South Africa) just adds to this impression of some personal fixation or ... I don´t know what, but it seems like he´s just got some incomprehensible personal grudge - really useless for any understanding of wider events.As for the idea that I am this site's most loyal opposition, if 11 posts over more than 3 years is the most loyal opposition you lot have had then that might explain how very stale you've all become.
Quote:
As for the idea that I
As for the idea that I am this site's most loyal opposition, if 11 posts over more than 3 years is the most loyal opposition you lot have had then that might explain how very stale you've all become.
This bickering appears to me
The work code 'reform' was
The work code 'reform' was confirmed in the national assembly today when the government survived a vote of no-confidence.
BorisJobson wrote:
Re post
BorisJobson
Re post #39: https://libcom.org/forums/news/france-protests-against-new-labour-law-17032016?page=1#comment-576902
-jef costellooffers (for translation)bedfordtkonly 4 very mainstream bourgeois, 2 mainstream Stalinist - ie l'humanite - sites (well-known for its consistent sabotage of all forms of class struggle for about 100 years), plus a couple of indymedia sites renowned for information and analysis that never differentiates between dire and diamond. It´s not that such sites are useless, but by ignoring more clearly radical sites, you give the impression that there´s nothing but dominant bullshit out there. In fact, the following anarchist sites are a lot more consistent at least, and yet JC, who I doubt is unaware of them, doesn't suggest them as a source for translation:
http://www.non-fides.fr/http://attaque.noblogs.org/http://lechatnoiremeutier.noblogs.org/http://exploitesenerves.noblogs.org/http://cettesemaine.info/breves/
I believe Libération was actually maoist to begin with.I do not recognise any of those sites, I'm not going to waste anyone's time by asking why on earth you think I would deliberately ignore radical sites.
Quote:
The work code 'reform'
The work code 'reform' was confirmed in the national assembly today when the government survived a vote of no-confidence.
So today is a momentous day in the struggle of the classes. The bourgeoisie achieves it's goal; it pushes through it's attack on the French working class, and hence the global working class, but at what price? What was the pressure force that determined the manner in which these new measures were passed through parliament? The force on the streets. And certainly not the most intense class warfare the world has witnessed; more like a circus (no disrespect to those who's heads were smashed in). Everything has changed, yet on the surface everything appears the same.
...every social reform remains a utopia until the proletarian revolution and the feudalistic counter-revolution measure swords in a world war.
Karl Marx, to the Workingmen's Club in Brussels, December 1847
http://www.taranisnews.com/post/144320329078/rennes-la-bataille-pour-le-centre-ville-part-6
This site, taranisnews, generally has good image and videos.
In Rennes the building that had been occupied for about a week was taken by the police yesterday morning. Later in the day a wild demonstration of a few hundred took place(in the link above). For today the police have banned gatherings in Rennes, according to mainstream media.
julio27:
Quote:
A new Mai 68
julio27:
A new Mai 68 in Paris?
https://www.youtube.com/watch?v=xsL_tNNac4E
Loved seeing the union stewards squirming and petrified at 9:40. It made the wait worthwhile.
Yes
police & security squad =
Yespolice & security squad = same strugglethey are shoutingthat's what the "paris lutte"-site is about, I believe
live ticker 19/5
https://paris-luttes.info/jeudi-19-mai-greves-et-5738
http://paris-luttes.info/
Good pick!
- A quick translation of the stream for yesterday.
Walls said that he will use the police to break 'economic blockades' and he has ordered the SO (March stewards) to work with the police to stop casseurs ( bank windows and advertising have been targeted)
At least 83 CRS trucks at Nation, they started searching people coming out of the station and confiscating protective equipment. They then started frisking people in the street.
At least 5000 at the head of the march. A lot of tear gas used to protect banks at St Marcel. Banks and insurance companies on the route so far have been targeted. Severl protesters injured by gas grenades.
MArchers stood their ground against tear gas attacks. Clashes in front of the Police station in the 13th.At least three arrests, including a CNT steward.
After being pushed back by a police charge the CNT and SUD blocs manage to reach Place d'ItalieThe police kettle the area, keepin gone exit open. Several arrests, a few projectiles thrown at police in front of the town hall.Plain-clothes brigade police who have been infiltrating the march pushed out by demonstrators.
100 or so people assembled outside the police station in the 20th and the CNT steward was eventualy released at about 10pm.
-A few extras.
- Lycée Mozart, in the suburbs, Blanc-MEsnil, was blockaded today by the students protesting against saliva tests for drugs. The school was labelled the most drugged up school by minister Valérie Pécresse (The protests in 2006 were against the 'loi Pécresse')
- Student contract workers at BULAC, one of the biggest libraries, have gone on strike to demand official recognition of their status and to no longer have to make up the hours if they are absent due to sickness or if the library is closed for bank holidays.students make up a fifth of the workforce but 45% of the customer services and work anti-social hours. The stirke is ongoing and began on May 14th.
At least three arrests, including a CNT steward. After being pushed back by a police charge the CNT and SUD blocs manage to reach Place d'Italie.
Tomorrow will be the day of the manif at Lille against the cops raid against the local CNT-F office and the charges against CNT-F members. We will see whats gonna happen there.
For the french CNT-F the situation has been getting somewhat difficult. While a lot of people have been flocking into the union in the past weeks and they (re-)gained a notable «street credibility», the attempts to criminalize the union are multiplying. A couple of days ago for instance, a Bordeaux newspaper in some sort of witch hunt accused the CNT-F to be responsible for the riots in the city. In Paris cops tried to prevent CNT-F union members from leafletting etc.
The french government in its attempt to bypass the parliament with the law 49.3 «El Khomri» is reacting more and more nervous as people do not stop striking and continue to take to the streets even under conditions of state of emergency.
Strikes and blockades are
Strikes and blockades are continuing at a number of oil refineries. Some refineries have been closed for the last couple of days with another refinery blockade since last night. So far these blockades have caused some petrol shortages and closed a number of stations.
http://www.bbc.com/news/business-36353099http://www.leparisien.fr/economie/carburant-6-raffineries-sur-8-en-greve-blocage-du-depot-de-fos-23-05-2016-5820733.php
Yes, there is nothing about it here. It would be great if we could have some stuff about it in news. Jef thanks very much for those translations, that's great. Don't know if you would have time to do some translations of that feed on a regular basis? Something brief like that, bullet pointed each day or two with a picture or video or two would be amazing! (No worries if you don't have time but thought no harm in asking!)
So, what's the relationship
So, what's the relationship in France between the Socialist Party and the unions, just out of curiosity?
The BBC has picked it up here
The BBC has picked it upherefocusing on petrol shortages.
Socialist party is in
Socialist party is in government and has pushed through the law so the relationship isn't too close at the moment but will doubtless be rekindled in the future.The CGT is usually the closest and they were the ones who had accusations of stewards handing people over to the police although I think that is relatively rare (but it does happen)The fuel shortages were mainly in Nantes (militant) and PAris (big demand) but have been spreading. BLockades at six out of eight blockaded sites were lifted by negotiations or force (Friday) but four more were blockaded Saturday. At least three, in the north and west, are still blockaded other sources state five or six refineries but it's unclear. Most mention of unions is of the CGT, one source mentioned FO.
2031 out of 12000 petrol stations are out of petrol according to the app that has been launched.shortages map: (not showing properly, it's a google widget so no idea what's happening.
Map of sites: circles are the eight refineries, the rounded squares are depots, x symbolises that it's blockaded.
The CGT has called an all-out strike from June 2 on public transport in Paris (RATP), it's the biggest union, they're asking for salary increases (300e a month) and repeal of the law. The second biggest union, UNSA has withdrawn it's threat to strike during the Euros in exchange for some concessions (another union cge-cgc has also reached a settlement)
Last night someone fired 12 shots from a 9mm pistol into the shutters of a closed Socialist Party office in Isère in Grenoble.
Others have had grafitti dran on them
There's a demo today at the Ministry of work by undocumented workers, asking for papers and that employers not be fined 1000 for hiring them.The inter-union councils at the ministry support this, unions involved: CGT-TEFP, Snutefe-FSU,Sud Travail
There's been a call for a demo tonight outside the offices of the 'sûreté nationale' in Nanterre, quite a few schoolchildren from Levallois have been given prevention orders for demos (at least 13) and three are being held in custody.
Lycée Dorian in Paris, 11th district, Four students have been excluded for up to 8 days for peaceful actions (unclear what, but not blockading) so there's a solidarity demonstration tomorrow at 11am. There was a meeting this afternoon between representatives from various schools, not sure what they've decided.
Call centres for one of the banks have been out on strike since the 17th, 70% observance.
btw, I'm only going to mention published actions, just in case.
I'd like to do a bit more, throwing together quick translations doesn't take too long, but finding the information and then collating / checking does. This is all pulled off a few mainstream sites and parisluttes.
Quote:
The BBC has picked it
The BBC has picked it up here focusing on petrol shortages.
That story led me to this one, http://www.bbc.co.uk/news/world-europe-36324358. The BBC caption reads:
Police officers in Paris were able to flee their car before it was set alight
I watched a video of this incident and the caption is untrue. The car is set alight. The cop gets out of the car, faces up to a man clad in black and wielding a length of plastic tube; the cop takes several blows across the body without wincing, his assailant is pulled away, and the cop turns and walks casually up the street.
It seems that this movement
It seems that this movement "Nuit debout" is part of a policy of French capital to refresh its forces of the left and make the issue one of "putting pressure on the bosses", ultimately by the means of the polling booths where the working class become discontented impotent "citizens". This particular manoeuvre of the French bourgeoisie follows on from the endless and mindless processions organised by the French unions against the new labour laws. It's not a French phenomenon and follows the likes of Corbyn in Britain, Podemos in Spain and Sanders in the US.
Various leftists. "altermondistes" and leftist intellectuals were involved in its beginnings and its electoral and divisive aim is clear in its allusion to the victory "as in '81". The victory of 1981 was a Socialist government that unleashed the worst attacks on the working class since the Second World War.
There are no doubt many sincere and angry workers on the streets along with close elements of the population. But this is not the left of capital jumping onto a proletarian bandwagon but a capitalist set-up, denouncing the "bad" capitalists intending to promote the "citizenship" of France.
Below is a link from the ICC in French. If there's a translation, I'll post it.
http://fr.internationalism.org/revolution-internationale/201605/9369/quelle-veritable-nature-du-mouvement-nuit-debout
Thanks for the update Jef!
union blockades forced by
union blockades forced by police/army , refinery workers going on strike (1 of 8 production sites working)
https://www.youtube.com/watch?v=a6Lp0EPswgc
https://www.youtube.com/watch?v=r8-PwKOUfhs
https://www.youtube.com/watch?v=KPjaob1RanA
If the Markets are any
If the Markets are any indication, the Unions have subsumed this wave of struggle but only time (the action of our class) will be the ultimate test.
Following on baboon's post 78
Following on baboon's post 78 there is this translation of a leaflet from a small Ex-ICC group on the current situation:http://libcom.org/forums/organise/france-against-government-capitalist-state-23052016The basic political analysis seems sound and the call to action at the end, but as with similar efforts by these tiny (and feuding) fractions of the dispersed libertarian and left communist milieu it isn't matched by the experienced forces on the ground to have any substantial impact in the right direction.
Quote:
Strikes in production
Strikes in production imply collective class action and decision-making.
France : Against the Government and the Capitalist State, An All Out Strike in Every Sector of Production? Now is the Time! (May 21st 2016)
Or do they signify that the Unions are attempting to railroad the class struggle?
The national library (BNF)
The national library (BNF) has been on strike the last three saturdays, continuing this week. (Online strike fund has reached 1558e)Like the workers at BULAC they are vacataires, these are temporary positions under contract that cannot become permanent (as far as I know) For teachers many vacataires have been working for years and still have no official status or job security. Although they work under a contract they don't have a personal contract and work whatever hours they are given (usually on a termly basis) and have to invoice for the work (paymeny at least two months in arrears but six months isn't unusual and most vacataires will be working at three or more establishments and pretty much everyone had at least one that had a delay of over six months and quite a few of a year or more.
There's an online strike fund for teachers but it has only raised 110e and it's been open since Friday iirc.
RATP : the call for an unlimited strike starting June 2nd is still valid.
RailwaysStrikes and pickets at technicentre Landy (La Plaine)Strikes, continuing monday in the sectors Paris Nord (Gare du nord et al) and Paris Estand at the station gare d’Austerlitz.Strike at gare Saint-Lazare and the depots at Mantes and Achères
CGT has called for an unlimited strike starting may 31st at 7pm for the whole rail serviceThe inter-union council CGT-SUD-UNSA has given notice for a strike to start the same day in the sector Paris-Sud-Est (stations Gare de Lyon, Melun, Montargis, Laroche)
Lycée Mozart is still on strike
Lycée Rostand (93) is now on strike (staff)
Postal workers in the 92 has been on strike since May 10 against replacement of workers by temps and casual staff.
more to follow if I have time.
Whilst talking about responses and ideas emanating from small political groups with ambitions to promote something more radical in response to the growing strike movement against the French labour reforms this site under it's 'Social Strike' slogan has an interesting article comparing the French reform programme with the earlier German 'Agenda 2010' and hints at a new Euro 'Agenda 2020'. Might be worth a look?http://www.transnational-strike.info/2016/05/20/the-big-brother-of-the-loi-travail-the-german-agenda-2010/
It's an interesting post and I wouldn't disagree with most of what it says. I hadn't heard much about the elements of self-organisation in Germany against its new labour laws, my impression being that they were led by the unions. But, as the author says, they weren't enough. For the author above "to stand against the labour laws ... is to stand against the world". The CGT is very much against them as are other elements of the French state and the danger for the working class is that it is mobilised by these elements..
The situation of the attacks in Germany. Agenda 2010, launched in 2003, and successfully implemented relatively quickly with the French complaining of German "wage dumping"at the time, shows the weaknesses and difficulties that the working class has been showing for some time now. The disorientation suffered by the working class world-wide by the1989 "collapse of communism" and the "victory of capitalism" was particularly intense in Germany not least along with the effects of unification. The German bourgeoisie, as is its history, was ruthless in its attacks on the working class and the latter unable to respond. One lesson for the working class in France today is that sectionalised, unionised or democratically based responses are traps that will lead to defeat.
Apparently from yesterday all
Apparently from yesterday all oil refineries in France have voted to go on strike, following a violent police attack and water cannoning of a picket
Why is the just not getting
Why is the just not getting covered in the English-language media???
Any estimates on the total number of workers out at this point?
Thanks all round for the updates.
EDIT: TBF, this is the lead article on the BBC website at the moment: http://www.bbc.com/news/world-europe-36385778
Couple of posts on the
Couple of posts on the Guardian:Strike hits French oil refineries as police break up Marseille picketFrench riot police use water cannon to break up fuel depot blockade
Nuclear power workersset to join the strike today..
Fucking love the French.. :)
Mark my words: the industrial
Mark my words: the industrial action will be contained within French borders and the whole affair will have blown over in time for the footie! Unless the working class can break out from the constraints imposed upon it by the unions and national borders, which is unlikely as the CGT, the French State and it's bourgeoisie have a lot more to lose than it's opposition does.
if it is to be compared with
if it is to be compared with anything, the fight between the government and working class resembles pretty much Thatcher against the miners in 1983/4...
French CGT is fighting for survival
For those who read french:
http://www.lemonde.fr/economie-francaise/live/2016/05/26/loi-travail-suivez-en-direct-la-8e-journee-de-mobilisation_4926575_1656968.html
live-stream today: union pickets/blockades all over the country, mainly on french ports. nuclear plants joining struggle.
(leaving the thread for a while)
Chilli Sauce wrote:
Why is
Chilli Sauce
Why is the just not getting covered in the English-language media???
They never do.
-Collection for the collective defence associationhttps://www.helloasso.com/associations/cadecol/collectes/defcol
Cops have been confiscating protective equipment from protesters and street medics have been stripped of their supplies/equipment.
Between 7_23 MAy there have been at least 43 people held in custody in Paris, no data for the banlieue aside from the four kids in Levallois.
As well as violence and repression police have been trying other tactics, closing roads and metro stations to prevent marchers meeting up for example.
-In terms of strikes not sure of numbers:
-the call-centres for caisse d'epargne are still out after ten days, 70% observance.
-Posties in the 92 : Posties are based in four centres:75 à 80 % Asnières, 70 % Malakoff, 58 % Colombes 30 % Issy les moulineux
There's also an open strike fund. https://www.yoongo.com/fr-c-caisse-de-greve-des-postiers-du-92
They have ben trying to co-ordinate strikes with other postal workers and to contact other strikers and workers from different industries.
Strike votes pending in two districts of PAris.
- Aulnay et Sevran (93)Teachers, AED ( teaching assistants who sometimes are in class, sometimes supervise break times and generally do a lot of admin and other stuff) and CPE (handle discipine, but are the point of contact between school and family usually) were all out on strike on the 20th at four collèges: Christine de Pisan, Victor Hugo, Paul Painlevé and Evariste Galois. Striking against the precarious conditions of the AED. Strike observance around 100%
- Air Tahiti has been on strike since the 17th (related to their sector)The umbrella co-ordiation for aviation unions has given notice of a strike the 3,4,5 of June.
-All the refineries are closed, some blockaded. Petrol is running out, although like in England in 2000 that's at least partly due to people dashing out to stock up. The government have used the CRS to break blockades and have started to release the strategic reserve to break the stirke, although according to the papers 4000 out of 12000 stations are still having trouble getting supplies. And the self-reporting/crowd-sourced app reports 4856 out of 10254 having partially or totally run out of stocks.
- Workers at Le Parisien are striking today. The CGT's 'book section' has pledged to block publishing of national newspapers today. AFP (Agences France Presse) on strike 23-25. Radio France : unlimited strike notice from the 30th after sacking of a technician.
- Strikes in some branches of McDonalds, following on from strikes in MArch, but no data about sites/observance etc.
- Nogent-sur-Seine: staf at nuclear power plant have voted to stop producing power.
- One week strike at IBM starting today after 360 redundancies announced (260 immediate) and the transferring of staff to an outside contractor (Manpower)
-Today is a strike / action day.The CGT has blockaded the construction site at La Samaritaine (a huge former department store in central Paris).In Paris there are solidarity visits to pickets and a march later on.There was also an 'economic blockade' named 'Rio Grande' they blockaded the bridge at Genevilliers, cutting of France's largest river port from the road network. They blockaded it for two hours, unclear if they stopped or were forced off by police, but I think the latter. It was called by the 'interprofessional assembly' but seemed to have a student contingent and were talking about not depending on petrol and transport workers and spreading and generalising the strike.
Several schools in Paris blockaded and on strike. BLockades by students, some teachers striking but not many.
Nantes and Rennes solidarity visits to pickets and delegations between pickets as well as a demo.
PAris 11th two nights ago a job centre was tagged and had a few windows broken. Another in the twentieth as well. Yesterday one in Rennes got the same treatment.
In other news a suposed undercover infiltrator in Hamburg autonomist circles ahs been unmasked.Astrid Opperman / schutt
Schmoopie you are absolutely
Schmoopie you are absolutely correct, if they don't manage to move across borders then it will be limited to France.The CGT is heavily involved, but at least part of that will be a power grab as they have lost influence within the socialist party both through the diminution of the French Communist Party and in general. (The Socialists won as much by targeting communist votes as by taking them from the opposition, lots of the communist red crown was taken by the SP or by 'left lists'.)
As we're coming towards the end of term the involvement of school students will change, I don't know if they will strike during the holidays and for some, during the exams.
There's certainly a perception that the government is weak, but there's also exasperation. Teachers haven't had any salary increase since 2010 and unlike other civil servants they don't get a bonus so they haven't had any compensation that way either, the 1.2% he gave to all civil servants a month or two was not only a transparent bribe but a pretty feeble one, given that it doesn't even cover cost of living increases. (although teachers can still get council houses here, wish I'd managed to get one. )
From the BBC
From the BBC today:
Dozens of people broke away from a demonstration in Paris on Thursday and set about smashing shop windows and parked cars in a side street. Masked youths hurled bottles at police, who responded with tear gas.
Elsewhere in France on Thursday:—Clashes broke out in the eastern city Lyon after a march by at least 3,300 protesters;—In the port city of Le Havre, in Normandy, hundreds of workers took to the streets after blocking off a major bridge;—Riot police held back protesters in the central city of Tours;—Demonstrators invaded high-speed railway lines in the western city of Rennes;—Protest marches were reported in the southern cities of Marseille, Montpellier and Bordeaux.
Building on Schmoopie's
Building on Schmoopie's point: he could well be right (probably is, tbh).. but it may also be worth noting that Belgium is also currently undergoing its own protest movement against its own labour reforms..
Over 60,000 union workers protest labor reform plans in BrusselsRail Workers Strike Paralyzes Southern Belgium
From over here in the UK I'm hoping for the best..
Video coverage of the
Video coverage of the manifestation on may 26. The cops had occupied a part of Place de la Nation and ordered the crowd to leave. The result was, what in France is called « des incidents ».
https://www.periscope.tv/pibzedog/1eaKbwRvNWdGX
jef:
Quote:
Schmoopie you are
jef:
Schmoopie you are absolutely correct, if they don't manage to move across borders then it will be limited to France.
Not my words Mr Costello.
...action will be contained within French borders and the whole affair will have blown over in time for the footie! Unless the working class can break out from the constraints imposed upon it by the unions.
Today we witnessed many countermeasures by the working class to break free of the national constraints imposed upon it ( seepost #94).
This is starting to get some
This is starting to get some coverage in English language news, today Sky News was covering it, focussing almost exclusively on potential fuel shortages thanks to refinery strikes.
And the BBC radio news service is covering, focussing on the opposition to the labour reform laws. Still not much from the mainstream.
Oh and the Morning Star's given it somecoverage
robot wrote:
Video coverage
robot
Video coverage of the manifestation on may 26. The cops had occupied a part of Place de la Nation and ordered the crowd to leave. The result was, what in France is called « des incidents ».
https://www.periscope.tv/pibzedog/1eaKbwRvNWdGX
Cops look pretty nervous in that video and their snatch squads are often pretty poorly organised. But they still hurt a lot of people.
IT's good that people are filming because generally the police are far worse than anyone else and that we need to publicise things, but you do sometimes get the feeling that too many people think the whole point of a demo is to get a good photo. Each time someone started blowing bubbles they got swarmed by people with cameras.
It might be a good idea to use camera phones a bit like body cameras. MAke it harder for the cops to snatch and break them too. Also make sure your phone is password protected and saves to the phone memory, not a card, otherwise they can view / delete things.
In Rennes last night a police station was paint bombed and someone had painted AC on the front. I'm guessing they got interrupted.
1800- 3000 marching in Cherboug, gas supplies to 650 homes cut off. The communist mayor killed and a CGT militant severely injured in a car accident near to the march.
18-19000 in PAris according to police, an increase on the last marches, 100000 according to Union Force Ouvrière
Caen a case of 'self-defence' by a police officer.https://youtu.be/S69HPswDhbEAt least three arrests
PRime Minister MAnuel Valls has said that the law might be subject to revisions or improvements.
Belgian Rail workers have voted to continue their strike until Friday at least.
iexist, you are right, my statement was a little hackneyed. I am ashamed to say the BBC got the upper hand on this one:
Dozens of people broke away from a demonstration in Paris on Thursday and set about smashing shop windows and parked cars in a side street. Masked youths hurled bottles at police, who responded with tear gas.Elsewhere in France on Thursday:—Clashes broke out in the eastern city Lyon after a march by at least 3,300 protesters;—In the port city of Le Havre, in Normandy, hundreds of workers took to the streets after blocking off a major bridge;—Riot police held back protesters in the central city of Tours;—Demonstrators invaded high-speed railway lines in the western city of Rennes;—Protest marches were reported in the southern cities of Marseille, Montpellier and Bordeaux.
Yesterday's news from the BBC
ITV 6.30 news was weird...
ITV 6.30 news was weird... seemed to be mainly about how people in France are "very very angry" about having to wait ages for their petrol. Fucking bobbins.
It appears to me that the
It appears to me that the union's tactics of divide and rule have succeeded in exhausting an already weakened working class. Here's an English translation from the ICC's French section that I mentioned earlier: http://en.internationalism.org/icconline/201605/13953/what-real-nature-nuit-debout-movement
iexist:
Quote:
Your the
iexist:
Your the person who gives us left coms a bad name!
Defeat of our struggles is hard to stomach but scapegoating one communist will not ease the burden. However, if we can learn from our defeats we may eventually reach a point where they are no longer repeated; if not we are lost.
There are numerous reasons to
There are numerous reasons to be extremely cautious about what is happening in France and not to get carried away by the appearance of a massive movement. The article baboon links to confirms earlier assessments (eg in the Mouvement Communiste statement) that the Nuit Debout 'assembly' was planned well in advance by the new left coalitions arising in France in parallel with the likes of Syriza, Podemos, Corbynism, Sanders etc etc. And the current situation, dominated by the blockades of oil and power stations by the CGT, should give further pause for thought, since the French Stalinists have used this tactic before to create images of paralysis and radicalism, for example in 2010 in the protests against pension 'reforms'(which also, in retrospect were less radical than we ourselves thought at the time). But in reality these blockades are not the action of a class that is taking control of its own struggles on a massive scale, and that is why the Stalinists are very adept in using them.We could be wrong of course, but it would be unwise to dismiss the possibility that the French bourgeoisie, which confronts a fraction of the world working class that has a very evident and real revolutionary tradition, is being obliged to employ a division of labour, a series of feints and manoeuvres, both to distort the lessons of real movements like the one against the CPE in 2006 or the Indignados in 2011, and to derail a mounting discontent which lacks any real perspective or even a sense of class identity.
Alf wrote:
There are numerous
Alf
There are numerous reasons to be extremely cautious about what is happening in France and not to get carried away by the appearance of a massive movement. The article baboon links to confirms earlier assessments (eg in the Mouvement Communiste statement) that the Nuit Debout 'assembly' was planned well in advance by the new left coalitions arising in France in parallel with the likes of Syriza, Podemos, Corbynism, Sanders etc etc. And the current situation, dominated by the blockades of oil and power stations by the CGT, should give further pause for thought, since the French Stalinists have used this tactic before to create images of paralysis and radicalism, for example in 2010 in the protests against pension 'reforms'(which also, in retrospect were less radical than we ourselves thought at the time). But in reality these blockades are not the action of a class that is taking control of its own struggles on a massive scale, and that is why the Stalinists are very adept in using them.
You could be wrong. And worse, you could be missing the point entirely. Which you are. The point being that there's no other way for the movement to develop other than "being planned well in advance by new left coalitions," or "blockades of oil and power stations by the CGT." If there already was an independent autonomous class-for-itself, we wouldn't be discussing this would we? We'd be discussing the success of the French revolution as the opening round of world revolution.
This is how struggles develop, springing forth from, and carrying the baggage of all the institutionalized failures that have preceded it. That's the history in the historical materialism. After all, who dominated the soviets in April 1917; and who replaced the Czar? Not the soviets, that's for sure.
The origins of the struggle are not the slightest reason in the world to hesitate or "be cautious." It's all the more reason to develop the demands, the organizations, the institutions, that break the domination of the archaic clusters of power-- including the CGT bureaucracy, the new left coalitions-- and clearly this movement contains exactly that potential-- particularly with the almost universal acceptance of the demand to "open the borders"-- to cease the distinction between documented and undocumented workers.
The key, as others have pointed out, is how quickly, clearly, and class consciously the French workers and students can link up with those in Spain, Portugal, Italy, Greece, Belgium, Ireland, Poland, Germany, etc. etc.
There seems to be some talk
There seems to be some talk in the media and perhaps sections of the government to try and find a possible way out by making some changes to the text. Assuming that the government and CGT negotiate at some point it would seem mostly likely to be along these lines; a modified law.
The demonstrations while spaced out a bit in time, roughly one major demonstration every week, don't seem to be declining in energy. The numbers attending have been steady, or have even grown, as well for the last couple of weeks. The various groupings-autonomous/random, black bloc, etc- that make up the front of the demonstrations has increased over time. The police struggle to control this each time and kind of keep a distance while a march is in progress and just try to stop blocs of people leaving a contained area. This ability of the blocs to defend themselves and keep the police back to some extent is increasing the confidence of the demonstrators each time.
The pictures on this article from Paris yesterday give some idea of the level of tension: http://www.liberation.fr/france/2016/05/27/le-policier-a-adopte-une-attitude-provocatrice_1455720
There is a balance of forces
There is a balance of forces between the classes in every social movement, and this will greatly influence whether or not the organs of capitalist control can be outflanked by an upsurge from below. This will also determine what is possible for revolutionaries and others who are in favour of the movement going beyond these organs; it will be the key element in deciding what kind of influence they can have on the movement. It also shapes the content of their intervention. At certain moments it is perfectly valid to focus on pushing forward the immediate potential of the struggle by raising practical proposals for extension and self-organisation. At other moments, when the ruling class and its institutions are not in danger of losing their grip, it is more appropriate to focus on the dangers and traps facing the struggle. I think that we are in the latter situation with this current movement in France, and that the possibilities of immediately linking up with with workers and students in all the other countries of Europe, who are also experiencing major difficulties in developing a resistance to the crisis of the system, are very limited at this juncture.
| https://libcom.org/comment/577144 |
Father and Son Duo Tackle Diabetes
Father and Son Duo Tackle Diabetes
From the Editor:
The following story first appeared in the Summer 2006 issue of Voice of
the Diabetic , our quarterly publication that not only deals with managing
diabetes, but frankly and constructively addresses the disease's ramifications.
Tom and Eileen Rivera Ley have been NFB leaders from the time they joined the
organization as students. Here is the inspiring story of their challenging life
today:
Five-year-old JonCarlos
Rivera Ley looks just like his papa, Tom. JonCarlos inherited his charming smile,
his delightful singing voice, and his goofy sense of humor. And a year ago JonCarlos
also inherited his father's Type 1 diabetes.
But JonCarlos enjoys an
important advantage that most diabetic children do not. He has an arsenal of
the three most important weapons against a chronic disease like diabetes: know-how,
a positive attitude, and terrific role models. One of JonCarlos's advantages
comes from the fact that both his parents are blind.
Step Outside Your
Fear
But how can blindness
possibly be an advantage? JonCarlos's mom Eileen, who has been legally blind
since birth, explains: "Tom and I know that being blind can be rather frustrating
at times, but it doesn't mean that a good life is over. We accept that we have
to make adjustments, and we get on with life."
Tom, a thirty-nine-year-old
devout Christian and self-described math geek, lost his sight to diabetes at
age seventeen. He is currently undergoing dialysis three times a week while
awaiting a kidney transplant. Nevertheless, he is relentlessly upbeat, positive,
and energetic. "You can always think of reasons why you can't, if you're coming
from a position of fear. But if you step outside your fear and try, you can
usually figure it out."
Much of Tom's hopefulness
comes from his strong faith. "I truly believe that God allows struggles in our
lives for our good. For example, if I had not become blind, I would never have
met my wonderful wife or had my children."
JonCarlos's fourteen-year-old
sister Maria agrees: "My parents have never let disabilities stand in their
way. Some people think that, because my parents are blind, I do everything for
them or that I get away with lots of stuff because they can't see. But it's
not that way at all. Mom and Tom are super independent, and, trust me, my mom
never lets me get away with anything." Maria is really proud of her family.
In fact Maria recently gave a speech to her entire middle school about the strength
she and her little brother have gained from their parents' approach to adversity.
Find the People
Who Know
The Leys put their positive
attitude to work to handle their son's diagnosis. "When JonCarlos developed
diabetes," Eileen says, "we knew that handling diabetes would be a lot like
handling blindness. The key was to find the real experts, people living with
the problem every day. Those people are always out there, folks who are living
with the problem and have already found solutions."
The Leys learned this networking
strategy from the National Federation of the Blind. When Tom became blind in
high school due to diabetic retinopathy, he and his parents were distraught.
A gifted math and science student, Tom had dreamed of becoming an electrical
engineer. Shortly after he became blind, his father took down a volume of the
encyclopedia from the bookshelf and opened it to "blindness." There he read
that blind people succeed at many jobs, "and," Tom recalls with a smile, "lo
and behold, one of the jobs listed in the encyclopedia was electrical engineer!"
That experience planted
the seed of hope, but hope began to bloom fully when Tom met the National Federation
of the Blind. Joanne Wilson, then president of the NFB of Louisiana, reached
out to Tom. "It was truly amazing. She did things that I never dreamed blind
people could do. She had five children!" Tom adds, "Every time I talked to her,
she would mention something new, and I'd think, �How does she do that? How does
she go grocery shopping, or do her job?'" Dr. Wilson introduced Tom to people
in the NFB Diabetes Action Network, who taught him how to manage his diabetes
independently.
Eileen joined the Federation
while a student at Harvard College. Her life has never been the same since.
"It was a real relief to meet other blind people who were achieving their goals.
It took a lot of pressure off me. I no longer had to be a super blind woman.
I could just be myself."
Over the years Tom and
Eileen have benefited from the advice and support of dozens of successful blind
and visually impaired people. Today Tom is a software development manager for
UPS, and Eileen is a strategic planning and fundraising consultant and works
on
Voice of the Diabetic
. Now they mentor others dealing with blindness
and diabetes.
The Leys reached out to
another, different supportive community when JonCarlos was just nine months
old and was diagnosed with severe hemophilia, an extremely rare, genetic bleeding
disorder. Eileen: "We were shocked--no one in our families had hemophilia. But
we handled it the same way we handled blindness: we knew the key was to find
people who had done it before." They found the Hemophilia Foundation of Maryland,
and through the foundation's families learned how to manage their son's hemophilia
and, Eileen adds, "still help him have a normal childhood." With special IV
infusions of a blood clotting factor every other day, JonCarlos's hemophilia
is controlled.
So when Tom and Eileen
learned that JonCarlos had diabetes, they immediately put their NFB experience
to work again. First they sought advice from their friends in the NFB's Diabetes
Action Network, who assured Eileen that she could manage the glucose testing
and insulin dosing safely and effectively. Next they set about finding other
families raising diabetic preschoolers. Eileen recalls, "While we were in the
hospital dealing with the diagnosis, a dear friend got on the Internet and found
the Children with Diabetes Web site. Through it she found several families in
our area who have other boys JonCarlos's age with diabetes." With the support
of those families, Tom and Eileen learned things like how to train their son's
babysitters and preschool teachers.
Managing Diabetes
Is All Day, Every Day
Of course their positive
attitude does not mean that the Leys are Pollyannas. They recognize the challenges
and fears of raising a diabetic child. Eileen recalls, "I couldn't believe my
little boy had yet another chronic disease. When he was first diagnosed, I was
nauseated all the time. Of course Tom has diabetes, but he manages it on his
own. He's the family expert, but he was at work and I was home with JonCarlos.
Managing diabetes is all day, every day. I was terrified that I would forget
to give him his insulin or give him the wrong food or something."
JonCarlos's diagnosis was
particularly difficult for Tom. Tom recalls, "I had so many mixed feelings.
I had gone blind and gotten kidney disease as a result of my diabetes. I didn't
want my son to have to suffer. Now, with all the intensive therapies and better
insulins, I'm hopeful he won't have to suffer complications at all."
He continues, "I don't
want to sugar-coat it. Diabetes is a tough disease. You have to be a full-time
manager of your diabetes. You're always thinking about it, always planning for
it throughout the day. The sooner you embrace this life and accept it as your
new normal, the sooner you can move on and keep living your life."
Managing with
Adaptations
Managing diabetes can
be challenging for anyone, but it is even more so for blind people. As Tom explains,
"There are three basics to day-to-day management: giving insulin, testing blood
sugar, and counting carbs. Those are all things that blind people can't do without
some adaptation."
The Leys employ a number
of adaptations to manage JonCarlos's diabetes. For administering insulin, they
use the NovoPen Junior by Novo Nordisk to administer Novolog and the OptiClik
by Aventis to administer Lantus insulin. The two pen devices are shaped differently,
which greatly simplifies identification. The dials on the ends of the pens measure
the insulin, and they make audible clicks for accurate dosing. Before switching
to his insulin pump, Tom used the Count-a-Dose, a device that provides audible
clicks so that a standard syringe can be accurately filled without sight.
For testing blood sugar,
the Leys use both talking and nontalking blood glucose meters. Tom uses a talking
meter, the ACCU-CHEK VoiceMate, while JonCarlos uses a traditional meter with
a visual display, the ACCU-CHEK Compact, and reports the numbers on the display
to his parents.
Counting carbs is a bit
more challenging. "When a new food comes into the house," Tom explains, "we
put a label on it, in Braille and large print, with the serving size and the
carbs per serving. After a while, we've come to know from experience how many
carbs are in our favorite foods." The Leys use their talking computer to access
special Web sites like CalorieKing.com where they can find carb counts.
One of the most helpful
strategies they used in managing JonCarlos's diabetes, Eileen recalls, was educating
their friends and family on how to manage the disease. "When we first started
meeting parents with diabetic children, we heard stories of parents who could
never go out on a date or leave their children at all and grandparents who wouldn't
watch their grandchildren because they were afraid of dealing with the diabetes.
There was no way we were going to accept that." Eileen invested some time in
explaining diabetes management to the parents of JonCarlos's friends, "and now
he goes on playdates like any other little boy."
But even a glance at this
remarkable family reveals that JonCarlos is not like any other little boy, and
his family is not like any other family. Diabetes, blindness, kidney failure,
hemophilia--it seems that they can overcome anything. Eileen laughs, "One of
the diabetes educators I know told me that blind diabetics like Tom are a real
inspiration to her sighted patients. She tells them, �If these blind people
can manage their diabetes and not complain, then you can do it too!'"
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Forests | Free Full-Text | Mixed Forest of Larix principis-rupprechtii and Betula platyphylla Modulating Soil Fauna Diversity and Improving Faunal Effect on Litter Decomposition
This research performed a comparison study to investigate how mixed forest affects the abundance, groups, and diversity of soil fauna and the effects of soil fauna on litter decomposition. We comparatively studied two forests, Larix principis-rupprechtii forest (LF) and mixed Larix principis-rupprechtii and Betula platyphylla forest (MF), which hold 30 years of stand age and are the representative forests in the mountainous area of northwestern Hebei, China. The field experiments were conducted from May to November 2020, with soil fauna and litter samples taken every one and a half months. A total of 540 soil samples (replicated samples, 3) were collected in each forest and the soil faunas were extracted from the samples by Tullgren methods in laboratory. Litter samples were incubated separately in the sampled forests using litterbags with two mesh sizes (0.01 and 4 mm) to observe the decomposition rate. In total, 2958 (inds.) soil faunas belonging to 4 phyla, 11 classes, and 20 orders, were found, with Acarina (1079/2958; 36.48%) and Collembola (1080/2958; 36.51%) being the dominant groups. The total abundance of soil fauna in the MF (1581 inds.) was higher than that in the LF (1377 inds.), and the significantly more abundant predatory functional group in the MF (p < 0.05) may indicate a more complex soil fauna food web structure. Comparatively, the higher Shannon–Wiener index (1.42–1.74) and Pielou evenness index (0.58–0.71) and the lower Simpson dominance index (0.22–0.32) in the MF suggested that the MF promoted the soil fauna diversity. The cumulative litter decomposition rate of litterbags with 4 mm aperture in the MF (54.52% in 300 days) was higher than that in the LF (32.81% in 300 days). Moreover, the litter decomposition rate was positively correlated with the total abundance and the number of groups, and was negatively with the Simpson dominance index, implying that the soil fauna activity effectively improved litter decomposition in the MF. Via the comparison, we found that the mixture of plant species in the forest can modulate the soil fauna diversity and accelerate the litter decomposition. The results in this study may provide an interesting reference for forest restoration and sustainable management.
Mixed Forest of Larix principis-rupprechtii and Betula platyphylla Modulating Soil Fauna Diversity and Improving Faunal Effect on Litter Decomposition
by Huayong Zhang * , Guixuan Han , Tousheng Huang , Yu Feng , Wang Tian and Xiaochang Wu
Research Center for Engineering Ecology and Nonlinear Science, North China Electric Power University, Beijing 102206, China
*
Author to whom correspondence should be addressed.
Forests 2022 , 13 (5), 703; https://doi.org/10.3390/f13050703
Received: 2 April 2022 / Revised: 27 April 2022 / Accepted: 29 April 2022 / Published: 30 April 2022
(This article belongs to the Section Forest Soil )
Abstract
This research performed a comparison study to investigate how mixed forest affects the abundance, groups, and diversity of soil fauna and the effects of soil fauna on litter decomposition. We comparatively studied two forests,
Larix principis-rupprechtii
forest (LF) and mixed
Larix principis-rupprechtii
and
Betula platyphylla
forest (MF), which hold 30 years of stand age and are the representative forests in the mountainous area of northwestern Hebei, China. The field experiments were conducted from May to November 2020, with soil fauna and litter samples taken every one and a half months. A total of 540 soil samples (replicated samples, 3) were collected in each forest and the soil faunas were extracted from the samples by Tullgren methods in laboratory. Litter samples were incubated separately in the sampled forests using litterbags with two mesh sizes (0.01 and 4 mm) to observe the decomposition rate. In total, 2958 (inds.) soil faunas belonging to 4 phyla, 11 classes, and 20 orders, were found, with Acarina (1079/2958; 36.48%) and Collembola (1080/2958; 36.51%) being the dominant groups. The total abundance of soil fauna in the MF (1581 inds.) was higher than that in the LF (1377 inds.), and the significantly more abundant predatory functional group in the MF (
p
< 0.05) may indicate a more complex soil fauna food web structure. Comparatively, the higher Shannon–Wiener index (1.42–1.74) and Pielou evenness index (0.58–0.71) and the lower Simpson dominance index (0.22–0.32) in the MF suggested that the MF promoted the soil fauna diversity. The cumulative litter decomposition rate of litterbags with 4 mm aperture in the MF (54.52% in 300 days) was higher than that in the LF (32.81% in 300 days). Moreover, the litter decomposition rate was positively correlated with the total abundance and the number of groups, and was negatively with the Simpson dominance index, implying that the soil fauna activity effectively improved litter decomposition in the MF. Via the comparison, we found that the mixture of plant species in the forest can modulate the soil fauna diversity and accelerate the litter decomposition. The results in this study may provide an interesting reference for forest restoration and sustainable management.
Keywords:
mixed forest
;
soil fauna
;
functional group
;
diversity
;
litter decomposition
1. Introduction
Soil faunas are an essential part of the forest ecological system [ 1 ], with their feeding and activity being involved in the decomposition and mineralization of soil organic matter [ 2 ], improving soil structure [ 3 , 4 ], and regulating the structure, function, and succession of plant communities [ 5 , 6 ]. They are an important guarantee for the material and energy cycle of the soil ecosystem [ 1 , 7 ]. The community composition, distribution characteristics, and diversity of soil fauna have often been studied. In recent years, researchers have discussed the influencing factors of soil fauna diversity on a large scale (climate conditions, geographical location, etc.) or meso-micro scale (vegetation types, pH value, temperature and humidity, mineral elements, etc.). The research showed that soil macrofauna diversity decreased as the elevation increased, which was affected by annual mean precipitation, altitude, annual radiation quantity, and annual mean temperature [ 8 ]. Xu [ 9 ] confirmed that forests with small gaps harbored the most species, with the most even distribution, and the highest diversity.
All kinds of soil faunas differ greatly in size and activity ability, and their activity patterns are different. However, many species are similar in function. They form the same functional group, mainly saprozoite, phytophage, predator, and omnivore. Studying soil fauna communities based on the functional groups can help to better understand the food web structure and the soil ecological function process. The density and group number of saprophytic soil faunas are more prominent in the forests with high canopy density, moist soil, and rich litters [
10
]. Santos [
11
] found that periodically flooded forests favored groups from the saprophagous groups, while fragments and anthropic fields in the Atlantic Forest favored predator and herbivore groups, reflecting the predominant functional groups in the two different understory microhabitats. The proportions of functional groups are important biological indices to measure ecosystem function and soil fertility.
The soil fauna play an important role in litter decomposition, which is one of the most important pathways in the terrestrial ecosystem’s energy transformation and material cycles. The soil fauna directly feed on and break litter or affect the litter decomposition by affecting soil microorganisms. Many studies have shown that changing vegetation types can affect species composition and soil fauna community structure, which, in turn, affects litter decomposition [
12
]. Meanwhile, environmental factors are also critical. Studies have shown that temperature and moisture can directly mediate litter decomposition, but in opposite directions [
13
]. Njoroge [
14
] highlighted the importance of soil fauna in mixed litter decomposition, most strongly in dry environments.
Researchers pay great attention to the productivity of mixed forests and their effects on forest biodiversity, with soil fauna communities being one of the research focuses. Many studies have shown a positive trend for increased tree richness or when broad-leaved species are introduced into coniferous stands. Hu [
15
] confirmed that the mixed planting of
Larix principis-rupprechtii
and
Betula platyphylla
could increase soil fauna groups, individuals, and diversity levels, especially the increase of phytophagous groups was conducive to the initial decomposition of fresh litter. In general, the composition of the soil fauna communities is closely related to the composition of surface vegetation, and the interactions are highly complex and dynamic [
16
]. Therefore, research of the soil fauna community characteristics in vegetation restoration in specific regions can contribute to sustainable ecosystems management.
Owing to human destruction such as overgrazing and over-harvesting, the forest vegetation has been greatly damaged and the ecosystem function has been seriously reduced in the mountainous area of northwestern Hebei, China. In the 1990s, China set this area as a key area of forestry ecological construction and strengthened the construction of artificial forests to promote ecological restoration.
Larix principis-rupprechtii
seedlings were planted in the mountainous area of northwestern Hebei, with some areas growing into pure
Larix principis-rupprechtii
forest. Meanwhile, some
Larix principis-rupprechtii
seedlings were planted near the secondary
Betula platyphylla
forests, where the seedlings of
Betula platyphylla
also invaded, and then the seedlings of the two species competed to grow into a mixed forest. Based on previous research works, we hypothesized that the mixture of plant species can promote better restoration of soil fauna communities, leading to higher abundance, group number, and diversity of the soil fauna. Additionally, the faunal effect on litter decomposition in the mixed forest can be improved simultaneously with the soil fauna diversity. Thus, in this study, we take the
Larix principis-rupprechtii
forest (LF) as well as the mixed
Larix principis-rupprechtii
and
Betula platyphylla
forest (MF) as research objects to comparatively investigate the restoration outcomes of the soil fauna diversity and faunal effect on the litter decomposition. We analyzed the temporal and vertical distribution of soil fauna communities and the response of soil fauna to soil properties, and then explored the relationship between soil fauna and litter decomposition by investigating litter mass-loss rates in litterbags with different mesh sizes. We expected to conclude that the MF will improve the abundance, groups and diversity of soil fauna compared with the LF. We also expected to find a difference in litter decomposition rate between the two sampled forests, i.e., a higher decomposition rate in the MF than in the LF. This research may improve the understanding on the restoration of forest ecosystem function and provide an interesting reference for forest sustainable management.
2. Materials and Methods
2.1. Study Site
The study site is located in the Taizicheng River catchment in the mountain area of northwestern Hebei, China (
Figure 1
,
Table 1
). The study site belongs to the cold temperate sub-arid zone of the continental monsoon climate [
17
]. Due to the climate being rather mountainous, the temperature rises quickly, and precipitation is poor in spring (May–June). Summer (July–August) is cool and short, with a significant temperature difference between day and night and concentrated rainfall. The first frost appears earlier in autumn (September–October). Cold air is frequent in winter (November–April). The vegetation period in the mountain area of northwestern Hebei is about 90 days. Over a year, the average temperature is 3.7 °C, and the average precipitation is 483.3 mm. More than 2100 species of terrestrial wild plants belong to 513 genera and 120 families in the northwestern Hebei (Zhangjiakou Municipal People’s Government;
www.zjk.gov.cn
Figure 1. Location of the study site.
Table 1. The basic situation of the sample plots in the study site.
2.2. Experimental Design
A 100 m × 100 m sample plot was set in each forest type, respectively. According to the diagonal method, three subplots, each of which measured 30 m × 30 m, were established in each sample plot on the upslope, mesoslope, and downslope. Three replicate sampling points with similar habitats were selected for each 30 m × 30 m subplot, and the three samples were mixed into a composite sample. In early May, mid-June, early August, mid-September, and early November 2020, specimens were collected five times at fixed points in the plots. The sampling sites were required to be free of rocks, human disturbances, and soil fauna nests. Soil samples were collected with a 200 mL volumetric ring knife (height: 5 cm) in four soil layers of 0–5 cm, 5–10 cm, 10–15 cm, and 15–20 cm below the surface, called layer I, layer II, layer III, and layer IV, respectively. A total of 1080 samples (i.e., 360 composite samples) were collected in the two sampled forests, including replicated samples, and statistics were averaged. Manual sorting and a modified Tullgren funnel method were used to collect the soil fauna. The excavated soil sample was placed in a stainless-steel tray to hand-picking soil macrofauna. Then, the collected faunas were extracted using the modified Tullgren funnel method for 48 h in the laboratory. All of the extracted soil fauna samples were preserved in 75% ethanol. They were counted and identified into order, family, and other classification elements under a stereoscopic microscope (OLYMPUS SZX16; OLYMPUS in Tokyo, Japan) [
18
]. According to their feeding characteristics, the soil faunas were classified as saprozoite, phytophage, predator, and omnivore based on the monographic and related literature [
19
]. Further, the various soil fauna groups were classified based on the number of individuals as follows: (1) dominant groups: >10% of the total number of individuals captured; (2) common groups: 1–10% of the total number of individuals; (3) rare groups: <1% of the total number of individuals.
Litter samples were collected in September 2019. Only the existing intact litters that had not been decomposed in the sample plot were collected as test samples to ensure the consistency of freshness of litters. Soil and other impurities were removed in the laboratory and air-dried to a constant weight of 65 °C. Litterbags with specifications of 20 × 20 cm, aperture of 4 mm (allowing all soil fauna to enter) and 0.01 mm (excluding the influence of soil fauna) were loaded with 20 g (accurate to 0.001 g). Litterbags were stitched together with nylon mesh with corresponding apertures [
20
], and were placed in the corresponding plot in January 2020 and decomposed under natural conditions. In mid-June, early August, mid-September, and early November 2020, three litterbags were randomly taken from each sampling site and brought back to the laboratory. The litter was dried and weighed to measure the decomposition rate. Since the study area was covered with snow from January to May 2020, sampling was not carried out considering the feasibility of practical work.
Environmental factors analyzed included soil bulk density (BD), pH, organic matter (SOM), total nitrogen (TN), and total phosphorus (TP). Undisturbed soil samples collected with a ring knife were used to measure BD. The collected soil samples were air-dried, ground, and made to pass through 0.25 mm sieves for laboratory analyses. The soil sieved with the 0.25 mm mesh screen was utilized to measure TN and TP contents. Soil TN content was determined using the semi-micro Kjeldahl method [
21
]. Soil TP content was measured using molybdenum-antimony colorimetry. Soil pH was measured using an acidimeter (soil:water = 1:2.5,
w
/
v
) [
22
]. Basic soil properties in the two forest types are shown in
Table 2
.
Table 2. Quality parameters of soil in the sampled forests.
2.3. Statistical Analyses
The diversity of soil fauna communities was quantified using the Shannon–Wiener index (
H
) [
23
], Pielou evenness index (
J
) [
24
], and Simpson dominance index (
C
) [
25
]. The calculation formulas are as follows:
H = − ∑ i = 1 n P i ln ( P i ) ,
(1)
J = H / ln S ,
(2)
C = ∑ ( n i / N ) 2 ,
(3)
where
S
is the number of soil fauna groups,
P i
is the proportion of the individuals of
i
-th group to the total individuals,
n i
is the number of individuals in the
i
-th group, and
N
is the total number of individuals in all groups.
Litter mass residual rate (
R M
) [
26
]:
R M = M t / M 0 × 100 % ,
(4)
where
R M
is litter mass residual rate (%);
M t
is the mass of litters at t decomposition time (g);
M 0
is the initial mass of litter (g).
Olson model of litter decomposition [
27
]:
M t / M 0 = a e − k t ,
(5)
Time required for 50% decomposition of litter and 95% decomposition of litter:
t 50 % = − ln 0.5 / k , t 95 % = − ln 0.05 / k ,
(6)
where
a
is the modified parameter;
k
is the decomposition rate of litter;
t
is the decomposition time of litter.
Contribution of soil fauna to litter decomposition (
L
) [
28
]:
L = L f a u n a / L t o t a l × 100 % ,
(7)
where
L f a u n a
refers to the litter loss caused by the soil fauna (the difference in litter loss rate between the 4 mm diameter and the 0.01 mm diameter litterbags);
L t o t a l
refers to the litter loss caused by the soil fauna, microorganisms, and abiotic factors (the litter loss rate of the 4 mm diameter litterbags).
The properties of soil fauna abundance, functional groups, and diversity in each composite sample were compared by one-way ANOVA, and the LSD procedure and contrasts with a probability level of 0.05 was used to identify significant differences. Using the Pearson correlation coefficient, the ecological indices of soil fauna community soil faunal in mid-June, early August, mid-September, and early November were used to analyze the monthly average mass loss of litterbags from 0 to 165 d, 165 to 210 d, 210 to 255 d, and 255 to 300 d. Redundancy analysis (RDA) was applied to analyze the relationships between soil fauna communities and soil properties using CANOCO 5.0 (Biometris, Wageningen, Netherlands). In addition, the significance of the first axis and all axes was evaluated by Monte Carlo tests (499 times,
p
< 0.05). Statistical analyses were conducted via SPSS 25 (IBM Corp., Armonk, NY, USA). Figures were made using the drawing software Origin 2018 (OriginLab., Northampton, MA, USA).
3. Results
3.1. Soil Fauna Community Characteristics
3.1.1. Temporal and Vertical Distribution of Soil Fauna Community
A total of 2958 (inds.) soil faunas were captured in this study, belonging to 4 phyla, 11 classes, 20 orders, and 39 families, including 22 groups ( Table 3 ). Acarina (1079/2958; 36.48%) and Collembola (1080/2958; 36.51%) were dominant groups. The common groups were Isoptera (156/2958; 5.27%), Diptera (larvae) (191/2958; 6.46%), Enchytraeidae (59/2958; 1.99%), Araneae (97/2958; 3.28%), and Geophilomorpha (32/2958; 1.08%); the rest were rare (98/2958; 3.31%).
Table 3. Composition of the soil fauna community.
A total of 1377 (inds.) soil faunas, including 19 groups, were captured in the LF (
Table 3
). The dominant groups were Acarina (543/1377; 39.43%) and Collembola (503/36.53; 36.53%). The common endemic groups of the LF were Isopoda (17/1377; 1.23%) and Psocoptera (42/1377; 3.05%) in the two sampled forests. The abundance of dominant and common groups was large in the LF, accounting for 75.96% and 19.75% of the total abundance, respectively, constituting the basic components of soil fauna in the LF. The abundance of rare groups accounted for only 4.29%, whereas 10 fauna groups were included in rare groups, accounting for 52.63% of the total groups in the LF, which were indispensable components of improving soil fauna diversity. The total abundance of soil fauna changed significantly with the seasons (
p
< 0.05) and showed a unimodal trend from May to November. The abundance of Diptera (larvae) showed a decreasing trend and was common in early May but rare in early November.
A total of 1581 (inds.) soil faunas, including 19 groups, were captured in the MF (
Table 3
). The dominant groups were also Acarina (536/1581; 33.90%) and Collembola (577/1581; 36.50%), Thysanoptera (76/1581; 4.81%) and Geophilomorpha (29/1581; 1.83%) were the common endemic groups of the MF in the two sampled forests. The MF modulated the abundance of dominant, common and rare groups of soil fauna. Similar to the LF, the abundance of rare groups in the MF was low (2.46%), whereas the proportion of fauna groups included in the rare groups was high (52.63%). However, the abundance of common groups in the MF (27.24%) was higher than that in the LF (19.75%). The abundance of the MF varied more significantly than that of LF by month, especially the total abundance (
p
< 0.05). In early August, the individuals of dominant groups were 6–7 times that of early May.
The soil fauna community tended to gather on the soil surface in the vertical distribution (
Figure 2
). In the LF, the abundance of total soil fauna and dominant groups in soil layer I differed significantly from that in layer II (
p
< 0.05), and the difference between adjacent soil layers III and IV was at the least significant level (
p
< 0.05). The surface aggregation of soil fauna in the MF was more pronounced than that in the LF except for Acarina in
Figure 2
, indicating that the soil surface of the MF provided more ample food resources. The surface aggregation of the common groups in the MF was the most significant level in
Figure 2
(
p
< 0.05), and the abundance advantage of common groups in the MF was mainly in layer I compared with the LF.
Figure 2. Vertical distribution of the soil fauna community. ( a ) The total abundance; ( b ) the abundance of common groups; ( c ) the abundance of Acarina; ( d ) the abundance of Collembola. Different letters indicate significant differences between soil layers of the same forest at the 0.05 probability level.
The functional groups of soil fauna were mainly saprozoite (721/1377; 52.36%) and omnivore functional group (546/1377; 39.65%), with a small proportion from the phytophage (57/1377; 4.14%) and predator functional group (53/1377; 3.85%) in the LF. During the study period, phytophagous soil fauna obviously responded to seasonal dynamics with an inverted U-type distribution (
Figure 3
a). In the vertical distribution, the proportion of omnivorous soil fauna showed minimal change (36.95%–40.97%) (
Figure 3
b). The functional groups of soil fauna were mainly saprozoite (840/1581; 53.13%) and omnivore (539/1581; 34.09%), followed by predator (186/1581; 11.76%) and phytophage (16/1581; 11.76%) in the MF. There was a strong response by saprozoite to seasonal dynamics, accounting for the highest proportion (354/611; 57.94%) in early August (
Figure 3
a). Predator’s temporal and vertical distribution ratios were relatively constant, and community stability was high (
Figure 3
b).
Figure 3. Temporal and vertical distribution of functional groups in the two forest types. ( a ) Temporal distribution; ( b ) vertical distribution.
The mixed forest modulated different functional groups to different degrees ( Table 4 ). In terms of abundance and proportion of each functional group, the MF had the strongest modulation effects on predator, which increased by 250.94% and 205.78%, respectively. However, the functional groups with the weakest effects were different, namely omnivore (1.18%) and saprozoite (1.73%). Regarding the abundance of functional groups, phytophage and omnivore showed a decreasing trend in the MF, whereas only phytophage showed a decreasing trend in proportion.
Table 4. Effects of mixed forest on the abundance and composition of functional groups.
The diversity of the soil fauna in the MF was higher than that in the LF, with both showing the same dynamic trend over time (
Figure 4
). The changing curves of the Shannon–Wiener index (
H
) were both inverted U-type in the two sampled forests; that is, they reached their highest values in early August. The variation trend of the Pielou evenness index (
J
) was opposite to that of the Simpson dominance index (
C
) in the two sampled forests, showing the W and M types, respectively. The tendency of the soil fauna diversity differed between the LF and the MF (
Figure 4
). The Shannon–Wiener index (
H
) was the highest in layer II (
H
; 1.69) in the LF, whereas highest (
H
; 1.80) in layer I in the MF.
Figure 4. Temporal and vertical distribution of diversity indices of the soil fauna. ( a ) The Shannon–Wiener index ( H ); ( b ) the Pielou evenness index ( J ); ( c ) the Simpson dominance index ( C ).
3.1.2. Correlation Analysis between the Soil Fauna and Soil Properties
The gradient relationship between the soil fauna and soil properties can be established by sorting [
29
]. The soil fauna and soil properties were sorted into two-dimension using redundant analysis (
Figure 5
). After the continuous optimization of Interactive Forward Selection, the main soil properties were selected as environmental factors to explain the community characteristics of the main fauna groups. The first canonical axis was determined by BD, pH, TN, and SOM; it explained 35.62% of the total variation (
Table 5
;
F
= 3.9,
p
= 0.024 < 0.05; Monte Carlo test with 499 permutations). The second canonical axis comprised TP; it explained 18.76% of the variation (
F
= 2.7,
p
= 0.006 < 0.01; Monte Carlo test with 499 permutations).
Figure 5. Redundancy analysis between main groups of the soil fauna and the selected properties of soil. Red arrows represent soil properties labeled as: soil bulk density (BD), soil pH value (pH), soil organic matter (SOM), total nitrogen (TN), and total phosphorus (TP). Black arrows represent groups of soil fauna labeled as: Acarina ( Aca. ), Araneae ( Ara. ), Collembola ( Col. ), Dermaptera ( Der. ), Diplopoda ( Dip. ), Diptera adult ( Dip. (A) ), Diptera larvae ( Dip. (L) ), Enchytraeidae ( Enc. ), Isoptera ( Iso. ), Psocoptera ( Pso. ), and Thysanoptera ( Thy. ).
Table 5. Eigenvalues and taxa-environment correlation coefficients for the RDA ordination axes.
Isoptera, Thysanoptera, and Araneae were more significantly related to TN and SOM than the other groups. TP and pH had a weak impact on soil fauna. The analysis of simple term effects showed that TN (explained 32.8%,
F
= 4.9,
p
= 0.002) and TP (explained 15.8%,
F
= 2.8,
p
= 0.02) had greater explanation rates and significant correlations with the soil fauna.
3.2. Effects of Soil Fauna on Litter Decomposition
3.2.1. Dynamic Characteristics of Litter Decomposition
The net decomposition rate of litter during the decomposition process was calculated (
Figure 6
). During litter decomposition, the net decomposition rates of litter gradually increased from 0 to 210 d and gradually decreased after 210 d in both forest types. The cumulative decomposition rate of litter with different mesh sizes was MF–1 (54.52%) > MF–2 (40.64%) > LF–1 (32.81%) > LF–2 (27.41%), and the soil fauna activity improved litter decomposition rate. With the same mesh size, the cumulative litter decomposition rate in the MF was significantly higher than that in the LF (
p
< 0.05), indicating that litter quality is an essential factor affecting the litter decomposition rate.
Figure 6. Dynamic changes in the net decomposition rate of litter. MF–1: Mixed Larix principis-rupprechtii and Betula platyphylla forest, 4 mm litterbags; MF–2: Mixed Larix principis-rupprechtii and Betula platyphylla forest, 0.01 mm litterbags; LF–1: Larix principis-rupprechtii forest, 4 mm litterbags; LF–2: Larix principis-rupprechtii forest, 0.01 mm litterbags.
The residual mass rates and decomposition times fit the Olson exponential decay model (
Figure 7
). LF–2 (
R
2
= 0.889) had the best fitting effect, whereas MF–1 (
R
2
= 0.745) had the poorest. The litter decomposition rate in the 4 mm litterbags was faster than in the 0.01 mm litterbags in the same forest type. The decomposition in the 4 mm litterbags in the MF was the fastest, with decomposition times of 0.789 a and 3.408 a for 50% and 95%, respectively. The decomposition in the 0.01 mm litterbags in the LF was the slowest, with a residue rate of 72.591% after 300 a of decomposition, and decomposition times of 1.810 a and 7.822 a for 50% and 95%, respectively.
Figure 7. Olson negative index regression relation between litter residues and time.
3.2.2. Contribution of the Soil Fauna Community to Litter Decomposition
As decomposition progressed, the contribution rate of the soil fauna to litter decomposition showed an increasing trend ( Figure 8 ). The contribution rate of the soil fauna was positively correlated with the decomposition time. The litter decomposition rate was different between the LF and the MF, and the contribution rate of the soil fauna to the MF (30.58%) was much higher than that of the LF (8.54%).
Figure 8. Contributions of soil fauna to litter decomposition.
The Pearson correlation analysis was used to analyze the relationship between the soil faunal ecological indices and the decomposition rate (
Table 6
). There was a significant positive correlation between litter decomposition rates and the total abundance and the abundance of dominant groups (
p
< 0.05). The litter decomposition rates were significantly positively correlated with the Shannon–Wiener index (
H
) in the LF (
p
< 0.05). The litter decomposition rates were significantly positively correlated with the number of groups in the MF (
p
< 0.05). The Simpson dominance index (
C
) was negatively correlated with the litter decomposition rates in both forest types, and significantly correlated with the LF (
p
< 0.05).
Table 6. Correlation coefficients between decomposition rate and abundance, group numbers, ecological indices of soil fauna.
4. Discussion
4.1. Soil Fauna Community Characteristics
The community structure of the soil fauna is closely related to the forest vegetation composition, and microhabitat heterogeneity created by that stand structure has an important effect on the soil fauna community [ 30 , 31 , 32 ]. In this study, the total abundance of soil fauna in the MF was higher than that in the LF, and there were more common groups present, which resulted in a higher food web structure complexity for the soil fauna. The quality and quantity of litter can affect the soil fauna [ 33 , 34 , 35 , 36 ]. Chauvat [ 37 ] highlighted that incorporating beech into pure spruce forests increased the presence of new food sources and significantly increased the soil fauna density. The presence of Larix principis-rupprechtii ensured the accumulation of litterfall. At the same time, the addition of Betula platyphylla enriched the composition of the litterfall, so the composition of soil fauna in the mixed forest was richer and more stable.
Dividing the soil fauna into different functional groups based on the food source, feeding mode, and life history strategy can facilitate the study of the function of the soil fauna groups in the ecosystem [ 38 , 39 ]. The responses of different functional groups to environmental changes result in a different distribution of each functional group among the stands [ 40 , 41 , 42 ]. The proportion of predatory functional groups in the MF was higher than that in the LF, and the range of variation was low, indicating that the predatory soil faunas were at a higher trophic level in the food chain, and the community stability was high. Phytophagous soil fauna had a strong response to seasonal dynamics owing to their feeding habits.
The diversity index of soil fauna can reflect the complexity of community composition and reveal the response characteristics of the soil fauna community to environmental changes [ 43 ]. In this study, the Shannon–Wiener index ( H ) in the MF was higher than in the LF, consistent with the higher soil fauna diversity in other mixed forest areas [ 44 , 45 , 46 ]. When coniferous forests have a single tree species, the litter does not decompose easily, and the soil is relatively barren. Therefore, the living environment formed is not suitable for the survival of many soil faunas [ 47 ]. The mixed forest is species-rich, and has diverse microhabitats, and abundant litter species, which effectively maintain the soil surface water [ 48 , 49 , 50 ]. Broad-leaved litter can rapidly decompose into the soil and form organic matter, increasing soil fertility and improving the soil physical structure [ 51 , 52 ]. In this study, SOM, TN, and TP levels in the MF were higher than those in the LF, which was beneficial to the survival of various soil fauna groups and improved diversity.
Soil characteristics are critical environmental factors affecting the soil fauna community, and mixed planting indirectly affects the soil physical and chemical properties through changes in the standing vegetation composition. Chang [ 53 ] confirmed that soil organic matter and water content are closely related to the Collembola community. Yang [ 16 ] believed that soil water content, soil organic matter, and total litter nitrogen had a pronounced effect on the distribution of the main groups in the northern Loess Plateau. RDA ordination analysis showed that BD, SOM, TN, and pH significantly affected the soil fauna in this study, which was similar to the results by Tang [ 54 ]. Most soil fauna showed a significant negative response to soil pH, which is a limiting factor for the diversity of soil fauna [ 55 ]. Acarina, Collembola, Araneae, Isoptera, and Thylaptera were negatively correlated with BD and pH in this study. Nitrogen is the primary nutrient for protein construction and the development of soil fauna, which significantly affects the soil fauna community [ 56 , 57 ]. In this study, the total nitrogen content in layer I of the MF was the highest, which could provide more nitrogen for soil fauna to meet their growth and development requirements. Bartz [ 58 ] found a significant positive correlation between earthworm abundance and soil organic matter content. However, there was no close correlation between earthworm abundance and soil properties in the present study.
4.2. Effects of Soil Fauna on Litter Decomposition
The litter decomposition rate is mainly controlled by hydrothermal conditions [ 59 ], litter quality [ 60 , 61 ], and the soil fauna [ 62 , 63 , 64 ]. In this study, the decomposition rate in summer (210–255 d) was higher than that in other seasons because the good hydrothermal conditions in summer promoted the mineralization of soil, and the activity of soil microorganisms and soil fauna increased, which enabled the decomposition of lignin and other refractory substances in the litter. This is consistent with the results of previous studies [ 65 , 66 , 67 , 68 , 69 ]. Leaching and physical fragmentation under the effect of precipitation directly promote the decomposition of litter and increase the water content of litter, thereby affecting the decomposition rate [ 70 , 71 , 72 ]. It is also beneficial to the growth and reproduction of soil microorganisms and fauna, enhances their activity, and promotes litter decomposition. Under certain regional climate conditions, litter substrate quality is usually the main influencing factor. In this study, the litter decomposition rate of the MF was higher than that of the LF, indicating that mixed planting significantly promoted litter decomposition. Birch leaves contain different nutrients from larch leaves. The two species’ interactions of the litter increased the decomposition rate, while mixed forest litter substrate changes attracted increasing soil fauna colonization, increasing the crushing effect of litter. This is in line with the results of previous studies [ 73 , 74 , 75 ].
In this study, the difference in litter decomposition rates in the two types of mesh size litterbags in the same forest type indicated that soil fauna promoted litter decomposition, and litter decomposition rate was positively correlated with the abundance, group number, and diversity of soil fauna, which is consistent with the results of many previous studies [
62
,
63
]. The dominant groups accounted for 77.45% and 67.56% of the total soil fauna in the LF and the MF, respectively, and were the main groups involved in litter decomposition. Correlation analysis showed that the dominant groups (Acarina and Collembola) had a significant promoting effect on litter decomposition. In addition, correlation analysis showed that the Simpson dominance index (
C
) of the soil fauna was negatively correlated with the litter decomposition rate and reached a significant level in the LF (
p
< 0.05), suggesting that some critical groups in common and rare groups played a decisive role in the litter decomposition. In this study, the diversity of the soil fauna in the MF was higher than that in the LF. The number of groups and the Pielou evenness index (
J
) were more strongly correlated with the litter decomposition rate, whereas the Simpson dominance index (
C
) was more negatively correlated with the litter decomposition rate, indicating that the diversity of soil fauna could significantly promote litter decomposition, whereas the litter decomposition rate was severely restricted when the soil fauna group was less diverse.
5. Conclusions
The abundance and groups of soil faunas in the MF were higher than those in the LF. The dominant groups of the two forest types were the same, namely, Acarina and Collembola, which showed universal adaptability to the different microhabitats. The proportion of common groups in the MF was higher, indicating that the soil faunas were more abundant. There was a strong similarity in the composition of the functional groups between the two forest types. Under the influence of the dominant groups, saprozoite and omnivore were the main components. In the two forest types, the soil fauna had a strong response to seasonal dynamics, and the abundance and groups peaked in August when the hydrothermal conditions were good. Due to air permeability and food resources, soil fauna tended to gather on the soil surface in a vertical distribution. The soil fauna showed more obvious surface clustering characteristics in the MF. The soil fauna diversity in the MF was higher than in the LF. The Shannon–Wiener index (
H
), Pielou evenness index (
J
), and Simpson dominance index (
C
) of soil fauna in the MF were higher than that in the LF during the study period, which indicated that the stability and diversity of soil fauna communities in the MF were stronger. Microhabitat factors have an important effect on soil fauna community composition and diversity, and different soil fauna groups are affected differently by environmental factors. In this study, SOM and TN significantly affected soil fauna, whereas BD and pH were the limiting factors for some soil fauna groups.
The quality and quantity of litter in the MF were improved, and the decomposition rate was higher than that in the LF. The soil fauna community had an important influence on litter decomposition. The litter decomposition rate was positively correlated with the total abundance and the number of groups, and it was negatively correlated with the Simpson dominance index (
C
), indicating that the soil fauna community diversity improved the litter decomposition rate. The litter decomposition rate was significantly correlated with the number of groups only in the MF due to more abundant soil fauna groups.
In conclusion, the mixed
Larix principis-rupprechtii
and
Betula platyphylla
forest can effectively improve the abundance, groups, and soil fauna diversity by regulating vegetation’s composition and structure. Moreover, the litter decomposition is further improved, which is conducive to the nutrient cycling of the forestry ecosystem and greatly benefits vegetation restoration in mountainous areas.
Author Contributions
Conceptualization, H.Z. and T.H.; methodology, H.Z. and G.H.; software, G.H.; writing—original draft preparation, H.Z., G.H. and T.H.; writing—review and editing, T.H. and G.H.; visualization, G.H.; supervision, H.Z. and T.H.; funding acquisition, H.Z.; Data curation, Y.F. and X.W.; project administration, W.T. All authors have read and agreed to the published version of the manuscript.
Funding
This research was supported by the National Science and Technology Major Project for Water Pollution Control and Treatment (2017ZX07101002).
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Location of the study site.
Figure 2. Vertical distribution of the soil fauna community. ( a ) The total abundance; ( b ) the abundance of common groups; ( c ) the abundance of Acarina; ( d ) the abundance of Collembola. Different letters indicate significant differences between soil layers of the same forest at the 0.05 probability level.
Figure 3. Temporal and vertical distribution of functional groups in the two forest types. ( a ) Temporal distribution; ( b ) vertical distribution.
Figure 4. Temporal and vertical distribution of diversity indices of the soil fauna. ( a ) The Shannon–Wiener index ( H ); ( b ) the Pielou evenness index ( J ); ( c ) the Simpson dominance index ( C ).
Figure 5. Redundancy analysis between main groups of the soil fauna and the selected properties of soil. Red arrows represent soil properties labeled as: soil bulk density (BD), soil pH value (pH), soil organic matter (SOM), total nitrogen (TN), and total phosphorus (TP). Black arrows represent groups of soil fauna labeled as: Acarina ( Aca. ), Araneae ( Ara. ), Collembola ( Col. ), Dermaptera ( Der. ), Diplopoda ( Dip. ), Diptera adult ( Dip. (A) ), Diptera larvae ( Dip. (L) ), Enchytraeidae ( Enc. ), Isoptera ( Iso. ), Psocoptera ( Pso. ), and Thysanoptera ( Thy. ).
Figure 6. Dynamic changes in the net decomposition rate of litter. MF–1: Mixed Larix principis-rupprechtii and Betula platyphylla forest, 4 mm litterbags; MF–2: Mixed Larix principis-rupprechtii and Betula platyphylla forest, 0.01 mm litterbags; LF–1: Larix principis-rupprechtii forest, 4 mm litterbags; LF–2: Larix principis-rupprechtii forest, 0.01 mm litterbags.
Figure 7. Olson negative index regression relation between litter residues and time.
Figure 8. Contributions of soil fauna to litter decomposition.
Table 1. The basic situation of the sample plots in the study site.
Stands Slope Aspect Longitude and Latitude Altitude m·a·s·l a Stand Density (Trees/ha) Average Height of Trees (m) Diameter at Breast Height (cm) Major Understory Vegetation Larix principis-rupprechtii forest (LF) Southwest 115°26′58′′ E 40°58′53′′ N 1985 1138 7.6 10.29 Potentilla fruticose , Rubus swinhoei Hance, Malus baccata , etc. Mixed Larix principis-rupprechtii and Betula platyphylla forest (MF) Northeast 115°27′51′′ E 40°58′37′′ N 1904 2201 9.8 10.57 Rubus swinhoei Hance , Crataegus pinnatifida Bunge, Rosa bella , Ribes rubrum, Malus baccata , etc.
a : Meters above sea level.
Table 2. Quality parameters of soil in the sampled forests.
BD (g·cm −3 ) pH SOM (g·kg −1 ) TN (g·kg −1 ) TP (g·kg −1 ) Larix principis-rupprechtii forest 0–10 cm upslope 0.96 ± 0.00 6.61 ± 0.02 57.28 ± 0.26 2.94 ± 0.06 0.54 ± 0.01 mesoslope 1.33 ± 0.00 6.98 ± 0.03 48.72 ± 0.94 2.66 ± 0.04 0.64 ± 0.01 downslope 0.99 ± 0.00 6.90 ± 0.04 55.05 ± 0.39 2.96 ± 0.05 0.76 ± 0.03 10–20 cm upslope 1.35 ± 0.00 6.80 ± 0.01 43.59 ± 0.74 2.36 ± 0.05 0.59 ± 0.00 mesoslope 0.96 ± 0.00 7.10 ± 0.01 46.84 ± 0.54 2.41 ± 0.04 0.67 ± 0.02 downslope 1.06 ± 0.00 7.09 ± 0.03 51.40 ± 0.41 2.83 ± 0.03 0.81 ± 0.01 Mixed Larix principis-rupprechtii and Betula platyphylla forest 0–10 cm upslope 0.83 ± 0.00 6.19 ± 0.05 94.87 ± 2.28 4.80 ± 0.04 0.97 ± 0.01 mesoslope 0.80 ± 0.00 6.29 ± 0.02 74.11 ± 0.88 3.88 ± 0.05 0.94 ± 0.01 downslope 0.73 ± 0.00 6.72 ± 0.01 88.87 ± 1.92 4.39 ± 0.04 0.83 ± 0.02 10–20 cm upslope 0.82 ± 0.00 6.82 ± 0.02 75.85 ± 1.39 3.85 ± 0.04 0.95 ± 0.01 mesoslope 0.88 ± 0.00 6.38 ± 0.04 68.32 ± 1.73 3.49 ± 0.06 0.94 ± 0.01 downslope 0.90 ± 0.00 6.71 ± 0.02 60.50 ± 1.69 2.91 ± 0.06 0.78 ± 0.02
Table 3. Composition of the soil fauna community.
Groups Larix principis-rupprechtii Forest Mixed Larix principis-rupprechtii and Betula platyphylla Forest May. Jun. Aug. Sep. Nov. Total May. Jun. Aug. Sep. Nov. Total Individuals Individuals Percentage Abundance Individuals Individuals Percentage Abundance Acarina 50 c 104 b 145 a 134 a 110 b 543 39.43 +++ 30 d 54 c 173 a 194 a 85 b 536 33.90 +++ Collembola 34 c 101 ab 157 a 117 ab 94 b 503 36.53 +++ 28 d 54 c 218 a 212 a 65 b 577 36.50 +++ Hemiptera 0 0 4 0 0 4 0.29 + 0 0 0 0 0 0 0.00 – Isoptera 4 7 16 9 3 39 2.83 ++ 5 12 74 20 6 117 7.40 ++ Orthoptera 1 4 0 0 0 5 0.36 + 0 0 5 0 0 5 0.32 + Thysanoptera 0 3 8 1 0 12 0.87 + 0 3 51 11 11 76 4.81 ++ Dermaptera 3 0 0 0 0 3 0.22 + 0 0 0 0 0 0 0.00 – Coleoptera (adult) 5 3 3 2 0 13 0.94 + 0 0 0 0 0 0 0.00 – Coleoptera (larvae) 0 2 3 3 0 8 0.58 + 0 0 0 2 2 4 0.25 + Diptera (adult) 1 4 10 2 0 17 1.23 ++ 0 0 13 0 4 17 1.08 ++ Diptera (larvae) 47 23 21 10 8 109 7.92 ++ 4 6 42 20 10 82 5.19 ++ Lepidoptera (larvae) 0 0 0 0 0 0 0.00 – 0 1 1 1 0 3 0.19 + Formicidae 0 0 0 0 0 0 0.00 – 2 0 0 1 0 3 0.19 + Gastropoda 0 0 0 0 0 0 0.00 – 0 0 3 0 0 3 0.19 + Diplopoda 0 1 0 4 0 5 0.36 + 0 2 1 0 0 3 0.19 + Protura 0 0 0 5 0 5 0.36 + 0 0 0 0 1 1 0.06 + Isopoda 0 9 5 3 0 17 1.23 ++ 0 6 0 0 0 6 0.38 + Psocoptera 0 0 30 12 0 42 3.05 ++ 0 1 3 3 1 8 0.51 + Enchytraeidae 1 0 19 2 3 25 1.82 ++ 1 7 6 18 2 34 2.15 ++ Araneae 2 1 0 1 19 23 1.67 ++ 5 4 16 47 2 74 4.68 ++ Geophilomorpha 1 1 1 0 0 3 0.22 + 6 13 5 2 3 29 1.83 ++ Symphyla 0 0 1 0 0 1 0.07 + 2 0 0 1 0 3 0.19 + Number of groups 10 13 14 13 6 19 9 11 13 13 12 19 Sum 149 d 263 bc 423 a 305 b 237 c 1377 86 e 163 d 611 a 532 b 192 c 1581
Degree of dominance; +++: Dominant groups; ++: Common groups; +: Rare groups; –: Uncollected. Abundance with the same letters ( a, b, c , or d ) at the row of the same forest type is not significantly different (ANOVA with LSD test, p < 0.05). Table 3 shows the mean number of individuals extracted from the samples, multiplied by 6.94 to calculate individuals per square meter in 0–20 cm soil layer.
Table 4. Effects of mixed forest on the abundance and composition of functional groups.
Saprozoite Phytophage Predator Omnivore Abundance (inds.) LF 721 ± 70 57 ± 4 53 ± 0 546 ± 33 MF 840 ± 30 16 ± 3 186 ± 13 539 ± 14 Modulated ratio (%) 16.86 ± 7.34 −71.67 ± 7.07 250.94 ± 24.01 −1.18 ± 3.30 Proportion (%) LF 52.31 ± 3.52 4.14 ± 0.18 3.85 ± 0.12 39.71 ± 3.59 MF 53.12 ± 1.02 1.01 ± 0.20 11.76 ± 0.62 34.13 ± 1.44 Modulated ratio (%) 1.73 ± 4.90 −75.37 ± 5.80 205.78 ± 25.41 13.92 ± 4.14
Modulated ratio (%): the increasing ratio in abundance (inds.) or proportion (%) of a certain functional group in the MF compared with the LF.
Table 5. Eigenvalues and taxa-environment correlation coefficients for the RDA ordination axes.
Parameters Axis 1 Axis 2 Axis 3 Axis 4 Eigenvalues 0.3562 0.1876 0.0402 0.0195 Explained variation (%) (cumulative) 35.62 54.38 58.4 60.35 Pseudo–canonical correlation 0.916 0.9323 0.6247 0.4654 Explained fitted variation (%) (cumulative) 59.02 90.1 96.76 100 Monte Carlo test after 499 permutations Text on the first axis pseudo– F = 3.9, p = 0.024 Text on all axes pseudo– F = 2.7, p = 0.006
Table 6. Correlation coefficients between decomposition rate and abundance, group numbers, ecological indices of soil fauna.
LF MF Total abundance 0.995 ** 0.894 ** The number of groups 0.671 0.877 ** Shannon–Wiener index ( H ) 0.893 ** 0.654 Pielou evenness index ( J ) 0.285 0.061 Simpson dominance index ( C ) –0.880 ** –0.586 Collembola 0.991 ** 0.866 ** Acarina 0.846 * 0.746 *
**: p = 0. 01; *: p = 0. 05.
Zhang, Huayong, Guixuan Han, Tousheng Huang, Yu Feng, Wang Tian, and Xiaochang Wu. 2022. "Mixed Forest of Larix principis-rupprechtiiand Betula platyphyllaModulating Soil Fauna Diversity and Improving Faunal Effect on Litter Decomposition" Forests13, no. 5: 703.
https://doi.org/10.3390/f13050703
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Zhang, H.; Han, G.; Huang, T.; Feng, Y.; Tian, W.; Wu, X. Mixed Forest of Larix principis-rupprechtiiand Betula platyphyllaModulating Soil Fauna Diversity and Improving Faunal Effect on Litter Decomposition. Forests 2022, 13, 703.
https://doi.org/10.3390/f13050703
AMA Style
Zhang H, Han G, Huang T, Feng Y, Tian W, Wu X. Mixed Forest of Larix principis-rupprechtiiand Betula platyphyllaModulating Soil Fauna Diversity and Improving Faunal Effect on Litter Decomposition. Forests. 2022; 13(5):703.
https://doi.org/10.3390/f13050703
Chicago/Turabian Style
Zhang, Huayong, Guixuan Han, Tousheng Huang, Yu Feng, Wang Tian, and Xiaochang Wu. 2022. "Mixed Forest of Larix principis-rupprechtiiand Betula platyphyllaModulating Soil Fauna Diversity and Improving Faunal Effect on Litter Decomposition" Forests13, no. 5: 703.
https://doi.org/10.3390/f13050703
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Cancers | Free Full-Text | Citrus Consumption and the Risk of Non-Melanoma Skin Cancer in the Women’s Health Initiative
Evidence from animal studies suggests that furocoumarins, compounds present in citrus products, can increase the risk of non-melanoma skin cancer (NMSC) when combined with ultraviolet radiation. The objective of this study was to determine the relationship between citrus intake and NMSC risk among postmenopausal women from the Women’s Health Initiative (WHI) Observational Study, who were aged 50–79 years at enrollment (1993–1998). The consumption of citrus fruit, citrus juice, and non-citrus fruit and juice were measured at the baseline of the study using a food frequency questionnaire (FFQ). NMSC cases (basal or squamous cell carcinomas) were self-reported during annual follow-up surveys. The outcome data used for this analysis were collected through March 2020. The relative risk (RR) for incident NMSC by citrus consumption was calculated. Among 49,007 non-Hispanic white participants, there were 8642 cases of incident NMSC. Using less than one serving of citrus juice per week as reference, the RRs and 95% confidence intervals (CI) for incident NMSC by citrus juice intake were 1.03 (0.95, 1.10) for one serving/week, 1.06 (1.00, 1.12) for two to four servings/week, 0.98 (0.90, 1.07) for five to six servings/week, and 1.08 (1.02, 1.13) for one or more serving/day (p-trend = 0.007). Subgroup analyses did not reveal meaningful associations by sun exposure variables. In conclusion, there were indications of a slightly higher risk of incident NMSC among citrus juice consumers; however, further longitudinal and mechanistic studies are needed to confirm the key risk factors.
Citrus Consumption and the Risk of Non-Melanoma Skin Cancer in the Women’s Health Initiative
Melissa M. Melough 1 ,
Mary B. Roberts 2 ,
Charles B. Eaton 3 ,
Aladdin H. Shadyab 4 ,
Abrar A. Qureshi 5 ,
Ock K. Chun 1,* and
Eunyoung Cho 5,*
1
Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA
2
Brown Center for Primary Care and Prevention, Care New England Medical Group/Primary Care & Specialty Services, Pawtucket, RI 20860, USA
3
Department of Family Medicine, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA
4
Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, CA 92093, USA
5
Department of Dermatology, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA
*
Authors to whom correspondence should be addressed.
Cancers 2021 , 13 (9), 2173; https://doi.org/10.3390/cancers13092173
Received: 16 March 2021 / Revised: 15 April 2021 / Accepted: 27 April 2021 / Published: 30 April 2021
(This article belongs to the Special Issue Medicinal Plants and Their Active Ingredients in Cancer )
Simple Summary
Citrus products are rich in furocoumarins, which can increase the risk of incident non-melanoma skin cancer (NMSC) when combined with ultraviolet radiation. However, few observational studies have evaluated the link between citrus intake and NMSC incidence. The aim of this study was to determine whether citrus intake was related to the NMSC incidence in participants of the Women’s Health Initiative Observational Study. The results of this study indicated that high citrus juice consumption was associated with a higher risk of incident NMSC compared to low consumption. These findings add further evidence of the potentially carcinogenic nature of certain citrus products and highlight the need to continue investigations in identifying risk factors and mechanisms.
Abstract
Evidence from animal studies suggests that furocoumarins, compounds present in citrus products, can increase the risk of non-melanoma skin cancer (NMSC) when combined with ultraviolet radiation. The objective of this study was to determine the relationship between citrus intake and NMSC risk among postmenopausal women from the Women’s Health Initiative (WHI) Observational Study, who were aged 50–79 years at enrollment (1993–1998). The consumption of citrus fruit, citrus juice, and non-citrus fruit and juice were measured at the baseline of the study using a food frequency questionnaire (FFQ). NMSC cases (basal or squamous cell carcinomas) were self-reported during annual follow-up surveys. The outcome data used for this analysis were collected through March 2020. The relative risk (RR) for incident NMSC by citrus consumption was calculated. Among 49,007 non-Hispanic white participants, there were 8642 cases of incident NMSC. Using less than one serving of citrus juice per week as reference, the RRs and 95% confidence intervals (CI) for incident NMSC by citrus juice intake were 1.03 (0.95, 1.10) for one serving/week, 1.06 (1.00, 1.12) for two to four servings/week, 0.98 (0.90, 1.07) for five to six servings/week, and 1.08 (1.02, 1.13) for one or more serving/day (
p
-trend = 0.007). Subgroup analyses did not reveal meaningful associations by sun exposure variables. In conclusion, there were indications of a slightly higher risk of incident NMSC among citrus juice consumers; however, further longitudinal and mechanistic studies are needed to confirm the key risk factors.
Keywords:
citrus
;
furocoumarin
;
non-melanoma skin cancer
;
cohort
;
women’s health initiative
1. Introduction
Non-melanoma skin cancer (NMSC), consisting primarily of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common cancer with increasing incidence rates [ 1 , 2 ] and predominately affects those with fair-skin [ 3 ]. While the potential for mortality is lower than that of melanoma (the mortality rates are 0.05% and 0.7% for BCC and SCC, respectively, totaling up to 2000 deaths in the US annually [ 4 ]), NMSC results in significant morbidity in the form of lesions [ 1 ], loss of function, disfigurement, and significant health care expenditures [ 5 ]. The history of NMSC increases the risk of other cancers, such as prostate, lung, breast, and colon [ 6 , 7 ], highlighting the importance of preventing NMSC.
There are several known risk factors for NMSC, including having a skin type that easily burns and/or tans poorly, fair complexion, increasing age, being male, and lifetime exposure to ultraviolet (UV) light [ 8 ]. UV light exposure has long been recognized as a major environmental factor for skin cancer pathology [ 9 ]. In the presence of UV radiation, naturally occurring photoactive compounds, called furocoumarins, have also been known to increase skin cancer risk [ 10 , 11 , 12 , 13 , 14 ]. Psoralen and ultraviolet A (PUVA) therapy, which uses orally or topically applied psoralen—a furocoumarin congener—in conjunction with UVA radiation to treat skin diseases, such as psoriasis, is well-known to increase the risk of skin cancer if used long term [ 13 , 15 , 16 , 17 ].
This raises a concern that dietary furocoumarins may potentially increase the risk of developing NMSC. Furocoumarins are largely found in citrus fruit, such as grapefruit, oranges, lemons, and limes [ 18 , 19 , 20 ]. Data from two prospective cohort studies, the Health Professionals Follow-Up Study/Nurses’ Health Study (HPFS/NHS) [ 21 ] and European Prospective Investigation into Cancer and Nutrition (EPIC) study [ 22 ] have provided epidemiological evidence indicating that citrus consumption is associated with an increased risk of incident NMSC. The participants enrolled in the HPFS/NHS were physicians and nurses, and the EPIC study participants were recruited solely in Europe, thus, highlighting the limited generalizability and representation from the US. Therefore, the objective of this study was to evaluate the association between citrus consumption and NMSC risk in a large US cohort.
2. Results
2.1. Baseline Characteristics
All measured characteristics differed between those in different categories of citrus intake. Women with higher citrus intake were older, had a higher educational level, lower BMI, and were more physically active than those consuming less citrus ( Table 1 ). They also had greater energy and alcohol intake but consumed less coffee. With regard to sun exposure, participants who consumed more citrus tended to spend more time outdoors in the summer as a child and currently, more frequently indicated having a skin type that tans but does not burn and used a high SPF sunscreen.
Table 1. Baseline characteristics of participants from the Women’s Health Initiative ( n = 49,007) according to the frequency of total citrus consumption.
2.2. Citrus Consumption and Risk of Incident NMSC
In total, there were 8642 cases of incident NMSC reported during an average follow-up period (mean ± standard deviation) of 14.4 ± 6.5 years. The relative risks (RR) for incident NMSC by categories of citrus intake are presented in
Table 2
. The highest frequency of citrus juice consumption (≥1 serving/day) was associated with a higher risk of incident NMSC in the age-adjusted model (RR (95% confidence interval) (CI): 1.12 (1.07, 1.18)) using the lowest category as reference (<1 serving/week). Adjusting for confounders, including age, BMI, education, physical activity, alcohol intake, regional solar radiation, skin reaction to sun, time spent outdoors, and sunscreen use, slightly attenuated the risk; however, the result was still significant (RR and 95% CI: 1.08 (1.02, 1.13)). Non-citrus fruit and juice intake was associated with a lower risk (highest vs. lowest category, RR and 95% CI: 0.96 (0.89, 1.03)) of NMSC in the fully-adjusted model but was not statistically significant (
p
-trend = 0.116). Neither the total citrus nor citrus fruit intake was associated with the incident NMSC risk.
Table 2. The relative risk for incident non-melanoma skin cancer according to the frequency of citrus consumption among Women’s Health Initiative participants ( n = 49,007).
To investigate the possibility of effect modification, stratified analyses were conducted with the variables that had significant interaction with citrus juice consumption and NMSC risk: regional solar radiation, skin reaction to sun, time outdoors in summer currently, and sunscreen use (
Table 3
). With the exception of regional solar radiation, all potential effect modifiers revealed a slightly elevated RR (1.07–1.12) for NMSC in the highest vs. lowest categories in the respective subgroups, and there was little difference in the magnitude of association. In other words, there was no difference in the RR estimates between subgroups of the effect modifiers except for regional solar radiation. For regional solar radiation, there was a higher risk of NMSC among the highest vs. lowest category of citrus juice consumption (adjusted RR (95% CI): 1.12 (1.04, 1.19)) only among those with low regional solar radiation exposure (300–350 Langleys). There was no significant association between citrus juice consumption and NMSC risk among those with high regional solar radiation exposure (375–500 Langleys).
Table 3. The relative risk for incident non-melanoma skin cancer according to frequency of citrus juice consumption among Women’s Health Initiative participants ( n = 49,007) by subgroups of potential effect modifiers.
3. Discussion
In this prospective cohort study, data from 49,007 postmenopausal women were used to evaluate the relation between citrus consumption and the incident NMSC risk. Citrus juice consumption was moderately associated with the NMSC risk, but non-citrus fruit and juice, citrus fruit, and total citrus consumption were not associated with NMSC risk in models adjusting for sociodemographic variables, BMI, physical activity, alcohol consumption, and sun-related variables. The stratified analyses did not reveal meaningful interactions among the subgroups of sun-related variables and NMSC.
The association between citrus intake and NMSC risk has been evaluated in few cohorts. In the EPIC study, among >250,000 participants across ten European countries, citrus juice intake was also found to be positively associated with both BCC and SCC [ 22 ]. Citrus fruit was also a risk factor for incident SCC, but not BCC, in the EPIC study, while, in our study, the total citrus fruit consumption was not associated with the risk of NMSC. In the HPFS/NHS, orange juice, but not grapefruit juice, was positively associated with the risk of incident BCC and SCC [ 21 ].
In both the current study and the HPFS/NHS, there was a lower risk of NMSC among participants in the highest vs. lowest categories of non-citrus fruit and juice intake. Thus, there was a pattern of opposing trends in the NMSC risk between citrus and non-citrus products, with particular concern for citrus juice. Furocoumarins are highly abundant in citrus fruit [ 18 , 19 , 20 ], including grapefruit juice and orange juice, which may contribute to the NMSC pathology [ 23 ]. Participants with a higher baseline citrus intake were then likely to have had a higher furocoumarin intake, in addition to being older and having spent more time outdoors, which may increase the NMSC risk. Observational studies investigating the risk of developing other forms of skin cancer, specifically malignant melanoma, similarly described a possible connection between citrus intake and skin cancer, although the results are equivocal [ 24 , 25 , 26 ].
In the subgroup analysis of NMSC risk factors, there was a slightly elevated risk of NMSC among subgroups for each of the four sun-related potential effect modifiers, with the exception of no significant risk among those with high exposure to regional solar radiation. These results indicate that the risk of NMSC by citrus juice consumption was not mediated by proxies of exposure to UV radiation or reaction to the sun. Others have reported an increased risk of incident melanoma or NMSC among high citrus juice consumers who spent a large amount of time outdoors in the summer [
25
] and had a skin type prone to burning quickly [
27
], which is consistent with the current hypothesis that UV radiation is a mediator between citrus consumption and NMSC risk.
The finding that citrus juice consumption was not related to the NMSC risk among those with high regional solar radiation exposure was somewhat unexpected given our initial hypothesis that UV radiation concomitant with citrus consumption is an important mediator for NMSC risk. This may suggest that citrus juice increases the NMSC risk through non-UV-related means. However, it may simply be a spurious result arising from the lower statistical power obtained from subgroup analyses, arising from the lower number of cases within this subgroup.
The biological mechanism underlying the association between citrus juice intake and NMSC risk is likely related to the photoactivation of furocoumarins and the resulting damage to DNA. Furocoumarins are carcinogenic compounds [ 10 , 28 ] and are known to induce skin tumors in animals when combined with UV radiation [ 11 , 14 , 28 ]. First, furocoumarins bind to the pyrimidine base of DNA via weak bonding (hydrogen bonding and Van der Waal’s attractions) [ 29 ]. Second, irradiation with UVA light causes a cycloaddition photoreaction with the furocoumarin and the pyrimidine base, forming a monoadduct.
Subsequently, the monoadduct can absorb additional UV photons and cause the furocoumarin to bind to the thymine on the complementary DNA strand, forming a diadduct or crosslink [ 30 ]. These mono- and diadducts are capable of disrupting DNA transcription and conferring carcinogenicity [ 31 , 32 , 33 , 34 ]. Apart from furocoumarins’ interactions with DNA, it is possible that furocoumarins can confer carcinogenic effects from other mechanisms, such as through singlet oxygen production, lipid peroxide production, and forming adducts with protein, such as with phospholipids [ 15 ].
Interestingly, citrus fruit was not found to be associated with the NMSC risk in this study. A plausible explanation could be due to the fact that whole fruit tends to have different furocoumarin profiles compared with the juices [ 18 , 35 , 36 ]. There are furocoumarins that are uniquely abundant in the peels of citrus fruit, which are not typically consumed; however, they can migrate into the juice during the juicing process, giving juice a different furocoumarin profile [ 35 ]. Some of these furocoumarins have different carcinogenic potentials, therefore, possibly explaining the differences in cytotoxicity with respect to NMSC pathophysiology [ 37 , 38 ]. However, as the indexing of the carcinogenicity of the numerous furocoumarin compounds is still in its nascent stages, future investigations are needed for confirmation.
This study had several notable strengths. First, this analysis using data from the WHI Observational Study included a large sample size and long period of follow-up. Second, the cohort was well-characterized and contained detailed data on a large number of confounders, including some that are not typically measured, such as sun-related variables.
However, there were several limitations. First, the results from this study may not be generalizable to men or those who are not non-Hispanic white. Second, misclassification of skin cancer may have occurred due to the lack of adjudication for NMSC cases. Additionally, over-reporting of NMSC is possible when pre-malignant or non-cancer lesions are removed, and due to the likelihood that those with higher education (and higher citrus intake in this population) have greater access to dermatologic care. However, self-reported skin cancer data has been previously validated in other populations with high validity [ 39 , 40 ].
Third, there is a possibility of misclassification of exposure and covariate data. For example, while the FFQ we used was validated [ 41 ], we had dietary intake at baseline only and were not able to incorporate any changes during follow up. Similarly, the covariate information was assessed at baseline only. However, these differences would likely be non-differential and would potentially bias results towards the null. Fourth, due to the questionnaire structure, differences by NMSC type (BCC or SCC) could not be assessed.
Fifth, the FFQ grouped oranges, grapefruits, and tangerines together in one question, and therefore analyses by type of citrus fruit could not be performed. Grapefruit contains a large amount of several furocoumarin compounds, such as bergaptol, 6′7′-dihydroxybergamottin, epoxybergamottin, and bergamottin, while oranges contain a relatively small amount of bergamottin, highlighting the differences in the total furocoumarin content. The amount of total furocoumarin compounds present in grapefruit is five orders of magnitude greater than that of oranges [
18
]. Therefore, there may be substantial differences in the NMSC risk between citrus fruit type if this association is driven by furocoumarin content.
Finally, while our analyses were limited to non-Hispanic whites only, we lacked information on exact color of the skin and eye color to adjust for skin phototype in the analyses.
4. Materials and Methods
4.1. Study Population
The Women’s Health Initiative (WHI) is a large clinical investigation of strategies for the treatment and prevention of chronic diseases in postmenopausal women, consisting of separate clinical trial and observational study components. It enrolled participants who were aged 50–79 years at baseline from 40 clinical centers in the United States from 1993 to 1998. The division into the clinical trial and the observational study concluded in 2005, and follow-up from the observational study is ongoing. Complete details on the study design are available elsewhere [ 42 , 43 , 44 ].
For the current study, we only included participants from the Observational Study (
n
= 93,676) because those in the clinical trial lacked information on sun exposure. The data from participants available through March 2020 were used. Exclusion criteria consisted of those with a history of any cancer including NMSC (
n
= 32,311), missing food frequency questionnaire (FFQ) data (
n
= 4897), or missing sun exposure data (
n
= 10,847). Additionally, due to the relatively lower incidence of NMSC in non-white people [
45
], those who were not non-Hispanic white were excluded from this study (
n
= 28,267). The final analytic cohort consisted of 49,007 participants from the WHI Observational Study.
4.2. Citrus Consumption and Other Dietary Variables
At baseline, the participants were asked to report the frequency at which they consumed a wide variety of food and beverages over the past 3 months via an FFQ. Response options ranged from “never” to “2+ servings per day.” Total citrus consumption was considered as the sum of citrus fruit and citrus fruit juice intakes, each determined by a single FFQ item. Citrus fruit was determined by the consumption of “oranges, grapefruits, and tangerines” (one orange or half a grapefruit) while citrus fruit juice was determined by the consumption of “orange juice and grapefruit juice” (6-ounce glass).
The total non-citrus fruit and juice consumption was calculated as the sum of 12 items that contained at least partial amounts of fruit/juice: apples/pears; bananas; peaches/nectarines/plums; cantaloupes/oranges; melons/muskmelons/mangoes/papayas; watermelons/red melons; other melons; apricots; other dried fruits; strawberries/kiwis; other fruit, such as fruit cocktails/berries/grapes/applesauce/pineapples; Tang
®
/Kool-Aid
®
/Hi-C
®
/other fruit drinks; and other fruit juices, such as apple or grape. The intakes of the total energy, alcohol, and coffee were also derived from the FFQ. Nutrient estimates from the FFQ were similar to those measured from 4-day dietary records and 24-h dietary recalls in a subset of this population [
41
].
4.3. NMSC Case Ascertainment
The primary outcome of interest was the occurrence of incident NMSC during the follow-up period. The data on NMSC incidence was self-reported by participants and not adjudicated by physicians.
4.4. Covariates
Participants were asked to report behavioral and lifestyle information, including physical activity, education, smoking, and postmenopausal hormone use via baseline questionnaires. Data on other potential risk factors for skin cancer, including regional solar radiation (in Langleys of the participant’s clinical center), the average daily time spent outdoors in the summer as a child, the average daily time spent outdoors in the summer currently, the SPF of sunscreen used, and the skin’s reaction to the sun were collected. Weight and height were measured by trained clinical staff and were used to calculate the body mass index (BMI).
4.5. Statistical Analysis
Chi-square tests of association and one-way ANOVA were carried out to evaluate differences in the categorical and continuous variables, respectively, between participants in differing categories of total citrus intake.
Since incidence data on NMSC were collected annually (without the exact date of diagnosis), we were unable to conduct a Cox proportional hazards analysis. Instead, the relative risks (95% CI) were calculated for each category of citrus consumption using the lowest consumers as the referent category. The primary analysis examined the total citrus, citrus fruit, citrus juice, and non-citrus fruit, and juice intakes as the exposures of interest. Stratified analyses were conducted with the variables (dichotomized) that had significant interaction with citrus juice consumption and NMSC risk.
The initial model adjusted for age while model 1 (minimally-adjusted) additionally adjusted for BMI, education, physical activity, alcohol intake, regional solar radiation, skin reaction to sun, average daily time spent outdoors currently, and sunscreen SPF use. Model 2 (fully-adjusted) additionally included other dietary and behavioral characteristics, including total calorie intake, coffee consumption, smoking, hormone therapy status, and average daily time spent outdoors in the summer as a child. Statistical analyses were conducted using SAS software version 9.4 (SAS Institute, Cary, NC, USA). All statistical tests were two-tailed, and
p
-values < 0.05 were determined to be statistically significant.
5. Conclusions
In conclusion, high citrus juice consumption was moderately associated with a higher risk of NMSC in a prospective cohort of postmenopausal non-Hispanic white women. However, additional studies are needed to determine whether various NMSC risk factors modify the risk of NMSC among citrus juice consumers. Further longitudinal studies and mechanistic studies using relevant animal models are needed to elucidate the mechanisms underlying the association, particularly to identify the specific furocoumarins, foods, or beverages that may increase skin cancer risks.
Author Contributions
Informed consent was obtained from all subjects involved in the study.
Data Availability Statement
Conflicts of Interest
The authors declare no conflict of interest.
References
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Table 1. Baseline characteristics of participants from the Women’s Health Initiative ( n = 49,007) according to the frequency of total citrus consumption.
Total Citrus Serving Category <2/wk 2–4/wk 5–6/wk 1–1.4/d ≥1.5/d Total N (%) 13,991 (28.6) 10,870 (22.2) 5002 (10.2) 11,841 (24.2) 7303 (14.9) Median intake/day 0.09 0.50 0.78 1.08 1.72 Age, years (mean, SD) 61.9 (7.1) 63.0 (7.1) 63.1 (7.2) 63.9 (7.1) 63.7 (7.3) 63.0 (7.2) Regional solar radiation Langleys (g-cal per cm 2 ) (n, %) 300–325 4150 (29.7) 3650 (33.6) 1722 (34.4) 4388 (37.1) 2599 (35.6) 16,509 (33.7) 350 2792 (20.0) 2234 (20.6) 1060 (21.2) 2683 (22.7) 1779 (24.4) 10,548 (21.5) 375–380 1539 (11.0) 1248 (11.5) 530 (10.6) 1281 (10.8) 769 (10.5) 5367 (11.0) 400–430 2632 (18.8) 1733 (15.9) 782 (15.6) 1552 (13.1) 942 (12.9) 7641 (15.6) 475–500 2878 (20.6) 2005 (18.5) 908 (18.2) 1937 (16.4) 1214 (16.6) 8942 (18.3) Average daily time outdoors in summer as a child (n, %) <30 min 338 (2.4) 239 (2.2) 104 (2.1) 245 (2.1) 159 (2.2) 1085 (2.2) 30 min to 2 h 3648 (26.1) 2975 (27.4) 1252 (25.0) 3139 (26.5) 1755 (24.0) 12,769 (26.1) 2+ h 10,005 (71.5) 7656 (70.4) 3646 (72.9) 8457 (71.4) 5389 (73.8) 35,153 (71.7) Average daily time outdoors in summer currently (n, %) <30 min 4646 (33.2) 3209 (29.5) 1337 (26.7) 3366 (28.4) 2044 (28.0) 14,602 (29.8) 30 min to 2 h 6802 (48.6) 5556 (51.1) 2647 (52.9) 6160 (52.0) 3583 (49.1) 24,748 (50.5) 2+ h 2543 (18.2) 2105 (19.4) 1018 (20.4) 2315 (19.6) 1676 (23.0) 9657 (19.7) Sunscreen SPF (n, %) None 7443 (53.2) 5146 (47.3) 2338 (46.7) 5532 (46.7) 3349 (45.9) 23,808 (48.6) Something but don’t know 210 (1.5) 154 (1.4) 70 (1.4) 169 (1.4) 102 (1.4) 705 (1.4) 2–14 658 (4.7) 607 (5.6) 281 (5.6) 607 (5.1) 367 (5.0) 2520 (5.1) 15–24 3621 (25.9) 3157 (29.0) 1509 (30.2) 3626 (30.6) 2228 (30.5) 14,141 (28.9) 25+ 2059 (14.7) 1806 (16.6) 804 (16.1) 1907 (16.1) 1257 (17.2) 7833 (16.0) Skin reaction to sun (n, %) No change 830 (5.9) 644 (5.9) 298 (6.0) 653 (5.5) 395 (5.4) 2820 (5.8) Tans, does not burn 4224 (30.2) 3381 (31.1) 1577 (31.5) 3652 (30.8) 2338 (32.0) 15,172 (31.0) Burns, then tans 3600 (25.7) 2793 (25.7) 1330 (26.6) 3153 (26.6) 1933 (26.5) 12,809 (26.1) Burns, then tans minimally 3731 (26.7) 2941 (27.1) 1303 (26.1) 3224 (27.2) 1901 (26.0) 13,100 (26.7) Burns, does not tan 1606 (11.5) 1111 (10.2) 494 (9.9) 1159 (9.8) 736 (10.1) 5106 (10.4) Education (n, %) <High school graduate 545 (3.9) 309 (2.8) 113 (2.3) 256 (2.2) 145 (2.0) 1368 (2.8) High school graduate 2675 (19.1) 1795 (16.5) 805 (16.1) 1730 (14.6) 1001 (13.7) 8006 (16.3) Some college 5270 (37.7) 4060 (37.4) 1681 (33.6) 4107 (34.7) 2487 (34.1) 17,605 (35.9) College graduate 5388 (38.5) 4641 (42.7) 2375 (47.5) 5671 (47.9) 3618 (49.5) 21,693 (44.3) BMI, kg/m 2 (mean, SD) 27.4 (6.0) 27.1 (5.9) 27.1 (5.7) 26.7 (5.6) 26.7 (5.9) 27.0 (5.8) Physical Activity (n, %) Inactive (0–1.7) 3119 (22.5) 1774 (16.5) 744 (15.0) 1788 (15.3) 961 (13.3) 8386 (17.3) Low Activity (1.8–8.3) 3835 (27.7) 2857 (26.5) 1269 (25.6) 2892 (24.7) 1695 (23.4) 12,548 (25.9) Mod Activity (8.4–20) 3914 (28.3) 3415 (31.7) 1559 (31.4) 3871 (33.0) 2299 (31.7) 15,058 (31.0) High Activity (>20) 2971 (21.5) 2731 (25.3) 1387 (28.0) 3168 (27.0) 2291 (31.6) 12,548 (25.9) Cigarette Smoking Status (n, %) Never 6383 (46.2) 5468 (50.9) 2523 (51.0) 6093 (52.1) 3845 (53.3) 24,312 (50.2) Past 6346 (45.9) 4716 (43.9) 2206 (44.6) 5144 (44.0) 3070 (42.5) 21,482 (44.4) Current 1088 (7.9) 568 (5.3) 221 (4.5) 452 (3.9) 304 (4.2) 2633 (5.4) Alcohol, g/day (mean, SD) 5.6 (11.6) 6.1 (11.1) 6.6 (12.1) 6.6 (11.2) 6.4 (11.4) 6.2 (11.4) Coffee, cups/day (mean, SD) 2.3 (1.8) 2.2 (1.7) 2.3 (1.7) 2.2 (1.6) 2.1 (1.7) 2.2 (1.7) Hormone Therapy Status (n, %) Never 3503 (25.5) 2875 (26.9) 1317 (26.9) 3296 (28.4) 2121 (29.6) 13,112 (27.3) Past 2653 (19.3) 1984 (18.6) 934 (19.1) 2267 (19.6) 1325 (18.5) 9163 (19.1) Current 7600 (55.3) 5825 (54.5) 2640 (54.0) 6031 (52.0) 3711 (51.9) 25,807 (53.7) Total energy intake, kcal (mean, SD) 1479 (567.9) 1540 (562.2) 1610 (562.3) 1626 (548.2) 1771 (604.5) 1585 (575.1) Citrus Fruit, medium servings (mean, SD) 0.06 (0.08) 0.21 (0.18) 0.38 (0.26) 0.40 (0.37) 0.81 (0.69) 0.32 (0.42) Citrus Juice, medium servings (mean, SD) 0.05 (0.07) 0.28 (0.19) 0.40 (0.27) 0.70 (0.38) 1.16 (0.66) 0.46 (0.51) Non-Citrus Fruit and Juice, medium servings (mean, SD) 1.64 (1.33) 1.81 (1.23) 1.99 (1.29) 2.05 (1.36) 2.60 (1.89) 1.96 (1.44)
Table 2. The relative risk for incident non-melanoma skin cancer according to the frequency of citrus consumption among Women’s Health Initiative participants ( n = 49,007).
Serving Category p -Trend Total Citrus <2/wk 2–4/wk 5–6/wk 1–1.4/d ≥1.5/d No. of cases (%) 2275 (16.3) 1903 (17.5) 873 (17.5) 2257 (19.1) 1334 (18.3) Age-adjusted RR (95% CI) (ref) 1.06 (1.01, 1.13) 1.06 (0.98, 1.14) 1.15 (1.09, 1.22) 1.11 (1.04, 1.18) <0.001 Model 1: Minimally-adjusted RR (95% CI) (ref) 1.02 (0.96, 1.08) 1.00 (0.93, 1.07) 1.08 (1.03, 1.14) 1.03 (0.97, 1.10) 0.065 Model 2: Maximally-adjusted RR (95% CI) (ref) 1.01 (0.96, 1.07) 1.00 (0.93, 1.07) 1.08 (1.02, 1.14) 1.02 (0.96, 1.09) 0.127 Citrus Fruit Never <1/wk 1/wk 2–4/wk ≥5/wk No. of cases (%) 1362 (16.4) 3295 (17.6) 1156 (18.2) 1257 (18.2) 1572 (18.0) Age-adjusted RR (95% CI) (ref) 1.07 (1.01, 1.13) 1.09 (1.02, 1.17) 1.09 (1.02, 1.17) 1.08 (1.01, 1.15) 0.453 Model 1: Minimally-adjusted RR (95% CI) (ref) 1.01 (0.96, 1.07) 1.00 (0.93, 1.08) 1.01 (0.94, 1.08) 0.98 (0.92, 1.05) 0.295 Model 2: Maximally-adjusted RR (95% CI) (ref) 1.01 (0.95, 1.07) 0.99 (0.92, 1.06) 1.00 (0.93, 1.07) 0.97 (0.91, 1.04) 0.337 Citrus Juice <1/wk 1/wk 2–4/wk 5–6/wk ≥1/d No. of cases (%) 3572 (16.7) 768 (17.4) 1531 (18.4) 508 (17.0) 2263 (19.0) Age-adjusted RR (95% CI) (ref) 1.04 (0.97, 1.11) 1.08 (1.02, 1.14) 1.01 (0.93, 1.10) 1.12 (1.07, 1.18) <0.001 Model 1: Minimally-adjusted RR (95% CI) (ref) 1.02 (0.95, 1.09) 1.07 (1.01, 1.13) 0.98 (0.90, 1.07) 1.08 (1.03, 1.14) 0.002 Model 2: Maximally-adjusted RR (95% CI) (ref) 1.03 (0.95, 1.10) 1.06 (1.00, 1.12) 0.98 (0.90, 1.07) 1.08 (1.02, 1.13) 0.007 Non-Citrus Fruit and Juice <0.75/d 0.75–1.2/d 1.3–1.9/d 2.0–2.9/d ≥3/d No. of cases (%) 1321 (16.2) 1738 (17.4) 2126 (18.2) 1926 (18.3) 1531 (17.9) Age-adjusted RR (95% CI) (ref) 1.06 (1.00, 1.14) 1.11 (1.05, 1.19) 1.11 (1.04, 1.19) 1.09 (1.02, 1.16) 0.029 Model 1: Minimally-adjusted RR (95% CI) (ref) 1.02 (0.95, 1.09) 1.04 (0.97, 1.10) 1.02 (0.96, 1.09) 0.99 (0.92, 1.06) 0.440 Model 2: Maximally-adjusted RR (95% CI) (ref) 1.01 (0.95, 1.08) 1.03 (0.96, 1.09) 1.00 (0.93, 1.07) 0.96 (0.89, 1.03) 0.116
Model 1: adjusted for age (continuous), BMI (<25.0, 25.0–29.9, 30.0–34.9, ≥35.0 kg/m 2 ), education (less than high school graduate, high school graduate, some college, and college graduate), physical activity (inactive, low activity, moderate activity, and high activity), alcohol consumption (continuous), regional solar radiation (300–325, 350, 375–380, 400–430, and 475–500 Langleys), skin reaction to sun (no burns, with or without tanning; burns, and with or without tanning), average daily time outdoors currently (<30 min, 30 min–2 h, and 2+ h), and sunscreen SPF use (none, something but does not know, SPF 2–14, SPF 15–24, and SPF 25+). Model 2: Model 1 plus adjustment for the total calorie intake (continuous), coffee consumption (continuous), smoking (never, past, and current), hormone therapy status (never, past, and current), and average daily time outdoors in summer as a child (<30 min, 30 min–2 h, and 2+ h).
Table 3. The relative risk for incident non-melanoma skin cancer according to frequency of citrus juice consumption among Women’s Health Initiative participants ( n = 49,007) by subgroups of potential effect modifiers.
Citrus Juice Serving Category p -Trend <2/wk 2–4/wk 5–6/wk 1–1.4/d ≥1.5/d Regional solar radiation 300–350 Number of cases (%) 1640 (15.1) 390 (15.9) 824 (17.1) 267 (16.2) 1321 (18.1) Adjusted RR (95% CI) (ref) 1.04 (0.94, 1.15) 1.09 (1.00, 1.17) 1.03 (0.92, 1.16) 1.12 (1.04, 1.19) 0.002 375–500 Number of cases (%) 1932 (18.4) 378 (19.2) 707 (20.3) 241 (18.0) 942 (20.3) Adjusted RR (95% CI) (ref) 1.00 (0.91, 1.11) 1.05 (0.97, 1.14) 0.93 (0.83, 1.06) 1.04 (0.97, 1.12) 0.353 Skin reaction to sun No burn, with or without tanning Number of cases (%) 1094 (14.0) 218 (13.7) 488 (15.3) 163 (15.1) 683 (15.9) Adjusted RR (95% CI) (ref) 0.98 (0.85, 1.12) 1.06 (0.96, 1.17) 1.06 (0.91, 1.24) 1.09 (1.00, 1.20) 0.034 Burn, with or without tanning Number of cases (%) 2478 (18.3) 550 (19.5) 1043 (20.4) 345 (18.1) 1580 (20.7) Adjusted RR (95% CI) (ref) 1.04 (0.95, 1.13) 1.07 (1.01, 1.15) 0.95 (0.86, 1.05) 1.08 (1.02, 1.14) 0.028 Time Outdoors in Summer Currently <30 min/day Number of cases (%) 1004 (15.1) 186 (14.8) 402 (16.7) 149 (17.9) 597 (17.4) Adjusted RR (95% CI) (ref) 0.95 (0.82, 1.10) 1.07 (0.96, 1.19) 1.15 (0.98, 1.34) 1.10 (1.01, 1.21) 0.015 >30 min/day Number of cases (%) 2568 (17.5) 582 (18.5) 1129 (19.1) 359 (16.7) 1666 (19.6) Adjusted RR (95% CI) (ref) 1.04 (0.96, 1.13) 1.07 (1.00, 1.14) 0.93 (0.84, 1.03) 1.07 (1.01, 1.13) 0.040 Sunscreen Use No sunscreen use Number of cases (%) 1471 (13.6) 285 (13.9) 589 (14.8) 199 (14.0) 865 (15.6) Adjusted RR (95% CI) (ref) 1.01 (0.90, 1.14) 1.06 (0.97, 1.16) 0.99 (0.86, 1.14) 1.10 (1.02, 1.19) 0.020 Sunscreen Use (any or unknown SPF) Number of cases (%) 2101 (19.9) 483 (20.4) 942 (21.7) 309 (19.8) 1398 (21.9) Adjusted RR (95% CI) (ref) 1.03 (0.94, 1.12) 1.07 (1.00, 1.15) 0.98 (0.88, 1.09) 1.07 (1.01, 1.14) 0.042
Adjusted for age (continuous), BMI (<25.0, 25.0–29.9, 30.0–34.9, ≥35.0 kg/m 2 ), education (less than high school graduate, high school graduate, some college, and college graduate), physical activity (inactive, low activity, moderate activity, and high activity), alcohol consumption (continuous), regional solar radiation (300–325, 350, 375–380, 400–430, and 475–500 Langleys), skin reaction to sun (no burns, with or without tanning; burns, and with or without tanning), average daily time outdoors currently (<30 min, 30 min–2 h, and 2+ h), and sunscreen SPF use (none, something but does not know, SPF 2–14, SPF 15–24, and SPF 25+). The stratifying variable was removed in its stratified analysis.
Sakaki, J.R.; Melough, M.M.; Roberts, M.B.; Eaton, C.B.; Shadyab, A.H.; Qureshi, A.A.; Chun, O.K.; Cho, E. Citrus Consumption and the Risk of Non-Melanoma Skin Cancer in the Women’s Health Initiative. Cancers 2021, 13, 2173.
https://doi.org/10.3390/cancers13092173
AMA Style
Sakaki JR, Melough MM, Roberts MB, Eaton CB, Shadyab AH, Qureshi AA, Chun OK, Cho E. Citrus Consumption and the Risk of Non-Melanoma Skin Cancer in the Women’s Health Initiative. Cancers. 2021; 13(9):2173.
https://doi.org/10.3390/cancers13092173
Chicago/Turabian Style
Sakaki, Junichi R., Melissa M. Melough, Mary B. Roberts, Charles B. Eaton, Aladdin H. Shadyab, Abrar A. Qureshi, Ock K. Chun, and Eunyoung Cho. 2021. "Citrus Consumption and the Risk of Non-Melanoma Skin Cancer in the Women’s Health Initiative" Cancers13, no. 9: 2173.
https://doi.org/10.3390/cancers13092173
MDPI and ACS Style
Sakaki, J.R.; Melough, M.M.; Roberts, M.B.; Eaton, C.B.; Shadyab, A.H.; Qureshi, A.A.; Chun, O.K.; Cho, E. Citrus Consumption and the Risk of Non-Melanoma Skin Cancer in the Women’s Health Initiative. Cancers 2021, 13, 2173.
https://doi.org/10.3390/cancers13092173
AMA Style
Chicago/Turabian Style
Sakaki, Junichi R., Melissa M. Melough, Mary B. Roberts, Charles B. Eaton, Aladdin H. Shadyab, Abrar A. Qureshi, Ock K. Chun, and Eunyoung Cho. 2021. "Citrus Consumption and the Risk of Non-Melanoma Skin Cancer in the Women’s Health Initiative" Cancers13, no. 9: 2173.
https://doi.org/10.3390/cancers13092173
| https://www.mdpi.com/2072-6694/13/9/2173/xml |
(PDF) CHINA-NIGERIA TRADE RELATIONS: DOES CHINA TRADE BALANCE MATTER FOR NIGERIA?
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CHINA-NIGERIA TRADE RELATIONS: DOES CHINA TRADE BALANCE MATTER FOR NIGERIA?
Abstract
Nigeria and China have had a long bilateral trade relation. Outside the Middle East, Nigeria is a major export destination of China. This study investigates the response of Nigeria's trade balance to the dynamics of China's trade balance using monthly time series data spanning 1995M01 to 2019M12. We employed the linear and nonlinear Autoregressive distributed lag models and discovered that China's trade balance significantly affects Nigeria's trade balance in the short run and long run. Also, the lag values of China's trade balance significantly explain current value of Nigeria's trade balance in the long run. While we found changes in Nigerian exchange rate having increasing effects on the country's trade balance in the long run, China's exchange rate appreciation and depreciation appeared to hurt Nigeria's trade balance in the short run. We further found no evidence of asymmetric effects of oil price, the Nigeria exchange rate, and China's exchange rate on Nigeria's trade balance in the short and long run. We therefore, suggest that Nigeria's investors and the government should consider China's trade balance and exchange rate behaviours in trading decisions.
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CHINA-NIGERIA TRADE RELATIONS: DOES CHINA TRADE BALANCE
MATTER FOR NIGERIA?
Abiodun Moses Adetokunbo 1 and Joel Ede Owuru 1
1 Department of Economics, Augustine University, Ilara-Epe, Lagos State, Nigeria
Abstract
Nigeria and China have had a long bilateral trade relation. Outside the Middle East, Nigeria
is a major export destination of China. This study investigates the response of Nigeria’s trade
balance to the dynamics of China’s trade balance using monthly time ser ies data spanning
1995M01 to 2019M12. We employed the linear and nonlinear Autoregre ssive distributed lag
models and discovered that China’s trade balance significantly affects Nigeria’s trade balance
in the short run and long run. Also, the lag values of China’s trade balance signific antly explain
current value of Nigeria’s trade balance in the long run. While we found changes in Nigerian
exchange rate having increasing effects on the country’s trade balance in the long run, China’s
exchange rate appreciation and depreciation appeared to hurt Nigeria’s trade balance in the
short run. We further found no ev idence of asymmetric e ffects of oil price, the Nigeria exchange
rate, and China’s exchange rate on Nigeria’s trade balance in the short and long run. We
therefore, suggest that Nigeria ’s investors and the government should consider China’s trade
balance and exchange rate behaviours in trading decisions.
Keywords: Asymmetries, Exchange rate, China-Africa relations; Oil price, Trade balance.
JEL Codes: C51, F10, F14, F31, L72
1 Introduction
Nigeria a nd china have long established bilateral relations in different spheres. These cut across
economic and trade relations as well as scientific and technological cooperation. With the
setting up of economic and trade relations, the quantum of trade volumes of these countries in
terms of exports and imports have surged to US$ 1.86 billion, representing a 59% growth in
2003 and slightly declined to US$ 609 million (17.6%) within the first quarter of 2004 where
Nigeria's export to China reg istered a growth of 330% (MF A, 2004). In fact, between 2001 and
2010, the spate of China-Nigeria bilateral agreements increased (Egbula and Zhe ng, 2011) and
No bilateral China-Africa relationship is noted to have evolved faster with more impacts on
people than the one between China and Nigeria. In this case, from less than USD 2 billion in
2000, trade between China and Nigeria reached nearly USD 18 billion in 2010 (Egbula and
Zheng, 2011).
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Trade-importation of consumables and manufactured goods from China to Nigeria takes a
larger proportion of activities in this Sino-Nigeria relation as Nigeria is a net importer of
manufactured Chinese goods. The Nigeria ’s teeming population with high appetite for foreign
and cheap products favours low cost Chinese consumer goods as substitute to the western
goods. Consequently, Chinese companies in their variant fo rms and sizes have also find their
location across several cities in Nigeria, hence stiffening competition for local firms. With the
export promotion laws, Nigeria has increased her trade drive. Egbula and Zheng (2011) further
revealed that Nigeria has a share of 1.5%, 11.3% and 6.2% in China’s import, export and total
trade respectively in Africa with a total of 11%, 10%, 9%, 9%, 3%, and 38% respectively for
vehicles, electrical equipment, textile products & telecom equipment, industrial machinery,
agro food products, and other manufactures to Nigeria as at 2010. On the other hand, China’s
imports from Nigeria by product as at 2010 constitutes 87% petroleum and gas, 3% Leather
manufactures, 7% metal, 2% other raw materials, and 1% others. I ndeed, these trends of
bilateral trade between China and Nigeria accounted for nearly one third of the trade between
China and West Africa, indicating the import ance of Nigeria to China in her West African
regional market (Egbula and Zheng, 2011).
While around 87 percent of Nigeria’s exports to China are oil and gas products, China exports
diversified range of goods to Nigeria (m achinery, equipment and manufactured commodities
inclusive). Oil, is indeed a major commodity in the international commodity market and
exchange rate and trade balance. This is because oil is considered as a leading indicator of
exchange rate movements since an increase in oil prices reduces the wealth of oil -importing
nations by transferring their income to oil -exporting nations through trade balance (Turhan et
al., 2014). This provides justification for including oil price and exchange rate in examining
the interaction of Nigeria’s trade balance with China’s trade balance.
Moreover, Sino-Nigeria trade nexus has, in recent times surged. China exported $17.4 Billion
worth of products to Nigeria in 2020 while her import stood at $2.54 billion for the same time
and while total e xport of China to Nigeria increased within the last 2.5 decades at an annualized
rate of 20.9% from $151 Million in 1995 to $17.4 Billion in 2020, exports of Nig eria to China
however reclined around 16.9% from $51M in 1995 to $2.54B in 2020 (OEC, 2020). This has
increasingly depicted the lopsided nature of the bilateral trade relations of China with Nigeria
and Africa in general (Salisu and Owuru, 2018). Here, there exists trade imbalance in China-
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Nigeria trade relations as Nigeria’s exports to China witnessed low trade intensity than China’s
exports to Nigeria.
We therefore modeled and tested for the possibility of asymmetric response of Nigeria’s trade
balance to the trade balance of China. We achieved this by employing d ynamic econometric
approach of linear and nonlinear autoregressive distributed lag (ARDL & NARDL) in the spirit
of Pesaran et al., (2001) and Pesaran and Shin (2004). To the best of our knowledge, this study
is the first of its kinds that tests whether China’s trade balance matters in modeling the
dynamics of Nigeria’s trade balance.
Following th e introduction, the remainder of this paper is organized as follows: review of
literature and the methodolo gy of the stud y are respectively detailed in section two and thre e.
We present the empirical results and discussion of the findings in section four and five while
section six concludes the study with appropriate policy suggestions.
2. Review of Literatu re
Existing studies have empirically investigated the relationship between exchange rates and
balance of trade within the context of Marshall-Lerner (ML) condition and the J-curve theory.
The condition states that the depreciation of local currency would eventually benefit the
balance of trade if the sum of the demand elasticities of imports and exports surpassed unity
(Marshall, 1923; Bahmani-Oskooee, 1985). Studies have also shown, however, that
depreciation of a local currency could have immediate adverse effects on the balance of trade
due to the time lag between existing and new contracts. Magee (1973) earlier argued that the
balance of trade worsens following depreciation because there is an adjustment process
between depreciation and change in agent’s (consumers, importers and exporters) behaviour.
Thus, the balance of trade worsens following the depreciation of the local currency, which is
referred to as the exchange rate pass-through in the international t rade literature (Bahmani-
Oskooee & Ra tha, 2004; Madura, 2011). Over time, imports will end up becoming more
expensive a nd the demand will decline, while exports become relatively cheaper and the
demand for exports would likely increase. Both the immediate and eventual effects of
depreciation will cre ate a skewed J-curve on the balance of trade (Magee, 1973 ; Dixit &
Norman, 1980; Bahmani-Oskooee et al, 2016 ; Bahmani-Oskooee & Fariditavana, 2016). This
is known as the J-curve theory.
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Magee (1973) tested the ML condition and showed that U.S. balance of trade initially
deteriorates and eventually improves, forming a J-curve. In a different study, while
investigating the effect of currency d evaluation in 13 developed countries i ncluding the U.S.,
U.K., and Canada, Junz and Rhomberg (1973) found complementa ry evidence supporting the
postulations of Magee (1973) and the J-curve theory. Nonetheless, the empirical approach used
in the studies of Magee (1973) and Junz and Rhomberg (1973) has been criticized b y Miles
(1979) on the grounds that these studies omit other critical influential factors, such as monetary
policy and economic growth rates.
International trade enhances the quality of goods and services for consumers. It also increases
the competition between domestic and foreign firms (Song et al, 2012; Isik, 2015; Dogru &
Bulut, 2018; Isik et al, 2018 ). This competition extends to domestic and foreign fiscal polic y
managements of both domestic and foreign governments due to the potential consequences of
trade de ficit that cross border trade might have for a national economy in the competitive g lobal
markets (Croes, 2006; Madura, 2011).
Countries may have surpluses in their trade balance within their overall economy or in certain
industries; they may also have a balance of trade deficit between their trading partners, which
can be disadvantage ous in global competitiveness. The balance of trade deficit may not
necessarily be financially damaging, howe ver, it needs to be controlled by the country's internal
systems of government to protect na tional economic interests (Madura, 2011). Higher demand
for imports than for locall y produced goods will lower the production output and adversely
affect employment. Due to low demand for domestic goods, the demand for employment will
also weaken and jobs would likely shift to foreign countries (Dixit & Norman, 1980; Madura ,
2011).
Bahmani-Oskooee and Fariditavana (2015) postulated that the empirical methodologies
employed to analyze the relationship between the exchange rate and balance of trade assumes
a symmetric relationship between the exchange rate and balance of trade. However, currency
depreciation might have different impacts on balance of trade than appreciation. In their more
recent study, Bahmani-Oskooee and Fariditavana (2016) replicated the study of Rose and
Ye llen (1989) utilizing the nonlinear ARDL cointegration approach and found evidenc e of a J-
curve pattern, contrar y to the previous findings. These results suggest that assuming a
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symmetric relationship b etween the exchange rate and balance of trade may yiel d misleading
empirical inferences.
In a similar study, Bahmani-Oskooee et al. (2016) analyzed the effect of exchange rates on
bilateral balance of tra de between Mexico and six of its trading partners utilizing the nonlinear
ARDL model and found that a ppreciation of the peso deteriorated the trade balance of Mexico
with the U.S. and Canada, whereas dep reciation of the Peso improved the trade balance of
Mexico with all of these six trading partners. It has also been suggested that these conflicting
analyses could be contingent on the bilatera l trade agreements. Owuru and Adetokunbo (2021)
found that increases in oil price significantly produced s ymmetrical negative effects on trade
balance of Ni geria in the long run and insignificant negative effect on trade balance of South
Africa in the short run, while exchang e rate depreciation significantly affected trade balance of
Nigeria but showed insignificant effects on trade balance of South Africa.
Furthermore, the extent and magnitude of the effect of China’s tr ade balance and exchange rate
on Nigeria’s tr ade balance is rarely reported in literature. Though, previous studies have
analyzed Nigeria’s trade relations with China, there are still some noteworthy knowledge gaps
in this area of research. Majority of the available studies (Agubamah, 2014; Ogunkola et al,
2008; Umo-Udo and Or ifa, 2018) on trade relations between Nigeria and China do not employ
detail econometrical tools that could have yielded more inferences. S canty literature (Azu &
Abu-obe, 2014) that examined Nigeria-China trade relations using econometric tools had
focused on determinants of Nigeria’s trade with China and not how China’s balance of trade
influences Nigeria’s trade balance. While Owuru and Adetok unbo (2021) ex amined response
of trade balance to exchange rate and oil price, the study investigated the dynamics of Nigerian
and South African trade balances independently. This study however investigated the effect of
China’s trade balance, e xchange rat e appreciation, depreciation and oil price on Nigeria
balance of tr ade and we hope that this will provide policy guide for tr aders, investors, and
Nigeria’s government on trade and policy decisions.
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3. Methodology
3.1 The model
The model adapted for this study follows that of Bahmani-Oskooee and Faridikavana (2016).
(1)
Where is the logarithmic value of trade balances between a countr y and its trade partner
i at a given time period and is defined as the diff erence between the country imports ( ) from
its partner i and her exports ( to partner i over a given period of time. Y is the measure of
economic activity in a country,
is the measure of economic a ctivity in partner i, while
is the exchange rate and it is defined in a wa y that a decline reflects a real depreciation of the
rand. Equation (1) is a b ilateral trade model. Thi s model was modified to capture the trade
balance model of Nigeria while accommodating for China’s trade balance effects. Hence,
equation (1) becomes:
(2)
In this study, is trade balance (current US $). This variable is measured as the difference
between total monetary values of export of g oods and services and import of goods and services
for each country. Trade balance mostly exhibits negative values, and to be able to interpret the
empirical results in logarithmic forms, it is taken as a ratio of gross domestic product (current
US $) in percentage at time t.
is the logarithm of gross domestic product p er capita at time
t (constant 2010 US $). is the logarithm of Nigeria’s real excha nge rate at time t. is
the logarithm of oil price at time t. is the logarithm of China’s real exchange rate at
time t. is the logarithm of China’s trade balance at time t. This variable is external balance
on goods and services as a percentage of gross domestic product. Accounting for the short run
trade balance, equation (2) is modified in an Autoregressive Distributed lag model (ARDL) as:
(3)
t k t k t k t k t k t k t
n
o k k t k t
n
k k t k t k t
n
k k t
k t
n
k k t k t
n
k k t k t
n
k k t t
lCtb lCrex lO x lN lY Tb
lCtb lCrex lO
x lN lY Tb Ntb
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Where and k represent s hort run change and optimal lag order of the vari ables, and other
variables remain as previously defined.
Equation (3) follows Pesaran et al, (2001) who included linear combination of lagged level
variables instead of lagged error term from as in moving average model and proposed applying
the F-test for joint significance of the lagged level variables as a sign of cointegration. Once
conitegration is established, we normalize - by to get long run effects of all the four
variables on the trade balance. Short run effects are reflected in the coefficient estimates that
are attached to first-differenced variables.
We recognized asymmetric adjustments and shocks in exchange rate and oil price as in Kilian
(2009) and account for their effects on trade balance by decomposing changes in exchange rate
and oil price into positive and negative shocks to account for nonlinearities in trade balance -
exchange rate-oil price nexus. Hence, the nonli near ARDL (NARDL) following the seminar
work of Sh in et al. (2014) and used by Fasanya et al (2018). Thus, the partial sum
decomposition of positive and negative changes in both countries exchange rate and oil price
is structured in equation (4a and b), (5a and b) and (6a and b) as:
(4a)
(4b)
(5a)
(6b)
Thus, by utilizing these decomposed asymmetric changes in exchange rate and oil price from
equation (4), (5) and (6), our estimated NARDL model is stated in equation (7) as:
t
j j
t
j j t x lN x lN x lN
1 1
) 0 , Re ma x( Re Re
t
j j
t
j j t x lN x lN x lN
1 1
) 0 , Re mi n( Re Re
t
j j t x lC x lC x lC
1 1
) 0 , Re m ax( Re Re
t
j j
t
j j t x lC x lC x lC
1 1
) 0 , Re m in ( Re Re
t
j j
t
j j t lO lO lO
1 1
) 0 , max (
j j
t
j j t lO lO lO
1 1
) 0 , mi n(
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(7)
Where are the partial sum of positive and
negative changes of exchange rate and oil price while represent the
short run coefficients of the partial sum of positive and negative changes of exchange rate and
oil price respectively, while are the long run coefficients of the partial sum of positive
and negative changes of exchange rate and oil price respectively.
Based on the work of Shin et al (2014), equation (7) is referred to as a nonlinear ARDL (Auto
Regression Distributed Lag) model whereas; equation (3) is called th e linear ARDL model.
From (7), it is hypothesized that the estimate of
(for instanc e)is different from the estimate
of
a t the same lag k. If they are not equal, that will be an indication of short run
asymmetric effects. If and ; and and and takes
different lag order respecti vely, that will be an indication of sho rt run adjustment asymmetry.
*: 1 percent level of significance
Source: Authors computation
From table 1, the mean value of the Nigeria’s trade balance , gross domestic product pe r capita,
Nigeria’s real exchange rate, oil price, China’s trade balance and real ex change rate is 2.5%,
3.2%, 2.1%, 1.6%, 0.8% and 3.5% respectively. It is evident, based on the average values of
trade balance of both countries that China traded more than Nigeria.
All the series are negatively skewed except for Nigeria’s and China’s trade balances that fall
to the right hand side of the mean dist ribution. In terms of kurtosis, it is shown that Nigeria’s
trade balance, Nigeria’s real exchange rate and China’s trade balance are hi ghly peaked since
they are below the threshold value of 3 , hence they are leptokurtic. Nigeria’s gross domestic
product, oil price and China’s rea l exchange rate are conversely platykurtic. Jarque-Bera
statistics provides comprehensive information as it combines skewness and kurtosis properties.
The Jarque-Bera probability value for the variables as indicated by the level of their probability
significance shows that the series are not normally distributed within the period of the study.
The stationarity properties of the series were examined using Augmented Dickey Fuller (ADF)
and Phillips-Perron (PP) test for unit root (see tabl e 2). The motivation for this test is to avoid
running spurious regressions that would yield misleading poli cy evidence with our specified
model. Thus, the orders of int egration of the series are symbolized in the remark section of
table 2. The result of the unit root indicates that all the series are stationary at first difference,
I (1) except Nigeria’s trade balance that is stationary at level, I (0). This mixture of order of
integration suggests that autoregressive Distributed lag (ARDL) approach of Pesaran, et al.,
(2001) is followed in the model estimation process.
Source: Author’s computation. *, **, and *** indicate the rejection of null hypothesis of non-stationary at 1 percent,
Table 3: The Bound test for cointegrating relationship of the variables
ARDL
NARDL
Null: No levels relationship
Test Statistic
Value
K
Test Statistic
Value
K
F-statistic
5.043
5
F-statistic
4.538
8
Critical Value Bounds
Critical Value Bounds
Significance
I(0)
3.77
Source: Author’s Computation.
In Table 3, the bound test result shows that the computed F-statistic value for the ARDL and
NARDL model is 5.043 and 4.538 and it is higher than the upper and lower bound critical
values. It therefore confirms that the null hypothesis of no long run relationship among
variables stands rejected . Hence, there is long run relationship among variables.
The optimal lag for the ARDL and the NARDL model is 7 and 6 respectively. This is confirmed
by la g order selection criteria. Akaike information criterion (AIC) and Final prediction error
Turhan, M. I., Sensoy, A., & Hacihasanoglu, E. (2014). A comparative analysis of the dynamic
relationship between oil prices and exchange rates. Journal of International Financial
Markets,Institutions and Money , 32 , 397-414.
Testing Asymmetric Response of Trade Balance of Nigeria and South Africa to Exchange rate and Oil price Dynamics
This study tests the response of trade balance of Nigeria and South Africa to symmetric and asymmetric change in oil price and exchange rate using disaggregated monthly data for the period of 1995M01 to 2018M12 within the framework of Autoregressive Distributed Lag (ARDL) model and found that increases in oil price significantly produced symmetrical negative effects on trade balance of Nigeria in the long run and insignificant negative effect on trade balance of South Africa in the short run. Also, exchange rate depreciation significantly affected trade balance of Nigeria but showed insignificant effects on trade balance of South Africa. Finally, accounting for asymmetry in oil price and exchange rate may be implausible in predicting the dynamics of trade balance of the two countries within the time span of the study. We therefore recommend increased diversification of the economy and pursuant of exchange stability policy to achieve favorable balance of trade.
Oil Revenue Shocks and the Current Account Balance Dynamics in Nigeria: New evidence from Asymmetry and Structural Breaks
In this paper, we model the relationship between oil revenue and current account balance dynamics in Nigeria using quarterly data from 1987Q1 to 2015Q4. We employ both the Linear ARDL and Nonlinear ARDL models and we also account for multiple structural breaks using a test that allows for multiple structural changes in regression models. The following were noticed from our analyses. First, we observe the existence of an asymmetric effect on the current account balance both in the short and long run. Second, accounting for structural breaks play an important role when modelling the relationship between oil revenue and current account balance. Third, the paper finds that oil revenue has a significant positive effect on current account balance, however, puzzling that both positive and negative shocks affect the current account balance in the same manner. Overall, the positive changes in oil revenue have considerably larger impact than negative changes. The implications for policy are designed based on gathered findings.
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Economic Determinants of Nigeria’s Trade with China: A Cointegration Approach
The China-Nigeria trade volume has been increasing over the years with no signs of slowing down any time soon. This work examined the long-and-short run economic catalysts that stimulate this trade relation with focus on Nigeria’s economic factors as well as the Third Country’s Factors. Japan’s REER was adopted as a Third Country’s Factor and Johansen and Juselius cointegration technique was used to determine the result. The outcome revealed that GDP, trade openness and FDI inflow possess significant positive influence on China-Nigeria trade relations while bilateral exchange rate and Third Country’s Factor are negative determinants, suggesting that improvement in domestic prices and increased real exchange rates of Japan could undermine China-Nigeria bilateral trade, howbeit, in the long-run. So, both countries should gear towards improving domestic prices, efficiency and competitiveness relative to the Third Country’s Effect to curtail its excessive influence on bilateral trade and particularly, Nigeria should focus on redefining its business environment politically and otherwise to attract further FDI and ameliorate its trading sector.
Foreign Direct Investment in Tourism: Panel Data Analysis of D7 Countries
This paper uses the panel data of foreign direct investment (FDI) and tourism development (TD) for Developed 7 (D7) countries from 1980 to 2012. Panel data analysis is used in order to analyze the causal relationship between foreign direct investment and tourism development. Conducted structural and diagnostic test results of the final model has proved that tourism development affected the foreign direct investment in D7. It is crucial to see the directions of causality between these two variables for the policy makers. The findings of this study have important implications in deciding tourism policy and it shows that this issue still deserves further attention in future research.
Is tourism an engine for economic recovery? Theory and empirical evidence
TOURISM MANAGE
The purpose of this study is to examine the causal relationships between tourism development and economic growth. For this purpose, the Dumitrescu and Hurlin (2012) technique was employed to analyze the casual link between tourism development and economic growth in seven European countries. The results showed that there is bidirectional causality between growth in tourism receipts and economic growth, suggesting that economic growth and tourism development are interdependent and that tourism development stimulates economic growth and vice versa in these countries. Theoretical and practical implications are discussed within the realms of growth, conservation, feedback, and neutrality hypotheses.
Not all oil price shocks are alike: Disentangling demand and supply shocks in the crude oil market
Mexican Bilateral Trade and the J- Curve: An Application of the Nonlinear ARDL Model
Recent advances in time-series and cointegration analysis have allowed for the estimation of the nonlinear effects of currency depreciations on countries’ trade balances. This study examines Mexico’s bilateral trade with 13 trade partners, applying both the linear and the nonlinear versions of the Autoregressive Distributed Lag (ARDL) cointegration and error-correction methodologies, to test whether peso appreciations affect trade differently than do peso depreciations. The linear ARDL model generates significant long-run coefficients for six partners, implying that while peso depreciations improve Mexico’s trade balance with them, peso appreciation hurt it. However, the nonlinear ARDL model finds that peso appreciation hurts Mexico’s trade balance with three additional partners, and that peso depreciation improves it with one additional partner. Additional statistical tests reveal that indeed the effects of peso appreciation are significantly different than effects of peso depreciation, supporting the asymmetric effects of real exchange rate changes.
Nonlinear ARDL Approach and the J-Curve Phenomenon
Since introduction of cointegration and error-correction modeling, the definition of the J-curve has changed to reflect short-run deterioration combined with long-run improvement of the trade balance due to currency depreciation. Standard methods such as ARDL approach of Pesaran et al. (2001) assume that adjustment of variables follow a linear path. It is now recognized that the adjustment process could be nonlinear. Application of Non-linear ARDL approach of Shin et al. (2013) provides more evidence of the J-curve supporting non-linear adjustment of variables as well as asymmetric effects of exchange rate changes on the trade balance, using bilateral trade balance models of the U.S. with each of her six largest trading partners.
Nonlinear ARDL Approach, Asymmetric Effects and the J-Curve
| https://www.researchgate.net/publication/370183982_CHINA-NIGERIA_TRADE_RELATIONS_DOES_CHINA_TRADE_BALANCE_MATTER_FOR_NIGERIA |
(PDF) Effects of Ecological Restoration Measures on Soil Erosion Risk in the Three Gorges Reservoir Area Since the 1980s
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Effects of Ecological Restoration Measures on Soil Erosion Risk in the Three Gorges Reservoir Area Since the 1980s
DOI: 10.1029/2020GH000274
CC BY-NC-ND 4.0
Qinli Xiong
Abstract and Figures
Ecosystem degradation accompanied by soil erosion risk is caused by the interaction of many factors, including climate change and human activities. Therefore, before attempting the optimal form of ecological restoration, we must know the key factors responsible for soil erosion risk and determine their impacts on the ecosystem health. To test this approach, we conducted a case study in the Three Gorges Reservoir Area from 1980 to 2015, where extensive restoration (primarily afforestation) has been conducted. The results showed that climate was most important during Period I (1980 to 1984), and explained 84% of the variation in erosion. However, vegetation became equally important during Period II (1985 to 2006), when it accounted for 51% of the variation. Climate became as important as vegetation during Period III (2007 to 2015), when it accounted for 51% of the variation. The temporal variation in the dominant factors that controlled soil erosion risk suggests that the ecological effect of vegetation improvement resulting from ecological restoration in Three Gorges Reservoir Area has been gradually enhanced since the 1980s.
The location of the Three Gorges Reservoir area in China (TGD: Three Gorges Dam). …
Spatial distribution and changes over time in the land use and land cover (LULC) types from1980 to 2015. Spatial distribution of LULC in 1980 (a) and 2015 (b); Spatial distribution of increases (c) and decreases (d) of a given category of LULC. …
Spatial pattern and temporal dynamic of soil erosion (SE a ) in the Three Gorges Reservoir area from 1982 to 2015. (a) Spatial distribution of SE a . (b) Trends in annual SE a , with × indicating areas with a statistically significant trend (p < 0.05). …
(a) Detection of abrupt changes in annual soil erosion (SE a ) in the Three Gorges Reservoir area from 1982 to 2015. Turning points occur where the UF and UB curves intersect at a position above the threshold for statistical significance based on the Mann-Kendall mutation test. (b) Trends of annual SE a during the study period. Arrows indicate the significant turning points in 1984 and 2006 that were identified in (a). …
Changes from 1985 to 2015 in (a) the per capita real income of urban and rural residents and (b) the populations of rural and urban areas and the associated urbanization rate. …
Figures - available from: GeoHealth
Content available from GeoHealth
Effects of Ecological Restoration Measures on Soil
Erosion Risk in the Three Gorges Reservoir Area
Since the 1980s
Yang Xiao
1,3
, Qiang Xiao
2
, Qinli Xiong
1
, and Zhipeng Yang
4
1
CAS Key Laboratory of Mountain Ecological Restoration and Bioresource Utilization and Ecological Restoration
Biodiversity Conservation Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of
Sciences, Chengdu, China,
2
Institute of Ecology, China West Normal University, Nanchong, China,
3
College of Biology
and Environmental Sciences, Jishou University, Jishou, China,
4
National Natural Science Foundation of China, Beijing,
China
Abstract Ecosystem degradation accompanied by soil erosion risk is caused by the interaction of many
factors, including climate change and human activities. Therefore, before attempting the optimal form of
ecological restoration, we must know the key factors responsible for soil erosion risk and determine their
impacts on the ecosystem health. To test this approach, we conducted a case study in the Three Gorges
Reservoir Area from 1980 to 2015, where extensive restoration (primarily afforestation) has been conducted.
The results showed that climate was most important during Period I (1980 to 1984), and explained 84%
of the variation in erosion. However, vegetation became equally important during Period II (1985 to 2006),
when it accounted for 51% of the variation. Climate became as important as vegetation during Period III
(2007 to 2015), when it accounted for 51% of the variation. The temporal variation in the dominant factors
that controlled soil erosion risk suggests that the ecological effect of vegetation improvement resulting
from ecological restoration in Three Gorges Reservoir Area has been gradually enhanced since the 1980s.
1. Introduction
Ecosystem degradation is causing major environmental problems around the world, including soil erosion
and deserti fi cation. Ecological degradation affects 36 × 10
6
km
2
of land around the world, which amounts
to 25% of the total land area, leading to a direct economic loss as high as US$850 × 10
9
annually (Liu &
Diamond, 2008). Ecosystem degradation is particularly serious in China, where the area of degraded ecosys-
tems accounts for one third of the total land area. As a result, the livelihood of 400 × 10
6
people is threatened,
and 12 × 10
6
people have been plunged into poverty, accounting for 28.5% of China's impoverished popula-
tion (Lusiana et al., 2012).
In China's Three Gorges Reservoir area, the landforms (many hills and sloping land) and human activities
have contributed to increasingly serious ecosystem degradation and loss of arable land. However, as part
of the reservoir construction activities, large ‐ scale ecological restoration projects have been carried out to
protect the soils surrounding the reservoir against erosion and reduce siltation of the reservoir (Chen
et al., 2020). Because this is a key vulnerable ecological area that lies between the middle and lower reaches
of the Yangtze River, its ecosystem health directly affects the comprehensive bene fi ts provided by the Three
Gorges Project and the ecological security of the middle and lower reaches of the Yangtze River (Xiao
et al., 2017). Thus, determining the optimal form of ecological restoration to permit sustainable development
of the region's resources, including recycling and improved utilization of these resources, is essential for suc-
cessful development (Gou et al., 2020).
Ecosystem degradation in the reservoir area results from interactions among many natural and human fac-
tors. Landforms, climate change, and human activities all strongly in fl uence vegetation change, and changes
in the vegetation, in turn, affect the climate and human activities (Leman et al., 2016). Some natural science
researchers believe that the predicted climate change will degrade ecosystems by adversely affecting the soil
quality, vegetation cover, biodiversity, and hydrologic cycle. However, few studies have quanti fi ed the simul-
taneous effects of the interaction among multiple factors (both natural and human) based on long ‐ term
monitoring data (Valero et al., 2014). This is particularly problematic because of the importance of human
©2020. The Authors.
This is an open access article under the
terms of the Creative Commons
Attribution ‐ NonCommercial ‐ NoDerivs
License, which permits use and distri-
bution in any medium, provided the
original work is properly cited, the use
is non ‐ commercial and no modi fi ca-
tions or adaptations are made.
RESEARCH ARTICLE
10.1029/2020GH000274
Key Points:
• The government's restoration
programs, and particularly
afforestation, have improved the
vegetation cover and decreased soil
erosion
• The temporal variation factors that
controlled soil erosion suggests that
effect of vegetation resulting from
ecological restoration
• We found that precipitation was
most important during Period I
(1980 to 1984)
Correspondence to:
Q. Xiao and Q. Xiong
xiaoqiang1617@hotmail.com;
xiongql@cib.ac.cn
Citation:
Xiao, Y., Xiao, Q., Xiong, Q., & Yang, Z.
(2020). Effects of ecological restoration
measures on soil erosion risk in the
Three Gorges Reservoir area since the
1980s. GeoHealth , 4 , e2020GH000274.
https://doi.org/10.1029/2020GH000274
Received 1 APR 2020
Accepted 17 NOV 2020
Accepted article online 20 NOV 2020
Yang Xiao and Qinli Xiong contributed
equally to this work.
Author Contributions:
Conceptualization: Yang Xiao, Qiang
Xiao, Qinli Xiong
(continued)
XIAO ET AL. 1o f1 3
factors; methods and data from the social sciences have not been combined with those from the natural
sciences, thereby weakening the foundation for environmental management and making it dif fi cult to
improve environmental protection (Sun, Miao, AghaKouchak, et al., 2019).
Before the creation of the Three Gorges Reservoir, the region's ecosystem health was already under consid-
erable stress from a combination of climatic factors (e.g., drought) and human activities (e.g., unsustainable
agriculture in sloping land). Moreover, the regional characteristics (e.g., topography, climate) combined
with changes in the region's natural environment caused by the reservoir construction, population growth,
and increased pollution due to socioeconomic development, make the region's inherently fragile ecosystem
become more complex and fragile due to the impacts of these external in fl uences. To counteract these pro-
blems, China's government has invested more than US$3.22 × 10
9
to carry out large ‐ scale afforestation activ-
ities since the 1980s. It has consecutively implemented the Yangtze River Basin Shelter Forest Project,
Natural Forest Protection Project, Grain for Green Program, Afforestation Project on Both Sides of the
Yangtze River, and other key ecological projects. It has also established a preliminary ecological security sys-
tem with the establishment of forests as the primary component, and with a combination of shrub and grass-
land planting as an additional component. However, few studies have quanti fi ed the effects of these
ecological projects and of the ecological policy on soil erosion risk (Cao et al., 2014). Furthermore, the simul-
taneous effects of climate change and the Three Gorges Project on the regional climate and ecosystems make
it dif fi cult to distinguish the impacts of climate change from those of the Three Gorges Project itself (Zhao
et al., 2014). Because of the huge area affected by the Three Gorges Project and its long existence, the envir-
onmental impact should be assessed on large spatial and temporal scales to adequately describe the project's
impacts. Most notably, the reservoir has severely reduced fl ows of water into downstream regions, creating
persistent drought in the lower reaches of the Yangtze River in Hubei, Hunan, Jiangxi, and Zhejiang
provinces (Xiao & Xiao, 2018). The lack of water has destroyed 3 × 10
6
ha of farmland and has left
millions of people and livestock short of water (Liu & Yang, 2012).
If we can understand how natural and human factors interact to produce degraded ecosystems in TGRA, we
can manage these ecosystems in ways that permit optimal ecological restoration (Loizeau et al., 2018). To do
this, we must fi rst identify the key driving forces responsible for degradation and restoration and quantify
their impacts on ecosystem health. Ecological restoration can only be successful if it accounts for both the
ecological environment (e.g., climate, topography) and the productive and living behaviors of the inhabi-
tants of the degraded area. Accounting for both natural and human factors can avoid the shortcomings of
traditional projects, which neglect human factors, and thereby improve the effectiveness of ecological pro-
tection. The goal of the present study was to account for ecological factors, as well as human activities, that
lead to ecosystem health changes. This knowledge can be used to support the development of effective
restoration strategies based on improved utilization of soil and water resources and can thereby reduce
the impacts of soil erosion risk on the ecological environment.
2. Study Area and Methods
2.1. Study Area
The Three Gorges Reservoir area is located between Chongqing City and Hubei Province and covers a total
area of 57,802 km
2
that is home to a total population of nearly 20 million people. This area includes 26 cities
and counties, most of which are rugged terrain (Figure 1). About 74.0% of the area is mountainous, 21.7% is
hilly, and only 4.3% is plains (Bao et al., 2018). The elevation is high in the east and low in the west. The
dominant soil types are Ultlsols based on USDA soil taxonomy (Xiao et al., 2019). The region has a subtro-
pical monsoon climate. The mean annual precipitation reaches ~1,100 mm. And, for most of the year, it
experiences humid conditions with an annual mean temperature of 17 – 19°C.
The Three Gorges Reservoir has strongly affected the Yangtze River Basin, both because the Yangtze River
Basin is the largest river basin in the world and because the Three Gorges Dam is the largest hydropower
project in the world (Jiang et al., 2018). The dam's construction occurred from 1993 to 2009, with a total
reservoir capacity of 39.3 × 10
9
m
3
. In the 16 years before 2009, 1.25 million people were displaced by this
project as the reservoir inundated 245 km
2
of farmland and orchards, about 35 km
2
of residential areas,
and 824 km of roads. The construction resulted in wide ‐ scale land use/land cover (LULC) change and cli-
matic change that are expected to change regional soil conservation patterns.
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XIAO ET AL. 2o f1 3
Data curation: Qiang Xiao, Zhipeng
Yang
Formal analysis: Yang Xiao, Qinli
Xiong, Zhipeng Yang
Funding acquisition: Qiang Xiao,
Qinli Xiong
Investigation: Yang Xiao, Qinli Xiong,
Zhipeng Yang
Methodology: Qinli Xiong, Zhipeng
Yang
Project administration: Yang Xiao,
Qinli Xiong
Resources: Qiang Xiao, Zhipeng Yang
Software: Qiang Xiao
Supervision: Yang Xiao, Qinli Xiong,
Zhipeng Yang
Validation: Yang Xiao, Qiang Xiao
Visualization: Qinli Xiong
Writing ‐ original draft: Yang Xiao,
Zhipeng Yang
Writing – review & editing: Yang
Xiao
2.2. Data Sources
Because of the long time span of our study and its large area, we used Landsat images of the reservoir area
with a spatial resolution of 60 m (MSS) and 30 m (TM/OLI) from 1980 (MSS), 1990 (TM), 2000 (TM), 2005
(TM), 2010 (TM), and 2015 (OLI) to extract LULC data. We selected these images according to their availabil-
ity and the quality of the data set. We used version 9.3 of ArcInfo (https://www.esri.com) to superimpose
images from two consecutive years to identify changes in LULC. Comparing areas with ground ‐ based data
(387 samples), the overall accuracy of LULC maps were above 89.1% for the fi ve periods concerned. The
Vegetation Cover date set from 1982 to 2015 was calculated by mixed pixel decomposition model (Ivits
et al., 2013) based on the Global Inventory Modeling and Mapping Studies (GIMMS) Normalized
Difference Vegetation Index (NDVI) (https://ecocast.arc.nasa.gov).
We obtained meteorological data from the China National Meteorological Information Center (http://data.
cma.cn) (precipitation and temperature) and interpolated to raster data with a resolution of 0.05° by kriging
method (Xiao & Xiao, 2019). Soil maps and related soil properties were obtained from the second national
soil survey conducted by the Institute of Soil Science, Chinese Academy of Sciences, with a scale of
1:1000000 (http://www.issas.cas.cn). We derived a digital elevation map of the study area from the data
set produced by the Terra satellite's Advanced Space ‐ borne Thermal Emission and Re fl ection Radiometer
(ASTER), with a resolution of 30 m (http://www.gscloud.cn). All cartographic raster data were converted
to the same Albers coordinate system and spatial resolution of 100 m.
2.3. Methods
2.3.1. Model Description
Because soil erosion by water is the main cause of ecosystem degradation in the study area, excessive soil
erosion and sediment deposition will both damage local ecosystems and gradually decrease the reservoir's
hydroelectric power generation, and will also cause structural damage to the Three Gorges Dam. To estimate
the magnitude of the annual soil erosion in the study area, we used the universal soil loss equation:
Figure 1. The location of the Three Gorges Reservoir area in China (TGD: Three Gorges Dam).
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XIAO ET AL. 3o f1 3
SE a ¼ R × K × LS × C × P (1)
where SE
a
represents the annual soil loss under the current LULC conditions (t ha
− 1
yr
− 1
); R is the rain-
fall erosion coef fi cient (MJ mm ha
− 1
hr
− 1
yr
− 1
); K is the soil erodibility factor (t ha hr ha
− 1
MJ
− 1
mm
− 1
);
LS is a dimensionless topographic factor; C is a dimensionless vegetation cover factor; and P is a dimen-
sionless conservation practice factor. We will describe the calculation of these variables in the rest of this
section.
2.3.1.1. Rainfall Erosivity Factor ( R )
We calculated R from 1980 to 2015 using the proposed formula based on monthly rainfall (Fu et al., 2011):
R ¼ Σ 1 : 735 × 10 1 : 5log Pi 2 = P ðÞ – 0 : 818 (2)
where P
i
is the total rainfall (mm) in month i and P is the total annual rainfall (mm).
2.3.1.2. Soil Erodibility Factor ( K )
Soil erodibility describes the vulnerability of soil particles to being mobilized by raindrops and surface run-
off. We used the Erosion/Productivity Impact Calculator (EPIC) formula to calculate K . To make the equa-
tion applicable to the nature of the Chinese soils in the study area, we used the following parameterization:
K EPIC ¼ 0 : 2 þ 0 : 3 exp – 0 : 0256 m sand 1 – m silt = 100 ðÞ ½
fg
× m silt = m clay þ m silt
0 : 3 ×1 – 0 : 25 orgC = orgC ½
f
þ exp 3 : 72 – 2 : 95 orgC ð Þg ×1 – 0 : 71 – m sand = 100 ðÞ = 1 – m sand = 100 ðÞ þ exp – 5 : 51 þ 22 : 91 – m sand = 100 ðÞ ½ fg fg
(3)
K ¼ – 0 : 01383 þ 0 : 51575 K EPIC
ðÞ ×0 : 1317 (4)
where K
EPIC
and K are soil erodibility factors (t ha hr ha
− 1
MJ
− 1
mm
− 1
) before and after revision, respec-
tively; and m
sand
, m
silt
, m
clay
, and orgC are the percentages of sand, silt, clay, and organic carbon,
respectively.
2.3.1.3. Topographic Factors ( LS )
Topographic factors re fl ect the effects of slope length ( L ) and steepness ( S ) on soil erosion. We calculated the
LS factor using improved L and S equations and an Arc Macro Language (AML) script in ArcGIS. The equa-
tions are as follows:
L ¼ λ = 22 : 13 ðÞ
m (5)
m ¼ β = 1 þ β ðÞ (6)
β ¼ sin θ = 0 : 089
ðÞ
= 3 : 0 sin θ 0 : 8 þ 0 : 56
(7)
S ¼
10 : 8 sin θ þ 0 : 03 θ <5 : 14°
16 : 8 sin θ − 0 : 55 : 14° ≤ θ <1 0 : 20°
21 : 91 sin θ − 0 : 96 10 : 20° ≤ θ <2 8 : 81°
9 : 5988 θ >2 8 : 81°
8
>
>
>
<
>
>
>
:
(8)
where LS is a dimensionless topographic factor, L is a dimensionless slope length factor; S is a dimension-
less slope steepness factor that depends on the slope gradient θ (°); λ is the slope length (m); and m is the
slope length index, which also depends on θ .
2.3.1.4. Vegetation Cover Factor ( C )
Soil erosion has a negative exponential relationship with vegetation cover, which therefore plays an impor-
tant role in controlling soil erosion. We determined the value of C for our study area using a look ‐ up table
based on vegetation cover and LULC (Table 1).
2.3.1.5. Erosion Control Practices Factor ( P )
Based on previous research (Fu et al., 2011), in our study area, this factor was only relevant for cultivated
farmland. This soil erosion is a key factor in our study area, since about 74% of the land is mountainous
and therefore at high risk of erosion. We calculated P as follows:
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XIAO ET AL. 4o f1 3
P ¼ 0 : 2±0 : 03 α (9)
where α is the slope gradient (°).
Based on the calculations described earlier in this section, Figure 2 shows
the spatial distribution of the abovementioned parameters of the universal
soil loss equation model that we used in this study.
2.3.2. Model Validation
To verify the regional applicability and reliability of the universal soil loss
equation model, we veri fi ed our results using observational data from
2000 to 2010, which were obtained from the government's soil and water
conservation bulletin (http://slj.cq.gov.cn). The simulated soil erosion
agreed well with the observed values (Pearson's r = 0.810, n = 31,
P < 0.01). This indicates that the model and its parameters are suitable
for simulating soil and water conservation conditions in the study area.
2.3.3. Data Analyses
2.3.3.1. Trend Analyses
To detect changes in the soil erosion trend during the study period (1982 to 2015), we used least squares lin-
ear regression to fi t the soil erosion variables as a function of time (year) for each pixel. The least squares
linear regression method used the following equation (Xiao & Xiao, 2019):
y ¼ a þ bt þ ε (10)
where y represents a given soil erosion variable ( SE
a
), t is the year, a and b are fi tted variables ( a is the
intercept and b is the slope, which represents the trend), and ε is the residual error. If b > 0, soil erosion
increases. Conversely, if b < 0, erosion decreases. We used the t test to identify signi fi cant differences in
the trends for the annual erosion time series, with signi fi cance de fi ned at P < 0.05.
2.3.3.2. Abrupt Changes
We used the Mann ‐ Kendall mutation test to identify abrupt changes in soil erosion (Yue & Wang, 2004). This
test assumes that if the forward trend sequence curve UF intersects the backward trend sequence curve UB
generated with the reverse data series of UF at a position above the threshold for statistical signi fi cance
(±1.96), then a statistically signi fi cant mutation point exists; on the other hand, if the intersection point lies
outside the threshold or if there are many intersections between the lines, then it is impossible to establish a
fi xed mutation point. In this case, we used the nonparametric Pettitt test to detect mutation points
(Pettitt, 1979).
Figure 2. The spatial distribution of the parameters of the universal soil loss equation.
Table 1
Values of the Vegetation Cover Factor (C) as a Function of Land Use and
Cover Types (LULC) and Vegetation Cover (VC)
C values based on VC (%)
LULC <10 10 – 30 30 – 50 50 – 70 70 – 90 >90
Forest 0.10 0.08 0.06 0.02 0.004 0.001
Shrubs 0.40 0.22 0.14 0.085 0.040 0.011
Grassland 0.45 0.24 0.15 0.09 0.043 0.011
Wetland 0
Cropland 0.221 – 0.595logVC
Built up land 0.01
Bare land 0.7
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XIAO ET AL. 5o f1 3
2.3.3.3. Correlation and Regression
To study the relationship between the soil erosion change and the driving forces, we used Pearson's
correlation coef fi cient ( r ) and stepwise regression for the relationships to reveal the relative contributions
of each factor to the spatial distribution of soil erosion. The statistical unit for more than 700 samples in
TGRA was analyzed in the IBM SPSS Statistics 20 (IBM Corp., Armonk, NY, USA), which were created by
ArcGIS 10.3 (URL: http://www.esri.com/) fi shnet tool according to the maximum resolution (8 km × km)
of all data.
3. Results
3.1. LULC Trends
The dominant LULC types in the reservoir area were forest and cropland, which occupied around 40.25%
and 32.77% of the land, respectively, in 1980, and 42.66 and 25.22% in 2015, respectively (Table 2). In abso-
lute terms, there was little change in LULC during the study; for example, the area of forest only increased by
2.41 percentage points, and that of cropland changed by only 7.55 percentage points. However, these small
percentage changes represented large areas (an increase of 1,404 km
2
for forest and a decrease of 4,405 km
2
for cropland). In addition, the area of built ‐ up land increased to nearly 10 times its 1980 value during the
36 ‐ year study period. In relative terms, the area of forest increased by 5.98% during the study period, and
the area of grassland increased by 1.00%. The wetland area (including rivers, lakes, and the reservoir) had
almost doubled. In contrast, the area of cropland decreased by ~23.04%.
From 1980 to 2015, LULC changed remarkably (Figure 3) in spatial perspective, driven by ecological and
developmental policies. Most of the changes occurred in the northeastern and central mountainous areas,
For example, 60% of the increase in forest area and 70% of the decrease in cropland area occurred in these
areas. Built up and forest areas are the two main LULC types that increased from 1980 to 2015. Almost all
of these increases occurred in areas where cultivated land decreased. Cultivated land was the main type of
LULC that decreased, with changes in this category accounting for 46.55% of the total change from 1980
to 2015.
3.2. Dynamic Characteristics of Soil Erosion
The total annual soil erosion reached 1.67 × 10
8
t. This represents an average rate of 28.69 t ha
− 1
. The annual
mean soil erosion was highly spatially variable, with the highest values in the northern and northeastern
parts of the reservoir area and smaller values in the southwestern part of the study area (Figure 4a). Areas
with high soil erosion (>100 t/ha) that suffered heavy soil loss were primarily located near the Daba
Mountains in the northeast.
Since 1989, many of the government's afforestation policies have been implemented in the reservoir area,
including the Yangtze River Shelter Forest Project, Natural Forest Conservation Project, and Grain for
Green Program. Under these programs, a large area of sloping farmland has been transformed into shrub
and forest vegetation (above 1,000 km
2
). The vegetation cover also increased as a result of the different affor-
estation programs. As a result of these changes, soil erosion fl uctuated but showed a signi fi cant overall
Table 2
Changes in the Areas of Each Land Use and Land Cover (LULC) and in the Corresponding Proportions of the Total Area From1980 to 2015
1980 1990 2000 2005 2010 2015
LULC 10
3
km
2
%1 0
3
km
2
%1 0
3
km
2
%1 0
3
km
2
%1 0
3
km
2
%1 0
3
km
2
%
Forest 23.48 40.25 23.52 40.32 23.63 40.50 24.26 41.58 24.35 41.74 24.89 42.66
Shrubs 10.51 18.02 10.56 18.10 10.67 18.30 10.48 17.96 10.35 17.74 10.22 17.51
Grassland 4.21 7.21 4.23 7.25 4.29 7.36 4.28 7.34 4.25 7.28 4.25 7.28
Wetlands 0.84 1.44 0.84 1.44 0.84 1.44 1.23 2.10 1.46 2.51 1.72 2.96
Cropland 19.12 32.77 18.95 32.48 18.14 31.09 16.88 28.93 15.98 27.40 14.72 25.22
Built up 0.13 0.22 0.19 0.33 0.72 1.24 1.19 2.04 1.93 3.31 2.53 4.34
Bare land 0.05 0.08 0.05 0.08 0.05 0.08 0.02 0.04 0.01 0.02 0.02 0.03
Total 58.34 100.00 58.34 100.00 58.34 100.00 58.34 100.00 58.34 100.00 58.34 100.00
Note . The relative change ratio is calculated based on the following formula: Change ratio = ([LULC
2015
− LULC
1980
]/LULC
1980
) × 100.
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XIAO ET AL. 6o f1 3
decreasing trend from 1980 to 2015, at − 3.35 × 10
6
ty r
− 1
). However, not all regions had a decreasing trend
(Figure 4b). The most notable decreases, many of which were statistically signi fi cant, occurred near the
Daba Mountains in the northern part of the study area. In contrast, soil erosion increased slightly in the
southwestern plains and in hilly areas, and some of these increases were also statistically signi fi cant.
To evaluate the long ‐ term changes in soil erosion we identi fi ed the dates when the Mann ‐ Kendall test
revealed abrupt changes. Figure 5a shows three periods with distinctly different trends: 1980 to 1984, 1985
to 2006, and 2007 to 2015. When we separately performed regression analysis for the data from each period
(Figure 5b), we found that soil erosion decreased signi fi cantly (at a rate of 1.52 × 10
8
ty r
− 1
, p < 0.01) before
1984. Subsequently, soil erosion fl uctuated, but with an overall decrease by 0.06 × 10
8
ty r
− 1
, p < 0.05) until
2006. During the last period (2006 to 2015), soil erosion again decreased gradually, at an overall rate of
0.10 × 10
8
ty r
− 1
, p < 0.05).
3.3. Driving Forces for Soil Erosion Changes
The Pearson's correlation analysis results (Table 3) showed that climate and vegetation were the main cor-
relation factor relating the soil erosion change. Moreover, their correlation coef fi cients changed over time, In
Periods 1 and 3, climate signi fi cantly affected soil erosion change, especially on precipitation ( r = 0.7 and
0.52, respectively). However, in Period 2, vegetation signi fi cantly affected soil erosion change, especially
for on vegetation cover ( r = 0.59).
In addition, we established statistical model to quantify the impacts of the driving forces in Table 4 on soil
erosion using multiple linear regression. In Periods 1 and 3, regression analysis indicated that precipitation
(standardized B = 0.664, and 0.637, respectively) was the signi fi cant key factor for soil erosion change.
However, in Period 2, vegetation became the signi fi cant key factor for soil erosion change (standardized
B = − 0.391). All models produced good regression results ( R
2
= 0.375 – 0.566; adjusted R
2
= 0.370 – 0.564).
The dominant factors that controlled soil erosion differed among the periods. The soil erosion reduction that
occurred during Period I (1980 to 1984) was controlled by changes in climate, which explained 84.05% of the
Figure 3. Spatial distribution and changes over time in the land use and land cover (LULC) types from1980 to 2015.
Spatial distribution of LULC in 1980 (a) and 2015 (b); Spatial distribution of increases (c) and decreases (d) of a given
category of LULC.
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XIAO ET AL. 7o f1 3
total variation in soil erosion. However, vegetation became as important as precipitation for controlling soil
erosion during Period II (1985 to 2006), accounting for 51.35% of the variation. Finally, climate became as
important as vegetation for controlling soil erosion during Period III (2007 to 2015), accounting for 51.65%
of the variation. This temporal change in the factors that controlled soil erosion suggested that effects of
the vegetation improvement under the government ecological restoration programs became more
pronounced over time.
3.4. The Relationship Between Urban Development and Soil Erosion
The real per capita income of residents of the study area increased signi fi cantly in both urban and rural
areas, but the gap between urban and rural incomes increased from a ratio of 1.8 in 1985 to 3.0 in 2015
(Figure 6a). At the same time, urbanization (migration of rural residents to cities) was accelerating in the
Three Gorges Reservoir area. The proportion of the total population living in an urban area increased by
0.02 annually, from about 0.32 in 1985 to about 0.89 in 2015, and increased particularly rapidly after 2009
(Figure 6b). As large numbers of people moved into cities, the built ‐ up area increased rapidly (Table 2).
We also found a statistically signi fi cant contribution of urbanization on the decreasing of soil erosion from
1980 to 2015 (Figure 7).
4. Discussion
With ongoing environmental degradation and increasingly fragile ecosystems, environmental managers
must look beyond traditional approaches that focus on ecology and begin to consider the human aspects
of the problem (Feng et al., 2015). To achieve this goal, it's necessary to account for the key forces that drive
ecosystem change, including both natural and human forces. We found that soil erosion in the Three Gorges
Reservoir area reached 170 Mt per year in 2015. Soil erosion in the eastern region was signi fi cantly higher
than that in the western region. The region with the largest amount of soil erosion was mainly located near
the Daba Mountains. In general, an ecosystem's resistance to soil erosion depends on the ecosystem type and
Figure 4. Spatial pattern and temporal dynamic of soil erosion ( SE
a
) in the Three Gorges Reservoir area from 1982 to
2015. (a) Spatial distribution of SE
a
. (b) Trends in annual SE
a
, with × indicating areas with a statistically signi fi cant
trend ( p < 0.05).
Figure 5. (a) Detection of abrupt changes in annual soil erosion ( SE
a
) in the Three Gorges Reservoir area from 1982 to
2015. Turning points occur where the UF and UB curves intersect at a position above the threshold for statistical
signi fi cance based on the Mann – Kendall mutation test. (b) Trends of annual SE
a
during the study period. Arrows
indicate the signi fi cant turning points in 1984 and 2006 that were identi fi ed in (a).
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XIAO ET AL. 8o f1 3
vegetation cover; for example, dense grasslands protect the soil better than sparse forests (Sun, Miao, Hanel,
et al., 2019). The soil conservation function of different ecosystem types is strongest for forest, followed by
shrub and grassland communities (Xiao et al., 2017). In addition, the higher the vegetation cover, the stron-
ger the soil conservation function. However, our results show that in addition to these factors, the actual soil
conservation function is determined by the climate, topography, and socioeconomic factors, with different
relative strengths for each group of factors in different periods.
Since 1989, many ecological restoration projects have been implemented in our study area; as a result, a large
amount of sloping farmland (4,280 km
2
) has been transformed into shrub communities and forests, and
vegetation cover has continuously increased. This increase has helped to reduce soil erosion. From 1980
to 2015, soil erosion showed an overall decreasing trend, with soil erosion decreasing by
3.36 × 10
6
ty r
− 1
). However, not all regions showed a decreasing trend (Kong et al., 2015). Soil erosion
increased in hilly regions in the west, resulting in serious losses of soil and water. This resulted mainly from
the rapid urbanization and expansion of the built ‐ up area in this region, leading to greatly increased inten-
sity of human activity, and from increased precipitation, which together exacerbated soil erosion in this
region (Cao et al., 2017).
To evaluate the long ‐ term changes of soil erosion, we used the Mann ‐ Kendall mutation test to identify
abrupt changes and revealed three distinct periods. In the fi rst period, from 1980 to 1984, soil erosion
decreased signi fi cantly, possibly because of the signi fi cant decrease in precipitation during this period. In
the second period, from 1985 to 2006, soil erosion fl uctuated, but decreased slowly overall. In the third per-
iod, which began in 2006 (around the start of construction of the Three Gorges Dam), soil erosion again
showed a signi fi cant downward trend. Due to increasing urbanization after 2000 and the construction of
Three Gorges Dam in 2006, the areas where LULC change occurred were mainly distributed in the eastern
Table 3
Pearson's Correlation Analysis Results for the Multiscale Factors and Time Period Indexes
Category
Independent
variable
1980 – 1984
Period ‐ 2
2007 – 2015
Period ‐ 3
1980 – 2015 whole
period
Climate change Precipitation 0.700
**
0.521
**
0.520
**
0.273
**
Temperature − 0.320
**
0.226
**
0.277
**
0.147
*
NDVI − 0.150
**
− 0.523
**
− 0.092
*
− 0.671
**
VC − 0.167
**
− 0.590
**
ns − 0.667
**
Evapotranspiration ns ns − 0.229
**
− 0.197
**
LULC change Forestation − 0.108
**
**
ns 0.104
**
ns
Note . Only statistically signi fi cant values of Pearson's correlation coef fi cient are displayed; ns represents a nonsigni fi -
cant result. Abbreviations: NDVI, the normalized ‐ difference vegetation index; VC, vegetation cover.
*
p < 0.05.
**
p < 0.01.
Table 4
Regression Analysis Results for the Multiscale Factors and Time Period Indexes
Category Independent variable 1980 – 1984 Period ‐ 1 1985 – 2006 Period ‐ 2 2007 – 2015 Period ‐ 3 1980 – 2015 Whole period
Climate change Precipitation 0.664
**
0.331
**
0.637
**
0.287
**
ns 0.112
**
− 0.098
**
Vegetation change NDVI ns − 0.177
**
ns − 0.349
**
VC ns − 0.391
**
− 0.346
**
− 0.371
**
Evapotranspiration 0.181
**
ns − 0.167
**
− 0.104
**
LULC change Forestation ns ns ns ns
Urbanization ns − 0.207
− 0.188
**
− 0.176
**
R
2
/Adjusted R 0.566/0.564 0.490/0.487 0.375/0.370 0.553/0.549
Note . Only statistically signi fi cant values of standardized coef fi cients are displayed; ns represents a nonsigni fi cant result. Dependent variables are the changing
trend in per ‐ unit ‐ area soil erosion for Period ‐ 1, Period ‐ 2, Period ‐ 3, and Whole Period, respectively. The R
2
values represent goodness of fi t for multiple linear
regression models that account for the effects of the variables in each category of driving forces. Abbreviations: NDVI, the normalized ‐ difference vegetation
index; VC, vegetation cover.
*
p < 0.05.
**
p < 0.01.
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XIAO ET AL. 9o f1 3
and western parts of the study area (Yang et al., 2018). The main change type in the eastern region was an
increase in the area of forest, whereas the main change type in the western region was urban expansion.
Both changes were at the expense of a decreased area of cropland. The expansion of forests in the east
showed that the implementation of the government's ecological projects played a positive role in increasing
forest cover in this region (Sun, Miao, Hanel, et al., 2019). The development of cities in the western region in
response to migration of residents from rural areas to urban areas reduced the disturbance of vegetation by
human activities in eastern rural areas to some extent (Dominati et al., 2014). The rapid development of
cities in the western region and the increase of government revenue from taxation of economic activities
in these cities may be able to support the continued implementation of the government's ecological projects.
Another possible reason for the increasing vegetation cover is that construction of the Three Gorges Dam has
increased the groundwater content in areas near the reservoir and this, combined with increasing rainfall at
the same time, combined to promote vegetation growth in most of the surrounding areas (Haghjou
et al., 2014). The government's vegetation restoration projects clearly played a positive role in reducing soil
erosion in the region. Of the driving forces we analyzed, vegetation accounted for a large proportion (70%) of
the total variation in soil erosion. By acting on local ecosystem or on local constraints that control ecological
restoration, accounting for these driving forces can improve restoration success (Karlen et al., 2014).
Our results are preliminary and apply best to our study area; they must be replicated and tested in areas with
different characteristics to con fi rm the overall validity of our method and learn how to adapt it for use in
other areas. Nonetheless, the problems solved by the new method deserve attention, particularly in terms
of how it accounted for human driving forces such as urbanization and LULC change (Zheng et al., 2019).
If the methodology is suitably modi fi ed to account for local conditions,
it will allow policy makers and restoration managers in other areas to
design more effective restoration strategies and will provide a theoretical
basis for simultaneously improving environmental protection and socioe-
conomic development (Krois & Schulte, 2014). As this approach matures,
it will provide important solutions to the poverty trap in China and
elsewhere.
As the proportion of the rural population in our study area continued to
decrease, the proportion of the labor force engaged in primary industries
such as agriculture also continued to decrease. As a result of this
long ‐ term social shift, the contradiction between traditional agriculture
(which creates high pressure on the environment) and ecological protec-
tion has gradually weakened, and this trend has been conducive to the
natural restoration of vegetation even in the absence of government
restoration programs. Previous research also found a signi fi cant positive
correlation between the urbanization rate and NDVI trends in our study
area (Lee et al., 2014).
Figure 7. Relative contribution importance of the driving forces associated
with changes in total annual soil erosion.
Figure 6. Changes from 1985 to 2015 in (a) the per capita real income of urban and rural residents and (b) the
populations of rural and urban areas and the associated urbanization rate.
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In general, environmental goals cannot be separated from economic development, since human survival
depends on a healthy environment. This dependence provides a clear path to success: in fl uencing the liveli-
hood of residents of environmentally fragile regions so that they can continue earning a living without
damaging their environment. Environmental degradation and poverty are mutually reinforcing processes
(i.e., they together create the poverty trap). Investing in environmental assets and management is a crucial
strategy to combat the poverty trap and simultaneously achieve both environmental restoration and poverty
alleviation (Miao et al., 2019). In the Three Gorges Reservoir area, urbanization has accelerated during the
study period, leading to less pressure on the rural environment and an increase in the built ‐ up area in cities.
Previous research showed that the growth rate of the built ‐ up areas in cities was faster than that of the non-
agricultural population in the urban area, which agrees with the present results (Zhang et al., 2014).
The effects of this trend are evident in our study area. Due to the rapid economic growth that has
occurred in the study area, the acceleration of urbanization, and the large and growing difference
between urban and rural incomes, a large proportion of the rural population has migrated to cities and
towns, and much of this migration came from the northeastern mountainous areas, with former residents
of these areas moving to the main urban areas in the western part of our study area. This large change in
the proportions of urban and rural residents suggest that an equally huge social transformation is under-
way (Liebig et al., 2014).
This migration has been accompanied by the implementation of a large number of ecological restoration
projects in the eastern region. The migration has weakened human impacts on the source region for the
migrants, while simultaneously improving vegetation cover in this region through government projects;
the result was greatly improved vegetation cover and greatly reduced soil erosion risk. Our research con fi rms
our hypothesis that measures to control the driving forces responsible for ecological degradation through
targeted ecological restoration measures can eliminate the blind spot in traditional ecological restoration
planning, which focused on ecological factors and largely ignored human factors. For example, large rural
populations place a proportionally large pressure on their environment (Xiao et al., 2020). To relieve this
pressure, migration to urban areas can be promoted through education, which allows migrants to obtain
other forms of employment, and social welfare programs, such as providing social services (e.g., access to
medical care and schools for their children) that make the move to a city easier. Ecological restoration in
the Three Gorges Reservoir area is aimed at achieving sustainable socioeconomic development (Marenya
et al., 2014). Therefore, in dealing with the relationship between ecological restoration and this develop-
ment, we should seek a balance between development and restoration rather than relying exclusively
(and simplistically) on vegetation restoration.
5. Conclusions
Research such as the present study is important because it reveals the response of soil erosion to both eco-
logical factors (climate, afforestation) and social factors (urbanization, ecological migration). In our study
of the Three Gorges Reservoir area, we found that both ecological and socioeconomic factors were driving
forces for mitigating soil erosion, but with different relative strengths at different times. Our study meth-
ods can, with suitable modi fi cation to account for local conditions, help guide the restoration of ecologi-
cally sensitive areas in other regions of China and elsewhere in the world. We found that soil erosion
gradually decreased throughout the study period, though at different rates during different parts of the
study period and with changes in the relative strengths of the driving forces between these periods.
During the fi rst part of the study period, soil erosion decreased signi fi cantly, and our correlation analysis
suggested that decreasing precipitation was responsible. During the second period, soil erosion fl uctuated
but still decreased slowly. During the third period, soil erosion again showed a signi fi cant decreasing
trend, but in this period, the change resulted from socioeconomic factors such as a rapidly increasing
urbanization rate.
Our results demonstrate that the government's restoration programs, and particularly afforestation, have
improved the vegetation cover and decreased soil erosion. However, they have also displaced large numbers
of rural residents to the region's rapidly growing cities. Because this migration will challenge the ability of
local residents to earn a living, we propose that the government continue to increase its afforestation efforts,
but that they complement these efforts with programs that improve employment opportunities for displaced
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XIAO ET AL. 11 of 13
residents. This approach will simultaneously support economic development and ecological restoration, and
particularly an ongoing reduction of soil erosion. Our proposed approach reveals that the government's pro-
grams in our study area have succeeded because they focused on the key driving forces (both ecological and
socioeconomic) that cause degradation or promote restoration. Moreover, our approach revealed different
dominant factors that controlled soil erosion in each part of the study period. These differences will help
restoration managers understand the changing factors that control both restoration and its relationship with
socioeconomic development, thereby offering opportunities to develop more effective programs for accom-
plishing both goals.
Con fl ict of Interest
The authors declare no con fl icts of interest relevant to this study.
Data Availability Statement
the fi gures and tables are available at this site (http://www.geodoi.ac.cn/edoi.aspx?DOI=10.3974/
geodb.2020.02.17.V1). All data sources are public record.
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Acknowledgments
This study was supported by the
National Natural Science Foundation of
China (Nos. 41571482 and 31700544),
the Science and Technology Project of
Chongqing Education Commission of
China (kj1501102), the Sichuan Sci &
Tech Department (grant number
2020YFS0029), the Chinese Academy of
Sciences (CAS) “ Light of West China ”
Program (grant number
2016XBZG_XBQNXZ_B_005), the CAS
Key Laboratory of Mountain Ecological
Restoration and Bioresource Utilization
& Ecological Restoration Biodiversity
Conservation Key Laboratory of
Sichuan Province Program (grant
number kxysws1901), the CAS
Research and Development of Scienti fi c
Instrument and Equipment Program
(grant number YJKYYQ20190064), and
the Ministry of Education of China Key
Research Center Projects (grant
number 16JJD630011). We thank Geoff
Hart for his help in writing this paper as
well as the journal's Editors and
anonymous reviewers for their
comments on an earlier version of this
manuscript.
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E409 – E426. https://doi.org/10.1175/BAMS ‐ D ‐ 18 ‐ 0258.1
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GeoHealth
XIAO ET AL. 13 of 13
... Soil erosion and sedimentation facilitate the transport of contaminants present in the sediment from terrestrial environments to aquatic systems (Wijesiri et al., 2019;Boardman and Foster, 2021), representing one of the principal mechanisms by which pollutants can pose a risk to human populations (Akram et al., 2018a,b;Hashmi and Varma, 2018). Consequently, among these environmental concerns, changes in surface processes, particularly soil erosion and sedimentation, have received significant attention (Bao et al., 2015a;Wang et al., 2020;
Xiao et al., 2020;
Ren et al., 2021). ...
Spatial and temporal variation of nearshore significant wave height in the Three Gorges Reservoir, China
Article
May 2023
ECOL INDIC
Hangyu Xie
Jiaorong Lyu
Yuhai Bao
Xiubin He
The study of wave characteristic changes is critical for understanding the role of wave erosion in the shoreline erosion of reservoirs and its subsequent impact on environmental pollution. This study utilizes RBRvirtuoso D-wave-pressure-based wave gauges to make in situ observations of the nearshore significant wave height (SWH) in the Three Gorges Reservoir. The differential and impact factors affecting the SWH under varying water levels, in the main and tributary streams, and shoreline sections are analyzed. This research also investigates the alteration of the frequency distribution of the SWH. The findings indicate that the average SWH increases as the water level increases, reaching 1.2 cm, 1.5 cm, and 1.9 cm for water levels of 150 m, 165 m, and 175 m, respectively, with a SWH frequency distribution curve that becomes increasingly smooth. The average SWH in the mainstream is 2.9 times larger than that in the tributaries, with the former having a smoother frequency distribution curve. The average SWHs in different shoreline sections are inconsistent at the same water level, with the Badong (down-stream) section near the Three Gorges Dam exhibiting a significantly higher average SWH than the Zhongxian (midstream) section further from the dam. When shipping activities intensify, there is often a marked increase in the magnitude of the SWH. The SWH in narrower reservoir sections is significantly greater than that in wider sections, with average measurements of 2.2 cm and 1.4 cm, respectively. Fluctuations of the water level, shipping activities, and other factors in the Three Gorges Reservoir have a significant impact on the alteration of the nearshore SWH, and changes in the SWH from low to high water levels may result in changes in both the spatial and temporal patterns of shoreline erosion. These alterations can, in turn, affect sediment and nutrient transport, potentially exacerbating environmental pollution issues.
... To assess variation trends of NDVI and climate (precipitation and temperature) throughout the 2000-2010 study period, we used a linear least-squares regression model to obtain the changing trends of every pixel by fitting a linear equation of NDVI or climate variables as a function of the variable of year to obtain an image of changing slopes [22]. The linear least-squares regression method, which is a commonly used method in trend analysis
[23]
, was applied as follows: ...
Vegetation Growth Trends of Grasslands and Impact Factors in the Three Rivers Headwater Region
Article
Full-text available
Dec 2022
Xiaoping Sun
Areas of grassland improvement and degradation were mapped and assessed to identify the driving forces of change in vegetation cover in the Three Rivers headwater region of Qinghai, China. Based on linear regression at the pixel level, we analyzed the vegetation dynamics of the grasslands of this region using MODIS NDVI data sets from 2000 to 2010. Correlation coefficients were computed to quantitatively characterize the long-term interrelationship between vegetation NDVI and precipitation/temperature variability during this period. The use of time series residuals of the NDVI/precipitation linear regression to normalize the effect of precipitation on vegetation productivity and to identify long-term degradation was extended to the local scale. Results showed that significant improvements occurred in 26.4% of the grassland area in the Three Rivers Headwater region between 2000 and 2010. The study area, which represents about 86.4% of the total grassland area of this headwater region, showed a general trend of improvement with no obvious trend of degradation.
... The soil conservation function has an important position in ecosystem services, has a fundamental role in many aspects, such as soil formation, water containment, and vegetation fixation, and provides ecological security and system services. The principles of soil conservation calculations in this study are as follows [58,
59]
. ...
Urban Expansion Was the Main Driving Force for the Decline in Ecosystem Services in Hainan Island during 1980–2015
Article
Full-text available
Nov 2022
Int J Environ Res Publ Health
Jia Geng
Mingsheng Yuan
Shen Xu
Dong Xu
Hainan Island is one of China’s most ecologically diverse areas. Human activities and climate change have recently influenced Hainan Island’s ecosystem services. Therefore, scientific methods are urgently needed to investigate the characteristics of these services’ spatial and temporal variations and their driving mechanisms for maintaining Hainan Island’s biodiversity and high-quality ecological conservation. Based on multivariate remote sensing and reanalysis data, this study analysed the spatial and temporal variations in water retention, soil conservation, carbon sequestration, and oxygen release services on Hainan Island during 1980–2015 using various ecosystem service models such as INVEST, CASA and RULSE. Then, we analysed different ecosystem service drivers using a random forest model. The results indicated that (1) from 1980 to 2015, the change characteristics of different ecosystem types (arable, forest, and grassland) decreased, and the proportion of decrease was 0.98%, 0.55% and 0.36%, respectively. Built-up and water increased significantly, and the proportion of increase reached 1.46% and 0.51%, respectively. (2) Hainan Island’s functions of water retention, soil conservation, carbon sequestration, and oxygen release services decreased from 23.31 billion m3, 2.89 billion t, 9.68 million t and 56.05 million t in 1980 to 23.15 billion m3, 2.79 billion t, 9.42 million t and 55.53 million t in 2015, respectively. The high value area was mainly distributed in Hainan Island’s central mountainous area, and the low value area was mainly distributed in the lower-elevation coastal area. (3) In the past 35 years, urban expansion has been the leading factor in the reduction of Hainan Island’s ecosystem service capacity. However, its central nature reserve and other forms of ecological protection have improved its ecosystem service capacity, which has alleviated the overall declining trend of its amount of ecosystem service functions. (4) The driving forces for the spatial distribution of Hainan Island’s ecosystem services were analysed using a random forest algorithm, which indicated that its spatial distribution was mainly driven by rainfall, soil moisture, actual evapotranspiration, maximum temperature, and minimum temperature. This study is expected to help planners develop effective environmental policies to accommodate the potential ecological risks associated with urban expansion during the construction of Hainan Island’s future free trade port while filling the gaps in existing studies.
... Xiao et al. (2018) studied the characteristics of soil erosion and conservation and assessed the ecosystem service potential in Chongqing City. Additionally, many researchers have studied the soil and water loss characteristics in the watershed of Three Gorges Reservoir which is the largest waterbody in Chongqing City (Liu et al. 2016;Chu et al. 2020;
Xiao et al. 2020)
. However, to the best of our knowledge, few studies are performed on the three regions in Chongqing City to provide references and guidelines for controlling regional soil and water loss. ...
Spatiotemporal changes of soil and water loss (2012–2019) in three government divided regions, Chongqing Municipality, China
Article
Full-text available
Oct 2022
Water Sci Tech Water Supply
Yi Zhang
Yang Lu
Jingsong Shi
Jianmei Yan
Understanding the changes in soil and water loss is important to make the regional sustainable development strategies for administrative department. This study compiled a series of datasets from 2012 to 2019 at the county scale to investigate the changes in soil and water loss in three government divided regions, i.e., urban region (UR), northeast region (NER) and southeast region (SER) in Chongqing Municipality, China. The area percentage of soil and water loss over moderate degree (OMD) in each year and change rate for the area of soil and water loss (CR) on the basis in 2012 for each region were compared. The area of soil and water loss decreased by 22.3%, 18.7% and 14.2% in the UR, NER and SER, respectively, from 2012 to 2019. The area of soil and water loss in NER almost accounted for 50% of the total area of soil and water loss in Chongqing City. The OMD decreased from 66.06% in 2012 to 24.84% in 2019. The CR always presented significantly declined trend (P < 0.05) with the year in the UR, NER and SER, respectively. Our results are valuable to developing reasonable conservation strategies for the local government to control soil and water loss.
HIGHLIGHTS
Changes in soil and water loss of UR, NER and SER in Chongqing City are examined.;
The UR shows the highest decline in soil and water loss from 2012 to 2019.;
The soil and water loss OMD reduces from 2012 to 2019.;
The change rate for the area of soil and water loss markedly decreases with the year across all regions.;
The strategies for the development of three regions are provided based on their specificities.;
... Consequently, the process of soil erosion gets augmented into a serious environmental and quasi-natural hazard which aAects the overall agricultural productivity and the consequent economic welfare of various nations. Soil erosion is frequently regarded as one of the important driving factors of ecological degradation in an area
(Xiao et al. 2020
). This hazard is extremely widespread and spreads across a variety of landscapes and ecosystems all over the world. ...
Monitoring the temporal dimension of soil erosion in the Mayurakshi Basin, India: A novel approach integrating RUSLE, Shannon’s Entropy and Landscape Ecological Metrics
Article
Jul 2022
Subha Roy
Somasis Sengupta
Sukhendu Mistry
Jaya Chatterjee
Post-farming land restoration schemes exhibit higher soil aggregate stability and organic carbon: Evidence in the Three Gorges Reservoir Area, China
Article
Jun 2023
CATENA
Chen Han
Minxin Song
Qiang Tang
A. L. Collins
Linking landscape dynamics to the relationship between water purification and soil retention
Article
Full-text available
Feb 2023
Chunbo Huang
Dengyue Zhao
Qipeng Liao
Mingzhu Xiao
Landscape pattern is vital for supplying ecosystem services, and demonstrating the interactions among landscape dynamics and multiple ecosystem services is a key scientific basis for ecosystem management. As a typical ecologically vulnerable region in China, the Three Gorges Reservoir Area (TGRA) suffers from both severe soil loss and non-point pollution. Although many ecological restoration projects have been implemented to control sediment and pollutants into the reservoir, it is still unclear whether and how reforestation improves both soil retention and water quality. Therefore, we proposed a conceptual framework to couple landscape dynamics and multiple ecosystem services, in which drivers could directly affect two ecosystem services or indirectly affect them by affecting landscape dynamics. Ecological models were applied to assess water purification and soil retention, and spatial analysis tools were adopted to demonstrate their spatial relationship. Structural equation model documented the effect values of the conceptual framework, meanwhile, relative importance analysis reported the contributions of drivers to forest cover, water purification and soil retention. Our results showed that nitrogen loss and soil loss of the TGRA both decreased from 2001 to 2015, indicating an improvement in both water purification and soil retention. However, correlation analysis revealed significant spatial heterogeneity in their relationship, which may partly be explained by the district and county differences in human activities and development policies. Structural equation model documented the correlation coefficient between nitrogen loss and soil retention was -0.71. Relative importance of forest cover to the nitrogen loss was more than 50%, indicating that water purification could mainly be explained by the effect of forest cover on nitrogen loss. Annual precipitation contributed 26.9% to soil retention, and the overall contribution of climate conditions was 52.1%, which indicated the direct and indirect effects of climate conditions are both important for soil retention. Moreover, the landscape plannings of vegetation restoration were suggested for these key ecological zones in the TGRA to synergistically improve two ecosystem services.
Balancing the international benefits and risks associated with implementation of ecological policy on the Qinghai-Tibet Plateau, China
| https://www.researchgate.net/publication/354099576_Effects_of_Ecological_Restoration_Measures_on_Soil_Erosion_Risk_in_the_Three_Gorges_Reservoir_Area_Since_the_1980s |
Fiscal policy, inequality, and the poor in the developing world | Request PDF
Request PDF | On Dec 1, 2016, Nora Lustig published Fiscal policy, inequality, and the poor in the developing world | Find, read and cite all the research you need on ResearchGate
Fiscal policy, inequality, and the poor in the developing world
December 2016
DOI: 10.35188/UNU-WIDER/2016/208-3
ISBN: 978-92-9256-208-3
... Several studies also suggest that poverty and inequality in South Africa could have been higher still without its current socio-fiscal policy, which is relatively more redistributive than in most African countries (Inchauste et al., 2015;Higgins and Lustig, 2016;
Lustig 2017;
World Bank, 2017). These studies are based on an incidence-based method, which consists in imputing taxes and benefits to households using surveys containing both household characteristics and information on tax liability and benefit receipt. ...
... Our approach is different and based on microsimulation techniques, which facilitate the simulation of counterfactual scenarios. Among these studies, Inchauste et al. (2015) showed that South Africa fared better in reducing income inequality compared to most Further evidence using fiscal incidence analyses shows that for Zambia, Tanzania, and Ghana, the poor are impoverished by the fiscal system; headcount poverty increased after taxes and state transfers compared to the before scenario (Higgins and Lustig, 2016;
Lustig, 2017;
de la Fuente et al., 2017). As shown later, we find supporting evidence using microsimulation techniques: in all countries but South Africa, and in particular Ghana, Zambia, and Mozambique, poverty increases after taxes and transfers while inequality is only marginally reduced. ...
... These effects are small, a reduction of 3-4 points, but not necessarily much smaller than in other developing regions of the world. On average, tax-benefit systems in Latin America decrease the Gini coefficient by 2.7 points (from 50.8 to 48.1), according to
Lustig (2017)
for the year 2011. Admittedly, a lot more redistribution is operated in rich countries: the Gini coefficient for the EU28 falls from 50.1 to 29.2 on average when market income is compared to disposable income. ...
Learning from the ʻbestʼ: The impact of tax-benefit systems in Africa
... Economists conducted a study on a sample of 17 countries and found that in 15 countries the tax system contributes to poverty reduction and is progressive, but in 10 of them at least a quarter of the poor pay more in taxes than they receive in transfers. Researchers call this financial impoverishment
(Lustig, 2016)
. It should be noted that financial impoverishment means that in many developing countries a large proportion of the population cannot pay for basic needs, such as food, health care, and education. ...
... The research methodology is based on a combination of linear regression and CEQ methodology that was designed by Lustig
(Lustig, 2016;
Lustig & Higgins, 2013) to analyse the impact of taxation and social spending on inequality and poverty in individual countries and provide a roadmap for governments, multilateral institutions, and nongovernmental organisations in their efforts to build societies with lower inequality and poverty. It should be noted that the consideration of social expenditures is counted in the equivalent of the cost of services provided. ...
Taxation, Inequality, and Poverty: Evidence from Ukraine
The aim of the article is to assess the impact of taxes on poverty and inequality in Ukraine and provide recommendations on how taxation should be used to address problems of inequality and poverty. The research methodology is based on a combination of linear regression and commitment to equity (CEQ) methodology, which was designed by Lustig to analyse the impact of taxation and social spending on inequality and poverty in individual countries. The dataset consists of data from the World Inequality Data Base and data from State Statistic Service of Ukraine.
The analysis shows that income tax reform in Ukraine should not take place in the context of changing tax rates and tax periods but in the context of shifting the tax burden from the poor to the rich and preventing aggressive tax planning. Also, the results of the analysis show that the Ukrainian government’s policy of reducing free education and health services may contribute to poverty if the government does not change its redistributive policies.
The article contributes to the academic literature on the impact of taxation on poverty and inequality in developing countries. The practical results obtained in the paper are useful for developing countries’ governments to design poverty- and inequality-sensitive tax policies.
... In summary, based on the evidence presented in this study, we can affi rm that fi scal policy, more specifi cally the structure of expenditures and taxes of the states, is important for reducing inequality in income distribution, which is in line with the literature (Chu et al., 2004;Afonso et al., 2010;Bastagli et al., 2012;Azevedo et al., 2014;
Lustig, 2016)
. However, those responsible for conducting the fi scal policies of the Brazilian states must be aware that an increase in special charges worsens inequality, and this is strongly shown in the results of this study. ...
Giving with one hand and taking away with the other
... The notable exceptions in this literature review are South Africa and Egypt, where the fiscal systems actually reduced poverty; other authors have similarly attributed national poverty reduction to the Namibia's fiscal system (Sulla et al. 2017). Five out of 25 countries have fiscal systems that increase poverty with respect to the extreme poverty line of US$1.25/day, rising to 15 countries when the poverty line is pegged at the US$4/day level
(Lustig, 2016a)
. ...
The Effects of Fiscal Policy on Poverty and Inequality in The Gambia
Research
The overall objective of this study is to assess the impact of the fiscal system on poverty and inequality in The Gambia as of 2015. Furthermore, it also evaluated the
distributional effects of recent fiscal policy reforms in The Gambia. The assessment was based on the Commitment to Equity (CEQ) Methodology with data from the Integrated Household Survey of 2015 and fiscal administrative data from various government agencies.
... For example, Ogbu (2012), observing the poverty problem in Nigeria, suggests how industrial policies focused on improving the manufacturing sector, in addition to government expenditure that is targeted at infrastructure investment 1 In this regard, several other studies have found that spending on higher education that is disproportionate to basic education spending can also lead to higher income inequality. See, for example,
Lustig (2016)
and Inchauste and Lustig (2017). and transforming the agriculture sector may support inclusive growth. ...
When Does Foreign Direct Investment Lead to Inclusive Growth?
Foreign Direct Investment (FDI) is widely considered among the most effective instruments for the promotion of economic development. However, not all FDI leads to inclusive economic growth, lifting the welfare of the poorest groups. This paper examines the conditions under which FDI can effectively lead to inclusive growth. By using a fixed effects regression with annual data for 67 countries from 1990 to 2015, we find that FDI has a positive effect on inclusive growth when there is a sufficiently large manufacturing sector and infrastructure base in the host country. We also indirectly find that FDI has a positive effect on inclusive growth when the host country has a large service sector. These not very optimistic results emphasize the critical importance of the host country’s absorptive capacity. A smaller technological or knowledge gap with the foreign firms is required for FDI to lead to more linkages and spillovers, and ultimately job creation for the poor. The results cast doubt on development strategies that rely on FDI as a sufficient policy for inclusive growth.
... However, the importance of fiscal policy has regained its importance as a result of the work of Piketty (2015). The effect of fiscal policy on income inequality has recently gained momentum (Clifton et al., 2020;
Lustig, 2016;
Martorano, 2018). Applying the Kneller et al. (1999) and Muinelo and Roca-Sagales (2011) framework to the modelling of the impact of fiscal variables on inequality in Pakistan in period t will be the function of a set of fiscal variables (FV) and non-fiscal variables (NFV). ...
The Impact of Fiscal Policy on Income Inequality: A Case Study of Pakistan
Article
Full-text available
Jun 2021
Suhrab Khan
Ihtsham Ul Haq Padda
This study investigates the impact of various fiscal policy instruments on the income inequality of Pakistan using an Auto Regressive Distributed Lag (ARDL) model on annual data. We find that direct taxes reduce income inequality, measured using the Gini index, while indirect taxes increase disparities. As the major portion of tax revenues are indirect taxes, the current tax regime of Pakistan does not achieve income redistribution. Similarly, development expenditures have significantly reduced income inequality, likely through the creation of employment opportunities. On the other hand, the overall fiscal deficit increases income inequality, due to a rising public debt financed by (regressive) indirect taxes. This study suggests that in the case of Pakistan, where direct taxes are low, a large shadow economy exists, and weak tax administration prevails, an increase in development expenditures and broadening of the tax base of direct taxes should be the main fiscal policy tools for income redistribution. Moreover, persistent high fiscal deficits in the long run should be avoided. Finally, governments should reduce educational inequalities and promote democratic values in the country in order to promote greater fairness in distribution of income.
... In summary, based on the evidence presented in this study, we can affi rm that fi scal policy, more specifi cally the structure of expenditures and taxes of the states, is important for reducing inequality in income distribution, which is in line with the literature (Chu et al., 2004;Afonso et al., 2010;Bastagli et al., 2012;Azevedo et al., 2014;
Lustig, 2016)
. However, those responsible for conducting the fi scal policies of the Brazilian states must be aware that an increase in special charges worsens inequality, and this is strongly shown in the results of this study. ...
GIVING WITH ONE HAND AND TAKING AWAY WITH THE OTHER ° DANDO COM UM MÃO E TIRANDO COM A OUTRA
Article
Full-text available
Dec 2019
Estud. econ.
Carlândia brito santos Fernandes
Marina Silva Cunha
Marcos Roberto Vasconcelos
This study analyzes the impact of fi scal policy on income inequality for the Brazilian states over the period 2004-2014. Using the GMM system, we fi nd robust evidence that, while increases in total expenditure, spending with social assistance and security, and expenditure on infrastructure reduce inequality, total and capital revenues and expenditures related to public debt increase inequality. Thus, the net effect of fi scal policy on inequality may not be positive mainly because the tax system is still very regressive and many of the resources are spent on debt. Therefore, the discussion of how to determine and qualify social spending levels in Brazil, which are necessary to fi ght poverty and reduce social and income inequalities, is directly related to the revision of the tax collection system. Resumo Este estudo analisa o impacto da política fi scal sobre a desigualdade de renda para os estados brasileiros no período 2004-2014. Utilizando system GMM, encontra-mos evidências robustas de que, enquanto o aumento no gasto total, gastos com assistência social e segurança, e gastos em infra-estrutura reduzem a desigualdade, as receitas totais e de capital e os gastos relacionados à dívida pública aumentam a desigualdade. Assim, o efeito líquido da política fi scal sobre a desigualdade pode não ser positivo, principalmente porque o sistema tributário ainda é muito regres-sivo e muitos dos recursos são gastos em dívidas. Portanto, a discussão sobre como determinar e qualifi car os níveis de gastos sociais no Brasil, necessários para combater a pobreza e reduzir as desigualdades sociais e de renda, está diretamente relacionada à revisão do sistema de arrecadação de impostos. Palavras chave: política fi scal, gasto público, desigualdade, estados brasileiros. Códigos JEL: O10, O15, E62. Estudios económicos N° 73, Julio-Diciembre 2019. 43-70 45 GIVING WITH ONE HAND AND TAKING AWAY WITH THE OTHER
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Show abstract
... In summary, based on the evidence presented in this study, we can affi rm that fi scal policy, more specifi cally the structure of expenditures and taxes of the states, is important for reducing inequality in income distribution, which is in line with the literature (Chu et al., 2004;Afonso et al., 2010;Bastagli et al., 2012;Azevedo et al., 2014;
Lustig, 2016)
. However, those responsible for conducting the fi scal policies of the Brazilian states must be aware that an increase in special charges worsens inequality, and this is strongly shown in the results of this study. ...
GIVING WITH ONE HAND AND TAKING AWAY WITH THE OTHER ° DANDO COM UM MÃO E TIRANDO COM A OUTRA
Article
Full-text available
Dec 2019
Estud. econ.
Marina Silva Cunha
Marcos Roberto Vasconcelos
Carlândia brito santos Fernandes
This study analyzes the impact of fi scal policy on income inequality for the Brazilian states over the period 2004-2014. Using the GMM system, we fi nd robust evidence that, while increases in total expenditure, spending with social assistance and security, and expenditure on infrastructure reduce inequality, total and capital revenues and expenditures related to public debt increase inequality. Thus, the net effect of fi scal policy on inequality may not be positive mainly because the tax system is still very regressive and many of the resources are spent on debt. Therefore, the discussion of how to determine and qualify social spending levels in Brazil, which are necessary to fi ght poverty and reduce social and income inequalities, is directly related to the revision of the tax collection system. Resumo Este estudo analisa o impacto da política fi scal sobre a desigualdade de renda para os estados brasileiros no período 2004-2014. Utilizando system GMM, encontra-mos evidências robustas de que, enquanto o aumento no gasto total, gastos com assistência social e segurança, e gastos em infra-estrutura reduzem a desigualdade, as receitas totais e de capital e os gastos relacionados à dívida pública aumentam a desigualdade. Assim, o efeito líquido da política fi scal sobre a desigualdade pode não ser positivo, principalmente porque o sistema tributário ainda é muito regres-sivo e muitos dos recursos são gastos em dívidas. Portanto, a discussão sobre como determinar e qualifi car os níveis de gastos sociais no Brasil, necessários para combater a pobreza e reduzir as desigualdades sociais e de renda, está diretamente relacionada à revisão do sistema de arrecadação de impostos. Palavras chave: política fi scal, gasto público, desigualdade, estados brasileiros. Códigos JEL: O10, O15, E62. Estudios económicos N° 73, Julio-Diciembre 2019. 43-70 45 GIVING WITH ONE HAND AND TAKING AWAY WITH THE OTHER
... Em resumo, a partir das evidências apresentadas neste trabalho, pode se afirmar que a política fiscal, mais especificamente a estrutura de gastos das unidades federativas, mostra-se importante para a redução da desigualdade da distribuição de renda, em consonância com a literatura (Chu et al., 2004;Afonso, Schuknecht e Tanzi, 2010;Bastagli, Coady e Gupta, 2012;Azevedo et al, 2014;
Lustig, 2016)
. No entanto, os responsáveis pela condução das políticas fiscais das unidades federativas brasileiras precisam estar atentos ao fato de que o aumento dos encargos especiais piora a desigualdade. ...
IMPACTOS DA POLÍTICA FISCAL NA DESIGUALDADE DA DISTRIBUIÇÃO DE RENDA: UMA ANÁLISE PARA AS UNIDADES DA FEDERAÇÃO BRASILEIRA
Conference Paper
Full-text available
Jul 2018
Carlândia brito santos Fernandes
Marina Silva Cunha
Marcos Roberto Vasconcelos
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(Lustig 2016;
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Wolfgang Hein
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| https://www.researchgate.net/publication/337248849_Fiscal_policy_inequality_and_the_poor_in_the_developing_world |
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Literature Review
The dorsal motor nucleus of the vagus and regulation of pancreatic secretory function: Dorsal vagal nucleus and the pancreas
June 2012
Experimental Physiology98(1)
DOI: 10.1113/expphysiol.2012.066472
Source
PubMed
Authors:
<here is a image 510b7b6397e7077a-1b86464cba35fb7f>
Bashair M. Mussa
University of Sharjah
<here is a image 2a5b636dd27c146c-2ae59fe1e195a208>
Anthony Verberne
University of Melbourne
Abstract and Figures
Recent investigation of the factors and pathways that are involved in regulation of pancreatic secretory function (PSF) has led to development of a pancreatic vagovagal reflex model. This model consists of three elements including pancreatic vagal afferents, the dorsal motor nucleus of the vagus (DMV) and pancreatic vagal efferents. The DMV has been recognized as a major component of this model and so this review focuses on the role of this nucleus in regulation of PSF. Classically, the control of the latter has been viewed as being dependent on gastrointestinal (GI) hormones and vagovagal reflex pathways. However, recent studies have suggested that these two mechanisms act synergistically to mediate pancreatic secretion. The DMV is the major source of vagal motor output to the pancreas and this output is modulated by various neurotransmitters and synaptic inputs from other central autonomic regulatory circuits including the nucleus of the solitary tract. Endogenously occurring excitatory (glutamate) and inhibitory (γ-aminobutyric acid, GABA) amino acids have a marked influence on DMV vagal output to the pancreas. In addition, a variety of neurotransmitters and receptors for GI peptides and hormones have been localized in the DMV emphasizing the direct and indirect involvement of this nucleus in control of PSF.
<here is a image 80415738ce457aca-7f834eb4c1987022>
Schematic diagram depicting the relationship between the area postrema (AP), the dorsal motor nucleus of the vagus (DMV), the nucleus of the solitary tract (NTS) in the dorsal medulla oblongata and the branches of the thoracic and subdiaphragmatic abdominal vagal nerve trunks …
<here is a image 6abe719199a7f8c8-68cb86bb47eec9db>
Schematic diagram showing the basic components of the pancreatic vagovagal reflex Vagal afferents arising from the pancreas, as well as from the stomach and other parts of the gastrointestinal tract, have their somata in the nodose ganglion and project into the NTS. The NTS neurons, in turn, project to the preganglionic vagal motor neurons of the DMV. Abbreviations: DMV, dorsal motor nucleus of the vagus; and NTS, nucleus of the solitary tract. …
Figures - uploaded by
Bashair M. Mussa
Experimental Physiology
Exp Physiol 98.1 (2013) pp 25–37 25
Review Article
Review Article
The dorsal motor nucleus of the vagus and regulation of
pancreatic secretory function
Bashair M. Mussa and Anthony J. M. Verberne
University of Melbourne, Department of Medicine, Clinical Pharmacology and Therapeutics Unit, Austin Health, Heidelberg, Victoria 3084, Austral ia
New Findings
! What is the Topic of this review?
This review describes new evidence for the control of pancreatic exocrine and endocrine
secretion by the dorsal motor nucleus of the vagus. It describes the effects of several
gastrointestinal peptides on pancreatic secretion and considers their sites of action in the
vago-vagal reflex pathway.
! What advances does it highlight?
This review draws together recent electrophysiological, anatomical and pharmacological
studies to provide a state-of-art view of the parasympathetic control of the exocrine and
endocrine pancreas.
Recent investigation of the factors and pathways that are involved in regulation of pancreatic
secretory function (PSF) has led to development of a pancreatic vagovagal reflex model. This
model consists of three elements, including pancreatic vagal afferents, the dorsal motor nucleus
of the vagus (DMV) and pancreatic vagal efferents. The DMV has been recognized as a major
component of this model and so this review focuses on the role of this nucleus in regulation of
PSF. Classically, the control of the PSF has been viewed as being dependent on gastrointestinal
hormones and vagovagal reflex pathways. However, recent studies have suggested that these two
mechanisms act synergistically to mediate pancreatic secretion. The DMV is the major source of
vagal motor output to the pancreas, and this output is modulated by various neurotransmitters
and synaptic inputs from other central autonomic regulatory circuits, including the nucleus of
the solitary tract. Endogenously occurring excitatory (glutamate) and inhibitory amino acids
(GABA) have a marked influence on DMV vagal output to the pancreas. In addition, a variety of
neurotransmitters and receptors for gastrointestinal peptides and hormones have been localized
in the DMV, emphasizing the direct and indirect involvement of this nucleus in control of PSF.
(Received 3 April 2012; accepted after revision 28 May 2012; first published online 1 June 2012)
Correspondin g author A. J. M. Verberne: University of Melbourne, Clinical Pharmacology & Therapeutics Unit, Austin
Health, Heidelberg, Victoria 3084 Australia.Email: antonius@unimelb.edu.au
The dorsal motor nucleus of the vagus (DMV) is
considered to be the main, if not the sole, source
of the vagal innervation of various organs within the
gastrointestinal (GI) tract, including the stomach and the
pancreas (Kalia, 1981; Loewy & Spyer, 1990; Hornby &
Wade, 2011). The secretomotor function of the DMV
has been recognized for more than 30years, and so its
role in regulation of GI secretion, motility and pancreatic
secretory function (PSF) has been well documented (Kerr
& Preshaw, 1969; Loewy & Spyer, 1990; Hornby & Wade,
2011). Recent developments in neural–pancreatic research
have revealed that, in addition to the pancreatic hormones
and peptides, the DMV is a major brain region involved
in mediating pancreatic secretion (PS). It is evident that
the DMV is the site of origin of vagal efferent neurons that
innervate both the endocrine and the exocrine pancreas
C
⃝ 2012 The Authors. Experimental Physiology C
⃝ 2012 The Physiological SocietyDOI: 10.1113/expphysiol.2012.066472
26B. M. Mussa and A. J. M. Verberne Exp Physiol 98.1 (2013) pp 25–37
(Rinaman & Miselis, 1987; Berthoud & Powley, 1991;
Jansen et al. 1997).
Several neurophysiological studies have shown that
electrical and chemical stimulation of the DMV activates
both endocrine and exocrine secretion via a cholinergic
pathway. An early study by Ionescu and colleagues
showed that unilateral electrical stimulation of the DMV
produced a 100–200% increase in plasma insulin levels.
These increases were completely blocked by atropine
methonitrate and vagotomy, suggesting that the influence
of the DMV on the endocrine pancreas is vagal in
nature (Ionescu et al. 1983). In addition, another
study demonstrated that bilateral electrical stimulation
of the medial and the lateral DMV elicited significant
increases in gastric acid secretion and in insulin and
glucagon secretion, respectively (Laughton & Powley,
1987). Recently, we have found that bilateral chemical
activation of the DMV using bicuculline methiodide
(GABA A receptor antagonist) increased the exocrine
and endocrine PS significantly. Treatment with atropine
methonitrate (a muscarinic receptor antagonist that does
not cross the blood–brain barrier) completely abolished
these excitatory effects, emphasizing the involvement of a
cholinergic mechanism (Mussa & Verberne, 2008; Mussa
et al. 2011). The present review aims to summarize the key
findings from the recent literature on the physiological
roles of the DMV in the control of PS.
Functional anatomy of the DMV
The DMV was first described by Stilling in 1843, and since
then, researchers have investigated different anatomical,
histological, physiological and functional aspects of this
structure. The DMV has been acknowledged as the largest
source of parasympathetic preganglionic neurons within
the lower brainstem (Stilling & Wallach, 1843; Huang
et al. 1993). It is located in the dorsomedial caudal
medulla oblongata, close to the floor of the fourth ventricle
(Fig. 1). In the horizontal plane, the DMV replicates the
‘Y’ appearance of the nucleus of the solitary tract (NTS)
and lies medial and ventral to this nucleus throughout
the rostrocaudal extent of the medulla oblongata. More
specifically, in the caudal part of the medulla oblongata,
the DMV fuses close to the mid-line dorsolateral to the
central canal. In the rostral medulla oblongata, both
sides of the DMV lie ventromedial to the NTS as the
fourth ventricle opens. Similar to the NTS, the DMV is
apairedbilateralandsymmetricalnucleus,whichsends
projections to the viscera of the abdomen (stomach, liver,
pancreas, small intestine and proximal large intestine) in
a bilateral fashion (Bystrzycka & Nail, 1985; Loewy &
Spyer, 1990; Powley et al. 1992; Blessing, 1997; Jordan,
2011). Electrophysiological and histological studies have
shown that neurons in the DMV are heterogeneous
with respect to size, physiological type and morphology.
However, two major types have been classified, namely
multipolar neurons in the rostral and caudal DMV and
bipolar neurons in the intermediate DMV with transverse
diameterrangesbetween12and30 µ m (Bystrzycka &
Nail, 1985; Nosaka, 1986). The afferentinputs and efferent
outputs of the DMV will be discussed in more detail in the
following two subsections.
Afferent projections to the DMV. The DMV receives
myelinated and unmyelinated vagal afferent input from
the periphery, as well as afferent input from CNS
structures. In vitro studies have demonstrated the presence
of visceral vagal afferent projections within the DMV.
However, these projections seem to be thinly distributed
along the dorsal and the lateral edges of the nucleus
(Shapiro & Miselis, 1985; Champagnat et al. 1986;
Neuhuber & Sandoz, 1986). A review by Loewy and
Spyer across various species has revealed that the DMV
also receives a range of projections from other areas
within the CNS, including the insular cortex, the central
nucleus of the amygdala, the paraventricular hypothalamic
nucleus, the lateral hypothalamic area, the dorsomedial
hypothalamic nucleus, the posterior hypothalamus, the
mesencephalic central grey matter, the parabrachial
nucleus, the A5 catecholamine cell group,the NTS, the
medullary reticular formation and the raph ´
e obscurus
nucleus (ter Horst et al. 1984; Loewy & Spyer, 1990).
Injection of the retrograde neuronal tracer horseradish
Figure 1.Schematic diagram depicting the relationship
between the area postrema (AP), the dorsal motor nucleus of
the vagus (DMV), the nucleus of the solitary tract (NTS) in the
dorsal medulla oblongata and the branches of the thoracic and
subdiaphragmatic abdominal vagal nerve trunks
C
⃝ 2012 The Authors. Experimental Physiology C
⃝ 2012 The Physiological Society
Exp Physiol 98.1 (2013) pp 25–37 Dorsal vagal nucleus and the pancreas27
peroxidase into the DMV revealed a wide distribution of
labelled neurons within the lower brainstem (ter Horst
et al. 1984; Loewy & Spyer, 1990).
Efferent projections of the DMV. Eighty per cent of the
neurons in the DMV give rise to the parasympathetic
preganglionic fibres that innervate GI organs, including
the pancreas. Although the majority of these neurons
are cholinergic and non-cholinergic, centrally projecting
neurons were also identified within the DMV. It has been
found that the centrally projecting DMV neurons project
to the parabrachial nucleus, the cerebellar cortex and the
cerebellar nuclei (Loewy & Spyer, 1990). The efferent
component of the DMV that innervates the abdominal
viscera is organized into a series of longitudinally arrayed
columnar subnuclei that correspond to specific branches
of the abdominal vagus (Fox & Powley, 1985; Norgren
& Smith, 1988; Powley et al. 1992). Four of these
columnar subnuclei form bilateral and symmetrical pairs
of preganglionic neurons projecting from both sides of
the medulla oblongata, whereas preganglionic neurons
within the fifth column are distributed through the
longitudinal extent of the left DMV. The medial columnar
subnucleus, which occupies the medial two-thirds of the
DMV on each side of the medulla oblongata, contains
preganglionic neurons corresponding to the gastric vagal
branches. The lateral pole of each side of the DMV contains
preganglionic neurons that give rise to the two coeliac
branches (left DMV, accessory coeliac branch; right DMV,
coeliac branch). In contrast, the fifth columnar subnucleus
contains preganglionic neurons corresponding to the
hepatic branch. Compared with the gastric branch, this
branch contains 10% fewer efferent fibres (Fox & Powley,
1985; Norgren & Smith, 1988; Powley et al. 1992).
The DMV and GI hormones
It is interesting to note that most GI peptides and
hormones that are involved in regulation of PS are secreted
locally in the GI tract and have receptors within the DMV,
NTS or area postrema (AP; Fig. 2; Travagli & Browning,
2011). This supports the notion that DMV has both a
direct and an indirect influence on PSF.
Pancreatic polypeptide (PP). Pancreatic polypeptide is
secreted from the endocrine pancreas postprandially to
Figure 2.Schematic diagram showing the release sites of several gastrointestinal hormones and the
location of their receptors within the dorsal vagal complex
Vagal afferents project to neurons in the NTS which, in turn, influence vagal motor neurons of the DMV.
Preganglionic vagal motor neurons are excitatory (cholinergic), while postganglionic neurons are either
inhibitory (nitrergic?) or excitatory. Abbreviations: AP, area postrema; DMV, dorsal motor nucleus of the
vagus; GI, gastrointestinal; GLP-1, glucagon-like peptide-1; NO, nitric oxide; NTS, nucleus of the solitary
tract; PP, pancreatic polypeptide; and TRH, thyrotrophin-releasing hormone.
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⃝ 2012 The Authors. Experimental Physiology C
⃝ 2012 The Physiological Society
28B. M. Mussa and A. J. M. Verberne Exp Physiol 98.1 (2013) pp 25–37
inhibit PS in vivo in a variety of species (Lin et al. 1977;
Taylor et al. 1978, 1979; Adrian et al. 1979; Schwartz,
1983). It has been demonstrated that PP inhibits both
endocrine and exocrine PS (Lee et al. 1988). Interestingly,
these effects of PP on PS seem to be dependent on a
cholinergic mechanism (Jung et al. 1987). However, in
vitro studies on isolated pancreatic acini, which were
prepared by enzymatic digestion of rat pancreas, failed
to reproduce the inhibitory effect of PP on PS, suggesting
that PP acts indirectly and probably centrally to mediate
this effect (Louie et al. 1985; Jung et al. 1987). In addition,
several studies have shown that GI tract tissues, including
pancreatic acini and ductal cells, lack PP receptors,
with the exceptionof the basolateral membranesof
the canine small intestine (Louie et al. 1985; Gilbert
et al. 1988; Sheikh et al. 1991). Using in vitro receptor
autoradiography, Whitcomb et al. (1990) have localized
high-affinity PP receptors in high concentration within
the DMV. In addition, it was found that microinjection of
PP into the DMV produced significant inhibition of PS,
and this effect was site specific, because microinjection
of PP outside the DMV did not affect PS (Okumura
et al. 1995 a ). Furthermore, an electrophysiological study
in rats has shown that PP influences vagal outflow
to the pancreas directly via modulation of DMV
pancreas-projecting neurons or indirectly via modulation
of a synaptic connection between these neurons and the
NTS and the AP (Browning et al. 2005 b ). It has also been
found that lesions of the AP, a structure which lies outside
the blood–brain barrier, alters the effects of peripheral
PP on PSF (Deng et al. 2001). Together, these findings
led to the suggestion that PP, which is released from the
pancreas into the circulation after meal ingestion, gains
access to the DMV via the AP. There, PP suppresses vagal
excitatory inputs to the pancreas via direct modulation of
the DMV pancreatic vagal outflow (for review see Travagli
et al. 2006; Fig. 2).
Similar to PP, neuropeptideY (NPY) and peptideYY
(PYY) exert their inhibitory effects on PS via activation of
Y 1 and Y 2receptors within the DMV, producing inhibition
of pancreatic cholinergic vagal outflow (Leslie et al.1988;
Lynch et al. 1989; Dumont et al. 1990; Masuda et al.1994;
Naruse et al. 2002; Browning & Travagli, 2003).
Ghrelin. Ghrelin is known to be involved in stimulation
of PS. This peptide acts as an endogenous ligand for the
growth hormone secretagogue receptor and is produced
by endocrine cells in the oxyntic glands of the stomach and
intestine, as well as by neurons of the hypothalamic arcuate
nucleus (Kojima et al. 1999; Dateet al. 2000; Cummings
et al. 2001). Intravenous injection of ghrelin increases
PS in a dose-dependent manner, and this effect was
abolished in the presence of atropine and hexamethonium,
suggesting an involvement of a cholinergic mechanism (Li
et al. 2006). It has been shown that PS was significantly
increased in response to intracerebroventricular infusion
of ghrelin. Vagotomy completely blocked this effect,
demonstrating that ghrelin acts centrally via vagal
pathways to stimulate PS (Li et al. 2006). In addition,
experiments in conscious and anaesthetized rats have
shown that both intracerebroventricular and intravenous
administration of ghrelin induced c-fos expression in the
DMV, the NTS and the AP (Date et al. 2001; Li et al.
2006). Interestingly, c-fos expression in the DMV and the
NTS after intravenous infusion of ghrelin was significantly
reduced after lesions of the AP (Li et al. 2006). Moreover,
astudybyZigman et al. (2006) has demonstrated that the
highest expression of ghrelin receptor mRNAwas obser ved
in the AP, supporting the hypothesis that ghrelin gains
access to the brain primarily via the AP and influences
the neuronal activity of the NTS and the DMV. On the
contrary, ghrelin receptor immunoreactivity was found in
the NTS and DMV but not the AP (Lin et al. 2004). Indeed,
ghrelin has also been shown to inhibit the activation of
NTS catecholamine neurons by visceral inputs, although
this response is probably associated with the effects of
ghrelin on feeding (Cui et al. 2011). These findings suggest
that ghrelin stimulates PS via activation of a vagovagal
reflex which, in turn, increases the vagal outflow from the
DMV to the pancreas.
Glucagon-like peptide-1 (GLP-1). Glucagon-like peptide-
1, 7–36/7–37 amide is a signal peptide which is involved
in stimulation of insulin release via an interaction with
specific receptors. Glucagon-like peptide-1 is an incretin
hormone and is released from the enteroendocrine
L-cells of the intestinal mucosa into the circulation
postprandially in response to the presence of luminal
nutrients, including fat and carbohydrates (Fehmann et al.
1992; Schirra & G ¨
oke, 2005). Glucagon-like peptide-
1stimulatesinsulinsecretioninaglucose-dependent
manner via activation of its receptors expressed on
islet β -cells. Glucagon-like peptide-1 is considered to
be a unique pancreatic secretagogue because it also
replenishes insulin stores via activation of proinsulin gene
transcription. It also suppressesglucagon secretion from
islet α -cells (Drucker et al. 1987; Fehmann et al. 1992,
1995; Drucker, 1998). Several studies have used a variety
of techniques, including immunohistochemistry, receptor
binding, radioimmunoassay and chromatography, to
demonstrate the presence of GLP-1 in the CNS, and the
highest density of GLP-1 binding sites and mRNA was
detected in the NTS and DMV (Shimizu et al. 1987;
Jin et al. 1988; Kanse et al. 1988; Kreymann et al. 1989;
Uttenthal et al. 1992; G ¨
oke et al. 1995; Larsen et al.
1997; Fig. 2). This suggests that besides the direct action
of GLP-1 on the endocrine pancreas, GLP-1 may also
act indirectly via central vagal pathways to stimulate
insulin release. A study by Kastin et al. (2002) has
supported this suggestion by demonstrating that GLP-1
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Exp Physiol 98.1 (2013) pp 25–37 Dorsal vagal nucleus and the pancreas29
gains access to the brain by simple passive diffusion.
Furthermore, an electrophysiological study has shown
that superfusion of GLP-1 onto DMV neurons excites a
subpopulation of pancreas-projecting preganglionic vagal
motorneurons (Wan et al. 2007 a ). The selectivity of this
effect was confirmed using a specific GLP-1 receptor
agonist (exendin-4) and antagonist [exendin-(9–39)],
which mimicked and prevented this excitatory effect,
respectively. This finding emphasized the hypothesis that
GLP-1 also influences endocrine secretion via a direct
activation of its receptors on the DMV or on the NTS,
which modulates neural input to the DMV. The latter, in
turn, excites the efferent output to the endocrine pancreas
(Wan et al. 2007 a ).
Thyrotrophin-releasing hormone (TRH). Thyrotrophin-
releasing hormone is another hormone that stimulates
PS via an action in the DMV. Thyrotrophin-releasing
hormone was originally described as a hypothalamic
hormone that is synthesized and released from
hypothalamic neurons to stimulate the release of
thyrotrophin secretion from the anterior pituitary gland
(Taylor et al. 1990; Rang et al. 1999). Thyrotrophin-
releasing hormone was also detected in different GI
organs, including the pancreas (Morley et al. 1977;
Dutour et al. 1987). Thyrotrophin-releasing hormone is
co-localized with insulin within the islet cells and is
secreted in response to a high level of glucose, whereas
TRH release is inhibited by insulin in isolated pancreatic
islets (Leduque et al. 1987; Benicky & Strbak, 2000). It
also modulates the basal secretion of glucagon in vitro ,
and this response was inhibited by immunoneutralization
of TRH with specific antibodies (Ebiou et al. 1992). Several
studies have demonstrated the presence of TRH receptors
and immunoreactive fibres in various medullary areas,
including the DMV and the NTS (Manaker & Rizio,
1989; Fig. 2). This suggests that TRH may act centrally to
regulate pancreatic function (Kubek et al. 1983; Palkovits
et al. 1986; Manaker & Rizio, 1989; Rinaman et al. 1989;
Rinaman & Miselis, 1990). This suggestion is supported
by the finding that application of TRH or a TRH analogue
into the cerebrospinal fluid stimulates PS in rats (Kato
&Kanno,1983).Morespecifically,otherstudieshave
shown that microinjection of a TRH analogue into the
dorsal vagal complex (DVC), a term used to refer to the
two closely interacting groups of neurons in the DMV
and the NTS, stimulates PS in a dose-dependent manner.
Microinjection of the same analogue into the brain-
stem but outside the DVC did not produce any changes
in PS (Okumura et al. 1995 b ). Vagotomy and atropine
completely blocked this excitatory effect, confirming the
involvementof vag al cholinergic pathways (Okumura et al.
1995 b ). Likewise, a study by Yoneda et al. (2005) has
shown that pancreatic blood flow (PBF) was increased in a
dose-dependent manner in response to microinjection of a
TRH analogue into the DVC. In contrast, microinjection
of vehicle into the DVC or microinjection of the TRH
analogue outside the DVC produced no change in the
PBF. Cervical vagotomy and atropine administration
blocked the excitatory effects of TRH microinjection
into the DVC, suggesting that the peptide increased PBF
via vagal cholinergic pathways. Moreover, involvement
of nitric oxide pathways was also suggested, because
intravenous administration of L -NAME (a nitric oxide
synthase inhibitor) inhibited TRH-induced stimulation
of PBF, and this inhibition was abolished in the presence
of L -arginine (Yoneda et al. 2005).
Nitric oxide. Recent interest in NO research has led to
the establishment of a very clear relationship between
this molecule and pancreatic endocrine and exocrine
secretion. It is well documented that NO acts as a
widespread neurotransmitter or neuromodulator in the
brain (Knowles et al. 1989; Bredt et al. 1990; Moncada
et al. 1991; Bredt & Snyder, 1992). Nitric oxidesynthase
(NOS) activity has been detected in various areas within
the medulla oblongata, including the NTS (Forstermann
et al. 1990; Vincent & Kimura, 1992). A study by Lu
et al. has shown that NADPH-diaphorase, which can
be used to identify NOS in the CNS, was detected
in different regions of the NTS where the majority
of the visceral vagal afferents terminate. The NADPH-
diaphorase activity was eliminated upon removal of
the nodose ganglion, which contains the cell bodies of
visceral vagal afferents, confirming the role of NO as the
neuromodulator in these afferents (Lu et al. 1994; Lin et al.
1998). Moreover, evidence obtained in vivo and in v itrohas
demonstrated excitatory effects of NO on NTS neurons,
because intravenous and direct administration of L -NAME
significantly reduces the discharge of NTS neurons (Ma
et al. 1995). Interestingly, several immunohistochemical
studies in rats and cats have shown that NOS-containing
neurons are localized in the DMV (Mizukawa et al. 1989;
Krowicki et al. 1997). In fact, NADPH-diaphorase activity
was detected in two populations of preganglionic neurons
in the DMV, suggesting that NO may play a role in the
control of some GI functions (Travagli & Gillis, 1994;
Krowicki et al. 1997). In addition, it has been found that
the firing rate of DMV neurons increased in response to
the presence of NO or its donors. Several lines of evidence
support this finding by showing that NMDA-induced
increases in DMV neuronal firing rate were blocked by
NO inhibitors and scavengers (Travagli & Gillis, 1994).
Taking into account all these findings, along with the
fact that NO within the DMV is involved in regulation
of gastric secretion (Beltr ´
an et al. 1999), we have proposed
that DMV NO may also be involved in mediationof PS.
This hypothesis was supported by our recent findings that
the excitatory effects of chemical stimulation of the DMV
on insulin secretion were significantly enhanced after
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blockade of peripheral NOS, suggesting that NO exerts
an inhibitory influence on insulin secretion (Mussa et al.
2011).
The DMV and vagovagal reflexes
Vagovagal reflexes constitute major extrinsic neural
pathways that are involved in control of many GI and
pancreatic functions (for review see Chang et al. 2003;
Travagli & Browning, 2011). The vagovagal reflex pathway
consists of first-order vagal sensory afferents whose cell
bodies are located within the nodose ganglion, neurons
of the NTS and efferent vagal motor neurons of the
DMV. Although an extensive amount of work has been
done to identify the components of the vagovagal reflexes
that regulate gastric motility and secretion, less is known
about the vagal pathways that are involved in control
of PSF. Our hypothesis was that GI hormones, such
as cholecystokinin (CCK) and 5-HT, activate receptors
on pancreatic vagal afferents that terminate onto and
activate neurons within the NTS via glutamate receptors
(Liao et al. 2005). These neurons, in turn, influence
pancreatic preganglionic neurons (PPNs) projecting from
the DMV and modulate the vagal output to the pancreas
via glutamatergic and GABAergic inputs (Travagli et al.
1991, 2006; Buijs et al. 2001; Love et al. 2007; Mussa &
Verberne, 2008; Fig. 3). We have previously shown that the
vagal output to the pancreas is mainly under GABAergic
control (Mussa & Verberne, 2008). Although a variety
of neurotransmitters have been localized in the DMV, it
is evident that endogenous glutamate and GABA have a
major impact on DMV vagal output (Travagli etal. 1991).
Excitatory and inhibitory postsynaptic currents recorded
from DMV neurons that were elicited by electrical
stimulation of the NTS were mediated by glutamate and
GABA, respectively (Love et al. 2007). Furthermore, a
recent study by Babic et al. (2011) has demonstrated
that a majority of DMV neurons are modulated by tonic
glutamatergic and GABAergic inputs.
Several lines of evidence strongly support the existence
of a pancreatic vagal sensory innervation. Using retrograde
tracing techniques, Sharkey & Williams (1983) described
the morphology of pancreatic vagal afferents. Injection of
the fluorescent retrograde tracer True Blue into multiple
parts of the pancreas, including the duodenal and splenic
lobes, resulted in extensive labelling of cells in the nodose
ganglion. The number of labelled cells was significantly
reduced by treatment with capsaicin, which is known
to destroy unmyelinated and small-diameter myelinated
afferent fibres selectively. This suggests that the majority of
pancreatic vagal afferents are also unmyelinated or small-
diameter myelinated fibres (Sharkey & Williams, 1983).
Similar findings were reported in a study in which the
pancreatic vagal innervation was labelled using horse-
radish peroxidase as a retrograde axonal tracer (Carobi,
1987). Following injection of horseradish peroxidase into
Figure 3.Schematic diagram showing the basic components of the pancreatic vagovagal reflex
Vagal afferents arising from the pancreas, as well as from the stomach and other parts of the
gastrointestinal tract, have their somata in the nodose ganglion and project into the NTS. The NTS
neurons, in turn, project to the preganglionic vagal motor neurons of the DMV. Abbreviations: DMV,
dorsal motor nucleus of the vagus; and NTS, nucleus of the solitary tract.
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the pancreas via the common bile duct, many labelled
neurons were detected in the right and left nodose
ganglion. Capsaicin treatment led to a complete loss of
the small labelled neurons of the nodose ganglion and
areductioninthenumberofthelabelledneuronswith
a larger diameter, indicating that most of the pancreatic
vagal afferents are capsaicin-sensitive fibres with small-
diameter unmyelinated axons (Carobi, 1987).
In view of these findings, we investigated the effects
of systemic administration of CCK and the 5-HT 3
receptor agonist phenylbiguanide (PBG) on pancreatic
vagal afferent discharge (PVAD). Furthermore, we wished
to identify the receptors that were involved in these effects.
In good agreement with previous reports, the results of this
study have demonstrated that pancreatic vagal afferents
are also highly sensitive to CCK and 5-HT (Mussa et al.
2008). Almost 30 years ago, Niijima studied the effects of
glucose, 2-deoxyglucose, CCK and 5-HT on pancreatic
vagal afferents (Niijima, 1981). However, compared with
Niijima’s study, we found that CCK produced more rapid
and larger increases in PVAD. This may have been due
to several differences between the two studies including
the following: (i)CCK dose range; (ii)route of CCK
administration; and (iii)the branch of the pancreatic
vagus nerve that was used to record the afferent discharge.
Intravenous administration of CCK and PBG doses in
random order increased PVAD significantly in a dose-
related manner. The responses to these two substances
did not change after cervical vagotomy, indicating that
the pancreatic vagal nerve discharge was afferent in
nature (Mussa et al. 2008). Moreover, blockade of CCK 1
and 5-HT 3 receptors using specific antagonists produced
significant reductions in the PVAD response to CCK and
PBG, respectively. This finding suggests that CCK 1 and 5-
HT 3 receptors mediate CCK- and PBG-induced activation
of pancreatic vagal afferents. Pancreatic vagal efferents also
play a key role in regulation of PSF, and the following
section reviews this issue in more detail.
The DMV and pancreatic secretagogues: a focus
on CCK and 5-HT
Cell bodies of preganglionic parasympathetic neurons
that innervate the pancreas arise mainly from the
DMV (Kalia, 1981; Loewy & Spyer, 1990). Several GI
hormones are known to be involved in regulation of PSF,
including the inhibitory peptide hormones PP, NPY, PYY
and somatostatin and the excitatory hormones secretin,
CCK, 5-HT, gastrin, secretin-releasing peptide and CCK-
releasing peptide, ghrelin, GLP-1 and TRH. However, CCK
and 5-HT are the principal mediators of PS in various
species (Chey & Chang, 2001; Konturek et al. 2003).
Early studies of the effects of CCK in various parts of
the brain have shown that ionophoretic application of
CCK excites neurons within the substantia nigra and the
dorsal horn and inhibits neurons within the NTS (Jeftinija
et al. 1981; Morin et al. 1983; Hommer et al. 1985). In
addition, immunohistochemical and tracing studies have
demonstrated the presence of CCK-responsive neurons in
a variety of regions within the CNS (Fallon & Seroogy,
1985; Herbert & Saper, 1990). Furthermore, several
reports have demonstrated that peripheral administration
of CCK induces Fos expression in restricted regions of
the DMV (Rinaman et al. 1993, 1994). It has been
shown previously that local application of CCK-8 to
identified DMV neurons in vitro has led to depolarization
and hyperpolarization of 43 and 11% of these neurons,
respectively.
Furthermore, a non-active form of CCK-8, non-
sulphated CCK-8, had no effect on the electrophysiological
properties of these neurons, suggesting the presence of
CCK-8 receptors within the DMV and the selectivity
of the DMV neuronal responses to CCK-8 (Plata-
Salam ´
an et al. 1988). A recent whole-cell patch-clamp
electrophysiological study conducted using brainstem
slices has examined the effect of CCK on pancreas-
projecting DMV neurons identified by retrograde tracing
from the pancreas (Wan et al. 2007 b ). In that study,
perfusion of the pancreas-projecting DMV neurons
with CCK-8 activated about 60% of the neurons
tested. This response was mediated by CCK 1 receptors,
because pretreatment with lorglumide, a CCK 1 receptor
antagonist, significantly attenuated the excitatory effect
of CCK-8. Agonists of CCK 2 receptors, even at a high
concentration, did not affect the neural discharge of
pancreas-projecting DMV neurons. In addition to the
direct action of CCK-8 on pancreas-projecting DMV
neurons, indirect actions of CCK-8 on the synaptic inputs
to the DMV have also been proposed. This was supported
by the finding that tetrodotoxin was able to reduce the
excitatory effects of CCK-8 on pancreas-projecting DMV
neurons significantly by blockade of action potential-
dependent synaptic inputs to the DMV (Wan et al.
2007 b ).
Although it is well documented that CCK-8 acts in a
paracrine fashion to activate a vagovagal reflex to influence
PS, a direct mechanism of action of CCK on DVC has also
been suggested. Recently, it was found that microinjection
of CCK-8 in the DVC produced excitatory effects on PS in
control and vagal deafferented rats (Viard et al. 2007). In
line with previous findings, CCK 1 receptors are likely to
mediate the central effects of CCK-8 on PS. This suggestion
is based on the fact that perfusion of the fourth ventricle
with lorglumide significantly attenuated the increases in
PS produced by release of endogenous CCK (Viard et al.
2007).
Recent compelling evidence suggests that 5-HT may
play a fine-tuning role in regulation of DMV neural
activity, because several subtypes of 5-HT receptors,
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32B. M. Mussa and A. J. M. Verberne Exp Physiol 98.1 (2013) pp 25–37
including 5H-T 1A ,5H-T
1B ,5H-T
2 and 5H-T 3 ,arefound
within the DMV (Twarog & Page, 1953; Manaker &
Ve r d er a m e ,1 9 9 0 ;T h o r et al. 1992 a , b ; Steward et al.
1993; Wright et al.1995). In addition, 5-HT-containing
neurons were immunohistochemically localized and
widely distributed within the DMV (Steinbusch, 1981;
Sykes et al. 1994). In vivo and in vitro studies have shown
that activation of 5-HT receptors produced excitatory
effects on DMV neurons. It was found that 95% of
DMV neurons were strongly excited in response to 5-HT
in vitro. It is more likely that this effect was mediated
via activation of the 5-HT 2 receptors, because application
of a 5-HT 2 receptor antagonist blocked this excitatory
effect. 5-Hydroxytryptamine receptor antagonists at other
subtypes were only partly effective or not effective at all
(Albert et al. 1996). In agreement with this finding, an
electrophysiological study by Browning & Travagli (1999)
has demonstrated that exogenous application of 5-HT
had excitatory effects on different subgroups of identified
DMV neurons. They noted that 69 and 47% of DMV
intestinal and gastric neurons, respectively, were excited
in response to application of 5-HT into the DMV, and
these responses were completely abolished in the presence
of ketanserin, a 5-HT 2 receptor antagonist. In contrast,
another study by Wang et al. (1996) has investigated the
effects of ionophoretic application of PBG on identified
neurons of the DMV. That study demonstrated that the
majority of the DMV preganglionic neurons were excited
by PBG. Intravenous and ionophoretic administration
of the 5-HT 3 receptor antagonists, granisetron and
tropisetron, either abolished or attenuated the excitatory
effects of PBG, suggesting that these effects were mainly
mediated via 5-HT 3 receptor activation. Interestingly, 5-
HT 2 and 5-HT 1A receptor antagonists did not alter the
excitatory effects of PBG, excluding the possibility that
these receptor subtypes participate in the PBG-induced
excitation of DMV neurons (Wang et al. 1996). A follow-
up study demonstrated that PBG-induced excitation of
DMV neurons by PBG was mediated by facilitation of
glutamatergic inputs to these neurons. This conclusion
was drawn by taking into account several findings,
including the finding that ionophoretic application of
Mg 2 + and Cd 2 + onto the identified neurons abolished
the PBG-induced excitation of the DMV neurons (Wang
et al. 1998). In contrast, an in vivo study has shown that
ionophoretic application of 5-HT into the DMV had both
excitatory and inhibitory effects on vagal preganglionic
neurons. The excitatory effects of 5-HT seem to be
mediated via 5-HT 1A receptors, because ( ± )-pindolol and
WAY-100635, 5-HT 1A receptor antagonists, attenuated
these effects (Wang et al. 1995). A plausible explanation
for these different findings is that the effects of 5-HT are
largely dependent on the 5-HT receptor subtypes present
in the DMV.
Most of these previous studies were performed in vitro
and used tracing techniques to localize the DMV neurons,
and these techniques have several limitations, including
potential leakage of tracers to other organs outside the
pancreas. In addition, in vitro studies are unable to
examine the effects of modulators that act upon vagal
afferent neurons that, in turn, influence DMV neurons
via a relay in the NTS. Therefore, it was important to
localize DMV PPNs in vivo to allow a more detailed
investigation of the acute effects of CCK and PBG on the
activity of PPNs. To achieve this aim, we made extracellular
single-unit recordings from DMV PPNs identified by
antidromic activation from the pancreatic branch of the
vagus (Mussa et al. 2010). Although three populations of
dorsal vagal preganglionic neurons were identified based
on their responses to CCK and PBG, some properties were
common to all neurons studied, including uniform axonal
conduction velocities in the Cfibre range and their basal
firing rates. Pancreatic preganglionic neurons within the
caudal DMV were activated by CCK and PBG, but their
number was very small compared with PPNs within the
intermediate and rostral DMV that were inhibited by or
were insensitive to CCK and PBG, respectively (Mussa
et al. 2010). In agreement with previous reports, this
study demonstrated that the DMV is a heterogeneous
nucleus. Three unique subpopulations of PPNs have not
been described previously and may represent different
functional roles. This also suggests that the influence of
the pancreatic secretagogues, CCK and PBG, on DMV
PPNs is more complex than previously thought.
Conclusion
The DMV is a crucial component of the pancreatic
| https://www.researchgate.net/publication/225095071_The_dorsal_motor_nucleus_of_the_vagus_and_regulation_of_pancreatic_secretory_function_Dorsal_vagal_nucleus_and_the_pancreas |
Aster Communities v Chapman - Viewing document - ICLR
ICLR.4
Aster Communities v Chapman
[2021] EWCA Civ 660
2021 April 15; May 7
King , Newey , Phillips LJJ
Landlord and tenant
—
Covenant
—
Service charge
—
Tribunal finding landlord in breach of statutory requirement to consult with tenants before carrying out works
—
Landlord applying for dispensation from consultation requirements
—
One tenant giving evidence that she would have acted differently had consultation requirements been complied with
—
Tribunal finding “credible case of relevant prejudice” to all tenants
—
Tribunal granting dispensation on conditions removing prejudice
—
Whether tribunal erring in applying one tenant’s evidence of prejudice to other tenants
—
Whether incumbent on each tenant to demonstrate individual prejudice
—
Landlord and Tenant Act 1985 ( c 70 ) , s 18(1), ss 20(1), 20ZA(1)
—
Service Charges (Consultation Requirements) (England) Regulations 2003 (SI 2003/1987) , Sch 4, Pt 2, para 4(5)
Sections 18–30 of the Landlord and Tenant Act 1985 deal with service charges imposed by landlords on tenants. Section 20(1) of the 1985 Act provides for the “relevant contributions of tenants” to be: “limited in accordance with subsection (6) or (7) (or both) unless the consultation requirements have been either— (a) complied with in relation to the works or agreement, or (b) dispensed with in relation to the works or agreement by (or on appeal from) the appropriate tribunal”.
Section 20ZA(4) of the 1985 Act provides for “the consultation requirements” to be prescribed by statutory instrument. The relevant “consultation requirements” are set out at paragraph 4(5) of Part 2 of Schedule 4 to the Service Charges (Consultation Requirements) (England) Regulations 2003, which provides: “(5) The landlord shall, in accordance with this sub-paragraph and sub-paragraphs (6) to (9)— (a) obtain estimates for the carrying out of the proposed works; (b) supply, free of charge, a statement (‘the paragraph (b) statement’) setting out— (i) as regards at least two of the estimates, the amount specified in the estimate as the estimated cost of the proposed works; and (ii) where the landlord has received observations to which (in accordance with paragraph 3) he is required to have regard, a summary of the observations and his response to them; and (c) make all of the estimates available for inspection.”
The landlord was a substantial social landlord and the freehold owner of a development comprising 160 flats. 114 of the flats were let on long leases, each of which provided for the tenant to pay by way of service charge a proportion of costs incurred in respect of their block. The landlord supplied each tenant with a notice of intention to carry out works on the flats and a “paragraph (b) statement”, pursuant to paragraph 4(5) of Part 2 of Schedule 4 to the Service Charges (Consultation Requirements) (England) Regulations 2003. The notice and statement listed the proposed works, but it was not suggested that the works would involve replacement of the balcony asphalt. The estimates in the paragraph (b) statement were the tenderers’ priced specifications and they included provision for replacement of balcony asphalt. One tenant (“Tenant A”) took advantage of the opportunity to inspect the estimates and submitted observations, none of which related to the replacement of the balcony asphalt. Subsequently, the landlord brought an application before the First-tier Tribunal, pursuant to section 27A of the Landlord and Tenant Act 1985, for a determination in respect of on-account service charges demanded from the tenants. The FTT found that full replacement of all balcony asphalt was unnecessary, that the replacement of the balcony asphalt had not been part of the consultation and that even if the landlord could eventually justify the balcony asphalt replacement, an application for dispensation from consultation requirements under section 20ZA of the 1985 Act would be required. Accordingly, the landlord brought an application before the FTT for dispensation under section 20ZA. Tenant A gave evidence of what she would have done differently had the landlord complied with the full statutory consultation process, maintaining that had she been made aware of the landlord’s intention she would have been able to find a cheaper alternative to replacing the balcony asphalt. The FTT held that it was appropriate to grant dispensation but that, relying particularly on the evidence of Tenant A, a credible case of relevant prejudice had been made out in relation to the balcony asphalt. Accordingly dispensation was granted on conditions removing prejudice, including a direction that the landlord was to pay the reasonable costs of an expert nominated by the tenants to advise them on the necessity of replacing all the balcony asphalt. The judge dismissed the landlord’s appeal, holding that the FTT had been entitled to conclude, relying in particular on Tenant A’s evidence, that had the extent of the balcony works been properly communicated to the tenants, it was likely that the tenants would have referred to an expert. Accordingly, the tenants had been “unable, in the course of the consultation exercise, to take the necessary steps to satisfy themselves that the works intended were necessary and appropriate”. The landlord appealed and the issue arose as to whether the tenants could rely on the fact that Tenant A would have acted differently had the consultation requirements been complied with. The landlord contended that, even supposing that Tenant A would have acted differently, the other tenants should not be considered to have suffered relevant prejudice. It was incumbent on each tenant to demonstrate what they would have done and a tenant who would have done nothing different should not benefit from the terms of a conditional dispensation ordered because another tenant was prejudiced.
On the landlord’s appeal—
Held, appeal dismissed. The consultation for which the Service Charges (Consultation Requirements) (England) Regulations 2003 provided was a group process in which a landlord had to supply every tenant with notice of its intention to carry out works and a “paragraph (b) statement” pursuant to paragraph 4(5) of Part 2 of Schedule 4 to the 2003 Regulations including, among other things, a summary of observations made by other tenants. More than that, a landlord sought dispensation against tenants generally. If all tenants suffered prejudice because a defect in the consultation process meant that one of their number did not persuade the landlord to limit the scope or cost of works in some respect, there was no reason why the FTT should be unable to make dispensation conditional on every tenant being compensated. The reduction in the scope or cost of works would have accrued to the benefit of each of them, and so, if dispensation was to be granted against them all, the totality of the prejudice should be addressed. That was not to say that the positions of individual tenants would be irrelevant. Thus, there could be no question of all tenants in a block having their service charges cut by the same figure if they shared the relevant service charges in differing proportions. If, for example, one tenant bore 10% of service charges and another just 5%, a reduction in recoverable service charges should benefit the two tenants in the ratio 2:1. Likewise, in a case in which the FTT found that a failure to consult correctly had resulted in higher service charges for one block of flats, but not for any other block, it would have been appropriate to impose a condition limiting the service charges for only the block of flats with higher service charges. In the present case, the FTT had found that the tenants had made out a case of relevant prejudice, namely that the tenants would be asked to pay for inappropriate works. It reached its conclusion, having cited in particular to evidence of Tenant A, to the effect that she would have commissioned a report and asked to see the landlord’s advice and that that might have resulted in a cheaper approach. Had a cheaper approach been adopted, service charges would have been lower for all tenants, not merely Tenant A. The failure to refer to the balcony works in the notice of intention accordingly gave rise to a “credible case of relevant prejudice” to every tenant, and the FTT was entitled to take that into account. The fact that the prejudice might have been attributable to what Tenant A alone would have done did not mean that the FTT was confined to considering prejudice to her (paras 44–46, 52, 54, 55).
Daejan Investments Ltd v Benson [ 2013 ] 1 WLR 854 , SC(E) applied.
Decision of Upper Tribunal (Lands Chamber) [2020] UKUT 177 (LC) affirmed.
Ranjit Bhose QC(instructed by Capsticks Solicitors LLP) for the landlord.
Philip Rainey QCand Robyn Cunningham(instructed by Talbot Walker LLP, Andover) for 33 of the tenants.
Isabella Cheevers , Barrister
Referenced Legislation
Landlord and Tenant Act 1985 (c 70) , s 18(1), ss 20(1), 20ZA(1)
Service Charges (Consultation Requirements) (England) Regulations 2003 (SI 2003/1987), Sch 4, Pt 2, para 4(5)
| https://www.iclr.co.uk/document/2020005162/casereport_b5dac6e1-9a09-4981-8e12-453efd539db3/html |
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(PDF) Multi-Classifier of DDoS Attacks in Computer Networks Built on Neural Networks
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Multi-Classifier of DDoS Attacks in Computer Networks Built on Neural Networks
DOI: 10.3390/app112210609
Abstract and Figures
The great commitment in different areas of computer science for the study of computer networks used to fulfill specific and major business tasks has generated a need for their maintenance and optimal operability. Distributed denial of service (DDoS) is a frequent threat to computer networks because of its disruption to the services they cause. This disruption results in the instability and/or inoperability of the network. There are different classes of DDoS attacks, each with a different mode of operation, so detecting them has become a difficult task for network monitoring and control systems. The objective of this work is based on the exploration and choice of a set of data that represents DDoS attack events, on their treatment in a preprocessing phase, and later, the generation of a model of sequential neural networks of multi-class classification. This is done to identify and classify the various types of DDoS attacks. The result was compared with previous works treating the same dataset used herein. We compared their classification method, against ours. During this research, the CIC DDoS2019 dataset was used. Previous works carried out with this dataset proposed a binary classification approach, our approach is based on multi-classification. Our proposed model was capable of achieving around 94% in metrics such as precision, accuracy, recall and F1 score. The added value of multiclass classification during this work is identified and compared with binary classifications using the models presented in the previous.
Visual representation of defined model. …
Distribution of labels in the loaded dataset. …
Performance evaluation for the training rate of the model. …
Performance evaluation of the different rates for dropout layer. …
Hyperparameter settings for the proposed model. …
Figures - available via license: Creative Commons Attribution 4.0 International
applied
sciences
Article
Multi-Classifier of DDoS Attacks in Computer Networks Built
on Neural Networks
Andr é s Chartuni and Jos é M á rquez *
Citation: Chartuni, A.; Márquez, J.
Multi-Classifier of DDoS Attacks in
Computer Networks Built on Neural
Networks. Appl. Sci. 2021 , 11 , 10609.
https://doi.org/10.3390/
app112210609
Academic Editor: Ugo Vaccaro
Received: 26 September 2021
Accepted: 22 October 2021
Published: 11 November 2021
Publisher’s Note: MDPI stays neutral
with regard to jurisdictional claims in
published maps and institutional affil-
iations.
Copyright: © 2021 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Computer Science and Engineering Department, Universidad del Norte, Barranquilla 080020, Colombia;
achartuni@uninorte.edu.co
* Correspondence: jmarquez@uninorte.edu.co
Featured Application: Authors are encouraged to provide a concise description of the specific
application or a potential application of the work. This section is not mandatory.
Abstract:
The great commitment in different areas of computer science for the study of computer
networks used to fulfill specific and major business tasks has generated a need for their maintenance
and optimal operability . Distributed denial of service (DDoS) is a frequent threat to computer
networks because of its disruption to the services they cause. This disruption results in the instability
and/or inoperability of the network. There are different classes of DDoS attacks, each with a different
mode of operation, so detecting them has become a difficult task for network monitoring and control
systems. The objective of this work is based on the exploration and choice of a set of data that
represents DDoS attack events, on their treatment in a prepr ocessing phase, and later, the generation
of a model of sequential neural networks of multi-class classification. This is done to identify and
classify the various types of DDoS attacks. The result was compared with previous works treating
the same dataset used herein. We compared their classification method, against ours. During this
research, the CIC DDoS2019 dataset was used. Previous works carried out with this dataset proposed
a binary classification approach, our approach is based on multi-classification. Our proposed model
was capable of achieving around 94% in metrics such as precision, accuracy , recall and F1 score. The
added value of multiclass classification during this work is identified and compared with binary
classifications using the models presented in the previous.
Keywords:
computer networks; data preprocessing; DDoS attack; machine learning; neural networks
1. Introduction
Computer network systems have been deployed to achieve interconnectivity between
devices and carry out essential business tasks. However, this has created great dependence
on the main functions of an entity regarding its connection systems [
1
]. Main areas such as
banks, health entities and service providers are exposed to risks of instability because of
their strong and necessary dependence on computer networks. Because of this dependency,
it is essential to keep networks in an optimal state, specifically to maintain connectivity ,
performance, and security . Network performance can be strongly affected by a security
failure, causing instability to the point of network inoperability [ 2 ].
T o generate an anomaly in the network, different types of attacks have been used.
Among these, one of the main ones is the denial of service (DoS) attack. There has been an
increase in the number of such attacks in the last ten years, establishing them as a significant
threat to the stability of networks resulting from the alteration of various services [ 3 ].
A very common deployment mode of this attack is better known as distributed denial
of service (DDoS). This deploys a DoS attack simultaneously across a computer network. A
successful DDoS attack results in the exhaustion of bandwidth, routing device processing,
network or processing resources, memory , database, and bandwidth of server input and
output operations [ 4 , 5 ].
Appl. Sci. 2021 , 11 , 10609. https://doi.org/10.3390/app112210609 https://www.mdpi.com/journal/applsci
Appl. Sci. 2021 , 11 , 10609 2 of 15
There are measures to prevent these attacks. However , it is important to identify the
attack characteristics to take optimal actions to avoid its recurrence [
6
]. Unfortunately, the
characteristics of these attacks can vary considerably , so it is important to be able to identify
the type of alteration.
Network systems are in constant transformation, making dataset age an important
attribute at the time of their selection. Different datasets have been proposed. First
are DARP A ’98 and ’99 [
7
], which have categorized information for intrusion detection.
However, their implementation dates ar e very old and there is a risk of not representing
current information correctly . On the other hand, there are the datasets provided by CAIDA,
which were captured with the most recent date in the year 2019. However, the information
is not categorized and cannot be used for supervised learning in ML [ 8 ].
The Canadian Institute for Cybersecurity (CIC) has generated a dataset called CIC
DDoS2019 [
9
]. This dataset was produced in 2019 and has around 25 GB of labeled
information, making it an ideal source of information for DDoS attack detection work.
Furthermore, the reason why we opted for CIC DDoS2019 dataset is due to its high
reliability and its similarity to real world attacks [ 9 ].
Different ML detection proposals using the CIC dataset have been used to detect DDoS
attacks, obtaining excellent results [
10
,
11
]. However, their detection models operate with
the training of one attack per model, resulting in a binary classification of flow detection,
i.e., benign and malignant.
This work proposes the implementation of a sequential ML model, a data processing
framework and its subsequent processing, which allow detection at a multiclass level of
attacks instantiated in the CIC dataset [ 9 ].
Previous works using the CIC DDoS2019 dataset are based on binary classification.
Our approach’s novelty is the implementation of a multi-classification model. This will
allow for a better solution in the scenario when a malign flow is detected due to the model’s
capability of outputting the type of attack present in the flow . Furthermore, we propose
to combine labels resulting into one label that succeeds at classifying two types of attack
given their similarities.
The paper presents a section of previous work that describes and analyzes advances
related to the detection of DDoS attacks using ML techniques. This is followed by a method-
ology section, which explains the various procedures performed during the research. These
steps include dataset selection, information preprocessing, and definition of the model
used. The third section includes an evaluation of the defined model and the results. Finally ,
future work and conclusions of the research are addr essed.
2. Previous Works
This section describes the latest work and progress in detecting DDoS attacks, as
well as a description of the deployments and data used to obtain the published results.
He et al. [ 12 ]
obtained data from a simulation of four types of attacks: SSH brute force,
ICMP flooding, DNS reflection, and TCP SYN. Network traffic is generated by virtual
machines and in turn a monitoring system captures this traffic, which later feeds a dual
ML system. That system is made up of two layers. The first consists of an already trained
model and the second of a process that feeds that model at runtime to adjust it to values
evaluated during execution.
The ML system proposed by He et al. [
12
] is composed of a set of different methods
applied to the information collected. Each method is tested against a set of four attacks
generated and scores are compared between those methods. The methods applied by
He et al.
were linear regression (LR); support vector machines (SVM; linear kernel, radial
basis function and poly); decision tree, naive Bayes (NB); random forest (RF), unsupervised
K-means and Gaussian expectation-maximization.
The results show that the best method of the compendium used by
He et al. [ 12 ]
for the
dataset generated is random forest because of its high precision during the
evaluation stage.
Appl. Sci. 2021 , 11 , 10609 3 of 15
Aamir et al. [
13
] proposed a framework based on four main phases: obtaining the
dataset, feature engineering, evaluating the ML model, and results. The dataset is obtained
by systematically exploring published and validated datasets that contain evidence of
DDoS attacks. Once the dataset has been selected, feature engineering is carried out. In the
feature engineering stage, the dataset is analyzed in order to recognize its environment and
perform tasks of duplication and collinearity identification between different attributes.
Similarly , an adjustment is made to make it suitable for training the selected ML model.
Model evaluation includes a first stage of training, adjustment of hyperparameters
based on the results, and evaluation of the resulting model following its modifications.
] evaluated five machine learning models: SVM, RF, artificial neural
network (ANN), NB, and knearest neighbors (KNN). The author highlighted the impor-
tance of the processes before deployment of the ML models and attributed the results
of precision, false positives and recall of the different methods to the established work
framework. Adjusting the hyper-parameters allows the model designer to fine tune cer-
tain settings which, depending on the qualities of the data, can significantly impact the
model’s result.
Elyased et al. [
10
] used the same dataset as the present investigation, i.e., that proposed
by the authors of the CIC [
9
]. This dataset is the same one used in our research. That work
implemented a method based on deep learning structured with a recurrent neural network
(RNN) and an autoencoder.
The method of Elyased et al. contains a data preprocessing stage in which certain
network attributes are not considered for model training. The training phase is carried out
to obtain a binary classification model. The model is trained in order to classify whether
a specific attack flow is malignant or benign by dividing the dataset by attack type and
feeding the model in this way .
The model is composed of an input layer and then, in the hidden layer, a RNN
is implemented with an autoencoder, ending with an output layer in which the binary
of the input information to then perform decoding, in which the coded attributes are
reconstructed to generate an output in the final layer that assimilates information belonging
to the label of the registry [ 14 ].
The result of the above research is a model called DDosNet that has high accuracy
in classifying benign and malignant flows. In their section on future works, Wang et al.
stressed that although it is important to identify whether the flow is malignant or benign,
it is also desirable to be able to detect the specific type of attack evidenced by the flows.
This implementation is proposed as work to be done in new DDoSNet implementations.
Li [
11
] used the CIC dataset, the same dataset used in our research. Li proposed
the evaluation of three models, which use concepts such as dense neural networks, self-
encoders, and Pearson’s correlation coefficient (PCC). Dense neural networks are made up
by layers whose neurons are fully connected be- tween each layer , i.e., each neuron in each
layer receives information from all neurons in the previous layer and sends information
to all neurons in the next layer [
15
]. In this case, the PCC attempts to measure linear
correlation between two attributes of the dataset. Once PCC is applied to the attributes, a
value is obtained between
−
1 and 1. There is no linear correlation if the value is 0, 1 if the
−
1 if there is totally negative linear correlation [
16
].
In Li et al.’s work, five major processes were executed: analysis and engineering of
dataset attributes, dataset training, adjustments based on results of the training, testing with
information not previously seen, and comparison with traditional ML methods. The three
resulting models perform a binary classification of the flow , i.e., like Elyased et al. [
10
], the
model is limited to binary classification as benign or malignant. The composite models can
be understood as a disaggregation of the proposed steps. That is, the initial model is a dense
neural network, the second a dense neural network with an implemented autoencoder, and
the third a dense neural network with an autoencoder that receives information subsets as
Appl. Sci. 2021 , 11 , 10609 4 of 15
input data which through the PCC analysis does not include attributes that have strong
linear correlation.
In the third model from Li et al., the training is executed with a subset of the dataset
that only contains one type of attack and based on the PCC analyses, the attributes of the
subset that contain a PCC value greater than 0.9 and less than − 0.9 are eliminated.
The three proposed models give different results depending on the attack classification
as malignant or benign. In general, the model constructed only with dense neural networks
neural network with autoencoding and, lastly , the dense neural network with autoencoder
and PCC analysis.
The limitations of the existing works relay on the classification score and its behavior
on each label. The models’ score tends to variate considerably between the labels with a
model’s scores varying between the 0.5 and 0.9 on average.
3. Methodology
3.1. Dataset Selection
Datasets constitute a main element in the ML field. When initiating any type of con-
ceptualization of a ML model, it is essential to obtain or develop a dataset that assimilates
realworld situations or events to be classified in order to conduct successful training and a
validation phase [ 17 ].
For the choice of dataset in our research, three sources of information wer e consid-
ered: “DDoS Attack 2007” [
18
]; “Anonymized Internet T races” [
19
] provided by CAIDA;
“CICDDoS2019” [ 9 ] provided by CIC.
The two remaining datasets have very complete information on network traffic cap-
tures and both provide a compilation of information exceeding 20 GB. Therefore, the
amount of information is more than enough for ML model training. However, the data
from the Anonymized Internet T races dataset lacks preprocessing and therefore labels in
its records. Consequently , training a model like the one used in the present work with this
information would involve an arduous phase of data labeling.
Based on the assessment and analysis of the datasets explored, we decided to use the
CIC dataset for training and validation of the model used.
The dataset provided by CIC is designed to provide reliable information for training
DDoS attack detection models. Unlike previously proposed datasets, CIC seeks to remedy
drawbacks of these, such as the lack of categorized information, attackers with implemen-
tation of simple-level intrusions, and a lack of generation of modern attacks such as NTP ,
NetBIOS, and TFTP [ 9 ].
The attacks implemented in the CIC dataset were classified into two main branches,
Reflection-based DDoS and Exploitation-based DDoS.
•
Reflection-based DDoS is a type of attack in which the attacker remains hidden during
its execution through the legitimate use of third-party components. The attacker sends
packets to reflecting servers with the source IP configured as the victim’s IP , ther eby
overloading the victim with responses from these servers. The attacks evidenced
in this dataset can be subcategorized as TCP (MSSQL, SSDP), UDP (CharGen NTP ,
TFTP), or TCP/UDP (DNS, LDAP , NetBIOS, SNMP , PortMap). That is, they can be
performed using both protocols [ 9 ].
•
Exploitation-based DDoS, in concept, are similar to Reflection-based DDoS with the
difference that these attacks can be conducted through application-layer protocols
using transport-layer protocols. The attacks evidenced in this dataset can be subcate-
gorized as TCP (Syn-Flood) or UDP (UDP Flood, UDP-Lag) [ 9 ].
The taxonomy of attacks proposed by Sharafaldin et al. [ 9 ] is illustrated in Figure 1 .
Appl. Sci. 2021 , 11 , 10609 5 of 15
Appl. Sci. 2021 , 11 , x FOR PEER REVIEW 5 of 16
• Exploitation-based DDoS, in concept, are similar to Reflection-based DDoS with the
difference that these attacks can be cond ucted through application-layer protocols
using transport-layer protocols. The attacks evidenced in this dataset can be subcat-
egorized as TCP (Syn-Flood) or UDP (UDP Flood, UDP-Lag) [9].
The taxonomy of attacks proposed by Sharafaldi n et al. [9] is illustrated in Figure 1.
Figure 1. DDoS attack taxonomy [8].
The dataset is available in two formats, packet capture (PCAP) and comma-separated
values (CSV).
The PCAP files contain raw information ca ptured by the network monitoring tool
and are not categorized. However, a table is pr ovided that specifies the period of the at-
tacks. On the other ha nd, CSV files are categorized and processed to record in rows the
flow of information over the network. These files were generated from the PCAP files
using the CICFlowMeter [20] tool, which consis ts of the generation of traffic flow across
the network.
Model training and evaluation was mainly done using the files already preprocessed
and offered by CIC. Based on information about the q uality of these files, as set out by Li
[11] in reference to obtaining fewer invalid values (NaN, and infinite) in the new files
generated by CICFlowMeter, these new files generated by CICFlowMeter are in the CSV
format. However, this did not improve the accuracy of our model.
The total amount of information in the dataset i s 28.1 GB in CSV extension files and
19.1 GB in PCAP extension, considered sufficient for model training and validation [21].
The CIC DDoS dataset contains 87 attribut es, of which 83 were generated by the
CICFlowMeter application and four instantiated by Sh arafalding et al. [9]. However, net-
work attributes were eliminated so the model can be deployed in future work in another
network structured differently than that in which the CIC data were captured. In total, 78
attributes were used. For an in-depth look at these attributes, refer to Sharafaldin et al.
table of attributes [9].
3.2. Data Preprocessing
It is possible to train the model with the data after removing certain unwanted attrib-
utes, as mentioned above. However, deploymen t of a data preprocessing phase results in
more robust training and thereby a more acc urate model [22].
First, each file belonging to the dataset is unified into an information in stance. Each
file contains mostly one type of attack. Because the main objective is the implementation
of a model capable of classifying whether ther e was a benign or malignant flow and if the
Figure 1. DDoS attack taxonomy [ 8 ].
The dataset is available in two formats, packet capture (PCAP) and comma-separated
values (CSV).
The PCAP files contain raw information captured by the network monitoring tool and
are not categorized. However, a table is provided that specifies the period of the attacks.
On the other hand, CSV files are categorized and processed to record in r ows the flow of
information over the network. These files were generated from the PCAP files using the
CICFlowMeter [
20
] tool, which consists of the generation of traffic flow across the network.
Model training and evaluation was mainly done using the files already preprocessed
and offered by CIC. Based on information about the quality of these files, as set out by
Li [
11
] in reference to obtaining fewer invalid values (NaN, and infinite) in the new files
generated by CICFlowMeter, these new files generated by CICFlowMeter ar e in the CSV
format. However, this did not improve the accuracy of our model.
The total amount of information in the dataset is 28.1 GB in CSV extension files and
19.1 GB in PCAP extension, considered sufficient for model training and validation [ 21 ].
The CIC DDoS dataset contains 87 attributes, of which 83 were generated by the
CICFlowMeter application and four instantiated by Sharafalding et al. [
9
]. However,
network attributes were eliminated so the model can be deployed in future work in another
network structured differently than that in which the CIC data wer e captured. In total,
78 attributes
were used. For an in-depth look at these attributes, refer to Sharafaldin et al.
table of attributes [ 9 ].
3.2. Data Preprocessing
It is possible to train the model with the data after removing certain unwanted at-
tributes, as mentioned above. However, deployment of a data preprocessing phase results
First, each file belonging to the dataset is unified into an information instance. Each
file contains mostly one type of attack. Because the main objective is the implementation of
a model capable of classifying whether there was a benign or malignant flow and if the
flow is malignant to output the name of the attack, it is necessary to feed the model with
information that considers different labels.
The unified dataset contains values invalid for training. There are inputs of NaN and
infinite values, which are discarded to execute model training. About 3% of the data were
removed in this procedure.
The objective with the model is multiclass classification in the context of DDoS attacks.
T o do this, an encoding procedure is necessary . For this procedure, it is necessary to
transform the dataset labels so they can be used by the model. In our research, we used
Appl. Sci. 2021 , 11 , 10609 6 of 15
One Hot Encoder (OHE). OHE processing assigns a new column for each label represented
in the dataset and a value of 1 if the record belongs to this category or 0 otherwise [
23
]. The
need for this encoding is based on the implementation of an output layer with a Softmax
activation function. The Softmax function transforms a vector of k real values to one of k
real values that add to unity [ 24 ].
In the next step of the data preprocessing, the data are normalized based on the L2
normalization. The use of L1 normalization was contemplated but results in the training
phase showed small values of the model’s accuracy metric. The L2 standard was applied
x
being each occurrence of a
record, define the normalization Formula (1) as:
|| x | | 2 = s n
∑
i = 1
| x i | 2 , (1)
Normalizing the dataset records generally results in much faster training [
25
]. This
behavior is evidenced in our model. In addition to improvement in convergence during
the training phase, this normalization yielded better model accuracy owing to the handling
of a uniform range of dataset attributes.
W e conducted transformation by quartiles after the data normalization. This method
transforms the attribute values of each dataset input in order to follow a uniform or normal
distribution. For the model used, we decided to follow a normal distribution because of
improvement in the accuracy metric compared to the uniform distribution.
In analyzing the information of the unified dataset, an imbalance of classes was
detected, which resulted in a classification biased to a certain class because of its high
frequency in the dataset. Table 1 presents the occurr ence count according to the classes in
the dataset.
T able 1. Distribution of labels in the loaded dataset.
TFTP 975,826 37.605%
DrDoS_SNMP 257,240 9.913%
DrDoS_DNS 245,654 9.467%
Syn 228,521 8.806%
DrDoS_MSSQL 220,052 8.480%
DrDoS_NetBIOS 198,815 7.662%
UDP 159,751 6.156%
DrDoS_SSDP 128,614 4.956%
DrDoS_LDAP 107,084 4.127%
DrDoS_NTP 59,736 2.302%
Portmap 8831 0.340%
BENIGN 4754 0.183%
UDPLag 91 0.004%
As seen in T able 1 , the TFTP class has a strong presence in the dataset, whereas labels
of the BENIGN or UDPLag type had small percentages of occurrence. Therefore, balancing
the dataset is necessary for better training of the model.
In this research we propose the use of a fully balanced dataset, i.e., an equivalent
percentage between the classes. There are three ways of balancing: duplicity of the labels
to be balanced; elimination of label occurrences with the highest percentage in the dataset;
a synthetic minority oversampling technique (SMOTE) [ 26 ].
The first balancing method resulted in a successful training phase. However, in the
test phase, we validated a case of overfitting in the dataset used for training, because
training phase.
Appl. Sci. 2021 , 11 , 10609 7 of 15
The second method, eliminating records belonging to strongly represented labels
in the dataset, was applied and tested. In this case, the training phase produced low
model precision. W e conclude that the results of this technique are attributable to a
strong reduction of the dataset in order to find class balance. SMOTE was applied in our
model as a class balancing technique for the dataset. SMOTE was proposed in 2002 by
Chawla et al. [ 26 ] as an alternative to class balancing to generate synthetic information.
Because the generation operation is run in attribute space, use of the technique is
more general. The SMOTE mode of operation is based on identification of class records to
generate synthetic information and the union of these occurrences, equivalent to
k
close
neighbors of the same class, by means of lines. After this step, synthetic occurrences
S s
are
generated by taking the difference between the vector of attributes
S
, i.e., an occurrence of
the class and closest neighbor
S n
in the
range 0 to 1 and added to the vector of attributes
S
, resulting in the selection of a random
point on the line segments of two specific attributes (2) [ 26 , 27 ]:
S s = S + r × ( S − S n ) , (2)
This method resulted in a better accuracy metric for both the training and testing phase,
unlike the two aforementioned techniques. It is important to note that this oversampling
technique was applied only to the training data and not the test data.
The dataset was split in two subsets resulting in one subset referring to information
for use in training, which was equivalent to 80% of the total information; 20% of the
information was used during the model testing phase.
3.3. Definition of Proposed Model
In this subsection, the model architecture proposed for this resear ch is defined. First
is the definition of the model, which is made up of layers of densely connected neural
networks. The model has a sequential architectur e with seven layers one input, five hidden,
and one output.
The initial layer, the input layer , has 78 neurons, which encapsulates the 78 attributes
of the dataset used. The hidden layers segment is defined by densely connected layers,
which can be understood as those in which each neuron receives an input from all the
neurons instantiated in the previous layer [ 28 ].
A rectified linear activation function (ReLU) is handled in each layer . ReLU evaluates
equal to 0. The decision to use ReLU as the main activation function of the model was a
consequence of its computational simplicity and its being an evaluation function of the
maximum between the input value and 0 [ 29 ].
In this model, a layer called Dropout was used. The function of this layer is to ignore
a rate of nodes in a random fashion. This in part represents an effect in which neurons can
modify the way in which they correct the errors of other neurons, which entails complex
co-adaptations that do not generalize unseen information, as raised by Srivastava et al. [
30
].
The model output layer is instantiated with a Softmax activation function. The choice
of this function is associated with the main task of the model, which is classification in
a multiclass context. This function will return a probability of the maximum value in an
array , which is interpretable as the most probabilistically accurate label for the sample
being evaluated [ 31 ].
The loss function used in the model is categorical cross-entropy [
32
], also known as
Softmax loss, and the instantiated optimizer is Adam [
33
]. A representative image of the
defined model is in Figure 2 .
Appl. Sci. 2021 , 11 , 10609 8 of 15
array, which is interpretable as the most probabilist ically accurate label for the sample
being evaluated [31].
The loss function used in the model is cate gorical cross-entropy [32], also known as
Softmax loss, and the instantiated opt imizer is Adam [33]. A representative image of the
defined model is in Figure 2.
Figure 2. Visual representation of defined model.
4. Model Evaluation
The information is initially divided for training and testing, with training information
constituting 80% of the total information and 20% for testing. Of the 20% of the test infor-
mation, 10% is used for hyperparameter tuning and the other 10% is treated as p reviously
unseen information for the model.
For the evaluation, we considered three scenar ios that focus on the labels used during
the training phase. The first scenario consider s all the labels in the dataset. The second
considers 10 labels that do no t present similarity in the attribute space. The third performs
a union of labels with strong simil arity in the attribute space. The main re ason for this
separation of scenarios is because of the stro ng similarity between labe ls in terms of at-
tributes caused by the information generated by the attack an d is captured by the instru-
ments used by Sharafaldin et al. [9].
For all three scenarios, the model structure re mains largely constant with a modification
in the output layer due to the difference in number of classified labels. The metrics used
for evaluation of the hyperparameter selectio n and evaluation o f the scenarios and, in
turn, the model metrics, are defined as follows:
𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒𝑠 (3)
𝑝𝑟𝑒𝑐𝑖𝑠𝑖𝑜𝑛 = 𝑡
𝑡 +
𝑓
(4)
Figure 2. Visual representation of defined model.
4. Model Evaluation
The information is initially divided for training and testing, with training information
constituting 80% of the total information and 20% for testing. Of the 20% of the test
information, 10% is used for hyperparameter tuning and the other 10% is treated as
previously unseen information for the model.
For the evaluation, we considered three scenarios that focus on the labels used during
the training phase. The first scenario considers all the labels in the dataset. The second
considers 10 labels that do not present similarity in the attribute space. The third performs
a union of labels with strong similarity in the attribute space. The main reason for this sep-
aration of scenarios is because of the strong similarity between labels in terms of attributes
caused by the information generated by the attack and is captured by the instruments used
by Sharafaldin et al. [ 9 ].
For all three scenarios, the model structure remains lar gely constant with a modifica-
tion in the output layer due to the difference in number of classified labels. The metrics
used for evaluation of the hyperparameter selection and evaluation of the scenarios and, in
turn, the model metrics, are defined as follows:
numb er o f sa mpl es (3)
preci sion = t p
t p + f p (4)
rec all = t p
t p + f n (5)
f 1 score = 2 × preci sion × re call
preci sion + re call (6)
where t p = true positives, t n = true negatives, f p = false positives and f n = false negatives.
Appl. Sci. 2021 , 11 , 10609 9 of 15
4.1. Hyperparameter Tuning
Firstly , a tuning of the hyperparameters was done to determine the optimal settings for
model training. The hyperparameters were configured following a model of configuration,
testing, and selection of the best option for the configuration in question. W e initially
selected the depth of the neural network, i.e., its number of layers. For this choice, a depth
in the hidden-layer block of 2, 3 and 4 is proposed. Based on the result, a depth of 3 was
chosen, owing to model accuracy and the time spent in its training.
The number of neurons instantiated in each layer was configured based on the choice
of best configuration candidate. During this procedure, about 10 different configurations
were evaluated, and the structure (128,256,512) was chosen, which refers to the number of
neurons of the 3 layers previously configured and belonging to the block of hidden layers.
The learning rate of the Adam optimizer is configured based on three candidate
rates,
and
1 × 10 − 6 .
T able 2 shows the results according to the learning
rate used.
T able 2. Performance evaluation for the training rate of the model.
Rate Accuracy Precision Recall F1 Score
0.001 0.9370 0.9389 0.9352 0.9370
0.0001 0.9421 0.9421 0.9403 0.9412
0.00001 0.9379 0.9400 0.9359 0.9379
Based on this test, we selected the learning rate corresponding to 1
×
10
− 4
for configu-
ration of the Adam optimizer. As defined above, the dropout layer contains a rate of total
number of neurons to ignore.
For this model, we discovered that the rate of 0.3 gave the best tradeoff between
time of convergence of the model and its accuracy . Table 3 compares the rates used for
configuration of the Dropout layer . The training time in minutes (TTM) column represents
the maximum time that the accuracy metric did not vary by more than 0.0001 units.
T able 3. Performance evaluation of the different rates for dropout layer.
Rate Accuracy TTM Recall F1 Score
0.30 0.9421 30 0.9403 0.9412
0.35 0.9366 33 0.9299 09360
4.2. Results of the Model
Before presenting the results of the model, T able 4 indicates the hyperparameters
chosen for the model. Hyperparameters like the number of epochs, batch size and neurons
per layer were configured using the same approach as the others hyper-parameters. In
other words, a set of configurations was tested, and the best performing setting was chosen.
T able 4. Hyperparameter settings for the proposed model.
Hyperparameter Configuration
Number of layers 3
Adam optimizer learning rate 1 × 10 − 4
Dropout rate 0.30
Epochs 100
Batch size 128
Neurons per layer (layer #1 through layer #3) 128,256,512
In order to evaluate our model, we proposed three differ ent scenarios. Each scenario
has a different experiment configuration. The differences are within the number of labels.
Appl. Sci. 2021 , 11 , 10609 10 of 15
The reason behind this methodology is to see how the model performs under different
condition and to evaluate which would be the best condition in which the model would
perform optimally .
The results presented were obtained via cross validation. The setting for the cross
These settings were maintained throughout the three differ ent scenarios.
4.2.1. First Scenario
For this scenario, the model was trained to categorize 13 labels belonging to the dataset,
equivalent to those shown in T able 1 . The model evaluation for this scenario resulted in
the following values for the metrics of accuracy , precision, recall, and F1 score pr esented in
T able 5 .
T able 5. Model training results for the first scenario.
Accuracy Precision Recall F1 Score
0.8177 0.831 0.7995 0.8149
The confusion matrix resulting from the test is displayed in Figure 3 . This matrix
provides more detailed information on the labels, for which the model had a precision less
than the average reflected in T able 5 .
Appl. Sci. 2021 , 11 , x FOR PEER REVIEW 10 of 16
Table 4. Hyperparameter settings for the proposed model.
Hype
r
paramete
r
Configuration
Number of layers 3
Adam optimizer learning rate 1×1 0
Epochs 100
Batch size 128
Neurons per layer (layer #1 through layer #3) 128,256,512
In order to evaluate our model, we proposed three different scenarios. Each scenario
has a different experiment configuration. The differences are within the number of labels.
The reason behind this methodology is to see how the model performs under different
condition and to evaluate which would be the best condition in which the model would
perform optimally.
The results presented were obtained via cross validation. The setting for the cross
validation was a 5-fold validation for scores such as: accuracy, p recision, recall and F1
score. These settings were maintained throughout the three different scenarios.
4.2.1. First Scenario
For this scenario, the model was trained to categorize 13 labels belonging to the da-
taset, equivalent to those shown in Table 1. The model evaluation for this scenario resulted
in the following values for the metrics of accuracy, precision, recall, and F1 score pre-
sented in Table 5.
The confusion matrix resulting from the test is displayed in Figure 3. This matrix
provides more detailed information on the labels, for which t he model had a precision
less than the average reflected in Table 5.
Table 5. Model training results for the first scenario.
Accuracy Precision Recall F1 Score
0.8177 0.831 0.7995 0.8149
Figure 3. Confusion matrix for the first scenario.
In this scenario, the model exhibits confusion for the DrDoS DNS-DrDoS LDAP labels.
This confusion lies in the nature of the attacks and their similarity , as the information
captured by the network monitoring instrument is similar . The values reflected in the
dataset attributes will also have this similarity , thereby negatively affecting the metrics of
the model. The same behavior is observed for the Portmap, UDP, SSDP , and NetBios labels.
4.2.2. Second Scenario
For this scenario, the model was trained for the categorization of 10 labels: BENIGN,
DNS, MSSQL, NTP , NETBIOS, SNMP, SSDP , SYN, UDP-LAG, and TFTP . The attacks such
Appl. Sci. 2021 , 11 , 10609 11 of 15
as Portmap, UDP , and LDAP were removed from the testing subset, the training was made
using the same labels as scenario 1. Accuracy, pr ecision, recall and F1 score metrics are
listed in T able 6 . This is the result of model training in this scenario.
T able 6. Model training results for the second scenario.
Accuracy Precision Recall F1 Score
0.9457 0.9475 0.9438 0.9456
The confusion matrix of the model evaluation stage is shown in Figure 4 .
Appl. Sci. 2021 , 11 , x FOR PEER REVIEW 11 of 16
In this scenario, the model exhibits co nfusion for the DrDoS DNS-DrDoS LDAP la-
bels. This confusion lies in the nature of t he attacks and their similarity, as the information
captured by the network monitoring instrument is similar. The values reflected in the da-
taset attributes will also have this similarity, thereby negatively affecting the metrics of
bels.
4.2.2. Second Scenario
For this scenario, the model was trained for the categorization of 10 labels: BENIGN,
DNS, MSSQL, NTP, NETBIOS, SNMP, SSDP, SYN, UDP-LAG , and TFTP. The attacks such
as Portmap, UDP, and LDAP were removed from the testing subset, the training was
made using the same labels as scenario 1. Accu racy, precision, recall and F1 score metrics
are listed in Table 6. This is the result of model training in t his scenario.
Table 6. Model training results for the second scenario.
Accuracy Precision Recall F1 Score
0.9457 0.9475 0.9438 0.9456
The confusion matrix of the model evalua tion stage is shown in Figure 4.
Figure 4. Confusion matrix for the second scenario.
This matrix reveals a better result compared to Figure 3, owing to the non-consider-
ation of labels with values that are over-lapp ed in the attribute space. Although the scores
in this scenario are good, this scenario is mainly deployed to have a better idea on whether
the model is finding a high simi larity in between the labels.
4.2.3. Third Scenario
Figure 4. Confusion matrix for the second scenario.
This matrix reveals a better result compared to Figure 3 , owing to the non-consideration
of labels with values that are over-lapped in the attribute space. Although the scores in this
scenario are good, this scenario is mainly deployed to have a better idea on whether the
model is finding a high similarity in between the labels.
In the development of the third scenario, it was decided to unify the attacks with
strong similarity in the attribute space. These new labels are composed of the names
of the attacks that show this similarity . The new labels are DrDoS DNS/LDAP , DrDoS
NetBIOS/Portmap, and DrDoS SSDP/UDP . The model was retrained under the newly
created mixed labels. Also, the testing subset possess the newly created labels instead of
the previous labels, bringing the total of labels to 10 and still maintaining the same number
of attacks. Table 7 demonstrates the similarity between the labels in attribute space. The
name of the subset is equivalent to the union of labels made; this subset contains only the
two labels that show strong similarity .
Appl. Sci. 2021 , 11 , 10609 12 of 15
T able 7. Summary of subsets created for labels with strong similarity .
Subset ACV AFR0, % ASAH, %
DNS/LDAP 12 24, 99.9 38, 96.8
NetBIOS/Portmap 12 31, 98.0 41, 98.3
SSDP/UDP 12 25, 99.9 32, 97.9
The abbreviation ACV refers to attributes with constant value, AFR0 encapsulates the
attributes with a high frequency (
>
98%) of zeros, and ASAH contains the attributes that
have a strong bias due to a strong homogeneity of their values (
≥
96%). AFR0 and ASAH
also contain the respective percentages according to the metric.
The results of training of this model are shown in T able 8 .
T able 8. Model training results for the third scenario.
Accuracy Precision Recall F1 Score
0.9421 0.9421 0.9403 0.9412
The resulting confusion matrix from the testing phase is presented in Figure 5 .
Appl. Sci. 2021 , 11 , x FOR PEER REVIEW 12 of 16
In the development of the third scenario, it was decided to unify the attacks with
strong similarity in the attribute space. Th ese new labels are composed of the names of
the attacks that show this similarity. Th e new labels are DrDoS DNS/LDAP, DrDoS Net-
BIOS/Portmap, and DrDoS SSDP/UDP. The model was retrained under the newly created
mixed labels. Also, the testing subset possess the newly created labels instead of the pre-
vious labels, bringing the total of labels to 10 and still maintaining the same number of
attacks. Table 7 demonstrates the similarity between the labels in attribute space. The
name of the subset is equivalent to the union of labels made; this subset contains only the
two labels that show strong similarity.
The abbreviation ACV refers to attributes with constant value, AFR0 encapsulates
the attributes with a high frequency ( 98% ) of zeros, and ASAH contains the attributes
that have a strong bias due to a strong homogeneit y of their values ( 96% ). AFR0 and
ASAH also contain the respective percentages according to the metric.
Table 7. Summary of subsets created for labels with strong similarity.
Subset ACV AFR0, % ASAH, %
DNS/LDAP 12 24, 99.9 38, 96.8
NetBIOS/Portmap 12 31, 98.0 41, 98.3
SSDP/UDP 12 25, 99.9 32, 97.9
The results of training of this model are shown in T able 8.
Table 8. Model training results for the third scenario.
Accuracy Precision Recall F1 Score
0.9421 0.9421 0.9403 0.9412
The resulting confusion matrix from the testing phase is presented in Figure 5.
Figure 5. Confusion matrix for the third scenario.
Figure 5. Confusion matrix for the third scenario.
5. Discussion
The main contribution of this work is a framework for data preprocessing and a
classification model in a multiclass context for DDoS attacks. Compared to previously
reviewed proposals in the literature, in addition to categorizing the flow as malignant
or benign, the present model provides the type of attack evidenced in the flow (if it
is malignant). This characteristic is relevant when developing a security strategy for
deployment in a network that has experienced or is at risk of a DDoS attack.
The prop osed model for t he categoriz ation of DDoS att acks can be depl oyed in the appl i-
cation lay er within an SDN s oftware-d efined netwo rk, as propos ed by
Sharafal din et al. [ 9 ]
Appl. Sci. 2021 , 11 , 10609 13 of 15
and based on the implementation in Alshamrani et al. [
34
]. The aim is to be able to block
malignant flows or route them to analyze the flow and feed the future training of the model
and increase its stability [ 35 ].
A summary table stating the contribution of this paper, appr oach, dataset, limitation
and metrics related to the proposed model is presented in T able 9 .
T able 9. Result comparison with related works.
Author [Reference] Approach Average
(Precision, Recall, F1 Score)
Can et al. [ 36 ] 82 features + FS 91.16, 79.41, 79.43
Ferrang et al. [ 37 ] * DNN 70.00
RNN 70.00
CNN 66.46
Sharafaldin et al. [ 9 ] Naive Bayes 30.30, 17.51, 7.35
SVM 62.44, 57.97, 55.50
Decision T ree 61.15, 58.32, 55.15
Random Forest 50.76, 36.91, 39.57
Our approach DNN 94.21, 94.03, 94.12
* No distinction for the metrics is stated by the author.
In T able 9 , we can see how our approach outperforms those presented by Can et al. [
36
]
Ferrang et al. [
37
] and Sharafaldin et al. [
9
], the latter being the benchmark. We attribute the
scores achieved by our model due to processing phase of the research and the combined
labels proposed previously .
Our proposed model is limited by the labels used in the training phase, meaning, it
will not be able to detect accurately whether a new attack is not present before is detected
in a malign flow . In the case an attack is present in a flow set to be evaluated by the model,
the model will classify as malign, but it will output an incorrect type of attack. This can be
solved by providing a new label during the training phase with the name NEW . This will
encapsulate a new attack and reduce the ambiguity of the output.
6. Conclusions and Future Work
In this work, a preprocessing stage and multiclass classification neural network model
are presented. During the preprocessing stage, various transformation techniques were
applied to the dataset. This improved the accuracy metrics and training time of the
proposed model.
Different datasets were evaluated for model training, and it was decided to conduct
this work with the dataset provided by researchers from the CIC. During the pr oposed
preprocessing stage, it was possible to perform a cleaning of NaN-type and null values.
Similarly , a data normalization and quantile transformation were performed on the dataset.
T o obtain a balanced dataset in the context of classes, the SMOTE technique was applied
only to the sample used for model training.
The model was tuned based on a hyperparameter configuration. From the results of
model training and validation, the tuning was applied mainly to the number of hidden
layers, the rate used in the Dropout layer , and the learning rate. The model was trained
and evaluated in three different scenarios. The results, metrics, and confusion matrix were
presented for each scenario.
The results show the third scenario as the best. This analysis was based on the
performance metrics of the scenarios and number of labels used in the training phase.
Scenario 2 yielded a 94.57% accuracy , greater than Scenario 3 by 0.31%. However, it was
not trained with the 13 labels available in the dataset, unlike the third scenario, which was
trained with all labels. The added value of the proposed model consists in identifying
the type of attack evidenced in a flow , as compared with the binary classification of
recent works.
Appl. Sci. 2021 , 11 , 10609 14 of 15
As future work, we propose to deploy and evaluate the model in a computer network
that has a flow not previously seen by the model. This deployment will consist of a model
evaluation phase. Depending on the results, we propose to conduct a model training
phase with the captured data. Once the model has been trained and validated, it could be
instantiated as a network traffic manager whose objective is to reject or accept network
flows based on the evaluation performed. Furthermore, this could be deployed in an
intrusion-tolerant-system in order to prevent denial of service attacks, as proposed by
Kwon et al. [ 38 ].
Author Contributions:
Conceptualization, A.C. and J.M.; methodology, A.C. and J.M.; software,
A.C.; validation, A.C. and J.M.; formal analysis, A.C.; investigation, A.C.; resources, A.C.; data
curation, A.C.; writing—original draft preparation, A.C. and J.M.; writing—review and editing, J.M.;
visualization, A.C. and J.M.; supervision, J.M.; project administration, J.M. All authors have read and
agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement:
The data used in this study a re openly available in Canad ian Institute for
Cybersecurity at http s://www .unb.ca/cic/datasets/ ddos-2019.html (accessed on 12 January 2021 ).
Acknowledgments:
Our highest recognition for the Systems Engineering department of the Univer-
sidad del Norte.
Conflicts of Interest: The authors declare no conflict of interest.
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... Numerous ML/DL-based systems were proposed and demonstrated utilizing the CIC-DDoS2019 dataset. However, many of these solutions either do binary classification detecting only benign and attack traffic, or detect limited number of attacks
[12]
[13] [14]. However, each type of DDoS attack has unique way of operation. ...
... Several researchers used state-of-the-art DL-based approach to detect DDoS attacks and compared their performance with shallow machine learning models. However, many studies utilized old datasets that do not contain recent attack scenarios
[12]
. In addition, many of these datasets do not include packetbased bi-directional traffic flow and do not contain complete network traffic [33]. ...
... One limitation of the proposed approach is that, it constrained by the labels used in the training phase, which means it won't be able to detect whether a new attack is present before it is recognized in a malicious traffic flow. If an attack is present in a traffic flow set to be assessed by the model, the model will identify it as malicious, but it will return the wrong type of attack
[12]
. ...
A Multi-Classifier for DDoS Attacks Using Stacking Ensemble Deep Neural Network
Conference Paper
Full-text available
May 2022
Moinul Islam Sayed
Ibrahim Mohammed Sayem
Sajal Saha
Anwar Haque
DDoS (Distributed Denial of Service) attacks have emerged as a serious menace to the security and integrity of data and information systems. The primary aim of this attack is to take down the targeted system and prevent legitimate users from accessing its services. Identifying a DDoS attack is a challenging task, and it must be performed before initiating any countermeasure. DDoS attack detection has been effectively applied in many studies using Machine Learning (ML) and Deep Learning (DL). However, many existing models are unable to recognize the distinct and dynamic behavior of DDoS attacks because they employ datasets that were produced a long time ago and lack up-to-date attack scenarios, do not include packet-based bi-directional traffic flow, and do not contain complete network traffic. In addition, most studies carried out binary classification, however, there are many types of DDoS attacks, each with its unique characteristics. Classifying DDoS attacks can be useful when thwarting the attack and taking preventive measures. This paper presents a multi-classifier model using stacking ensemble deep neural networks that identify several types of DDoS attacks to address the issues mentioned above. Our proposed hybrid model incorporates Convolution Neural Network (CNN), Long Short Term Memory (LSTM), and Gated Recurrent Unit (GRU), and we show that while evaluating models with large datasets such as CIC-DDoS2019, ensemble technique increases model performance. According to experimental results, our proposed model can reach an accuracy of 89.4%, which outperforms other similar methods.
... Unlike a DoS attack, a DDoS attack is performed from multiple devices and addresses at once, as shown in Fig. 2. A DDoS attack is a hacker attack that paralyzes websites in a short period of time [10]. DDoS attacks are not intended to disrupt the victim's system but cause the service to fail
[11]
. The most serious malware among industrial hazards is called Flame. ...
... An SVM classifier
[11]
defines a hyperplane, dividing the input data into several classes. This hyperplane tries to separate the data in the best way. ...
Comprehensive DDoS Attack Classification Using Machine Learning Algorithms
Article
CMC-COMPUT MATER CON
Olga Ussatova
Aidana Zhumabekova
Yenlik Begimbayeva
Nikita Ussatov
The fast development of Internet technologies ignited the growth of techniques for information security that protect data, networks, systems, and applications from various threats. There are many types of threats. The dedicated denial of service attack (DDoS) is one of the most serious and widespread attacks on Internet resources. This attack is intended to paralyze the victim’s system and cause the service to fail. This work is devoted to the classification of DDoS attacks in the special network environment called Software-Defined Networking (SDN) using machine learning algorithms. The analyzed dataset included instances of two classes: benign and malicious. As the dataset contained twenty-two features, the feature selection techniques were required for dimensionality reduction. In these experiments, the Information gain, the Chi-square, and the F-test were applied to decrease the number of features to ten. The classes were also not completely balanced, so undersampling, oversampling, and synthetic minority oversampling (SMOTE) techniques were used to balance classes equally. The previous research works observed the classification of DDoS attacks applying various feature selection techniques and one or more machine learning algorithms. Still, they did not pay much attention to classifying the combinations of feature selection and balancing methods with different machine learning algorithms. This work is devoted to the classification of datasets with eight machine learning algorithms: naïve Bayes, logistic regression, support vector machine, k-nearest neighbors, decision tree, random forest, XGBoost, and CatBoost. In the experimental results, the Information gain and F-test feature selection methods achieved better performance with all eight ML algorithms than with the Chi-square technique. Furthermore, the accuracy values of the oversampled and SMOTE datasets were higher than that of the undersampled and imbalanced datasets. Among machine learning algorithms, the accuracy of support vector machine, logistic regression, and naïve Bayes fluctuates between 0.59 and 0.75, while decision tree, random forest, XGBoost, and CatBoost allowed achieving values around 0.99 and 1.00 with all feature selection and class balancing techniques among all the algorithms.
... XGBoost, on the other hand, further optimises the gradient Boosting method through the use of parallelization, tree pruning, hardware optimization, regularisation, sparsity awareness, and cross-validation. This technique is extremely scalable in all cases and performs faster on a wide variety of memory-constrained platforms
[37]
. We utilised the term "friedman Mean Squared Error" to quantify the quality of a split. ...
Defensive mechanism against DDoS attack based on feature selection and multi-classifier algorithms
Article
Full-text available
Dec 2022
TELECOMMUN SYST
Anupama Mishra
Neena Gupta
Brij B. Gupta
Distributed denial of service attacks are common and very severe threat to various computing technology like Cloud, IoT and Blockchain because of the disruption they cause to the services that are provided. Many different types of DDoS attacks are there, each with a unique action, making it difficult for network monitoring and control systems to identify and prevent them. The objective of this research work is to explore and select a set of data to represent DDoS attack events and attack traffic information. A pre-processing phase is used to clean and transform the data, and afterwards the generation of a model of machine learning for multi-class classification is done. This is carried out to identify the various classification of different types of DDoS attacks. We have used CIC dataset for the experiment which contains all types of DDoS attack and huge in number of records. Random Forest, Support Vector Machine, Naive Bayes, Decision Tree, XGBoost, and AdaBoost are six different types of machine learning algorithms employed in this research. FRom the results, AdaBoost achieves the best accuracy of 99.87% in 27.4 s of computation time. Naive Bayes has the fastest computing time (3.2 s) with 94.15% accuracy, where as Support Vector Machine has the slowest time, a lazy learner (229m26s for training and 0.2 s for prediction) and has the low accuracy (95.73%).
... It is a supervised learning approach; it divides the different classes using a hyper plane and then constructs a model that is capable of detecting previously unseen samples [25][26]
[27]
. For multilabel classification, LinearSVC from Sci-Kit Learn was used using the parameter "ovr" one-vs-rest, which stands for oneversus-rest. ...
Prediction Approach against DDoS Attack based on Machine Learning Multiclassfier
Preprint
Full-text available
Apr 2022
Anupama Mishra
DDoS attacks, also known as distributed denial of service (DDoS) attacks, have emerged as one of the most serious and fastest-growing threats on the Internet. Denial-of-service (DDoS) attacks are an example of cyber attacks that target a specific system or network in an attempt to render it inaccessible or unusable for a period of time. As a result, improving the detection of diverse types of DDoS cyber threats with better algorithms and higher accuracy while keeping the computational cost under control has become the most significant component of detecting DDoS cyber threats. In order to properly defend the targeted network or system, it is critical to first determine the sort of DDoS assault that has been launched against it. A number of ensemble classification techniques are presented in this paper, which combines the performance of various algorithms. They are then compared to existing Machine Learning Algorithms in terms of their effectiveness in detecting different types of DDoS attacks using accuracy, F1 scores, and ROC curves. The results show high accuracy and good performance.
New Denial of Service Attacks Detection Approach Using Hybridized Deep Neural Networks and Balanced Datasets
Article
Full-text available
Jun 2023
COMPUT SYST SCI ENG
Ouail Mjahed
Salah El hadaj
Emahdi Guarmah
Soukaina Mjahed
Denial of Service (DoS/DDoS) intrusions are damaging cyber-attacks, and their identification is of great interest to the Intrusion Detection System (IDS). Existing IDS are mainly based on Machine Learning (ML) methods including Deep Neural Networks (DNN), but which are rarely hybridized with other techniques. The intrusion data used are generally imbal-anced and contain multiple features. Thus, the proposed approach aims to use a DNN-based method to detect DoS/DDoS attacks using CICIDS2017, CSE-CICIDS2018 and CICDDoS 2019 datasets, according to the following key points. a) Three imbalanced CICIDS2017-2018-2019 datasets, including Benign and DoS/DDoS attack classes, are used. b) A new technique based on K-means is developed to obtain semi-balanced datasets. c) As a feature selection method, LDA (Linear Discriminant Analysis) performance measure is chosen. d) Four metaheuristic algorithms, counting Artificial Immune System (AIS), Firefly Algorithm (FA), Invasive Weeds Optimization (IWO) and Cuckoo Search (CS) are used, for the first time together, to increase the performance of the suggested DNN-based DoS attacks detection. The experimental results, based on semi-balanced training and test datasets, indicated that AIS, FA, IWO and CS-based DNNs can achieve promising results, even when cross-validated. AIS-DNN yields a tested accuracy of 99.97%, 99.98% and 99.99%, for the three considered datasets, respectively, outperforming performance established in several related works.
A DNN Architecture Generation Method for DDoS Detection via Genetic Alogrithm
Article
Full-text available
Mar 2023
Jiaqi Zhao
Ming Xu
Yunzhi Chen
Guoliang Xu
Nowdays, DNNs (Deep Neural Networks) are widely used in the field of DDoS attack detection. However, designing a good DNN architecture relies on the designer’s experience and requires considerable work. In this paper, a GA (genetic algorithm) is used to automatically generate the DNN architecture for DDoS detection to minimize human intervention in the design process. Furthermore, given the complexity of contemporary networks and the diversity of DDoS attacks, the objective of this paper is to generate a DNN model that boasts superior performance, real-time capability, and generalization ability to tackle intricate network scenarios. This paper presents a fitness function that guarantees the best model generated possesses a specific level of real-time capability. Additionally, the proposed method employs multiple datasets to joint models generated, thereby enhancing the model’s generalization performance. This paper conducts several experiments to validate the viability of the proposed method. Firstly, the best model generated with one dataset is compared with existing DNN models on the CICDDoS2019 dataset. The experimental results indicate that the model generated with one dataset has higher precision and F1-score than the existing DNN models. Secondly, model generation experiments are conducted on the CICIDS2017 and CICIDS2018 datasets, and the best model generated still performs well. Finally, this paper conducts comparative experiments on multiple datasets using the best model generated with six datasets and the best model generated by existing methods. The experimental results demonstrate that the best model generated with six datasets has better generalization ability and real-time capability.
A Review of DDoS Attack Detection and Prevention Mechanisms in Clouds
Conference Paper
Oct 2022
Muhammad Tehaam
Salman Ahmad
Hassan Shahid
Kashif Munir
Prediction of DDoS Attacks Using Machine Learning Algorithms Based on Classification Technique
Chapter
Dec 2022
Anupama Mishra
Deepesh Rawat
Distributed denial of service attacks often know as network threat is a severe threat, and are a type of cyber-attack that are directed at a particular system or network in an effort to make that system or net-work out of reach and unusable for a period of time. The improved detection of a wide variety of dis-tributed denial-of-service (DDoS) cyber threats by utilizing advanced algorithms and a higher level of accuracy while maintaining a manageable level of computational cost has consequently emerged as the utmost essential part of detecting DDoS in today’s world. The DDoS attack that has been launched against the targeted network or system must be determined in view of defending the machines in a net-work that has been targeted. In this paper, a number of ensemble classification techniques are dis-cussed, which combine the performance of various algorithms to improve overall performance. Using many performance metrics such as a receiver operating characteristics (ROC) curves, precision, accuracy, recall and F1 scores, we present and analyzed the performance of algorithms used in our proposed approach.KeywordsDistributed denial of service attackMachine learningRandom forestNaïve BayesDecision tree
Enhancing QoS of Network Traffic Based on 5G Wireless Networking Using Machine Learning Approaches
Chapter
Full-text available
Dec 2022
Shivani Saini
Sharvan Kumar Garg
Pankaj Pratap Singh
Akhilesh Pandey
5G wireless networks are based on heterogeneous networks. Heterogeneous networks offer a higher quality of service (QoS) and let you better utilize the resources of the network. Control of traffic on a network is complicated when a multiplicity of heterogeneous networks are present. When different protocols and data transmission rates are used, heterogeneous networks face the problem of managing and managing network traffic appropriately. In this paper our objective is to reduce Network Traffic and improve QoS for 5G wireless Network thus we have discuss some Supervised and Unsupervised Algorithm of Machine Learning Approach. So we have implemented K-mean algorithm in this paper will reduce traffic and improve the efficiency of 5G wireless Network. The K-mean is an iterative grouping technique that moves data objects between cluster sets until one desired set is reached. The dataset for K-mean Algorithm divides the traffic into two classes and then weighted mean is calculated for each cluster until the resultant output is identical weighted mean. If there are two clusters have identical weighted mean then there are no changes in cluster of classes.KeywordsHeterogeneous networkTraffic classificationMachine learningSupervised learningUnsupervised learning
Detection of Distributed Denial of Service (DDoS) Attacks Using Computational Intelligence and Majority Vote-Based Ensemble Approach
Article
Full-text available
Jan 2022
Anupama Mishra
Bineet Kumar Joshi
Varsha Arya
Kwok Tai Chui
The term “distributed denial of service” (DDoS) refers to one of the most common types of attacks. Sending a huge volume of data packets to the server machine is the target of a DDoS attack. This results in the majority of the consumption of network bandwidth and server, which ultimately leads to an issue with denial of service. In this paper, a majority vote-based ensemble of classifiers is utilized in the Sever technique, which results in improved accuracy and reduced computational overhead, when detecting attacks. For the experiment, the authors have used the CICDDOS2019 dataset. According to the findings of the experiment, a high level of accuracy of 99.98% was attained. In this paper, the classifiers use random forest, decision tree, and naïve bayes for majority voting classifiers, and from the results and performance, it can be seen that majority vote classifiers performed better.
DDoSNet: A Deep-Learning Model for Detecting Network Attacks
Software-Defined Networking (SDN) is an emerging paradigm, which evolved in recent years to address the weaknesses in traditional networks. The significant feature of the SDN, which is achieved by disassociating the control plane from the data plane, facilitates network management and allows the network to be efficiently programmable. However, the new architecture can be susceptible to several attacks that lead to resource exhaustion and prevent the SDN controller from supporting legitimate users. One of these attacks, which nowadays is growing significantly, is the Distributed Denial of Service (DDoS) attack. DDoS attack has a high impact on crashing the network resources, making the target servers unable to support the valid users. The current methods deploy Machine Learning (ML) for intrusion detection against DDoS attacks in the SDN network using the standard datasets. However, these methods suffer several drawbacks, and the used datasets do not contain the most recent attack patterns-hence, lacking in attack diversity. In this paper, we propose DDoSNet, an intrusion detection system against DDoS attacks in SDN environments. Our method is based on Deep Learning (DL) technique, combining the Recurrent Neural Network (RNN) with autoencoder. We evaluate our model using the newly released dataset CICDDoS2019, which contains a comprehensive variety of DDoS attacks and addresses the gaps of the existing current datasets. We obtain a significant improvement in attack detection, as compared to other benchmarking methods. Hence, our model provides great confidence in securing these networks.
Developing Realistic Distributed Denial of Service (DDoS) Attack Dataset and Taxonomy
Oct 2019
This paper applies an organized flow of feature engineering and machine learning to detect distributed denial-of-service (DDoS) attacks. Feature engineering has a focus to obtain the datasets of different dimensions with significant features, using feature selection methods of backward elimination, chi2, and information gain scores. Different supervised machine learning models are applied on the feature-engineered datasets to demonstrate the adaptability of datasets for machine learning under optimal tuning of parameters within given sets of values. The results show that substantial feature reduction is possible to make DDoS detection faster and optimized with minimal performance hit. The paper proposes a strategic-level framework which incorporates the necessary elements of feature engineering and machine learning with a defined flow of experimentation. The models are also validated with cross-validation and evaluated for area-under-curve analyses. It provides comprehensive solutions which can be trusted to avoid the overfitting and collinearity problems of data while detecting DDoS attacks. In the case study of DDoS datasets, K-nearest neighbors algorithm overall exhibits the best performance followed by support vector machine, whereas low-dimensional datasets of discrete feature types perform better under the Random Forest model as compared to high dimensions with numerical features. The accuracy scores of dataset with the lowest number of features remain competitive with other datasets under all machine learning models, leading to a substantially reduced processing overhead. The experiments show that approximately 68% reduction in the feature space is possible with an impact of only about 0.03% on accuracy.
Categorical Features Transformation with Compact One-Hot Encoder for Fraud Detection in Distributed Environment: 16th Australasian Conference, AusDM 2018, Bahrurst, NSW, Australia, November 28–30, 2018, Revised Selected Papers
Fraud detection for online banking is an important research area, but one of the challenges is the heterogeneous nature of transactions data i.e. a combination of numeric as well as mixed attributes. Usually, numeric format data gives better performance for classification, regression and clustering algorithms. However, many machine learning problems have categorical, or nominal features, rather than numeric features only. In addition, some machine learning platforms such as Apache Spark accept numeric data only. One-hot Encoding (OHE) is a widely used approach for transforming categorical features to numerical features in traditional data mining tasks. The one-hot approach has some challenges as well: the sparseness of the transformed data and that the distinct values of an attribute are not always known in advance. Other than the model accuracy, compactness of machine learning models is equally important due to growing memory and storage needs. This paper presents an innovative technique to transform categorical features to numeric features by compacting sparse data even if all the distinct values are not known. The transformed data can be used for the development of fraud detection systems. The accuracy of the results has been validated on synthetic and real bank fraud data and a publicly available anomaly detection (KDD-99) dataset on a multi-node data cluster.
| https://www.researchgate.net/publication/356168276_Multi-Classifier_of_DDoS_Attacks_in_Computer_Networks_Built_on_Neural_Networks |
Can't seem to manage my little flock | BackYard Chickens - Learn How to Raise Chickens
I have three girls who've been raised together since they were 13 weeks. They have an established pecking order. They have about 100 sq ft with roosts and...
Thread starter meadrian Start date Jun 2, 2010
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Jun 2, 2010 #1
meadrian
Songster 10 Years
May 22, 2009 219 13 159 San Francisco, CA
I have three girls who've been raised together since they were 13 weeks. They have an established pecking order. They have about 100 sq ft with roosts and a pecking block.
The lowest in the pecking order gets her feathers pecked occassionaly. She sits there and lets them do it. Over time she's lost alot of contour feathers, but no skin breaks or blood. Feather loss mainly. Lots of them. But again, this happened over time.
I've separated her during the day. They can see each other and sometimes sit near each other with the fence in between. When I get home I put them together and watch with squirt bottle in hand. This has gone on four 4+ weeks.
I'm wondering if there will EVER be a time they don't pick on her. It seems like she's just slowly pecked at all the time. HELP!!!!! I need them to be able to live together at some point. Any suggestions, please!
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Jun 2, 2010 #2
tigerrrrrrrlilly
Songster 9 Years
Mar 27, 2010 768 8 131 San Diego, CA
Maybe the chickens are lacking enough protien in their diet, this can cause feather picking. I use game bird feed and scrambled eggs to increase protien for my bantams.
Reply
Jun 2, 2010 #3
karl E lutz
Songster 9 Years
Jan 29, 2010 1,037 3 140
Only if she is dead once it starts it never ends
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Jun 2, 2010 Thread starter #4
meadrian
Songster 10 Years
May 22, 2009 219 13 159 San Francisco, CA
They get meal worms and eggs, too. In fact I worried I was giving too much protein at one point.
So, what you're saying is this will never stop? At least until she's dead or removed permanently?
Reply
Jun 2, 2010 #5
Keri78
Songster 10 Years
Oct 17, 2009 849 10 141 NJ
can you free range them and just lock them up at night? Sometimes being out
& about gives them better things to do than pick at each other. If not maybe a chickie apron will help?
Reply
Jun 2, 2010 #6
karl E lutz
Songster 9 Years
Jan 29, 2010 1,037 3 140
It may stop but if they get a bloody spot separate her or they may peck her to death.
Reply
Jun 2, 2010 #7
triggfamily5
Songster 9 Years
Mar 30, 2010 268 0 119 Moorcroft, WY
I have that happen occasionally. I spray wound-kote or blu-kote ALL over their back and where it's bare, and let it dry before I put her back. It's a continuing process. I still have 2 that I am working on, but it has helped many of the others.
Is she a different breed or coloring than the others?
Reply
Jun 2, 2010 #8
tigerrrrrrrlilly
Songster 9 Years
Mar 27, 2010 768 8 131 San Diego, CA
They aren't trying to pick her to death by the sounds of it, it's not aggressive behavior, right? They want to be with eachother. They are eating the feathers because they lack something in their diet-- protien is most likely. You may also end up with egg-eating problems too if this is the case. What do you feed them?
Reply
Jun 2, 2010 Thread starter #9
meadrian
Songster 10 Years
May 22, 2009 219 13 159 San Francisco, CA
I got the chicken apron right away and she's been wearing it all this time. They get about 100 sq ft that's fenced to run around in during the day. That's as much "safe" free range I can give them during the day. This happened while they were in that space and over a long period of time. A peck here, a peck there, months go by and I have a chicken who's feathers are pulled.
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Jun 2, 2010 #10
Penturner
Songster 9 Years
Feb 1, 2010 889 22 131 Reno Nevada
Keep in mind that a lack of protein could be caused by the inability to metabolize the proteins they are eating. pay attention to all those other vitamins and minerals as well. Purine Nutri Blend is supposed to be a completely balanced food. Something like that might put an end to it if it is nutritionally caused.
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Moderate, but not heavy, tea drinking decreased the associated risk of gallstones in a Taiwanese population | Request PDF
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Moderate, but not heavy, tea drinking decreased the associated risk of gallstones in a Taiwanese population
March 2019
European Journal of Clinical Nutrition 73(Suppl 1)
DOI: 10.1038/s41430-018-0265-0
Authors:
National Cheng Kung University Hospital
National Cheng Kung University
National Cheng Kung University
Show all 7 authors Hide
Abstract
Background/objectives:
The aim of the present study was to investigate the relationship between tea drinking and gallstones, specifically to evaluate the amount and time of tea consumption by gender.
Subjects/methods:
A total of 14,555 eligible adults receiving health examinations were included. The participants were divided into three subgroups with tea consumption of none, <240/day and ≥240 ml/day. We defined 120 ml for each traditional Chinese teapot as a "cup," and the variable "cup-year" was obtained by multiplying the cups per day by the years of tea consumption. Based on the findings of abdominal ultrasound examination, gallstones was defined by the presence of movable or gravity-dependent intraluminal hyperechoic foci that attenuated ultrasound transmission.
Results:
Among the participants, 1040 (7.1%) had gallstones. In multivariate analysis, the inverse relationship between tea drinking habit and gallstones was significant (OR = 0.807; 95% CI = 0.685-0.951, p = 0.010). Daily consumption of 1-240 ml (OR = 0.741; 95% CI = 0.584-0.941, p = 0.014), but not ≥240 ml, was associated with reduced risk of gallstones. In addition, the 1-19 cup-year group had significantly lower associated risk of gallstones (OR = 0.677; 95% CI = 0.534-0.857, p = 0.001), while the ≥19 cup-year group did not. By gender, subjects with tea consumption of 1-19 cup-year exhibited a low associated risk of gallstones in both males (OR = 0.678; 95% CI = 0.504-0.913, p = 0.010) and females (OR = 0.671; 95% CI = 0.453-0.994, p = 0.047), while subjects with ≥19 cup-years did not.
Conclusions:
Appropriate tea drinking if less than 240 ml/day or 19 cup-years was associated with a decreased risk of gallstones in both genders.
A preview of this full-text is provided by Springer Nature.
Content available from European Journal of Clinical Nutrition
European Journal of Clinical Nutrition (2019) 73:401 – 407
https://doi.org/10.1038/s41430-018-0265-0
ARTICLE
Food and health
Moderate, but not heavy, tea drinking decreased the associated risk
of gallstones in a Taiwanese population
Fei-Lin Su 1 ● Chung-Hao Li 1 ● Yin-Fan Chang 1,2 ● Jin-Shang Wu 1,2 ● Chih-Jen Chang 1,2 ● Feng-H wa Lu 1,2 ●
Yi-Ching Yang 1,2
Received: 4 December 2017 / Revised: 24 May 2018 / Accepted: 2 July 2018 / Published online: 22 August 2018
© Springer Nature Limited 2018
Abstract
Background/Objectives The aim of the present study was to investigate the relationship between tea drinking and gallstones,
speci fi cally to evaluate the amount and time of tea consum ption by gender.
Subjects/Methods A total of 14,555 eligible adults recei ving health examinations were included. The participa nts were
divided into three subgroups with tea consumption of none, <240/day an d ≥ 240 ml/day. We de fi ned 120 ml for each
traditional Chinese teapot as a “ cup, ” and the variable “ cup-year ” was obtained by multiplying the cups per day by the years
of tea consumption. Based on the fi ndings of abdominal ultrasound examination, gallston es was de fi ned by the presence of
movable or gravity-dependent intraluminal hyperechoic foci that attenuated ultrasound trans mission.
Results Among the participants, 1040 (7.1%) had gallstones. In multivariate analysis, the inver se relationship between tea
drinking habit and gallstones was signi fi cant (OR = 0.807; 95% CI = 0.685 − 0.951, p = 0.010). Daily consum ption of 1
− 240 ml (OR = 0.741; 95% CI = 0.584 − 0.941, p = 0.014), but not ≥ 240 ml, was associated wi th reduced risk of gallstones.
In addition, the 1 − 19 cup-year group had signi fi cantly lower associated risk of gallston es (OR = 0.677; 95% CI = 0.534
− 0.857, p = 0.001), while the ≥ 19 cup-year group did not. By gender, subjects with tea consumption of 1 − 19 cup-year
exhibited a low associated risk of gallstones in both males (OR = 0.678; 95% CI = 0.504 − 0.913, p = 0.010) and females
(OR = 0.671; 95% CI = 0.453 − 0.994, p = 0.047), while subjects with ≥ 19 cup-years did not.
Conclusions Appropriate tea drinking if less than 240 ml/day or 19 cup-years was associated with a decreased risk of
gallstones in both genders.
Introduction
Gallst ones are a com mon gastr ointes tinal di sorder wor ldwide ,
with a prev alence of great er than 10% i n the West [ 1 , 2 ].
Although gallstones have a low mortality rate, the socio-
economic burden increases with morbidity and its complica-
tions. Because of the incr easingly Westernized diet a nd
environ ment in T aiwan, g allsto nes have a lso beco me a publi c
health problem in this context, with a prevalence of between
4.3 and 10.7 % [ 3 , 4 ]. Femal e gende r, increa sing age, o besity ,
family history of gallstones, oral contraceptive use, numb er of
pregna ncies, me nopau se [ 5 ], hepatitis C infection [ 6 ]a n d
chroni c kidney di sease [ 4 ] are asso ciated wi th increa sed risk
of gallstones. Moreover, a sedentary lifestyle [ 7 ], cigarette
smoking [ 8 ], and low levels of coffee drinking [ 9 ] have bee n
reported as modi fi able associated factors.
As for the relationship between tea consumption and
gallstones, only a few studies have been conducted and an
inconsistent association was found in these [ 9 – 12 ]. One
study reported a number of possible protective dietary
factors, including vegetables, and found that tea/coffee were
negatively associated with gallstones [ 12 ]. Other studies
showed an insigni fi cant association between tea consump-
tion and gallstones in men [ 9 , 11 ] but an inverse relation-
ship in women [ 11 ]. The aim of the present study was thus
to investigate the relationship between gallstones and tea
consumption by gender.
* Feng-Hwa Lu
fhlu@mail.ncku.edu.tw
* Yi-Ching Yang
yiching@mail.ncku.edu.tw
1 The Department of Family Medicine, National Cheng Kung
University Hospital, Tainan, Taiwan
2 The Department of Family Medicine, College of Medicine,
National Cheng Kung University, Tainan, Taiwan
... Tea consumption as another addictive behavior with caffeine intake (including black and green tea) has been associated with a GSD risk decreased in both genders within the population of Asia, and caffeine can stimulate cholecystokinin secretion and release bile acids into the intestine
(40,
41). Our MR verified this causal association in a European population, and tea polyphenol (mainly found in green tea) was also found to be causally associated with GSD risk, despite only one instrument being used. ...
Min Zhang
M.S. Srikanth
| https://www.researchgate.net/publication/327167780_Moderate_but_not_heavy_tea_drinking_decreased_the_associated_risk_of_gallstones_in_a_Taiwanese_population |
I. Statute Archives - The Reporters Committee for Freedom of the Press
I. Statute
Posts
Alabama
The primary legislative statement regarding the right of individuals to inspect and copy public records of the State of Alabama is contained in Alabama Code § 36-12-40, as follows:
Every citizen has a right to inspect and take a copy of any public writing of this state, except as otherwise expressly provided by statute. Provided, however, registration and circulation records and information concerning the use of the public, public school or college and university libraries of this state shall be exempted from this section. Provided further, any parent of a minor child shall have the right to inspect the registration and circulation records of any school or public library that pertain to his or her child. Notwithstanding the foregoing, records concerning security plans, procedures, assessments, measures, or systems, and any other records relating to, or having an impact upon, the security or safety of persons, structures, facilities, or other infrastructures, including without limitation information concerning critical infrastructure (as defined at 42 U.S.C. § 5195c(e) as amended) and critical energy infrastructure information (as defined at 18 C.F.R. § 388.113(c)(1) as amended), the public disclosure of which could reasonably be expected to be detrimental to the public safety or welfare, and records the disclosure of which would otherwise be detrimental to the best interests of the public shall be exempted from this section. Any public officer who receives a request for records that may appear to relate to critical infrastructure or critical energy infrastructure information, shall notify the owner of such infrastructure in writing of the request and provide the owner an opportunity to comment on the request and on the threats to public safety or welfare that could reasonably be expected from the public disclosure of the records.
In Stone v. Consolidated Publishing Co., 404 So. 2d 678 (Ala. 1981), the Supreme Court of Alabama defined "public writing" to include both:
[A]ll written, typed or printed books, papers, letters, documents and maps made or received in pursuance of law by the public officers of the state, counties, municipalities and other subdivisions of government in the transactions of public business and shall also include any record authorized to be made by any law of this state belonging or pertaining to any court of record or any other public record authorized by law or any paper, pleading, exhibit or other writing filed with, in or by any such court, office or officer[,]
Ala. Code § 41-13-1 (2000), and "such a record as isreasonably necessary to record the business and activities required to be done or carried on by a public officer so that the status and condition of such business and activities can be known by our citizens." 404 So. 2d 678, 681 (Ala. 1981); s ee also Walsh v. Barnes, 541 So. 2d 33, 35 (Ala. Civ. App. 1989) (referring to and applying the two Stone standards — the stricter standard ("required by law to be kept") and the lesser standard ("reasonably necessary").
Two additional statutes specifically require public officers and servants to make and keep records and to produce those records upon request, as follows:
All public officers and servants shall correctly make and accurately keep in and for their respective offices or places of business all such books or sets of books, documents, files, papers, letters and copies of letters as at all times shall afford full and detailed information in reference to the activities or business required to be done or carried on by such officer or servant and from which the actual status and condition of such activities and business can be ascertained without extraneous information . . . .
Ala. Code § 36-12-2 (2001); see alsoAla. Code § 36-12-41 (2001) ("Every public officer having the custody of a public writing which a citizen has a right to inspect is bound to give him, on demand, a certified copy of it, on payment of the legal fees therefor . . . .").
The Supreme Court of Alabama also established the following rules of statutory construction, presumptions, and burden of proof for the Public Records Law:
"It is clear from the wording of § 36-12-40 that the legislature intended that the statute be liberally construed," Chambers v. Birmingham News Co ., 552 So. 2d 854, 856 (Ala. 1989);
"There is a presumption in favor of public disclosure of public writings and records expressed in the language of § 36-12-40," 552 So. 2d at 856; and
"[B]ecause there is a presumption of required disclosure, the party refusing disclosure shall have the burden of proving that the writings or records sought are within an exception and warrant nondisclosure of them," 552 So. 2d at 856-57.
Alaska
This outline attempts to comprehensively catalogue those instances in which the Alaska Statutes require that information be kept confidential. There are often additional or complementary requirements of confidentiality in the administrative regulations adopted pursuant to these various statutes. [The range of regulatory provisions requiring confidentiality is extremely broad, and a person seeking access to information should check regulations in the pertinent subject area if a question arises. Presumably, the agency would cite any regulation imposing confidentiality as a basis for denying records. Once the legal basis for the denial is established, the regulation can be compared to the statute for consistency and to determine whether there is authority for the regulation. The information kept confidential by these regulatory provisions runs the gamut from student test results, 4 AAC 6.735, to the biological and management data collected by on-board observers from catcher/processor and floating processor vessels that process shell fish, 5 AAC 39.64.5, to employee petitioner interest cards in support of a showing of interest in a union organizing drive, 8 AAC 97.060(d), to applications for concealed handgun permits, 13 AAAC 30.800.]
A few of the administrative regulations most significant to news reporters have been addressed in this outline. No attempt has been made to deal with all the administrative regulations of the various state agencies (or likewise, with local government charters, ordinances and policies), but the reader should be aware that they exist and may be asserted as a basis for denying access to records. At the same time, it should not be assumed that a municipal code provision purporting or interpreted to restrict access to records should be given effect.
See, e.g.
,
Griswold v. Homer City Council
,
P.3d
, 2018 WL 4375455, at *7 (Alaska, September 14, 2018) (noting that because the Public Records Act applies to municipalities, the municipal code “applies only to the extent it narrows the exceptions to disclosure and requires that more records be disclosed”). Similarly, an agency seeking not to disclose a record on the basis of an agency regulation requiring confidentiality might cite as authority AS 40.25.120(4), which provides that "records required to be kept confidential by a federal law or regulation or by a state law" are not subject to public inspection. But note that the statute does not make an exception for records required to be kept confidential by a "federal or state law or regulation." Only federal regulations, and not state regulations, form the basis for this exception. The legislature apparently intended to reserve to itself the power to make decisions about when documents should be exempt from public disclosure. By not allowing an exception to the public disclosure requirement based on state administrative regulations alone, the legislature refrained from giving administrative agencies carte blanche to keep documents that agency employees decided would be best kept confidential. Although the issue has not squarely been addressed by the Alaska Supreme Court, trial courts in cases brought by the
Anchorage Daily News
concerning access to public records have interpreted the statute this way, and refused to deny access to records on the basis of administrative regulations purporting to make them confidential.
Arizona
(This section is blank. See the subpoints below.)
Arkansas
(This section is blank. See the subpoints below.)
view more
California
Colorado
Connecticut
Delaware
District of Columbia
Florida
Georgia
Consistent with the state’s strong public policy in favor of open government, the Act provides at the outset that it “shall be broadly construed to allow the inspection of governmental records.” O.C.G.A. § 50-18-70(a). Echoing prior court decisions, the Georgia legislature expressly found and declared in its 2012 revision to the statute “that the strong public policy of this state is in favor of open government; that open government is essential to a free, open, and democratic society; and that public access to public records should be encouraged to foster confidence in government and so that the public can evaluate the expenditure of public funds and the efficient and proper functioning of its institutions.” Id.Further, “there is a strong presumption that public records should be made available for public inspection without delay.” Id.
Hawaii
The basic purpose of the UIPA, Hawai'i's revised open records law, which became effective July 1, 1989, is to afford public access to all government records unless access is restricted or closed by law. Haw. Rev. Stat. § 92F-11(a) (1996). It seeks to "[e]nhance government[] accountability" and to "[m]ake government accountable to individuals in [its] collection, use, and dissemination of information [about] them." Id.§§ 92F-2(3), (4). The UIPA complements the requirements of the Hawai'i Administrative Procedure Act [HAPA], which also mandates that government agencies make information under their control available for public inspection. Id.§ 91-2 (1996).
A significant constraint on the statutorily sanctioned philosophy of access comes from the Hawaii Constitution's explicit guarantees of privacy. Haw. Const. art. I, §§ 6, 7. The UIPA acknowledges that "[t]he policy of conducting government business as openly as possible must be tempered by a recognition of the right of the people to privacy . . . ." Haw. Rev. Stat. § 92F-2 (referring to Haw. Const. art. I, §§ 6, 7). The OIP often cites the UIPA's provision providing an exception to the general rule of public access based on unwarranted invasion of privacy as the reason for denying or limiting access. While the UIPA's invasion of privacy exception applies only to natural persons, id.§ 92F-14(a), it accords with the HAPA provisions mandating confidentiality of agency records about individuals and entities. Id.§ 91-2(b) (1996). Under the UIPA, agencies receive the effective equivalent of "privacy" protection when disclosure falls within UIPA's exception based on frustration of legitimate government purpose. Id.§ 92F-13(3).
The UIPA lists three other bases that might support a denial of access to government records, see id. § 92F-13, including the most frequently cited: specific statutes or court orders. Records Not Available to Public, OIP Openline (newsletter), July 1992, at 2; Haw. Rev. Stat. § 92F-13(4) (Supp. 1999). The remaining two exceptions supporting denials of access primarily serve to protect government interests in undiscoverable materials associated with the prosecution or defense of judicial or quasi-judicial "action[s] to which the state or any county is or may be a party," Haw. Rev. Stat. § 92F-13(2); and "inchoate and draft working papers of legislative committees . . . ," legislative investigative committees, and "personal files of members of the legislature," id. § 92F-13(5).
Idaho
view more
Illinois
view more
Indiana
Iowa
"The purpose of chapter 22 is to remedy unnecessary secrecy in conducting the public's business." US West Commc’ns, Inc. v. Office of Consumer Advocate, 498 N.W.2d 711, 713 (Iowa 1993). “The Act carries with it ‘a presumption of openness and disclosure.’” In re Langholz, 887 N.W.2d 770, 776 (Iowa 2016) (citing Iowa Film Prods. Servs. v. Iowa Dep’t of Econ. Dev., 818 N.W.2d 207, 217 (Iowa 2012) (citation omitted)). Rather, the purpose of the Act is to ensure transparency, “open the doors of government to public scrutiny,” and prevent the government from acting in secret. Iowa Film Prods. Servs., 818 N.W.2d at 217 (quoting Rathmann v. Bd. of Dirs., 580 N.W.2d 773, 777 (Iowa 1998) (citation omitted)); Press-Citizen Co. v. Univ. of Iowa, 817 N.W.2d 480, 484 (Iowa 2012).
Kansas
Kentucky
The basic policy of Kentucky’s Open Records Act is that “free and open examination of public records is in the public interest and the exceptions … provided by law shall be strictly construed, even though such examination may cause inconvenience or embarrassment to public officials or others.” Ky. Rev. Stat. 61.871.
Louisiana
Maine
Maryland
Massachusetts
Michigan
(This section is blank. See the subpoints below.)
view more
Minnesota
view more
Mississippi
Missouri
Montana
Article II, Section 9 has been implemented by statute: Mont. Code Ann. §2-6-1001 et. seq.§2-6-1002 defines a public record as “information” fixed in any medium and retrievable in usable form prepared, owned used or retained by any public agency relating to the transaction of official business.
Nebraska
Nevada
New Hampshire
New Jersey
New Mexico
Procedures are similar to the Federal Freedom of Information Act.
New York
North Carolina
view more
North Dakota
In North Dakota, all public records are open records, unless there is a specific statutory exception for a particular type of record. The North Dakota Constitution states:
Unless otherwise provided by law, all records of public or governmental bodies, boards, bureaus, commissions, or agencies of the state or any political subdivision of the state, or organizations or agencies supported in whole or in part by public funds, or expending public funds, shall be public records, open and accessible for inspection during reasonable office hours.
North Dakota Constitution, Article XI, Section 6.
The North Dakota open records statute contains essentially the same language:
Except as otherwise specifically provided by law, all records of a public entity are public records, open and accessible for inspection during reasonable office hours.
N.D.C.C. § 44-04-18(1).
The North Dakota Supreme Court has concluded, “Thus, for an exception to the open-records law to exist under our constitutional and statutory provisions, it must be specific, i.e., the Legislature must directly address the status of the record in question, for a specific exception, by the plain terms of those provisions, may not be implied.” Hovet v. Hebron Pub. Sch. Dist., 419 N.W.2d 189 (N.D. 1988).
Although the state constitution and the statute are clear that unless an express exception applies, public records are open records, there are nonetheless specific statutes declaring that certain records are open records. For example, the statutes address the records of the State Highway Department (N.D.C.C. § 24-02-11(1)), the State Engineer (N.D.C.C. § 61-03-06), the Water Conservation Commission (N.D.C.C. § 61-02-11), school districts (N.D.C.C. § 15.1-07-25(1)), and irrigation district boards of directors (N.D.C.C. § 61-06-21.1). Additionally, city real property assessment rolls (N.D.C.C. § 40-19-03) and master lists of potential jurors (N.D.C.C. § 27-09.1-05(3)) are listed as open records.
Ohio
Oklahoma
The Oklahoma Open Records Act is a series of laws located at title 51, sections 24A.1 to 24A.33 of the Oklahoma Statutes. The purpose of the Act is as follows:
As the Oklahoma Constitution recognizes and guarantees, all political power is inherent in the people. Thus, it is the public policy of the State of Oklahoma that the people are vested with the inherent right to know and be fully informed about their government. The Oklahoma Open Records Act shall not create, directly or indirectly, any rights of privacy or any remedies for violation of any rights of privacy; nor shall the Oklahoma Open Records Act, except as specifically set forth in the Oklahoma Open Records Act, establish any procedures for protecting any person from release of information contained in public records. The purpose of this act is to ensure and facilitate the public’s right of access to and review of government records so they may efficiently and intelligently exercise their inherent political power. The privacy interests of individuals are adequately protected in the specific exceptions to the Oklahoma Open Records Act or in the statutes which authorize, create or require the records. Except where specific state or federal statutes create a confidential privilege, persons who submit information to public bodies have no right to keep this information from public access nor reasonable expectation that this information will be kept from public access; provided, the person, agency or political subdivision shall at all times bear the burden of establishing such records are protected by such a confidential privilege. Except as may be required by other statutes, public bodies do not need to follow any procedures for providing access to public records except those specifically required by the Oklahoma Open Records Act.
Oregon
Pennsylvania
Rhode Island
South Carolina
South Dakota
Tennessee
The Tennessee open records law (the "Act") provides for a Tennessee citizen's personal inspection of all state, county and municipal records at all times during business hours unless the records are statutorily declared to be confidential. A public record is defined as follows:
all documents, papers, letters, maps, books, photographs, microfilms, electronic data processing files and output, films, sound recordings, or other material, regardless of physical form or characteristics, made or received pursuant to law or ordinance or in connection with the transaction of official business by any governmental entity.
T.C.A. § 10-7-503(a)(1)(A)(i). See alsoT.C.A. § 10-7-403 (defining "Public records within the county"). The determination of whether a document has been received "in connection with the transaction of official business" requires an examination of the totality of the circumstances. Griffin v. City of Knoxville, 821 S.W.2d 921, 924 (Tenn. 1991) (suicide notes taken into police custody are public records). Tennessee courts have had occasion to determine that certain records claimed to be exempt were in fact intended to be open: applications of those seeking the position of school superintendent, Board of Education of Memphis City Schools v. Memphis Publishing Co., 585 S.W.2d 629 (Tenn. Ct. App. 1979); payroll records of a public hospital, Cleveland Newspapers Inc. v. Bradley County Memorial Hospital Board of Directors, 621 S.W.2d 763 (Tenn. Ct. App. 1981); and closed investigative files of a police department, Memphis Publishing Co. v. Holt, 710 S.W.2d 513 (Tenn. 1986). Forty eight categories of exceptions to the mandate of openness are contained in the Act itself under the rubric of "confidential records." T.C.A. § 10-7-504. The legislature has enacted numerous other statutes providing that certain records be deemed confidential or closed.
A 1988 survey by a special committee of the Tennessee General Assembly found a total of 89 exemptions either limiting or barring public access to various public records. Since that time, the General Assembly has frequently enacted additional exemptions. The attached Appendix lists 365 exemptions, but a list of exemptions the OORC released on January 30, 3018 finds 538 statutory exemptions with only two scheduled to sunset, which means the General Assembly has been passing exemptions at the rate of 15.5 per year since 1988. The OORC list was prepared for the General Assembly with the understanding that it might review the list to determine if more exception should be eliminated. The OORC list may be found athttp://www.comptroller.tn.gov/openrecords/. The difference between this list and the attached Appendix maybe partly one of interpretation.
Texas
Utah
Vermont
PUBLIC RECORDS ACT
“Officers of government are trustees and servants of the people and it is in the public interest to enable any person to review and criticize their decisions even though such examination may cause inconvenience or embarrassment. All people, however, have a right to privacy in their personal and economic pursuits, which ought to be protected unless specific information is needed to review the action of a governmental officer. Consistent with these principles, the general assembly hereby declares that certain public records shall be made available to any person . . . . To that end, the provisions of this subchapter shall be liberally construed . . . .”
1 V.S.A. § 315.
The Public Records Act has recently been amended, with certain changes having gone into effect on January 1, 2019 and others having gone into effect on July 1, 2019. See1 V.S.A. § 317. These changes primarily impact the expiration and renewal process for exemptions to the statute.
Virginia
Washington
Note: Pursuant to RCW 42.56.570, the Washington Attorney General’s Office (AGO) has prepared a set of model rules regarding the Public Records Act. See WAC Ch. 44-14. Each state and local agency is urged to adopt these rules to provide greater clarity and uniformity in terms of how public records requests are handled. The original model rules, adopted in 2006, indirectly provided a good overview regarding interpretation of the Public Records Act and a guide to agency “best practices.” The rules were revised and, to some extent, watered down, in 2018.
West Virginia
The Freedom of Information Act's declaration of policy, which is quoted in the Foreword, is the only indication of the legislative intent underlying the statute. There is no recorded legislative history relating to either the statute's original enactment in 1977 or its subsequent amendments. However, the state Supreme Court of Appeals has quoted the FOIA policy declaration repeatedly in its opinions. See e.g., Daily Gazette v. W. Va. Dev. Office, 198 W. Va. 563, 482 S.E.2d 180 (1996); Ogden Newspapers v. City of Charleston, 192 W. Va. 648, 453 S.E.2d 631 (1994). West Virginia's Supreme Court has mandated "the fullest responsible disclosure" of information concerning government. Hechler v. Casey, 175 W. Va. at 445, 333 S.E.2d at 808.
Wisconsin
Wyoming
The remedial purpose of the Public Records Act is "to permit access to public records unless disclosure would inflict irreparable harm contrary to protected rights." Id.
| https://www.rcfp.org/open-government-sections/i-statute/ |
Applied Sciences | Free Full-Text | Blast Loaded Columns—State of the Art Review
The ever-present threat of terrorist attacks in recent decades gives way to research towards blast-resistant design of structures. Columns, as one of the main load-bearing elements in residential buildings and bridges, are becoming interesting targets in bombing attacks. Research of column blast load behavior leads toward increased safety by identifying shortcomings and problems of those elements and acting accordingly. Field tests and numerical simulations lead to the development of new blast load mitigation technics, either in the design process or as a retrofit and strengthening of existing elements. The article provides a state-of-the-art literature review of filed blast load tests and numerical simulations of a bridge and building columns.
Blast Loaded Columns—State of the Art Review
by Sanja Lukić and Hrvoje Draganić *
Department for Materials and Structures, Faculty of Civil Engineering and Architecture Osijek, Josip Juraj Strossmayer University of Osijek, Vladimira Preloga 3, HR-31000 Osijek, Croatia
Author to whom correspondence should be addressed.
Appl. Sci. 2021 , 11 (17), 7980; https://doi.org/10.3390/app11177980
Received: 30 July 2021 / Revised: 23 August 2021 / Accepted: 26 August 2021 / Published: 28 August 2021
(This article belongs to the Special Issue Blast and Impact Engineering on Structures and Materials )
Abstract
Keywords:
blast load
;
concrete columns
;
experimental testing
;
numerical modeling
1. Introduction
In the last five decades, terrorist attacks have become more frequent. There are different types of terrorist attacks, but according to data provided by the National Consortium for the Study of Terrorism and Response to Terrorism [ 1 ], in the last two decades, explosive attacks exceed 50% of the total number of incidents, shown in Figure 1 . The attacks on The Twin Towers of the World Trade Center on 11 September 2001 and bridges in California and New York have an impact on the design of structures in the United States and also in the rest of the world [ 2 ]. In every country, the transportation system is essential for performing everyday activities, so the Blue Ribbon Panel (BRP) indicates the transportation system as one of the viable targets for a bombing attack. Due to a large number of bridges worldwide, lots of potential casualties, high repair costs, and importance in everyday life, the bridges are increasingly in the focus of terrorist attacks. This is confirmed by the fact that in the last few attacks in Nigeria in 2020, seven bridges were destroyed. It is important to identify which bridges are vulnerable due to their easy accessibility to protect against attacks. Moreover, BRP states that the columns are one of the most critical components on all types of bridges [ 3 ]. As there are many types of bridges and many ways to attack the bridge, it is difficult to predict the construction’s response to the blast loadings [ 4 ]. When detonation of an explosion is under the bridge, then columns are exposed to large lateral forces, depending on standoff distance, which can result in large deformations leading to flexural or shear failures. The contact explosion can breach the column to render it incapable of supporting the dead loads. For small standoff distance, blast waves can cause a serious reduction in a concrete cross-section in terms of spalling and cratering. Since the column failure depends on the position and amount of explosives, all examined attack scenarios were observed.
Figure 1. Percentages of terrorist attack types, based on data from [ 1 ].
The main objective of this review article is an extensive literature overview of experimental and numerical research conducted on blast-loaded columns. Both building and bridge columns are considered due to differences in their static and blast behavior. A systematic summary is given of column behavior, possible damage and failure modes, and a review of software used for blast load simulation and analysis.
2. Experimental Testing
There are no experiments on real scale specimens of bridge columns due to the experimental setup complexity and high costs, while the building columns are mainly conducted in full scale due to their maximum height of 2.5 to 3 m. Moreover, these types of experiments require special testing ground (usually military field ranges) and trained personnel for handling explosives. Even these special testing grounds have limitations regarding the maximum amount of explosives that can be used in one detonation. This also limits the scale of specimens. Research conducted in recent decades has shown that scale tests provide reliable results and the necessary knowledge to analyze the effects of blast load on full-scale structures [
5
].
If considering building and bridge columns, except specimen dimensions, there is a difference in their behaviors due to different levels of axial load capacity. Therefore, it is recommended to analyze bridge and building columns separately [ 4 ]. A list of conducted experimental research is provided in Table 1 .
Table 1. Summary of experimental research.
2.1. Bridge Columns
The experiments were carried out on standard RC columns, additionally retrofitted columns, and improved composite concrete columns. The columns are exposed to various scenarios of explosive attacks. In addition to the type of column, the scenarios also differ in the position, type, and amount of explosives.
Williamson et al. [ 32 ] provided the list of possible terrorist courses of action and indicated that the hand placed explosives on the column and large truck-bomb below the bridge superstructure can destroy columns and cause bridge collapse.
Due to similarities between the effects of the explosions and earthquakes, Bruneau et al. [ 6 ] developed a multi-hazard pier concept that they expect to provide a satisfying level of protection against failure under both loadings. All specimens were concrete-filled circular steel columns (CFCSC) with three different diameters (10.16 cm (4″), 12.7 cm (5″), 15.24 cm (6″)) and a minimum steel thickness of 3.2 mm. Specimens were made in 1:4 scale of the prototype bridge columns. Due to security reasons, the actual values of charge weights and standoff distances are not provided. Experimental results showed that even a minimal increase in standoff distance and column diameter significantly reduces column deformation. The CFCS columns showed ductile behavior and high resistance to the effects of the explosion [ 6 ]. The same scale and scenario when the explosive was located under the bridge in a car placed near to the column were examined in [ 7 ]. They assumed the charge weight similar to the blast weights predicted in FEMA (2003) [ 33 ] and FHWA (2003) [ 34 ]. Charges are set at heights of 0.25 m and 0.75 m, which correspond to the actual height of 1 m (car bomb) and the half column height, respectively. They concluded that only steel jacketing is not enough to provide adequate resistance to the large shear forces influencing the bottom of the column. Therefore, they found that a better solution is using a fully concrete-filled steel tube (CFST) continuously embedded into the footing. CFST columns provided ductile behavior and sufficient resistance to the lateral forces from earthquakes and explosions. Moreover, the advantage of CFST columns is that they do not have a breach and a spall of concrete, i.e., they do not produce flying debris [ 7 ]. Figure 2 shows the connection concept between the foundation beam and the CFST column, which provides the full moment capacity of the column. At a rotation of 3.8° of the bottom of the column, plastic deformation is visible but without cracking of the concrete. The first cracks occur at a rotation of 8.3°, while the fracture of the steel tube occurs at 17°. At the height of the explosive charge, pits and notches appeared on the steel tube, while concrete cracks occurred on the tension side at the bottom and top of the column due to the rigid boundary conditions [ 7 ]. They assumed the same blast scenario as Fujikura et al. [ 7 ] in their work at the same scale of 1:4, but there were four columns in the test specimen while the bridge prototype has three. Figure 3 shows the test setup for the same blast load scenario but on different types of columns. The RC column exhibited shear failure at the base and cracking of concrete along the column [ 9 ], RC SJ shear failure [ 9 ], and CFST column flexural failure and buckling [ 7 ]. Fujikura and Bruneau [ 9 ], in their work, presented experimental and analytical investigations of seismically ductile RC columns and non-ductile RC columns retrofitted with steel jackets. The charge was set to a height of 0.25 m which corresponds to the actual height of 1 m (car bomb), and at this height, the column experienced the maximum deflection. All columns failed in direct shear at the base, but RC columns with steel jackets did not experience any structural damage, and the RC column experienced spalling of concrete at the bottom. Compared to the CFST columns, these columns did not exhibit a ductile behavior.
Figure 2. CFST column—details of column-to-foundation beam connection [ 7 ].
Figure 3. Test setup in [ 7 ] and [ 9 ].
Davis et al. [ 8 ] conducted an experiment in two phases. In the first phase, they tested eight small-scale columns where they first changed the standoff distance and then the amount of explosive charge while the scaled distance was kept fixed. In the second phase, they tested 16 columns in half scale (1:2), where 10 of them were set at a small standoff to observe the mode of failure (flexure or shear) like in [ 4 ], and the remaining six were to sustain local damage (spall and breach patterns). In all samples, concrete strength, clear cover, concrete class, and reinforcement grade were unchanged. Boundary conditions for tested columns were assumed to be pinned at the top and fixed at the bottom. The test setup did not include axial load because low levels of axial loads provide greater capacity to the column, and without axial load, tests are on the conservative side. Five experimental observations and guidelines for the design of blast-loaded columns are provided in [ 4 , 8 , 35 ]:
Using protective fences and barriers for vehicles to increase the standoff distance;
The circular cross-section can maintain a lower pressure of up to 1/3 concerning a square cross-section of the same dimensions, so the second guideline is to use circular columns, and also, the pressure reducing factors on the circular column were proposed by Winget et al. [ 2 ], Marchand et al. [ 36 ], and Fujikura et al. [ 7 ], respectively, as 0.80, 0.75, and 0.45;
Increase in the reinforcement in the column, as this increases the shear capacity, ductility, and confinement of the concrete;
Use of continuous reinforcement because discrete hoops can be extracted during a blast load;
Placing longitudinal splices away from the charge if they cannot be completely avoided.
They also proposed three design categories (A, B, C) that depend on the scaled distance and require a different approach to designing, i.e., gravity, seismic, blast. In the C category (
Z
≤ 0.6 m/kg
1/3
), columns are exposed to the higher loads than columns in A (
Z
> 1.2 m/kg
1/3
) and B (0.6 <
Z
≤ 1.2 m/kg
1/3
).
Williamson et al., in Part II [ 35 ], provided a review of experiments represented in Part I [ 4 ]. Square columns experienced greater net resultant impulse than circular columns under the same blast loads and also had a larger cross-section area, so less shear occurred at the base. To increase the shear capacity of the column at the base and the ductility, it is necessary to increase the amount of transverse reinforcement. Moreover, columns with continuous spirals had a better performance than columns with discrete ties, which confirms the recommendation given in [ 8 ]. Due to changes in column design, the weight of charge, and standoff distance, several levels of damage were obtained [ 37 , 38 ]. The test setup is shown in Figure 4 . Superficial damage means that the column performed well and has only surface damage and cracks, while minor damage means spalling of the concrete cover and cracks along the column. Deformations, flexural cracking, and spalling of concrete all together are extensive damage, while the failure of the column means that a shear occurred at the base [ 4 ].
Figure 4. Test setup [ 4 , 8 ].
Echevarria et al. [ 18 ] tested RC and Concrete-Filled Fiber-Reinforced Polymer (FRP) tube (CFFT) bridge columns at a scale of 1:5. CFFT columns are reinforced only with longitudinal reinforcement, while RC columns have spiral hoops in addition to longitudinal reinforcement, shown in Figure 5 . The quantity and distance of the explosives were not provided for safety reasons. The columns experienced minimal visual damage, but measurements showed that both concrete and steel experienced large loads and strains. In the residual test, CFFT columns showed greater strength and ductility than RC columns.
Figure 5. Reinforcement position in specimens: ( a ) RC column and ( b ) CFFT column; specimen position: ( c ) test setup [ 18 ].
Fouché et al. [ 5 ] made the same prototype of the bridge columns as [ 9 ] and exposed them to the same blast load scenario. To improve the behavior of the steel jacked columns to the explosion, they added structural steel collars at the top and bottom of the column. The steel collar at the base of the steel jacked RC column is shown in Figure 2 in [ 5 ] . They concluded that the modified column was effective in preventing direct shear and had increased ductility. The obtained maximum base rotation ranges from 8.6 to 10.3°, and all the columns showed satisfactory behavior.
Yuan et al. [
23
] experimentally tested two RC bridge columns in scale 1:3 under 1kg TNT contact explosion placed at the height of 33 cm from the ground. As a retaining structure that prevents the rotation and displacement of the column at the top, they used a wall with the opening that was placed at a distance of 1.4 m from the detonation point. Both columns experienced spallation and crushing of concrete cover, but the stirrup fracture was observed only in the square column. The damages to the front and back sides of the circular and square columns are shown in
Figure 6
. Therefore, the test results showed that the square column had more severe damage than the circular column.
Figure 6. Comparison of damages of circular and square RC columns after the detonation of 1 kg of TNT: ( a ) front side and ( b ) back side [ 23 ]. Copyright permission obtained from authors.
Wang et al. [
29
] investigated the impact of contact explosions of 1 kg, 2 kg, and 3 kg of TNT on the mode of failure and original and residual axial capacity of Ultra-High Performance Cementitious Composite Filled Steel Tube (UHPCC-FST) bridge column. The columns were made in 1:4 scale and are tested horizontally, and the views of the test setup are shown in
Figure 7
. The top of the column is pinned, and the bottom of the column is fixed. The cylindrical explosive is placed at a distance of 25 cm from the lower support, which represents the actual position of the explosive in the vehicle at the height of 1 m. Quantities of explosives of 1 and 2 kg made only a crater in the column, while 3 kg fractured the tube and crushed the core, as shown in
Figure 8
. In the axial compression test, all columns experienced diagonal shear failure.
Figure 7. Schematic and field views of test setup [ 29 ]. Copyright permission obtained from authors.
Figure 8. Damage of UHPCC-FST columns after detonation of: ( a ) 1 kg; ( b ) 2 kg and ( c ) 3 kg of TNT [ 29 ]. Copyright permission obtained from authors.
Based on the reviewed literature of bridge columns, maximum support rotations in field blast tests are shown in Table 2 . The information can be used as a preliminary, fast damage assessment of blast-loaded columns based on the measured post-blast column rotations.
Table 2. Maximum support rotations (blast at low height).
2.2. Building Columns
In addition to bridges, interesting targets of terrorist attacks are buildings. By damaging the ground floor columns, the whole building loses stability, so in most of the new buildings, the ground floor columns are designed also considering the blast loads. Building columns differ from bridge columns in the magnitude of the axial loads. Moreover, the dimensions of building columns are significantly smaller, so most of the experiments conducted on building columns were in full or half-scale.
Burrell et al. [
11
] tested two half-scale reinforced concrete columns and six Steel Fiber-Reinforced Concrete columns (SFRC) with steel fiber content from 0 to 1.5% by volume of concrete (non-seismic and seismic detailing) at shock tube. In the experiment, the axial load equal to 30% load capacity was applied using a hydraulic jack. According to their experiments, columns designed seismically (38 mm distance between transverse reinforcement) have smaller maximum displacements and can withstand larger blast loads. Moreover, SFRC columns with non-seismic detailing (75 mm distance between transverse reinforcement) showed smaller maximum displacements and no secondary blast fragments.
Aoude et al. [
13
] experimentally tested nine Ultra-High-Performance Fiber Reinforced Concrete (UHPFRC) columns designed with Compact Reinforced Composite (CRC). Tests were performed in a shock tube, and a hydraulic jack was used to input the axial load. The applied blast pressures varied from 69 kPa to 689 kPa. Dimensions of the cross-section were 152 mm × 152 mm, and the free span of the column was 1980 mm. The results showed that the UHPFRC columns reduce secondary blast fragments. Increasing the proportion of fibers from 2% to 4% had a positive effect on the decrease in displacement, but a higher proportion of fibers did not result in improvements in blast behavior.
Zhang et al. [ 12 ] experimentally blast tested three square columns and one circular column. The columns were made from steel tubes filled with concrete (CFST). Specimens were placed horizontally with a simple boundary condition at both ends. A pneumatic jack was used to input the axial load, shown in Figure 9 . The entire length of the specimen was 2.5 m. In the experiment, an emulsion explosive, which has a TNT-equivalent of 0.7, was used. The maximum and residual column deformations are provided for blast loads utilizing 17.5 to 35 kg TNT equivalence at a standoff distance of 1.5 m. The concrete inside the steel tube reduced local deformations, and the energy was dissipated through the global response of the element. Zhang et al. [ 20 ] tested two types of CFDST columns, circular and square, with inner and outer tubes, as shown in Figure 10 . They concluded that columns filled with normal strength concrete experienced greater crushing of concrete and higher steel buckling than columns filled with UHPC. Moreover, UHPC proved to be very resistant to spalling or crushing. The tested CFDST and CFST samples have similar oscillation periods and displacements, so it is concluded that they behave similarly. Zhang et al. [ 21 ] tested six ultra-high-performance concrete-filled double skin tube columns with square hollow sections. At a standoff distance of 1.5 m, the specimen exposed to 35 kg of TNT did not experience any localized damage or steel buckling. Moreover, the axial load (25% of the maximum load) contributed to the reduction in maximum deflection in the middle of the column. They concluded that the ratio of the cavity and the section influence the overall column deflection and period of oscillation; therefore, it is recommended not to go above 0.5. Wang et al. [ 19 ] exposed four circular Reactive Powder Concrete Filled Steel Tubular columns to explosion and fire durations of 0, 60, and 105 min. Fixed supports were simulated, and on one side, an axial load was introduced. Steel tube protects columns against cracks and spalling of concrete. After the detonation of the 17.5 kg explosive, the column experienced bending and after 35 kg bending–shearing deformations. With an increase in the number of explosives and with longer exposure to fire, maximum and residual displacements increased. Wang et al. [ 24 ] studied four square and four circular CFST columns under close-range blasts. The column length was 2.5 m, and the thickness of the steel tube was 2.8 mm or 3.8 mm. The standoff distance of the emulsion explosive was 1.5 m, and the charge weight expressed through the TNT equivalence was from 25 to 50 kg. Only a 10% increase in the amount of explosive in square columns increases mid-span deflection by 200%, which is assumed to be caused by a large surface exposed to the blast load. Moreover, increasing the thickness of the steel tube by 1 mm (from 2.8 to 3.8 mm) significantly reduced the displacement (by over 50%). Global failure mode was a flexural failure, and after removing the steel, the square columns sustained spalling and crushing of concrete. Circular columns were broken into several parts. Figure 11 shows the damage to the concrete after removing the steel tube after the blast load.
Figure 9. Test setup [ 24 ] and test pit [ 21 ]. Copyright permission obtained from authors.
Figure 10. Cross-sections of two CFDST specimens [ 20 ]. Copyright permission obtained from authors.
Figure 11. Columns after blast test [ 24 ]. Copyright permission obtained from authors.
Codina et al. [ 14 ] investigated the effects of close-in blast loading on the full-scale reinforced concrete column. They conducted experimental tests and numerical simulations to calibrate the numerical model. The observed column had a square cross-section of 230 mm × 230 mm and a free height of 2.44 m. The column was tested in a horizontal position, and the standoff distance from the center of the charge (8 kg of equivalent TNT—the used explosive is Gelamon VF65, which is equivalent in a mass to 65% TNT) to column 1 was 100 cm and to column 2 was 60 cm. Both columns experienced flexural damage, spallation of the concrete on the bottom side, and crushing of concrete on the exposed side, shown in Figure 12 .
Figure 12. Damage of the RC columns after detonation at 100 cm and 60 cm standoff [ 14 ]. Copyright permission obtained from authors.
Codina et al. [ 15 , 16 ] investigated the behavior of RC columns and RC columns with two types of protection (steel jacket and reinforced polyurethane bricks) exposed to a near field explosion. At a standoff distance of 60 cm, 8 kg of TNT equivalent shaped into a cylinder was placed, resulting in a scaled distance Z = 0.30 m/kg 1/3 . Comparing the test results of three types of columns, the steel-jacked column had the best results in residual capacity and in reducing final deflection. Polyurethane bricks are lighter and have cheaper protection for columns but give three times worse results than steel jacketing. It is recommended to set bricks of higher density to improve the effect in the area of blast load. In [ 16 ], they also examined reinforced resin panels with insulation layers as a possible improvement of the column. This protection system gave the best results, minimizing column damage and the greatest deflection reduction. The protection system in the field test is shown in Figure 13 . Codina et al. [ 22 ], after their research on plain RC columns [ 14 ], tested RC columns covered with reinforced resin panels with an insulation layer and steel jacketing. From the obtained results, it can be concluded that a significant reduction in damage and displacement was achieved with the cladding system, but the spalling and burst of concrete cannot be prevented. Figure 14 shows a schematic representation of all specimens and their damage covered by the studies of Codina et al.
Figure 13. RC columns reinforced with: ( a ) polyurethane bricks [ 15 , 16 ] and ( b ) resin panels and insulation layer [ 22 ]. Copyright permission obtained from authors.
Figure 14. Damage after blast load on RC members: ( a ) without protection; ( b ) with steel jacketing; ( c ) with polyurethane bricks, and ( d ) with reinforced resin panels [ 15 , 16 , 22 ]. Copyright permission obtained from authors.
Xu et al. [ 17 ] subjected four Ultra-High-Performance Fiber Reinforced Concrete (UHPFRC) and four High Strength Reinforced Concrete (HSRC) square columns to the effects of blast loads. Columns were tested under varied charge weights from 1.4 kg to 48 kg of emulsion explosive (TNT equivalence factor is 1.4). The standoff distance was fixed at 1.5 m in all tests. Specimens were placed horizontally, and the axial load was applied using a pneumatic jack. The results showed that UHPFRC columns could better withstand overpressure and shock waves, reducing the maximum displacements.
Li et al. [ 25 ] tested 10 Ultra-High-Performance Concrete (UHPC; six reinforced with twisted fiber and four reinforced with micro fiber) and 5 High Strength Reinforced Concrete (HSRC) columns. The length of the specimens was 2.5 m, and the cross-section was square with dimensions 0.2 m × 0.2 m. In experiments, the standoff distances of the explosive from the columns were constantly 1.5 m in all tests, but the explosive weight was changed. For the UHPC columns, weights of 17.5, 25, and 35 kg, and for the HSRC 8, 17.5 and 25 kg were used. Residual load capacity tests showed that UHPC columns after blast loads did not lose much on the axial load capacity. UHCP columns also showed much better load capacity after 35 kg TNT detonation than HSRC columns after 8 kg TNT detonation.
Fouché et al. [ 26 ] experimentally tested 12 columns at a scale of 1:4 under the blast load. They varied the void ratio, diameters, and thicknesses of the outer and inner steel tubes. The specimens’ cross-section generally experienced denting, and that deformation helped to energy absorption from the overpressure from the near-contact explosions. The inner steel tube played the role of a dowel preventing direct shear failure, and this is the advantage of the CFDST columns over CFST and RC columns. On the tensile side of the column, the concrete was crushed, or horizontal flexure cracks appeared.
Dua et al. [ 27 ] tested three RC columns (30 cm × 30 cm × 375 cm) in full scale with the same material and geometrical properties on contact explosion at the bottom of the column. They used 0.1 kg of plastic explosive (PEK—TNT equivalent 1.15) and 0.5 kg and 1 kg of TNT. The TNT charge of 1 kg made a hole in the column; 0.5 kg destroyed the concrete cover, and the remaining core has no residual capacity; 115 g TNT equivalent caused the spalling of the concrete cover. Column damage profiles are shown in Figure 15 . A contact explosion causes significant local damage on at least three sides of the column, while a far-field explosion causes the worst damage on the front, exposed side. Dua et al. [ 28 ] investigated the same blast load scenario on the column concerning the increase in the cross-sectional width of the column. They experimentally tested columns of dimensions 50 cm × 30 cm, 70 cm × 30 cm, and 90 cm × 30 cm. Rectangular columns showed better behavior under contact explosion than squares. They examined the residual load-bearing capacity of the column and determined the column damage index. When the width dimension of the column subjected to the blast load is greater two and more times from depth, the damage index is lower.
Figure 15. Column damages after blast loads: ( a ) 1 kg; ( b ) 0.5 kg and ( c ) 115 g TNT [ 27 ]. Copyright permission obtained from authors.
Kadhom et al. [ 30 ] examined five half-scale RC columns. Three columns are strengthened with unidirectional and woven CFRP laminates while the other two remained unprotected. They were first tested in the shock tube on the induced blast load, and thereafter, their residual axial capacity was examined. The column strengthened with CFRP laminates with ±45° woven fibers showed the best blast behavior and the most ductile response.
Fujikake and Aemlaor [ 43 ] investigated how longitudinal and shear reinforcement ratios, concrete strength, and the number of explosives affect the demolition of RC building columns. Their primary research goal is not terrorist attacks but the demolition of dilapidated concrete buildings. They used a Composite 4 (C4) explosive because of its stability and ease of shaping and placed it in the core of the column. They found that shear reinforcement plays a significant role in the residual bearing capacity after blasting; the strength of the concrete also affects the increase in residual compressive and flexural resistance capacities. The quantities of explosives and reinforcement cannot be applied to the external action of the explosion, but certainly, conclusions about the role of reinforcement and the strength of concrete are useful.
Roller et al. [ 44 ] observed two scenarios: first is a contact explosion with the amount of PETN that fits in the suitcase, and the second is the close-in scenario when the explosive is in the vehicle. They investigated the impact on RC columns and strengthened columns. Polymer concrete, SIFCON (Slurry Infiltrated Fiber Concrete), DUCON (Ductile Concrete), and Ultra-High-Performance Concrete (UHPC) were used to improve the resistance of the bridge and building columns. The appearances of column damages after contact explosion and the residual load capacities are shown in Table 3 . The results showed an increase in residual bearing capacity by up to 70%.
Table 3. Damaged columns after contact detonation and the residual load capacities [ 44 ].
Xu et al. [ 45 ] tested five columns in an explosion containment vessel (ECV). The columns were exposed to an explosion of 40 g charge mass, and the distance of the explosive was changed in each test from a contact explosion to a standoff distance of 50 cm. They installed four smart aggregates (SAs) in each specimen for internal damage detection, shown in Figure 16 . The propagation of the stress wave energy decreases with the formation of cracks under the blast load, and hence the amplitude of the time-domain signal recorded by piezometric smart aggregate sensors decreases with the appearance of cracks. This method of detecting internal damage has proven to be useful for completing the picture of the condition of the structure because internal cracks have a greater impact on the damage index of the structure than surface cracks.
Figure 16. Position and appearance of the SA sensors [ 45 ].
Vapper and Lasn [ 31 ] examined columns measuring 100 mm × 100 mm × 1000 mm on the action of a different amount of explosion placed at a vertical standoff distance of 300 mm. They tested four types of columns: reinforced concrete columns, columns reinforced with steel fibers, and both types strengthened with Glass Fiber Reinforced Polymer (GFRP). Plain concrete showed higher compressive strength compared to steel fiber reinforced concrete. GFRP in reinforced concrete columns did not contribute to the increase in the residual strength, while in steel fiber reinforced columns, the contribution was significant. A reduction in surface damage to GFRP-wrapped columns was also observed.
3. Numerical Modeling
Due to the increasing number of terrorist attacks, new challenges were posed to engineers. It is necessary to have a good understanding of computer programs, their capabilities, and their limitations to predict individual attack scenarios. The use of numerical simulations gives a clearer insight into the blast effects on the entire bridge and individual components. It provides the possibility of determining the most critical parts and problems that cannot be numerically simulated and need to be examined experimentally. Thus, one of the most important and difficult parts of this analysis is to properly define air blast loadings. Table 4 summarizes the software used to predict the effects of explosions on different types of columns.
Table 4. Summary of software for prediction and calculation of blast loads.
Conventional Weapon Effects Predictions (ConWep) [ 80 ] and BlastX [ 81 ] are programs used to calculate the effect of a blast wave from different types of detonation. ConWep is more used for air-blast calculations, including free-field and reflected blast pressure histories from the free-air, surface, and hemispherical burst explosions, and BlastX calculates internal blast pressure histories. BlastX is based on semi-empirical methods, including nonlinear addition laws for blast pressures from multiple reflecting surfaces based on computational fluid dynamics. Second-order Hydrodynamic Automatic Mesh Refinement Code (SHAMRC) [ 82 ] is also used to investigate high explosive and blast effects based on finite-difference computational fluid dynamics (CFD) code. Nonlin [ 83 ] does not make the empirical adjustments just for blast loads because it is initially designed for earthquake loads. It has similarities with SPAn32 [ 84 ] because it performs a nonlinear dynamic response history analysis taking bilinear material properties. Both programs are based on the analysis of a system with a single degree of freedom (SDOF). MSC.Dytran [ 85 ] is an explicit finite element analysis (FEA) solution for simulating blast load effects and analyzing the complex nonlinear behavior that structures undergo during detonation. Ansys Autodyn [ 86 ], LS-Dyna [ 87 ], and Abaqus [ 88 ] are programs that provide the ability to simulate detonation, wave propagation from an explosion, interaction with a structure, and nonlinear material behavior, which are known as hydrocode programs specialized for simulations in fluid dynamics.
Ray et al. [ 46 ], in their research, compared three methods with three different resolutions for air blast prediction. In the scenario of below-deck detonation, ConWep has a low resolution of air blast prediction, and the charge can be observed as hemispherical or spherical, while BlastX has a medium resolution and considers the shape of the charge and reflections of the blast pressure. The 3D bridge and blast load can be modeled in the SHAMRC because it is an advanced Eulerian-based finite difference code that has high resolution. Research shows that the highest resolution is not always necessary, as it is a mostly low resolution that provides a conservative design. The authors stated that additional analysis is needed to determine the most economical and sufficiently precise tool for a particular problem [ 46 ]. The shape of the explosive also drastically affects the resulting pressure and impulse, so it is necessary to use a program that allows the input of charge geometry.
Marchand et al. [ 36 ] determined concrete breaching using ConWep and calculated flexural response and support rotation on a reduced diameter column in SPAn32. They concluded that the strength of concrete does not significantly affect the maximum rotation of the support, but it does affect breaching, i.e., the lower strength causes greater breaching.
Winget et al. [ 2 ] use SPAn32 to calculate the flexural response of the columns and to define the equivalent SDOF stiffness and mass parameters based on the column properties. For the calculation of the blast load pressure history, the BlastX program was used. Other useful programs are AT Blast [ 89 ] and Nonlin. For the calculation of the pressure-impulse history using AT Blast, it is necessary to know the charge weight, angle of incidence, and standoff distance. However, AT Blast does not consider the effects of multiple reflections under the bridge explosions. They list four categories of bridge design concerning their importance, where category 1 represents very important bridges, and category 4, unimportant. Winget et al. did not take the real conditions of the ground and energy absorption by creating craters but the ideal reflecting surface. Footing instability, however, could also result from large ground deformations, and this aspect of behavior must also be addressed.
Wu et al. [ 48 ] numerically simulated RC and composite columns in LS-Dyna for the contact-placed TNT charges from 2.5 to 25 kg. In the simulations, they obtained a higher residual bearing capacity of the column when the explosive was placed at the height of 1.5 m from the bottom than when it was placed at the bottom.
Fujikura et al. [ 7 ], for calculation of impulse variations per unit length along the height of the column, were using the Bridge Explosive Loading (BEL) [ 90 ] program. BEL also considers the reflected pressure of the blast wave on the surface of the superstructure and on the ground.
Rutner et al. [ 47 ] studied the behavior of four types of column cross-sections in MSC.Dytran software on blast load: single-cell hollow steel section, multi-cell hollow steel section, single-cell hollow composite column, and multi-cell composite column. Compared to steel columns, the composites showed negligible deflection on blast load. The best stress distribution in the element was achieved with multi-cell composite columns, which is also visible by the displacements shown in Figure 17 .
Figure 17. Time history of displacements for 4 column types [ 47 ].
Hao et al. [ 49 ] analyzed three reinforced concrete columns with the same dimensions, material strengths, and reinforcement ratios but subjected to blast loads of different scaled distances. They wanted to find the failure probability using the computer code CARLER, which is verified with Monte Carlo simulations. They defined four damage levels ( D ) that depend on the ratio of residual axial load carrying capacity ( N residual ) when the column is damaged and the axial load of the undamaged column ( N 0 ), shown in Table 5 . Through numerical simulations, they concluded that neglecting some of the material properties of the column has minimal impact on the probability of failure, while the random changes in the blast loading have a much greater role.
Table 5. Damage levels of RC column in terms of axial load capacity.
Williams and Williamson [ 51 ] emphasized the spalling of side-cover concrete because, in previous works, only the spalling of concrete off the back of reinforced concrete columns was mentioned. The aim of their research was to make and validate a numerical model with respect to the experiment explained in [ 38 ] and justified the cross-sectional response mechanisms that cause loss of side-cover concrete. For numerical simulations, they used the LS-Dyna program and the Karagozian and Case concrete (KCC) material model.
Numerical simulations in LS-Dyna showed that the shape of the column cross-section has a large influence on the resulting impulse. The authors developed expressions for calculating column shape factors for circular and square columns. The expressions are used when the R / D ratio is less than 4.5 because they provide sufficiently conservative loads but less than those experimentally determined on the walls [ 52 ].
Crawford [ 10 ] performed numerical simulations in LS-Dyna of RC columns and columns retrofitted with fiber-reinforced plastic (FRP). FRP increases the resistance of the RC columns to the blast load. For numerical modeling, the choice of concrete material model is very important, and the analysis was performed with four different concrete models (KC, Winfrith, Continuous Smooth Cap, and RHT model). The best results were obtained with the KC model.
Magali et al. [ 53 ] performed a parametric numerical analysis in Abaqus to see which of the six varied parameters (section ratio, compressive strength of concrete, column height and thickness, charge radius, and ratio between standoff distance to the charge radius) had the greatest impact on column damage. It was shown that the column thickness, charge radius, and the ratio of standoff distance to charge radius play a significant role in the column response. They give an empirical formula based on the conducted simulations to predict the damage index of the column. Comparing the results obtained by formula and numerical simulations, the deviations are up to a maximum of 15% what is in an acceptable range.
Eisa [ 54 ] modeled RC columns in Abaqus. The position of the spherical charge remained unchanged, but the charge weight, column height, longitudinal steel reinforcement, columns aspect ratio, and transverse steel ratio were varied. Fixed boundary conditions are provided at the top and bottom of the column. In addition to column damage, they measured acceleration and displacement concerning varied parameters. Four quantities of explosives were used (45.36, 226.80, 453.59, and 1016.05 kg) and placed at a distance of 4.87 m. The increase in the lateral reinforcement in the column had the effect of reducing the displacement in the middle of the column. It is recommended to examine the influence of the axial force during the blast load and to include additional parameters such as the variation in the standoff distance of the charge.
In numerical simulations using Autodyn, Abladey and Braimah [ 55 ] tested three columns designed for different loads in accordance with the Canadian reinforced concrete design code [ 91 ]. The first type of column is designed only for gravity loads, and the distance between the transverse reinforcement is 300 mm, and the other two types of columns are designed for seismic loads, but in the second type, the distance between transverse reinforcement is 150 mm, and in the third 75 mm. Column damage is significantly less with denser reinforcement, especially at small-scaled distances. They have proven in research that regardless of the same scaled distance, in a situation where a larger amount of explosive is detonated, the column has a higher deflection.
Li and Hao [ 56 ] calibrated the numerical model for RC slab in LS-Dyna according to a previously performed experiment and then used that numerical model for RC column simulation. For good simulation of concrete spallation, the erosion criterion using principle tensile strain of 0.01 was defined. Through simulations, they concluded that denser reinforcement and greater column depth reduced spall damage, i.e., increase the confinement of concrete. The boundary conditions and column height do not play a significant role in the level of spall damage in close-in cases.
Shi and Stewart [ 57 ] analyzed a spatial and non-spatial simulation of the blast load on RC columns in LS-Dyna. They used three quantities of ANFO explosives, 50, 100, and 1000 kg, at distances from 0 to 30 m. The analysis is based on axial load-carrying capacity and concluded that the variability of the results in the spatial model is lower, and the probability of damage is significantly higher. They consider the spatial model more reliable and recommended it for future research with an additional assessment of the scale of fluctuation.
Elsanadedy et al. [ 50 ] used LS-Dyna for analyzing the behavior of the exterior building RC circular column and strengthened column with Carbon Fiber Reinforced Polymer (CFRP) sheets under blast load. Four different charge weights (100, 200, 500, and 1000 kg) of TNT at three different standoff distances (1, 4, and 15 m) and at 1 m height from the ground were analyzed. They modeled columns with different boundary conditions, first with both fixed ends and a second type with both hinged ends. For calculation of blast load parameters in all assumed scenarios, they used the software ConWep. The use of CFRP is increasing the shear capacity of the column and the strength of the column, which results in less lateral displacement, and more layers of CFRP can undergo more intense blast loads [ 50 ]. Moreover, at the scaled distance from 0.50 to 0.68 m/kg 1/3 , columns with CFRP showed better behavior than RC columns.
Ashalekshmi and Subha [ 92 ] modeled a bridge column in the Ansys Autodyn software to analyze the impact of concrete grade and spacing of ties under the blast load. They observed total deformation and principal stress for concrete grades M40 and M50 and ties spacings of 10 and 20 cm in the near and far-field. In the near field, the explosive is placed at the same standoff distance of 2 m, and the charge weight varies from 250 to 1500 kg. The influence of the concrete grade on the maximum deformation is visible only at the weight of explosives greater than 750 kg. With concrete M50, the principal stress is higher, but there is no big difference in it when increasing the weight of explosives. In the far-field, the explosive was placed at a standoff distance of 10 m, and the weight also varied from 250 to 1500 kg. There is a slight difference in total deformation concerning the grade of concrete. The principal stress exceeds the strength of concrete, and the difference in stress is visible for the grade of concrete. The effect of tie spacing is visible in the near field only in the increase in the maximum principal stress, while in the far-field, there is no effect on either deformation or principal stress.
Liu et al. [ 58 ] modeled the bridge column and bent it in the LS-Dyna for three design categories provided in [ 35 ]. They determined six damage mechanisms in the models, four of the column and two of bent. In all three design categories (A, B, C), spalling of concrete and crushing of the bent concrete were observed. Plastic joints in the column and shear of bent occur only in B and C categories. The shear or flexure failure of the column is most probable in category C, i.e., at the highest blast load. They found that increasing the transverse reinforcement reduces damage. In LS-Dyna, they received underestimated blast load, and therefore they used the ConWep program to calculate pressure-time diagrams.
Cui et al. [ 59 ] concluded through numerical simulations of columns in LS-Dyna that a larger cross-section and reinforcement ratio, smaller spacing between the stirrups, and a thinner concrete cover for columns exposed to close-in explosions give less damage.
Zhang et al. [ 12 ] analyzed circular and square CFST (Concrete Filled-Steel Tube) columns with tube thicknesses of 2.8 and 3.8 mm. The Emulsion explosive was used, with TNT equivalences of (0.7) 17.5, 25, and 35 kg. A numerical simulation of the columns was performed in LS-Dyna, see Figure 18 , but to reduce the computation time and model congestion, an air blast model was made in the ConWep program and then imported into LS-Dyna. By comparing the obtained periods of oscillation and maximum displacements, a good match between the numerical model and the experiment was obtained. Differences are found only in residual deflections but are not considered crucial to the accuracy of the model.
Figure 18. The numerical model of the blast test [ 12 ]. Copyright permission obtained from authors.
Zhang et al. [ 21 ] numerically modeled CFDST columns with steel-fiber reinforced concrete using LS-Dyna and compared them with experimentally obtained results. For concrete, the KC model was used, and for the steel tube, the Material model 24 was used. The parameters for the concrete model were modified ( f t —tensile strength, B 1 —parameter for residual strength, w lz —strain softening, ω— confinement effect, λ, and η— damage parameters) because UHPC was used. Column erosion occurs when the maximum shear strain value reaches 0.045. Numerical research concluded that the axial load up to a certain limit has a favorable effect on the deflection in the middle of the column. It is not recommended to use columns with a hollow section ratio greater than 0.5. Increasing the thickness of the outer steel tube affects the decrease in deflection in the middle of the column. Columns filled with UHPC have less plastic deformation than columns filled with normal strength concrete, shown in Figure 19 .
Figure 19. Failure mode of CFDST column with: ( a ) normal strength concrete and ( b ) UHPC [ 21 ]. Copyright permission obtained from authors.
Codina et al. [ 14 ] compared the numerical simulation with an already conducted experiment. The used explosive was Gelamon VF65 (65% TNT equivalence), 8 kg TNT equivalence at distances of 1 m and 0.60 m from the column, which is classified as a near-field range. Overpressure, impulse, deflection, acceleration, and visual damage to the column were measured and compared. For numerical modeling, the Ansys Autodyn program was used in which air and explosives were modeled through an Euler processor and the column through Lagrange. The optimal mesh size of concrete, steel, and the air was 10 mm. The authors made models with default RHT values and with the values proposed in [ 93 ] but concluded that the parameters that affect the strength degradation (damage factors D 1 and D 2 , and e m i n f a i l ) and the residual strength, Y * fric (parameters B and M ) should be changed in the model. For good prediction of spallation, the instantaneous geometric strain was used for erosion type with a value of 0.5. The obtained column damage with different RHT parameters is shown in Table 6 . The parameters of the RHT material model (shown in Table 3 ) are validated for scaled distances ( Z ) from 0.5 to 0.3 m/kg 1/3 .
Table 6. Column damage obtained: (a) experimentally and numerically using (b) default RHT model parameters; (c) parameters provided in [ 93 ]; (d) modified parameters by [ 14 ].
Arowojolu et al. [ 60 ] studied, using LS-Dyna numerical models, the influence of axial and blast load on the RC column of the bridge. For the concrete model, they used CSCM (Continuous Surface Cap Model) and for reinforcement MAT 24. Exact quantities of explosives and distances are not given, but scaled distances from 1.77 to 0.45 m/kg 1/3 . They concluded that when an axial load ratio of 0.25 is applied, the displacement in the middle of the column decreases but the damage of the column increases.
Eamon and Aslendi [ 61 ] made a numerical model of the column, experimentally tested in [ 4 ] using LS-Dyna software. The influence of concrete strength, reinforcement ratio, axial load, and the column wrapping with SFRP (Steel Fiber Reinforced Polymer) was observed. The Johnson–Holmquist–Cook (JHC) model was used for concrete modeling and the elastic–plastic kinematic model for steel reinforcement. The impact of the blast load was determined in the ConWep software, and the detonation point was placed 5 cm above the ground, 40 cm from the column. SFRP proved to be an inexpensive and ductile retrofit. One layer has the largest contribution in blast capacity, while all additional layers have a small effect on increasing the capacity. They obtained a linear relationship between the concrete strength and the increase in the blast load capacity.
Kravchenko et al. [ 62 ] performed numerical simulations of the RC column in LS-Dyna. The concrete was modeled using the CSCM concrete model (type 159 material) and reinforced using the plastic–kinematic model (type 3 material). They observed the influence of detonation of 10 kg of TNT at a distance of 1.2 m from the ground and 1 m from the column. They also concluded that the reinforcement ratio has a significant impact on the behavior of columns under the blast load and that the columns in the ground floor and bases need to be better reinforced due to their easy accessibility.
Kyei and Braimah [ 63 ] modeled three RC columns in LS-Dyna, which differ in the distance between the transverse reinforcement. They designed the columns according to the instructions for the level of seismicity in the Canadian concrete design code [ 91 ]. Concrete was modeled using the Continuous Surface Cap Model (MAT_CSCM_159), and for reinforcement, they used Material Piecewise Linear Plasticity (MAT_024) model, while blast load was calculated in ConWep and then imported with Load Blast Enhanced (LBE) in LS-Dyna. They performed simulations with mesh sizes from 5 to 100 mm, and with 15 mm, they obtained a good ratio of the time spent for the calculation and the accuracy of the results compared with the experiment in [ 94 ]. The used explosive was ANFO (100, 250, 500, and 1000 kg) at scaled distances of 0.8, 1.0, and 1.5 m/kg 1/3 . In near-field explosions, the distance between the transverse reinforcement has a significant effect on the reduction in displacement, while in far-field explosions, this effect is negligible. At a high axial load ratio (0.35), the seismically designed columns showed better behavior at scaled distances than the standard ones.
Yuan et al. [ 23 ] performed numerical simulations in LS-Dyna of the circular and square columns of the bridge, exposed to the contact explosion of 1 kg of TNT. To reduce the computation time, at the height of 1 m, in the area of the contact explosion, they placed a denser mesh (8 mm), while on the rest of the column, the mesh size was courser (20 mm), shown in Figure 20 . The principal strain of 0.5 was used as the erosion criterion. Numerical simulations well described the damage on the front sides of the column, while on the back, there are differences. They concluded that the damage was greater on the square column due to the flat surface and the higher stress concentration than on the circular column. The damage of the columns is shown in Figure 21 .
Figure 20. Detailed views of a mesh of 3D column models [ 23 ]. Copyright permission obtained from authors.
Figure 21. Comparison of damages of circular and square RC columns after the detonation of 1 kg of TNT: ( a ) front side and ( b ) back side [ 23 ]. Copyright permission obtained from authors.
Yuan et al. [ 77 ] investigated the effect of axial load on RC bridge columns subjected to far-field, close-in, and contact explosion. Columns in the far-field have mainly a flexure response, and the axial load affects the reduction in the maximum displacement in the middle of the column. In the case of a close-in detonation, a shear failure is expected, and the axial load affects the increase in the damage of the column and should not be neglected. In contact detonation, the concrete covers at the front and backside of the column spall off. The axial load reduces the damage of the concrete but increases the stress in the reinforcement and must be considered.
Li et al. [ 65 ] conducted numerical investigations on CFDST columns under contact explosion in LS-Dyna. CFDST columns have proven to be good for two reasons: the first is that the confinement of concrete by steel tube allows better energy absorption, and the second is the prevention of the spallation of the concrete cover. In work [ 73 ], the researchers concluded that increasing the cross-sectional area and the ratio of reinforcement plays a significant role in the post-blast residual capacity of CFDST columns under contact explosion. In [ 67 ], the behavior of CFDST columns subjected to close-in blast loading was studied. They concluded that the influence of the charge shape significantly affects the response and behavior of the column at scaled distances from 0.079 m/kg 1/3 to 0.175 m/kg 1/3 .
Liu et al. [ 66 ] performed a dynamic and static analysis of the bridge columns in LS-Dyna. Dynamic analysis is based on the comparison of accelerations and static analysis on the determination of damage through the ratio of the residual to the ultimate axial bearing capacity. They examined the damage to the column concerning the position of the explosives, at the bottom, in the middle, and at the top, shown in Figure 22 . In all three cases, bending deformation occurs at the column, but the position of the crack formation differs.
Figure 22. Shock wave propagation depending on the position of the explosive [ 66 ].
Liu et al. [ 68 ] performed a parametric analysis in LS-Dyna to determine the influence of longitudinal and transverse reinforcement ratios, longitudinal force, and boundary conditions. They concluded that at smaller-scaled distances, the increase in transverse and longitudinal reinforcement reduces the displacement in the middle of the column. It is recommended that the percentage of longitudinal reinforcement does not exceed 6% of the cross-sectional area of the column because too much reinforcement can lead to brittle failure. Analyzing the influence of the axial compressive load, they found that in an amount of up to 40%, it reduces the maximum displacement in the mid-span of the column due to the increase in moment capacity. The conclusions are based on close-in blast loading; a recommendation for future research is to conduct a parametric analysis for near and far filed scenarios.
Liu et al. [ 69 ] made numerical models of RC columns strengthened with CFRP in LS-Dyna. The size of the mesh elements for all materials was 10 mm, and for air, 20 mm. The 1 kg and 2 kg TNT charges were placed in contact with the column at the height of 30 cm. The numerical results show that the dragging force of the blast load separates the CFRP from the concrete, but despite this, CFRP protects the column from contact explosion. Column damage is shown in Figure 23 .
Figure 23. Column damages after detonation of 1kg TNT: ( a ) RC and ( b ) RC + CFRP column [ 69 ]. Copyright permission obtained from authors.
Thai et al. [ 70 ] modeled in LS-Dyna RC steel jacked columns (25 cm × 25 cm × 360 cm) and observed the influence of steel thickness, scaled distance, and longitudinal compressive force on the behavior of the columns under the blast load. The columns are designed according to Eurocode 2. A 10 mm mesh was used for the column, while 5 mm elements were used for the explosive. Placing 8 kg of TNT in the middle of the column causes less global damage to the column, while placing the same amount at a distance of 32 cm from the ground causes significant local damage. The scaled distance was varied from 0.10 to 0.40 m/kg 1/3 . Increasing the steel thickness from 3 mm to 6 mm did not result in less damage.
Abedini et al. [ 33 ] investigated numerically in LS-Dyna the influence of charge and scaled distance on the level of column damage and influence of column width, concrete strength, and reinforcement ratio on the residual axial load capacity.
Dua et al. [ 72 ] performed a parametric analysis in LS-Dyna on the RC columns exposed to the contact explosion. They used from 115 g to 1000 g TNT, varied the compressive strength of concrete from 20 to 55 MPa, and reduced the distance of the transverse reinforcement from 200 to 50 mm. Increasing the transverse reinforcement reduces the damage to the concrete core, and higher compressive strength of concrete contributes to the reduction in cracks and peeling. The columns under contact explosion have local damage, while the global damage is negligible. Dua et al. [ 28 ] investigated in LS-Dyna the influence of the column cross-sectional width under the contact explosion. They concluded that a larger cross-sectional width (greater by two or more times from the depth) has a favorable effect on the behavior and damage of the column.
Rajkumar et al. [ 74 ] examined 45 numerical models of reinforced concrete columns in scale 1:4 (85 mm × 85 mm × 900 mm) in LS-Dyna. In the models, the behavior of four different cross-sections (circular, octagonal, hexagonal and square) on the blast load was examined. The circular column retains the lowest peak pressures and has the smallest deflection in the middle, while the square has the highest pressures and the largest deflection. The edges in cross-sections at small-scaled distances play a significant role in pressure retention, while with increasing scaled distance, the shape influence decreases. An increase in reinforcement in cross-section affects the improvement of the behavior of the columns during the blast load, especially in shapes that retain higher pressures.
Vavilala et al. [ 75 ] numerically simulated polymeric foam retrofitted RC columns (35.5 cm × 35.5 cm × 348 cm) in Abaqus. They used a 10 mm mesh for reinforcement and 20 mm for concrete. Columns coated with 5 mm, 8 mm, and 10 mm thick foam were exposed to 10, 25, and 50 kg of TNT. The greatest reduction in displacement in the middle of the column was obtained under 10 kg of TNT when the column was coated with 10 mm thick foam.
Zhang et al. [ 76 ] compare in LS-Dyna the behavior of a segmental CFST column with monolithic and prestressed monolithic columns. The columns were exposed to 20 and 50 kg of TNT at a standoff distance of 1.5 m. The segmental column showed a smaller residual displacement, and numerical analysis proved that a larger number of segments had a more favorable effect on the behavior of the column. Moreover, increasing the steel thickness had a beneficial effect on reducing concrete damage.
Yan et al. [ 78 ] and Hu et al. [ 79 ] used LS-Dyna for numerical simulations of RC columns retrofitted with CFRP subjected to the close-in explosion. CFRP sheets reduce the deformation and spalling of concrete. The CFRP thickness, wrapping, and dimensions ratio of the charge also had a large impact on the damage of the column and peak pressure. Debonding of CFRP is the most common form of failure, but despite this, CFRP has a role in reducing column damage during the blast load, and it may even have a role in changing the failure mode from shear to flexural deformation. The setting of the CFRP on both sides of the column needs to be further investigated because direct shear is possible due to over-reinforcement.
4. Discussion and Conclusions
4.1. Experimental Testing
Most of the experiments were conducted for the scenario of an attack by an auto-bomb located near a bridge or building column. Experimental tests on building columns are mostly full-scale, while tests on bridge columns predominate on scales of 1:3 and 1:4, due to the high cost of performing such experiments, the need for trained personnel to handle explosives, large quantities of explosives, and the field where such tests can be carried out.
Experiments showed that even a minimal increase in the cross-sectional dimensions of a column could favorably affect the behavior of the column under the blast load. Moreover, a minimal increase in the standoff distance reduces the impact and intensity of the blast load, and therefore it is necessary whenever possible to fence the column, increase visibility around the column, and reduce its accessibility. In addition to the dimensions of the column, the shape of the column plays a significant role. Circular columns retain less impulse from the blast load than square ones of the same dimensions. Squares have a larger cross-sectional area and, therefore, can better withstand shear. On the action of the contact explosion, the circular column suffered less damage than the square. However, comparing a square and a rectangular column, when the width dimension of the rectangular column is greater two and more times from depth, damage of the column is lower. The shape of the column on the blast load needs to be further investigated. In RC columns, position, quantity, anchoring, and reinforcement overlap have a great impact. Therefore, seismically designed columns have better blast load behavior than standard designed columns.
Comparing steel jacked columns, CFST and CFDST with RC columns, all showed better ductility, less cracking of the concrete, and the absence of flying debris. However, CFDST showed the best behavior, as the inner steel tube contributes to the prevention of direct shear. With this type of column, it is important that the ratio of the cavity to the column cross-section is not greater than 0.5 and that the thickness of the steel tube is well determined (a thickness of 3.8 mm gave satisfactory results).
Columns with Ultra-High-Performance Concrete and with various Fiber-Reinforced Polymers showed better load-bearing capacity than High-Strength Reinforced Concrete.
The influence of axial load up to 30% of the total load capacity has shown a favorable effect on the reduction in the maximum displacement, but this percentage needs to be further investigated.
Recent research applies smart aggregates to measure internal cracks and internal damage because the column can be damaged and reduced load-bearing capacity without being visible on the outside. Therefore, post-blast tests are performed to determine the residual strength and ductility of the column.
4.2. Numerical Modeling
Numerical simulations make it possible to study the effect of large amounts of explosions (more than 1000 kg) on columns in full-scale. The most widely used software for analyzing the nonlinear behavior of elements on blast load is LS-Dyna. The most accurate simulation of the blast pressure requires as finer mesh as possible, which leads to a long duration of simulations and congestion of the computer processor. Due to the use of a larger mesh size than recommended, the LS-Dyna underestimates the pressures. Most researchers use the ConWep program to calculate pressures and import the resulting pressures into LS-Dyna.
Defining a model of concrete material is the most demanding because many parameters affect its behavior. Karagozian and Case (KC) concrete is mostly used in LS-Dyna. The proper definition of erosion criteria has proven to be very important in modeling column damage.
The position of the explosive plays a significant role in the behavior of the column. Placing the charge in the far-field causes a uniformly distributed load per column and global response, while a charge placed in the near-field, close-in, and contact creates local damage.
Moreover, the columns exposed to the charge placed in the lower half showed greater damage and lowered residual capacity than the columns where the charge was placed in the middle.
In all fields (far, near, close-in), changes in the quantity, shape, and position of the explosives showed a great impact on column behavior. The shape of the column, the ratio of reinforcement, and the concrete grade showed an influence only at small-scaled distances. The concrete grade does not affect the rotation of the column but does affect the reduction in concrete breach and spallation.
Until recently, the axial load on bridge columns was neglected in the calculation because it was considered to be on the safe side. However, numerical simulations showed that axial load has a large impact on increasing damage when the charge is placed near the column or in contact with the column and should not be neglected.
Author Contributions
Conceptualization, S.L. and H.D.; methodology, S.L. and H.D.; resources, S.L. and H.D.; data curation, S.L.; writing—original draft preparation, S.L.; writing—review and editing, H.D.; visualization, S.L.; supervision, H.D.; project administration, H.D.; funding acquisition, H.D. All authors have read and agreed to the published version of the manuscript.
Acknowledgments
This paper has been supported in part by Croatian Science Foundation (HRZZ) under the project UIP-2017-05-7041 “Blast Load Capacity of Highway Bridge Columns”, and support for this research is gratefully acknowledged.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Percentages of terrorist attack types, based on data from [ 1 ].
Figure 2. CFST column—details of column-to-foundation beam connection [ 7 ].
Figure 3. Test setup in [ 7 ] and [ 9 ].
Figure 4. Test setup [ 4 , 8 ].
Figure 5. Reinforcement position in specimens: ( a ) RC column and ( b ) CFFT column; specimen position: ( c ) test setup [ 18 ].
Figure 6. Comparison of damages of circular and square RC columns after the detonation of 1 kg of TNT: ( a ) front side and ( b ) back side [ 23 ]. Copyright permission obtained from authors.
Figure 7. Schematic and field views of test setup [ 29 ]. Copyright permission obtained from authors.
Figure 8. Damage of UHPCC-FST columns after detonation of: ( a ) 1 kg; ( b ) 2 kg and ( c ) 3 kg of TNT [ 29 ]. Copyright permission obtained from authors.
Figure 9. Test setup [ 24 ] and test pit [ 21 ]. Copyright permission obtained from authors.
Figure 10. Cross-sections of two CFDST specimens [ 20 ]. Copyright permission obtained from authors.
Figure 11. Columns after blast test [ 24 ]. Copyright permission obtained from authors.
Figure 12. Damage of the RC columns after detonation at 100 cm and 60 cm standoff [ 14 ]. Copyright permission obtained from authors.
Figure 13. RC columns reinforced with: ( a ) polyurethane bricks [ 15 , 16 ] and ( b ) resin panels and insulation layer [ 22 ]. Copyright permission obtained from authors.
Figure 14. Damage after blast load on RC members: ( a ) without protection; ( b ) with steel jacketing; ( c ) with polyurethane bricks, and ( d ) with reinforced resin panels [ 15 , 16 , 22 ]. Copyright permission obtained from authors.
Figure 15. Column damages after blast loads: ( a ) 1 kg; ( b ) 0.5 kg and ( c ) 115 g TNT [ 27 ]. Copyright permission obtained from authors.
Figure 16. Position and appearance of the SA sensors [ 45 ].
Figure 17. Time history of displacements for 4 column types [ 47 ].
Figure 18. The numerical model of the blast test [ 12 ]. Copyright permission obtained from authors.
Figure 19. Failure mode of CFDST column with: ( a ) normal strength concrete and ( b ) UHPC [ 21 ]. Copyright permission obtained from authors.
Figure 20. Detailed views of a mesh of 3D column models [ 23 ]. Copyright permission obtained from authors.
Figure 21. Comparison of damages of circular and square RC columns after the detonation of 1 kg of TNT: ( a ) front side and ( b ) back side [ 23 ]. Copyright permission obtained from authors.
Figure 22. Shock wave propagation depending on the position of the explosive [ 66 ].
Figure 23. Column damages after detonation of 1kg TNT: ( a ) RC and ( b ) RC + CFRP column [ 69 ]. Copyright permission obtained from authors.
Table 1. Summary of experimental research.
Author Year Structural Element Experiment Type Material Scale Bruneau et al. [ 6 ] 2006 Multicolumn bents Field CFCSC 1:4 Fujikura et al. [ 7 ] 2008 Multicolumn bents Field CFST 1:4 Davis et al. [ 8 ] 2009 Bridge column Field RC S. s. + 1:2 Fujikura and Bruneau [ 9 ] 2010 Multicolumn bents Field RC and RC SJ 1:4 Williamson et al. [ 4 ] 2011 Bridge column Field RC 1:2 Crawford [ 10 ] 2013 Building column Field RC + FRP + SJ 1:1 Burrell et al. [ 11 ] 2015 Column Shock tube SFRC 1:2 Zhang et al. [ 12 ] 2015 Building column Field CFST 1:1 Aoude et al. [ 13 ] 2015 Building column Shock tube UHPFRC 1:1 Codina et al. [ 14 ] 2016 Building column Field RC 1:1 Codina et al. [ 15 , 16 ] 2016 Building column Field RC, RC SJ, RC + polyurethane bricks 1:1 Xu et al. [ 17 ] 2016 Column Field UHPFRC + HSRC 1:1 Echevarria et al. [ 18 ] 2016 Bridge column Field CFFT + RC 1:5 Fouché et al. [ 5 ] 2016 Multicolumn bents Field RC MSJ 1:4 Wang et al. [ 19 ] 2016 Column Filed RPC-FST 1:1 Zhang et al. [ 20 ] 2016 Column Field CFDST infilled with UHPC 1:1 Zhang et al. [ 21 ] 2017 Column Field CFDST 1:1 Codina et al. [ 22 ] 2017 Building column Field RC + reinforced resin panels 1:1 Yuan et al. [ 23 ] 2017 Bridge column Field RC 1:3 Wang et al. [ 24 ] 2017 Building column Field CFST 1:1 Li et al. [ 25 ] 2017 Building column Field UHPC + HSRC 1:1 Fouché et al. [ 26 ] 2017 Bridge column Field CFDST 1:4 Dua et al. [ 27 ] 2018 Column Field RC 1:1 Dua et al. [ 28 ] 2019 Column Field RC 1:1 Wang et al. [ 29 ] 2020 Bridge column Field UHPCC-FST 1:4 Kadhom et al. [ 30 ] 2020 Column Shock tube RC and RC + CFRP 1:2 Vapper and Lasn [ 31 ] 2020 Building column Filed RC, RC + GFRP 1:2
Note: CFCSC—Concrete-Filled Circular Steel Columns, CFST—Concrete-Filled Steel Tube, RC—Reinforced Concrete, SJ—Steel Jacket, MSJ—Modified Steel Jacket, FRP—Fiber-Reinforced Plastic, SFRC—Steel Fiber-Reinforced Concrete, UHPFRC—Ultra-High Performance Fiber Reinforced Concrete, HSRC—High Strength Reinforced Concrete, CFDST—Concrete-Filled Double-Skin Tubes, UHPC—Ultra-High Performance Concrete, SFRP—Steel Fiber Reinforced Polymer, UHPFRC—Ultra-High-Performance Fiber-Reinforced Concrete, CFFT—Concrete-Filled Fiber-Reinforced Polymer (FRP) tube, RPC-FST—Reactive Powder Concrete Filled Steel Tubular, HSRC—High Strength Reinforced Concrete, S. s.—small scale, GFRP—Glass Fiber Reinforced Polymer.
Table 2. Maximum support rotations (blast at low height).
Top Bottom Crack Patterns of Concrete Deformation CFST [ 7 ] 1.2° 3.8° No available Plastic 2.2° 8.3° Tension side Plastic 4.9° 17.0° Opening of core concrete On-set of fracture of column 18.7° - Blew away Post-fracture of column RC MSJ [ 5 ] - 8.6–10.3° Satisfactory ductile behavior RC [ 2 , 36 , 39 ] * - 1.3° Slight to moderate damage - 2° Moderate to heavy damage - 3° Lose structural integrity RC [ 40 ] - 2° Minor damage Onset of shear failure at base - 4° Collapse Shear failure at base RC (UFC 3-340-02) [ 41 ] 2–5° Moderate damage 5–12° Severe damage RC (AISC 341) [ 42 ] 2.3° Highly ductile
* Based on experimental testing of concrete beam elements in flexure.
Table 3. Damaged columns after contact detonation and the residual load capacities [ 44 ].
RC Polymer Concrete SIFCON DUCON UHPC Type Damage Residual load capacity 5.5% 68.6% 69.6% 49.3 (coarse)– 65.9 (fine) % -
Table 4. Summary of software for prediction and calculation of blast loads.
Author Year Structural Element Software Ray et al. [ 46 ] 2003 Bridge deck and column ConWep, BlastX, SHAMRC Marchand et al. [ 36 ] 2004 Bridge columns BlastX, ConWep, SPAn32 Winget et al. [ 2 ] 2005 Bridge concrete girders, deck, columns BlastX, SPAn32, Nonlin Rutner et al. [ 47 ] 2006 Steel and composite bridge columns MSC.Dytran Wu et al. [ 48 ] 2009 RC and composite building columns LS-Dyna Hao et al. [ 49 ] 2010 RC building columns CARLER Elsanadedy et al. [ 50 ] 2011 RC building columns + CFRP LS-Dyna Williams et al. [ 51 ] 2011 RC bridge columns LS-Dyna Williams et al. [ 52 ] 2011 RC bridge columns LS-Dyna Crawford [ 10 ] 2013 RC building columns + FRP + SJ LS-Dyna Magali et al. [ 53 ] 2013 RC building columns Abaqus Eisa [ 54 ] 2014 RC building columns Abaqus Abladey and Braimah [ 55 ] 2014 RC building columns Autodyn Li and Hao [ 56 ] 2014 RC column LS-Dyna Shi and Stewart [ 57 ] 2015 RC building column LS-Dyna Liu et al. [ 58 ] 2015 RC bridge pier-bent model LS-Dyna, ConWep Cui et al. [ 59 ] 2015 RC column LS-Dyna Zhang et al. [ 12 ] 2015 CFST building columns LS-Dyna Codina et al. [ 14 ] 2016 RC building column Autodyn Zhang et al. [ 21 ] 2016 CFDST columns LS-Dyna Arowojolu et al. [ 60 ] 2017 RC bridge column LS-Dyna Eamon and Aslendi [ 61 ] 2017 RC bridge columns + SFRP LS-Dyna Kravchenko et al. [ 62 ] 2017 RC building columns LS-Dyna Kyei and Braimah [ 63 ] 2017 RC building columns LS-Dyna Yuan et al. [ 23 ] 2017 RC bridge columns LS-Dyna Abedini et al. [ 64 ] 2018 RC building columns LS-Dyna Li et al. [ 65 ] 2018 CFDST bridge columns LS-Dyna Liu et al. [ 66 ] 2018 RC bridge piers LS-Dyna, ConWep Li et al. [ 67 ] 2019 CFDST bridge columns LS-Dyna Liu et al. [ 68 ] 2019 RC building columns Autodyn, LS-Dyna Liu et al. [ 69 ] 2019 RC bridge column + CFRP LS-Dyna Thai et al. [ 70 ] 2019 RC column + SJ LS-Dyna Abedini et al. [ 71 ] 2019 RC column LS-Dyna Dua et al. [ 72 ] 2019 RC columns LS-Dyna Dua et al. [ 28 ] 2020 RC columns LS-Dyna Li et al. [ 73 ] 2020 CFDST columns LS-Dyna Rajkumar et al. [ 74 ] 2020 RC columns LS-Dyna Vavilala et al. [ 75 ] 2020 RC building columns + polymeric foam Abaqus Zhang et al. [ 76 ] 2020 Segmental CFST column LS-Dyna Yuan et al. [ 77 ] 2020 RC column LS-Dyna Yan et al. [ 78 ] 2020 RC columns + CFRP LS-Dyna Hu et al. [ 79 ] 2021 RC column + CFRP LS-Dyna
Note: CFRP—Carbon Fiber Reinforced Polymer; FRP—Fiber-Reinforced Plastic; SJ—Steel Jacket; CFST—Concrete-Filled Steel Tube; CFDST—Concrete-Filled Double Steel Tube; SFRP—Steel Fiber Reinforced Polymer.
Table 5. Damage levels of RC column in terms of axial load capacity.
Level of Damage [ 49 ] D = 1 − N r e s i d u a l N 0 Damage Limit States [ 57 ] Low damage 0–0.2 Low damage Medium damage 0.2–0.5 Repairable damage High damage 0.5–0.8 Repairable damage Collapse 0.8–1.0 Collapse
Table 6. Column damage obtained: (a) experimentally and numerically using (b) default RHT model parameters; (c) parameters provided in [ 93 ]; (d) modified parameters by [ 14 ].
Parameters (a) Autodyn (Default) [ 86 ] (b) Tu and Lu [ 93 ] (c) Codina et al. [ 14 ] (d) B 1.6 0.7 0.35 M 0.61 0.8 0.55 RHT damage model D 1 0.04 0.015 0..8 D 2 1 1 1 e m i n f a i l 0.01 8.00 × 10 −4 0.03
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A structure-free digital microfluidic platform for detection of influenza A virus by using magnetic beads and electromagnetic forces | Request PDF
Request PDF | A structure-free digital microfluidic platform for detection of influenza A virus by using magnetic beads and electromagnetic forces | H1N1, a subtype of influenza A virus, has emerged as a global threat in the past decades. Due to its highly infectious nature, an accurate and... | Find, read and cite all the research you need on ResearchGate
A structure-free digital microfluidic platform for detection of influenza A virus by using magnetic beads and electromagnetic forces
January 2020
Lab on a Chip20(36)
DOI: 10.1039/C9LC01126A
Authors:
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Po-Hsien Lu
Po-Hsien Lu
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe>
Yu Dong Ma
National Tsing Hua University
<here is a image 11d615793d4903f3-eccc6099be1af4ee>
Chien-Yu Fu
National Tsing Hua University
<here is a image bc30499e844160b0-b9cbcfbac64e9cad>
Gwo-Bin Lee
National Tsing Hua University
Abstract
H1N1, a subtype of influenza A virus, has emerged as a global threat in the past decades. Due to its highly infectious nature, an accurate and rapid detection assay is...
<here is a image 175d1bd4b7439d95-754927124da715c1>
... In 2014, they utilized an integrated microfluidic system for successfully screening an influenza A/H1N1 virus-specific aptamer in a highly efficient and automated assay [183]. Subsequently, several integrated microfluidic-based aptasensors were reported [194][195]
[196]
. A novel integrated microfluidic aptasensor based on a single universal aptamer was proposed to detect three kinds of viruses (H1N1, H3N2, and influenza B) [195]. ...
... Through the level of fluorescence intensity to differentiate different types of influenza viruses. Moreover, they firstly proposed an ELISA-like assay-based structure-free digital microfluidic platform
[196]
. ...
... On the one hand, the performance of sensors is not enough to meet clinic diagnosis, including sensitivity, repeatability, and simplicity. To improve the detection performance of aptasensors, several ways should be taken: 1) utilizing nanomaterials as immobilization substrates, which provides a larger surface area for immobilizing aptamers, such as gold nanoparticles [36,176], multi-walled carbon nanotubes [134,143], reduced graphene oxide [180], etc. 2) forming microfluidic chip which can achieve on-site sensor for one-step sample purification and detection [120,133,
196]
. 3) proposing novel strategies and developing novel aptasensors [171], etc. ...
Aptamer-based biosensors for virus protein detection
Article
Jul 2022
TRAC-TREND ANAL CHEM
Beibei Lou
Yanfei Liu
Meilin Shi
<here is a image 6e21540a184828b6-368d4a19d5ed8e04> Zhenbao Liu
Virus threatens seriously life health. The accurate early diagnosis of the virus is vital for clinical control and treatment of virus infection. Aptamers are small single-stranded oligonucleotides (DNAs or RNAs). In this review, we summarized aptasensors of viral detection in recent years according to the classification of the viral target protein and illustrated common detection mechanisms in the aptasensor (colorimetry, fluorescence assay, surface plasmon resonance (SPR), surface-enhanced raman spectroscopy (SERS), electrochemical detection, and field-effect transistor (FET)). Furthermore, aptamers against the different target proteins of the same viruses were summarized. The relationships between the different biomarkers of the viruses and the detection methods and their performances were revealed. In addition, the challenges and future directions of aptasensors were discussed. This review will provide valuable references for constructing on-site aptasensors for detecting viruses, especially the SARS-CoV-2.
... Specific aptamers can be used to capture the virus, which is then exposed to a primary antibody that binds to the virus surface. The primary antibody enables the linkage to a secondary antibody with a fluorescent element, therefore generating an optically detectable signal
[89]
. When fighting against pathogens such as viruses, the human body produces several antibodies that will circulate the blood system and potentially neutralize the infectious agent. ...
... It is a common practice to use fluorescent elements to indicate the detection of a target. These elements can be added to the device [63,
89,
93], attached to the target element [84,90,132] or replicated during amplification steps [5,101,133]. Examples of fluorescent elements used in microfluidics are cyanine-5 (Cy5), methylene blue (MB) [79], fluorescein [77], fluorescein amidites (FAM), hexachlorinated fluorescein (HEX) [110], SYTO-82 [134], AF 488 [56], EvaGreen and SYBR Green [81,107]. ...
... Fluorescence is a very versatile method that can be used in different materials (e.g. paper [41], polymers [63] and structure-free
[89]
). It can also be adapted to automated analysis via smartphones or desktop scanners [107,135]. ...
Microfluidic devices for the detection of viruses: Aspects of emergency fabrication during the COVID-19 pandemic and other outbreaks
Article
Full-text available
Nov 2020
<here is a image dd180719577ea3ee-9794abc653dae674> Rafaela Grecco Machado
<here is a image 9f6043c9ad4465e8-345873d9a7fe227d> José Alvim Berkenbrock
<here is a image e8b2c57485fefc6b-2bba876c7550298d> Sven Achenbach
Extensive testing of populations against COVID-19 has been suggested as a game-changer quest to control the spread of this contagious disease and to avoid further disruption in our social, healthcare and economical systems. Nonetheless, testing millions of people for a new virus brings about quite a few challenges. The development of effective tests for the new coronavirus has become a worldwide task that relies on recent discoveries and lessons learned from past outbreaks. In this work, we review the most recent publications on microfluidics devices for the detection of viruses. The topics of discussion include different detection approaches, methods of signalling and fabrication techniques. Besides the miniaturization of traditional benchtop detection assays, approaches such as electrochemical analyses, field-effect transistors and resistive pulse sensors are considered. For emergency fabrication of quick test kits, the local capabilities must be evaluated, and the joint work of universities, industries, and governments seems to be an unequivocal necessity.
... Therefore, it has a strong advantage in improving the performance of viruses and potential biomarker detection. For example, Lu and his co-workers developed a magnetic digital microfluidic platform using an ELISAlike assay to detect Influenza A ( Figure 5F)
(Lu et al., 2020)
. Magnetic microbeads coated with H1N1-specific aptamers were used to actuate the microfluid. ...
... (E) Scheme of ULISA for counting single molecules of PSA (Farka et al., 2017). (F) Schematic diagram of influenza virus diagnostic process using magnetic beads in a structure-free digital microfluidic platform
(Lu et al., 2020)
. been established. ...
Recent advances in immunoassay technologies for the detection of human coronavirus infections
Article
Full-text available
Jan 2023
... The FRET process was disrupted in the presence of target bacteria S. aureus, and the emission of complex Apt-Van-QDs@CNPs switched to the blue channel with a stoke shift of ∼260 nm (Fig. 8b). The platform utilizing ELISA-like assay for influenza A H1N1 virus detection
[121]
. Magnetic beads served as threedimensional substrates for H1N1-specific aptamers to capture the virus, while an HRP-conjugated antibody was used to form sandwich complexes with activate tyramidetetramethylrhodamine (TTMR) to generate amplified fluorescent signals. ...
... The employment of aptamers in POCT would enable discrimination and real-time monitoring of diseasecausing pathogens for subsequent personalized therapy. Some LSPR, paper-based lateral flow assay, electrochemical and microfluidic aptasensing platforms listed in the "Aptasensors for pathogen detection" section have showcased their potential for the development of POCT devices as proof-of-concept models [75,85,105,118,[120]
[121]
[122]141]. In this section, we would like to highlight some ready-to-use devices, focusing on addressing the urgent needs of currently prevalent COVID-19, and the brief details of the selected aptamers are summarized in Table 3 for reference. ...
The epidemic of infectious diseases caused by contagious pathogens is a life-threatening hazard to the entire human population worldwide. A timely and accurate diagnosis is the critical link in the fight against infectious diseases. Aptamer-based biosensors, the so-called aptasensors, employ nucleic acid aptamers as bio-receptors for the recognition of target pathogens of interest. This review focuses on the design strategies as well as state-of-the-art technologies of aptasensor-based diagnostics for infectious pathogens (mainly bacteria and viruses), covering the utilization of three major signal transducers, the employment of aptamers as recognition moieties, the construction of versatile biosensing platforms (mostly micro and nanomaterial-based), innovated reporting mechanisms, and signal enhancement approaches. Advanced point-of-care testing (POCT) for infectious disease diagnostics are also discussed highlighting some representative ready-to-use devices to address the urgent needs of currently prevalent coronavirus disease 2019 (COVID-19). Pressing issues in aptamer-based technology and some future perspectives of aptasensors are provided for the implementation of aptasensor-based diagnostics into practical application.
Graphical Abstract
... Immunoagglutination, which involves the detection of clumps of magnetic beads conjugated to antibodies, is a technique used to carry out immunoassays such as ELISA. Immunoagglutination has been used for detection of viruses including influenza [10,
67]
, and is often used in combination with a DMF platform as in the studies by Coarsey et al. [68] and Lu et al. [67]. The latter used magnetic beads conjugated to H1N1 aptamers for detection of H1N1 virus by ELISA-like assay. ...
... Immunoagglutination, which involves the detection of clumps of magnetic beads conjugated to antibodies, is a technique used to carry out immunoassays such as ELISA. Immunoagglutination has been used for detection of viruses including influenza [10,67], and is often used in combination with a DMF platform as in the studies by Coarsey et al. [68] and Lu et al.
[67]
. The latter used magnetic beads conjugated to H1N1 aptamers for detection of H1N1 virus by ELISA-like assay. ...
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Sophie N. Kelley
<here is a image be0ee8d7544da5a3-a978cc3daf9b8a8c> Hadis Torabi
<here is a image 0878f1360681af6d-ea32a8b80c9b7d71> A. Doostmohammadi
<here is a image 0bd493cb4603b71b-0653759c9d26146c> Pouya Rezai
With the COVID-19 pandemic, the threat of infectious diseases to public health and safety has become much more apparent. Viral, bacterial and fungal diseases have led to the loss of millions of lives, especially in the developing world. Diseases caused by airborne viruses like SARS-CoV-2 are difficult to control, as they are easily transmissible and can circulate in the air for hours. To contain outbreaks of viruses such as SARS-CoV-2 and institute targeted precautions, it is important to detect them in air and understand how they infect their targets. Point-of-care (PoC) diagnostics and point-of-need (PoN) detection methods are necessary to rapidly test patients and environmental samples, so precautions can immediately be applied. Traditional benchtop detection methods such as ELISA, PCR and culture are not suitable for PoC and PoN monitoring, because they can take hours to days and require specialized equipment. Microfluidic devices can be made at low cost to perform such assays rapidly and at the PoN. They can also be integrated with air- and liquid-sampling technologies to capture and analyze airborne and body fluid-based viruses. Here, conventional and microfluidic virus detection methods are reviewed and compared. The use of air sampling devices to capture and concentrate viruses is discussed first, followed by a review of analysis methods such as immunoassays, RT-PCR and isothermal amplification in conventional and microfluidic platforms. This review provides an overview of the capabilities of microfluidics in virus handling and detection, which will be useful to infectious disease researchers, biomedical engineers, and public health agencies.
... For the first time, Lu et al. demonstrated a structure-free digital microfluidic platform for detection of influenza virus A (H1N1).
133
In their study, an electromagnetically driven force was used to manipulate the droplets (20 μl) containing magnetic beads, and a new ELISA-like assay with an amplified fluorescent signal was employed for H1N1 detection. The hydrophobicity gradient surface and the hydrophilic droplet surface energy trap enabled the droplet manipulation without any structure. ...
BIOMICROFLUIDICS
With the global outbreak of SARS-CoV-2, the inadequacies of current detection technology for respiratory viruses have been recognized. Rapid, portable, accurate, and sensitive assays are needed to expedite diagnosis and early intervention. Conventional methods for detection of respiratory viruses include cell culture-based assays, serological tests, nucleic acid detection (e.g., RT-PCR), and direct immunoassays. However, these traditional methods are often time-consuming, labor-intensive, and require laboratory facilities, which cannot meet the testing needs, especially during pandemics of respiratory diseases, such as COVID-19. Microfluidics-based techniques can overcome these demerits and provide simple, rapid, accurate, and cost-effective analysis of intact virus, viral antigen/antibody, and viral nucleic acids. This review aims to summarize the recent development of microfluidics-based techniques for detection of respiratory viruses. Recent advances in different types of microfluidic devices for respiratory virus diagnostics are highlighted, including paper-based microfluidics, continuous-flow microfluidics, and droplet-based microfluidics. Finally, the future development of microfluidic technologies for respiratory virus diagnostics is discussed.
... The automated chemiluminescence detection of procalcitonin may be accomplished in less than 12 min by driving the MBs to move and react along a sequence of droplets that were pre-loaded with reagents with a detection limit of 0.044 ng/mL [127]. The entire analysis can be carried out flexibly in droplets containing MBs by fine-tuning the magnetic density to alter the extraction of the beads (<320 mT) and the delivery of the droplets (>320 mT)
[128]
. In addition, the sensitivity of the assay is increased by combining digital microfluidics with the nucleic acid amplification techniques isothermal cycling to cyclic amplification [129], reverse transcription-polymerase chain reaction [130], and digital polymerase chain reaction [131]. ...
Magnetic nanoparticles (MNPs) are attracting increasing attention in bioanalysis, due to their large surface area and excellent steerable properties. Meanwhile, the booming development of microfluidics is offering a faster, lower consumption, and more effective approach to bioanalysis. MNPs-assisted microfluidic bioanalysis enables enhanced analytical performance by introducing functionalized magnetic nanomaterial into microchip devices. This work reviews the advances of MNPs-assisted microfluidic bioanalysis in the recent decade. The preparation and modification methods of MNPs are summarized as having a bioanalysis capability in microchips. These MNPs can be used for sample pretreatment materials and/or biosensing tags. In sample pretreatment, MNPs enable effective magnetic separation, preconcentration, and mass transport. In detection, MNPs act as not only magnetic sensing tags but also as the support for optical sensors. Finally, the overviews and challenges in microfluidic bioanalysis with the assistance of MNPs are discussed.
... The authors concluded that the system would allow for the rapid clinical diagnosis of AB in the near future. Lu et al.
[143]
introduced a new type of digital microfluidic facility for H1N1 virus detection, which utilizes a one-aptamer/two-antibody assay on magnetite-based nanoparticles. Aptamers, which have high specificity towards H1N1 viruses, were conjugated with magnetite-based nanoparticles such that they could be specifically captured and detected. ...
... Lee's group proposed a digital microfluidic platform for the detection of H1N1 virus
[60]
. This platform drives magnetic beadcontaining droplets by electromagnetic force and modified magnetic beads with aptamer to capture H1N1 virus. ...
Microfluidic biosensors integrating fluid control, target recognition, as well as signal transduction and output, have been widely used in the field of disease diagnosis, drug screening, food safety and environmental monitoring in the past two decades. As the central part and technical characteristics of microfluidic biosensors, the fluid control is not only associated with accuracy and convenience of the sensors, but also affects the material selection and working mode of the sensors. This review summarizes the fluid driving forces for microfluidic biosensors, including gravity, capillary force, centrifugal force, pressure, light, sound, electrical, and magnetic forces. Then, the recent advances in microfluidic biosensors for the detection of viruses, cells, nucleic acids, proteins and small molecules are discussed. Finally, we propose the current challenges and future perspectives of microfluidic biosensors. We hope this review can provide readers with a new perspective to understand the technical characteristics and application potential of microfluidic biosensors.
... Microdroplet arrays can also be generated using droplet stamping where the droplets are stamped into the hydrophilic region using a microstructure. Once the droplets are formed, they can undergo the ELISA process using magnetic bead capture and immunocomplex formation
[11]
. An early work demonstrated a typical sandwich ELISA using inkjet printing to generate droplets for the reaction [12]. ...
Recent Advances in Digital Biosensing Technology
Digital biosensing assays demonstrate remarkable advantages over conventional biosensing systems because of their ability to achieve single-molecule detection and absolute quantification. Unlike traditional low-abundance biomarking screening, digital-based biosensing systems reduce sample volumes significantly to the fL-nL level, which vastly reduces overall reagent consumption, improves reaction time and throughput, and enables high sensitivity and single target detection. This review presents the current technology for compartmentalizing reactions and their applications in detecting proteins and nucleic acids. We also analyze existing challenges and future opportunities associated with digital biosensing and research opportunities for developing integrated digital biosensing systems.
... Fluorescent elements to identify COVID-19 targeting the nanoparticles provides features such as large target surfaces, which contribute to the rapid identification of viral infections and play an important role in the COVID-19 detection system [76][77]
[78]
. Nanoparticles can influence target elements [79,80] and amplification or sequencing steps [81,82], giving a better control with the overall detection methodology. ...
Microfluidics-Based POCT for SARS-CoV-2 Diagnostics
<here is a image 3159e6d82212a68d-95f8079668e82cec> A S M Muhtasim Fuad Sohan
<here is a image 192c4d80f966269f-10c56ee37c1c794c> Binfeng Yin
<here is a image 93c6dbf71f19ac6b-52741784e122f7ff> Xiaodong Lin
<here is a image dceb160894d012b0-0c85b9b818d2cadf> Xinhua Wan
A microfluidic chip is a tiny reactor that can confine and flow a specific amount of fluid into channels of tens to thousands of microns as needed and can precisely control fluid flow, pressure, temperature, etc. Point-of-care testing (POCT) requires small equipment, has short testing cycles, and controls the process, allowing single or multiple laboratory facilities to simultaneously analyze biological samples and diagnose infectious diseases. In general, rapid detection and stage assessment of viral epidemics are essential to overcome pandemic situations and diagnose promptly. Therefore, combining microfluidic devices with POCT improves detection efficiency and convenience for viral disease SARS-CoV-2. At the same time, the POCT of microfluidic chips increases user accessibility, improves accuracy and sensitivity, shortens detection time, etc., which are beneficial in detecting SARS-CoV-2. This review shares recent advances in POCT-based testing for COVID-19 and how it is better suited to help diagnose in response to the ongoing pandemic.
... Chemiluminescence immunoassay (CLIA) is an analytical method that combines a chemiluminescence system with an immune reaction and has the advantages of high sensitivity, a wide linear range of detection, and no radioactive pollutants (Rongen et al., 1994;Pei et al., 2013) At present, CLIAs have been widely used in the fields of life science, clinical diagnosis, environmental monitoring, food safety and drug analysis (Li et al., 2017;Yang et al., 2021;Xu et al., 2020;Liu et al., 2020) In current CLIAs, 96-well plates or nitrocellulose membranes are extensively used as carriers to fix antibodies/antigens (Deng et al., 2018;Sun et al., 2020) However, their low specific surface area affects the efficiency of antigen-antibody recognition and reduces detection sensitivity. Magnetic beads (MBs), with the advantages of a large specific surface area, supermagnetism, and excellent biological compatibility, can function as reaction carriers and separation tools in the field of modern diagnostics Wang et al., 2019) At the same time, Immunoassays based on MBs are easy to manipulate by an external magnetic field, enabling automated detection, which not only reduces manual operation, such as adding sample, discarding liquid and washing but also improves detection throughput and consistency (Ben Ismail et al., 2018;
Lu et al., 2020)
Therefore, a MB-based CLIA has the advantages of high sensitivity, a straightforward nature, and automation in the detection of food poisoning. ...
An Automated and Highly Sensitive Chemiluminescence Immunoassay for Diagnosing Mushroom Poisoning
Jianyu Zhu
<here is a image 004523331859d2fc-5b3bcb08a7fc8de6> Leina Dou
Shibei Shao
<here is a image e40e787b6eddbc5b-7ec56eefaf4bf48a> Wenbo Yu
Mushrooms containing Amanita peptide toxins are the major cause of mushroom poisoning, and lead to approximately 90% of deaths. Phallotoxins are the fastest toxin causing poisoning among Amanita peptide toxins. Thus, it is imperative to construct a highly sensitive quantification method for the rapid diagnosis of mushroom poisoning. In this study, we established a highly sensitive and automated magnetic bead (MB)-based chemiluminescence immunoassay (CLIA) for the early, rapid diagnosis of mushroom poisoning. The limits of detection (LODs) for phallotoxins were 0.010 ng/ml in human serum and 0.009 ng/ml in human urine. Recoveries ranged from 81.6 to 95.6% with a coefficient of variation <12.9%. Analysis of Amanita phalloides samples by the automated MB-based CLIA was in accordance with that of HPLC-MS/MS. The advantages the MB-based CLIA, high sensitivity, repeatability, and stability, were due to the use of MBs as immune carriers, chemiluminescence as a detection signal, and an integrated device to automate the whole process. Therefore, the proposed automated MB-based CLIA is a promising option for the early and rapid clinical diagnosis of mushroom poisoning.
... In a microfluidic device, the color is produced in a reflecting path on a transparent substrate to improve signal-to-noise levels. Some complex microfluidic structures make use of 3D-printable transparent polymers such as polymethyl methacrylate (PMMA)
[69]
. The digital assay applies an electromagnetic field to manipulate and mix individual droplets on a superhydrophobic plate (reducing the risk of physical contamination). ...
A Cross-Disciplinary View of Testing and Bioinformatic Analysis of SARS-CoV-2 and Other Human Respiratory Viruses in Pandemic Settings
<here is a image d60c385fa3c90d0a-a448c9bf8ea8a81a> Md Arafat Hossain
<here is a image ae66768e67fab290-365fbf918dacce93> Barbara Patricia Brito
<here is a image 28d5ffbe95b591be-b5a25295f505fbcd> Lisa M Sedger
<here is a image 8723b0c2cd784605-d4fad37abd5c5e85> John Canning
The SARS-Coronavirus-2 (SARS-CoV-2) infectious disease, COVID-19, has spread rapidly, resulting in a global pandemic with significant mortality. The combination of early diagnosis via rapid screening, contact tracing, social distancing and quarantine has helped to control the pandemic. The absence of real time response and diagnosis is a crucial technology shortfall and is a key reason why current contact tracing methods are inadequate to control spread. In contrast, current information technology combined with a new generation of near-real time tests offers consumer-engaged smartphone-based “lab-in-a-phone” internet-of-things (IoT) connected devices that provide increased pandemic monitoring. This review brings together key aspects required to create an entire global diagnostic ecosystem. Cross-disciplinary understanding and integration of both mechanisms and technologies for effective detection, incidence mapping and disease containment in near real-time is summarized. Available measures to monitor and/or sterilize surfaces, next-generation laboratory and smartphone-based diagnostic approaches can be brought together and networked for instant global monitoring that informs Public Health policy. Cloud-based analysis enabling real-time mapping will enable future pandemic control, drive the suppression and elimination of disease spread, saving millions of lives globally. A new paradigm is introduced – scaled and multiple diagnostics for mapping and spreading of a pandemic rather than traditional accumulation of individual measurements. This can do away with the need for ultra-precise and ultra-accurate analysis by taking mass measurements that can relax tolerances and build resilience through networked analytics and informatics, the basis for novel swarm diagnostics. These include addressing ethical standards, local, national and international collaborative engagement, multidisciplinary and analytical measurements and standards, and data handling and storage protocols.
... Proposed ultraviolet colorimetric assay method-magnetic nanoenzyme linked immunosorbent assay (MagLISA). Here the [297]
[298]
[299][300][301][302][303] authors combined a silica shell with magnetic nanoparticles (MagNBs) and gold nanoparticles for influenza A virus (0.02 pg/ml) monitoring. The main concepts of the developed sensing platform for rapid and sensitive detection of influenza A virus are two different probes capable of specifically recognizing the target virus. ...
Advances and insights in the diagnosis of viral infections
<here is a image e7044bb7955bf02c-d9229ed464f39887> Julija Dronina
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Urte Bubniene
Arunas Ramanavicius
Viral infections are the most common among diseases that globally require around 60 percent of medical care. However, in the heat of the pandemic, there was a lack of medical equipment and inpatient facilities to provide all patients with viral infections. The detection of viral infections is possible in three general ways such as (i) direct virus detection, which is performed immediately 1–3 days after the infection, (ii) determination of antibodies against some virus proteins mainly observed during/after virus incubation period, (iii) detection of virus-induced disease when specific tissue changes in the organism. This review surveys some global pandemics from 1889 to 2020, virus types, which induced these pandemics, and symptoms of some viral diseases. Non-analytical methods such as radiology and microscopy also are overviewed. This review overlooks molecular analysis methods such as nucleic acid amplification, antibody-antigen complex determination, CRISPR-Cas system-based viral genome determination methods. Methods widely used in the certificated diagnostic laboratory for SARS-CoV-2, Influenza A, B, C, HIV, and other viruses during a viral pandemic are outlined. A comprehensive overview of molecular analytical methods has shown that the assay's sensitivity, accuracy, and suitability for virus detection depends on the choice of the number of regions in the viral open reading frame (ORF) genome sequence and the validity of the selected analytical method.
... In a microfluidic device, the color is produced in a reflecting path on a transparent substrate to improve signal-to-noise levels. Some complex microfluidic structures make use of 3D-printable transparent polymers such as polymethyl methacrylate (PMMA)
[61]
. The digital assay applies an electromagnetic field to manipulate and mix individual droplets on a superhydrophobic plate (reducing the risk of physical contamination). ...
Network Diagnostics for Rapid Testing, Mapping and Bioinformatics Analysis of SARS-CoV-2 and Other Human Respiratory Viruses in Pandemic Settings
Under review in IEEE J-BHI (first submitted on 02 December 2020)
... In a microfluidic device, the color is produced in a reflecting path on a transparent substrate to improve signal-to-noise levels. Some complex microfluidic structures make use of 3D-printable transparent polymers such as polymethyl methacrylate (PMMA)
[61]
. The digital assay applies an electromagnetic field to manipulate and mix individual droplets on a superhydrophobic plate (reducing the risk of physical contamination). ...
Network Diagnostics for Rapid Testing, Mapping and Bioinformatics Analysis of SARS-CoV-2 and Other Human Respiratory Viruses in Pandemic Settings
<here is a image b089f8ddd78d233a-0f82a6f2099f9b03> Md. Arafat Hossain
Under review in IEEE J-BHI (first submitted on 02 December 2020)
| https://www.researchgate.net/publication/338485720_A_structure-free_digital_microfluidic_platform_for_detection_of_influenza_A_virus_by_using_magnetic_beads_and_electromagnetic_forces |
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Judges 15:17
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When he had finished speaking, he threw the jawbone from his hand; and he named that place
Ramath-lehi.
Judges 15:18
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Then he became very thirsty, and he
called to the Lord and said, "You have given this great deliverance by the hand of Your servant, and now
shall I die of thirst
and fall into the hands of the uncircumcised?"
Judges 15:19
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But God split the hollow place that is in Lehi so that water came out of it. When he drank,
his
strength returned and he revived. Therefore he named it
En-hakkore, which is in Lehi to this day.
| https://www.studylight.org/study-desk.html?q1=jud+15%3A17-19&t1=eng_nas |
Ridings v. Ridings, 55 N.C. App. 630 (1982) | Caselaw Access Project
Full text of Ridings v. Ridings, 55 N.C. App. 630 (1982) from the Caselaw Access Project.
Ridings v. Ridings, 55 N.C. App. 630 (1982)
Feb. 2, 1982 · North Carolina Court of Appeals · No. 8121DC296
55 N.C. App. 630
Case outline
majority — morris, chief judge.
Ridings v. Ridings, 55 N.C. App. 630 (1982)
Feb. 2, 1982 · North Carolina Court of Appeals · No. 8121DC296
55 N.C. App. 630
MARVIN D. RIDINGS
v.
CORNELIA A. RIDINGS
MARVIN D. RIDINGS v. CORNELIA A. RIDINGS
No. 8121DC296
1. Rules of Civil Procedure § 56— unpleaded defenses raised by evidence — consideration on summary judgment motion
Unpleaded defenses, when raised by the evidence, should be considered in resolving a motion for summary judgment; however, it is the better practice to require a formal amendment to the pleadings.
2. Cancellation and Rescission of Instruments § 3; Husband and Wife § 12.1 — separation agreement — undue influence — ratification
Plaintiff ratified a separation agreement and was thus foreclosed from attempting to set it aside on the ground of undue influence where the undue influence allegedly occurred prior to the execution of the agreement and there was no evidence of undue influence after the date the agreement was signed; for some months after the agreement was signed, plaintiff accepted and retained benefits growing out of the agreement in that defendant made tax, mortgage and insurance premium payments on the dwelling owned by the parties as tenants in common, defendant contributed to its general maintenance, and defendant transferred to plaintiff certain property listed in the separation agreement, including title to a Cadillac automobile; and plaintiff made alimony payments for some months and conveyed to defendant the title to a Chevrolet automobile.
3. Cancellation and Rescission of Instruments § 3.1; Husband and Wife § 12.1 — separation agreement — mental incompetency — ratification
Even though plaintiff presented some evidence that he was incompetent at the time he signed a separation agreement, summary judgment was properly entered for defendant in plaintiffs action to set- aside the agreement where there was plenary evidence that plaintiff ratified the agreement and plaintiff offered no evidence that he continued to suffer from the alleged mental illness when his acts of ratification occurred.
Appeal by plaintiff from Alexander, Judge.Judgment entered 6 February 1981 Session of- FORSYTH County District Court. Heard in the Court of Appeals 21 October 1981.
Plaintiff sought to set aside a separation agreement entered into with defendant. Plaintiff’s complaint, filed 29 November 1978, alleged mental incompetency on his part, and undue influence at the time of execution of the agreement.
Plaintiff’s evidence showed that he had been under the care of several physicians, was depressed, and had been taking medications prior to the couple’s separation on 8 June 1978, the same*631day the agreement was signed. Plaintiff presented the affidavit of Dr. Thomas Cannon, in which Dr. Cannon expressed the opinion that plaintiff may have suffered from impaired judgment, affecting his ability intelligently to negotiate for the division of property at the time he signed the agreement.
Plaintiff also offered evidence that defendant exercised undue influence by asking him to leave home, by telling plaintiff, family and friends that he needed psychiatric help and that he was “crazy”, and by breaking his glasses.
The separation agreement was largely honored by both sides, the only breach thereof being plaintiffs nonpayment of alimony after October 1978.
Defendant filed a motion for summary judgment. The trial court found no issue of fact and granted defendant’s motion. Plaintiff appeals.
Pettyjohn and Molitoris, by Theodore M. Molitoris, for plaintiff appellant.
White and Crumpler, by Robert B. Womble, for defendant appellee.
MORRIS, Chief Judge.
Rule 56 does not require the movant to set forth the grounds upon which he bases a motion for summary judgment, Conover v. Newton,297 N.C. 506,256 S.E. 2d 216(1979), and, of course, the very nature of the motion obviates the necessity for findings of fact. We assume that the trial judge determined defendant’s evidence of ratification sufficient to meet her burden of persuasion on the affirmative defense, negating the existence of any genuine issue of material fact on the allegations of incompetency and undue influence. These grounds, which we find sufficient, are dispositive. Hence, we choose only to outline the basis of our determination that evidence of plaintiffs ratification of the separation agreement resulted in a lack of triable issue of fact.
[1]G.S. 1A-1, Rule 8(c) requires that “[i]n pleading to a preceding pleading, a party shall set forth affirmatively . . . any . . . matter constituting an avoidance or affirmative defense.” We note that defendants’ answer did not contain the defense of ratification. Rule 56, however, does not limit consideration of a motion for*632summary judgment to the pleadings. The court may consider depositions, answers to interrogatories, admissions on file and affidavits. Indeed,
[T]he nature of summary judgment procedure (G.S. 1A-1, Rule 56), coupled with our generally liberal rules relating to amendment of pleadings, require that unpleaded affirmative defenses be deemed part of the pleadings where such defenses are raised in a hearing on motion for summary judgment. Bank v. Gillespie, 291 N.C. 303 , 230 S.E. 2d 375 (1976). See also 6 Moore, Federal Practice (2d ed. 1976) § 58-736.
Cooke v. Cooke,34 N.C. App. 124, 125,237 S.E. 2d 323, 324, cert. denied,293 N.C. 740,241 S.E. 2d 513(1977). Thus, although it is better practice to require a formal amendment to the pleadings, unpleaded defenses, when raised by the evidence, should be considered in resolving a motion for summary judgment. Bank v. Gillespie,291 N.C. 303,230 S.E. 2d 375(1976).
[2]A transaction procured by undue influence may be ratified by the victim, foreclosing a subsequent suit to vitiate the contract. Link v. Link,278 N.C. 181,179 S.E. 2d 697(1971). The pleadings, answers to interrogatories and affidavits clearly show that plaintiff acceded to the separation agreement. Plaintiff maintains that the acts constituting defendant’s exercise of undue influence occurred prior to execution of the agreement, and he does not allege, nor does the record reveal, any undue influence after 8 June 1978, the date the agreement was signed. Plaintiff, between 8 June 1978 and the filing of his action on 29 November 1978, accepted and retained all benefit growing out of the agreement. Defendant made all the tax, mortgage, and insurance premium payments on the dwelling owned by defendant and plaintiff as tenants in common. She also contributed to its general maintenance. She transferred to plaintiff certain property listed in the separation agreement, including title to and possession of a 1974 Cadillac automobile. Plaintiff recognized the legitimacy of the agreement by continued performance thereunder after any purported duress had terminated. He made alimony payments from July until November of 1978. He further acknowledged the validity of the agreement by conveying full possession and title to the parties’ 1967 Chevrolet automobile. Plaintiff thus acquiesced for months in the separation agreement which he would now*633avoid. He has shown no ground for rescission based upon the exercise of undue influence.
[3]Plaintiff, in addition, was unable to show that he could support his position on incompetency by the offer of proof at trial. With regard to the standard of competency required validly to enter a contract,
[w]e have said . . . that ... a person has mental capacity sufficient to contract if he knows what he is about [Moffit v. Witherspoon, 32 N.C., 185 ; Paine v. Roberts, 82 N.C., 451 ], and that the measure of capacity is the ability to understand the nature of the act in which he is engaged and its scope and effect, or its nature and consequences, not that he should be able to act wisely or discreetly, nor to drive a good bargain, but that he should be in such possession of his faculties as to enable him to know at least what he is doing and to contract understandingly.
The party seeking to exercise the privilege of avoidance has the burden of proof on the question of whether he was mentally ill. Everyone is presumed to be sane until the contrary appears. 2 Stansbury’s N.C. Evidence § 238 (Brandis rev. 1973). Also, when the movant has satisfied his burden on a motion for summary judgment, the respondent may not simply rely on the allegations in the pleadings, but must reply by submitting contrary informa*634tion showing that a genuine issue of fact exists. Hotel Corp. v. Taylorand Fletcher v. Foremans, Inc.,301 N.C. 200,271 S.E. 2d 54(1980).
Though there is some evidence of incompetency at the time the agreement was signed, the record contains no information as to how long plaintiff continued to suffer the allegedly debilitating mental illness. Plaintiff could not have ratified the separation agreement as long as his condition remained unchanged. See Walker v. McLaurin,227 N.C. 53,40 S.E. 2d 455(1946). Yet there is plenary evidence of ratification. We deem it incumbent upon plaintiff, in the face of the presumption of competence, the evidence of ratification, and defendant’s motion for summary judgment, to offer evidence of his continued incapacity which would counter defendant’s affirmative defense. This, plaintiff failed to do.
The court awarded summary judgment in favor of the party with the burden of proof. Such grant is appropriate if the movant’s evidence is not self-contradictory and there is no question of witness credibility, as here. The evidence in this case is also direct, without gaps, and does not require application of any legal principle upon which reasonable minds could differ. See generally Kidd v. Early,289 N.C. 343,222 S.E. 2d 392(1976). We thus find that defendant met the burden of persuasion on the affirmative defense of ratification by the strength of her own evidence, even though her affidavits and supporting material were not challenged.
The order of summary judgment for defendant was appropriately entered. The court’s judgment is, therefore,
Affirmed.
Judges Arnold and Becton concur.
| https://cite.case.law/nc-app/55/630/ |
Upper Tribunal (Immigration and asylum chamber), 2011-11-25, [2011] UKUT 445 (IAC) (AMM and others (conflict; humanitarian crisis; returnees; FGM)) - Case Law - VLEX 787383785
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Case Law
Upper Tribunal (Immigration and asylum chamber), 2011-11-25, [2011] UKUT 445 (IAC) (AMM and others (conflict; humanitarian crisis; returnees; FGM))
Jurisdiction UK Non-devolved Court Upper Tribunal (Immigration and Asylum Chamber) Judge Mr H J E Latter, Mr P R Lane, Dr R Kekic Status Reported Date 25 November 2011 Published date 28 November 2011 Hearing Date 15 July 2011 Subject Matter conflict; humanitarian crisis; returnees; FGM Appeal Number [2011] UKUT 445 (IAC)
Upper Tribunal
(Immigration and Asylum Chamber)
AMM and others (conflict; humanitarian crisis; returnees; FGM) Somalia CG [2011] UKUT 00445 (IAC)
THE IMMIGRATION ACTS
Heard at Field House Determination Promulgated On 13 to 21 June and 15 July 2011 …………………………………
Before
UPPER TRIBUNAL JUDGE LATTER
UPPER TRIBUNAL JUDGE P R LANE
UPPER TRIBUNAL JUDGE KEKIĆ
Between
AMM
MW
ZF
FM
AF
Appellants
and
THE SECRETARY OF STATE FOR THE HOME DEPARTMENT
Respondent
THE UNITED NATIONS HIGH COMMISSIONER FOR REFUGEES
Intervening
Representation
:
For Appellants AMM: Ronan Toal, instructed by South Manchester Law Centre
For Appellant MW: Harriet Short, instructed by Avon & Bristol Community Law Centre
For Appellant ZF: Mark Schwenk, instructed by Parker Rhodes Hickmotts, Solicitors
For Appellant FM: Mark Symes, instructed by Wilson Solicitors LLP
For Appellant AF: Ronan Toal, instructed by Wilson Solicitors LLP
For the Respondent: Tim Eicke QC and Christopher Staker, instructed by the Treasury Solicitor
For the UNHCR: Tom Hickman, instructed by Baker & McKenzie LLP
Law
1) Whilst section 2 of the Human Rights Act 1998 and its associated case law requires United Kingdom tribunals in general to give effect to the jurisprudence of the European Court of Human Rights, including that Court’s guidance on how to approach evidence in international protection cases, the weighing of evidence and the drawing of conclusions as to the relative weight to be placed on items of evidence adduced before a United Kingdom tribunal are ultimately matters for that tribunal. Whilst the factual finding the Strasbourg Court has made as a result of applying its own guidance is something to which the domestic tribunal must have regard, pursuant to section 2 , it is not bound to reach the same finding.
2) There is nothing jurisprudentially problematic with the Strasbourg Court’s judgment in Sufi & Elmi v the United Kingdom [2011] ECHR 1045, as regards Article 3 of the ECHR . The Court’s finding, that the predominant cause of the humanitarian crisis in southern and central Somalia was due to the current warring parties, meant that the high threshold (identified, inter alia, in N v United Kingdom [2008] ECHR 453) for finding an Article 3 violation in the case of naturally occurring phenomena did not need to be met.
3) That high threshold is, however, still capable of being crossed in cases of sufficient exceptionality. In deciding what constitutes an exceptional case, regard must be had to all the factors, including the actions of the parties to a conflict, albeit that those actions are not the predominant cause of the humanitarian crisis.
4) Despite the suggestion in the judgment in Sufi & Elmi that there is no difference in the scope of, on the one hand, Article 3 of the ECHR (and, thus, Article 15(b) of the Qualification Directive) and, on the other, Article 15(c) of the Directive, the binding Luxembourg case law of Elgafaji [2009] EUECJ C-465/07 (as well as the binding domestic authority of QD (Iraq) [2009] EWCA Civ 620 ) makes it plain that Article 15(c) can be satisfied without there being such a level of risk as is required for Article 3 in cases of generalised violence (having regard to the high threshold identified in NA v United Kingdom [2008] ECHR 616 ) . The difference appears to involve the fact that, as the CJEU found at [33] of Elgafaji , Article 15(c) covers a “more general risk of harm” than does Article 3 of the ECHR ; that Article 15(c) includes types of harm that are less severe than those encompassed by Article 3 ; and that the language indicating a requirement of exceptionality is invoked for different purposes in NA v United Kingdom and Elgafaji respectively.
5) Article 10 of the Qualification Directive requires the holding of some sort of belief, comprising a coherent and genuinely held system of values, whether these be theistic, non-theistic or atheistic, and is not satisfied in the case of a person who holds no such belief. Social restrictions, such as bans on watching football or television, do not comprise an interference with the right to religion, in the case of a person whose religious etc beliefs do not require him or her to participate in those activities. It is immaterial that a person may be permitted, according to those beliefs, to participate in the activities concerned.
6) Even where the motivation for a law is religious, the religious aspect will not, without more, lay the basis of a claim to international protection in relation to anyone who might fall foul of that law. However, the more such religiously motivated laws interfere with someone’s ability to hold and practise their religious or other beliefs, the more intense will be the scrutiny.
7) The necessary religious element to satisfy Article 1(A) of the Refugee Convention is not satisfied solely by reference to the persecutor; but that element can be satisfied if the persecutor ascribes to the victim a perceived religious opinion.
8) There is no general legal principle that, in determining a person’s entitlement to international protection, the Tribunal must leave out of account any possibility of that person’s carrying out an act in the country of proposed return, which – if carried out in the United Kingdom – would constitute a criminal offence. A genuine conscientious objection to complying with unjust laws or demands may, however, provide an entitlement to such protection.
9) On the assumption that Al-Shabab’s likely behaviour towards those who transgress its rules is as found in this determination, the position is as “extreme” as the factual basis in RT (Zimbabwe) [2010] EWCA Civ 1285 . In the light of RT, a person from an Al-Shabab area who can show they do not genuinely adhere to Al-Shabab’s ethos will have a good claim to Refugee Convention protection, once outside Somalia (subject to internal relocation and exclusion clause issues), regardless of whether the person could and would “play the game”, by adhering to Al-Shabab’s rules. As can be seen from a comparison with Sufi & Elmi , the effect of RT is, accordingly, to take the Refugee Convention beyond the comparable ambit of Article 3 ECHR protection.
10) There is no legal burden on the Secretary of State to prove that there is a part of the country of nationality etc of an appellant, who has established a well-founded fear in their home area, to which the appellant could reasonably be expected to go and live. The appellant bears the legal burden of proving entitlement to international protection; but what that entails will very much depend upon the circumstances of the particular case. In practice, the issue of internal relocation needs to be raised by the Secretary of State in the letter of refusal or (subject to procedural fairness) during the appellate proceedings.
11) It will then be for the appellant to make good an assertion that, notwithstanding the general conditions in the proposed place of relocation, it would not be reasonable to relocate there. In an Article 3 claim, a similar position pertains, in that, although the test of reasonableness/undue harshness does not formally apply, unduly harsh living conditions etc – albeit not themselves amounting to a breach of Article 3 – may nevertheless be reasonably likely to lead to a person returning to their home area, where such a breach is reasonably likely.
12) An appellant who pursues their appeal on asylum and humanitarian protection grounds, following a grant of leave, is entitled to have their appeal decided on the hypothetical basis (if the facts so demonstrate) that family members would be reasonably likely to return with the appellant and that potential harm to those family members would cause the appellant to suffer persecution or Article 15(b) harm.
13) A person is not entitled to protection under the Refugee Convention, the Qualification Directive or Article 3 of the ECHR , on the basis of a risk of harm to another person, if that harm would be willingly inflicted by the person seeking such protection.
14) Article 8(1) of the Qualification Directive provides that Member States may determine that a person is not in need of international protection “if in a part of the country of origin there is no well-founded fear of being persecuted or no real risk of suffering serious harm and the applicant can reasonably be expected to stay in that part of the country. Article 8(3) states that Article 8(1) applies “notwithstanding technical obstacles to return to the country of origin”. Although the Court of Appeal in HH & Others [2010] EWCA Civ 426 found that Article 8 was “to do principally with internal relocation”, there is nothing in that judgment or in the Qualification Directive that demonstrates the Article is so confined, and it would be illogical for it to be so. Accordingly, difficulties in securing documentation to effect a return to a person’s home area may not entitle that person to international protection, whether or not there are real risks to that person in some other area of the country concerned.
15) In assessing the effect of an appellant’s lies (whether to the Secretary of State or a judicial fact-finder), it is unnecessary to construct a prescribed set of steps from the...
| https://vlex.co.uk/vid/upper-tribunal-immigration-and-787383785 |
Akoustis Signs Definitive Agreement to Acquire 120,000 Sq. Ft. Wafer Manufacturing Facility in Canandaigua, NY - New York Photonics
Akoustis Technologies, Inc. (NASDAQ:AKTS), a manufacturer of patented single-crystal BulkONE® bulk acoustic wave (BAW) high-band RF filters for mobile and other…
Akoustis Signs Definitive Agreement to Acquire 120,000 Sq. Ft. Wafer Manufacturing Facility in Canandaigua, NY
In Acquisitions , National Photonics Initiative , New York Photonics , Photonics , STC MEMS
Tag NYPhotonics , STCMEMS , SUNY Polytechnic Institute
STC MEMS, former Infotonics Center, most recently a division of SUNY POLY
Akoustis Technologies, Inc.(NASDAQ:AKTS), a manufacturer of patented single-crystal BulkONE® bulk acoustic wave (BAW) high-band RF filters for mobile and other wireless applications, announced today it has entered into binding, definitive agreements to acquire assets from theResearch Foundation for the State University of New York(RF-SUNY) and Fuller Road Management Corporation (FRMC), an affiliate of RF-SUNY. The assets being acquired include STC-MEMS, a semiconductor wafer manufacturing operation andmicroelectromechanical systems(MEMS) business with associated wafer production tools, as well asreal estate associated with the facility located in Canandaigua, New York, near Rochester.
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Under the terms of the agreements, Akoustis will pay $2.75 million in cash at closing to RF-SUNY and FRMC, subject to certain adjustments and customary closing conditions. The transaction is expected to be completed in the second quarter of calendar year 2017. As part of the signed definitive agreements, Akoustis plans to acquire all of the following:
120,000 sq. ft. commercial wafer manufacturing facility located in Canandaigua, NY, which includes Class 100/Class 1000 cleanroom space (“NY Facility”).
57-acres of real property associated with the NY Facility.
150-mm silicon MEMS wafer fab operations, including all semiconductor manufacturing tools.
Existing silicon-based MEMS business with annual revenues of approximately $3M from multiple customers, including a tier-1 mobile wireless solutions OEM.
Trusted Foundry accreditation for MEMS processing, packaging and assembly.
Two existing tenants with multi-year leases.
Dr. Art Geiss, Co-Chairman of Akoustis, said, “Akoustis will merge its patented BulkOne® BAW RF filter process into the STC-MEMS foundry, an operating silicon-wafer-based MEMs manufacturer. Since there is significant overlap between the tools and processes used to produce our BAW devices and silicon-based MEMS, transferring our process into the STC-MEMS foundry will accelerate the technology into production. In addition, we believe that some of the foundry processes used in silicon-based MEMS manufacturing may be utilized in new ways to make further performance improvements in Akoustis’ single-crystal BAW RF filters.”
<here is a image 395bba77d788b04b-88802ba8b9370996>
Jerry Neal, Co-Chairman of Akoustis, added, “This acquisition is an enormous win for Akoustis and is consistent with our capital-efficient business model. A comparable manufacturing facility to build and qualify for production would take up to 2-years and cost well over $50 million, not to mention the challenges of recruiting and training qualified personnel.”
<here is a image 6e066a30353d5fd7-902b4c100c38467d>
The transaction allows Akoustis to internalize manufacturing providing substantial capacity and control of its wafer supply chain for single crystal BAW RF filters. Akoustis plans to utilize the NY Facility to consolidate all aspects of wafer manufacturing for its disruptive and patented high-band RF filters targeting the multi-billion mobile and other wireless markets. This planned consolidation of the Company’s supply chain into the NY Facility is expected to shorten time-to-market for its RF products, greatly enhancing the Company’s ability to service customers. Shorter time-to-market cycles provide the Company the opportunity to increase the number of customer engagements.
Empire State Development President, CEO & Commissioner Howard Zemsky said, “When combined with its skilled workforce, the Finger Lakes region’s burgeoning R&D and advanced manufacturing industry cluster create the perfect environment for innovative companies like Akoustis to grow and thrive. The addition of new research and manufacturing jobs in Canandaigua will diversify and strengthen the local economy and help to ensure the region continues moving in the right direction.”
Jeff Shealy, CEO of Akoustis, commented, “We look forward to welcoming the dedicated professionals at STC-MEMS into the Akoustis family, and thank Governor Cuomo and his entire organization for their tireless efforts attracting Akoustis to New York State.”
Akoustis plans to maintain the existing customer engagements which are transferred as part of the transaction. The Company plans to maintain the existing Trusted Foundry accreditation for MEMS processing, packaging and module assembly and will seek to expand the accreditation for the NY facility to include BAW RF filters and sensors.
Concern regarding the Department of Defense Trusted Foundry in Canandaigua ran high in Rochester’s Optics, Photonics and Imaging Community since last year’s indictment of SUNY POLY, New York State, and construction officials by U.S. Attorney Preet Bharara for bid-rigging. This is a very welcome announcement.
<here is a image 51164cd4df7a7487-3ec4adf305ac408c>
Left to right: Dr. Jerry D. Neal, co-chairman, Akoustis; Mary Winters, Director of Business Development, STC MEMS; Jeff Shealy, CEO and Founder, Akoustis; Paul Tolley, VP for Disruptive Technologies, STC MEMS; Art Geiss, co-chairman, Akoustis
| https://newyorkphotonics.org/2017/03/24/akoustis-signs-definitive-agreement-to-acquire-120000-sq-ft-wafer-manufacturing-facility-in-canandaigua-ny/?ajaxCalendar=1&id=1335845977&yr=2023 |
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1962-03-13_001 | TriCollege Libraries Digital Collections
1962-03-13_001
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Swarthmore Phoenix, 1962-03-13
Description
An archive of the Phoenix student newspaper from Swarthmore College in Pennsylvania
Place Published
Swarthmore (Pa.)
Physical Form
Text
Genre
newspapers
Date Created
1962-03-13
Subject (Topic)
Student newspapers and periodicals
Subjects (name)
Swarthmore College
Language
English
Extent
1 item
Resource Type
Text
Digital Origin
digitized microfilm
Institution
Swarthmore College
Library
pschi
Department
Swarthmore College Archives
Bibliographic Record
Phoenix (Swarthmore, Pa.)
Local Identifier
19620313_001
PID
sc:234655
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psc
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IN COPYRIGHT - EDUCATIONAL USE PERMITTED
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Publisher: Swarthmore College undergraduate staff.
Action: Image was scanned by Backstage Library Works in Bethlehem, PA. Archival Image is an 8-bit greyscale tiff that was scanned from microfilm at 400 dpi. The original file size was 3567.46 KB.
Transcription
The Phoenix Volume 82 Number 36 SWARTHMORE COLLESE, SWARTHMORE, PA. Tuesday. March 13, 1962 Brzezinski Discusses Interplay Of Communism, New Nations by David V. Edwards THE POSSIBILITY that the lessons which developing nations learn from Communist societies may eventually cause the Soviets to realize the inadequacy and irrelevance of Marxist ideology in today's world was suggested by Zbigniew Brzezinski in Sunday's Cooper lecture on "Communism and the Developing Societies " Professor Bzezinski, Director of the Research Institute on Communist Affairs at Columbia, delivered the fourth lecture in this year's Cooper Foundation series on self-government in developing nations. Brzezinski contended that the need for social engineering in the developing nations makes certain features of Communist society especially relevant. These include political centralization, the predominance of a revolutionary elite, access to and mobilization of the masses, the use of violence and coercion to socialize and eventually politicize the masses, rapid socioeconomic development, and the use of collectivism in social organization and social behavior. a concept of "national democracy" which will incorporate any movements seeking independence, economic development, domestic "popular democracy." and relations with the Communist nations. The Chinese Communists, doctrinal heirs of Stalin in this as in other contemporary controversies, have vigorously opposed large programs of economic aid to young nations on the grounds that they simply dilute revolutionary fervor—grounds which Professor Brzezinski accepted. The Chinese argue that their own revolution, more recent than the Bolshevik upheaval, and grounded in the peasantry rather than in urban work- The obvious movement of developing societies in the direction of these Communist characteristics has produced an optimism among Communist leaders. But because it has been Russian experience rather than Communist ideology that has been found relevant, the Communist approach has had a marked political bias and ideology has been de-emphasized. But Communist circles rave" been far from unanimous in their choice of approaches to these nations. For 60 jears battle has raged between those Leninists and now Khrushchevists who support any anti-imperialistic mew government, and the Stalinists who advocate supporting only the truly revolutionary governments which are free of bourgeois exploitation. In the face of this disagreement, the Khrushchev forces have developed OCACCondemns McCarren Act by Steve Savran SUNDAY MORNING OCAC met for more than three action-filled hours, during which the resolution on the McCarren Act which will be presented to the student body very soon was re-drafted. OCAC's objections to the act as it stands are as manifold as the various political beliefs of the members of the committee. It states, very briefly, that all members of any group judged as wishing to overthrow the government of the United States must register themselves with the Attorney General and are subject to the following measures if they do so: They will We no permission to travel in foreign lands (no passports), no social security benefits, no freedom of speech, they must state the name of the party they represent before making any speeches, and they must label all their mail and state that they are compelled under the Act to do so. If they do not register, and are later learned to be members of such a party they are liable to fines of $lO,OOO and five years in jail PER DAY of not registering. This seems like a gross infringement on the rights of students to learn both sides of any issue as well as being a violation of the First and Fifth amendments of the Constitution. Last fall, the City of New York ordered that no Communists could speak before the City Colleges. Although the order was shortly repealed, it showed just what such a law could do to academic freedom. After the members of OCAC were fully awake and the issue was hashed Christian Addresses Philosophy Club by Steve Livernash THE PHILOSOPHY Club heard Prof. William Christian this Sunday afternoon on "Basic Religious Propositions." Mr. Christian is an Associate Professor at Yale, and has taught briefly at Swarthmore. His interest was in classifying the types of propositional statements made in religion. That is, what classes of assertions are made in religion. Mr. Christian distinguished four classes: 1. Basic Suggestions, which are concrete propositions ("The walls fell down") which suggest or lend support to religious beliefs. 2. Basic Suppositions, which name the entity which the basic suggestions imply. ("Something exists which made the walls fall down.") 3. Basic Proposals, which are fundamental propositions about the nature of the Supreme Being, principle, or intelligence. ("God is an omnipotent, beneficent being.") Student Administration tension Brought to Council's Attention STUDENT COUNCIL took little action last Sunday night, but there was much recurrent discussion of tension which seems to have arisen recently between the Administration and the students. SC President Cratsley expressed to SC the feeling of the Administration that the Student Body and Student Council had been unfair and in certain areas incorrect, in their .views on Administrative action related to Expansion and the Folk Festival. He further reported that it was felt that Council in both its discussion and its action on certain issues had emphasized a Student Body-Administration split which was detrimental to the efforts of both groups to solve some of our problems. More specifically it was felt that SC, in its statement of last week on expansion, had overlooked repeated Administrative offers for student opinion and thus was misinterpreting their desire for student participation in discussion of the Expansion question. With this in' mind, Council, after long and-disorderly debate, passed a Statement apologizing for the tone and the errors of their last week's statement and accepted the invitation of President Smith to meet with him for discussion of this and other questions. SC also re-discussed their position of last week on the codification of dress rules, but decided to postpone action on the matter until the Social Rules Committee had presented their report, which is now in preparation, and which includes consideration of the issue. A number of reports were presented to SC concerning the recent conferences and exchanges. Jim Storozuk spoke on FICDAC, Sue Ehrlich and Omogi Calleb for the NSA region, al conference. Several exchangees returning from Bryn Mawr, Howard, Sarah Lawrence and Haverford also presented their impressions. Moving on to other matters, SC heard and approved the statement of purpose of the Swarthmore Minority Opinion Club (SMOC), dedicated to the presentation of "the other point of view" in this case the conservative one. Bob Kapp and Sandy Woodward then reported on some of their own efforts toward discussion of Social Rules. A series of forums and informal discussions has been planned, to take place after Spring Recess. Faculty, students, and Administration will all participate in the study of the "philosophy" of rules in the college and Swarthmore's particular problems.President Cratsley then turned to the budget of the 3-College Dance. But the work sheet as it was drawn up was so ambiguous that the meeting was finally disbanded (rather than adjourned) to permit discussion of it in privacy. Sigma Xi Scientific Society Symposium on Crystals Luminescence of Crystals DR. FRED Williams, Chairman of the Physics Department at the University of Delaware, discussed "Luminescence of Crystals" giving both a general picture of the phenomenon and some of the theoretical treatment of the subject. Photoluminescence can be likened to a spectroscopy of the solid state. When a dielectric material is treated, or doped, with trace amounts of an impurity (e.g. zinc sulfide treated with copper) and then exposed to a source of high energy excitation such as ultraviolet light, an electron beam, or an applied electric field, the material emits a glowing light, the color of which is characteristic only of the starting material. All parts of the spectrum can be covered by picking a suitable dielectric. The phenomenon exhibits some interesting characterstics. Emission is independent of the temperature, although at high temperatures the intensity may suddenly drop out entirely. The decay of residual emission after cessation of excitation is, however, temperature dependent. The trace impurities present in the system are absolutely essential for emission to take place but have no effect on the wavelength of the emission. Dr. Williams made reference to the Diffusion in Crystals C. E. BIRCHENALL, Professor of Chemical Engineering at the University of Delaware, outlined the study- of diffusion in crystals. Diffusion in solids is caused by impurities in the crystalline structure of the solid. There are several kinds of imperfections but only one of these can provide a practical mechanism for diffusion. This is the vacancy mechanism. An imperfection produced by removing an atom from the crystal lattice is called a vacancy. A hole thus exists in the lattice and an atom can "jump" into this vacancy and thereby move the vacancy to a new position in the lattice. This process can repeat itself and vacancy diffusion is the result. The self-diffusion of a metal can be studied by fusing a sample of the metal to a sample of the radioactive metal. After the system has been maintained at a constant temperature for a definite time, slices are cut off and the radioactivity of each layer is measured with a Geiger counter. The self-diffusion constant of the metal in the metal can readily be calculated from the observed distribution of activity. Another example of diffusion is the growth of "necks" between materials. Bozell Urges Forceful Spread of West's Ideals ACTIVE SPREADING of Western Christian ideals, by force if necessary, to combat Communism was urged Friday night by L. Brent Bozell, Washington Editor of the conservative National Review, in a lecture at the duPont ledture hall. Bozell addressed some 200 students and visitors in a lecture sponsored by the Swarthmore Minority Opinion Club. He was accompanied by fellow To our chief of mission in the Congo: "Change sides." * * To the chief of the C.1.A.: "Encourage liberation movements in every nation of the world under Communist domination." In calling for these measures, Bozell pointed out that Western civilization has its basis in the Christian religion and traditions. This civilization, he said, is threatened by an enemy who believes in the subjugation of man's soul to the state. For the West to be saved, he stressed that it must believe in its ideals and traditions enough to be willing to make it possible, using force if necessary, for other nations to learn of them. Bozell said that: "There is goood aggression and bad aggression.*' A nuclear war, he feels, is morally justified if it will help achieve the goal of spreading Western Christian ideals. Bozell conceded that an invasion of Cuba might touch off riots or even leftist revolutions in South America. However, he felt that we must take this chance, rather than stand by and editor Frank S. Meyer, because, he explained, "We of the National Review always travel in pairs, especially when we are going to a place like Swarthmore." He proceeded to state that conservatism is the wave of the future and pointed out that it is now spreading from campus to campus. With regard to the active spreading of Western ideals, Bozell called for new orders in American foreign policy. These included: To the Joint Chiefs of Staff: "Prepare for an immediate landing in Havana." To the commander in Berlin: "Tear down the wall." —Photo by Bob Tinker Brent Bozell, a Washington editor of the National Review, speaking in duPont on Friday. Gordon Speaks On Economic Policy ON SUNDAY, Dr. Kermit Gordon of the President's Council on Economic Advisers, spoke to the Economics Club, concerning himself mainly with the function of the Council and the present issues of economic policy. The Council, established under the Employment Act of 1946, has the duty of making recommendations aimed at establishing full employment and maintaining full purchasing power. The central concerns of the Council are the use of monetary and fiscal policy to achieve these goals. In addition to the problem of unemployment, the Council has become concerned with three other major areas of economic policy: increasing the rate of growth, maintaining equilibrium in the balance of payments, and maintaining a stable price level. One of the greatest difficulties facing the economic decision makers is the conflict of policy measures in these four main areas. Wilson Fellowships SIXTEEN SWARTHMORE students have won Woodrow Wilson fellowships, the largest number from Swarthmore ever to win this coveted grant. The winners and the fields in which they won their fellowships are: 1. Peter E. Biskind (English) 2. David Edwards (Int'l Rel.) 3. John H. Hand (Economics) 4. James A. Henretta (History) 5. Nancy R. Kramer (English) 6. Robert Kramer (History) 7. Lloyd B. Kreuzer (Physics) 8. David K. Lewis (Philosophy) 9. Stephen W. Mark (English) 10. Judith B. Markham (History) 11. Nicholas Passell (Mathematics) 12. Robert A. Rescorla (Psychology) 13. Jane Shelby (Philosophy) 14. Noel F. Snyder (Biology) 15. Walter F. Taylor (Mathematics) 16 John B. Thompson (Int'l Rel.) Swarthmore's total of 16 was the second highest in the region in which it competed (Region 4 including all colleges and universities in New Jer- (Continued on Page 4) (Continued on Page 4) (Continued on Page 2) (Continued on Page 8) (Continued on Page 4) (Continued on Page 8) (Continued on Page 3) (Continued on Pa*« 4) Collection Kenneth S. Rawson will apeak on Collection this Thursday. His topic is: "Camels of the Red Centre." The address will be a report of his trip to Australia and the research work done there. This talk will be illustrated by color slides.
| https://digitalcollections.tricolib.brynmawr.edu/object/sc234655 |
Mathematics | Free Full-Text | Analysis of the In-Host Dynamics of Tuberculosis and SARS-CoV-2 Coinfection
The coronavirus disease 2019 (COVID-19) is a respiratory disease that appeared in 2019 caused by a virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is still spreading and causing deaths around the world. There is a real concern of SARS-CoV-2 coinfection with other infectious diseases. Tuberculosis (TB) is a bacterial disease caused by Mycobacterium tuberculosis (Mtb). SARS-CoV-2 coinfection with TB has been recorded in many countries. It has been suggested that the coinfection is associated with severe disease and death. Mathematical modeling is an effective tool that can help understand the dynamics of coinfection between new diseases and well-known diseases. In this paper, we develop an in-host TB and SARS-CoV-2 coinfection model with cytotoxic T lymphocytes (CTLs). The model investigates the interactions between healthy epithelial cells (ECs), latent Mtb-infected ECs, active Mtb-infected ECs, SARS-CoV-2-infected ECs, free Mtb, free SARS-CoV-2, and CTLs. The model& rsquo;s solutions are proved to be nonnegative and bounded. All equilibria with their existence conditions are calculated. Proper Lyapunov functions are selected to examine the global stability of equilibria. Numerical simulations are implemented to verify the theoretical results. It is found that the model has six equilibrium points. These points reflect two states: the mono-infection state where SARS-CoV-2 or TB occurs as a single infection, and the coinfection state where the two infections occur simultaneously. The parameters that control the movement between these states should be tested in order to develop better treatments for TB and COVID-19 coinfected patients. Lymphopenia increases the concentration of SARS-CoV-2 particles and thus can worsen the health status of the coinfected patient.
Analysis of the In-Host Dynamics of Tuberculosis and SARS-CoV-2 Coinfection
by Ahmed M. Elaiw 1,* and Afnan D. Al Agha 2
1
Department of Mathematics, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
2
Department of Mathematical Science, College of Engineering, University of Business and Technology, Jeddah 21361, Saudi Arabia
*
Author to whom correspondence should be addressed.
Mathematics 2023 , 11 (5), 1104; https://doi.org/10.3390/math11051104
Received: 13 January 2023 / Revised: 18 February 2023 / Accepted: 20 February 2023 / Published: 22 February 2023
Abstract
:
The coronavirus disease 2019 (COVID-19) is a respiratory disease that appeared in 2019 caused by a virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is still spreading and causing deaths around the world. There is a real concern of SARS-CoV-2 coinfection with other infectious diseases. Tuberculosis (TB) is a bacterial disease caused by Mycobacterium tuberculosis (Mtb). SARS-CoV-2 coinfection with TB has been recorded in many countries. It has been suggested that the coinfection is associated with severe disease and death. Mathematical modeling is an effective tool that can help understand the dynamics of coinfection between new diseases and well-known diseases. In this paper, we develop an in-host TB and SARS-CoV-2 coinfection model with cytotoxic T lymphocytes (CTLs). The model investigates the interactions between healthy epithelial cells (ECs), latent Mtb-infected ECs, active Mtb-infected ECs, SARS-CoV-2-infected ECs, free Mtb, free SARS-CoV-2, and CTLs. The model’s solutions are proved to be nonnegative and bounded. All equilibria with their existence conditions are calculated. Proper Lyapunov functions are selected to examine the global stability of equilibria. Numerical simulations are implemented to verify the theoretical results. It is found that the model has six equilibrium points. These points reflect two states: the mono-infection state where SARS-CoV-2 or TB occurs as a single infection, and the coinfection state where the two infections occur simultaneously. The parameters that control the movement between these states should be tested in order to develop better treatments for TB and COVID-19 coinfected patients. Lymphopenia increases the concentration of SARS-CoV-2 particles and thus can worsen the health status of the coinfected patient.
Keywords:
tuberculosis
;
COVID-19
;
coinfection
;
immune response
;
global stability
;
healthcare
MSC:
34D20; 34D23; 37N25; 92B05
1. Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 and caused the viral disease coronavirus disease 2019 (COVID-19). Based on the World Health Organization (WHO) report published on 8 January 2023, over 659 million confirmed cases and over 6.6 million deaths have been registered globally [
1
2
]. Tuberculosis is a bacterial disease caused by Mycobacterium tuberculosis (Mtb). According to the WHO, 1.6 million people died from TB in 2021, which makes TB the second leading infectious killer after COVID-19 [
3
]. Indeed, SARS-CoV-2 coinfection with TB has been found in many countries, including Belgium, Spain, Brazil, Singapore, Italy, Switzerland, India, China, and Russia [
4
]. As both diseases are greatly infectious, understanding the dynamics of TB and SARS-CoV-2 coinfection is critical for developing better treatments for coinfected patients.
SARS-CoV-2 is an RNA virus that belongs to the Betacoronavirus genus [
5
]. It utilizes the angiotensin-converting enzyme 2 (ACE2) receptor to get into the host cell [
6
]. SARS-CoV-2 primarily invades the alveolar epithelial type-II cells in the lungs [
7
]. Similarly, Mtb targets the same type of cells through mannose receptors, CD14 receptors, toll-like receptors, and complement receptors [
8
]. SARS-CoV-2 and Mtb can invade cells of different organs [
7
]. However, the lung is the prime site of infection for both pathogens [
9
]. As SARS-CoV-2 and Mtb share the same host, this can increase the severity of illness in coinfected patients [
5
]. Both diseases are transmitted via respiratory droplets [
2
]. The most common symptoms of TB and SARS-CoV-2 coinfection are fever, cough, fatigue, weight loss, and dyspenea [
2
]. Several risk factors of TB and SARS-CoV-2 coinfection have been recognized, such as age, as well as comorbidities such as HIV infection, diabetes, cancer, and hypertension [
2
,
4
]. The immune response in the coinfection encompasses T cells [
9
]. In particular, cytotoxic T lymphocytes (CTLs) kill Mtb- and SARS-CoV-2-infected epithelial cells (ECs). In the moderate cases, the immune response can eliminate Mtb and SARS-CoV-2 infections from the body [
4
]. It has been proposed that SARS-CoV-2 patients with Mtb are more likely to die or develop severe illness and worse outcomes than patients with only SARS-CoV-2 infection [
2
,
4
,
9
]. In addition, it has been suggested that SARS-CoV-2 infection can activate latent Mtb infection in coinfected patients [
4
,
5
]. Furthermore, it has been reported that coinfected patients have a reduction in lymphocyte count to less than
1.5
9
per liter [
2
,
9
]. Therefore, understanding TB and SARS-CoV-2 coinfection dynamics is crucial to choosing better ways to treat coinfected patients.
Mathematical modeling has been rated as a robust tool that supports medical studies and accelerates developing treatments for new infections. Mathematical models in the biological field are mainly divided into epidemiological (between-hosts) models and in-host models. Epidemiological models are devoted to address the transmission of a disease between individuals in a population. Further, in-host models describe the interactions between pathogens and different cells inside the human body. TB models have been extensively studied in the literature. These models come in the form of epidemiological models (for example, [ 10 , 11 , 12 , 13 ]) and in-host models (for example, [ 14 , 15 , 16 , 17 , 18 ]). SARS-CoV-2 models have also been developed as epidemiological models (for example, [ 19 , 20 , 21 , 22 , 23 , 24 , 25 ]) and in-host models (for example, [ 26 , 27 , 28 ]). A variety of models for SARS-CoV-2 coinfection with other diseases have been developed and analyzed. For example, an in-host SARS-CoV-2 and malaria coinfection model with antibody immunity, was studied in [ 29 ]. It was found that the shared immune response can reduce the severity of SARS-CoV-2 infection in SARS-CoV-2/malaria coinfected patients. In [ 30 ], a SARS-CoV-2 coinfection model was explored. This model exhibits SARS-CoV-2 coinfection with other respiratory viruses such as influenza A virus and parainfluenza virus. According to this model, SARS-CoV-2 infection is suppressed when initiated simultaneously with another respiratory virus. However, if the secondary infection is initiated after SARS-CoV-2 infection, the coinfection can occur. In [ 31 ], an in-host model of SARS-CoV-2 coinfection with HIV was developed. Based on the results of this model, the weak immune response in coinfected patients causes an increase in the densities of infected epithelial cells and viral particles. This can lead to severe SARS-CoV-2 infection in HIV patients. In [ 32 ], a fractional order epidemiological model of SARS-CoV-2/HIV coinfection was studied, and the epidemiological results were provided. In [ 33 ], a new model for SARS-CoV-2, dengue, and HIV co-dynamics using three different fractional derivatives was developed. It was concluded that keeping the spread of SARS-CoV-2 low has a significant impact on reducing the coinfection of SARS-CoV-2 with HIV or dengue.
Some TB and SARS-CoV-2 coinfection models have been proposed in the form of epidemiological models (for example, [ 34 , 35 , 36 , 37 ]). These models examine the possibility of coinfection and the spread of these two diseases between individuals. However, they do not reflect the internal connections such as the effect of TB and SARS-CoV-2 on the concentration of healthy cells, or the role of immune responses during coinfection. As the spread dynamics of coinfection depends on the in-host dynamics, building in-host models is a must. To the best of our knowledge, no TB and SARS-CoV-2 coinfection model has been formulated yet. In this article, we develop an in-host model of TB and SARS-CoV-2 coinfection. The model is composed of seven ordinary differential equations (ODEs) that characterize the interactions between healthy ECs, latently Mtb-infected ECs, actively Mtb-infected ECs, SARS-CoV-2-infected ECs, free Mtb, free SARS-CoV-2, and CTLs. This model is built using the same principles that were applied to construct in-host models of TB [ 14 , 15 , 16 , 17 , 18 ] and SARS-CoV-2 [ 26 , 27 , 28 ] single infections. We validate the nonnegativity and boundedness of model’s solutions. In addition, we calculate all equilibria and define their existence conditions. Furthermore, we demonstrate the global stability of all states. Finally, we conduct numerical simulations to visualize the theoretical results.
2. TB and SARS-CoV-2 Coinfection Model with Immunity
The model is composed of seven ODEs that take the form
{
d
U
(
t
)
d
t
=
λ
−
U
(
t
)
B
(
t
)
−
η
2
U
(
t
)
V
(
t
)
−
ϵ
(
t
)
,
d
L
(
t
)
d
t
=
η
1
U
(
t
)
B
(
t
a
L
(
t
)
,
d
I
B
(
t
)
d
t
=
a
L
(
t
)
−
d
t
=
η
2
U
(
t
)
V
(
t
)
−
γ
I
V
(
t
)
Z
)
−
ϵ
3
I
V
(
t
)
,
d
B
(
t
)
d
t
=
μ
1
ϵ
B
(
t
)
−
ϵ
4
B
(
t
)
,
d
V
(
t
)
d
t
=
μ
V
(
t
)
−
ϵ
5
V
(
t
)
,
d
Z
(
t
)
d
t
=
(
, and
)
measure the densities of healthy ECs, latent Mtb-infected ECs, active Mtb-infected ECs, SARS-CoV-2-infected ECs, free Mtb, free SARS-CoV-2, and CTLs, respectively. In this model, both Mtb and SARS-CoV-2 have a single type of target cell. Additionally, we assume that CTLs kill Mtb-infected ECs and SARS-CoV-2-infected ECs at the same rate constant. Furthermore, they are stimulated by these two types of infected cells at the same rate constant. Healthy ECs are recruited at a fixed rate
, become latently infected by Mtb at rate
, become infected by SARS-CoV-2 at rate
t
)
V
(
t
)
, and die at rate
ϵ
1
U
(
t
)
. Latent Mtb-infected ECs are turned into active cells at rate
a
L
(
t
)
. These active Mtb-infected cells are killed by CTLs at rate
(
t
)
Z
(
t
)
and die at rate
ϵ
2
I
B
(
t
)
. SARS-CoV-2-infected ECs are eliminated by CTLs at rate
γ
I
V
(
t
(
t
)
and die at rate
ϵ
3
I
V
(
t
)
. Mtb particles are produced at rate
μ
1
ϵ
2
I
B
(
t
)
and die at rate
4
B
(
t
)
. SARS-CoV-2 particles are generated from infected cells at rate
μ
2
I
V
(
t
)
and die at rate
ϵ
5
V
(
t
)
. CTLs die at rate
)
, and they are stimulated by Mtb and SARS-CoV-2 at rates
and
−
ξ
)
ω
I
V
(
t
)
Z
(
t
)
, respectively. The parameter
ξ
measures the impact of lymphopenia on the efficacy of CTL immune response against infected cells. A brief description of all positive parameters is given in
Table 1
.
3. Properties of Solutions
The basic properties of the solutions, including nonnegativity and boundedness, are needed for their biological acceptance.
Theorem
1.
There exist θ i > 0 for i = 1 , 2 , 3 , 4 , 5 such that the compact set Θ = ( U , L , I B , I V , B , V , Z ) ∈ R + 7 : 0 ≤ U ( t ) , L ( t ) , I V ( t ) ≤ θ 1 , 0 ≤ I B ( t ) ≤ θ 2 , 0 ≤ B ( t ) ≤ θ 3 , 0 ≤ V ( t ) ≤ θ 4 , 0 ≤ Z ( t ) ≤ θ 5 is positively invariant set for system ( 1 ).
Proof.
For model (
1
), we have
d
U
d
t
|
U
=
0
=
λ
>
0
,
d
L
d
t
|
L
=
0
=
η
1
U
(
t
)
B
(
t
)
≥
0
∀
U
(
t
)
,
B
(
t
)
≥
0
,
d
I
B
d
t
|
I
B
=
0
=
a
L
(
t
)
≥
0
∀
L
(
t
)
≥
0
,
d
I
V
d
t
|
I
V
=
0
=
η
2
U
(
t
)
V
(
t
)
≥
0
∀
U
(
t
)
,
V
(
t
)
≥
0
,
d
B
d
t
|
B
=
0
=
μ
1
ϵ
2
I
B
(
t
)
≥
0
∀
I
B
(
t
)
≥
0
,
d
V
d
t
|
V
=
0
=
μ
2
I
V
(
t
)
≥
0
∀
I
V
(
t
)
≥
0
,
d
Z
d
t
|
Z
=
0
=
0
.
This proves that
U
for all
V
(
0
)
,
Z
(
0
)
∈
R
+
7
.
To show the boundedness of solutions, we introduce the following function:
Γ
1
(
t
)
=
U
(
t
)
+
L
(
t
)
+
I
V
(
t
)
.
(2)
By differentiating (
2
) w.r.t
t
, we obtain
d
Γ
1
(
t
)
d
t
=
λ
−
ϵ
1
U
(
t
)
−
a
L
(
t
)
−
γ
I
U
(
where
. Therefore, we obtain
where
There is a set of threshold parameters R 0 , R 1 , R 2 , and R 3 such that model ( 1 ) has six equilibria as follows:
The healthy equilibrium E 0 always exists;
The Mtb mono-infection equilibrium with inactive CTLs E 1 exists if R 0 > 1 ;
The SARS-CoV-2 mono-infection equilibrium with inactive CTLs E 2 exists if R 1 > 1 ;
The Mtb mono-infection equilibrium with active CTLs E 3 exists if R 2 > 1 ;
The SARS-CoV-2 mono-infection equilibrium with active CTLs E 4 exists if R 3 > 1 ;
The Mtb and SARS-CoV-2 coinfection equilibrium with active CTLs E 5 exists if ( 1 − ξ ) λ ω η 2 μ 2 ϵ 4 ϵ 2 ϵ 5 ( 1 − ξ ) ω ϵ 1 ϵ 4 + η 1 μ 1 ϵ 2 ϵ 6 + 1 > ϵ 3 ϵ 2 + R 2 , ( 1 − ξ ) λ ω η 1 μ 1 ϵ 2 ϵ 5 ϵ 3 ϵ 4 ( 1 − ξ ) ω ϵ 1 ϵ 5 + η 2 μ 2 ϵ 6 + 1 > ϵ 2 ϵ 3 + R 3 , R 1 R 0 > 1 , ϵ 2 > ϵ 3 , and η 1 μ 1 ϵ 2 ϵ 5 η 2 μ 2 ϵ 4 > 1 .
Proof.
The equilibria of model (
1
) can be obtained by solving the following algebraic system:
Then, we obtain
(1)
The healthy equilibrium
, which always exists.
The Mtb mono-infection equilibrium with inactive CTLs
. The components are computed as follows:
where
. We see that
, while
,
, and
are positive if
. Therefore,
is defined when
. The parameter
is a threshold that determines the initiation of Mtb infection in the absence of CTL immunity.
(3)
The SARS-CoV-2 mono-infection equilibrium with inactive CTLs
E
2
=
2
,
0
,
0
,
,
. Its components are formalized as follows:
U
2
=
ϵ
3
ϵ
5
η
2
μ
2
,
I
2
V
=
ϵ
1
ϵ
5
=
where
if
. Thus,
exists if
is a threshold that sets the start of the SARS-CoV-2 infection, where the immune response is not active.
(4)
. We note that
,
,
, and
are always positive, while
. This implies that
E
exists if
. The parameter
R
2
is a threshold that specifies the start of CTL immunity against Mtb-infected epithelial cells.
(5)
The SARS-CoV-2 mono-infection equilibrium with active CTLs
4
. The components are defined as
where
. Hence,
exists when
. Here,
is a threshold that determines the activation state of CTL immunity against SARS-CoV-2-infected epithelial cells.
(6)
The Mtb and SARS-CoV-2 coinfection equilibrium with active CTLs
. The components are given by the following formulas:
exists and the coinfection occurs when these conditions are hold.
□
4. Global Properties
We introduce a function
and let
Theorem
3.
The equilibrium E 0 is globally asymptotically stable (GAS) if R 0 ≤ 1 and R 1 ≤ 1 .
Proof.
We define
By computing the time derivative of
, we obtain
In terms of
and
, we can write
| https://www.mdpi.com/2227-7390/11/5/1104 |
(PDF) Professions, Proficiency, and Place: An Introduction
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Professions, Proficiency, and Place: An Introduction
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DOI: 10.1007/978-3-031-24910-5_1
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In book: Professions and Proficiency (pp.1-12)
Authors:
<here is a image dd6c561447bc35d4-3f8f4ba5fba3fc8d>
Johannes Glückler
Universität Heidelberg
<here is a image aaa0d61c5a922266-79203308c1b51506>
Anna Mateja Punstein
Universität Heidelberg
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Christopher Winch
Christopher Winch
Abstract
The 18th volume of the interdisciplinary series on Knowledge and Space looks at how people learn, create and transfer knowledge within and across social groups, such as professions, scholarly disciplines or communities. On the one hand, creating knowledge across social groups is important for innovation, especially for creating more radical and unconventional novelty. On the other hand, social circles often frame what and how its members think and learn, and so erect structural boundaries to innovation. This introductory chapter emphasizes the collective nature and social process of knowledge creation. Moreover, it suggests combining the study of professions and proficiency with a geographical understanding of the place-specificity of those dynamics that finally enable change, learning and cross-fertilization, especially beyond the boundaries of individual professions and communities.
<here is a image 175d1bd4b7439d95-754927124da715c1>
1
Chapter 1
Professions, Prociency, andPlace:
AnIntroduction
JohannesGlückler, AnnaMatejaPunstein,andChristopherWinch
The 18th volume of the interdisciplinary series on Knowledge and Space looks at
how people learn, create and transfer knowledge within and across social groups,
such as professions, scholarly disciplines or communities. On the one hand, creat-
ing knowledge across social groups is important for innovation, especially for creat-
ing more radical and unconventional novelty (Nooteboom, van Haverbeke, Duysters,
Gilsing, & van den Oord, 2007; Norman & Verganti, 2014; Uzzi, Mukherjee,
Stringer, & Jones, 2013). On the other hand, social circles often frame what and
how its members think and learn, and so erect structural boundaries to innovation
(Abbott, 1988; Fleck, 1935).
Professions are particularly important for the framing of domain-specic
knowledge: “The professions dominate our world. They heal our bodies, measure
our prots, save our souls” (Abbott, 1988, p.1). Scholarly research on professions
started at least as early as in the 1950s, when Parsons ( 1951) proposed the term to
distinguish professionals from bureaucrats (Siebert & Windrum, 2023 ). Whereas
earlier studies looked at how professions institutionalize distinctively within differ-
ent national contexts (e.g., Abbott, 1988; Freidson, 1994; Larson, 1977; Macdonald,
1995 ), more recent research has explored the concept of professionalism within
organizational elds, how professionalism varies across space and time, and how
professions play a role in institutional and organizational change as well as the par-
titioning of organizational elds (e.g.,Aldridge & Evetts, 2003; Evetts, 2003 ;
J. Glückler ( *)
Department of Geography, Heidelberg University, Heidelberg, Germany
e-mail: glueckler@uni-heidelberg.de
A. M. Punstein
Formerly associated with Department of Geography, Heidelberg University,
Heidelberg, Germany
C. Winch
School of Education, Communication and Society, King’s College London, London, UK
© The Author(s)2023
J. Glückler et al. (eds.), Professions and Prociency , Knowledge and Space 18,
https://doi.org/10.1007/978-3-031-24910-5_1
2
Faulconbridge, 2008 ; Faulconbridge & Muzio, 2021; Macdonald, 1995; Muzio,
Brock, & Suddaby, 2013; Noordegraaf 2011).
In this book, we aim to take a broader perspective and inquire into the intersection
of professions, knowledge and space. Chapters in this volume will address key
questions regarding how social groups create, use and spread knowledge, and how
these processes relate to geographical space and place, including such questions as:
How do professions frame, build and train prociency? How do members of a pro-
fession govern professional competence, knowledge and skill?What are the geo-
graphical conditions and social contexts in which these processes are helped or
hindered? To answer these questions, scholars from philosophy, sociology, political
science, geography, psychology, and history contribute conceptual and empirical
work from multiple disciplinary perspectives, including case studies on translators
in Israel, engineers in Canada, architects in the UK, or psychologists in Argentina.
Previous volumes in this series have highlighted that social contexts in
geographical places shape the meanings, interactions and structures of professions
and organizations (Coraiola, Suddaby, & Foster, 2018; Glückler, Suddaby, & Lenz,
2018 ; Meusburger, 2009). Others have pointed to the important role of institutions,
that is, the relatively stable patterns of interaction based on mutually shared
normative expectations, in the rise of new and the demise of incumbent professions
and practices, such as the Journeyman tradition in Germany (Glückler & Lenz,
2018 ). What do we know about the role of social processes in professions and
knowledge creation? In the following section, we adopt a perspective of the social
process of learning as a framing of the relation between profession and prociency,
and to which the individual chapters in this volume contribute differently.
Professions: Social Groups OrganizedAround Knowledge
In everyday life as well as in academia, the term “profession” is used do denote a type
of work or occupation that requires particular expertise and knowledge, which pro -
fessionals attain by means of special education, training and practice. Professions are
associated with occupations that develop more complex or advanced forms of knowl -
edge bases, non-routine practices and conceptual or “white-collar” work (Adams,
2020 ; McDonald,2000 ), such as teachers, accountants, architects, medical doctors,
engineers or lawyers (Kuus, 2021). Professions frame the creation, valuation, and
reproduction of knowledge. On the one hand, members of a profession together
decide what kinds of knowledge are legitimate, valid and useful (Fleck, 1935 , 1979 ).
They make knowledge accessible, reproducible, and they share and educate that
knowledge across society and space. On the other hand, professions control access to
and so exclude non-members from their professional knowledge (Abbott, 1988 ). The
literature suggests several characteristics that encourage a perspective of the social
process of learning and interaction: First, members of a profession collectively stan -
dardize and regulate knowledge exchange and services (Freidson, 1994; Siebert &
Windrum, 2023 ); second, professions are built on a commonly approved knowledge
base (Crompton, 1990); third, professionals are reinforced through training and
J. Glückler et al.
3
education of a dened set of skills and competences (Winch, 2023); fourth, members
of a profession share a common thought style and language (Fleck, 1935 , 1979 ;
Punstein & Glückler, 2020); fth, professions are linked to social status, power and
elite structure (Adams, 2020; Eyal & Pok, 2015; Fleck, 1935 , 1979).Yet how exactly
do professions produce knowledge and prociency?
Prociency: TheSocial Process ofGaining Knowledge
Creating knowledge and gaining prociency depends on social mechanisms and on
the spatial context in which professions are embedded. A generic understanding of
prociency is the “ability to do something well because of training and practice”
(Oxford Dictionary, 2022), a notion commonly applied in the context of language
education. Knowledge, a term most diversely conceived throughout the volumes of
this book series, broadly refers to the human understanding of concrete and abstract
phenomena (Glückler, Herrigel, & Handke, 2020).And because it is neither given
to anyone in its totality (von Hayek, 1945), nor independent from the specic con-
text of meaning, the creation and use of knowledge is subject to the social process:
“Knowledge in general, and scientic knowledge in particular, is not only a poten-
tial means of access to the secret of the world but also the coming into being of the
world” (Stehr, 2010, p.26). Facts are always recognized and understood within a
social, psychological, local and situational context (Fleck, 1935). A key question,
then, is how professions master the trade-off between the enduring need for new and
unconventional (Mukherjee, Uzzi, Jones, & Stringer, 2017) knowledge, and the
need for conventionalization and transfer of existing knowledge.
Extant research has comprehensively appraised the collective nature and social
process of knowledge creation. Several concepts and approaches, including epis -
temic cultures (Knorr-Cetina, 1981 , 1999 ), communities of practice (Lave & Wenger,
1991 ; Wenger, 1998 ), or epistemic communities(Cohendet, Grandadam, Simon, &
Capdevila, 2014 ; Haas, 1992) highlight knowledge production as a collective pro -
cess enacted by social groups (Table 1.1).Yet, whereas adherents to community
perspectives of learning have contributed greatly to unpacking the forms, mecha -
nisms and instruments of within-group processes of knowledge creation, important
questions remain: If members of a profession constitute the quality and level of
expertise or skill necessary to be considered procient, how can individuals be pro -
cient in more than one eld (Baneld, 2023)? And how can professional knowl -
edge be mobilized across the boundaries of a profession (Punstein & Glückler, 2020)?
Perhaps the relatively neglected, yet most subtle approach to studying knowledge
creation within and across social groups is Ludwik Fleck’s theory of thought
collectives (Fleck, 1935 , 1979). Apart from developing a coherent conceptual lan-
guage to decipher processes of education, training and learning within a thought
collective, Fleck pays dedicated attention to the challenges that collectives face vis-
à-vis their external environment and through the course of time (see Table 1.1 ).
Empirical research on inter-professional learning suggests that cross-fertilization
and co-creation of new knowledge across professional boundaries often fails due to
1Professions, Prociency, andPlace: AnIntroduction
4
Table 1.1 Four approaches to the social production of knowledge
Epistemic
cultures
Community of
practice
Epistemic
community
Thought
collective
Social
structure
Science-specic,
individual vs.
collaborative
Core–periphery
structure; multiple
membership
Agenda-specic
structure around
members with
legitimacy
Universal structure of
esoteric (experts) and
exoteric circles (lay);
dogmatic vs. democratic
structure
Learning at
individual
level
Adapt to a
culture by
working in a
scientic eld
Identify with a
community’s
competence
regime
Commit to an
agenda;
manifesto and
codebook
Education; stylish
thinking; thought
charms; thought
solidarity
Learning at
collective
level
Paradigm shifts
in science
Negotiation of
new elements
brought in by
(new) members
Radical shifts in
the community
lead to changes
in the codebook
Endogenous learning by
exoteric or esoteric
pushes; exogenous
learning through new
members
Inter-group
transfer and
learning
n.a. Adjust language;
boundary objects
(blueprints) or
brokers
(managers)
Rewrite the
codebook to
convince people
to join an agenda
Master ‘hallucination’;
translate thoughts into
‘less deep’ language;
collective mood
Note. Adapted from Punstein and Glückler ( 2020, p.547). Copyright 2019 by Oxford University
Press. Adapted with permission
the social construction of (in)commensurability (Punstein & Glückler, 2020 ). When
professions institutionalize their own specic thought styles (Fleck, 1935 , 1979),
the thinking of one professional may easily clash with that of another profession.
The “hallucination” that may (or may not) occur can hinder joint knowledge cre-
ation, as an in-depth study of learning and co-creation across the professions of
industrial engineering and industrial design has demonstrated (Punstein & Glückler,
2020 ).Yet, asAbbot argues, “interprofessional relations are potentially the central
feature of professional development” (Abbott, 1988, p.18). Hence, learning pro-
cesses and the governance of intangibles and knowledge within groups are impor-
tant to understand what happens if knowledge is transferred from one social context
to another (Baneld, 2023).
Space: TheContext ofProfessional Learning
One way to stimulate change within a profession, is to facilitate exposure, contact
and interaction with members of another profession by means of encounter and
colocation in a geographical place. The places, where members of different profes-
sions meet, create opportunities for local variation in thought styles and potential
cross-fertilization (Punstein & Glückler, 2020). Geographers have emphasized the
place-specicity of professional knowledge (Agnew, 2007; Gertler, 1995 ;
J. Glückler et al.
5
Meusburger, 2009 ; Storper & Venables, 2004). Space, place and spatial networks
shape the traveling of ideas, professions and expertise (Kuus, 2021). Spatial context
matters at different scales. Obviously, professions are regulated at the national level,
causing problems of recognition or accreditation in other jurisdictions. A lawyer or
medical doctor trained in one country usually has to acquire additional certication
to be allowed for professional practice in another. Variation and friction, however,
also occur at subnational, regional levels (Kuus, 2021; Sassen, 2018).Hence, forms
of collective knowledge production are inuenced by and embedded in various lev-
els of space, such as local and national environments, institutional and socio-
economic contexts, and socio-spatial relationships. The book collects a set of
original contributions that shed light from distinct disciplinary perspectives on the
interdependencies between professions, prociency, and the geographical contexts
and diversity in which these relations unfold.
StructureoftheBook
The chapters in this book offer original conceptual and empirical views on how
social collectives learn within professions (Part I), how intangible qualities of pro-
fessions transform (Part II), and nally, how professional life unfolds in space and
across different scales and geographical contexts (Part III).
LearningWithinProfessions
In Part I, researchers analyze the social processes within professions and explore
how professionals gain prociency. In Chapter 2 , Christopher Winchlooks at the
standardization of professional competence and asks if professional qualications
are (still) the guarantee of professional ability of its holder. He argues that designers
of professional curricula need to focus on more than just “the skills” of the future
professionals to construct and maintain professional qualications sustainably. He
draws on the example of professionals in low-energy construction to show that
besides skills, systematic (theoretical) and non-systematic (conditional) knowledge,
as well as know-how and personal characteristics, such as individual and social
attitude and capacity are important attributes of prociency (Winch, 2023).
In Chapter 3 , Janet Baneldreconceptualizes the notion of prociency and
challenges the idea of disciplinary professionalization at the intersection of three
different scientic disciplines—geography, psychology, and the arts (Baneld,
2023 ). She demonstrates inventively that professional prociency is connected to
disciplinary legitimacy. Interdisciplinary expertise seems to be sanctioned,
undesirable and “inprocient” in academic careers by the members of each discipline
(Baneld, 2023 ). She provides a new understanding of interdisciplinary expertise
1Professions, Prociency, andPlace: AnIntroduction
6
and how disciplinary spaces can restrict the acceptance of new knowledge. By doing
so, this chapter emphasizes the need for interdisciplinary work on how practitioners
can overcome disciplinary boundaries to enable knowledge generation across
professions.
Chapter 4 combines the perspectives of expertise, knowledge and strategies and
goes one step further into knowledge creation . Patricia Alexander intersects the
perspective of domain-specic knowledge with individuals’ strategic abilities and
interest in order to investigate how expertise develops over time. Introducing the
Model of Domain Learning (MDL) she takes a psychological and educational view
and contributes to a deeper conceptual understanding of expertise (Alexander,
2023 ). Her three-stages model—acclimation, competence, and prociency—helps
to understand which strategies individuals use to become a procient expert within
a professional domain. She proposes that societal changes may inuence the nature
of expertise in the future: The developmentof AI and the technology-rich world
change the conditions for professional prociency and learning.
In Chapter 5 , Rakefet Sela-Sheffy looks at the profession of translators and argues
that professional identity makes a translator procient in his or her eld of expertise
(Sela-Sheffy, 2023 ). Building on a qualitative case study in Israel, she critically
reects the concept of professions and the role of professionalization as status
mechanism. She argues that competencies within professions are socially learned
and controlled and embodied in the professionals’ dispositions and self-perception,
instead of being regulated by organizations or institutional agencies. Professional
translators deliberately reject the formalization of their work but are not seen as
unqualied workers in this very case. The chapter introduces the idea of counter-
professionalization and provides a new understanding of the status structure of this
occupation.
GoverningProfessions
Part II includes several chapters that examine the dynamics that transform the
intangible qualities of a profession, including data, intellectual property, and
professional legitimacy. Chapters 6and 7investigate two professions—British
architects and US scientists—and show how internal and external professional
dynamics (Siebert & Windrum, 2023, Chap. 6) and societal changes (Haas, 2023 ,
Chap. 7) inuence the legitimacy and power of professions.
In Chapter 6 , Michael Siebertand Paul Windrum illustrate how the control, the
roles and the knowledge of the architectural profession have changed over the post-
war period in the UK.Architects used to be one of the most important actors within
the private residential sector (Siebert &Windrum, 2023), and their profession was
the main catalyzer to organize and integrate the entire work ow, including manag-
ing the contractors and legal agencies.Yet, as the authors argue, architectures have
gradually lost their powerful position within the housing industry due to endoge-
nous and exogenous factors, and professional practice and knowledge has trans-
formed accordingly.
J. Glückler et al.
7
In Chapter 7 , Peter M.Haas takes a political science perspective and elaborates
on the social foundations of the legitimacy (and authority) of science. In particular,
he focuses on the challenges that scientic evidence and its use in politics have had
to face in the course of contemporary climate denialism. Analyzing ten criteria of
legitimacy Peter Haas shows that three criteria have been the driver of the delegiti-
mization process of scientists in the context of political governance: consensus
within the scientic groups, accuracy of their predictions and impartiality. To restore
their legitimacy Haasdiscusses further social legitimacy criteria.
Chapter 8 puts the governance of intangibles, data, and intellectual property
under the microscope. Ahmed Bounfourconnects to research on intangibles, such as
intellectual property rights, and focusses on the role that intangibles and the accel-
eration of time and space play for innovation and future forms of knowledge pro-
duction (Bounfour, 2023). New forms of value creation and business models, such
as platforms, show new ways how value is produced and governed. For these rea-
sons, and in contrast to traditional production systems (e.g., Lean), he introduces the
concept of the acceluction regime to explore the accelerated production of (digital)
links in contemporary economies. His concept offers a new analytical perspective to
evaluate the role of intangibles for innovation, but also points to political and social
issues which may inuence economic performances, new dynamics of economic
powers, competition, and property rights.
The Spatial Dimension toShaping Professions
Although the importance of space has become visible explicitly and implicitly in all
previous chapters, Part III of this book includes four original chapters that explicitly
address the question how professional work unfolds in places and across space.
More specically, the contributions analyze three professions—psychology, engi-
neering, and academia—at several different spatial scales and social dimensions.
In Chapter 9 , Hugo Klappenbachanalyzes the development of the profession of
psychology in Argentina since the end of the nineteenth century (Klappenbach,
2023 ). He shows the evolution and progressive steps of standardization of psychol-
ogy as a profession within the national context of Argentina: starting with assistance
for other professions (such as medicine), followed by the establishment of an under-
graduate program in psychotechnics, and nally by a university degree in psychol-
ogy. His historical reconstruction demonstrates how institutional and political
factors shaped the establishment of the profession in Argentina. Overall, his study
illustrates how the evolution of professions, and their geographical origin have built
the roots for place-specic practices and knowledge.
Wolfgang König, the author of Chapter 10, undertakes a deep historical analysis
of a well-known industrial leadership personality (König, 2023). He examines the
case of William Siemens (1823–1883), engineer and founder of Siemenscorpora -
tion, who had been educated in Germany and then moved to England. This compara -
tive case study design facilitates researching the physical, cultural, and technological
spaces of professional action in two nations. He argues that the places of England
1Professions, Prociency, andPlace: AnIntroduction
8
and Germany had shaped the technological evolution as well as the performance and
transformation of the engineering profession differently in each country.
Chapter 11 portrays the engineering profession in Canada and illustrates that the
national and work-place context has forced change in the practice of engineers and
professional knowledge. New organizational requirements, such as increasing ef-
ciency, have affected the prociency of engineers nowadays. In her qualitative case
study Tracey Adams shows that “training-on-the-job” which has been a primary and
well-established part of the engineering education has been experiencing a loss of
legitimacy during the last years. She argues that the change at the workplace has
encouraged new engineers to pursue “information gathering, rather than building
deep knowledge”. She argues that engineers are likely to face long-term implica-
tions for their duciary responsibilities (Adams, 2023).
In the nal Chapter 12 , ArianeBerthoin Antaland Julian Hamannfocus on
German academia and claim that the mantra of efciency risks to offset inter-disci-
plinary and creative knowledge acquisition.The prociency of academics is linked
to their dedication to becoming a specialist in their area of expertise (Berthoin Antal
& Hamann, 2023). The authors argue that “streamlined professionalization” in aca-
demia hinders “playful deviations”— Spielwiesen—from the primary disciplinary
path into different social and intellectual spaces. The chapter proposes the concept
of Spielwiesen as spaces, where academics can engage with new elds of knowl-
edge. National education systems, disciplinary contexts and career stages provide
different opportunities to enable spaces of off-disciplinary learning.
Conclusion
In this book, scholars analyze how the creation, use and sharing of knowledge is
bound to collective agency. Professions and prociency co-evolve. Professions build
knowledge, while, at the same time, knowledge institutionalizes the profession. The
validity of knowledge depends to some extent on the legitimacy of professional
members and leaders as well as on the spatial context. Cultural and institutional
spaces help to stabilize but also change the prociency of a profession. Places and
spaces that stimulate inter-disciplinary learning will become more and more impor -
tant in the digital age. In order to educate future generations, it is necessary to open a
professional and expert-centric view and to understand the new kinds of mechanisms
and practices that procient persons need to know in their eld of work and expertise.
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Johannes Glückler is Professor of Economic and Social Geography and Fellow of the Marsilius
Center for Advanced Studies at Heidelberg University. In his research he adopts a relational per-
spective to theorize social networks and institutions in the study of the geography of knowledge
and regional development. He is a founding board member of the German Society for Social
Network Research DGNet and co-founder of the M.Sc. Governance of Risks and Resources at the
Heidelberg Center for Latin America in Santiago de Chile.
Anna Mateja Punstein currently works as a corporate quality engineer. She was a Research
Associate in Economic Geography at the Institute of Geography at Heidelberg University, Germany
until early 2022. She received her PhD from Heidelberg University in Geography in 2020. Her
elds of interest include geographical research on innovation, business services and epistemology,
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as on cooperation during product development.
Christopher Winch currently isProfessor of Educational Philosophy and Policy in the School of
Education, Communication and Society at King’s College London. He is a philosopher of educa-
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the assessment of professional competence. He has taken part in research projects concerned with
professional qualications in Europe, including work on the European Qualication Framework.
This appeared as “Knowledge, Skills and Competence in the European Labour Market, 2011”,
co-authored with Linda Clarke, Michaela Brockmann, Georg Hanf, Philippe Méhaut and Anneke
Westerhuis. He is also the author of “Dimensions of Expertise” 2010, an analysis of professional
know-how and expertise.
1Professions, Prociency, andPlace: AnIntroduction
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Professions, Knowledge, and Workplace Change: The Case of Canadian Engineers
Chapter
Full-text available
Mar 2023
<here is a image 2a822372f8fadee8-a646f91f6189b4db> Tracey L Adams
In North America, training in engineering has long been balanced between formal university education and on-the-job training. Over the last few decades, however, Canadian engineering workplaces have changed. In the drive for efficiency and profit, firms are increasingly reluctant to invest in training. This paper’s author draws on interviews with 53 Ontario, Canada, engineers to explore how workplace change impacts professional skills, and to identify the implications for professional knowledge. From her findings, she concludes that engineers have fewer opportunities to learn on the job than in the past. Increasingly, many are asked to learn in their own time, or on an ad-hoc basis to complete pressing tasks. This encourages information gathering, rather than building deep knowledge. Moreover, knowledge benefiting employers is emphasized at the expense of knowledge benefiting society, with potential long-term implications for engineers’ fiduciary responsibilities.
What Does It Take to Be a Professional Translator? Identity as a Resource
Chapter
Full-text available
Mar 2023
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Rakefet Sela-Sheffy
This study’s author proposes integrating the lens of identity research into critical discussions of professions, questioning the role of professionalization as a status mechanism. Addressing under-professionalized occupational domains, drawing largely from Bourdieu, she conceives “professionalism” as symbolic capital negotiated by workers, to account for the ambiguity of professional knowledge and skills. She views professional competencies as socially learned and controlled, embodied in workers’ dispositions and self-perception (and not in institutional regulation). Translators provide a quintessential (though under-researched) case of extremely under-professionalized occupation, despite being in great demand. Using in-depth-interviews and miscellaneous popular documents, the author analyzes Israeli translators’ discursive construction of professional identities as where their professional capital is produced. She shows that translation sectors engage in counter-professionalization —the deliberate rejection of formalization and standardization—as a prevailing status strategy. Locating professionalism in personal natural abilities, she reveals how this strategy helps rebutting the image of unqualified workers, providing the axis for this occupation’s status structure.
The Changing Fortunes of the Architectural Profession in Postwar Britain: Complexity, Technological Change, and the (Re)construction of Knowledge
Chapter
Full-text available
Mar 2023
Michael Siebert
Paul Windrum
Professions are one means of organizing the delivery of goods and services. In this paper, the authors consider how the power and control of professional groups can change within specific fields of work due to a combination of endogenous and exogenous factors. Their case study is the changing role of UK architects within the private residential sector over the post-war period. The architect was once the primary actor who brought together, organized, and integrated the workflow of a myriad of contractors, legal agencies, and planning authorities, but this is no longer the case. To understand how this occurred, and whether the architectural profession could regain a key position in the UK housing industry, the authors conduct a broad historical analysis of the factors at play within the UK architectural profession and the industry as a whole that have resulted in this shift in knowledge, roles and power.
The Beginnings of Psychologist Profession in Argentina: Science, Institutional Context and Society
Chapter
Full-text available
Mar 2023
<here is a image ad9c73c272e72d47-ad49aeec0db6d297> Hugo Klappenbach
The chapter analyzes the first developments in psychology at the end of the nineteenth century and beginnings of the twentieth century. In those years, psychology appeared to be a knowledge usable for professions like medicine, pedagogy or legal profession. Moreover, the chapter exhibits a very import shift that happened in the middle of twentieth century when some undergraduate programs started in the field of psychology. Usually, such programs were not found in psychology, but in psychotechnics and professional guidance . The chapter analyzes the scientific orientation of such programs, based on French psychology, as well as the institutional and political factors promoting psychological programs. Last, the chapter will expose the re-orientation of psychology education at universities since the second half of the 1960s, when psychology became synonymous with psychoanalysis . On the one hand, it will analyze the institutional and political background for the constitution of the profession of psychologist. On the other hand, it will exhibit the main ways supporting psychologist psychoanalytically biased profession: epistemological and theoretical approaches within science and psychology education, clinical practices in public institutions, and a virtual repudiation of alternative models of knowing and practicing.
Preserving the Epistemic Authority of Science in World Politics
Chapter
Full-text available
Mar 2023
<here is a image ef886b54fc25bc69-47e49751a23a0b9f> Peter Haas
Governments rely extensively on expertise, and arguably many of the major accomplishments over the last 50 years reflect the ideas and involvement of experts. Yet expertise in world politics is increasingly contested. This chapter looks at the role of science and expertise in the world politics, and the multiple criteria of legitimacy that frame its reception. It concludes with a discussion of how scientific legitimacy can be defended.KeywordsLegitimacyExpertiseScienceUnited NationsClimate change
| https://www.researchgate.net/publication/369320672_Professions_Proficiency_and_Place_An_Introduction |
Controlling inflammatory and immune responses | EurekAlert! Science News
Researchers at the IRCM, led by geneticist Dr. Jacques Drouin, recently defined the interaction between two essential proteins that control inflammation. This important breakthrough will be published in tomorrow's print edition of the scientific journal Molecular Cell.
Controlling inflammatory and immune responses
An important breakthrough by IRCM researchers contributes to a better understanding of the human genome
Institut de recherches cliniques de Montreal
Researchers at the IRCM, led by geneticist Dr. Jacques Drouin, recently defined the interaction between two essential proteins that control inflammation. This important breakthrough will be published in tomorrow's print edition of the scientific journal Molecular Cell.
IRCM scientists study glucocorticoids, a class of steroid hormones that suppress the immune system and reduce inflammation. They are used in medicine to treat diseases such as allergies, asthma, and autoimmune diseases.
"In molecular biology and genetics, proteins known as transcription factors bind to DNA in order to control the expression (or transcription) of genetic information," explains Dr. Drouin, Director of the Molecular Genetics research unit at the IRCM. "Our work defined the genome-wide interaction between two transcription factors: Stat3 and the glucocorticoid receptor (GR)."
While Stat3 acts on pro-inflammatory gene targets, glucocorticoids are widely used for their anti-inflammatory properties and their receptor, GR, interacts with Stat3 to control these actions. GR can be found in almost every cell in the body and regulates genes that control development, metabolism, and inflammatory and immune response.
Transcription factors can control the flow of information alone or along with other proteins, either by promoting (as an activator) or blocking (as a repressor) the recruitment of enzymes required for the expression of specific genes. Transcription factors can bind directly to DNA or attach themselves to another DNA-bound protein.
"In some cases, the proteins will behave differently depending on how they are connected to a DNA sequence," says David Langlais, former doctoral student in Dr. Drouin's laboratory and first author of the article. "We were interested in understanding why some transcription factors could act as activators when bound directly to DNA, but act as repressors if they are recruited by another protein. The molecular basis for this dual action remained unclear until now."
Jacques Drouin's research is funded by the Canadian Institutes for Health Research (CIHR). Catherine Couture and Aurélio Balsalobre, both researchers in Dr. Drouin's laboratory, also contributed to this research project.
###
About Dr. Jacques Drouin
Jacques Drouin obtained his Doctor of Science in Physiology from the Université Laval. He is IRCM Research Professor and Director of the Molecular Genetics research unit. Dr. Drouin is a professor in the Department of Biochemistry at the Université de Montréal. He is also associate member of the Department of Medicine (Division of Experimental Medicine), adjunct professor of the Department of Anatomy and Cell Biology, and adjunct member of the Department of Biochemistry at McGill University. In addition, he is an elected member of the Academy of Sciences of the Royal Society of Canada.
About the Institut de recherches cliniques de Montréal (IRCM)
Founded in 1967, the IRCM (www.ircm.qc.ca) is currently comprised of 36 research units in various fields, namely immunity and viral infections, cardiovascular and metabolic diseases, cancer, neurobiology and development, systems biology and medicinal chemistry. It also houses three specialized research clinics, eight core facilities and three research platforms with state-of-the-art equipment. The IRCM employs 425 people and is an independent institution affiliated with the Université de Montréal. The IRCM clinic is associated to the Centre hospitalier de l'Université de Montréal (CHUM). The IRCM also maintains a long-standing association with McGill University.
| https://archive.eurekalert.org/pub_releases/2012-07/idrc-cia071212.php |
Electronic Thesis/Dissertation | Stochastic Drought Risk Analysis and Projection Methods For Thermoelectric Power Systems | ID: fq977t840 | Hyrax
Electronic Thesis/Dissertation
Stochastic Drought Risk Analysis and Projection Methods For Thermoelectric Power Systems Öffentlichkeit
Combined effects of socio-economic, environmental, technological and political factors impact fresh cooling water availability, which is among the most important elements of thermoelectric power plant site selection and evaluation criteria. With increased variability and changes in hydrologic statistical stationarity, one concern is the increased occurrence of extreme drought events that may be attributable to climatic changes. As hydrological systems are altered, operators of thermoelectric power plants need to ensure a reliable supply of water for cooling and generation requirements. The effects of climate change are expected to influence hydrological systems at multiple scales, possibly leading to reduced efficiency of thermoelectric power plants. This study models and analyzes drought characteristics from a thermoelectric systems operational and regulation perspective. A systematic approach to characterize a stream environment in relation to extreme drought occurrence, duration and deficit-volume is proposed and demonstrated. More specifically, the objective of this research is to propose a stochastic water supply risk analysis and projection methods from thermoelectric power systems operation and management perspectives. The study defines thermoelectric drought as a shortage of cooling water due to stressed supply or beyond operable water temperature limits for an extended period of time requiring power plants to reduce production or completely shut down. It presents a thermoelectric drought risk characterization framework that considers heat content and water quantity facets of adequate water availability for uninterrupted operation of such plants and safety of its surroundings. In addition, it outlines mechanisms to identify rate of occurrences of the said droughts and stochastically quantify subsequent potential losses to the sector. This mechanism is enabled through a model based on compound Nonhomogeneous Poisson Process. This study also demonstrates how the systematic approach can be used for better understanding of pertinent vulnerabilities by providing risk-based information to stakeholders in the power sector. Vulnerabilities as well as our understanding of their extent and likelihood change over time. Keeping up with the changes and making informed decisions demands a time-dependent method that incorporates new evidence into risk assessment framework. This study presents a statistical time-dependent risk analysis approach, which allows for life cycle drought risk assessment of thermoelectric power systems. Also, a Bayesian Belief Network (BBN) extension to the proposed framework is developed. The BBN allows for incorporating new evidence, such as observing power curtailments due to extreme heat or lowflow situations, and updating our knowledge and understanding of the pertinent risk. In sum, the proposed approach can help improve adaptive capacity of the electric power infrastructure, thereby enhancing its resilience to events potentially threatening grid reliability and economic stability.The proposed drought characterization methodology is applied on a daily streamflow series obtained from three United States Geological Survey (USGS) water gauges on the Tennessee River basin. The stochastic water supply risk assessment and projection methods are demonstrated for two power plants on the White River, Indiana: Frank E. Ratts and Petersburg, using water temperature and streamflow time series data obtained from a nearby USGS gauge.
Author
Bekera, Behailu Belamo
Language
en
Stichwort
Compound NHPP
Climare Risk Modeling
Energy Loss Modeling
Thermoelectric Power Plants
Probabilistic Risk Assessment
Bayesian Belief Nets
Date created
2016
Type of Work
Thesis or Dissertation
Rights statement
In Copyright
GW Unit
Engineering Mgt and Systems Engineering
Degree
Ph.D.
Advisor
Francis, Royce A
Committee Member(s)
Santos, Joost R
Omitaomu, Olufemi A
Shittu, Ekundayo
Mazzuchi, Thomas A
Persistent URL
https://scholarspace.library.gwu.edu/etd/fq977t840
License
All rights reserved
| https://scholarspace.library.gwu.edu/concern/gw_etds/fq977t840?locale=de |
Impacte ecològic i efectivitat de l'aplicació de l'antagonista Candida sake CPA-1 al camp, per al control biològic de la podridura blava en poscollita de mançanes "golden delicious"
Impacte ecològic i efectivitat de l'aplicació de l'antagonista Candida sake CPA-1 al camp, per al control biològic de la podridura blava en poscollita de mançanes "golden delicious"
Author
Teixidó i Espasa, Neus
Director
Viñas Almenar, Inmaculada
Date of defense
1997-12-16
ISBN
9788469317730
Legal Deposit
L-356-2010
Department/Institute
Universitat de Lleida. Departament de Tecnologia d'Aliments
Abstract
El desenvolupament de resistència als fungicides per part de molts patògens en<br/>postcollita de fruita i vegetals, una manca d'adequats substituts pels fungicides i<br/>una preocupació creixent de la societat respecte als perills sanitaris i<br/>mediambientals que comporten els pesticides i els seus residus, han generat un<br/>gran interès pel desenvolupament de mètodes alternatius, efectius però més<br/>respectuosos amb el medi ambient. El control biològic mitjançant la utilització de<br/>microorganismes ha sorgit com una de les alternatives més prometedores. La soca<br/>CPA-1 del llevat Candida sake, el qual s'ha aïllat de la superfície de,mançanes al<br/>nostre laboratori, ha demostrat tenir una bona capacitat antagònica enfront els<br/>principals fongs patògens en postcollita de fruita de llavor. L'aplicació<br/>d'antagonistes en precollita per controlar les malalties de la fruita de llavor en<br/>postcollita podria ser un mètode avantatjós ja que podria prevenir infeccions<br/>latents, permetria una menor manipulació de la fruita i disminuiria potencialment<br/>els danys i ferides que es donen durant qualsevol dels tractaments de postcollita.<br/>Així mateix, es reduiria el període entre la collita i l'emmagatzemament en fred i<br/>s'evitaria la contaminació addicional per patògens que suposa el tractament químic<br/>de la fruita en el "drencher". No obstant, fins ara l'aplicació d'agents de biocontrol<br/>en el camp s'ha vist limitada per la sensibilitat que aquests tenen a l'estrès<br/>mediambiental, ja que els microorganismes tenen uns intervals de creixement molt<br/>limitats tant pel que fa a la temperatura com a la humitat.<br/>Els objectius del present estudi han estat la determinació de la dinàmica<br/>poblacional de la microflora natural de les mançanes "Golden Delicious" durant<br/>diferents estadis de desenvolupament (Capítol 2), durant la conservació en fred i<br/>durant el període de simulació de la comercialització o "shelf life" de la fruita, i<br/>avaluar l'efecte que té el tractament amb C. sake en la microflora pròpia de les<br/>mançanes (Capitol 3). D'altra banda, volia avaluar-se el potencial pràctic de la<br/>utilització de l'antagonista al camp per aconseguir un bon control de l'agent<br/>causant de la principal malaltia en postcollita de mançanes, Pénicillium expansum<br/>(Capitol 4). Tantmateix, els estudis detallats sobre l'ecofisiologia de C. sake han<br/>permès identificar mètodes per millorar la tolerància de les cèl·lules a l'estrès<br/>mediambiental, la seva viabilitat i adaptació (Capítols 5 i 6); i, mitjançant la<br/>manipulació del contingut de les reserves endògenes acumulades, millorar el<br/>creixement en el camp i aconseguir un bon nivell de biocontrol de la podridura<br/>causada per Pénicillium mitjançant el tractament a camp (Capítol 6).<br/><br/>La població microbiana total va variar segons l'estat de desenvolupament del fruit,<br/>així com també amb les condicions climàtiques. La microflora predominant en les<br/>mançanes durant el seu desenvolupament van ser les floridures Cladosporium,<br/>Alternaria spp. i els llevats blancs. D'altra banda, les floridures patògenes més<br/>importants en postcollita, P. expansum i Botrytis cinérea, rarament es van aïllar<br/>durant el desenvolupament del fruit. En canvi, la presència del gènere Pénicillium<br/>en les mançanes va esdevenir important durant la seva conservació en fred i durant<br/>el període de "shelf life" després de la conservació. La població bacteriana va ser<br/>màxima a l'estadi de borró i va disminuir durant el període de desenvolupament<br/>del fruit, essent rarament aïllades durant la collita i la conservació en fred.<br/>L'aplicació de C. sake en mançanes, dos dies abans de la collita, va reduir<br/>significativament la població de Cladosporium i Pénicillium spp. al final de la<br/>conservació en fred i durant el període de simulació de la comercialització. No<br/>obstant, l'aplicació del llevat antagonista en precollita, en mançanes foradades i<br/>inoculades artificialment va resultar menys efectiva contra la podridura per<br/>P. expansum que el tractament en postcollita amb C. saké. La població de<br/>l'antagonista aplicada en precollita sobre mançanes "Golden Delicious" i amb<br/>danys artificials, disminueix abans i més ràpidament que quan es tracta en<br/>postcollita. Es fa necessària doncs, més recerca per entendre la raó per la qual es<br/>dóna aquesta supervivència més baixa de C. sake quan s'aplica en precollita i<br/>després s'emmagatzema en fred.<br/>Es van dur a terme estudis detallats d'ecologia i fisiologia de C. sake per a<br/>identificar l'efecte de l'activitat d'aigua (ow), temperatura, pH i la seva interacció<br/>en el seu creixement per així identificar els seus límits de creixement<br/>mediambientals. Es va trobar que les condicions mediambientals en les que l'agent<br/>de biocontrol pot desenvolupar-se estan limitades per una aw mínima entre 0.90 i<br/>0.92. C. sake va resultar tolerant a un ampli rang de pH (entre 3 i 7),<br/>independentment de l'aw i la temperatura.<br/>Els polihidroxialcohols i els sucres que es van acumular en major proporció en les<br/>cèl·lules de C. sake crescudes en medi basal no modificat (NYDB) van ser arabitol,<br/>trealosa i glucosa, amb petites quantitats de glicerol i eritritol. En experiments<br/>in vitro, el creixement de C. sake en medi amb aw reduïda (0.96) va resultar en una<br/>modificació d'aquestes reserves endògenes i una millora de la viabilitat a baixaow<br/>quan es compara amb cèl·lules no modificades. En assaigs de laboratori, les<br/>cèl·lules de C. sake modificades van mantenir la seva efectivitat i fins i tot la van<br/>millorar enfront la podridura causada per P. expansum en mançanes "Golden<br/>Delicious". En assaigs de camp, però, no es van observar millores significatives en<br/>el control de la podridura per P. expansum en postcollita de mançanes foradades<br/>artificialment i infectades quan comparem cèl·lules no modificades i cèl·lulestolerants a aw baixes. Immediatament després de l'aplicació de l'antagonista en<br/>precollita, es va observar que les cèl·lules no modificades es van adherir millor a la<br/>superfície de la poma que no pas les modificades. No obstant, després d'unes hores<br/>sota condicions de camp, la població de cèl·lules aw-tolerants va augmentar<br/>significativament, mentre que la població de cèl·lules no modificades va romandre<br/>constant. És possible que els requeriments energètics per a la producció d'elevades<br/>concentracions de reserves endògenes puguin resultar en una modificació de la<br/>concentració o característiques de la matriu extracel.lular del llevat.Probablement<br/>una millora de l'adherència de les cèl·lules modificades podria donar lloc a<br/>millores en l'efectivitat.<br/>Així doncs, aquest enfoc es presenta com una via interessant per a poder<br/>aconseguir alguns avantatges en la formulació dels antagonistes, intentant fer-los<br/>més tolerants a baixes aw permetent-los-hi així, un establiment més efectiu al camp,<br/>conservant l'eficàcia com a agents de biocontrol. En aquest aspecte, l'estudi va<br/>demostrar que existeix un gran potencial per a la utilització de mitjans<br/>ecofisiològics que millorin l'adaptació ecològica dels agents de biocontrol aplicats<br/>al camp.
El desarrollo de resistencia a los fungicidas por parte de muchos patógenos de<br/>postcosecha de frutas y vegetales, la falta de substitutos adecuados a los<br/>fungicidas, y el creciente interés social sobre los peligros ambientales y de salud<br/>que tienen estos pesticidas, han generado un gran interés en el desarrollo de<br/>métodos de control alternativos que sean ambientalmente más favorables. El<br/>control biológico empleando microorganismos ha surgido como una de las<br/>alternativas más prometedoras. La levadura Candida sake (cepa CPA-1), aislada en<br/>nuestro laboratorio a partir de manzanas, ha demostrado tener actividad antagónica<br/>frente a los principales patógenos de postcosecha en fruta de pepita. Su aplicación<br/>en precosecha para el control de las enfermedades presentes en fruta de pepita en<br/>postcosecha sería beneficiosa por varias razones. En primer lugar conseguiríamos<br/>una prevención de infecciones latentes, además se requeriría una menor<br/>manipulación de la fruta y disminuiría la posibilidad de daños y heridas durante los<br/>tratamientos de postcosecha. Los períodos de tiempo entre la cosecha y la<br/>conservación en frío se reducirían y finalmente se evitaría la contaminación<br/>adicional debida a patógenos fúngicos procedentes de los tratamientos químicos de<br/>la fruta en el "drencher". Sin embargo, la aplicación de agentes de biocontrol en<br/>campo se ve limitada por la sensibilidad de los microorganismos al estrés<br/>ambiental, especialmente a la humedad relativa y a la temperatura.<br/>Los objetivos del presente estudio han sido, la determinación de la dinámica de<br/>población microbiana propia de las manzanas "Golden Delicious" a lo largo de las<br/>diferentes fases de su crecimiento (Capítulo 2), durante la conservación en frío y el<br/>período de vida útil o "shelf life", y la evaluación del efecto del tratamiento de<br/>C. sake sobre la microflora natural (Capítulo 3) . También se han llevado a cabo<br/>estudios de la aplicabilidad del agente de biocontrol en precosecha; para ello se<br/>realizaron inoculaciones en campo del antagonista con el fin de lograr un control<br/>adecuado del agente causal de la principal enfermedad de postcosecha de<br/>manzanas, P. expansum (Capítulo 4). Los estudios detallados de la ecofisiología de<br/>C. sake han fijado los métodos para mejorar la tolerancia de las células al estrés<br/>ambiental, su viabilidad y adaptación ecológica (Capítulos 5, 6) y, mediante<br/>manipulación del contenido de azúcares y polialcoholes intracelulares, el aumento<br/>de su crecimiento en campo y el mantenimiento del biocontrol de la podredumbre<br/>de Pénicillium en el tratamiento en precosecha (Capítulo 7).<br/>Se ha encontrado que la población microbiana total varía con el estado de<br/>desarrollo de la fruta y con las condiciones climáticas. La flora predominante<br/>durante el desarrollo de las manzanas fueron los mohos filamentosos<br/>Cladosporium y Alternaria spp. y las levaduras blancas. Sin embargo, los patógenos más importantes en postcosecha, P. expanswn y Botrytis cinérea,<br/>raramente fueron aislados de manzanas durante los diferentes estadios de<br/>desarrollo. Por el contrario, la presencia del género Pénicillium llegó a ser<br/>importante en las manzanas durante las etapas finales de la conservación en frío y<br/>en el período de "shelf life". La población bacteriana fue máxima en el estadio de<br/>yema y disminuyó durante el período de desarrollo de las manzanas, aislándose<br/>raramente en el momento de la cosecha y durante la conservación en frío. La<br/>aplicación en precosecha de C. saké a las manzanas dos días antes de su<br/>recolección disminuyó significativamente las poblaciones de Cladosporium y<br/>Pénicillium spp. al final de las condiciones de conservación en frío y durante el<br/>período de vida útil ambiental. Sin embargo, la aplicación en precosecha de la<br/>levadura antagonista fue menos efectiva contra la podredumbre de Pénicillium en<br/>manzanas artificialmente heridas e inoculadas que el tratamiento de postcosecha<br/>con C. sake. Las poblaciones de C. sake aplicada en precosecha sobre manzanas<br/>"Golden Delicious" y con daños artificiales, disminuyen antes y más rápidamente<br/>que cuando el tratamiento es en postcosecha. Por esta razón se necesita una<br/>investigación adicional que permita entender por qué C. sake presenta una menor<br/>supervivencia cuando la aplicación se realiza en precosecha y posterior<br/>conservación en frío. Para ello, se llevaron a cabo estudios de la ecología y<br/>fisiología de C. sake con el fin de determinar el efecto de la actividad de agua (a .),<br/>temperatura, pH y su interacción en el crecimiento del microorganismo, y poder así<br/>fijar los límites ambientales del antagonista. Se encontró que las condiciones<br/>ambientales en las cuales este agente de biocontrol crece efectivamente estaban<br/>limitadas por una aw entre 0.90 - 0.92. C. sake fue tolerante a un amplio intervalo<br/>de pH (3-7), independientemente de la temperatura y de la aw.<br/>Los principales polihidroxialcoholes y los azúcares intracelulares acumulados en<br/>C. sake crecida en un medio base no modificado (NYDB) fueron el arabitol, la<br/>trealosa y la glucosa junto con pequeñas cantidades de glicerol y eritritol. En<br/>experiencias in vitro la producción de C. sake en un medio con aw reducida (0.96)<br/>dio como resultado una modificación significativa de estas reservas endógenas y<br/>una mejora en la viabilidad a baja aw, comparada con células no modificadas. El<br/>biocontrol de P. expansum en .manzanas "Golden Delicious" se mantuvo con este<br/>inoculo modificado tolerante a baja a , y en algunos casos, incluso fue mejor en<br/>ensayos de laboratorio. Sin embargo, no se observaron mejoras significativas en el<br/>biocontrol en postcosecha de la podredumbre de P. expansum en manzanas<br/>artificialmente heridas e inoculadas en ensayos de campo con células de C. sake<br/>« .-tolerantes y no modificadas. Inmediatamente después de la aplicación en<br/>precosecha del antagonista se observó una mejor adherencia a la superficie de la<br/>manzana de las células de levadura no modificadas frente a las del inoculo modificado. No obstante, después de unas pocas horas en condiciones de campo<br/>las poblaciones del inoculo aw-tolerantes aumentaron significativamente, mientras<br/>que las poblaciones del tratamiento no modificado permanecieron sin cambios.<br/>Estos resultados nos hacen pensar que la energía necesaria para la producción de<br/>altas concentraciones de reservas endógenas pueda producir una modificación de<br/>la concentración o características de la matriz extracelular de la levadura.<br/>Probablemente una mejora en la adherencia de las células modificadas podría<br/>traducirse en una mayor efectividad.<br/>Así pues, algunas de estas ventajas ecológicas deberían ser aprovechadas en la<br/>formulación del inoculo tolerante a aw bajas para de esta forma lograr una<br/>estabilidad más efectiva en el campo, conservando su eficacia en el biocontrol.<br/>Este aspecto del estudio demostró que el empleo de medios ecofisiológicos para<br/>mejorar la adaptación ecológica de los agentes de biocontrol y para su aplicación<br/>en campo es altamente prometedora, y que ésto podría tener un profundo impacto<br/>en el desarrollo de agentes de control biológico efectivos en precosecha.
The development of resistance to fungicides by many postharvest pathogens of<br/>fruits and vegetables, a lack of adequate fungicide replacements, and growing<br/>public concern over health and environmental hazards from pesticides, have<br/>together generated new interest in the development of alternative more<br/>environmentally friendly control methods. Biological control using<br/>microorganisms has emerged as one of the most promising alternatives. The yeast<br/>Candida sake (strain CPA-1), which was isolated from the apple surface in our<br/>laboratory, has been demonstrated to have antagonistic activity against the major<br/>postharvest pathogens of pome fruits. Preharvest antagonist application for<br/>postharvest control of pome fruit diseases would be advantageous as latent<br/>infections may be prevented, less fruit manipulation would be required, and it<br/>would decrease the potential for damage and injuries during any postharvest<br/>treatments. The time periods between harvest and cold storage would be reduced<br/>and additional contamination by pathogenic fungi from drenching solutions used<br/>during chemical treatments would be avoided. However, application of biocontrol<br/>agents in the field has been limited by sensitivity to environmental stresses<br/>including a narrow relative humidity and temperature range.<br/>The aims of the present study were to determine the microbial population dynamics<br/>on Golden Delicious apples during different developmental stages (Chapter 2),<br/>during cold storage and the ambient shelf-life period, and evaluate the effect of<br/>C. sake treatment on the resident microflora (Chapter 3). Studies of the practical<br/>potential of using field inoculation of the antagonist to achieve good control the<br/>responsible agent of the major postharvest disease of apples in Spain, Pénicillium<br/>expansum, was investigated (Chapter 4). Detailed studies of the ecophysiology of<br/>C. sake identified methods for improving the environmental stress tolerance of<br/>cells, their viability and ecological fitness (Chapters 5, 6); and by manipulation of<br/>intracellular sugar alcohol and sugar content, to enhance growth in the field and<br/>conserve biocontrol of Pénicillium rot by field treatment (Chapter 7).<br/>Total microbial populations were found to vary with development stage, and with<br/>prevailing climatic conditions. The predominant mycoflora on apples during<br/>development were the filamentous fungi Cladosporium mú Alternaria spp. and<br/>white yeasts. However, the most important postharvest pathogens/1, expansum and<br/>Botrytis cinérea were seldom isolated from ripening apples. On the contrary, the<br/>presence of the Pénicillium genus became important on apples during later cold<br/>storage and ambient shelf-life period. Bacterial populations were maximum at the<br/>bud stage and decreased during the development period of apples, isolated at harvest and during cold storage. Preharvest application of C. sake to<br/>apples two days before harvest significantly decreased populations of<br/>Cladosporium and Pénicillium spp. by the end of cold storage conditions and<br/>during ambient shelf-life period. However, preharvest application of the<br/>antagonistic yeast was less effective against Pénicillium rot in artificially<br/>inoculated and wounded apples than postharvest treatment with C. sake. C, sake<br/>populations decreased faster after preharvest application than when applied<br/>postharvest during subsequent cold storage. Further research was thus needed to<br/>understand the reason for the lower survival of C. sake, when applied preharvest<br/>during subsequent cold storage. Detailed studies were carried out on the ecology<br/>and physiology of C. sake to identify the effect water activity (aw), temperature, pH<br/>and their interaction on growth and identify environmental limits of the antagonist.<br/>The environmental niche within which this biocontrol agent will effectively grow<br/>was found to be limited by about 0.90-0.92 aw. C. sake was tolerant of a wide range<br/>of pH levels (3-7) regardless of aw and temperature. The major intracellular<br/>polyols/sugars accumulated in C. sake cells grown on unmodified basal medium<br/>(NYDB) were arabitol, trehalose and glucose with small amounts of glycerol and<br/>erythritol. Production of C. sake in reduced aw media (0.96) resulted in a<br/>significant modification of these endogenous reserves and an improvement in<br/>viability at lowered aw when compared to unmodified cells in in vitro experiments.<br/>Biocontrol of P. expansum on Golden Delicious apples by these modified low owtolerant<br/>inocula was maintained, and in some cases improved in laboratory assays.<br/>However, no significant improvements were observed in postharvest biocontrol of<br/>P. expansum rot in apples artificially wounded and infected in field trials with to<br/>compare unmodified and aw-tolerant cells of C. sake. Immediately after preharvest<br/>application of the antagonist it was notable that unmodified yeast cells adhered<br/>better to the apple surfaces than the modified inocula. However, after a few hours<br/>under field conditions populations of the ow-tolerant inocula increased<br/>significantly, while those of unmodified treatment populations remained<br/>unchanged. It is also possible that the energy requirements for the production of<br/>high concentrations of endogenous reserves could result in a modification of the<br/>concentration or characteristics of the matrix. Some ecological advantages may be<br/>gained in formulating low-aw tolerant inocula for more effective establishment in<br/>the field, while conserving biocontrol efficacy. This aspect of the study<br/>demonstrated that great potential exists for using ecophysiological means for<br/>improving the ecological fitness of biocontrol agents applied in the field, and this<br/>could have a profound impact on the development of effective preharvest<br/>biological control agents for use in the field.
Keywords
plagues agrícoles; malalties i plagues; control; pomes
Subjects
631 - Agriculture in general; 632 - Plant damage, injuries. Plant diseases. Pests, organisms injurious to plants. Plant protection; 633 - Field crops and their production
Knowledge Area
Tecnologia d'Aliments
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Land | Free Full-Text | Development of a Virtual Wetland Ecological System Using VR 360° Panoramic Technology for Environmental Education
In this study, the VR 360° panoramic technology is used to develop a virtual wetland ecological system for applications in environmental education. The system provides a virtual wetland environment for autonomous exploration, where the user can conduct inquiry-based learning by cardboard VR to obtain essential information and concepts in ecological protection. It contains the learning contents of wetland ecology and creatures in Hsinchu coastal areas, northern Taiwan. To investigate the learning effectiveness of the VR system, we recruited 42 seventh graders as participants and divided them evenly into two groups. The experimental group used the virtual wetland ecological system for learning and the control group learned with conventional teaching materials. The differences of the experimental results indicated: (1) the experimental group showed a high degree of satisfaction after using the virtual wetland ecological system; (2) the learning achievement of the experimental group was significantly higher than that of the control group; (3) the learning motivation of the experimental group was significantly higher than that of the control group. The virtual wetland ecological system can enhance the learning effectiveness and learning motivation using low-cost cardboard glasses, so it is a suitable tool for promoting environmental education in remote areas.
Development of a Virtual Wetland Ecological System Using VR 360° Panoramic Technology for Environmental Education
by Kuo-Liang Ou , Shun-Ting Chu and Wernhuar Tarng *
Institute of Learning Sciences and Technologies, National Tsing Hua University, Hsinchu 30013, Taiwan
Author to whom correspondence should be addressed.
Land 2021 , 10 (8), 829; https://doi.org/10.3390/land10080829
Received: 20 July 2021 / Revised: 5 August 2021 / Accepted: 5 August 2021 / Published: 7 August 2021
Abstract
:
In this study, the VR 360° panoramic technology is used to develop a virtual wetland ecological system for applications in environmental education. The system provides a virtual wetland environment for autonomous exploration, where the user can conduct inquiry-based learning by cardboard VR to obtain essential information and concepts in ecological protection. It contains the learning contents of wetland ecology and creatures in Hsinchu coastal areas, northern Taiwan. To investigate the learning effectiveness of the VR system, we recruited 42 seventh graders as participants and divided them evenly into two groups. The experimental group used the virtual wetland ecological system for learning and the control group learned with conventional teaching materials. The differences of the experimental results indicated: (1) the experimental group showed a high degree of satisfaction after using the virtual wetland ecological system; (2) the learning achievement of the experimental group was significantly higher than that of the control group; (3) the learning motivation of the experimental group was significantly higher than that of the control group. The virtual wetland ecological system can enhance the learning effectiveness and learning motivation using low-cost cardboard glasses, so it is a suitable tool for promoting environmental education in remote areas.
Keywords:
virtual reality
;
VR 360° panoramic technology
;
cardboard VR
;
inquiry-based learning
;
wetland ecology
;
environmental education
1. Introduction
The aims of environmental education are to cultivate a sense of ethical responsibility for the environment and to convey correct knowledge, attitudes, and skills to the public for protecting and maintaining the natural environments. Environmental protection is a practice of conserving environments for the benefit of the human being and all creatures on earth. Due to the pressures of population and economic development, the natural environment is being degraded. Therefore, excessive human interference and destruction should be prevented such that the ultimate goals of co-prosperity and coexistence between humans and their environments can be achieved. In the Belgrade Charter, proposed by the United Nations Educational, Scientific and Cultural Organization (UNESCO), specifics on the goals of environmental education and relevant contents were defined. The goal is to develop a world population that is aware of and concerned about the environment as well as its associated problems [
1
].
Ecosystems, in all their diversity, possess essential functions and critical services in a chain interaction between organisms and their environments. Wetlands provide habitats and food sources for aquatic creatures, divert the flow of water during flooding events, purify water, and affect food safety [ 2 ]. Due to the lack of knowledge on the necessity of their protection, wetlands are now fragmented and threatened by the impacts of economic development [ 3 ]. To ensure the sustainability of ecosystems, several researchers and educational institutions have promoted environmental education in which field trips and recreational activities are integrated in course design to enhance environmental awareness and understanding of wetland ecology [ 4 , 5 , 6 , 7 ].
Virtual reality is an information and communication technology (ICT) to create an immersive environment where users can react in a similar way they would in real life. They can interact with the virtual environment using various devices such as the head-mounted display (HMD) and data gloves to see, hear and feel as if situated in the real environment. The combination of visual, auditory and tactile sensations through VR creates an immersive environment without damaging actual environments or causing danger to the individual [
13
]. Dubovi, Levy and Dagan [
14
] constructed a virtual environment for the acquisition of knowledge on hospital administration by using the desktop VR simulation to practice relevant medication procedures. Although the learning effectiveness was high, the level of immersion was compromised because the desktop VR was susceptible to the environmental interference.
Broyer et al. [
15
] built a virtual laboratory to organize teaching activities related to laboratory safety, providing an immersive learning environment accessible through a high-resolution HMD. Despite its favorable learning outcomes, their approach is not suitable for classroom applications because of the high cost for building the VR environment and necessity of deploying the VR module for a large number of users. With advances in smartphones and 3D display technologies, the cardboard VR can display panoramic images of virtual scenes at a low cost. Compared with the desktop VR and HMD VR, the cardboard VR is a more suitable approach for classroom teaching. It provides an immersive environment through the VR 360° panoramic technology, easy to set up and operate, and its application is not limited by time or space [
16
].
In the recent years, the applications of VR in education have been successful because learners can operate VR devices themselves to explore the learning contents in an immersive environment, and this stimulated their interest in learning and enhanced their learning effectiveness [
17
,
18
]. Relevant studies on environmental education are summarized as follows. Markowitz et al. [
19
] developed an immersive VR system to simulate the ocean acidification process. Without venturing into the deep ocean, participants freely observed and explored in the virtual marine environment. The intervention aroused their interest and helped them acquire knowledge on the effects of ocean acidification. Tarng et al. [
20
] established a virtual campus ecological pool, where students could learn about the aquatic organisms through interactive operation. They considered the VR system more interesting than a real ecological pool. The experimental results indicated that the VR system could improve learning motivation and effectiveness. In short, VR simulations may increase the motivation of students more easily in learning abstract concepts.
Given the diversity of wetland ecosystems and the complexity of environmental issues, e.g., environmental impacts by overexploitation, inquiry skills are indispensable as they play an essential role in learning wetland ecology and may often improve the learning outcome effectively. For example, after raising a question for inquiry-based learning, the teacher can ask students to make assumptions, explorations, verifications, inductions, explanations, and discussions to infer the meaning of the knowledge they have obtained for understanding the concepts [
21
,
22
]. Inquiry-based learning is a learner-centered teaching model in which students are active builders of knowledge. It can cultivate the abilities of observation, posing questions, planning and experimentation, and is therefore suitable for the instructional design in environmental education.
Combining the VR technology with inquiry-based learning to develop a VR system can provide students with suitable learning contexts for applications in environmental education. The interactive user interface enables students to explore autonomously in the virtual ecological environment, observe wetland creatures (e.g., characteristics and habitual behaviors), and initiate induction and discussion. The incorporation of VR exploration into classroom teaching can facilitate a safer and deeper learning situation than on-site teaching while avoiding the damage of wetland ecology and danger to the individual. Such inquiry-based learning is richer in contents, less restricted by weather conditions, and more interesting than conventional teaching methods [
23
,
24
].
To develop a virtual learning system on wetland ecology that is inexpensive and easy to operate, we used the VR 360° panoramic technology to design the virtual scenes of three wetland areas in northern Taiwan, including (1) Chin Cheng Lake bird-watching area, (2) Hsiang Shan wetland and (3) Shin Feng mangrove forest. Students can conduct inquiry-based learning with cardboard VR to obtain essential information and concepts in wetland ecology. They can explore in the virtual scenes to observe wetland creatures and their habitats as well as characteristics, and complete the challenge mission to learn about wetland ecology and concepts of ecological protection.
The rest of this paper is structured as follows: The next section reviews the crucial articles related to this study. In the “Virtual Wetland Ecological System” section, we describe the methodology of building the 3D panoramic wetland ecological system. In the “Teaching Experiment” section, participants’ learning effectiveness, learning motivation, and learning satisfaction are analyzed. Then, the findings of this study are described in the “Discussion” section. Finally, the conclusions and future works are given at the end of this paper.
2. Theoretical Frameworks
In this section, the related researches of environmental education, virtual reality in education, and inquiry-based learning are discussed to form the frameworks of the study.
2.1. Environmental Education
In the 1970s, the promotion of environmental conservation in many countries was aimed at resolving environmental issues through the enactment of environmental protection laws and training of conservation and education personnel. In 1972, the United Nations held the Stockholm Conference to enhance understanding of the relationship between environments and human beings by emphasizing its importance. As a result, countries were more concerned about environmental education and the related issues. In 1974, the United Nations officially proposed the International Environmental Education Program in view of the fundamental assistance of education to resolve environmental problems [
25
]. The National Environmental Education Act was passed by the U.S. Congress in 1990, a crucial step to include the Office of Environmental Education in the U.S. Environmental Protection Agency (EPA), raising the environmental education initiatives to the federal level to strength its influence [
26
]. The objective is to guide the public to participate in environmental protection activities for solving environmental problems.
In Taiwan, the Ministry of Education (MOE) issued “General Guidelines of Grades 1–9 Curriculum for Elementary and Junior High School Education” [
27
], in which “Environmental Education” is an important topic. The goal is to educate students to understand and pay attention to environmental and other relevant issues. It can also help them acquire knowledge and develop necessary skills, attitudes, motivations, and commitments in resolving environmental problems and preventing further damage to the environment. The guideline has now become a lifelong learning process focused on how to accomplish the practice of protecting the natural environments by increasing the interest and motivation toward the resolution of environmental problems.
A wetland is an area where its soil is covered by water all year or for varying periods of time. Wetlands are vital for human survival because they are the major productive environments to provide aquatic and wildlife habitats which numerous species of plants and animals depend on for survival. They can also improve water quality, store flood water and maintain surface water flow during dry seasons. Therefore, understanding wetland ecology has been an important part in environmental education.
Cachelin, Paisley and Blanchard [
8
] analyzed the differences between on-site and classroom teaching on wetland ecosystems, reporting that on-site teaching possessed greater cognitive benefits. Moreover, on-site teaching established an emotional connection between students and the environment they explored. Although classroom teaching cannot provide a sense of presence, it is the simplest and more suitable method for the promotion of environmental education in educational institutions. To remedy the situation that on-site observation is not possible in classroom teaching, many instructors have incorporated relevant teaching aids. For example, Papapanagou, Tiniakou and Georgiadis [
28
] guided students to use hypermedia application/CD-ROM and worksheets in learning wetlands as a starting point for understanding these ecosystems.
To stimulate learning motivation, Gannon [
29
] tried to enhance the understanding of sustainability by composing a story about an encounter between children and animals in a wetland. The story served as a foundation where the children were encouraged to apply an inquiry-based method to examine the impacts of humanism on environmental education. Students had the ability to discover the connections between locations and natural waterways. In this way, they developed an emotional attachment to the wetland and acquired knowledge on emerging issues (e.g., creative participation, environmental responsibility, sustainability, and water management). Shih, Chao and Kao [
30
] investigated the effectiveness of applying board games to children’s environmental education, specifically, on the wetland food chain. They designed an unplugged game in which the related environmental elements (e.g., animals, plants, hillsides, and rocks) constituted the game elements. The board game had a positive effect on learning concentration and helping children link their prior knowledge with problem-solving skills.
2.2. Virtual Reality in Education
Virtual reality is a technology integrating computer graphics and human–computer interfaces to create an immersive 3D virtual world where the user can feel as if situated in the real world [
31
]. Tarng et al. [
20
] indicated that users could interact with virtual environments through their sense organs, similar to how they could do in a real environment. Virtual reality can avoid the danger while satisfying the major requirements and it can also reduce the cost and unnecessary waste. The immersive VR provides students with a meaningful learning context, so it can be applied in a wide range of research and education. It can also trigger the intrinsic motivation for performing contextual tasks. Makransky and Peterson [
12
] discovered that immersive virtual field trips facilitated learning the climate change because the high-level interaction could enhance learning outcomes. Similar to how images are often used to illustrate complex textual descriptions, VR has the potential to help learners conceptualize 3D space and the geometric shape of an object. When learners were immersed in a VR learning environment, accelerated cognition, increased attention, and improved critical thinking had been reported [
32
].
VR is divided into various categories according to the form of display and the method of construction. Desktop VR [
33
], the most economical VR system, displays 3D scenes on a computer screen. The typical input sources include the keyboard, mouse, and joystick. In general, immersion in such systems is difficult because of the interference outside the screen. However, the user can still focus on the virtual environment if the learning content has a high quality and is well presented. Simulator VR [
34
], a device-based and environment-oriented VR system, simulates the process and experience of operating a real machine in a specific environment and it is commonly used in training drivers and pilots. Projection VR [
35
] uses several projectors to create the entire scene around the user as a 360-degree panoramic environment. Immersive VR [
36
] is the most expensive system of all and it creates the most authentic perceptual experience. It requires specific input and output devices, such as an HMD, a motion tracker and data gloves, to enable full immersion in the virtual environment for providing a multi-sensory experience.
VR is widely applied in science education. For example, Chen et al. [
37
] developed a desktop VR system to simulate earth motion for classroom application. The VR system can facilitate the clarification of astronomical concepts. To enable the conceptual cognition of relative motion, Kozhevnikov, Gurlitt and Kozhevnikov [
38
] provided students with an immersive experience using the HMD and desktop VR to explore the effects of different VR environments on learning effectiveness. Lee and Wong [
39
] incorporated the V-Frog, a commercially available desktop VR system, into a course on frog anatomy. Differences in spatial ability and learning effectiveness under the VR system and conventional teaching were discussed. In a course on learning the nanostructure of 3D crystals, Tarng et al. [
40
] built a virtual transmission electron microscope (TEM) and investigated its performance on learning achievements and learning motivation. According to the results of the above research, VR can enhance spatial cognition, motivate learners to acquire scientific knowledge, and increase the understanding of abstract concepts.
Regarding the applications of VR in environmental education, Barbalios et al. [
41
] developed a virtual lacustrine environment for learning natural resource sharing. They guided students through the formulation of water extraction and irrigation methods, and evaluated their problem-solving skills and learning achievements. The research results showed that the mean score of students by using the virtual lacustrine environment was significantly higher than that of using the conventional textbook-based teaching method. After operating the VR system, students were able to examine complex problems and find out strategies for their management and resolution.
Markowitz et al. [
19
] developed a VR system to simulate the process of ocean acidification and the users could wear headsets for an immersive experience. The researchers examined whether the VR system exerted impacts on students’ learning achievements and attitudes toward environmental protection. The analytical results indicated that following the VR experience, participants became interested in learning about the causes and effects of ocean acidification. They were also willing to explore more elements related to climate change in the ocean environment. Chang, Hsu and Jong [
42
] developed a VR system for geography courses, in which 360° panoramic images of Yehliu Geopark, Taiwan, were displayed on a web page. Peer learning activities were conducted as an experimental method. According to the experimental results, the mean scores of learning achievements, motivation, self-efficacy, critical thinking ability, and creativity were higher for the students using the VR system through the integration of peer assessment.
2.3. Inquiry-Based Learning
Inquiry-based learning is a learner-centered approach of which the key attribute is the learning process stimulated by inquiry. In this approach, the role of a teacher is to establish the interaction between students and the learning contexts. When the students encounter a problem, the teacher points out the right direction rather than giving them the answer directly. Following the direction, students can predict, observe, and explain the problems. After that, they can develop the research skills and become life-long learners. Specifically, the process of predict–observe–explain (POE) is often used to trigger the metacognition in learners [
43
]. However, when learners were not given an environment to observe and therefore not able to develop enough interpretation skills, the expected learning outcomes could not be realized [
44
].
Several studies support the effectiveness of inquiry-based learning implemented by different strategies [ 45 ], such as those based on the 5E (engage, explore, explain, elaborate, and evaluate) model [ 46 ] and the POE strategy [ 47 ]. Under the POE strategy, when students encounter a cognitive conflict between the predictions regarding a scientific topic and the observation results, the teacher can provide them with appropriate media, guide them to make observations from different perspectives, and encourage them to present evidence and explanations for them to make predictions [ 48 , 49 ].
Different versions of the POE strategy have been developed. For example, Bajar-Sales, Avilla and Camacho [
50
] modified the original POE strategy into the predict–explain–observe–explain (PEOE) strategy, under which students were instructed to provide the rationale for their predictions. Costu, Ayas and Niaz [
51
] added a second discussion and a second explanation to the original POE process. After adjusting the order of actions, they proposed the predict–discuss–explain–observe–discuss–explain (PDEODE) strategy. The modification was made considering the requirement of supplementary activities under different circumstances or based on the characteristics of different types of knowledge. The procedures are considerably flexible; however, they all comply with the following rules proposed by White and Gunstone [
47
]:
Provide predictable situations in line with students’ understanding,
Provide real scenarios and relevant questions,
Enable students to make direct and reasonable observations,
Provide students with suitable prediction methods according to the scenarios.
For the application in environmental education, Hong et al. [
52
] combined inquiry-based learning with the POE strategy and modified it into the prediction–observation–quiz–explanation (POQE) strategy by incorporating a quiz into the process. The teaching model delivered information on green energy, where students’ cognitive flow, cognitive load, and self-efficacy in studying issues concerning the generation of green power were examined. Steele, Hives and Scott [
53
] incorporated inquiry-based learning into conventional environmental education, instructing students to describe learning process through storytelling. Students were guided through active participation in learning activities and clearly presented their learning outcomes on a poster to increase the learning motivation and learning effectiveness. Bush, Sieber, Seiler and Chandler [
54
] applied the inquiry-based learning in environmental education by asking children to discuss the effects of paper and plastic products on the environment. In real practice, the above research results indicate that inquiry-based learning not only facilitates the acquisition of knowledge but also encourages students to think deeply about their roles as consumers and how they intend to promote the relevant changes to protect the environment.
In this study, a virtual wetland ecological system was designed using the VR 360° panoramic technology and inquiry-based learning approach for applications in environmental education. A teaching experiment was conducted to investigate the performance of the VR system based on the statistical results of achievement tests and questionnaire results. According to the literature review and the research purpose of this study, the research questions are listed as follows:
(1)
Is there a significant difference in learning effectiveness between the students using the VR system and conventional classroom teaching?
(2)
Is there a significant difference in learning motivation between the students using the VR system and conventional classroom teaching?
(3)
What are the levels of satisfaction in usefulness and ease of use for the students after using the VR system?
3. Virtual Wetland Ecological System
The virtual wetland ecological system is designed using the VR 360° panoramic technology to create the virtual scenes of wetland ecosystems. The user can use a smartphone equipped with cardboard glasses to explore the learning contents of wetland ecology. Such devices are portable, easy to use, low in cost, and able to display panoramic images, allowing the user to conduct observation in the virtual wetland environment with a 360-degree view as if in the real world and use the focus point to trigger the designated events, e.g., observation, transfer, and viewing information. Unlike computer-generated scenes, the 3D panoramic scenes can faithfully present the original appearance of wetland ecology. When applied in classroom teaching, the immersive VR experience is like conducting on-site teaching, and students can observe animals and plants through cardboard VR to learn about wetland knowledge and concepts of ecological protection.
The virtual wetland ecological system is designed as a smartphone-based application (app) by following the development process as shown in
Figure 1
. First, the panoramic camera is used to take 3D photographs of wetlands. Then, the ordinary photography equipment is employed to take pictures and videos of wetland plants and animals. After that, Unity 3D is used to design the virtual scenes and add the interactive objects such as road signs and icons. Finally, the user interface for observation and scene transfer is designed (
Figure 2
). When the VR system is completed, it can be downloaded and installed on a smartphone with an Android operating system. The app is ready for use if a pair of cardboard glasses is selected as the HMD. Starting the app will divide the screen into two parts for displaying the stereo image pair. The user can put the smartphone in the cardboard compartment and mount it to face for viewing the virtual scene. In cardboard VR, the interaction is achieved by focusing the viewpoint at the built-in icons to trigger the events such as observation, information and moving to another scene.
3.1. VR 360° Panoramic Scenes
The virtual wetland ecological system was designed using Unity3D, a cross-platform 2D/3D game engine developed by Unity Technologies, mainly used to design games for the platforms of Windows, MacOS, Linux, iOS, and Android, etc. The virtual scenes and user interface were developed by Unity 3D and the Google VR software development kit (SDK). The C# language was selected in Visual Studio 2017 to develop the interactive programs for triggering events. The panoramic photographs were taken by Ricoh Theta V camera and the images of user interface were drawn by Adobe photoshop. The videos of animals and plants were edited by Adobe Premiere CS6. The development process includes: (1) compilation of learning contents on wetland ecology; (2) preparation of photographs, videos, textual descriptions, and voice quizzes corresponding to different wetland areas; (3) developing the virtual scenes and user interface of the wetland ecological system; (4) exporting the VR system into an app for installation.
A common format of the panorama image is the cylindrical projection, a single rectangular image that wraps 360 degrees horizontally and 180 degrees vertically (
Figure 2
). In this study, the panoramic images were captured with Ricoh Theta V camera. One can create the virtual scenes using the 3D mesh of a sphere, and map a panoramic texture to the inside of it. An alternative way is to use the Skybox feature and render the image via a skybox material. The benefits of using the Skybox feature is that there is no need to create any meshes or to write any code at all, but the drawback is that it will typically create a larger texture, making the app size larger. After building a skybox, it is required to create a material for the texture and add the material as the scene’s skybox.
Table 1 summarizes the hardware and software involved in this study and describes the functions of these types of equipment:
In this study, the learning contents of wetland ecology and their creatures, e.g., birds, crabs and plants in Hsinchu coastal area, northern Taiwan, were designed using the panoramic photos and videos of animals and plants as well as textual descriptions about their characteristics, allowing learners to understand the habits and food sources of animals as well as the organs and functions of plants in different wetland ecological environments. Three wetland ecological areas were selected as the learning targets by considering their special landscapes and representative creatures, including (1) Chin Cheng Lake bird-watching area, (2) Hsiang Shan wetland and (3) Shin Feng mangrove forest.
When determining the observation points and learning objects in these wetland areas, the aerial photographs of the three wetland areas were obtained from Google Maps, showing the distribution of trails and the locations of observation points where the pictures and videos of animals and plants were taken. The observation points marked on the aerial photographs also represent the locations where the user can watch the crabs, birds and plants in the virtual scenes of the wetland ecological system.
There are three scenic spots in Chin Cheng Lake bird-watching area: (1) Water pumping station: The pumping station is used to adjust the water level of Chin Cheng Lake and control the opening and closing of the sluice gate. (2) Chin Cheng Lake: The intertidal wetland is used to regulate the water level of the re-claimed land, and the sandbar in the middle of the lagoon becomes a place for birds to inhabit. (3) Memorial monument: The monument is to commemorate Professor Chin Cheng Wang, who died in a traffic accident during the construction of an embankment in his African expedition.
Figure 3
shows the observation points of Chin Cheng Lake bird-watching area, including (A1) Black Sickle, (A2) Heron, (A3) Little Egret, (A4) Common Moorhen (A5) Middle Egret and (A6) Black-wing Stilt. The characteristics and food sources of the creatures in Chin Cheng Lake bird-watching area are listed in
Table 2
.
There are three scenic spots in Hsiang Shan wetland: (1) Biological museum: It has a tourist center, an audio-visual classroom, a cafe and landscape areas for visitors to look around. (2) Crab-watching trail: The trail extends about 250 meters from the shore to the sand beach. There is a heart-shaped stone tidal weir, where one can see many intertidal creatures such as crabs and mudskippers. (3) Hsiang Shan wetland: There is a muddy wetland with a variety of crabs inhabiting, and it is a resting place for many birds during migration.
Figure 4
shows the observation points of Hsiang Shan wetland, including (B1) Fiddler Crab, (B2) Milky Fiddler crab, (B3) Sentinel Crab, (B4) Mudskipper, (B5) Short-body Big-eye Crab and (B6) Soldier Crab. The characteristics and food sources of the creatures in Hsiang Shan wetland area are listed in
Table 3
.
There are two learning topics in Shin Feng mangrove forest: (1) Mangrove forest: The same family of plants are collectively referred to as mangroves. Part of the bark can be refined into red dye, so its bark is called “mangrove bark”. (2) Functions of mangroves: Mangroves are shrubs or trees that grow along tropical and subtropical coasts or at the intersection of the sea and the river. They can serve as a windbreak forest, and also have the functions of setting sand, purifying water, and protecting banks.
Figure 5
shows the observation points of Shin Feng mangrove forest, including (C1) Helicid Crab, (C2) Red-claw Crab, (C3) Seaweed Breath Root, (C4) Mangrove Propagules and (C5) Mangrove Support Root. The characteristics and food sources (crabs) or functions (mangrove) of the creatures in Shin Feng mangrove forest are listed in
Table 4
.
3.2. Inquiry-Based Learning with Cardboard VR
The operating process of the virtual ecological system is exploring the three wetlands and completing all observation tasks ( Figure 6 ). The user can undergo the challenge mission to answer questions based on the findings of observation. The users must answer all questions correctly to complete the mission, or start again if missing a challenge.
Before the students began exploration in the virtual wetland ecological system, the teacher spent about 10 minutes teaching them how to operate the system and then raised some questions related to wetland ecology for them to make predictions. After conducting a pre-test to examine the background knowledge of wetland ecology, the students were asked to complete eight tasks of finding the designated creatures in the virtual wetland areas (
Figure 7
). They had to record the observation results on the worksheets for use in the group discussion. The tasks were named according to the characteristics or habitual behaviors of the wetland creatures, and the students could enter another wetland area to continue exploration after the current tasks were completed.
To support inquiry-based learning, the icons in the virtual scenes are designed to trigger certain events. There are several types of icons to trigger different events. Considering the virtual scene of bird-watching area in
Figure 8
, the arrow icon on the left can transfer the user to another virtual scene. In the middle, the binocular icon can display the information about the wetland creature under observation, and the exclamation icon on the right can provide information about the wetland ecology. The students could explore freely in the virtual environment, watching photographs and videos of wetland creatures, to obtain information about the wetland ecology. The process was continued until all the exploration tasks listed on their worksheets had been completed.
When the students entered the selected virtual scene, they could make an observation or move to another scene by focusing at an icon to trigger the event. The observation task supports inquiry-based learning by hiding some trigger points in the virtual scenes for the user to find out the creatures in an ecological environment according to the provided hints. For example, the common moorhen often floats on open water, so they could search for the common moorhen on the lake. If an observation point appears, the students could focus at the icon to obtain further information (
Figure 9
). The pop-up window will show the information and food sources of an animal, and they could focus at the button to play a video showing the habitual behavior of the creature.
The learning process was proceeded by following the steps specified by the worksheets. After visiting the three wetland areas and completing all observation tasks, students could undergo the challenge mission (
Figure 10
). A total of five challenges had to be completed and the questions in each challenge were randomly selected from the learning contents related to a wetland area. To complete the challenge mission, the students had to answer all questions correctly. Otherwise, they were directed to start the challenge mission again. After completing the mission, they were arranged to join the group to discuss and explain the findings during observation to complete the POE process.
4. Teaching Experiment
In this study, a teaching experiment was conducted to evaluate the learning effectiveness of the virtual wetland ecological system and the levels of satisfaction after using the system. We recruited 42 seventh graders (24 females and 18 males with ages between 12 to 13) from a junior high school in Pingtung County, southern Taiwan (not within the proximity of wetlands) as participants and divided them evenly into two groups (21 students in each group). All the participants did not have any experience of using AR nor VR equipment before this experiment. A quasi-experimental design was adopted. The experimental group used the VR system for learning and the control group used conventional teaching materials, respectively. The POE strategy and inquiry-based learning approach were implemented in the learning activities for both groups. The learning effectiveness and learning motivation were assessed using a wetland ecology achievement test (including pre-test and post-test) and a learning motivation scale. In addition, a system satisfaction questionnaire survey was conducted to understand the acceptance of the VR system by the experimental group (
Figure 11
).
According to the POE strategy, the learning process was divided into three stages. Before the interventions, the observation tasks, cause of wetland destruction and current enactments of wetland protection were explained to the students. Subsequently, a pre-test was performed to examine their background knowledge on wetland ecology. In the first stage, students were asked to predict the problems they would encounter in wetland environments. In the second stage, the control group was given multimedia teaching materials while the experimental group was instructed to use the VR system to perform observation tasks (
Figure 12
). The learning contents were related to the characteristics, habitats and food sources of wetland animals as well as the organs and functions of wetland plants. In the third stage, the students completed the post-test on wetland ecology after the group discussion by sharing their findings during observations and comparing their worksheets for correct solutions. In the teaching experiment, both groups were instructed by the same teacher for the same amount of time to ensure consistency and prevent learning outcomes from being affected by different teaching styles.
4.1. Learning Effectiveness
The performance of the VR system on learning achievements was evaluated in the context of environmental education by analyzing the difference between the pre-test and post-test (Cronbach’s α = 0.70) scores for each group through descriptive statistics. As shown in
Table 5
, the post-test score of the experimental group is higher than that of the control group, and the standard deviation of the experimental group is smaller than that of the control group, indicating the post-test score of the experimental group is distributed more concentrated. The paired-sample t-test results reveal significant differences between the pre-test and post-test scores for the experimental group (
t
= −13.26 and
p
< 0.001) and the control group (
t
= −8.41 and
p
< 0.001). The results suggest that the participants obtained knowledge on wetland ecology effectively through both types of teaching methods.
To further determine if two groups had a significant difference in learning achievements, a one-way analysis of covariance (ANCOVA) is conducted by using the pre-test score as the covariate, the learning method as the independent variable, and the post-test score as the dependent variable. As shown in Table 6 , the between-group difference is significant with F = 14.45 and p < 0.001, indicating a significant difference in progress between the two groups because different teaching tools were used.
It is inferred that the virtual wetland ecological system facilitated the experimental group to observe wetland creatures in the VR environments, enabling the acquisition of knowledge on wetland biology and leaving a deep impression after autonomous exploration. Therefore, combination of cardboard VR with inquiry-based learning could enhance the learning effectiveness on wetland ecology in this intervention.
4.2. Learning Motivation
The between-group differences in learning motivation after the interventions were examined using a 5-point Likert scale, with “strongly disagree” and “strongly agree” corresponding to 1 and 5 points, respectively. An expert in the study area of wetland ecology reviewed the questionnaire for examining its validity, and the Cronbach’s α = 0.93, showing a high reliability. The mean score and standard deviation for each question were analyzed through an independent sample
t
-test to analyze if there were significant differences in learning motivation about wetland ecology between the two groups due to the use of different learning tools (
Table 7
).
According to the questionnaire results, the mean scores of the experimental group for all questions were higher than those of the control group. About two-thirds of the questions received an average score higher than four, between the responses of agree and strongly agree. Only the means of questions 3, 5, 8, 9, and 12 were slightly less than four. A possible reason was that participants in the experimental group did not know how to use the VR system at the beginning and therefore they needed the teacher’s assistance (question 3). During the exploration tasks, some students focused on completing their worksheets and therefore seldom took off the cardboard glasses to discuss with others (question 5 and 9). After the class, some students realized that wetland ecology was very interesting, but they did not know how to learn or tell others about it (question 8 and 12). From the significant differences on questions 6 and 10, it can be inferred that the experimental group was able to observe the virtual wetlands and thus found it easier to learn. This also explains why the experimental group developed a greater interest in acquiring further knowledge on wetland ecology (questions 2, 11 and 12).
The results of independent sample
t
-test (
Table 8
) show the difference of learning motivation between the two groups. The mean (SD) of the experimental group is 53.24 (9.85), whereas the mean (SD) of the control group is 43.24 (10.33). The learning motivation of the experimental group was higher than that of the control group. The
t
-test results (
t
= −3.21 and
p
= 0.003 < 0.01) reveal that the combination of cardboard VR with inquiry-based learning was effective in stimulating learning motivation. Different from that of conventional teaching, the presentation of learning contents in the VR system increased the interest and willingness of students in exploring the knowledge of wetland ecology.
4.3. System Satisfaction
The system satisfaction was measured through a questionnaire survey, including 15 questions divided into three dimensions, i.e., interface design, learning content, and operating experience (
Table 9
). Each dimension contains five questions, evaluated by a 5-point Likert scale. The purpose of the questionnaire was to understand participants’ learning experience and collect their feedback on the VR system. The questionnaire has a high reliability with Cronbach’s α = 0.88. The results could be used as a reference for future improvement on the system design. The mean scores of most questions exceeded four points, indicating the levels of satisfaction mainly fall between “satisfied” and “highly satisfied”. The dimensional means of the interface design, learning contents, and operating experience (4.36, 4.31, and 4.15, respectively) all exceed four points, and the average score of overall satisfaction is 4.27, revealing most participants were satisfied with the experience of exploring the virtual wetland environments using the VR system.
Among all dimensions, only Question 12 (“I think this system is smooth and pleasant to use for ecological observation, including the transfer between scenes”) and Question 13 (“I did not feel dizzy when exploring the wetland environments”) had mean scores lower than four points. This is attributable to some participants’ reports of experiencing occasional physical discomfort when wearing cardboard glasses, specifically, the symptoms of dizziness and nausea resulting from motion sickness [ 55 ].
5. Discussion
According to the experimental results, students in both groups made significant progress in learning the knowledge of wetland ecology, indicating both the VR system and the traditional teaching method could improve their learning achievements. However, the ANCOVA results showed a significant difference between the progress of the two groups, and the experimental group performed better than the control group, indicating the VR system was more effective than the multimedia teaching materials because the former provided a virtual ecological environment where the learners could explore and observe wetland creatures to enhance the learning effectiveness. The results are the same as those reported in [
20
,
40
,
41
], showing that learners had better cognition, attention, and critical thinking in virtual learning environments to improve learning outcomes [
32
].
The questionnaire results indicated a significant difference in learning motivation between the two groups. The learning motivation for the experimental group was higher than that of the control group because the observation tasks in the VR system supported inquiry-based learning by hiding trigger points in the virtual scenes for learners to discover the creatures in an ecological environment according to their habitat information. It is more interesting than watching the pictures and videos of wetland ecology. The results are similar to those obtained in [
16
], indicating the immersive cardboard VR can provide positive educational experiences while reducing simulator sickness. The results also supported the findings in [
11
,
19
,
42
] because learners could conduct autonomous exploration in the virtual ecological environments and complete the challenge mission to obtain the knowledge about wetland ecology. Consequently, the learning motivation, critical thinking ability and creativity were higher than those receiving the conventional instruction, showing the VR 360° technology is suitable for environmental education.
The costs of cardboard VR devices are less than
$
20, much lower than that of the HMD. The users only need a smartphone, cardboard glasses and the VR system app for learning. In general, an HMD, including a fully immersive VR headset and a controller, costs more than
$
500, and the highly immersive VR application requires a lot of computing power compared to the cardboard VR devices. Besides, the HMD user needs a computer with powerful CPU and graphics card to execute the VR software. Despite the increasing popularity and applications, the immersive VR still has some drawbacks and limitations. For example, the heavy HMD equipment and VR motion sickness may affect the willingness of using VR software. Furthermore, when the users are wearing a VR device, they cannot see the surroundings and the lack of vision may cause an accident.
In summary, this study developed a cardboard VR application for students to learn wetland ecology; it has several advantages over other VR systems, including:
Low costs: Student have opportunities to learn with smartphones; therefore, they can observe the creatures of wetland ecological environments easily.
Easy to use: The light-weighted cardboard glasses allow students to be immersed in the virtual environment without wearing heavy HMD devices.
Ubiquity: Students can join the learning activities in a classroom or at home without computers or Wi-Fi connection.
Moreover, this study employed an inquiry-based learning approach and VR 360° panoramic technology for applications in environmental education. These innovative solutions supported students to observe the real scenarios of wetland ecology without damaging natural environments or causing danger to the individual. Meanwhile, an interactive user interface was designed for students to trigger the events in the virtual scenes. With the help of VR 360° virtual wetland ecological applications, students could learn by following the steps of POE strategy individually, and the learning outcomes, motivation, and satisfaction were better than those of traditional POE with worksheets only.
6. Conclusions and Future Works
Many wetlands are disappearing because of overdevelopment, corruption, and failure to enforce environment laws. To prevent further damage to these valuable ecosystems by protecting them and enabling their sustainable development, it is important that more people must learn the importance of wetland ecosystems. Environmental education plays an essential role in this context, particularly in formal education, to conserve the wetland ecosystems. How to increase students’ learning motivation and learning effectiveness still remains a tough challenge for educators to overcome. The application of VR technology in environmental education can enable the integration of conventional teaching strategies with immersive environments to simulate real-world situations. In this study, the VR 360° panoramic technology was combined with the inquiry-based learning approach to develop a virtual wetland ecological system for learners to obtain the knowledge of wetland ecology and concepts of environmental protection.
6.1. Research Findings
A teaching experiment was conducted to evaluate the performance of the VR system, and the learning contents included wetland ecology and characteristics of creatures. We recruited 42 seventh graders as participants from a junior high school, not within the proximity of wetlands. The participants completed the pre-test and post-test before and after the interventions as well as the motivation scale and satisfaction questionnaire to evaluate the learning effectiveness, learning motivation and user satisfaction after using the VR system. The experimental results are listed as follows:
(1)
The combination of virtual wetland ecology with inquiry-based learning was effective in enhancing learning achievements.
The experimental results revealed that the inquiry-based learning approach could enhance the learning achievements of experimental group and control group. According to the ANCOVA results, the effectiveness of the former is significantly higher than that of the latter, confirming the combination of inquiry-based learning with the VR system is more effective than that with the conventional multimedia.
(2)
The combination of the VR 360° panoramic technology with inquiry-based learning was effective in increasing learning motivation.
According to the questionnaire results, the scores of the experimental group in each question were higher than those of the control group, especially the stimulation of interesting learning and motivation in the exploration of wetland information. However, it is worth to note that some participants in the experimental group could only express their opinions or engage in discussion with peers when conducting the observation activities because it was difficult to do so while wearing the cardboard glasses. This problem requires special attention in the design of future interventions.
(3)
Participants were satisfied with the virtual wetland ecological system.
The system presents the panoramic scenes of real wetland environments for learners to explore autonomously. The advantages include a lower cost and easier operation. During the teaching experiment, each participant could use cardboard glasses for inquiry-based learning. Except for some participants who felt slightly dizzy while using the VR system, the others were mainly satisfied with its performance. The average scores for the dimensions of interface design, learning contents, and operating experience are 4.36, 4.31, and 4.15, respectively, and the overall average score of the VR system is 4.27, indicating most participants were satisfied with its usefulness and ease of use.
In summary, the virtual wetland ecological system is easy to use and useful in learning wetland ecology. Exploration and interaction with cardboard VR can help increase learning motivation and learning effectiveness. Therefore, it is a suitable tool for the promotion of environmental education in the context of formal education.
6.2. Future Works
The inquiry-based learning approach on VR systems can be applied to other courses, and our future works include the extension of educational applications to:
(1)
Learning space and time concepts in special theory of relativity.
The students can take a spacecraft approaching the light speed to travel in the universe and witness the phenomenon of “Moving rulers are shorter” and “Moving clocks run slow” as well as discover the oncoming spacecraft is moving only closer to instead of faster than the light speed. Virtual reality can concretize and visualize the space-time concepts by allowing learners to control the speed of the spacecraft to observe the change of time and length in different coordinate systems, which is helpful for understanding the abstract concepts in the special theory of relativity.
(2)
VR experimental systems for learning optics and electric circuits.
The students can use the concave lens, convex lens and a candlestick in the VR optical system to observe how the image of a candlestick is projected to the screen and the change of its size by adjusting the position of the candlestick from inside to outside of the focal length. They can also conduct an electric-circuit experiment using the VR circuit system to measure the current and voltage using the elements of batteries, wires, resistors and light bulbs for the cases of parallel and serial connections.
Author Contributions
Investigation and formal analysis; S.-T.C.; methodology and investigation: K.-L.O.; writing—review and editing: W.T. All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by the Ministry of Science and Technology (MOST), Taiwan under the grant number MOST 109-2511-H-007-006-MY3.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
The data presented in this study are available on request from the corresponding author.
Conflicts of Interest
The authors declare no competing interests regarding the publication of this paper.
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Figure 1. The virtual wetland ecological system for inquiry-based learning.
Figure 1. The virtual wetland ecological system for inquiry-based learning.
Figure 2. Using Unity3D to design the virtual scenes and user interface.
Figure 2. Using Unity3D to design the virtual scenes and user interface.
Figure 3. Chin Cheng Lake bird-watching area and its observation points.
Figure 3. Chin Cheng Lake bird-watching area and its observation points.
Figure 4. Hsiang Shan wetland and its observation points.
Figure 5. Shin Feng mangrove forest and its observation points.
Figure 5. Shin Feng mangrove forest and its observation points.
Figure 6. Operating process of the virtual wetland ecological system.
Figure 6. Operating process of the virtual wetland ecological system.
Figure 7. The observation tasks of finding creatures in the virtual wetland areas.
Figure 7. The observation tasks of finding creatures in the virtual wetland areas.
Figure 8. The icons for wetland or creature information and scene transfer.
Figure 8. The icons for wetland or creature information and scene transfer.
Figure 9. Searching for hidden icons to obtain the information about a creature.
Figure 9. Searching for hidden icons to obtain the information about a creature.
Figure 10. Answering a question in the challenge mission of Hsiang Shan wetland.
Figure 11. Flowchart of the teaching experiment by two groups.
Figure 11. Flowchart of the teaching experiment by two groups.
Figure 12. Learning activities of ( a ) the control group and ( b ) the experimental group.
Figure 12. Learning activities of ( a ) the control group and ( b ) the experimental group.
Table 1. The equipment and the functions involved in this study.
Table 1. The equipment and the functions involved in this study.
Category Equipment Name Function Hardware Smartphone Provids the user interface of displaying the virtual wetland ecological system scenes and supports the interactive interface for students’ inquiry-based learning. Cardboard glasses Transfer the stereo images on smartphone into VR 360° immmersive environment in HMD for students’ observation and learning. Panoramic camera Captures 360-degree panoramic pictures of wetlands for teachers to build the VR 360° scenes. Photography camera Captures ordinary pictures and movie clips of wetlands for teachers to build interactive learning materials. Software Unity 3D The editor for constructing the VR 360° wetland ecological system scenes. Visual Studio 2017 The editor for constructing the interactive functions of learning events. Adobe CS6 The editor for editing pictures and movie clips of learning meterials.
Table 2. Chin Cheng Lake bird-watching area and its creatures’ characteristics and food sources.
Table 2. Chin Cheng Lake bird-watching area and its creatures’ characteristics and food sources.
Wetland Creatures Characteristics and Food Sources A1. Black Sickle Characteristics The head and neck are black; the beak is also black, long and bent downward, and the body is white. It is an invasive species to snatch the original bird’s habitat. Food Sources The black sickle pecks food on the ground and its main food sources are insects, crustaceans, molluscs, fish, frogs, bird eggs and small mammals. A2. Heron Characteristics The back is pale gray and the beak is yellow. It is often standing on the shore of lakes or in shallow water, waiting to peck aquatic animals as they swim closer. Food Sources The food sources of herons are mainly fish, frogs, shrimps, crabs, snakes and chicks. Herons are invertebrates, and they eat plants occasionally. A3. Little Egret Characteristics The whole body is white, with a slender beak and black feet. It usually appears on flat ground, streams, paddy fields, estuaries and sandbars. Food Sources The little egert has a sharp beak to prey, mainly on fish, shrimp, frogs and aquatic insects, and sometimes shellfish and reptiles. A4. Common Moorhen Characteristics The whole body is black and gray. The beak is red, the tip of the beak is yellow, and the feet are yellow-green. The common moorhen can fly a short distance, and it often floats on open water. Food Sources It is omnivorous, eating plants and animals. The plants include algae, aquatic plants and seeds, and the animals are aquatic insects, shrimps and crabs, and small fish. A5. Middle Egret Characteristics The whole body has white feathers. The yellow beak is shorter than that of the little egret, but the body is larger. The middle egret often appears in fish farms, marshes, sandbanks, and estuaries. Food Sources The food consists of fish, frogs, shrimps, crabs, aquatic insects, grasshoppers, lizards and chicks. When foraging, they usually stand still at the water edge or in shallow water, waiting to peck the preys as they swim near. A6. Black-wing Stilt Characteristics The wings are black, the beak is slender and black, and the feet are slender and dark pink. When walking, the steps are steady and elegant, and they often feed on the water at the height of the foot joints in deep water. Food Sources The black-wing stilt mainly preys on aquatic animals, including aquatic insects and their larvae, crustaceans, tadpoles and small fish; it will sweep left and right in the water with its beak, and go forward to hunt prey.
Table 3. Hsiang Shan wetland area and its creatures’ characteristics and food sources.
Table 3. Hsiang Shan wetland area and its creatures’ characteristics and food sources.
Table 4. Shin Feng mangrove forest and its creatures’ characteristics, food sources and functions.
Table 4. Shin Feng mangrove forest and its creatures’ characteristics, food sources and functions.
Wetland Creatures Characteristics and Food Sources C1. Helicid Crab Characteristics The helicid crab has a thick blue-brown carapace with H-shaped dents. It inhabits the mudflats in the intertidal zone of the estuary and can burrow holes for home. Food sources It is omnivorous and preys on fish, shrimps and crabs, and also eats viviparous seedlings, algae, soil organic matter and organic debris. C2. Red-claw Crab Characteristics The body is dark green or black, and the four pairs of steps have long hairs. They inhabit the mudbanks of the estuary and the trunks of the mangroves. Food sources The red-claw crab feeds on fallen leaves, dead branches, and fruits of mangroves. It also preys on small fiddler crabs, insects and worms, but does not filter food. C3. Seaweed Breath Root Characteristics Due to the muddy ground being unstable and in an oxygen-deficient state, it is difficult to obtain sufficient oxygen. The roots of seaweed grow radially from the bottom of the tree trunk, and slender roots grow upward on the muddy ground. Functions The distribution area is active and wide, and it can grow steadily on mud, and many slender respiratory roots get more oxygen directly from the air. C4. Mangrove Propagules Characteristics The mangrove environment is not suitable for seed germination and seedling growth, so the viviparous fruit mechanism will develop. Functions The seeds remain on mother plants to absorb nutrients and germinate into seedlings, and then continue to grow and mature before falling off from the mother plant. C5. Mangrove Support Root Characteristics Due to the muddy ground being unstable and in an oxygen-deficient state, it is not easy to get enough oxygen, thus a special root structure has developed. Functions Standing stably on the mud ground, the roots are partially exposed in the air, with breathing and supporting functions for more oxygen to be obtained.
Table 5. Descriptive statistics of learning achievements and results of paired-sample t -test.
Table 5. Descriptive statistics of learning achievements and results of paired-sample t -test.
Group Pre-Test SD Post-Test SD t p Experimental Group ( n = 21) 40.95 15.78 87.14 10.79 −13.26 0.000 *** Control Group ( n = 21) 47.62 11.69 74.76 13.46 −8.41 0.000 ***
*** p < 0.001.
Table 6. ANCOVA results on learning effectiveness between the two groups.
Table 6. ANCOVA results on learning effectiveness between the two groups.
Source of Variance Type III Sum of Squares Degree of Freedom F p η 2 Pre-test Scores 569.25 1 4.12 0.049 * 0.096 Group 1994.22 1 14.45 0.000 *** 0.27 Deviation 5383.13 39 Sum 282800 42
* p < 0.05, *** p < 0.001.
Table 7. Questionnaire and independent sample t -test results on learning motivation for both groups.
Table 7. Questionnaire and independent sample t -test results on learning motivation for both groups.
Questions Experimental Group Control Group p Mean SD Mean SD 1. I think the wetland ecology is worthy of exploration and learning. 4.57 0.75 3.76 1.04 0.006 ** 2. I find it interesting to learn about the wetland ecosystems and the creatures in them. 4.29 1.06 3.62 0.86 0.031 * 3. I can acquire knowledge about wetland ecology by myself without my teacher’s assistance. 3.76 1.22 3.10 1.04 0.064 4. This course encourages me to actively acquire knowledge on wetland ecology. 4.14 1.06 3.33 0.97 0.014 * 5. I engaged in discussion with my classmates during the course. 3.86 1.28 3.62 1.02 0.509 6. I think the course content is clear, understandable, and easy to learn. 4.43 0.87 3.10 0.83 0.000 *** 7. I am curious about plants and animals in the wetland ecosystem and would like to know more about them. 4.14 1.06 3.48 0.93 0.036 * 8. After acquiring the knowledge on wetland ecology in this class, I would learn about them in other ways in my own time. 3.86 1.01 3.43 0.87 0.149 9. During the class, I proactively expressed my opinions in discussion. 3.86 1.11 2.86 1.06 0.005 ** 10. After the class, I would like to learn more about other ecosystems. 4.38 0.92 3.38 0.97 0.001 ** 11. Now that the class has ended, I would like to visit wetlands and make ecological observations. 4.29 1.23 3.33 1.02 0.009 ** 12. After the class, I would like to tell others about wetland ecology. 3.43 1.43 2.90 1.26 0.216 13. I would like to learn more about wetland ecosystems and protect them. 4.24 0.89 3.33 0.97 0.003 **
Table 8. Group means and results of independent sample t -test on learning motivation.
Table 8. Group means and results of independent sample t -test on learning motivation.
Group Samples Mean SD t p Experimental group 21 53.24/65 9.85 −3.21 0.003 ** Control group 21 43.24/65 10.33
** p < 0.01.
Table 9. Questionnaire results of user satisfaction for the experimental group.
Table 9. Questionnaire results of user satisfaction for the experimental group.
Dimension Questions Mean SD Interface Design 1. The icons and text descriptions were of appropriate size. 4.37 0.98 2. The direction guide icons were extremely helpful for ecological observation. 4.44 0.77 3. The task progress was clearly displayed. 4.23 1.11 4. The icons did not occupy an excessive portion of the field of view. 4.26 1.14 5. The observation point icons correspond to the locations of the actual scene. 4.49 0.74 Dimensional Satisfaction 4.36 0.95 Learning Contents 6. I clearly understood the textual descriptions of the plants and animals. 4.37 0.93 7. I was able to clearly observe the appearance and characteristics of the plants and animals. 4.33 0.87 8. The observation point icons can instantly indicate the location of the observation targets. 4.09 1.11 9. The text descriptions of the test questions were simple and clear. 4.28 0.98 10. This system enables me to understand the special behaviors of wetland organisms. 4.47 0.74 Dimensional Satisfaction 4.31 0.93 Operating Experience 11. This system is useful and easy to operate. 4.21 0.94 12. This system is smooth and pleasant to use for ecological observation, including the transfer between scenes. 3.84 1.17 13. I did not feel dizzy when exploring the wetland environments. 3.79 1.32 14. This system stimulates learners’ interest in exploring wetland ecosystems. 4.37 0.87 15. The system is applicable to learning content on other subjects. 4.53 0.74 Dimensional Satisfaction 4.15 1.01 Overall Satisfaction 4.27 0.96
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Ou, K.-L.; Chu, S.-T.; Tarng, W. Development of a Virtual Wetland Ecological System Using VR 360° Panoramic Technology for Environmental Education. Land 2021, 10, 829.
https://doi.org/10.3390/land10080829
AMA Style
Ou K-L, Chu S-T, Tarng W. Development of a Virtual Wetland Ecological System Using VR 360° Panoramic Technology for Environmental Education. Land. 2021; 10(8):829.
https://doi.org/10.3390/land10080829
Chicago/Turabian Style
Ou, Kuo-Liang, Shun-Ting Chu, and Wernhuar Tarng. 2021. "Development of a Virtual Wetland Ecological System Using VR 360° Panoramic Technology for Environmental Education" Land10, no. 8: 829.
https://doi.org/10.3390/land10080829
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Ou, K.-L.; Chu, S.-T.; Tarng, W. Development of a Virtual Wetland Ecological System Using VR 360° Panoramic Technology for Environmental Education. Land 2021, 10, 829.
https://doi.org/10.3390/land10080829
AMA Style
Ou K-L, Chu S-T, Tarng W. Development of a Virtual Wetland Ecological System Using VR 360° Panoramic Technology for Environmental Education. Land. 2021; 10(8):829.
https://doi.org/10.3390/land10080829
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Comparison of premature and full term milk allergic patients | Download Scientific Diagram
Download scientific diagram | Comparison of premature and full term milk allergic patients from publication: Milk allergy in the neonatal intensive care unit: comparison between premature and full-term neonates | There have been several reports on neonates with milk allergy in a neonatal ward. This type of allergy is mostly categorized as a non-IgE-mediated food allergy. Although most cases of milk allergy occur in the first few months of life, the differences in clinical... | Neonates, Newborn Infant and Prematurity | ResearchGate, the professional network for scientists.
Comparison of premature and full term milk allergic patients
Milk allergy in the neonatal intensive care unit: comparison between premature and full-term neonates
Full-text available
Harumi Ohtsuka
There have been several reports on neonates with milk allergy in a neonatal ward. This type of allergy is mostly categorized as a non-IgE-mediated food allergy. Although most cases of milk allergy occur in the first few months of life, the differences in clinical characteristics between premature and full-term neonates are still unclear.
This study...
Contexts in source publication
Context 1
... regard to maturity, 12 milk allergic patients were premature (7 males, 5 females) and 12 were full-term neonates (7 males, 5 females). Their characteristics are shown in Table 1. Seven premature patients were low birth weight infants, 3 were very low birth weight infants, and 2 were extremely low birth weight infants. ...
Context 2
... symptoms were observed most frequently, such as vomiting or bloody stools. Nonspecific symptoms, such as apnea and cyanosis, were present in some cases (Table 1). ...
Context 3
... features, such as eosinophil counts in peripheral blood, milk-specific IgE antibody, and positive C-reactive protein, are shown in Table 1. There were no differences in laboratory findings between premature and full-term patients. ...
Arnaldo Ganc
Allergic colitis is a clinical manifestation of food allergy during the first months of life. It is estimated that genetic factors play a role in the expression of this allergic disease. This case report described the clinical progress of infants who were cousins from two distinct family groups with allergic colitis. Five infants under six months o...
Citations
... The most common sign and symptoms of food allergy include tingling and itching in the skin and mouth, rashes, angioedema, dermatitis, as well as in the gastrointestinal tract including vomiting, abdominal cramping, nausea, diarrhea and in the respiratory tract disorder including rhinitis, asthma and laryngeal edema.
[23]
[24][25] Anaphylactic shock is the most frightening symptom which is induced by a particular food that is acute in onset, occurring within minutes or hours, and without proper treatment, it may lead to death badly. [26,27] Much other allergic disorder has been found in different organ systems that increase the risk of other allergic condition due to consuming allergic food items. ...
8
Although we are able to use oral food challenges and blood tests for diagnosis of food allergy, these methods are seldom undertaken during the neonatal period. 3,4 Especially the diagnosis by blood tests is also limited for ELBW infants because relatively huge amount of blood volume is required and it is affected by variable conditions such as NEC, neonatal sepsis etc. 3,4 Thus, diagnosis of food allergy in preterm baby most often is based on clinical suspicion, gastrointestinal symptoms after cow's milk product exposure and resolution of symptoms with bowel rest or change to an amino acidbased formula. ...
... 6,9 However, serum-specific IgE antibodies have been detected in few patient with atypical food protein-induced enterocolitis.
8,
10 Symptoms such as vomiting, diarrhea, abdominal distension, bloody stools, or lethargy are often associated with the initial signs of NEC in ELBW infants. 5,7 NEC may occur at any time, but symptoms of cow's milk-induced enterocolitis in neonate present usually after 32 weeks corrected gestational age and rarely develop before 6 weeks of life. ...
... 5,7 NEC may occur at any time, but symptoms of cow's milk-induced enterocolitis in neonate present usually after 32 weeks corrected gestational age and rarely develop before 6 weeks of life. 5,
8,
11 In preterm infant with cow's milk-induced enterocolitis, peripheral eosinophilia is commonly observed. 5,7,8 Several studies have reported that cases initially diagnosed with NEC are more likely to be cow's milk-induced enterocolitis, if they have less leukopenia, less thrombocytopenia, and more eosinophilia. ...
... It is postulated that premature infants require T helper 2 cell adaptive immune maturation for the development of allergic symptoms, which occurs between 30 and 32 weeks of age, and may account for delayed presentation until after this time.
25
However, challenges remain in the recognition and diagnosis of CMPA in the preterm infant. 8 Among a myriad of issues relating to prematurity, VLBW infants are at high risk of gastrointestinal complications including NEC and feed intolerances. ...
Feeding practices and the prevalence of cow's milk protein allergy in Irish preterm infants
Background
The prevalence of cow's-milk protein allergy (CMPA) is between 2% and 3% and symptoms vary depending on underlying immune mechanism at play. Breast milk is the optimal nutrition for premature infants and breast milk fortifiers (BMF) are commonly used to optimise growth and nutrition. BMF are typically derived from cow's milk and, as such, preterm infants are exposed to cow's milk in the first weeks of life. Previously, preterm infants were suspected to have a higher risk of allergen development because of early antigen exposure and increased gut permeability. The primary aim of the present study was to evaluate the prevalence of CMPA among very preterm (<32 weeks) and/or very low birth weight (VLBW) infants. The secondary aim was to describe feeding practices, specifically the breastfeeding rates and specialist, non-standard formula use in this cohort over the first 6 months of life.
Methods
This was a retrospective study performed in a large tertiary maternity hospital (8500 deliveries/year and 110 very preterm infants/year) in Dublin, Ireland over a 3-year period, 2017–2020. Infants born very preterm and/or VLBW who were followed in the outpatient clinic until 6 months corrected gestational age (CGA) were included. Hospital ethical approval was obtained.
Results
One hundred and forty-four infants were included with a median birth weight of 1338 g. No infant had a diagnosis of CMPA when leaving the neonatal intensive care unit (NICU) but, by 6 months CGA, this increased to 1.4% (n = 2). Upon discharge from the NICU, 88 infants (61%) were receiving at least some breast milk, decreasing to 13 (9.1%) at 6 months CGA. Those who were receiving exclusive breast milk at discharge were significantly more likely to still be receiving any breast milk at three (p ≤ 0.001) and 6 months ( p ≤ 0.001) CGA compared to those combined feeding or exclusively formula feeding. At 6 months CGA, 18.9% (n = 27) were attending a dietician and 31.5% (n = 45) were using specialist, non-standard infant formula.
Conclusions
The prevalence of CMPA in this cohort was 1.4%, which is similar to the reported prevalence of CMPA in the general paediatric population. Infants who were discharged from NICU exclusively breastfeeding were more likely to be receiving any breast milk at outpatient follow-up. This highlights the importance of on going dietetic and lactation support in the outpatient setting for this vulnerable cohort.
Key points
• The prevalence of CMPA in our cohort was similar to the previously determined prevalence in the general paediatric population.
• The significant use of specialist formula among ex preterm/VLBW infants during the first year of life conveys the need for accessible dietetic services.
• Breastfeeding rates were lower in the ex preterm cohort compared to term infants in Ireland. Breastfeeding initiation and support in the NICU is extremely important for sustaining breastfeeding rates at home following discharge.
... Numerous perinatal factors can influence the development of CMA and FAs, but the relationship between them is still controversial [59,
60]
. Sardecka et al. reported an increased risk of CMA in premature newborns, as previously noted [61], which may result from increased intestinal permeability [52]. ...
Cow's Milk Protein Allergy as a Model of Food Allergies
Full-text available
Cow's milk allergy (CMA) is one of the most common food allergies in infants, and its prevalence has increased over recent years. In the present paper, we focus on CMA as a model of food allergies in children. Understanding the diagnostic features of CMA is essential in order to manage patients with this disorder, guide the use of an elimination diet, and find the best moment to start an oral food challenge (OFC) and liberalize the diet. To date, no shared tolerance markers for the diagnosis of food allergy have been identified, and OFC remains the gold standard. Recently, oral immunotherapy (OIT) has emerged as a new therapeutic strategy and has changed the natural history of CMA. Before this, patients had to strictly avoid the food allergen, resulting in a decline in quality of life and subsequent nutritional, social, and psychological impairments. Thanks to the introduction of OIT, the passive approach involving rigid exclusion has changed to a proactive one. Both the heterogeneity in the diagnostic process among the studies and the variability of OIT data limit the comprehension of the real epidemiology of CMA, and, consequentially, its natural history. Therefore, well-planned randomized controlled trials are needed to standardize CMA diagnosis, prevention, and treatment strategies.
... It is widely accepted that cow's milk allergy is much less frequent in breastfed infants [6]. In a single-center retrospective study, Morita et al. reported that 83% of infants with cow's milk allergy were fed cow's milk-based formula
[7]
. Although breastfeeding has not been shown to reduce cow's milk protein allergy as reported in a recent systematic review [8], breastfeeding is regarded as having many benefits for infants and is a good option to manage neonatal cow's milk allergy [6,8]. ...
... In addition, a single-center study in the neonatal intensive care unit reported that gastrointestinal symptoms were the most common symptoms of neonatal cow's milk allergy, including vomiting (71%), bloody stool (63%), less vigorous sucking (21%), abdominal distention (8%), and gastric hemorrhage (4%). However, no ascites was reported
[7]
. We considered protein-losing gastroenteropathy caused by an immune reaction as the mechanism for ascites in this case, which is widely noticed in gastrointestinal food allergies in children [21]. ...
A Preterm Case of Cow’s Milk Allergy Presenting with Recurrent Ascites Treated with Donor Breast Milk
Full-text available
Shutaro Suga
Shinya Abe
Kazumoto Iijima
We report a case of a preterm infant who developed cow’s milk allergy. This male infant presented with recurrent ascites and was successfully treated with donated breast milk. He was born at 24 weeks’ gestation with a birthweight of 506 g. From day 20, infant formula, soy protein-based formula, and casein-hydrolyzed formula were used due to insufficient maternal lactation. This resulted in abdominal distention, generalized edema, and recurrent ascites. We diagnosed him with cow’s milk allergy since these symptoms improved on exclusive breast milk feeding. No recurrence of symptoms occurred when donated breast milk was used in combination with the mother’s own milk. Ascites should be regarded as a clinical symptom of neonatal cow’s milk allergy. Donated breast milk may be effective in the treatment of the allergy if breastfeeding is not available.
... The prevalence of CMPA in infants is approximately 2% to 3% (12,26,27), and it has been on a steady rise over the last years (28). Our findings were in line with previous studies suggesting that most infants with allergic colitis are symptomatic in the first month, and bloody stools were one of the most common manifestations of CMPA in infants at the time of onset (2,(29)
(30)
(31). Exclusive breastfeeding and avoiding the use of regular cow's milk formula as supplementary feed for breastfed infants in the first 6 months of life has been known to reduce and prevent CMPA (32)(33)(34)(35), and the lack of breast milk has been significantly associated with bloody stools (1,5,36). ...
Causes of bloody stools in neonates: a case series report
Article
Full-text available
Background:
Bloody stools in a neonate may stand for a spectrum of conditions ranging from benign to life-threatening. It is critical to detect the cases that have significant underlying pathology, especially those which require urgent surgical intervention. Previous studies always focused on one particular disease related to bloody stools in neonates, or the study only involved a small number of cases. This study aimed to investigate the common causes of bloody stools in neonates.
Methods:
This retrospective cohort study included the neonates admitted to our institution due to "bloody stools" over a 5-year period. We compared the differences among patients' characteristics, feeding choice, underlying diseases, and operation rate between preterm and term neonates.
Results:
A total of 300 patients were included, accounting for 1.1% of the total neonatal admissions. The overall rate of exclusive breastfeeding was 28.0%. The most common underlying causes for bloody stools were: cow's milk protein allergy (CMPA, 53.3%), swallowed blood syndrome (10.0%), viral enteritis (9.7%), necrotizing enterocolitis (NEC) > stage II (8.3%), non-specific enteritis (7.3%), and anal fissure (5.0%). The median [interquartile range (IQR)] onset age for bloody stools for all infants was 12 [3-22] days after birth. Preterm neonates had a lower rate of exclusive breastfeeding (P=0.844), higher incidence of NEC > stage II (P=0.014), later bloody stools onset age (P<0.001), and longer length of hospital stay than term neonates (P<0.001). For neonates with NEC, those with bottle-fed had an earlier onset age for bloody stools than those with breast-fed (P=0.027). Only 1.7% (n=5) required surgery (2 stage III NEC, 1 post-NEC stricture, and 2 volvuli). Survival at hospital discharge was 100%.
Conclusions:
Bloody stools in neonates is generally a benign, self-limiting disorder, not related to surgical conditions. The overall operation rate among neonates with bloody stools was only 1.7%. CMPA and NEC were the most common underlying non-surgical and surgical diseases, respectively, for neonates with bloody stools. Feeding choice is related to bloody stools in neonates, policies and strategies to support breastfeeding should be strengthened in the future.
... Poor tolerance or suspected cow's milk protein allergy was the second most common free text response (n = 12) for withholding BMF. In preterm infants, cows' milk protein allergy often presents as non-specific gastrointestinal symptoms, making it difficult to distinguish from poor feed tolerance, which is common as a result of gut immaturity
(30)
. Of note, both BMFs used in the UK are bovine-based, although the degree of protein hydrolysis differs. ...
The use of Breast Milk Fortifier in Preterm Infants by paediatric dietitians in the UK
Full-text available
Background
Breast milk is the feed of choice for premature infants, although its nutritional composition is not always sufficient to meet their raised nutritional requirements. The addition of a multi‐nutrient breast milk fortifier (BMF) to breastmilk is recommended; however, international guidelines on the use of BMF are inconsistent. The present study aimed to explore the use of BMF in preterm infants by paediatric dietitians in the UK.
Methods
A questionnaire was designed and sent to members of the British Dietetic Association neonatal specialist group (n = 100) using a secure online platform. Descriptive statistics were calculated.
Results
Forty dietitians completed the survey, all of whom used BMF. Local hospital BMF guidelines were available to 77.5% (n = 31). The most commonly used criteria for commencing BMF were: tolerating a feed volume of 150 mL kg⁻¹ day⁻¹ (72.5%, n = 29), a gestational age <34 weeks (67.5%, n = 27) and a birth weight <1500 g (60%, n = 24). The primary contraindication for the use of BMF was necrotising enterocolitis (NEC). The majority of respondents used standard fortification, with individualised fortification available to only 12.5% (n = 5). The most common indicators for discontinuing BMF were on discharge home (67.5%, n = 27), satisfactory growth (65%, n = 26) or feeding directly from the breast (62.5%, n = 25).
Conclusions
Although BMF is used more proactively in UK neonatal units than previously, variation in practice remains. Individualised fortification is very uncommon and caution remains regarding risk of NEC. The development of national guidelines on the use of BMF would help to standardise nutritional care in neonatal units.
... 7 angioedema, dermatitis, as well as in the gastrointestinal tract including vomiting, abdominal cramping, nausea, diarrhea and in the respiratory tract disorder including rhinitis, asthma, laryngeal edema.
[8]
[9][10][11] Anaphylactic shock is the most frightening symptom which is induced by a particular food that is acute in onset, occurring within minutes or hours, and without proper treatment, it may lead to death badly. 12,13 Much other allergic disorder has been found in different organ systems that increase the risk of other allergic condition due to consuming allergic food items. ...
Prevalence, severity and risk factors of food allergy and food addiction among the people of Tangail district, Bangladesh
Article
Full-text available
Md. Tarek Molla
Abstract
Background: Food allergy is an abnormal response of some particular foods triggered by the body’s immune system. Food addiction which generally shares a similar neurobiological and behavioral framework with substance addiction like foods. The aim of this study was to evaluate common food items responsible for food allergy along with food addiction among Bangladeshi people.
Methods: A cross-sectional study among 699 participants in the Tangail district of Bangladesh was done to record the presence of food allergy and food addiction patterns. Chi-square tests and logistic regression analysis were performed to assess the association between different factors with food allergy and food addiction.
Results: It was found that brinjal was the most frequent food item responsible for 28.3% of people’s food allergy. The main symptoms due to the food allergy were about 28.5% itching and 22.7% rash on the skin. According to this study, 50.4% of allergic patients took medicine and most of the allergic patients didn’t seek medical advice. A maximum of 72.8% of allergic patients also had an addiction to food. Street foods like jhalmuri, fried foods were the general food addicted items covering 34.9%. Food-addicted participants with food allergies reported significantly more problems with foods, where obesity and heart disease are recognized as clinical effects due to having higher amounts of fat and sugar to these foods.
Conclusions: The study revealed some important determinants of food allergic and food addiction that will help to increase our knowledge for the greater interest of our health and further research.
Keywords
Bangladesh, Food allergy, Food addiction, Hypersensitivity, Immune system, Knowledge
... Morita et al. classified 24 patients diagnosed as having CMA into preterm and term infants and examined their characteristics
9)
. They found no significant differences in the onset of clinical symptoms and enteral feeding, but the onset time was significantly different between the preterm (23 days) and the fullterm infants (3.5 days). ...
A male preterm infant with cow’s milk allergy to human milk fortifier showing only severe respiratory symptoms
Article
Full-text available
Naoto Takahashi
We report a male infant with a birthweight of 1,400 g at 29 weeks 2 days gestation diagnosed as having cow’s milk allergy (CMA) due to human milk fortifier, who developed severe respiratory symptoms. The infant had no gastrointestinal symptoms;rather, the initial symptoms were apnea attacks and wheezing with a prolonged expiratory phase that progressed to severe ventilatory insufficiency requiring mechanical ventilation. Aggravation of his general condition, which appeared to be due to sepsis, was improved by temporary starvation and respiratory care, but he relapsed on the resumption of enteral feeding of his mother’s milk with a human milk fortifier. As a result, this event was interpreted as a positive oral food challenge test. The infant resumed complete breastfeeding without the fortifier and has not relapsed since. Examination of his serial cytokine profiles from residual serum revealed that although interleukin-5 was not increased, interferon (IFN)-γ was increased, suggesting some relation between the time course of IFN-γ and the infant’s eosinophil count. These findings may indicate that the involvement of IFN-γ is one cause of the onset of this disease.
... Morita et al. classified 24 patients diagnosed as having CMA into preterm and term infants and examined their characteristics
9)
. They found no significant differences in the onset of clinical symptoms and enteral feeding, but the onset time was significantly different between the preterm (23 days) and the fullterm infants (3.5 days). ...
Cow's milk allergy and interferon -γ Fukushima
We report a male infant with a birthweight of 1,400 g at 29 weeks 2 days gestation diagnosed as having cow's milk allergy (CMA) due to human milk fortifier, who developed severe respiratory symptoms. The infant had no gastrointestinal symptoms ; rather, the initial symptoms were apnea attacks and wheezing with a prolonged expiratory phase that progressed to severe ventilatory insufficiency requiring mechanical ventilation. Aggravation of his general condition, which appeared to be due to sepsis, was improved by temporary starvation and respiratory care, but he relapsed on the resumption of enteral feeding of his mother's milk with a human milk fortifier. As a result, this event was interpreted as a positive oral food challenge test. The infant resumed complete breastfeeding without the fortifier and has not relapsed since. Examination of his serial cyto-kine profiles from residual serum revealed that although interleukin-5 was not increased, interferon (IFN)-γ was increased, suggesting some relation between the time course of IFN-γ and the infant's eosinophil count. These findings may indicate that the involvement of IFN-γ is one cause of the onset of this disease.
| https://www.researchgate.net/figure/Comparison-of-premature-and-full-term-milk-allergic-patients_tbl1_235604133 |
Surgical Treatment of Metastatic Femoral Fractures: Achieving an Improved Quality of Life for Cancer Patients | Anticancer Research
Surgical Treatment of Metastatic Femoral Fractures: Achieving an Improved Quality of Life for Cancer Patients
MASASHI MORISHIGE , KEIICHI MURAMATSU , YASUHIRO TOMINAGA , TAKAHIRO HASHIMOTO and TOSHIHIKO TAGUCHI
Anticancer Research January 2015, 35 (1) 427-432;
Abstract
Background: The femur is the most common long bone affected by metastatic carcinoma. We report our experience regarding treatment of metastatic femoral fracture using femoral head prosthesis (FHP) or intramedullary nailing (IM nail) with augmentation by polymethylmethacrylate (PMMA). Patients and Methods: Thirty-five complete fractures in 33 patients were treated surgically. Metastatic lesions were present in the femoral head to neck region (n=9), trochanteric to shaft region (n=23) and supracondular region (n=3). Results: Eight out of 9 patients with proximal femoral metastasis reconstructed by FHP were later able to walk outdoors. For the 11 patients with trochanteric metastasis, the short type of gamma nail was used for bony fixation. In two patients the inserted IM nails were broken. All other cases showed excellent clinical outcomes. For the 12 patients with femoral shaft metastasis, the long type of gamma nail was inserted. Nine cases showed excellent clinical outcomes without any serious complications. Conclusion: FHP is indicated for metastases in the femoral head to neck region. IM nailing is best indicated when the lesion is located in the proximal to mid shaft and the patient's life expectancy is <6 month.
Femur
metastasis
intramedullary nailing
polymethylmethacrylate
physical status
prognosis
Improvements in the treatment of primary cancers have led to increased survival times but also to an increased number of patients with skeletal-related metastatic events. Pathological fractures caused by metastatic tumors usually occur in the late disease stage and are accompanied by severe pain, instability and acute loss of function (1). The femur is the most common long bone affected by metastatic carcinoma and this directly influences daily living activities and the quality of life of cancer patients (2).
Adequate treatment of femoral metastasis provides immediate pain reduction, stability, increased mobility and local tumor control, thus easing the need for nursing care. Bisphosphonate treatment or radiotherapy for sensitive cancers helps to decrease skeletal complications (3) (Table I) but are not indicated for complete fractures. Because of poor results with conservative treatment, operative stabilization is now the recommended therapy for pathological femur fracture. However, the surgical indications and appropriate procedures for metastatic femur fracture are still controversial (1). Patients with a short life expectancy and inoperable condition are not suitable candidates for surgery. However, advances in adjuvant treatment and the increased survival of patients with metastatic bone disease have motivated surgeons to practice more aggressive treatments (4). This has led to the application of invasive surgical techniques, such as those already used for the treatment of primary sarcoma of bone, including curative resection and megaprosthesis (5-7).
Several factors must be considered in the treatment of femoral metastasis, including the location, estimated prognosis, nature of the fracture (complete or impending) (8) and general patient condition and wishes. Consequently, the treatment should be tailored to suit each individual case. We report here our experience treatment of metastatic femoral fracture using femoral head prosthesis (FHP) or intramedullary nailing (IM nail) with augmentation by polymethylmethacrylate (PMMA). We discuss the selection of different modalities and surgical procedures that may be appropriate for each cancer patient.
Patients and Methods
Patients. Since 2006 in the outpatient clinic of our institute, we experienced 62 consecutive cases with metastatic lesion of the femur, including lymphoma. The diagnoses were made using clinical history, radiographs, bone scintigrams, positron emission tomography and other imaging modalities. Amongst these cases, 35 complete fractures in 33 patients were treated surgically. The mean age of patients was 65.3 years (range, 32 to 81) and there were 19 men and 14 women. Metastatic lesions were present in the femoral
head to neck region (n=9), trochanteric to shaft region (n=23) and supracondular to condylar region (n=3). The primary tumors were kidney (n=10), lung (n=7), thyroid (n=4), lymphoma or myeloma (n=4), prostate (n=3), liver (n=2), breast (n=2), esophagus (n=2) and bladder (n=1). All patients were followed-up for at least one year or until death.
Table I.
Treatment options for metastatic femoral fracture.
Operative indications. The operative indications used in this study for femur metastasis were: (i) pain relief that could not be controlled even with opioid drugs; (ii) tumor progression that was rapid and tumor size that had become uncontrollable; (iii) instability of the fracture site that could not be controlled by cast or splint.
If at least one of these conditions was met, the doctor in charge was consulted regarding: (i) whether the survival prognosis was estimated to be more than 3 months and (ii) whether the general patient condition allowed surgical intervention.
If both these conditions were met, surgical treatment was recommended to the patient. The estimated prognosis was obtained by the Katagiri score (9) and from the opinion of the doctor in charge.
Surgical procedure.Preoperative local imaging studies included plain radiographs, computed tomography and magnetic resonance imaging. Careful attention was paid to the extent of tumor involvement, cortical breakthrough and soft tissue extension. In 26 patients, selective arterial embolization of the metastatic lesion was performed the day before surgery in order to decrease intraoperative blood loss.
Different operative procedures were used depending on the site of the metastatic lesion. For proximal metastasis that extended into the femoral head and across the neck, the tumor was exposed through a posterior approach in the lateral position and removed by intra-articular resection. After careful curettage of residual tumor, a FHP was inserted into the intramedullary cavity and fixed with PMMA containing gentamicin and adriamycin. None of the patients in this study were reconstructed by megaprosthesis. For trochanteric, subtrochanteric, femoral shaft and supracondylar metastasis, the proximal part of the metastatic lesion was reamed and the tumor carefully curated. Cryosurgery was performed as an adjuvant resection and involved freezing the tumor cavity by direct pouring of liquid nitrogen followed by thawing with warm saline. This was repeated three times. An antegrade IM nail with locking screw was used for reconstruction. For proximal metastases a short nail type was applied, while for femoral shaft metastases a long nail type was used. After stabilization of the femoral fracture, PMMA was applied to fill the bone cavity defect (Figure 1).
Evaluation. The following items were evaluated retrospectively: bony union at final follow-up, local recurrence, performance status both pre- and postoperative, local and systemic complications, activity of daily living and survival time after surgery. The performance status (PS) scoring system followed that of the Eastern Cooperative Oncology Group (10).
Results
FHP reconstruction.For the 9 patients with proximal femoral metastasis reconstructed by FHP, 8 were later able to walk outdoors with or without a T cane and maintained this ability until the final stages of life. The mean PS improved from a preoperative score of 2.6 to a postoperative score of 1.7. Eight patients survived longer than their estimated prognosis. One case with metastasis from renal cell cancer died 2 months after surgery without improvement in their PS, while another case suffered massive bleeding due to lack of embolization before operation.
Figure 1.
A 63-year-old male with renal cancer metastasis (left). After careful curettage of tumor, cryosurgery was performed as an adjuvant resection. An antegrade long IM nail with locking screw was used for reconstruction. After stabilization of the femoral fracture, PMMA was applied to fill the bone cavity defect (right).
Intramedullary nail with locking screw reconstruction.For the 11 patients with trochanteric to subtrochanteric metastasis, the short type of gamma nail was used for bony fixation. In two patients the inserted IM nails were broken at the fracture site. In a case with kidney cancer metastasis, the tumor resection and PMMA augmentation was not performed because the prognosis was estimated to be poor. This patient walked with full weight bearing against our recommendation and the stem was broken three weeks after surgery (Figure 2). A case with thyroid cancer metastasis underwent IM nail insertion and PMMA augmentation but the stem was broken 2 years after surgery. All other cases showed excellent clinical outcomes. Survival times were longer than the estimated prognosis demonstrating that the operative procedure was only marginally invasive and had little effect on the general condition. The mean PS improved from a preoperative score of 3.7 to a postoperative score of 1.9.
For the 12 patients with femoral shaft to supracondylar metastasis, the long type of gamma nail was inserted for bony fixation. Three cases did not undergo augmentation with PMMA due to estimation of poor prognosis but all could move themselves by wheelchair after surgery. One case with metastasis from lung cancer had bilateral femoral stabilization. The remaining 9 cases showed excellent clinical outcomes without any serious complications. All cases achieved daily living activities until the final periods. Breakage of long IM nails was not observed throughout the follow-up period. The mean PS improved from a
preoperative score of 3.4 to a postoperative score of 2.6. We could not confirm bony union in all cases. No revision surgery, because of local tumor recurrence or infection, was necessary.
Figure 2.
A 66-year-old male with renal cancer metastasis (left). The tumor resection and PMMA augmentation was not performed because the prognosis was estimated to be poor. This patient walked with full weight bearing against our recommendation and the stem was broken three weeks after surgery (right).
Discussion
Operative indication for femoral metastasis.Over the past decade, the prognosis and quality of life for patients with disseminated cancer has significantly improved thanks to newly-introduced medical and radiation therapies. However, this has led to an increased incidence of skeletal-related metastatic events, particularly in the lower extremity (11,12). The treatment of such events is not curative and serves only as local disease control for the cancer patient.
Femoral metastases are especially difficult to manage because the majority are osteolytic. The major problems associated with these events are pain and mechanical disruption. Different therapeutic approaches have been proposed for femoral metastasis. Nilsson and Gustafson reviewed 245 operations in 216 patients with this condition. (2) They concluded that patients can be operated safely and with an acceptable complication rate. Several authors have recommended surgical stabilization of femoral fractures to reduce pain and to improve quality of life (13-16). Pain can be controlled by pain-killer drugs but the mechanical disruption of bone should be treated surgically (12). To date however, the operative indications for femoral metastasis have not been clear (1). Because these patients have a relatively short lifespan and their general condition deteriorates over time, the initial operative intervention should be definitive. The orthopedic surgeon must assume the fractures will not unite and the fixation must be durable so that it lasts for the remaining lifetime of the patient. The operative method should be adapted on a case by case basis to reflect the individual circumstances.
Cammasio et al.(17) used the management protocol proposed by Capanna (18) for the operative indication of long bone metastasis. Lesions were divided into 4 classes, with class 1 to 3 patients indicated for surgical treatment. However, this protocol did not consider the prognosis or the general condition of the patient. In the present study, the factors of metastatic site, uncontrollable pain, uncontrollable tumor growth and uncontrollable instability were all taken into consideration. If at least one of these conditions was met the doctor in charge was consulted for the next two general conditions, comprising an estimated prognosis of >3 months and a suitable patient condition for surgical intervention. These treatment guidelines seem rational for femoral metastasis.
Appropriate operative procedure.The rapid progression of internal fixation devices and endoprosthesis over the past 20 years has improved the prognosis following surgical management of metastatic long bone fractures. However, the best way to treat femoral metastasis is still uncertain and complication rates are high (19). FHP is suitable for lesions in the femoral head to neck region. The best approach for lesions in the proximal femoral to shaft region is less clear.
Prosthetic replacement is now used more commonly for proximal femoral metastasis (5-7) (Table I). When the metastasis is located in the metaphyseal region, a wide resection and reconstruction with megaprosthesis may be indicated. Camnasio et al. reviewed 154 patients treated with prosthesis for metastatic bone disease, with metastatic breast and renal carcinoma accounting for 66% of lesions (17). The complication rate was acceptable and functional results showed improvement in 73% of patients with a proximal femur lesion. Hwang et al. reported on 315 patients who underwent resection of renal cell carcinoma metastasis and reconstruction with massive endoprosthetic replacement (6). They concluded that patients with solitary bone lesions and with no visceral metastases should be considered for megaprosthesis reconstruction. However, these prosthetic devices are more invasive, more expensive and are associated with higher rates of complications, such as infection and massive bleeding requiring longer hospital stays. Moreover, the attached gluteal and iliopsoas muscles are resected, thus decreasing the abductor strength and favoring dislocation of the hip joint.
Wedin and Bauer presented a retrospective series of 146 operations in 142 cases with proximal femur metastasis (19). In their study, postoperative complications were seen amongst patients operated with hip prosthesis. On the other hand, the risk of re-operation due to implant failure was twice as high in the group treated by osteosynthesis.
Doorn and Stapert reviewed 101 patients with femoral metastasis and stabilized with a long gamma nail (12). They reported that 92% of patients became mobile and that pain was absent or acceptable in 93%. Only two nails broke after surgery. Samsani et al. also reported that stabilization using a long gamma nail for femoral metastasis due to breast carcinoma is a safe and effective method with acceptable risk (20). Rosa et al. treated 21 patients with IM nailing, of which 8 patients were also treated with acrylic cement (11). Only one patient in their series was re-operated due to tumor progression and cement failure. Giannoudius et al. treated 30 patients with pathological femoral fracture by unreamed IM nailing (16). Only one was revised for implant failure through a distal metastasis at 6 months.
Our results confirmed that use of IM interlocking nails reduces pain and improves the quality of life in patients with femoral metastasis. Hip prosthesis is recommended for the increasing number of patients with proximal femoral metastasis. However, endoprosthetic replacement involves invasive surgery and is associated with increased morbidity (19). Indications for prosthetic joint replacement in patients with femoral metastasis include the prospect of long survival, isolated lesions, extensive bone loss and failed conventional reconstruction with osteosynthetic devices (Table I).
Complications of IM nailing for femoral metastasis.The major complications of IM nail stabilization for femoral metastasis involve infection, bleeding, tumor recurrence, deep venous thrombosis and implant breakage (13-16). In our series the latter event occurred in two cases.
The results of our study demonstrate that intramedullary stabilization of femoral metastasis can achieve the goal of surgical palliation with an acceptable risk of complication. None of our cases experienced uncontrollable tumor recurrence or growth, infection or deep venous thrombosis. Bleeding could be controlled by preoperative arterial embolization. Implant breakage is, however, a major issue. As described above, implant failure is not uncommon with these lesions and a failure rate of 10% has been reported with intramedullary implants such as long gamma nails (13-16). The implant failure rate will increase with longer survival times, as seen in our breast cancer patients. Unfortunately, femoral metastatic fractures did not show bony union, even with an IM nail. A strong fixation device is required so that it lasts for the remainder of the patient's life without the risk of implant failure.
The composition, diameter, rigidity and design of IM nails contribute to the strength of the implant. These should be able to withstand the strain of weight-bearing for the remainder of the patient's life. To prevent IM nail breakage, we recommend that patients use a T-cane and limit their weight-bearing activity. The level of activity following femoral stabilization should be set lower than full activity. Augmentation by PMMA is a beneficial tool to increase the durability of IM nails.
Removal of tumor and adjuvant procedures.The use of reaming prior to tumor curettage and insertion of the IM nail is a matter of debate (21,22). Reaming is necessary because a mechanical advantage can be obtained using a larger nail diameter. However, reaming may increase the diffusion of carcinoma into the distal end of the femur. The removal of metastatic carcinoma is an essential part of the management of femoral metastasis and is usually achieved by intralesional curettage. The empty cavity is filled with PMMA, thus conferring improved stability to the fixation construct. Moreover, local adjuvant treatments such as cryosurgery and adriamycin-containing PMMA can help to prevent local progression. For patients with poor prognosis (3 months or less), the removal of carcinoma is an invasive process and is, therefore, not warranted.
As an alternative, Ogura et al. reported an interesting case with hepatocellular carcinoma metastasis to the proximal femur (23). This patient was treated with radiofrequency ablation and prophylactic internal fixation. His postoperative course was uneventful and the patient was almost asymptomatic without local progression when he died 14 months after surgery. This case shows that femoral metastasis can be controlled without aggressive wide resection and megaprosthesis reconstruction.
Conclusion
The femur is the most common long bone affected by metastatic carcinoma. The major problems arising from femoral metastasis are pain and mechanical disruption. Short-term improvements in pain and functional status are particularly important for patients with limited life expectancy. Several authors have recommended surgical stabilization of femoral metastasis. The aim of surgical treatment should be to prevent or to stabilize the pathological fracture, relieve pain and permit an acceptable quality of life for the remainder of the patient's life.
Life expectancy should be longer than the time to recover from surgery. FHP is indicated for metastases in the femoral head to neck region. IM nailing is best indicated when the lesion is located in the proximal to midshaft and the patient's life expectancy is <6 months, especially if associated with an aggressive carcinoma.
Received September 3, 2014.
Revision received September 26, 2014.
Accepted October 6, 2014.
Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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| https://ar.iiarjournals.org/node/14176.full.print |
Oakland Promise - GuideStar Profile
GuideStar connects donors and grantmakers to non-profit organizations.
Oakland Promise
Opportunity Changes Everything.
aka Oakland Promise | Oakland, CA | www.oaklandpromise.org
Mission
Oakland Promise (OP) seeks to engage the Oakland community to advance equity and economic mobility through cradle-to-college and career achievement. OP offers every child the financial resources, support, mentorship and incentives they need from birth and throughout their school years to empower them to seek out and thrive in the higher education and career of their dreams.
Ruling year info
2003
Chief Executive Officer
Sandra Ernst
Main address
360 Grand Avenue #363
Oakland, CA 94610 USA
Contact Information
Contact
Email contact available with aPro subscription
Fundraising Contact
Ms. Arbour Decker
Chief Development Officer
Fundraising contact phone: (510) 255-5719
arbour@oaklandpromise.org
Physical Address
300 Frank Ogawa Plaza, Suite 430
Oakland, 94612
Payment Address
360 Grand Avenue #363
Oakland, CA 94610
Donation Payable
Legal name of organization: Oakland Promise
EIN for payable organization: 54-2103707
Formerly known as
East Bay College Fund
EIN
54-2103707
NTEE code info
Elementary, Secondary Ed (B20)
Financial Counseling, Money Management (P51)
Educational Services and Schools - Other (B90)
IRS filing requirement
This organization is required to file an IRS Form 990 or 990-EZ.
Sign in or create an account to view Form(s) 990 for 2020, 2019 and 2018.Register now
Communication
Programs and results
What we aim to solve
SOURCE: Self-reported by organization
Oakland Promise is one of the most ambitious, expansive cradle-to-career programs in the nation. Oakland Promise advances racial and economic equity through comprehensive and holistic strategies centering the needs of those ... furthest from opportunity. In Oakland, Black and Latinx students are not equitably served, and, as a result, graduate from high school and attend college at lower rates as compared to their white and Asian counterparts. Supporting students, especially those of color and from low-income backgrounds, in accessing college is more important than ever. Through targeted interventions across the cradle-to-career continuum, Oakland Promise’s programs support students and families holistically throughout their or their children’s educational journeys. To realize this vision, Oakland Promise partners with key public and nonprofit organizations to provide critical financial, educational, and community services, creating economic mobility through educational opportunity.Read more
Our programs
SOURCE: Self-reported by organization
What are the organization's current programs, how do they measure success,
and who do the programs serve?
Briliant Baby, Kindergarten to College, College Access and College Scholarships and Completion
OP is comprised of four programs supporting children and families at critical junctures: Brilliant Baby promoting a college-going culture from babies’ earliest days by offering under-resourced families college savings accounts, financial coaching, workshops, and community resources; Kindergarten to College providing early scholarships, college visits, and curricular materials to support students’ transitions from elementary, middle, and high school; College Access running school-based education hubs featuring college and financial aid application assistance, internship access, and career planning services; and College Scholarships and Completion equipping students with social and emotional supports necessary for postsecondary persistence through one-on-one mentoring, peer advising, counseling, and retreats. OP’s holistic programming is designed to promote a continuous culture of career and college preparedness in students, families, and educators.
Population(s) Served
Economically disadvantaged people
Ethnic and racial groups
Videos
Oakland Promise Overview
Our results
SOURCE: Self-reported by organization
How does this organization measure their results? It's a hard question but an important one.
Evaluation documents
Number of savings accounts used by clients
This metric is no longer tracked.
Totals By Year
2022
1,478
2021
1,030
2020
974
Population(s) Served
Low-income people, Families
Related Program
Briliant Baby, Kindergarten to College, College Access and College Scholarships and Completion
Type of Metric
Output - describing our activities and reach
Direction of Success
Increasing
Context Notes
Our Sustainable Development Goals
SOURCE: Self-reported by organization
Learn more aboutSustainable Development Goals.
Goals & Strategy
SOURCE: Self-reported by organization
Charting impact
Four powerful questions that require reflection about what really matters - results.
What is the organization aiming to accomplish?
Oakland Promise seeks to dramatically increase the number of college and technical school graduates from Oakland within the next decade. Oakland Promise supports children and families from birth through college and career to ensure that postsecondary success is a reality for all Oaklanders.
What are the organization's key strategies for making this happen?
Oakland Promise is a bold initiative designed to provide long-term and comprehensive support for students traditionally underrepresented in higher education through the following programs: Brilliant Baby helping parents raise thriving children by offering a supportive community, reducing financial stressors, and establishing a college savings account as early investment; Kindergarten to College (K2C) offering families early college scholarships of $100 for all Oakland public school kindergarten students, supporting families in opening 529 college savings accounts, and providing college-going culture school supports; College Access operating Future Centers, which are school-based advising centers in Oakland high schools to support students in applying for college, financial aid, scholarships, and high-leverage internships; and College Scholarships & Completion supporting Oakland students at postsecondary institutions with scholarships and persistence supports such as mentors.
What are the organization's capabilities for doing this?
Oakland Promise has a strong team that deeply understands the needs and opportunities of our constituents. We have a wealth of knowledge and have worked to deeply embed our work in the community. Oakland Promise is innovative in its comprehensive support--it starts earlier and goes later than any other Promise program in the country. Oakland Promise aims to improve the short- and long-term health, academic, and financial outcomes for students and families across the city. According to researcher Dr. William Ellliot III from the Center on Assets, Education, and Inclusion, “Oakland Promise’s innovative cradle-to-career design is the most comprehensive Children’s Savings Account program intervention to date. Its rigorous research design means that the Oakland Promise has the potential to not only affect the lives of children and families in Oakland, but across the country.” Former US Secretary of Education Arne Duncan said that “Oakland Promise is one of the most strategic and effective [initiatives] and has the potential to be a national model... it leverages private philanthropy for public dollars and has already achieved outstanding results. Oakland Promise changes the trajectory of our Oakland students from the time they are born, through the time they graduate from college and enter the workforce. Oakland Promise is truly a game changer for Oakland and its future generations.”
What have they accomplished so far and what's next?
Oakland Promise has achieved dramatic results in advancing racial and economic equity of thousands of students and families on an annual basis. Now serving 65 public schools in Oakland, OP is able to make a positive impact on K-12 students, a vast majority of whom come from low-income backgrounds and are students of color. Our external evaluations also demonstrate that we are having an impact on students of color, those from low-income backgrounds, and English language learners. For 2015-16 OP seniors, there was a 7% increase in college enrollment right after senior year, while rates stayed flat at comparison schools. Importantly, this includes gains of 11% for Latinx and 14% in African American enrollment. Brilliant Baby seeks to fundamentally change the trajectory of generations of Oakland’s children and families. Most BB families have experienced intergenerational poverty, and 77% have a household annual income of under $30K. Empirical evidence suggests that having a college savings account for a child from birth is particularly impactful for economically disadvantaged families, helping parents view their child as college-bound. Research also shows that children with $500 in a college savings account are 4 times more likely to graduate college. Our work can close the opportunity gap for thousands of children each year.
Financials
Oakland Promise
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Operations
The people, governance practices, and partners that make the organization tick.
Officers, directors, trustees, and key employees
Highest paid employees
Board of directors
Oakland Promise
Board of directors
as of
04/06/2023
SOURCE: Self-reported by organization
Board chair
Dr. Michael McAfee
Seth Hamalian
Rosaura Altamirano
Barb Fremder
Mark Friedman
Chuyi Fang
James Harrison
Colin Lacon
Dr. Michael McAfee
Leroy Morishita
Susie Poncelet
Tomiquia Moss
Robert Stark
Maria Pirner
Susan Stutzman
Riaz Taplin
Kim Thompson
Organizational demographics
Who works and leads organizations that serve our diverse communities?
Candid partnered with CHANGE Philanthropy on this demographic section.
Leadership
The organization's leader identifies as:
Race & ethnicity
Black/African American
Gender identity
Female
Race & ethnicity
Board members (20)
Staff (49)
Senior staff (12)
Asian/Asian American Black/African American Hispanic/Latino/Latina/Latinx Middle Eastern/North African Native American/American Indian/Alaska Native/Indigenous Native Hawaiian/Pacific Islander White/Caucasian/European Multiracial/Multiethnic People who prefer to identify with another race or ethnicity Unknown or decline to state
Gender identity
Board members (20)
Staff (49)
Senior staff (12)
Female Male Non-binary Unknown or decline to state
Disability
No data
| https://www.guidestar.org/profile/54-2103707 |
Publications - Global Disability Innovation Hub
The GDI Hub brings together academic excellence, innovative practice and co-creation; harnessing the power of technology for good.
Type
Journal Paper
Themes
Assistive & Accessible Technology
Seeking information about assistive technology: Exploring current practices, challenges, and the need for smarter systems
Jamie Danemayer,Cathy Holloway,Youngjun Cho, Nadia Berthouze, Aneesha Singh, William Bhot, Ollie Dixon, Marko Grobelnik, John Shawe-Taylor
Paper highlights: Assistive technology (AT) information networks are insular among stakeholder groups, causing unequal access to information. Participants often cited fragmented international marketplaces as a barrier and valued info-sharing across industries. Current searches produce biased results in marketplaces influenced by commercial interests and high-income contexts. Smart features could facilitate searching, update centralised data sources, and disseminate information more inclusively.
International Journal of Human-Computer Studies; 2023
Abstract
Seeking information about assistive technology: Exploring current practices, challenges, and the need for smarter systems
Ninety percent of the 1.2 billion people who need assistive technology (AT) do not have access. Information seeking practices directly impact the ability of AT producers, procurers, and providers (AT professionals) to match a user's needs with appropriate AT, yet the AT marketplace is interdisciplinary and fragmented, complicating information seeking. We explored common limitations experienced by AT professionals when searching information to develop solutions for a diversity of users with multi-faceted needs. Through Template Analysis of 22 expert interviews, we find current search engines do not yield the necessary information, or appropriately tailor search results, impacting individuals’ awareness of products and subsequently their availability and the overall effectiveness of AT provision. We present value-based design implications to improve functionality of future AT-information seeking platforms, through incorporating smarter systems to support decision-making and need-matching whilst ensuring ethical standards for disability fairness remain.
Seeking information about assistive technology: Exploring current practices, challenges, and the need for smarter systems
Type
Journal Paper
Themes
Assistive & Accessible Technology
Evaluating the use of a thermoplastic socket in Kenya: A pilot study
Giulia Barbareschi, Wesley Teerlink, Josepg Gakunga Njuguna, Purity Musungu, Mary Dama Kirino, andCatherine Holloway
According to estimates from the World Health Organization, in 2010, there were more than 30 million people in need of prosthetic and orthotic devices across Africa, Asia, and Latin America. 1This number is likely to have grown significantly in the past decade, in line with trends recorded for the general need of assistive technology. 2For many people who undergo a lower limb amputation, access to an appropriate prosthesis is essential to restore functional mobility and ensure good quality of life. 3Ultimately, an appropriate lower-limb prosthesis (LLP) can enable people with amputation to fulfill their desired role in their family, work, and community life. 4
Prosthetic and Orthotics International; 2022
Abstract
Evaluating the use of a thermoplastic socket in Kenya: A pilot study
Background:
Many people with amputations who live in low-resourced settings struggle to access the workshops where qualified prosthetists provide appropriate care. Novel technologies such as the thermoplastic Confidence Socket are emerging, which could help facilitate easier access to prosthetic services.
Objectives:
The objective of this study was to evaluate the satisfaction and the performance of transtibial prosthesis featuring the Confidence Socket.
Study design:
This is a longitudinal repeated-measures design study.
Methods:
A convenience sample of 26 participants who underwent transtibial amputation were fitted with the Confidence Socket. The performance of the socket was evaluated after a follow-up period between 1 month and 6 months using the L test of functional mobility and the amputee mobility predictor. Satisfaction with the prosthesis was measured using the Trinity Amputation and Prosthetic Experience Scales and purposefully designed 7-point Likert scales.
Results:
Ten of the 26 participants returned for follow-up. Perceived activity restriction and L test times improved significantly at follow-up, but the self-reported satisfaction with the Confidence Socket was lower at follow-up compared with that after fitting.
Conclusions:
The Amparo Confidence Socket represents a potentially viable alternative to improve access to appropriate prosthesis in Kenya, but some aspects of users’ self-reported satisfaction should be further investigated.
Barbareschi G, Teerlink W, Njuguna JG, Musungu P, Kirino MD, Holloway C. Evaluating the use of a thermoplastic socket in Kenya: A pilot study. Prosthet Orthot Int. 2022 Oct 1;46(5):532-537. doi: 10.1097/PXR.0000000000000130. Epub 2022 Mar 25. PMID: 35333813; PMCID: PMC9554758.
Type
Journal Paper
Themes
Assistive & Accessible Technology
Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges
Jamie Danemayer, Andrew Young, Siobhan Green, Lydia Ezenwa, Michael Klein
This study synthesizes learnings from three distinct datasets: innovator applications to the COVIDaction data challenges, surveys from organizers from similarly-aimed data challenges, and a focus group discussion with professionals who work with COVID-19 data. Thematic and topic analyses were used to analyze these datasets with the aim to identify gaps and barriers to effective data use in responding to the pandemic.
Data & Policy; 2023
Abstract
Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges
Innovative, responsible data use is a critical need in the global response to the coronavirus disease-2019 (COVID-19) pandemic. Yet potentially impactful data are often unavailable to those who could utilize it, particularly in data-poor settings, posing a serious barrier to effective pandemic mitigation. Data challenges, a public call-to-action for innovative data use projects, can identify and address these specific barriers. To understand gaps and progress relevant to effective data use in this context, this study thematically analyses three sets of qualitative data focused on/based in low/middle-income countries: (a) a survey of innovators responding to a data challenge, (b) a survey of organizers of data challenges, and (c) a focus group discussion with professionals using COVID-19 data for evidence-based decision-making. Data quality and accessibility and human resources/institutional capacity were frequently reported limitations to effective data use among innovators. New fit-for-purpose tools and the expansion of partnerships were the most frequently noted areas of progress. Discussion participants identified building capacity for external/national actors to understand the needs of local communities can address a lack of partnerships while de-siloing information. A synthesis of themes demonstrated that gaps, progress, and needs commonly identified by these groups are relevant beyond COVID-19, highlighting the importance of a healthy data ecosystem to address emerging threats. This is supported by data holders prioritizing the availability and accessibility of their data without causing harm; funders and policymakers committed to integrating innovations with existing physical, data, and policy infrastructure; and innovators designing sustainable, multi-use solutions based on principles of good data governance.
Danemayer, J., Young, A., Green, S., Ezenwa, L., & Klein, M. (2023). Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges. Data & Policy, 5, E11. doi:10.1017/dap.2023.6
Type
Conference Paper
Themes
Assistive & Accessible Technology
Culture and Participation
The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya
Giulia Barbareschi,Catherine Holloway, Katherine Arnold, Grace Magomere, Wycliffe Ambeyi Wetende, Gabriel Ngare, Joyce Olenja
We present the findings of a case study of mobile technology use by People with Visual Impairment (VIPs) in Kibera, an informal settlement in Nairobi. We used contextual interviews, ethnographic observations and a co-design workshop to explore how VIPs use mobile phones in their daily lives, and how this use influences the social infrastructure of VIPs. Our findings suggest that mobile technology supports and shapes the creation of social infrastructure. However, this is only made possible through the existing support networks of the VIPs, which are mediated through four types of interaction: direct, supported, dependent and restricted.
CHI '20: Proceedings of the 2020 CHI Conference; 2020
Abstract
Living in an informal settlement with a visual impairment can be very challenging resulting in social exclusion. Mobile phones have been shown to be hugely beneficial to people with sight loss in formal and high-income settings. However, little is known about whether these results hold true for people with visual impairment (VIPs) in informal settlements. We present the findings of a case study of mobile technology use by VIPs in Kibera, an informal settlement in Nairobi. We used contextual interviews, ethnographic observations and a co-design workshop to explore how VIPs use mobile phones in their daily lives, and how this use influences the social infrastructure of VIPs. Our findings suggest that mobile technology supports and shapes the creation of social infrastructure. However, this is only made possible through the existing support networks of the VIPs, which are mediated through four types of interaction: direct, supported, dependent and restricted.
Giulia Barbareschi, Catherine Holloway, Katherine Arnold, Grace Magomere, Wycliffe Ambeyi Wetende, Gabriel Ngare, and Joyce Olenja. 2020. The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya. In Proceedings of the 2020 CHI Conference on Human Factors in Computing Systems (CHI '20). Association for Computing Machinery, New York, NY, USA, 1–15.https://doi.org/10.1145/331383...
Type
Conference Paper
Disability design and innovation in computing research in low resource settings
Dafne Zuleima Morgado-Ramirez,Giulia Barbareschi, Maggie Kate Donovan-Hall, Mohammad Sobuh, Nida' Elayyan, Brenda T Nakandi, Robert Tamale Ssekitoleko, joyce Olenja, Grace Nyachomba Magomere, Sibylle Daymond, Jake Honeywill, Ian Harris, Nancy Mbugua, Laurence Kenney,Catherine Holloway
80% of people with disabilities worldwide live in low resourced settings, rural areas, informal settlements and in multidimensional poverty. ICT4D leverages technological innovations to deliver programs for international development. But very few do so with a focus on and involving people with disabilities in low resource settings. Also, most studies largely focus on publishing the results of the research with a focus on the positive stories and not the learnings and recommendations regarding research processes.
ASSETS '20: Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility; 2020
Abstract
Disability design and innovation in computing research in low resource settings
80% of people with disabilities worldwide live in low resourced settings, rural areas, informal settlements and in multidimensional poverty. ICT4D leverages technological innovations to deliver programs for international development. But very few do so with a focus on and involving people with disabilities in low resource settings. Also, most studies largely focus on publishing the results of the research with a focus on the positive stories and not the learnings and recommendations regarding research processes. In short, researchers rarely examine what was challenging in the process of collaboration. We present reflections from the field across four studies. Our contributions are: (1) an overview of past work in computing with a focus on disability in low resource settings and (2) learnings and recommendations from four collaborative projects in Uganda, Jordan and Kenya over the last two years, that are relevant for future HCI studies in low resource settings with communities with disabilities. We do this through a lens of Disability Interaction and ICT4D.
Dafne Zuleima Morgado-Ramirez, Giulia Barbareschi, Maggie Kate Donovan-Hall, Mohammad Sobuh, Nida' Elayyan, Brenda T Nakandi, Robert Tamale Ssekitoleko, joyce Olenja, Grace Nyachomba Magomere, Sibylle Daymond, Jake Honeywill, Ian Harris, Nancy Mbugua, Laurence Kenney, and Catherine Holloway. 2020. Disability design and innovation in computing research in low resource settings. In Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility (ASSETS '20). Association for Computing Machinery, New York, NY, USA, Article 11, 1–7.https://doi.org/10.1145/337362...
Type
Journal Paper
Themes
Assistive & Accessible Technology
Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey
Emma M Smith, Maria Luisa Toro Hernandez, Ikenna D Ebuenyi, Elena V Syurina,Giulia Barbareschi, Krista L Best,Jamie Danemayer,Ben Oldfrey, Nuha Ibrahim,Catherine Holloway, Malcolm MacLachlan
The coronavirus disease 2019 (COVID-19) pandemic has impacted all segments of society, but it has posed particular challenges for the inclusion of persons with disabilities, those with chronic illness and older people regarding their participation in daily life. These groups often benefit from assistive technology (AT) and so it is important to understand how use of AT may be affected by or may help to mitigate the impacts of COVID-19.Objective:The objectives of this study were to explore the how AT use and provision have been affected during the initial stages of the COVID-19 pandemic, and how AT policies and systems may be made more resilient based on lessons learned during this global crisis.
International Journal of Health Policy and Management; 2020
Abstract
Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey
Abstract
Background:The coronavirus disease 2019 (COVID-19) pandemic has impacted all segments of society, but it has posed particular challenges for the inclusion of persons with disabilities, those with chronic illness and older people regarding their participation in daily life. These groups often benefit from assistive technology (AT) and so it is important to understand how use of AT may be affected by or may help to mitigate the impacts of COVID-19.Objective:The objectives of this study were to explore the how AT use and provision have been affected during the initial stages of the COVID-19 pandemic, and how AT policies and systems may be made more resilient based on lessons learned during this global crisis.
Methods:This study was a rapid, international online qualitative survey in the 6 United Nations (UN) languages (English, French, Spanish, Russian, Arabic, Mandarin Chinese) facilitated by extant World Health Organization (WHO) and International Disability Alliance networks. Themes and subthemes of the qualitative responses were identified using Braun and Clarke's 6-phase analysis.
Results:Four primary themes were identified in in the data: Disruption of Services, Insufficient Emergency Preparedness, Limitations in Existing Technology, and Inadequate Policies and Systems. Subthemes were identified within each theme, including subthemes related to developing resilience in AT systems, based on learning from the pandemic.
Conclusion:COVID-19 has disrupted the delivery of AT services, primarily due to infection control measures resulting in lack of provider availability and diminished one-to-one services. This study identified a need for stronger user-centred development of funding policies and infrastructures that are more sustainable and resilient, best practices for remote service delivery, robust and accessible tools and systems, and increased capacity of clients, caregivers, and clinicians to respond to pandemic and other crisis situations.
Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey
Smith EM, Toro Hernandez ML, Ebuenyi ID, Syurina EV, Barbareschi G, Best KL, Danemayer J, Oldfrey B, Ibrahim N, Holloway C, MacLachlan M. Assistive Technology Use and Provision During COVID-19: Results From a Rapid Global Survey. Int J Health Policy Manag. 2022 Jun 1;11(6):747-756. doi: 10.34172/ijhpm.2020.210. PMID: 33201656;
Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey
Type
Journal Paper
Themes
Assistive & Accessible Technology
Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries
Margaret Savage, Sarah Albala, Frederic Seghers, Rainer Katte, Cynthia Liao, Mathilde Chaudron, Novia Afdhila
Development outcomes are inextricably linked to the health of the marketplace that delivers products and services to people in low- and middle- income countries (LMIC). Shortcomings in the market for assistive technology (AT) contribute to low access in LMIC. Market shaping is aimed at improving a market’s specific outcomes, such as access to high quality, affordable AT, by targeting the root causes of these shortcomings. The paper summarizes the findings of a market and sector analysis that was conducted under the UK aid funded AT2030 programme and aims to discuss how market shaping can help more people gain access to the AT that they need and what are the best mechanisms to unlock markets and commercial opportunity in LMICs.
Assistive Technology The Official Journal of RESNA; 2021
Abstract
Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries
Development outcomes are inextricably linked to the health of the marketplace that delivers products and services to people in low- and middle-income countries (LMIC). Shortcomings in the market for assistive technology (AT) contribute to low access in LMIC. Market shaping is aimed at improving a market’s specific outcomes, such as access to high quality, affordable AT, by targeting the root causes of these shortcomings. The paper summarizes the findings of market analyses conducted under the UK aid funded AT2030 programme in support of ATscale and aims to discuss how market shaping can help more people gain access to the AT that they need and what are the best mechanisms to unlock markets and commercial opportunity in LMICs. The paper also explores how market shaping for AT markets could be part of a mission-oriented approach AT policy. A mission-oriented approach can help accelerate progress toward a common objective among stakeholders, at country or global level. While market-shaping activities direct the outcomes of the market toward a specific end goal, such as access to quality, affordable products and services, missions are more comprehensive and include other policy interventions and stakeholder collaborations in order to create a robust and sustainable structure.
Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries
Margaret Savage, Sarah Albala, Frederic Seghers, Rainer Kattel, Cynthia Liao, Mathilde Chaudron & Novia Afdhila (2021) Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries, Assistive Technology, 33:sup1, 124-135, DOI: 10.1080/10400435.2021.1991050
Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries
Type
Journal Paper
Themes
Assistive & Accessible Technology
Assistive technology access in longitudinal datasets: a global review
Jamie Danemayer, Sophie Mitra,Cathy Holloway, Shereen Hussein
A person’s access to assistive products such as hearing aids, wheelchairs, and glasses, is an essential part of their ability to age in a healthy way. But, according to the World Health Organization, a staggering 90% of people who need assistive products worldwide, do not have access to them. In many instances access is limited or simply non-existent. This is often due to assistive products being too expensive, demand outweighing supply, not always being suitable to use in different environments, or even the lack of availability of trained providers. In such circumstances, people are more likely to age ‘unhealthily’ if they do not have access to assistive products that are designed to support their day to day functioning and independence.
International Journal of Population Data Science; 2023
Abstract
Assistive technology access in longitudinal datasets: a global review
Functional limitations become more prevalent as populations age, emphasising an increasingly urgent need for assistive technology (AT). Critical to meeting this need trajectory is understanding AT access in older ages. Yet few publications examine this from a longitudinal perspective.
This review aims to identify and collate what data exist globally, seeking all population-based cohorts and repeated cross-sectional surveys through the Maelstrom Research Catalogue (searched May 10, 2022) and the Disability Data Report (published 2022), respectively. Datasets incorporating functional limitations modules and question(s) dedicated to AT, with a wave of data collection since 2009, were included.
Of 81 cohorts and 202 surveys identified, 47 and 62 meet inclusion criteria, respectively. Over 40% of cohorts were drawn from high-income countries which have already experienced significant population ageing. Cohorts often exclude participants based on pre-existing support needs. For surveys, Africa is the most represented region (40%). Globally, 73% of waves were conducted since 2016. 'Use' is the most collected AT access indicator (69% of cohorts and 85% of surveys). Glasses (78%) and hearing aids (77%) are the most represented AT. While gaps in data coverage and representation are significant, collating existing datasets highlights current opportunities for analyses and methods for improving data collection across the sector.
Assistive technology access in longitudinal datasets: a global review
Danemayer, J., Mitra, S., Holloway, C. and Hussein, S. (2023) “Assistive technology access in longitudinal datasets: a global review”, International Journal of Population Data Science, 8(1). doi: 10.23889/ijpds.v8i1.1901.
Assistive technology access in longitudinal datasets: a global review
Type
Journal Paper
Themes
Assistive & Accessible Technology
Estimating need and coverage for five priority assistive products: A systematic review of global population based research
Jamie Danemayer, Dorothy Boggs, Vinicius Delgado Ramos, Emma M. Smith, Ariana Kular, William Bhot, Felipe Ramos Barajas, Sarah Polack,Catherine Holloway
Assistive technology (AT) includes assistive products (APs) and related services that can improve health and well-being, enable increased independence and foster participation for people with functional difficulties, including older adults and people with impairments or chronic health conditions. 1This paper uses the umbrella term ‘functional difficulty’ (FD) to refer to all of these groups. This systematic review was undertaken to identify studies presenting population-based estimates of need and coverage for five APs (hearing aids, limb prostheses, wheelchairs, glasses and personal digital assistants) grouped by four functional domains (hearing, mobility, vision and cognition).
BMJ Global Health; 2021
Abstract
Estimating need and coverage for five priority assistive products: A systematic review of global population based research
Introduction:To improve access to assistive products (APs) globally, data must be available to inform evidence based decision-making, policy development and evaluation, and market-shaping interventions.
Methods:This systematic review was undertaken to identify studies presenting population-based estimates of need and coverage for five APs (hearing aids, limb prostheses, wheelchairs, glasses and personal digital assistants) grouped by four functional domains (hearing, mobility, vision and cognition).
Results:Data including 656 AP access indicators were extracted from 207 studies, most of which (n=199, 96%) were cross-sectional, either collecting primary (n=167) or using secondary (n=32) data. There was considerable heterogeneity in assessment approaches used and how AP indicators were reported; over half (n=110) used a combination of clinical and self-reported assessment data. Of 35 studies reporting AP use out of all people with functional difficulty in the corresponding functional domains, the proportions ranged from 4.5% to 47.0% for hearing aids, from 0.9% to 17.6% for mobility devices, and from 0.1% to 86.6% for near and distance glasses. Studies reporting AP need indicators demonstrated >60% unmet need for each of the five APs in most settings.
Conclusion:Variation in definitions of indicators of AP access have likely led to overestimates/underestimates of need and coverage, particularly, where the relationship between functioning difficulty and the need for an AP is complex. This review demonstrates high unmet need for APs globally, due in part to disparate data across this sector, and emphasises the need to standardise AP data collection and reporting strategies to provide a comparable evidence base to improve access to APs.
Estimating need and coverage for five priority assistive products: A systematic review of global population based research
Danemayer J, Boggs D, Delgado Ramos V, et al. Estimating need and coverage for five priority assistive products: a systematic review of global population-based research. BMJ Global Health 2022;7:e007662. doi:10.1136/bmjgh-2021-007662
Estimating need and coverage for five priority assistive products: A systematic review of global population based research
Type
Workshop
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution
Sahan Bulathwela, María Pérez-Ortiz,Catherine Holloway, John Shawe-Taylor
This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies.
Workshop on Machine Learning for the Developing World (ML4D) at the Conference on Neural Information Processing Systems 2021; 2021
Abstract
Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution
Artificial Intelligence (AI) in Education has been said to have the potential for building more personalised curricula, as well as democratising education worldwide and creating a Renaissance of new ways of teaching and learning. Millions of students are already starting to benefit from the use of these technologies, but millions more around the world are not. If this trend continues, the first delivery of AI in Education could be greater educational inequality, along with a global misallocation of educational resources motivated by the current technological determinism narrative. In this paper, we focus on speculating and posing questions around the future of AI in Education, with the aim of starting the pressing conversation that would set the right foundations for the new generation of education that is permeated by technology. This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies. Finally, we ask what would it take for this educational revolution to provide egalitarian and empowering access to education, beyond any political, cultural, language, geographical and learning ability barriers.
Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution
Type
Workshop
Themes
Assistive & Accessible Technology
Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts
Tabish Ahmed, Sahan Bulathwela
The informational needs of people are highly contextual and can depend on many different factors such as their current knowledge state, interests and goals [1, 2, 3]. However, an effective information retrieval companion should minimise the human effort required in i) expressing a human information need and ii) navigating a lengthy result set. Using topical representations of the user history (e.g. [4]) can immensely help formulating zero shot queries and refining short user queries that enable proactive information retrieval (IR). While the world has digital textual information in abundance, it can often be noisy (e.g. extracted through Automatic Speech Recognition (ASR), PDF text extraction etc.), leading to state-of-the-art neural models being highly sensitive to the noise producing sub-optimal results [5]. This demands denoising steps to refine both query and document representation. In this paper, we argue that Wikipedia, an openly available encyclopedia, can be a humanly intuitive knowledge base [6] that has the potential to provide the world view many noisy information Retrieval systems need.
Published at the First Workshop on Proactive and Agent-Supported Information Retrieval at CIKM 2022; 2022
Abstract
Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts
Extracting useful information from the user history to clearly understand informational needs is a crucial feature of a proactive information retrieval system. Regarding understanding information and relevance, Wikipedia can provide the background knowledge that an intelligent system needs. This work explores how exploiting the context of a query using Wikipedia concepts can improve proactive information retrieval on noisy text. We formulate two models that use entity linking to associate Wikipedia topics with the relevance model. Our experiments around a podcast segment retrieval task demonstrate that there is a clear signal of relevance in Wikipedia concepts while a ranking model can improve precision by incorporating them. We also find Wikifying the background context of a query can help disambiguate the meaning of the query, further helping proactive information retrieval.
Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts
Type
Journal Paper
Themes
Assistive & Accessible Technology
Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes
Kate Mattick,Ben Oldfrey, Maggie Donovan-Hall, Grace Magomere, Joseph Gakunga,Catherine Holloway
An estimated 1.5 million people undergo limb amputation each year [1]. Low- and middle-income countries (LMICs) are projected to have a rapid increase in people living with an amputation in the coming years due to prevalence of non-communicable dis-ease, trauma and conflict [1–3]. This paper explores the personal and system factors that motivate and enhance outcomes for patients accessing a prosthetic service and using a lower-limb prosthesis within a low resource setting.
Disability and Rehabilitation; 2022
Abstract
Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes
PurposeTo explore the personal and system factors that motivate and enhance outcomes for patients accessing a prosthetic service and using a lower-limb prosthesis within a low resource setting.
Materials and methodsThis study employed a qualitative approach to explore the motivations and satisfaction of individuals with lower limb loss engaging with a prosthetic service in Mombasa, Kenya. In-depth interviews were conducted over Microsoft Teams with 10 lower limb prosthesis users and thematic analysis was applied.
ResultsFive key themes emerged: acceptance, self-determination, hope, clinician relationship and perception. These findings demonstrate the importance of hopeful thinking and a supportive community in overcoming physical and stigmatising challenges. The findings further highlight the value of the service provider relationship beyond just prescribing an assistive device.
ConclusionThese results have relevance in developing patient-centred services, assistive devices and personnel training that are responsive, motivating, and cognisant of the service user. This is of particular interest as assistive technology services are newly developed in low resource settings.
Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes
Kate Mattick, Ben Oldfrey, Maggie Donovan-Hall, Grace Magomere, Joseph Gakunga & Catherine Holloway (2022) Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes, Disability and Rehabilitation, DOI:10.1080/09638288.2022.2152875
Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes
Type
Journal Paper
Themes
Culture and Participation
Research Group
Social Justice
“Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone
Victoria Austin,Catherine Holloway, Ignacia Ossul Vermehren, Abs Dumbuya,Giulia Barbareschiand Julian Walker
The World Health Organisation (WHO) estimates that there are currently one billion people in the world who need access to assistive technology (AT). Yet over 90% currently do not have access to assistive products (AP)—such as wheelchairs, hearing aids, walking sticks and eyeglasses—they need, nor and the systems and services necessary to support their appropriate provision [1]. This shocking deficit is set to double by 2050, with about two billion of us likely to require AT but no anticipated reduction in lack of access. The World Health Organisation defines AT as the “the umbrella term covering the systems and services related to the delivery of assistive products and services”, which are products that “maintain or improve an individual’s functioning and independence, thereby promoting their well-being” [2], and the importance of AT provision is strongly highlighted in the Convention on the Rights of Persons with Disabilities (CRPD) [3]. AT has also been shown to be essential to achieving many of the United Nation’s Sustainable Development Goals (SDG) [4]. Without access to AT, many persons with disabilities are unable to go to school, be active in their communities, earn an income, or play a full role in their families [5]. As a recent study found, “AT can make the impossible possible for people living with a wide range of impairments, but a lack of access to basic AT …excludes individuals and reduces their ability to live full, enjoyable, and independent lives” [6].
International Journal of Environmental Research and Public Health; 2021
Abstract
“Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone
The importance of assistive technology (AT) is gaining recognition, with the World Health Organisation (WHO) set to publish a Global Report in 2022. Yet little is understood about access for the poorest, or the potential of AT to enable this group to participate in the activities of citizenship; both formal and informal. The aim of this qualitative study was to explore AT as mediator of participation in citizenship for persons with disabilities who live in two informal settlements in Freetown, Sierra Leone (SL). The paper presents evidence from 16 participant and 5 stakeholder interviews; 5 focus groups and 4 events; combining this with the findings of a house-to-house AT survey; and two national studies—a country capacity assessment and an informal markets deep-dive. Despite citizenship activities being valued, a lack of AT was consistently reported and hindered participation. Stigma was also found to be a major barrier. AT access for the poorest must be addressed if citizenship participation for persons with disabilities is a genuine global intention and disability justice is to become a reality.
Austin, V.; Holloway, C.; Ossul Vermehren, I.; Dumbuya, A.; Barbareschi, G.; Walker, J. “Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone. Int. J. Environ. Res. Public Health2021, 18, 5547.https://doi.org/10.3390/ijerph...
Type
Journal Paper
Themes
Assistive & Accessible Technology
Research Group
Local Productions
Additive manufacturing techniques for smart prosthetic liners
B Oldfrey, A Tchorzewska, R Jackson, M Croysdale, R Loureiro,C Holloway, M Miodownik
Elastomeric liners are commonly worn between socket and limb by prosthetic wearers. This is due to their superior skin adhesion, load distribution and their ability to form a seal. Laboratory tests suggest that elastomeric liners allow reduced shear stress on the skin and give a higher cushioning effect on bony prominences, since they are soft in compression, and similar to biological tissues [1]. However, they also increase perspiration reducing hygiene and increasing skin irritations. Prosthetic users in general face a myriad of dermatological problems associated with lower limb prosthesis such as ulcers, cysts, and contact dermatitis, which are exacerbated by the closed environment of a fitted socket where perspiration is trapped and bacteria can proliferate [2].
Medical Engineering & Physics; 2021
Abstract
Additive manufacturing techniques for smart prosthetic liners
Elastomeric liners are commonly worn between the prosthetic socket and the limb. A number of improvements to the state of the art of liner technology are required to address outstanding problems. A liner that conforms to the residuum more accurately, may improve the skin health at the stump-socket interface. Previous work has shown that for effective thermal management of the socket environment, an active heat removal system is required, yet this is not available. Volume tracking of the stump could be used as a diagnostic tool for looking at the changes that occur across the day for all users, which depend on activity level, position, and the interaction forces of the prosthetic socket with the limb. We believe that it would be advantageous to embed these devices into a smart liner, which could be replaced and repaired more easily than the highly costly and labour-intensive custom-made socket. This paper presents the work to develop these capabilities in soft material technology, with: the development of a printable nanocomposite stretch sensor system; a low-cost digital method for casting bespoke prosthetic liners; a liner with an embedded stretch sensor for growth / volume tracking; a model liner with an embedded active cooling system.
Additive manufacturing techniques for smart prosthetic liners
, Additive manufacturing techniques for smart prosthetic liners, Medical Engineering & Physics, Volume 87, 2021, Pages 45-55, ISSN 1350-4533,https://doi.org/10.1016/j.mede....
Type
Journal Paper
Themes
Assistive & Accessible Technology
Culture and Participation
Research Group
Disability Interactions
“When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya
Giulia Barbareschi, Mark T. Carew, Elizabeth Aderonke Johnson, Norah Kopi,Catherine Holloway
Stigmatizing attitudes and beliefs towards disability represent one of the most pervasive and complex barriers that limits access to health care, education, employment, civic rights and opportunities for socialization for people with disabilities [1,2,3]. The damaging impact of disability stigma is widely acknowledged and, according to article 8 of the UN Convention on the Rights of Persons with disabilities, developing strategies, campaigns, policies and other initiatives to combat disability stigma and ensure that all people with disabilities are treated with dignity and respect is also a duty of the 182 countries who ratified the treaty [4]. Although the majority of literature focused on understanding disability stigma has been carried out in high-income settings [5,6,7], in the last decade, an increasing number of scholars have conducted studies looking at the negative stereotypes, prejudices and inaccurate beliefs that shape disability stigma in the Global South [3,8,9,10]. Most of these studies have described how these stigmatizing beliefs are often driven by a combination of personal and societal factors, ranging from misconceptions concerning the causes of different impairments (e.g., disability to be seen as a form of curse or punishment); assumptions about the lack of capabilities of people with disabilities; or discriminatory practices that actively endorse separation between people with and without disabilities [3,9,11,12]. Yet, there is a dearth of comparative studies that examine the perspectives of both people with and without disabilities of disability stigma and discrimination, including how the use of assistive technology may shape stigmatizing interactions.
International Journal of Environmental Research and Public Health; 2021
Abstract
“When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya
Disability stigma in many low- and middle-income countries represents one of the most pervasive barriers preventing people with disabilities from accessing equal rights and opportunities, including the uptake of available assistive technology (AT). Previous studies have rarely examined how disability stigma may be shaped through factors endemic to social interactions, including how the use of assistive technology itself may precipitate or alleviate disability stigma. Through two strands of work, we address this gap. Via a series of focus groups with Kenyans without disabilities (Study 1) and secondary data analysis of consultations with Kenyans with disabilities and their allies (Study 2), we identify shared and divergent understandings of what shapes disability stigma and discrimination. Specifically, Kenyans with and without disabilities were cognizant of how religious/spiritual interpretations of disability, conceptions of impairments as “different” from the norm, and social stereotypes about (dis)ability shaped the experience of stigma and discrimination. Moreover, both groups highlighted assistive technology as an influential factor that served to identify or “mark” someone as having a disability. However, whereas participants without disabilities saw assistive technology purely as an enabler to overcome stigma, participants with disabilities also noted that, in some cases, use of assistive technologies would attract stigma from others.
“When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya
Barbareschi G, Carew MT, Johnson EA, Kopi N, Holloway C. “When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya. International Journal of Environmental Research and Public Health. 2021; 18(8):4272.https://doi.org/10.3390/ijerph...
Type
Journal Paper
Themes
Inclusive Design
Culture and Participation
Research Group
Disability Interactions
Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement
Giulia Barbareschi,Ben Oldfrey, Long Xin, Grace N. Magomere, Wyclife A. Wetende, Carol Wanjira, Joyce Olenja,Victoria Austin, andCatherine Holloway
The World Health Organisation estimate that there are approximately a billion people with disabilities who require access to appropriate assistive technology and this number is set to double by 2050 [82]. Assistive technologies (ATs) play a crucial role in the lives of people with disabilities and are necessary to be able to access essential services and participate in family and community life according to one’s aspirations [40, 62, 68, 81]. Although this is not often specifcally mentioned, the large majority of people with disabilities will routinely use more than one assistive device in their everyday lives [25, 26]. For example a person with a visual impairment is likely to use a white cane to navigate from their house to the office where they work and have a screen-reader, or an equivalent accessibility software, on their computer to be able to do their work once in the office [17].
ASSETS '20: Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility; 2020
Abstract
Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement
Living in informality is challenging. It is even harder when you have a mobility impairment. Traditional assistive products such as wheelchairs are essential to enable people to travel. Wheelchairs are considered a Human Right. However, they are difficult to access. On the other hand, mobile phones are becoming ubiquitous and are increasingly seen as an assistive technology. Should therefore a mobile phone be considered a Human Right? To help understand the role of the mobile phone in contrast of a more traditional assistive technology – the wheelchair, we conducted contextual interviews with eight mobility impaired people who live in Kibera, a large informal settlement in Nairobi. Our findings show mobile phones act as an accessibility bridge when physical accessibility becomes too challenging. We explore our findings from two perspective – human infrastructure and interdependence, contributing an understanding of the role supported interactions play in enabling both the wheelchair and the mobile phone to be used. This further demonstrates the critical nature of designing for context and understanding the social fabric that characterizes informal settlements. It is this social fabric which enables the technology to be useable.
Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement
Giulia Barbareschi, Ben Oldfrey, Long Xin, Grace Nyachomba Magomere, Wycliffe Ambeyi Wetende, Carol Wanjira, Joyce Olenja, Victoria Austin, and Catherine Holloway. 2020. Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal settlement. In Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility (ASSETS '20). Association for Computing Machinery, New York, NY, USA, Article 50, 1–13.https://doi.org/10.1145/337362...
Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement
Type
Book
Research Group
Disability Interactions
Disability Interactions Creating Inclusive Innovations
Catherine Holloway,Giulia Barbareschi
; 2021
Abstract
Disability Interactions Creating Inclusive Innovations
Disability interactions (DIX) is a new approach to combining cross-disciplinary methods and theories from Human Computer Interaction (HCI), disability studies, assistive technology, and social development to co-create new technologies, experiences, and ways of working with disabled people. DIX focuses on the interactions people have with their technologies and the interactions which result because of technology use. A central theme of the approach is to tackle complex issues where disability problems are part of a system that does not have a simple solution. Therefore, DIX pushes researchers and practitioners to take a challenge-based approach, which enables both applied and basic research to happen alongside one another. DIX complements other frameworks and approaches that have been developed within HCI research and beyond. Traditional accessibility approaches are likely to focus on specific aspects of technology design and use without considering how features of large-scale assistive technology systems might influence the experiences of people with disabilities. DIX aims to embrace complexity from the start, to better translate the work of accessibility and assistive technology research into the real world. DIX also has a stronger focus on user-centered and participatory approaches across the whole value chain of technology, ensuring we design with the full system of technology in mind (from conceptualization and development to large-scale distribution and access). DIX also helps to acknowledge that solutions and approaches are often non-binary and that technologies and interactions that deliver value to disabled people in one situation can become a hindrance in a different context. Therefore, it offers a more nuanced guide to designing within the disability space, which expands the more traditional problem-solving approaches to designing for accessibility. This book explores why such a novel approach is needed and gives case studies of applications highlighting how different areas of focus—from education to health to work to global development—can benefit from applying a DIX perspective. We conclude with some lessons learned and a look ahead to the next 60 years of DIX.
Disability Interactions Creating Inclusive Innovations
Type
Journal Paper
Themes
Assistive & Accessible Technology
Climate & Crisis Resilience
Research Group
Disability Interactions
Measuring assistive technology supply and demand: A scoping review
Jamie Danemayer,Dorothy Boggs, Emma M. Smith, Vinicius Delgado Ramos, Linamara Rizzo Battistella,Cathy Holloway,and Sarah Polack
An assistive product (AP) is defined as a product used exter-nally to the human body, whose primary purpose is to main-tain or improve an individual’s functioning and independence and thereby promote his or her well-being (WHO, 2016). Global population aging forecasts a rise in the need for solu-tions that support participation and independence, including APs. In this paper, we review current population-level AP supply and demand estimation methods for five priority APs and provide recommendations for improving national and global AP market evaluation.
Assistive Technology The Official Journal of RESNA; 2021
Abstract
Measuring assistive technology supply and demand: A scoping review
The supply of and market demand for assistive products (APs) are complex and influenced by diverse stakeholders. The methods used to collect AP population-level market data are similarly varied. In this paper, we review current population-level AP supply and demand estimation methods for five priority APs and provide recommendations for improving national and global AP market evaluation. Abstracts resulting from a systematic search were double-screened. Extracted data include WHO world region, publication year, age-groups, AP domain(s), study method, and individual assessment approach.497 records were identified. Vision-related APs comprised 65% (n = 321 studies) of the body of literature; hearing (n = 59), mobility (n = 24), cognitive (n = 2), and studies measuring multiple domains (n = 92) were proportionately underrepresented. To assess individual AP need, 4 unique approaches were identified among 392 abstracts; 45% (n = 177) used self-report and 84% (n = 334) used clinical evaluation. Study methods were categorized among 431 abstracts; Cross-sectional studies (n = 312, 72%) and secondary analyses of cross-sectional data (n = 61, 14%) were most common. Case studies illustrating all methods are provided. Employing approaches and methods in the contexts where they are most well-suited to generate standardized AP indicators will be critical to further develop comparable population-level research informing supply and demand, ultimately expanding sustainable access to APs.
Measuring assistive technology supply and demand: A scoping review
Jamie Danemayer, Dorothy Boggs, Emma M. Smith, Vinicius Delgado Ramos, Linamara Rizzo Battistella, Cathy Holloway & Sarah Polack (2021) Measuring assistive technology supply and demand: A scoping review, Assistive Technology, 33:sup1, S35-S49, DOI: 10.1080/10400435.2021.1957039
Measuring assistive technology supply and demand: A scoping review
Type
Journal Paper
Themes
Assistive & Accessible Technology
Research Group
Humanitarian & Disasters
Meeting AT needs in humanitarian crises: The current state of provision
Golnaz Whittaker, Gavin Adam Wood, Giulia Oggero,Maria Kett, Kirstin Lange
This paper discusses the evidence available in the literature for the scale and quality of AT provision interventions in crises, and what is known about the challenges and facilitators of provision. We conducted a search of the academic literature and retained literature that reported on any form of AT provision following crisis, where international humanitarian response was in place, published in English between January 2010 and June 2020.
Assistive Technology The Official Journal of RESNA; 2021
Abstract
Meeting AT needs in humanitarian crises: The current state of provision
Humanitarian coordination systems increasingly recognize and aim to respond to the needs of people with disabilities within populations affected by crises, spurred on by the UN Convention on the Rights of Persons with Disabilities (CRPD) which was adopted in 2006. Many agencies state their aim to meet the requirements of the CRPD using a “twin track” approach: ensuring the inclusion of people with disabilities in mainstream provision, alongside targeted support for their needs, which may include the need for Assistive Technology (AT). However, there is very little evidence of AT provision in humanitarian settings, which is a specific and urgent need for many people including the elderly and people with disabilities, and an implicit requirement of Article 11 of the CRPD and World Health Assembly resolution on improving access to assistive technology. There is also little evidence of effective mechanisms for AT provision in humanitarian settings. This is despite high and growing levels of unmet AT need in crises, and despite the legally binding requirement in the CRPD to provide AT for those who need it. AT provision faces unique challenges in humanitarian settings. This paper discusses the evidence available in the literature for the scale and quality of AT provision interventions in crises, and what is known about the challenges and facilitators of provision. We conducted a search of the academic literature and retained literature that reported on any form of AT provision following crisis, where international humanitarian response was in place, published in English between January 2010 and June 2020. We found very few examples in that academic literature of systematic and coordinated AT provision at the acute stage of crisis, and even less in the preparedness and post-acute stages. However, it is difficult to assess whether this is the result of insufficient academic attention or reflects a lack of provision. The small body of academic literature that describes AT provision in humanitarian settings paints a picture of small-scale provision, specialized to single types of impairments, and delivered by predominantly by NGOs. We also conducted a search of the gray literature, using the same inclusion criteria, in two countries: Afghanistan and South Sudan (case studies forthcoming). This gray literature provided supplementary evidence of the types of AT providers and AT provision available in those protracted crises. There are very few examples of how AT services can be scaled up (from a very low baseline) and maintained sustainably within a strengthened health system. The literature also describes more examples of provision of assistive products for mobility over assistive products for other impairments. If the paucity of literature on AT provision in humanitarian settings is a reflection of the scale of provision, this implies a deficiency in humanitarian response when it comes to providing people with AT needs with the essential products and services to which they have a right, and which will enable their access to basic, life-saving assistance. We conclude by providing recommendations for urgent actions that the AT and humanitarian community must take to fill this critical gap in the provision of essential products and services for a potentially marginalized and excluded group.
Meeting AT needs in humanitarian crises: The current state of provision
Golnaz Whittaker, Gavin Adam Wood, Giulia Oggero, Maria Kett & Kirstin Lange (2021) Meeting AT needs in humanitarian crises: The current state of provision, Assistive Technology, 33:sup1, S3-S16, DOI: 10.1080/10400435.2021.1934612
Meeting AT needs in humanitarian crises: The current state of provision
Type
Conference Paper
Themes
Assistive & Accessible Technology
Value beyond function: analyzing the perception of wheelchair innovations in Kenya
Barbareschi, G; Daymond, S; Honeywill, J; Singh, A; Noble, D; Mbugua, N; Harris, I;Austin, V;Holloway, C
The World Health Organization (WHO) defines Assistive Technology (AT) as “an umbrella term covering the systems and services related to the delivery of assistive products and services” [6]. This definition highlights how AT encompasses not only the physical and digital products used by millions of persons with disabilities (PWDs) worldwide, but also the systems and services that accompany the provision of these devices [78].
ASSETS '20: The 22nd International ACM SIGACCESS Conference on Computers and Accessibility.; 2020
Abstract
Value beyond function: analyzing the perception of wheelchair innovations in Kenya
Innovations in the field of assistive technology are usually evaluated based on practical considerations related to their ability to perform certain functions. However, social and emotional aspects play a huge role in how people with disabilities interact with assistive products and services. Over a five months period, we tested an innovative wheelchair service provision model that leverages 3D printing and Computer Aided Design to provide bespoke wheelchairs in Kenya. The study involved eight expert wheelchair users and five healthcare professionals who routinely provide wheelchair services in their community. Results from the study show that both users and providers attributed great value to both the novel service delivery model and the wheelchairs produced as part of the study. The reasons for their appreciation went far beyond the practical considerations and were rooted in the fact that the service delivery model and the wheelchairs promoted core values of agency, empowerment and self-expression.
Value beyond function: analyzing the perception of wheelchair innovations in Kenya
Type
Conference Paper
Themes
Assistive & Accessible Technology
Culture and Participation
Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh
Nusrat Jahan,Giulia Barbareschi, Clara Aranda Jan, Charles Musungu Mutuku, Naemur Rahman,Victoria Austin,Catherine Holloway
Worldwide it is estimated that there are over a billion people who live with some form of disability[1]. Approximately 80% of people with disabilities live in low-and-middle income countries (LMICs). The combination of an inaccessible environment compounded by socio-economic factors such as poverty and stigma, makes it more likely for people with disabilities to be marginalised and excluded from society[1]. Assistive Technologies (ATs) are known to bridge the accessibility gaps and allow for greater social inclusion. However, there is a lack of adequate access to ATs in LMICs, combined with often poorly designed services, which only magnifies these challenges, thus limiting the opportunities for persons with disabilities to live an independent life[2]. Despite the importance of AT, access to AT globally is inadequate with only 10 percent of those in need having access to the ATs that they need[2].
2020 IEEE Global Humanitarian Technology Conference
Abstract
Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh
Globally, mobile technology plays a significant role connecting and supporting people with disabilities. However, there has been limited research focused on understanding the impact of mobile technology in the lives of persons with disabilities in low or middle- income countries. This paper presents the findings of a participatory photovoice study looking at the role that mobile phones play in the daily lives of 16 persons with disabilities in Kenya and Bangladesh. Participants used a combination of pictures and voice recordings to capture their own stories and illustrate the impact that mobile phone use has on their lives. Through thematic analysis, we categorized the benefits of mobile phones captured by participants as 1) Improved social connection; 2) Increased independence and 3) Access to opportunities. While mobile phones are ubiquitously used for communication, for persons with disabilities they become essential assistive technologies that bridge barriers to opportunities which are not accessible otherwise. Our paper adds evidence to the need for mobile phones for persons with disabilities to enable communication and connectivity in support of development.
Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh
N. Jahan et al., "Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh," 2020 IEEE Global Humanitarian Technology Conference (GHTC), Seattle, WA, USA, 2020, pp. 1-8, doi: 10.1109/GHTC46280.2020.9342934.
Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh
Type
Conference Paper
Themes
Assistive & Accessible Technology
Research Group
Local Productions
A Preliminary Study to Understand How Mainstream Accessibility and Digital Assistive Technologies Reaches People in Lower- and Middle-Income Countries
Tigmanshu Bhatnagar, George Torrens, Ben Oldfrey, Priya MorjariaFelipe Ramos Barajas, Katherine PerryandCatherine Holloway
Access to information on digital platforms not only facilitates education, employment, entertainment, social interaction but also facilitates critical governmental services, ecommerce, healthcare services and entrepreneurship [1]. Article 9 of United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) enforces its signatories to commit to provide full accessibility to every citizen of the nation [2]. This has helped to spearhead accessibility directives such as the European Accessibility Act [3] that aims to improve the functioning of markets for accessible products and services. Such directives contribute to ensure that mainstream digital technologies (smartphones, computers etc.) are accessible for everyone and without being socially remarkable, they are able to assist in daily living. Additionally, there is evidence that improving access in mainstream technologies improves product experience and usability for everyone [4]. However, mainstream access has not been fully realized, leading to inferior opportunities for people with disabilities, a disparity which is more prominent in lower and middle-income countries [5].
RESNA Annual Conference; 2021
A Preliminary Study to Understand How Mainstream Accessibility and Digital Assistive Technologies Reaches People in Lower- and Middle-Income Countries
Type
Journal Paper
Themes
Assistive & Accessible Technology
Research Group
Local Productions
Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World?
Ben Oldfrey,Giulia Barbareschi, Priya Morjaria, Tamara Giltsoff, Jessica Massie, Mark Miodownik andCatherine Holloway
From multiple studies conducted through the FCDO AT2030 Programme, as well as key literature, we examine whether Assistive Technology (AT) provision models could look towards more sustainable approaches, and by doing this benefit not only the environment, but also address the problems that the current provision systems have.
Sustainability
Abstract
Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World?
From multiple studies conducted through the FCDO AT2030 Programme, as well as key literature, we examine whether Assistive Technology (AT) provision models could look towards more sustainable approaches, and by doing this benefit not only the environment, but also address the problems that the current provision systems have. We show the intrinsic links between disability inclusion and the climate crisis, and the particular vulnerability people with disabilities face in its wake. In particular, we discuss how localised circular models of production could be beneficial, facilitating context driven solutions and much needed service elements such as repair and maintenance. Key discussion areas include systems approaches, digital fabrication, repair and reuse, and material recovery. Finally, we look at what needs be done in order to enable these approaches to be implemented. In conclusion, we find that there are distinct parallels between what AT provision models require to improve equitable reliable access, and strategies that could reduce environmental impact and bring economic benefit to local communities. This could allow future AT ecosystems to be key demonstrators of circular models, however further exploration of these ideas is required to make sense of the correct next steps. What is key in all respects, moving forward, is aligning AT provision with sustainability interventions.
Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World?
Oldfrey, B.; Barbareschi, G.; Morjaria, P.; Giltsoff, T.; Massie, J.; Miodownik, M.; Holloway, C. Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World? Sustainability2021, 13, 10867.https://doi.org/10.3390/su1319...
Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World?
Type
Journal Paper
Themes
Assistive & Accessible Technology
Research Group
Local Productions
A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems
Catherine Holloway, Dafne Zuleima Morgado Ramirez,Tigmanshu Bhatnagar,Ben Oldfrey, Priya Morjaria, Soikat Ghosh Moulic, Ikenna D. Ebuenyi,Giulia Barbareschi,Fiona Meeks, Jessica Massie, Felipe Ramos-Barajas, Joanne McVeigh, Kyle Keane, George Torrens, P. V.M. Rao, Malcolm MacLachlan,Victoria Austin, Rainer Kattel, Cheryl D Metcalf & Srinivasan Sujatha
It is essential to understand the strategies and processes which are deployed currently across the Assistive Technology (AT) space toward measuring innovation. The main aim of this paper is to identify functional innovation strategies and processes which are being or can be deployed in the AT space to increase access to AT globally.
Assistive Technology The Official Journal of RESNA
Abstract
A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems
It is essential to understand the strategies and processes which are deployed currently across the Assistive Technology (AT) space toward measuring innovation. The main aim of this paper is to identify functional innovation strategies and processes which are being or can be deployed in the AT space to increase access to AT globally. We conducted a scoping review of innovation strategies and processes in peer-reviewed literature databases and complemented this by identifying case studies demonstrating innovation strategies. The review includes WHO world region, publication year, AT type and a sector analysis against the Systems-Market for Assistive and Related Technologies Framework. We analyzed the case studies and interviews using thematic analysis. We included 91 papers out of 3,127 after review along with 72 case studies. Our results showed that product innovations were more prevalent than provision or supply innovations across papers and case studies. Case studies yielded two themes: open innovation (OI); radical and disruptive innovation. Financial instruments which encourage OI are needed and we recommend pursuing OI for AT innovation. Embedding AT within larger societal missions will be key to success governments and investors need to understand what AT is and their translational socioeconomic value.
A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems
Catherine Holloway, Dafne Zuleima Morgado Ramirez, Tigmanshu Bhatnagar, Ben Oldfrey, Priya Morjaria, Soikat Ghosh Moulic, Ikenna D. Ebuenyi, Giulia Barbareschi, Fiona Meeks, Jessica Massie, Felipe Ramos-Barajas, Joanne McVeigh, Kyle Keane, George Torrens, P. V.M. Rao, Malcolm MacLachlan, Victoria Austin, Rainer Kattel, Cheryl D Metcalf & Srinivasan Sujatha (2021) A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems, Assistive Technology, 33:sup1, 68-86, DOI:10.1080/10400435.2021.1970653
A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems
Type
Journal Paper
Themes
Inclusive Design
Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities
Mikaela Patrick,Iain McKinnon
Public spaces, including recreational and social spaces, are often not prioritised. Inclusive public spaces are fundamental to participation and inclusive in society. Including persons with disabilities in the design and planning of the built environment supports equal rights and helps identify people’s aspirations for inclusive environments. Four city case studies will be discussed in this paper: Ulaanbaatar, Mongolia; Varanasi, India; Surakarta, Indonesia; and Nairobi, Kenya.
The Journal of Public Space
Abstract
Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities
This paper presents some of the findings from a global research study on inclusive infrastructure and city design and will focus on inclusive public spaces. Persons with disabilities can experience multi-dimensional exclusion from urban life, including but not limited to physical, attitudinal and social barriers. Public spaces, including recreational and social spaces, are often not prioritised. Inclusive public spaces are fundamental to participation and inclusive in society. Including persons with disabilities in the design and planning of the built environment supports equal rights and helps identify people’s aspirations for inclusive environments.Four city case studies will be discussed in this paper: Ulaanbaatar, Mongolia; Varanasi, India; Surakarta, Indonesia; and Nairobi, Kenya. Research participants and objectives are organised by three stakeholder groups:
People - first-hand experiences of persons with disabilities living in the city and their aspirations for a more inclusive city
Policy - the awareness and understanding of inclusive design among policy-makers
Practice - the awareness and understanding of inclusive design among practitioners including barriers to implementation, opportunities and the relationship with assistive technology
Methods include document reviews, interviews, photo diaries and co-design workshops with participatory and inclusive engagement of persons with disabilities throughout. Findings on public spaces are discussed in three ways:
The types of public spaces valued by participants in each of the four cities.
The barriers and challenges experienced by persons with disabilities in the public realm.
Aspirations for more inclusive public spaces and opportunities for inclusive design
The paper concludes by discussing how the targeted stakeholder groups of people, policy and practice also help represent three essential dimensions of inclusive city design and forming a framework for successful implementation and delivery and supporting targets set out through the UNCRPD and Sustainable Development Goals (SDGs).
Cite
Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities
Patrick, M. and McKinnon, I. (2022) “Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities”, The Journal of Public Space, 7(2), pp. 93–116. doi: 10.32891/jps.v7i2.1500.
Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities
Type
Journal Paper
Themes
Culture and Participation
Research Group
Social Justice
Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change
Jessica Noske-Turner, Emma Pullen, Mufunanji Magalasi, Damian Haslett, Jo Tacchi
Communication & Sport
Abstract
Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change
The purpose of this commentary is to discuss how Paralympic coverage in sub-Saharan Africa can be effectively mobilised to stimulate discursive and structural change around disability. Paralympic coverage has demonstrated its pedagogical power to engage public(s) and challenge stigma toward disability. Yet, the Global picture of Paralympic broadcasting is deeply uneven, with audiences in parts of the Global South afforded limited opportunities to watch the Games. Considering this, the International Paralympic Committee has begun to broadcast Paralympic coverage across sub-Saharan Africa with an explicit aim to challenge stigma toward disability. In this article, we draw on examples from research to argue that ideas from the field of Communication for Social Change (CfSC) can add value towards this aim. We begin by providing a brief overview of CfSC before critically examining one of the field’s key concepts – Communicative (E)ecologies. Following this, we critically reflect on the potential of Paralympic broadcasting as a vehicle for social change and disability rights agendas in sub-Saharan Africa. We argue that thinking with CfSC concepts show the importance of a ‘decentred’ media approach that engages with disability community advocacy groups, localised communication activities and practices, and culturally specific disability narratives.
Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change
Noske-Turner, J., Pullen, E., Magalasi, M., Haslett, D., & Tacchi, J. (2022). Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change. Communication & Sport, 10(5), 1001–1015.https://doi.org/10.1177/216747...
Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design
Troy Bodkin
Doctoral Thesis. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process.
Loughborough University
Abstract
Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design
For many years, the biggest issue that causes discomfort and hygiene issues for patients with lower limb amputations have been the interface between body and prosthetic, the socket. Often made of an inflexible, solid polymer that does not allow the residual limb to breathe or perspire and with no consideration for the changes in size and shape of the human body caused by changes in temperature or environment, inflammation, irritation and discomfort often cause reduced usage or outright rejection of the prosthetic by the patient in their day to day lives. To address these issues and move towards a future of improved quality of life for patients who suffer amputations, Loughborough University formed the Next Generation Prosthetics research cluster. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process. The research presented in this thesis is based on three primary studies. The first study involved the conception of a CAD criteria, deciding what features are needed to represent the various properties the future socket outlined by the research cluster needs. These criteria were then used for testing three CAD systems, one each from the Parametric, Non Uniform Rational Basis Spline (NURBS) and Polygon archetypes respectively. The result of these tests led to the creation of a hybrid control workflow, used as the basis for finding improvements. The second study explored emerging CAD solutions, various new systems or plug-ins that had opportunities to improve the control model. These solutions were tested individually in areas where they could improve the workflow, and the successful solutions were added to the hybrid workflow to improve and reduce the workflow further. The final study involved taking the knowledge gained from the literature and the first two studies in order to theorise how an ideal CAD system for producing future prosthetic sockets would work, with considerations for user interface issues as well as background CAD applications. The third study was then used to inform the final deliverable of this research, a software design specification that defines how the system would work. This specification was written as a challenge to the CAD community, hoping to inform and aid future advancements in CAD software. As a final stage of research validation, a number of members of the CAD community were contacted and interviewed about their feelings of the work produced and their feedback was taken in order to inform future research in this area.
Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design
Bodkin, Troy L. (2017): Specifying a hybrid, multiple material CAD system for next-generation prosthetic design. Loughborough University. Thesis.https://hdl.handle.net/2134/25...;
Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers
Giulia Barbareschi
Doctoral Thesis. This thesis makes two contributions to facilitate wheelchair users’ engagement in the participatory design process for ATs, while being mindful of the burden of participation. The first contribution is a framework that provides a modular structure guiding the participatory design process from initial problem identification and analysis to facilitating collaborations between wheelchair users and designers. The framework identifies four factors determining the need and adoption process for ATs: (i) People focuses on the target population, (ii) Person includes personal characteristics, (iii) Activity refers to the challenges associated with the task, and (iv) Context encompasses the effect of the environment in which the activity takes place. The second contribution constitutes a rich picture of personal and external elements influencing real world wheelchair transfers that emerged from four studies carried out to investigate the effect of the framework factors on the design process for ATs.
UCL (University College London)
Abstract
YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers
Transferring independently to and from their wheelchair is an essential routine task for many wheelchair users but it can be physically demanding and can lead to falls and upper limb injuries that reduce the person’s independence. New assistive technologies (ATs) that facilitate the performance of wheelchair transfers have the potential to allow wheelchair users to gain further independence. To ensure that users’ needs are addressed by ATs, the active involvement of wheelchair users in the process of design and development is critical. However, participation can be burdensome for many wheelchair users as design processes where users are directly involved often require prolonged engagement. This thesis makes two contributions to facilitate wheelchair users’ engagement in the participatory design process for ATs, while being mindful of the burden of participation. The first contribution is a framework that provides a modular structure guiding the participatory design process from initial problem identification and analysis to facilitating collaborations between wheelchair users and designers. The framework identifies four factors determining the need and adoption process for ATs: (i) People focuses on the target population, (ii) Person includes personal characteristics, (iii) Activity refers to the challenges associated with the task, and (iv) Context encompasses the effect of the environment in which the activity takes place. The second contribution constitutes a rich picture of personal and external elements influencing real world wheelchair transfers that emerged from four studies carried out to investigate the effect of the framework factors on the design process for ATs. A related outcome based on these contributions is a framing document to share knowledge between wheelchair users and designers to provide focus and promote an equal collaboration among participants.
YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers
Barbareschi, Giulia. “YouTransfer, YouDesign : a Participatory Approach to Design Assistive Technology for Wheelchair Transfers / Giulia Barbareschi.” Thesis (Ph.D.)--University College London, 2018., 2018. Print.
YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Understanding wrist splint user needs and personalisation through codesign
Charlotte Pyatt
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy at Loughborough University.
Loughborough University
Abstract
Understanding wrist splint user needs and personalisation through codesign
Wrist splints are a common treatment for rheumatoid arthritis, however their effectiveness is compromised by patients not wearing splints as often as prescribed. Previous research has identified a number of reasons for non-compliance, but typically lacks insights that could lead to improved splint design.
This thesis investigates the motivators for patients to wear and not wear their wrist splints and, the impact of personalisation of splint appearance on patient wear. The work is based on the premise that digital design and manufacturing processes, such as Computer-Aided Design (CAD) and 3D Printing, can produce bespoke splints on demand.
The research begins with a literature review across the core areas of: splinting, additive manufacture, product appearance and personalisation. This literature review identifies gaps in knowledge from which research questions are established for the work.
The research employs a qualitative, generative design research approach and, follows a codesign framework employing telling, making and enacting tools. The thesis is made up of three studies. The first study is a sensitisation study and uses design probes to prepare the participants for the research and begin exploring the problem space. The second is a comprehensive study into participants splint wear behaviour and uses context mapping and scenario picture card tools to investigate the motivators for participants to wear and not wear wrist splints, along with positive and negative outcomes or wearing/not wearing splints. The final study uses a personalisation toolkit to elicit patient needs for a future wrist splint design and investigate self-reported expectations regarding compliance of patients who used the toolkit.
The research finds that patient compliance is affected by practical and aesthetic limitations of current splints. It identifies 4 motivating factors to wear a splint and 10 motivating factors to not wear a splint. Additionally, it identifies 6 positive outcomes of wearing splints, 6 negative outcomes of wearing splints, 3 positive outcomes of not wearing splints and 3 negative outcomes of not wearing splints. Requirements for an improved splint design are established and form the basis of the design for a prototype personalisation toolkit. Testing of this toolkit reveals that patients are keen to own more than one splint and personalise splints to match the scenario in which it is to be worn. Patients reported that they expected to be more compliant with a personalised splint when compared to their current splint.
Understanding wrist splint user needs and personalisation through codesign
Pyatt, Charlotte (2018): Understanding wrist splint user needs and personalisation through codesign. Loughborough University. Thesis.https://doi.org/10.26174/thesi...;
Understanding wrist splint user needs and personalisation through codesign
Type
PhD
Themes
Assistive & Accessible Technology
Shared Control for Wheelchair Interfaces
Dr Chinemelu Ejiamatu Muoma Ezeh
Doctoral Thesis. Independent mobility is fundamental to the quality of life of people with impairment. Most people with severe mobility impairments, whether congenital, e.g., from cerebral palsy, or acquired, e.g., from spinal cord injury, are prescribed a wheelchair. A small yet significant number of people are unable to use a typical powered wheelchair controlled with a joystick. Instead, some of these people require alternative interfaces such as a head- array or Sip/Puff switch to drive their powered wheelchairs. However, these alternative interfaces do not work for everyone and often cause frustration, fatigue and collisions. This thesis develops a novel technique to help improve the usability of some of these alternative interfaces, in particular, the head-array and Sip/Puff switch.
UCL (University College London)
Abstract
Shared Control for Wheelchair Interfaces
Independent mobility is fundamental to the quality of life of people with impairment. Most people with severe mobility impairments, whether congenital, e.g., from cerebral palsy, or acquired, e.g., from spinal cord injury, are prescribed a wheelchair. A small yet significant number of people are unable to use a typical powered wheelchair controlled with a joystick. Instead, some of these people require alternative interfaces such as a head- array or Sip/Puff switch to drive their powered wheelchairs. However, these alternative interfaces do not work for everyone and often cause frustration, fatigue and collisions. This thesis develops a novel technique to help improve the usability of some of these alternative interfaces, in particular, the head-array and Sip/Puff switch. Control is shared between a powered wheelchair user, using an alternative interface and a pow- ered wheelchair fitted with sensors. This shared control then produces a resulting motion that is close to what the user desires to do but a motion that is also safe. A path planning algorithm on the wheelchair is implemented using techniques in mo- bile robotics. Afterwards, the output of the path planning algorithm and the user’s com- mand are both modelled as random variables. These random variables are then blended in a joint probability distribution where the final velocity to the wheelchair is the one that maximises the joint probability distribution. The performance of the probabilistic approach to blending the user’s inputs with the output of a path planner, is benchmarked against the most common form of shared control called linear blending. The benchmarking consists of several experiments with end users both in a simulated world and in the real-world. The thesis concludes that probabilistic shared control provides safer motion compared with the traditional shared control for difficult tasks and hard-to-use interfaces.
Ezeh, Chinemelu Ejiamatu Muoma. Shared Control for Wheelchair Interfaces. UCL (University College London), 2018. Print.
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Materials For Facial Prostheses In Resource Limited Countries
Sophia Esther Liiba Tetteh
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy of Loughborough University
Loughborough University
Abstract
Materials For Facial Prostheses In Resource Limited Countries
Facial prostheses are artificial devices that replace a missing body part in the facial and neck regions of the body. Defects or deformities in these regions can lead to functional deficiencies; social and psychological effects in addition to cosmetic defects. Restoration or rehabilitation in resource limited countries is usually provided by charities and organisations volunteering assistance overseas, with some training of local staff in the fabrication of these prostheses. Furthermore, these countries typically lack technical knowhow and trained personnel. In industrialised nations maxillofacial prosthetics has developed into a sophisticated medical speciality requiring highly skilled staff and expensive facilities. In resource limited countries surgical procedures may be an option for rehabilitation of these deformities/defects however, they tend to be unavailable or unaffordable and donated prostheses are not suitable. Hence, this research explores, from first principles, the appropriate and affordable local provision of maxillofacial prostheses in resource constrained regions. The investigation provides knowledge on identifying requirements for resource limited areas, resulting in the creation of a guideline constituting priorities, requirements and specifications. It further explores the viability of potentially cheaper, locally available candidate materials via weathering and antimicrobial methods in ascertaining material longevity.
Materials For Facial Prostheses In Resource Limited Countries
Tetteh, Sophia (2019): Materials for facial prostheses in resource-limited countries. Loughborough University. Thesis.https://doi.org/10.26174/thesi...;
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers
Rhys James Williams
Thesis: Firstly, the research provides a methodological contribution showing how to conduct mixed-methods research to obtain rich insights into complex prosthesis phenomena. Secondly, the research highlights the need to appreciate psychological and contextual factors when researching prosthesis wearer thermal comfort. The research contributions are also converted into an implication for prosthesis design. The concept of 'regaining control' to psychologically mitigate thermal discomfort could be incorporated into technologies by using 'on-demand' thermal discomfort relief, rather than 'always-on' solutions, as have been created in the past.
UCL, ProQuest Dissertations Publishing
Abstract
Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers
Amongst lower-limb prosthesis wearers, thermal discomfort is a common problem with an estimated prevalence of more than 50%. Overheating does not just create discomfort to the user, but it has been linked to excessive sweating, skin damage caused by a moist environment and friction. Due to impermeable prosthetic components and a warm moist environment, minor skin damage can result in skin infections that can lead to prosthesis cessation, increased social anxiety, isolation and depression. Despite the seriousness of thermal discomfort, few studies explore the issue, with research predominantly constrained to controlled laboratory scenarios, with only one out of laboratory study. In this thesis, studies investigate how thermal discomfort arises and what are the consequences of thermal discomfort for lower-limb prosthesis wearers. Research studies are designed around the principles of presenting lived experiences of the phenomenon and conducting research in the context of participants' real-life activities. A design exploration chapter investigates modifying liner materials and design to create a passive solution to thermal discomfort. However, this approach was found to be ineffective and unfeasible. Study 1 presents a qualitative study which investigates the user experience of a prosthesis, thermal discomfort and related consequences. Study 2 explores limb temperature of male amputees inside and outside the laboratory, with the latter also collecting perceived thermal comfort (PTC) data. Finally, Study 3 investigates thermal discomfort in the real-world and tracks limb temperature, ambient conditions, activities, and experience sampling of PTC. While there were no apparent relationships presented in sensor data, qualitative data revealed that in situations where prosthesis wearers perceived a lack of control, thermal discomfort seemed to be worse. When combined, the studies create two knowledge contributions. Firstly, the research provides a methodological contribution showing how to conduct mixed-methods research to obtain rich insights into complex prosthesis phenomena. Secondly, the research highlights the need to appreciate psychological and contextual factors when researching prosthesis wearer thermal comfort. The research contributions are also converted into an implication for prosthesis design. The concept of 'regaining control' to psychologically mitigate thermal discomfort could be incorporated into technologies by using 'on-demand' thermal discomfort relief, rather than 'always-on' solutions, as have been created in the past.
Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers
Williams, Rhys James. “Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers.” ProQuest Dissertations Publishing, 2020. Print.
Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Design rules for additively-manufactured wrist splints
Sarah Kelly
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy of Loughborough University.
Loughborough University
Abstract
Design rules for additively-manufactured wrist splints
Additive Manufacturing (AM) often known by the term three-dimensional printing (3DP) has been acknowledged as a potential manufacturing revolution. AM has many advantages over conventional manufacturing techniques; AM techniques manufacture through the addition of material - rather than traditional machining or moulding methods. AM negates the need for tooling, enabling cost-effective low-volume production in high-wage economies and the design & production of geometries that cannot be made by other means. In addition, the removal of tooling and the potential to grow components and products layer-by-layer means that we can produce more from less in terms of more efficient use of raw materials and energy or by making multifunctional components and products. The proposed Centre for Doctoral Training (CDT) in Additive Manufacturing and 3D Printing has the vision of training the next generation of leaders, scientists and engineers in this diverse and multi-disciplinary field. As AM is so new current training programmes are not aligned with the potential for manufacturing and generally concentrate on the teaching of Rapid Prototyping principles, and whilst this can be useful background knowledge, the skills and requirements of using this concept for manufacturing are very different. This CDT will be training cohorts of students in all of the basic aspects of AM, from design and materials through to processes and the implementation of these systems for manufacturing high value goods and services. The CDT will also offer specialist training on aspects at the forefront of AM research, for example metallic, medical and multi-functional AM considerations. This means that the cohorts graduating from the CDT will have the background knowledge to proliferate throughout industry and the specialist knowledge to become leaders in their fields, broadening out the reach and appeal of AM as a manufacturing technology and embedding this disruptive technology in company thinking. In order to give the cohorts the best view of AM, these students will be taken on study tours in Europe and the USA, the two main research powerhouses of AM, to learn from their international colleagues and see businesses that use AM on a daily basis. One of the aims of the CDT in AM is to educate and attract students from complementary basic science, whether this be chemistry, physics or biology. This is because AM is a fast moving area. The benefits of having a CDT in AM and coupling with students who have a more fundamental science base are essential to ensure innovation & timeliness to maintain the UK's leading position. AM is a disruptive technology to a number of industrial sectors, yet the CDTs industrial supporters, who represent a breadth of industrial end-users, welcome this disruption as the potential business benefits are significant. Growing on this industry foresight, the CDT will work in key markets with our supporters to ensure that AM is positioned to provide a real and lasting contribution & impact to UK manufacturing and provide economic stability and growth. This contribution will provide societal benefits to UK citizens through the generation of wealth and employment from high value manufacturing activities in the UK.
Design rules for additively-manufactured wrist splints
Kelly, Sarah (2020): Design rules for additively-manufactured wrist splints. Loughborough University. Thesis.https://doi.org/10.26174/thesi...;
Type
PhD
Themes
Assistive & Accessible Technology
Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece
Anna Vlachaki
The literature shows that research into the aesthetic aspects of prostheses is limited. Although there are suggestions that prostheses with high levels of emotionally-driven design may improve users’ well-being, they are based only on theoretical findings. Therefore, in this thesis the effects of emotionally-driven prostheses on users’ lives and society’s attitudes were explored, with respect to culture and more specifically, the theories of individualism/ collectivism. In order to investigate the effects of culture, the research was conducted in two countries with different cultures; the UK (individualistic) and Greece (collectivistic). The thesis began with a literature review across three core areas: user, product and environment, and revealed the importance of investigating an additional area; that of prosthetists. The research employed a qualitative approach and consisted of four studies.
Loughborough University
Abstract
Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece
The literature shows that research into the aesthetic aspects of prostheses is limited. Although there are suggestions that prostheses with high levels of emotionally-driven design may improve users’ well-being, they are based only on theoretical findings. Therefore, in this thesis, the effects of emotionally-driven prostheses on users’ lives and society’s attitudes were explored, with respect to culture and more specifically, the theories of individualism/ collectivism. In order to investigate the effects of culture, the research was conducted in two countries with different cultures; the UK (individualistic) and Greece (collectivistic). The thesis began with a literature review across three core areas: user, product and environment, and revealed the importance of investigating an additional area; that of prosthetists. The research employed a qualitative approach and consisted of four studies. Study I was an online questionnaire to explore users’ preferences towards prostheses, with respect to their culture. Study II consisted of semi-structured interviews and informational probes to comprehend the role of prostheses on users’ lives, with respect to prosthetic appearance. In Study III, the aim was to investigate prosthetists’ attitudes towards the needs of prosthetic users by conducting semi-structured interviews. Finally, Study IV was an online questionnaire to explore non-users’ attitudes towards the design of prostheses. The research showed that the use of prostheses for the completion of users’ body was not an adequate factor to improve their well-being, and a shift on users’ desires towards emotionally-driven prostheses has occurred. From the variables that were tested, sex, age, cause and area of limb-loss may affect people’s attitudes towards the design of prostheses. Furthermore, the results showed that prostheses with high emotionally-driven design evoked emotions, in both users and non-users, with higher levels of pleasantness and arousal than the emotions that were elicited by the prostheses of lower emotionally-driven designs and thus, they may trigger a greater behavioural reaction. This suggested that emotionally-driven prostheses may eliminate users’ stigmatisation by increasing their self-confidence and altering society’s attitudes. However, attention needs to be paid in collectivistic countries, as emotionally-driven prostheses may enhance users’ stigmatisation.
Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece
Vlachaki, Anna (2020): Emotionally-driven prostheses: exploring the effects on users’ lives and societies’ attitudes in the UK and Greece. Loughborough University. Thesis.https://doi.org/10.26174/thesi...;
Type
Journal Paper
| https://www.disabilityinnovation.com/publications?page=9&type=workshop+book+conference-paper+journal-paper+phd |
Metals | Free Full-Text | In Vitro Corrosion Performance of As-Extruded Mg& ndash;Gd& ndash;Dy& ndash;Zr Alloys for Potential Orthopedic Applications
In this study, different contents of rare earth elements with high solid solubility (Gd and Dy) were added into Mg and fabricated through homogenization and hot extrusion processes that enable few second phase formation to efficaciously inhibit the galvanic corrosion. The microstructure and phase characterization of the as-extruded Mg& ndash;Gd& ndash;Dy& ndash;Zr alloys were analyzed by scanning electron microscopy, electron backscattered diffraction, and X-ray diffraction. The in vitro biodegradation behavior of the as-extruded Mg& ndash;Gd& ndash;Dy& ndash;Zr alloys was investigated via the electrochemical measurement and immersion test. The results revealed that all the as-extruded alloys with different RE additions exerted fully recrystallized microstructures. The average grain size was appropriately 20 & mu;m to 30 & mu;m for all alloys and gradually increased by adding more RE. Only a few tiny second-phase particles less than 5 & mu;m dispersed for all the samples and the volume fraction of particles increased slightly with the increase in RE content. The as-extruded Mg& ndash;Gd& ndash;Dy& ndash;Zr alloys with low RE content (GD0.6) allowed for a satisfactory corrosion resistance in Hank& rsquo;s solution with a controlled corrosion rate less than 0.5 mm/year, which is considered as the tolerance limit for the corrosion rate of orthopedic implants. This study provides a cost-effective choice for promoting biodegradable magnesium alloys for potential orthopedic applications with low rare earth content in Mg alloys.
In Vitro Corrosion Performance of As-Extruded Mg–Gd–Dy–Zr Alloys for Potential Orthopedic Applications
*
Authors to whom correspondence should be addressed.
Metals 2022 , 12 (4), 604; https://doi.org/10.3390/met12040604
Received: 14 March 2022 / Revised: 26 March 2022 / Accepted: 28 March 2022 / Published: 31 March 2022
(This article belongs to the Special Issue Development and Applications of New Lightweighting Metal Technologies: High Strength Al and Mg Alloys )
Abstract
:
In this study, different contents of rare earth elements with high solid solubility (Gd and Dy) were added into Mg and fabricated through homogenization and hot extrusion processes that enable few second phase formation to efficaciously inhibit the galvanic corrosion. The microstructure and phase characterization of the as-extruded Mg–Gd–Dy–Zr alloys were analyzed by scanning electron microscopy, electron backscattered diffraction, and X-ray diffraction. The in vitro biodegradation behavior of the as-extruded Mg–Gd–Dy–Zr alloys was investigated via the electrochemical measurement and immersion test. The results revealed that all the as-extruded alloys with different RE additions exerted fully recrystallized microstructures. The average grain size was appropriately 20 μm to 30 μm for all alloys and gradually increased by adding more RE. Only a few tiny second-phase particles less than 5 μm dispersed for all the samples and the volume fraction of particles increased slightly with the increase in RE content. The as-extruded Mg–Gd–Dy–Zr alloys with low RE content (GD0.6) allowed for a satisfactory corrosion resistance in Hank’s solution with a controlled corrosion rate less than 0.5 mm/year, which is considered as the tolerance limit for the corrosion rate of orthopedic implants. This study provides a cost-effective choice for promoting biodegradable magnesium alloys for potential orthopedic applications with low rare earth content in Mg alloys.
Keywords:
Mg–Gd–Dy–Zr alloys
;
corrosion performance
;
orthopedic
1. Introduction
Magnesium and its alloys, serving as new generation biodegradable structural materials for bone implantable devices, have been widely documented in the literature and have been promoted by medical device companies due to their characteristics of biodegradability, good bone histocompatibility, and close modulus and density with natural bones [ 1 , 2 , 3 , 4 , 5 , 6 ]. However, the main drawbacks of magnesium and its alloys are their rapid corrosion rates and localized corrosion mode in the physiological environment, which can lead to premature loss of mechanical integrity of the implant, and to the formation of excessive hydrogen gas cavities that are not conducive to tissue healing, thus seriously deteriorating the therapeutic effect. Hence, the degradation rate control of magnesium alloys in a physiological electrolyte environment is the main bottleneck that hinders the orthopedic applications of magnesium alloys [ 7 , 8 , 9 ].
In the human body, magnesium alloys are degraded by galvanic corrosion, pitting corrosion, fatigue corrosion, and scour corrosion, among which galvanic corrosion is the main corrosion mode [ 10 , 11 , 12 , 13 , 14 ]. In addition to its natural characteristics, where the magnesium alloy surface cannot spontaneously form a protective surface film, the key reason why magnesium alloys are prone to corrosion is that the stable second phase of the magnesium alloy forms galvanic corrosion with the matrix [ 15 , 16 ]. Moreover, impurity elements such as Fe, Ni, and Cu gather at grain boundaries and the impurity elements such as Al 3 Fe that are distributed in the matrix have active cathodic properties, which promote the formation of microbatteries on the surface of magnesium alloys [ 7 , 17 , 18 ]. The second phase in the magnesium alloy shows extremely strong cathode characteristics, generally does not corrode, and it is difficult to form ions in the biodegradation process. The larger size of the second phase particles may form thrombus and other subsequent adverse effects [ 19 , 20 ]. This problem has become another doubt for the application of biological magnesium alloys.
For decades, magnesium alloys have mainly been designed to control the degradation rate by reducing the impurity content and alloying methods while considering biocompatibility to alleviate the limitations as described above. To reduce the impurity content in the alloy, harmful elements such as Fe, Ni, and Cu, with low solid solubility in the magnesium alloy, are mainly reduced to avoid their aggregation at grain boundaries and thus inhibit the microbattery reaction. Alloying can improve the corrosion property of magnesium to a certain extent, but inevitably gives rise to the formation of second phases, which easily form galvanic corrosion with the magnesium matrix [ 16 , 21 ]. Generally, material deformation and heat treatment are used to modify the size, morphology, and distribution of the second phases, and thereby to enhance the corrosion resistance, but the adverse effect of the second phase on the corrosion properties of the alloy cannot be completely eliminated [ 22 , 23 , 24 ].
Adding an appropriate amount of rare earth into the magnesium alloy can not only purify the melt, refine grain, improve mechanical properties [ 25 , 26 , 27 ], and corrosion resistance of the alloy [ 28 , 29 , 30 ], but also because most rare earth elements have no toxicity to the human body [ 31 , 32 ]. Trace rare earth elements can also improve immune function and promote DNA synthesis in liver cells [ 33 , 34 ]. Therefore, rare earth containing Mg alloy (Mg–RE) becomes an important alloy system in the study of biodegradable magnesium alloys. Elmar Willbold et al. conducted a systematic study on the biodegradability and biocompatibility of magnesium alloys with light rare earth alloys La, Ce, and Nd. In vitro and in vivo experiments showed that the alloys had a lower corrosion rate, and Nd showed better biocompatibility than La and Ce [ 35 ]. Feyerabend et al. studied the toxic effects of Gd, Y, Nd, Dy, Pr, Gd, La, Ce, Eu, and other rare earth elements on human osteosarcoma cell lines, peripheral cells of human umbilical cord blood vessels, and mouse macrophages and found that La and Ce had certain cytotoxicity, and the others had no toxicity or low toxicity [ 31 ]. Liu et al. individually fabricated binary Mg–RE model alloys with 16 kinds of REs into Mg including Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Du, Ho, Er, Tm, Yb, and Lu. The results showed that all kinds of Mg–RE model alloys showed no cytotoxic effect on the MC3T3-E1 cells and the hemolysis rates of all experimental Mg–RE model alloys were lower than 5%, except for Mg–Lu alloy model [ 36 ]. The German GKSS Light Metal Research Institute has developed high-purity Mg–Y [ 37 ], Mg–Gd [ 38 ], and other magnesium rare earth alloys that have been applied in degradable magnesium alloy orthopedic implant products developed by the German AAP Company.
Gd and Dy are considered as efficient solid solution strengtheners, grain refiners, and texture modifiers for the Mg matrix [
39
,
40
,
41
]. The maximum solid solubility of Gd and Dy in α-Mg reaches up to 23.5 wt% and 25.3 wt%, respectively, which enables few second phase formation, inhibiting the galvanic corrosion. Although it has been reported that the solid solubility decreases with decreasing temperature, Gd and Dy still maintained a high level in α-Mg compared with other alloying elements. In our previous studies, simultaneous addition of Gd and Dy in Mg alloys was used to weaken the extrusion basal texture of the Mg alloy and improve the mechanical properties [
25
]. However, the corrosion performance has not been systematically studied. In this study, the in vitro corrosion performance of as-extruded Mg–Gd–Dy–Zr alloys was analyzed and discussed for potential orthopedic applications.
2. Materials and Methods
2.1. Materials Preparation
The experimental Mg–xGd–0.5xDy–0.2Zr (x = 0.6, 1.2, 5.0, and 10.0, hereafter notated as GD0.6, GD1.2, GD5.0, GD10.0, respectively) alloys were fabricated. Pure Mg (99.9%) was molten in a high-purity graphite crucible under the protection of a mixed gas atmosphere of SF
6
(1 vol%) and carbon dioxide (CO
2
). Mg-20 wt% Gd master alloy, pure Dy (99.5%), and Mg-30 wt% Zr master alloy were orderly added to the melt at 720 °C in nominal amounts. The melting was held for 30 min and stirred with a graphite rod. The melt was then poured into a steel mold preheated at 300 °C. After casting, both the tops and bottoms of the ingots were cut away, and the middle parts were then homogenized at 520 °C for 24 h followed by quenching in water. The as-quenched ingots were hot extruded into bars at 400 °C with the extrusion ratio of 64:1 at a ram speed of 10 mm·s
−1
. The composition of the Mg–Gd–Dy–Zr alloys measured by inductively coupled plasma atomic emission spectrometry (ICP-AES, Optima 7300DV, PerkinElmer, Waltham, MA, USA) is listed in
Table 1
.
2.2. Microstructure and Phase Characterization
The samples (Φ8 × 3 mm
3
) for microstructural characterization were etched using acetic picral solution. The microstructure of the prepared samples was investigated using scanning electron microscopy (SEM, Quanta FEG250, FEI, Hillsboro, OR, USA) equipped with an energy dispersive spectrometer (EDS) operating at 20 kV. The electron backscattered diffraction (EBSD) analysis was performed using a FEI Quanta 650F SEM equipped with an HKL Channel 5 system, with a scanning step size of 3 μm. Specimens for EBSD testing were prepared by mechanical grinding and polishing, followed by electro-polishing in a 9:1 solution of ethanol and perchloric acid for 90 s at −20 °C. After electro-polishing, specimens were sonicated for 20 min in absolute ethanol to clean the surface.
Figure 1
shows the SEM test region and EBSD imaging reference plane for the as-extruded Mg–Gd–Dy–Zr alloys, which was perpendicular to the extrusion direction. X-ray diffraction (XRD) was performed using an X-ray diffractometer (Rigaku D/Max 2500PC, Tokyo, Japan) with Cu-Kα radiation to identify the crystal structure of the phases. The scanning angle ranged from 10° to 85° with a scanning speed of 4°·min
−1
. The XRD pattern was made with MDI Jade 5.0 software (Materials Data Inc., Livermore, CA, USA).
2.3. Electrochemical Measurement
The electrochemical corrosion behavior of the samples was investigated by electrochemical impedance spectroscopy and potentiodynamic polarization using an A Verserstat 3 (Gamry Reference 600+, Philadelphia, PA, USA) electrochemical workstation. Hank’s solution was served as the electrolyte for the electrochemical measurement. The chemical compositions are shown in
Table 2
. The solution with a pH value of 7.4 was prepared by A.R. grade chemicals. A typical three-electrode electrochemical system was used consisting of a sample as the working electrode, a saturated calomel electrode (SCE) as the reference electrode, and a platinum electrode as the counter electrode. The electrolyte was kept at 37 ± 0.5 °C. All samples were embedded in resin with 1 cm
2
area exposed to the solution. The samples were allowed to stabilize at the open circuit potential (OCP) for 30 min before the measurements. Impedance measurements were carried out at the OCP as the initial potential using a 10 mV root-mean-square perturbation from 100 kHz to 10 mHz. Potentiodynamic polarization tests were conducted at a sweep rate of 0.5 mV/s within a scan range of ±0.25 V with reference to OCP. Fitting was performed with ZSimpwin software (Gamry, Philadelphia, PA, USA). Three duplicates were taken for statistical analysis for each group in order to control the experimental scatter for statistics.
2.4. Immersion Test
The samples were immersed in Hank’s solution at 37 ± 0.5 °C for 14 days with an immersion surface demission to liquid volume ratio of 1.25 cm
2
/mL. The immersion solution was refreshed every day to simulate the in vivo condition. The pH value of the solutions was recorded during the immersion process at intervals. After the immersions for seven days and 14 days, respectively, samples were taken for photos after gently rinsing with distilled water and then dried in air. Weight loss was measured to calculate the corrosion rate of the samples after removal of the corrosion products in chromic acid (200 g/L chromium trioxide and 10 g/L silver nitrate). The corrosion rate was calculated by the following equation:
Corrosion rate = (K × W)/(A × T × D)
where the coefficient K = 8.76 × 10
4
; W is the weight loss (g); A is the sample area exposed to the solution (cm
2
); T is the exposure time (h); and D is the density of the experimental material (g/cm
3
).
3. Results and Discussion
3.1. Microstructure Characterization
The EBSD analysis technique was used to characterize the microstructure characterization of the as-extruded Mg–Gd–Dy–Zr alloys with different RE additions. The EBSD results of each alloy were obtained from 1200 µm× 1200 µm area perpendicular to the extrusion direction. Figure 2 a–d shows the EBSD inverse pole figure maps perpendicular to the direction of extrusion for the as-extruded Mg–Gd–Dy–Zr alloys, displaying that all four as-extruded alloys with different RE additions exerted fully recrystallized microstructures. Figure 2 e presents the grain size distribution of the as-extruded Mg–Gd–Dy–Zr alloys, which is similar to Gauss distribution for each alloy. The peak area became wider when the RE addition was higher, which demonstrates that the grain size changed to non-uniformity in the high RE addition samples. Figure 2 f shows the variation of average grain size with the increase in RE content in the as-extruded Mg–Gd–Dy–Zr alloys. The average grain size was appropriately between 20–30 μm for all the alloys and gradually increased by adding more RE. Such a phenomenon can also be found in other Mg–RE alloys [ 25 , 32 , 36 , 42 ]. This resulted from the combination of nucleation and growth for the recrystallization. The nucleation of recrystallization may be retarded when the rare earth element concentration is relatively high. However, once the nucleation formed, these recrystallized grains could grow without impinging by other grains. Eventually, it resulted in the larger grain size in high rare earth element concentration alloys compared with the low concentration alloys.
The main purpose of this paper was to improve the corrosion resistance of magnesium alloys by reducing the second phases to control galvanic corrosion. The XRD analysis was performed to preliminarily verify the presence or absence of the second phases in the as-extruded Mg–Gd–Dy–Zr alloys [
25
], and the results are shown in
Figure 3
. No sign of the second phases and only the constitution of α-Mg matrix could be detected in all XRD patterns. This indicates that the second phase can be efficaciously inhibited by adding alloying elements with high solid solubility in a magnesium alloy, in combination with homogenization heat treatment and extrusion deformation [
43
,
44
].
As XRD analysis has limited ability to detect the low content intermetallics in magnesium alloys, the SEM test was adopted to observe the second phase of alloys after the homogenization and extrusion process. Figure 4 a–d shows the SEM microstructure of the as-extruded Mg–Gd–Dy–Zr alloys. It can be seen that there were a few very small second-phase particles dispersed in the α-Mg matrix and at the grain boundaries, even for the low RE concentration samples. The particles also increased slightly with the increase in RE content. In addition, the EDS analysis was conducted for the red selected area in Figure 4 d and the distribution of elements is shown in Figure 4 e. The small rectangular white region, irregularly shaped white region, and the matrix are labeled with A, B, and C, respectively. For region A, the Gd and Dy contents were 23.09 at% and 20.6 at%, respectively, which were relatively higher than the stoichiometry of the Mg 5 RE compound, a typical second phase considered in previous Mg–RE publications [ 44 , 45 ]. For region B, the relative low RE content suggests that it is accompanied by precipitation and segregation. The precipitate size was less than 5 μm. The low Gd and Dy content in region C indicate that RE remained predominately in the solute state in the Mg matrix.
3.2. Electrochemical Behaviors
Electrochemistry measuring analysis was carried out to predict the corrosion resistance of the as-extruded Mg–Gd–Dy–Zr alloys. Electrochemical impedance spectroscopy uses small amplitude sine wave electrical signals to disturb the system. During the test process, it is close to the stable equilibrium state, which can reflect the corrosion behavior of the material in the stable equilibrium state. Impedance spectrum arc is composed of a high frequency region and low frequency region. The capacitive loop at high frequency is ascribed to the charge transfer resistance and that at low frequency is attributed to the diffusion through the outer surface layer [
15
]. The larger the arc diameter, the better the corrosion resistance of the material.
Figure 5
shows the Nyquist plots for the as-extruded Mg–Gd–Dy–Zr alloys in Hank’s solution. It can be seen from
Figure 5
that the shape of the impedance spectrum changes with the increase in RE content in the alloys. The sizes of the capacitive loop of GD0.6 and GD1.2 samples were relatively similar and obviously larger in comparison with those of the GD5.0 and GD10.0 samples in the same solution, which demonstrated that GD0.6 and GD1.2 should possess higher corrosion resistance. GD10.0 had the minimum capacitive loop radius and hence the worst corrosion resistance. Furthermore, for the GD5.0 and GD10.0 samples, an inductive loop could be observed, usually associated with adsorption phenomena.
Figure 6 shows the polarization curves of the as-extruded Mg–Gd–Dy–Zr alloy samples immersed in Hank’s solution. The corrosion potential (E 0 ), the current density (I 0 ), polarization resistance (R p ), and corrosion rate (CR) calculated according to the ASTM-G102-89 standard are listed in Table 3 . According to the results of Figure 6 and Table 3 , there were no significant differences among the PD curve changes for all Mg–Gd–Dy–Zr alloys. The E 0 was between −1.63 and −1.52 V and there was little significant difference among all the test samples. I 0 and R p were all intermediate in the same order of magnitude. The corrosion rate was judged under the influence of both anode and cathode reactions. In general, excellent corrosion resistance could be obtained with a more electropositive potential, lower I 0 , and higher R p at the same time. If the above conditions cannot be met at once, the corrosion rate should be considered comprehensively. The corrosion rates calculated by the Tafel fitting parameters were all less than 0.5 mm/year, which is considered as the tolerance limit for the corrosion rate of orthopedic implants by the electrochemistry test [ 46 ]. The minimum corrosion rate was only 0.05 mm/year, as acquired by GD1.2. However, potentiodynamic polarization is an instantaneous reaction experiment, which represents a corrosion snapshot during the performed time. It can show the early stages of corrosion, but does not necessarily represent all corrosion points in time.
3.3. Immersion Behaviors
Immersion tests were undertaken to evaluate the long-term corrosion resistance of the as-extruded Mg–Gd–Dy–Zr alloys. The changes in pH values of the as-extruded Mg–Gd–Dy–Zr alloys with different amounts of RE elements immersed in Hank’s solutions for 14 days are shown in
Figure 7
. The pH values of all four alloys increased first and then decreased with prolonged immersion time. This is because the magnesium matrix reacts with Cl
−
, CO
3
2−
, PO
4
3−
, and HPO
3
2−
plasma in Hank’s solution when the sample surface and solution make contact directly at the early stage of immersion, generating a large amount of Mg(OH)
2
and releasing a large amount of H
2
on the surface of sample. The increase in OH
−
caused the pH value to rise rapidly. With the extension of immersion time, corrosion products are generated on the sample surface, which reduces the direct contact between the material surface and the solution and inhibits the continuous corrosion, so the pH decreases to varying degrees. Comparing the pH values of the as-extruded Mg–Gd–Dy–Zr alloys with different contents of Gd and Dy, it can be found that after one day of immersion, the pH from high to low was GD10.0, GD5.0, GD1.2, and GD0.6, indicating that GD0.6 exhibited the best corrosion resistance at the early stage of corrosion. The pH value of GD0.6 was always the lowest with the immersion time extended. After immersion for 10 days, the pH curves of GD1.2 and after the formation of the product film on the surface of the materials, while the pH value of GD10.0 consistently remained at a high level, implying the worst corrosion resistance.
After cleaning the surface products of the samples with chromic acid, corrosion performance evaluations by weight loss after immersion of seven days and 14 days were analyzed and illustrated graphically as corrosion rates in
Figure 8
. The results showed that the corrosion rates of all the as-extruded Mg–Gd–Dy–Zr alloys after 14 days of immersion lower than those after seven days. This is mainly because with the progress of corrosion, degradation products produced on the sample surface could slow down the corrosion to a certain extent. These results are consistent with the pH variation shown in
Figure 7
. The in vitro corrosion rates of the as-extruded Mg–Gd–Dy–Zr alloys displayed an upward trend with increasing amounts of RE contents after both seven days and 14 days of immersion. The minimum corrosion rate of GD0.6 was 0.46 mm/year and 0.36 mm/year after seven days and 14 days, respectively. It was found that with the addition of Gd and Dy, the second phases precipitated in the α-Mg matrix and at grain boundaries. As confirmed by the microstructure and weight loss experimental results, the size and content of the precipitated phase of GD0.6 and GD10.0 were relatively small, but the corrosion rate was an order of magnitude different. It is speculated that more Gd and Dy elements dissolved in the α-Mg matrix have a negative effect on the corrosion resistance. Based on the results of the electrochemical experiment and immersion experiment, it is suggested that the as-extruded Mg–Gd–Dy–Zr alloys with low RE content (GD0.6) exhibited a satisfactory controlled degradation in Hank’s solution. Based on previous reports, despite the numerous positive aspects of RE elements that have been found in Mg alloys, their application is still hindered by the high cost at the commercial level for Mg alloys. Therefore, the magnesium alloy with low rare earth content obtained in this paper provides a choice for promoting biodegradable magnesium alloy for potential orthopedic applications with more cost-effective performance.
4. Conclusions
The microstructure characterization and in vitro degradation behavior of the as-extruded Mg–xGd–0.5xDy–0.2Zr (x = 0.6, 1.2, 5.0, and 10.0, mass fraction) alloys were studied. All four as-extruded alloys with different RE additions exerted fully recrystallized microstructures. The average grain size was from appropriately 20 to 30 μm for all alloys and gradually increased by adding more Gd and Dy. A few very small second-phase particles less than 5 μm dispersed, even for the low RE concentration samples. The volume fraction of particles increased slightly with the increase in RE content. The as-extruded Mg–Gd–Dy–Zr alloys with low RE content (GD0.6) allowed for a satisfactory corrosion resistance in Hank’s solution with a controlled corrosion rate of less than 0.5 mm/year, which is considered as the tolerance limit for the corrosion rate of orthopedic implants.
Author Contributions
Conceptualization, C.L. and J.W.; methodology, Y.F.; software, S.Z.; validation, C.L., J.W. and Y.X.; formal analysis, X.C.; investigation, Z.C.; resources, C.L.; data curation, J.H.; writing—original draft preparation, C.L.; writing—review and editing, C.L. and J.W.; visualization, Y.X.; supervision, J.W.; project administration, X.Z.; funding acquisition, C.L. and J.W. All authors have read and agreed to the published version of the manuscript.
Funding
This work was financially supported by the Major Special Projects of the Plan “Science and Technology Innovation 2025” (Nos. 2019B10105, 2019B10086, 2020Z096), Ningbo Natural Science Foundation (No. 202003N4340), and the National Natural Science Foundation of China (Project No.: 52073030).
Acknowledgments
The authors would like to thank the helps with experiments from all members of the Integrated Computational Materials Engineering lab, Beijing Institute of Technology, especially Xin Li. The assistance with data analysis from all researchers at the Light Metal group of Ningbo Branch of Chinese Academy of Ordnance Science are also greatly appreciated.
Conflicts of Interest
The authors declare no conflict of interest.
References
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Figure 1. Schematic showing the test region of the as-extruded Mg–Gd–Dy–Zr alloys for microstructure characterization.
Figure 1. Schematic showing the test region of the as-extruded Mg–Gd–Dy–Zr alloys for microstructure characterization.
Figure 2. EBSD inverse pole figure maps perpendicular to the direction of extrusion for ( a ) GD0.6, ( b ) GD1.2, ( c ) GD5.0, and ( d ) GD10.0; ( e ) grain size distribution; and ( f ) variation of average grain size with the increase in RE contents in the as-extruded Mg–Gd–Dy–Zr alloys.
Figure 2. EBSD inverse pole figure maps perpendicular to the direction of extrusion for ( a ) GD0.6, ( b ) GD1.2, ( c ) GD5.0, and ( d ) GD10.0; ( e ) grain size distribution; and ( f ) variation of average grain size with the increase in RE contents in the as-extruded Mg–Gd–Dy–Zr alloys.
Figure 3. XRD pattern of the as-extruded Mg–Gd–Dy–Zr alloys.
Figure 3. XRD pattern of the as-extruded Mg–Gd–Dy–Zr alloys.
Figure 4. Microstructure characterization of the as-extruded Mg–Gd–Dy–Zr alloys: SEM images of ( a ) GD0.6, ( b ) GD1.2, ( c ) GD5.0, ( d ) GD10.0, and ( e ) EDS analysis of the selected area in ( d ).
Figure 4. Microstructure characterization of the as-extruded Mg–Gd–Dy–Zr alloys: SEM images of ( a ) GD0.6, ( b ) GD1.2, ( c ) GD5.0, ( d ) GD10.0, and ( e ) EDS analysis of the selected area in ( d ).
Figure 5. Nyquist plots of as-extruded Mg–Gd–Dy–Zr alloys in Hank’s solution.
Figure 5. Nyquist plots of as-extruded Mg–Gd–Dy–Zr alloys in Hank’s solution.
Figure 6. Potentiodynamic polarization curves of as-extruded Mg–Gd–Dy–Zr alloys in Hank’s solution.
Figure 6. Potentiodynamic polarization curves of as-extruded Mg–Gd–Dy–Zr alloys in Hank’s solution.
Figure 7. pH monitoring of as-extruded Mg–Gd–Dy–Zr alloys during the in vitro immersion periods.
Figure 7. pH monitoring of as-extruded Mg–Gd–Dy–Zr alloys during the in vitro immersion periods.
Figure 8. Corrosion rates of as-extruded Mg–Gd–Dy–Zr alloys calculated by mass loss after an immersion of seven days and 14 days, respectively.
Table 1. Chemical composition of the Mg–Gd–Dy–Zr alloys (wt%).
Table 1. Chemical composition of the Mg–Gd–Dy–Zr alloys (wt%).
Alloy Code Gd Dy Zr Mg Mg–0.6Gd–0.3Dy–0.2Zr GD0.6 0.58 0.34 0.018 Bal. Mg–1.2Gd–0.6Dy–0.2Zr GD1.2 1.03 0.54 0.19 Bal. Mg–5Gd–2.5Dy–0.2Zr GD5.0 5.24 1.73 0.022 Bal. Mg–10Gd–5Dy–0.2Zr GD10.0 10.94 4.98 0.13 Bal.
Mg = magnesium; Gd = gadolinium; Dy = dysprosium; Zr = zirconium.
Table 2. Chemical compositions of Hank’s solution.
Table 2. Chemical compositions of Hank’s solution.
Chemical Composition Content (g/L) NaCl 8.00 KCl 0.40 CaCl 2 0.14 NaHCO 3 0.35 Na 2 HPO 4 0.12 MgSO 4 0.20 KH 2 PO 4 0.06 Glucose 1.00
Table 3. The Tafel fitting parameters obtained from the potentiodynamic polarization curves.
Table 3. The Tafel fitting parameters obtained from the potentiodynamic polarization curves.
As-Extruded Alloy E 0 (V) I 0 (μA/cm 2 ) β a (mV) β c (mV) R p (KΩ/cm 2 ) Corrosion Rate (mm/year) GD0.6 −1.58 4.87 410.9 327.9 79.18752 0.22 GD1.2 −1.52 1.1 33.2 142.9 11.69815 0.05 GD5.0 −1.63 4.88 491.0 300.4 80.92663 0.22 GD10.0 −1.57 1.93 25.4 265.8 10.06708 0.09
Liu, C.; Wang, J.; Xu, Y.; Fu, Y.; Han, J.; Cao, Z.; Chen, X.; Zhao, S.; Zhu, X. In Vitro Corrosion Performance of As-Extruded Mg–Gd–Dy–Zr Alloys for Potential Orthopedic Applications. Metals 2022, 12, 604.
https://doi.org/10.3390/met12040604
| https://www.mdpi.com/2075-4701/12/4/604/xml |
London - South Africa on a road bike - Horizons Unlimited - The HUBB
hey everyone, i'm still lurking around here reading huge travel reports and enjoying every minute of it... anyway what im wondering is if anyone can help me with the
Adventure is what you make itby Simon McCarthy."Alternative" bridge near Salavan, Laos
# 1 7 Dec 2008 Cold Kiwi Registered Users HUBB regular Join Date: Dec 2008 Location: London Posts: 20 London - South Africa on a road bike hey everyone, i'm still lurking around here reading huge travel reports and enjoying every minute of it... anyway what im wondering is if anyone can help me with the possibility of traveling south on my road bike (for your info its a kawasaki zzr600) from reading a few reports it seems that the majority of the way is passable...and there was talk of lots of tarmac going in down the west. if anyone knows more i would love to hear it. Share Share this post on Digg Del.icio.us Twitter Share on Facebook Reddit! Share on Google+
# 2 7 Dec 2008 Bossies Registered Users Veteran HUBBer Join Date: Sep 2005 Location: Poole, UK Posts: 316 I am a firm believer that anyone can go anywhere with any kind of vehicle, they will just take longer/quicker and a greater/lesser number of bruises/stories/smiles.So my question: why do you want to do it with a ZZR. No clue about West coasts so sorry can't help you there. If you decide to rather go via Easter africa you have tarmac all the way from London to Aswan (Egypt) and all the way from Isiolo (Kenya) to Cape Town. Assuming the tar roads will not be complete by end of this year you will need a lift for you bike from Wadi-Halfa to Dongola (Sudan), Metema to before Gondor turnoff (Ethiopia) and Moyale to Isiolo (Kenya). Share Share this post on Digg Del.icio.us Twitter Share on Facebook Reddit! Share on Google+ __________________ If there's a will there's a way so I will anyway! http://www.buyaikhaya.blogspot.com
# 3 7 Dec 2008 Vaufi Contributing Member Veteran HUBBer Join Date: Jan 2004 Location: Munich, the beer capital Posts: 1,031 I remember an article writen by a Dutch guy who had travelled down the eastern route to CT on a Honda Fireblade. Quite adventuresome I guess the northern connection between the border of Ethiopia and down into Kenya will be pretty rough, but south of that tarmac roads are plentifull. Same as Bossies, I believe you can go just about anywhere on any bike. Thinking back, in the fifties the bikes had rather minimal suspension and still the people did surprising feats of travelling to far-away countries on terrible roads Share Share this post on Digg Del.icio.us Twitter Share on Facebook Reddit! Share on Google+ __________________ Only when we pause to wonder do we go beyond the limits of our little lives. (Rod McKuen)
# 4 8 Dec 2008 Cold Kiwi Registered Users HUBB regular Join Date: Dec 2008 Location: London Posts: 20 hrm... just gotta find a bit more grip now! Share Share this post on Digg Del.icio.us Twitter Share on Facebook Reddit! Share on Google+
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Publications - Global Disability Innovation Hub
The GDI Hub brings together academic excellence, innovative practice and co-creation; harnessing the power of technology for good.
Type
Report
Themes
Assistive & Accessible Technology
Assistive Technology Changes Lives: an assessment of AT need and capacity in England
Vicki Austin,Dilisha Patel,Jamie Danemayer,Kate Mattick,Anna Landre,Marketa Smitova,Maryam Bandukda, Aoife Healy, Nachiappan Chockalingam,Diane Bell,Cathy Holloway
This report was prepared by Global Disability Innovation (GDI) Hub for the Disability Unit in the Cabinet Office His Majesty’s Government (HMG). The report presents findings from a Country Capacity Assessment (CCA) of AT access in England. Findings illustrate a complex state of AT in England. While delivery systems tend to provide quality products that have a strong, positive impact on people’s lives, processes are often slow and stressful for users and providers alike. Startlingly, there is also an AT access gap of 31% of disabled people not having the assistive products they need to flourish, thrive, or even participate in daily life.
The Cabinet Office; 2023
Abstract
Assistive Technology Changes Lives: an assessment of AT need and capacity in England
The aim of this research was to undertake a Country Capacity Assessment (CCA) to inform a more integrated approach to Assistive Technology (AT) provision in England. The results aim to support policymakers in identifying actions to strengthen service delivery to better meet disabled people’s needs, improving outcomes for AT users and reducing inefficiencies in the current approach.
The research was undertaken from November 2022 to March 2023 and led by the Global Disability Innovation (GDI) Hub, which is the World Health Organization (WHO) Global Collaborating Centre on AT access, using WHO tools in the Assistive Technology Assessment (ATA) suite.
Cite
Assistive Technology Changes Lives: an assessment of AT need and capacity in England
Suggested Citation: Austin, V, Patel, D, Danemayer, J, Mattick, K, Landre, A, Smitova, M, Bandukda, M, Healy, A, Chockalingam, N, Bell D, and Holloway, C; Assistive Technology Changes Lives: an assessment of AT need and capacity in England; Cabinet Office, HMG; 2023
Assistive Technology Changes Lives: an assessment of AT need and capacity in England
Type
Journal Paper
Themes
Assistive & Accessible Technology
Seeking information about assistive technology: Exploring current practices, challenges, and the need for smarter systems
Jamie Danemayer,Cathy Holloway,Youngjun Cho, Nadia Berthouze, Aneesha Singh, William Bhot, Ollie Dixon, Marko Grobelnik, John Shawe-Taylor
Paper highlights: Assistive technology (AT) information networks are insular among stakeholder groups, causing unequal access to information. Participants often cited fragmented international marketplaces as a barrier and valued info-sharing across industries. Current searches produce biased results in marketplaces influenced by commercial interests and high-income contexts. Smart features could facilitate searching, update centralised data sources, and disseminate information more inclusively.
International Journal of Human-Computer Studies; 2023
Abstract
Seeking information about assistive technology: Exploring current practices, challenges, and the need for smarter systems
Ninety percent of the 1.2 billion people who need assistive technology (AT) do not have access. Information seeking practices directly impact the ability of AT producers, procurers, and providers (AT professionals) to match a user's needs with appropriate AT, yet the AT marketplace is interdisciplinary and fragmented, complicating information seeking. We explored common limitations experienced by AT professionals when searching information to develop solutions for a diversity of users with multi-faceted needs. Through Template Analysis of 22 expert interviews, we find current search engines do not yield the necessary information, or appropriately tailor search results, impacting individuals’ awareness of products and subsequently their availability and the overall effectiveness of AT provision. We present value-based design implications to improve functionality of future AT-information seeking platforms, through incorporating smarter systems to support decision-making and need-matching whilst ensuring ethical standards for disability fairness remain.
Seeking information about assistive technology: Exploring current practices, challenges, and the need for smarter systems
Type
Journal Paper
Themes
Assistive & Accessible Technology
Evaluating the use of a thermoplastic socket in Kenya: A pilot study
Giulia Barbareschi, Wesley Teerlink, Josepg Gakunga Njuguna, Purity Musungu, Mary Dama Kirino, andCatherine Holloway
According to estimates from the World Health Organization, in 2010, there were more than 30 million people in need of prosthetic and orthotic devices across Africa, Asia, and Latin America. 1This number is likely to have grown significantly in the past decade, in line with trends recorded for the general need of assistive technology. 2For many people who undergo a lower limb amputation, access to an appropriate prosthesis is essential to restore functional mobility and ensure good quality of life. 3Ultimately, an appropriate lower-limb prosthesis (LLP) can enable people with amputation to fulfill their desired role in their family, work, and community life. 4
Prosthetic and Orthotics International; 2022
Abstract
Evaluating the use of a thermoplastic socket in Kenya: A pilot study
Background:
Many people with amputations who live in low-resourced settings struggle to access the workshops where qualified prosthetists provide appropriate care. Novel technologies such as the thermoplastic Confidence Socket are emerging, which could help facilitate easier access to prosthetic services.
Objectives:
The objective of this study was to evaluate the satisfaction and the performance of transtibial prosthesis featuring the Confidence Socket.
Study design:
This is a longitudinal repeated-measures design study.
Methods:
A convenience sample of 26 participants who underwent transtibial amputation were fitted with the Confidence Socket. The performance of the socket was evaluated after a follow-up period between 1 month and 6 months using the L test of functional mobility and the amputee mobility predictor. Satisfaction with the prosthesis was measured using the Trinity Amputation and Prosthetic Experience Scales and purposefully designed 7-point Likert scales.
Results:
Ten of the 26 participants returned for follow-up. Perceived activity restriction and L test times improved significantly at follow-up, but the self-reported satisfaction with the Confidence Socket was lower at follow-up compared with that after fitting.
Conclusions:
The Amparo Confidence Socket represents a potentially viable alternative to improve access to appropriate prosthesis in Kenya, but some aspects of users’ self-reported satisfaction should be further investigated.
Cite
Evaluating the use of a thermoplastic socket in Kenya: A pilot study
Barbareschi G, Teerlink W, Njuguna JG, Musungu P, Kirino MD, Holloway C. Evaluating the use of a thermoplastic socket in Kenya: A pilot study. Prosthet Orthot Int. 2022 Oct 1;46(5):532-537. doi: 10.1097/PXR.0000000000000130. Epub 2022 Mar 25. PMID: 35333813; PMCID: PMC9554758.
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Evaluating the use of a thermoplastic socket in Kenya: A pilot study
Type
Journal Paper
Themes
Assistive & Accessible Technology
Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges
Jamie Danemayer, Andrew Young, Siobhan Green, Lydia Ezenwa, Michael Klein
This study synthesizes learnings from three distinct datasets: innovator applications to the COVIDaction data challenges, surveys from organizers from similarly-aimed data challenges, and a focus group discussion with professionals who work with COVID-19 data. Thematic and topic analyses were used to analyze these datasets with the aim to identify gaps and barriers to effective data use in responding to the pandemic.
Data & Policy; 2023
Abstract
Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges
Innovative, responsible data use is a critical need in the global response to the coronavirus disease-2019 (COVID-19) pandemic. Yet potentially impactful data are often unavailable to those who could utilize it, particularly in data-poor settings, posing a serious barrier to effective pandemic mitigation. Data challenges, a public call-to-action for innovative data use projects, can identify and address these specific barriers. To understand gaps and progress relevant to effective data use in this context, this study thematically analyses three sets of qualitative data focused on/based in low/middle-income countries: (a) a survey of innovators responding to a data challenge, (b) a survey of organizers of data challenges, and (c) a focus group discussion with professionals using COVID-19 data for evidence-based decision-making. Data quality and accessibility and human resources/institutional capacity were frequently reported limitations to effective data use among innovators. New fit-for-purpose tools and the expansion of partnerships were the most frequently noted areas of progress. Discussion participants identified building capacity for external/national actors to understand the needs of local communities can address a lack of partnerships while de-siloing information. A synthesis of themes demonstrated that gaps, progress, and needs commonly identified by these groups are relevant beyond COVID-19, highlighting the importance of a healthy data ecosystem to address emerging threats. This is supported by data holders prioritizing the availability and accessibility of their data without causing harm; funders and policymakers committed to integrating innovations with existing physical, data, and policy infrastructure; and innovators designing sustainable, multi-use solutions based on principles of good data governance.
Cite
Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges
Danemayer, J., Young, A., Green, S., Ezenwa, L., & Klein, M. (2023). Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges. Data & Policy, 5, E11. doi:10.1017/dap.2023.6
Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges
Type
Editorial
Themes
Culture and Participation
COVID-19 as social disability: the opportunity of social empathy for empowerment
Ikenna D Ebueny, Emma M Smith,Catherine Holloway, Rune Jensen, Lucía D'Arino, Malcolm MacLachlan
Social empathy is ‘the ability to more deeply understand people by perceiving or experiencing their life situations and as a result gain insight into structural inequalities and disparities’. Social empathy comprises three elements: individual empathy, contextual understanding and social responsibility. COVID-19 has created a population-wide experience of exclusion that is only usually experienced by subgroups of the general population. Notably, persons with disability, in their everyday lives, commonly experience many of the phenomena that have only recently been experienced by members of the general population. COVID-19 has conferred new experiential knowledge
on all of us. We have a rare opportunity to understand and better the lives of persons with disabilities for whom some aspects of the COVID- 19 experience are enduring. This allows us greater understanding of the importance of implementing in full a social and human rights model of disability, as outlined in the UNCRPD.
BMJ Global Health; 2020
Abstract
COVID-19 as social disability: the opportunity of social empathy for empowerment
COVID-19 has conferred new experiential knowledge on society and a rare opportunity to better understand the social model of disability and to improve the lives of persons with disabilities.
The COVID-19 experience may offer contextual knowledge of the prepandemic lives of persons with disabilities and foster greater social awareness, responsibility and opportunities for change towards a more inclusive society.
Information, family and social relationships, health protection and healthcare, education, transport and employment should be accessible for all groups of the population. The means must be developed and deployed to ensure equity – the deployment of resources so that people with different types of needs have the same opportunities for living good lives in inclusive communities.
We have learnt from COVID-19 that inclusive healthcare and universal access should be the new normal, that its provision as a social good is both unifying and empowering for society as a whole.
Cite
COVID-19 as social disability: the opportunity of social empathy for empowerment
Ebuenyi ID, Smith EM, Holloway C , et alCOVID-19 as social disability: the opportunity of social empathy for empowerment BMJ Global Health2020;5:e003039.
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COVID-19 as social disability: the opportunity of social empathy for empowerment
Type
Editorial
Themes
Assistive & Accessible Technology
Research Group
Social Justice
Developing inclusive and resilient systems: COVID-19 and assistive technology
Emma M. Smith, Malcolm MacLachlan, Ikenna D. Ebuenyi,Catherine Holloway&Victoria Austin
While the inadequacies of our existing assistive technology systems, policies, and services have been highlighted by the acute and rapidly changing nature of the COVID-19 pandemic, these failures are also present and important during non-crisis times. Each of these actions, taken together, will not only address needs for more robust and resilient systems for future crises, but also the day-to-day needs of all assistive technology users. We have a responsibility as a global community, and within our respective countries, to address these inadequacies now to ensure an inclusive future.
Disability & Society; 2020
Abstract
Developing inclusive and resilient systems: COVID-19 and assistive technology
Assistive technology is a critical component of maintaining health, wellbeing, and the realization of rights for persons with disabilities. Assistive technologies, and their associated services, are also paramount to ensuring individuals with functional limitations have access to important health and social service information, particularly during a pandemic where they may be at higher risk than the general population. Social isolation and physical distancing have further marginalized many within this population. We have an opportunity to learn from the COVID-19response to develop more inclusive and resilient systems that will serve people with disabilities more effectively in the future. In this Current Issues piece, we present a starting point for discussion, based on our experiences working to promote access to assistive technologies through inclusive and sustainable systems and policies.
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Developing inclusive and resilient systems: COVID-19 and assistive technology
Emma M. Smith, Malcolm MacLachlan, Ikenna D. Ebuenyi, Catherine Holloway & Victoria Austin (2021) Developing inclusive and resilient systems: COVID-19 and assistive technology, Disability & Society, 36:1, 151-154, DOI:10.1080/09687599.2020.1829558
Developing inclusive and resilient systems: COVID-19 and assistive technology
Type
Journal Paper
Themes
Assistive & Accessible Technology
Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey
Emma M Smith, Maria Luisa Toro Hernandez, Ikenna D Ebuenyi, Elena V Syurina,Giulia Barbareschi, Krista L Best,Jamie Danemayer,Ben Oldfrey, Nuha Ibrahim,Catherine Holloway, Malcolm MacLachlan
The coronavirus disease 2019 (COVID-19) pandemic has impacted all segments of society, but it has posed particular challenges for the inclusion of persons with disabilities, those with chronic illness and older people regarding their participation in daily life. These groups often benefit from assistive technology (AT) and so it is important to understand how use of AT may be affected by or may help to mitigate the impacts of COVID-19.Objective:The objectives of this study were to explore the how AT use and provision have been affected during the initial stages of the COVID-19 pandemic, and how AT policies and systems may be made more resilient based on lessons learned during this global crisis.
International Journal of Health Policy and Management; 2020
Abstract
Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey
Abstract
Background:The coronavirus disease 2019 (COVID-19) pandemic has impacted all segments of society, but it has posed particular challenges for the inclusion of persons with disabilities, those with chronic illness and older people regarding their participation in daily life. These groups often benefit from assistive technology (AT) and so it is important to understand how use of AT may be affected by or may help to mitigate the impacts of COVID-19.Objective:The objectives of this study were to explore the how AT use and provision have been affected during the initial stages of the COVID-19 pandemic, and how AT policies and systems may be made more resilient based on lessons learned during this global crisis.
Methods:This study was a rapid, international online qualitative survey in the 6 United Nations (UN) languages (English, French, Spanish, Russian, Arabic, Mandarin Chinese) facilitated by extant World Health Organization (WHO) and International Disability Alliance networks. Themes and subthemes of the qualitative responses were identified using Braun and Clarke's 6-phase analysis.
Results:Four primary themes were identified in in the data: Disruption of Services, Insufficient Emergency Preparedness, Limitations in Existing Technology, and Inadequate Policies and Systems. Subthemes were identified within each theme, including subthemes related to developing resilience in AT systems, based on learning from the pandemic.
Conclusion:COVID-19 has disrupted the delivery of AT services, primarily due to infection control measures resulting in lack of provider availability and diminished one-to-one services. This study identified a need for stronger user-centred development of funding policies and infrastructures that are more sustainable and resilient, best practices for remote service delivery, robust and accessible tools and systems, and increased capacity of clients, caregivers, and clinicians to respond to pandemic and other crisis situations.
Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey
Smith EM, Toro Hernandez ML, Ebuenyi ID, Syurina EV, Barbareschi G, Best KL, Danemayer J, Oldfrey B, Ibrahim N, Holloway C, MacLachlan M. Assistive Technology Use and Provision During COVID-19: Results From a Rapid Global Survey. Int J Health Policy Manag. 2022 Jun 1;11(6):747-756. doi: 10.34172/ijhpm.2020.210. PMID: 33201656;
Assistive Technology Use and Provision During COVID19: Results From a Rapid Global Survey
Type
Editorial
Research Group
Social Justice
Assistive Technology (AT), for What?
Vicki Austin, Catherine Holloway
This year (2022) has seen the publication of the World’s first Global Report on Assistive Technology (GReAT) [1]. This completes almost a decade of work to ensure assistive technology (AT) access is a core development issue. The lack of access to assistive products (APs), such as wheelchairs, hearing aids, and eyeglasses, as well as less well-referenced products such as incontinence pads, mobile phone applications, or walking sticks, affects as many as 2.5 billion people globally. Furthermore, the provision of APs would reap a 1:9 return on investment [2]. This could result in a family in need netting (or living without) over GBP 100,000 in their lifetime [2] or more, if we count dynamic overspills in the economy such as employment of assistive technology services and manufacturing of devices [3].
Societies; 2021
Abstract
Assistive Technology (AT), for What?
Amartya Sen’s seminal Tanner lecture: Equality of What?began a contestation on social justice and human wellbeing that saw a new human development paradigm emerge—the capability approach (CA)—which has been influential ever since. Following interviews with leading global assistive technology (AT) stakeholders, and users, this paper takes inspiration from Sen’s core question and posits, AT for what?arguing that AT should be understood as a mechanism to achieve the things that AT users’ value. Significantly, our research found no commonly agreed operational global framework for (disability) justice within which leading AT stakeholders were operating. Instead, actors were loosely aligned through funding priorities and the CRPD. We suggest that this raises the possibility for (welcome and needed) incoming actors to diverge from efficiently designed collective action, due to perverse incentives enabled by unanchored interventions. The Global Report on Assistive Technology (GReAT) helps, greatly! However, we find there are still vital gaps in coordination; as technology advances, and AT proliferates, no longer can the device-plus-service approach suffice. Rather, those of us interested in human flourishing might explore locating AT access within an operational global framework for disability justice, which recognizes AT as a mechanism to achieve broader aims, linked to people’s capabilities to choose what they can do and be.
Assistive Technology (AT), for What?
Austin, V.; Holloway, C. Assistive Technology (AT), for What? Societies2022, 12, 169.https://doi.org/10.3390/soc120...
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Assistive Technology (AT), for What?
Type
Journal Paper
Themes
Assistive & Accessible Technology
Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries
Margaret Savage, Sarah Albala, Frederic Seghers, Rainer Katte, Cynthia Liao, Mathilde Chaudron, Novia Afdhila
Development outcomes are inextricably linked to the health of the marketplace that delivers products and services to people in low- and middle- income countries (LMIC). Shortcomings in the market for assistive technology (AT) contribute to low access in LMIC. Market shaping is aimed at improving a market’s specific outcomes, such as access to high quality, affordable AT, by targeting the root causes of these shortcomings. The paper summarizes the findings of a market and sector analysis that was conducted under the UK aid funded AT2030 programme and aims to discuss how market shaping can help more people gain access to the AT that they need and what are the best mechanisms to unlock markets and commercial opportunity in LMICs.
Assistive Technology The Official Journal of RESNA; 2021
Abstract
Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries
Development outcomes are inextricably linked to the health of the marketplace that delivers products and services to people in low- and middle-income countries (LMIC). Shortcomings in the market for assistive technology (AT) contribute to low access in LMIC. Market shaping is aimed at improving a market’s specific outcomes, such as access to high quality, affordable AT, by targeting the root causes of these shortcomings. The paper summarizes the findings of market analyses conducted under the UK aid funded AT2030 programme in support of ATscale and aims to discuss how market shaping can help more people gain access to the AT that they need and what are the best mechanisms to unlock markets and commercial opportunity in LMICs. The paper also explores how market shaping for AT markets could be part of a mission-oriented approach AT policy. A mission-oriented approach can help accelerate progress toward a common objective among stakeholders, at country or global level. While market-shaping activities direct the outcomes of the market toward a specific end goal, such as access to quality, affordable products and services, missions are more comprehensive and include other policy interventions and stakeholder collaborations in order to create a robust and sustainable structure.
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Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries
Margaret Savage, Sarah Albala, Frederic Seghers, Rainer Kattel, Cynthia Liao, Mathilde Chaudron & Novia Afdhila (2021) Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries, Assistive Technology, 33:sup1, 124-135, DOI: 10.1080/10400435.2021.1991050
Applying market shaping approaches to increase access to assistive technology in low- and middle-income countries
Type
Journal Paper
Themes
Assistive & Accessible Technology
Assistive technology access in longitudinal datasets: a global review
Jamie Danemayer, Sophie Mitra,Cathy Holloway, Shereen Hussein
A person’s access to assistive products such as hearing aids, wheelchairs, and glasses, is an essential part of their ability to age in a healthy way. But, according to the World Health Organization, a staggering 90% of people who need assistive products worldwide, do not have access to them. In many instances access is limited or simply non-existent. This is often due to assistive products being too expensive, demand outweighing supply, not always being suitable to use in different environments, or even the lack of availability of trained providers. In such circumstances, people are more likely to age ‘unhealthily’ if they do not have access to assistive products that are designed to support their day to day functioning and independence.
International Journal of Population Data Science; 2023
Abstract
Assistive technology access in longitudinal datasets: a global review
Functional limitations become more prevalent as populations age, emphasising an increasingly urgent need for assistive technology (AT). Critical to meeting this need trajectory is understanding AT access in older ages. Yet few publications examine this from a longitudinal perspective.
This review aims to identify and collate what data exist globally, seeking all population-based cohorts and repeated cross-sectional surveys through the Maelstrom Research Catalogue (searched May 10, 2022) and the Disability Data Report (published 2022), respectively. Datasets incorporating functional limitations modules and question(s) dedicated to AT, with a wave of data collection since 2009, were included.
Of 81 cohorts and 202 surveys identified, 47 and 62 meet inclusion criteria, respectively. Over 40% of cohorts were drawn from high-income countries which have already experienced significant population ageing. Cohorts often exclude participants based on pre-existing support needs. For surveys, Africa is the most represented region (40%). Globally, 73% of waves were conducted since 2016. 'Use' is the most collected AT access indicator (69% of cohorts and 85% of surveys). Glasses (78%) and hearing aids (77%) are the most represented AT. While gaps in data coverage and representation are significant, collating existing datasets highlights current opportunities for analyses and methods for improving data collection across the sector.
Cite
Assistive technology access in longitudinal datasets: a global review
Danemayer, J., Mitra, S., Holloway, C. and Hussein, S. (2023) “Assistive technology access in longitudinal datasets: a global review”, International Journal of Population Data Science, 8(1). doi: 10.23889/ijpds.v8i1.1901.
Assistive technology access in longitudinal datasets: a global review
Type
Journal Paper
Themes
Assistive & Accessible Technology
Estimating need and coverage for five priority assistive products: A systematic review of global population based research
Jamie Danemayer, Dorothy Boggs, Vinicius Delgado Ramos, Emma M. Smith, Ariana Kular, William Bhot, Felipe Ramos Barajas, Sarah Polack,Catherine Holloway
Assistive technology (AT) includes assistive products (APs) and related services that can improve health and well-being, enable increased independence and foster participation for people with functional difficulties, including older adults and people with impairments or chronic health conditions. 1This paper uses the umbrella term ‘functional difficulty’ (FD) to refer to all of these groups. This systematic review was undertaken to identify studies presenting population-based estimates of need and coverage for five APs (hearing aids, limb prostheses, wheelchairs, glasses and personal digital assistants) grouped by four functional domains (hearing, mobility, vision and cognition).
BMJ Global Health; 2021
Abstract
Estimating need and coverage for five priority assistive products: A systematic review of global population based research
Introduction:To improve access to assistive products (APs) globally, data must be available to inform evidence based decision-making, policy development and evaluation, and market-shaping interventions.
Methods:This systematic review was undertaken to identify studies presenting population-based estimates of need and coverage for five APs (hearing aids, limb prostheses, wheelchairs, glasses and personal digital assistants) grouped by four functional domains (hearing, mobility, vision and cognition).
Results:Data including 656 AP access indicators were extracted from 207 studies, most of which (n=199, 96%) were cross-sectional, either collecting primary (n=167) or using secondary (n=32) data. There was considerable heterogeneity in assessment approaches used and how AP indicators were reported; over half (n=110) used a combination of clinical and self-reported assessment data. Of 35 studies reporting AP use out of all people with functional difficulty in the corresponding functional domains, the proportions ranged from 4.5% to 47.0% for hearing aids, from 0.9% to 17.6% for mobility devices, and from 0.1% to 86.6% for near and distance glasses. Studies reporting AP need indicators demonstrated >60% unmet need for each of the five APs in most settings.
Conclusion:Variation in definitions of indicators of AP access have likely led to overestimates/underestimates of need and coverage, particularly, where the relationship between functioning difficulty and the need for an AP is complex. This review demonstrates high unmet need for APs globally, due in part to disparate data across this sector, and emphasises the need to standardise AP data collection and reporting strategies to provide a comparable evidence base to improve access to APs.
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Estimating need and coverage for five priority assistive products: A systematic review of global population based research
Danemayer J, Boggs D, Delgado Ramos V, et al. Estimating need and coverage for five priority assistive products: a systematic review of global population-based research. BMJ Global Health 2022;7:e007662. doi:10.1136/bmjgh-2021-007662
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Estimating need and coverage for five priority assistive products: A systematic review of global population based research
Type
Workshop
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution
Sahan Bulathwela, María Pérez-Ortiz,Catherine Holloway, John Shawe-Taylor
This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies.
Workshop on Machine Learning for the Developing World (ML4D) at the Conference on Neural Information Processing Systems 2021; 2021
Abstract
Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution
Artificial Intelligence (AI) in Education has been said to have the potential for building more personalised curricula, as well as democratising education worldwide and creating a Renaissance of new ways of teaching and learning. Millions of students are already starting to benefit from the use of these technologies, but millions more around the world are not. If this trend continues, the first delivery of AI in Education could be greater educational inequality, along with a global misallocation of educational resources motivated by the current technological determinism narrative. In this paper, we focus on speculating and posing questions around the future of AI in Education, with the aim of starting the pressing conversation that would set the right foundations for the new generation of education that is permeated by technology. This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies. Finally, we ask what would it take for this educational revolution to provide egalitarian and empowering access to education, beyond any political, cultural, language, geographical and learning ability barriers.
Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution
Type
Workshop
Themes
Assistive & Accessible Technology
Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts
Tabish Ahmed, Sahan Bulathwela
The informational needs of people are highly contextual and can depend on many different factors such as their current knowledge state, interests and goals [1, 2, 3]. However, an effective information retrieval companion should minimise the human effort required in i) expressing a human information need and ii) navigating a lengthy result set. Using topical representations of the user history (e.g. [4]) can immensely help formulating zero shot queries and refining short user queries that enable proactive information retrieval (IR). While the world has digital textual information in abundance, it can often be noisy (e.g. extracted through Automatic Speech Recognition (ASR), PDF text extraction etc.), leading to state-of-the-art neural models being highly sensitive to the noise producing sub-optimal results [5]. This demands denoising steps to refine both query and document representation. In this paper, we argue that Wikipedia, an openly available encyclopedia, can be a humanly intuitive knowledge base [6] that has the potential to provide the world view many noisy information Retrieval systems need.
Published at the First Workshop on Proactive and Agent-Supported Information Retrieval at CIKM 2022; 2022
Abstract
Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts
Extracting useful information from the user history to clearly understand informational needs is a crucial feature of a proactive information retrieval system. Regarding understanding information and relevance, Wikipedia can provide the background knowledge that an intelligent system needs. This work explores how exploiting the context of a query using Wikipedia concepts can improve proactive information retrieval on noisy text. We formulate two models that use entity linking to associate Wikipedia topics with the relevance model. Our experiments around a podcast segment retrieval task demonstrate that there is a clear signal of relevance in Wikipedia concepts while a ranking model can improve precision by incorporating them. We also find Wikifying the background context of a query can help disambiguate the meaning of the query, further helping proactive information retrieval.
Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts
Type
Journal Paper
Themes
Assistive & Accessible Technology
Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes
Kate Mattick,Ben Oldfrey, Maggie Donovan-Hall, Grace Magomere, Joseph Gakunga,Catherine Holloway
An estimated 1.5 million people undergo limb amputation each year [1]. Low- and middle-income countries (LMICs) are projected to have a rapid increase in people living with an amputation in the coming years due to prevalence of non-communicable dis-ease, trauma and conflict [1–3]. This paper explores the personal and system factors that motivate and enhance outcomes for patients accessing a prosthetic service and using a lower-limb prosthesis within a low resource setting.
Disability and Rehabilitation; 2022
Abstract
Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes
PurposeTo explore the personal and system factors that motivate and enhance outcomes for patients accessing a prosthetic service and using a lower-limb prosthesis within a low resource setting.
Materials and methodsThis study employed a qualitative approach to explore the motivations and satisfaction of individuals with lower limb loss engaging with a prosthetic service in Mombasa, Kenya. In-depth interviews were conducted over Microsoft Teams with 10 lower limb prosthesis users and thematic analysis was applied.
ResultsFive key themes emerged: acceptance, self-determination, hope, clinician relationship and perception. These findings demonstrate the importance of hopeful thinking and a supportive community in overcoming physical and stigmatising challenges. The findings further highlight the value of the service provider relationship beyond just prescribing an assistive device.
ConclusionThese results have relevance in developing patient-centred services, assistive devices and personnel training that are responsive, motivating, and cognisant of the service user. This is of particular interest as assistive technology services are newly developed in low resource settings.
Cite
Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes
Kate Mattick, Ben Oldfrey, Maggie Donovan-Hall, Grace Magomere, Joseph Gakunga & Catherine Holloway (2022) Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes, Disability and Rehabilitation, DOI:10.1080/09638288.2022.2152875
Experiences of lower limb prosthesis users in Kenya: a qualitative study to understand motivation to use and satisfaction with prosthetic outcomes
Type
Journal Paper
Themes
Culture and Participation
Research Group
Social Justice
“Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone
Victoria Austin,Catherine Holloway, Ignacia Ossul Vermehren, Abs Dumbuya,Giulia Barbareschiand Julian Walker
The World Health Organisation (WHO) estimates that there are currently one billion people in the world who need access to assistive technology (AT). Yet over 90% currently do not have access to assistive products (AP)—such as wheelchairs, hearing aids, walking sticks and eyeglasses—they need, nor and the systems and services necessary to support their appropriate provision [1]. This shocking deficit is set to double by 2050, with about two billion of us likely to require AT but no anticipated reduction in lack of access. The World Health Organisation defines AT as the “the umbrella term covering the systems and services related to the delivery of assistive products and services”, which are products that “maintain or improve an individual’s functioning and independence, thereby promoting their well-being” [2], and the importance of AT provision is strongly highlighted in the Convention on the Rights of Persons with Disabilities (CRPD) [3]. AT has also been shown to be essential to achieving many of the United Nation’s Sustainable Development Goals (SDG) [4]. Without access to AT, many persons with disabilities are unable to go to school, be active in their communities, earn an income, or play a full role in their families [5]. As a recent study found, “AT can make the impossible possible for people living with a wide range of impairments, but a lack of access to basic AT …excludes individuals and reduces their ability to live full, enjoyable, and independent lives” [6].
International Journal of Environmental Research and Public Health; 2021
Abstract
“Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone
The importance of assistive technology (AT) is gaining recognition, with the World Health Organisation (WHO) set to publish a Global Report in 2022. Yet little is understood about access for the poorest, or the potential of AT to enable this group to participate in the activities of citizenship; both formal and informal. The aim of this qualitative study was to explore AT as mediator of participation in citizenship for persons with disabilities who live in two informal settlements in Freetown, Sierra Leone (SL). The paper presents evidence from 16 participant and 5 stakeholder interviews; 5 focus groups and 4 events; combining this with the findings of a house-to-house AT survey; and two national studies—a country capacity assessment and an informal markets deep-dive. Despite citizenship activities being valued, a lack of AT was consistently reported and hindered participation. Stigma was also found to be a major barrier. AT access for the poorest must be addressed if citizenship participation for persons with disabilities is a genuine global intention and disability justice is to become a reality.
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“Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone
Austin, V.; Holloway, C.; Ossul Vermehren, I.; Dumbuya, A.; Barbareschi, G.; Walker, J. “Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone. Int. J. Environ. Res. Public Health2021, 18, 5547.https://doi.org/10.3390/ijerph...
“Give Us the Chance to Be Part of You, We Want Our Voices to Be Heard”: Assistive Technology as a Mediator of Participation in (Formal and Informal) Citizenship Activities for Persons with Disabilities Who Are Slum Dwellers in Freetown, Sierra Leone
Type
Editorial
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
The Digital and Assistive Technologies for Ageing initiative: learning from the GATE initiative
Chapal Khasnabis,Catherine Holloway, Malcolm MacLachlan
We are now in an era of assistive care and assistive living—whereby many people, of all ages, in good health, and those who are more frail, or with cognitive or functional impairments, are using a broad range of technologies to assist and enhance their daily living. Assistive living 1is becoming an important part of population health and rehabilitation, which can help to maximise an individual's abilities, regardless of age or functional capacity. This encouraging shift in ethos has been strengthened by the response to the COVID-19 pandemic, in which a plethora of digital and remote technologies have been used.
The Lancet; 2020
The Digital and Assistive Technologies for Ageing initiative: learning from the GATE initiative
Type
Journal Paper
Themes
Assistive & Accessible Technology
Research Group
Local Productions
Additive manufacturing techniques for smart prosthetic liners
B Oldfrey, A Tchorzewska, R Jackson, M Croysdale, R Loureiro,C Holloway, M Miodownik
Elastomeric liners are commonly worn between socket and limb by prosthetic wearers. This is due to their superior skin adhesion, load distribution and their ability to form a seal. Laboratory tests suggest that elastomeric liners allow reduced shear stress on the skin and give a higher cushioning effect on bony prominences, since they are soft in compression, and similar to biological tissues [1]. However, they also increase perspiration reducing hygiene and increasing skin irritations. Prosthetic users in general face a myriad of dermatological problems associated with lower limb prosthesis such as ulcers, cysts, and contact dermatitis, which are exacerbated by the closed environment of a fitted socket where perspiration is trapped and bacteria can proliferate [2].
Medical Engineering & Physics; 2021
Abstract
Additive manufacturing techniques for smart prosthetic liners
Elastomeric liners are commonly worn between the prosthetic socket and the limb. A number of improvements to the state of the art of liner technology are required to address outstanding problems. A liner that conforms to the residuum more accurately, may improve the skin health at the stump-socket interface. Previous work has shown that for effective thermal management of the socket environment, an active heat removal system is required, yet this is not available. Volume tracking of the stump could be used as a diagnostic tool for looking at the changes that occur across the day for all users, which depend on activity level, position, and the interaction forces of the prosthetic socket with the limb. We believe that it would be advantageous to embed these devices into a smart liner, which could be replaced and repaired more easily than the highly costly and labour-intensive custom-made socket. This paper presents the work to develop these capabilities in soft material technology, with: the development of a printable nanocomposite stretch sensor system; a low-cost digital method for casting bespoke prosthetic liners; a liner with an embedded stretch sensor for growth / volume tracking; a model liner with an embedded active cooling system.
Cite
Additive manufacturing techniques for smart prosthetic liners
, Additive manufacturing techniques for smart prosthetic liners, Medical Engineering & Physics, Volume 87, 2021, Pages 45-55, ISSN 1350-4533,https://doi.org/10.1016/j.mede....
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Additive manufacturing techniques for smart prosthetic liners
Type
Journal Paper
Themes
Assistive & Accessible Technology
Culture and Participation
Research Group
Disability Interactions
“When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya
Giulia Barbareschi, Mark T. Carew, Elizabeth Aderonke Johnson, Norah Kopi,Catherine Holloway
Stigmatizing attitudes and beliefs towards disability represent one of the most pervasive and complex barriers that limits access to health care, education, employment, civic rights and opportunities for socialization for people with disabilities [1,2,3]. The damaging impact of disability stigma is widely acknowledged and, according to article 8 of the UN Convention on the Rights of Persons with disabilities, developing strategies, campaigns, policies and other initiatives to combat disability stigma and ensure that all people with disabilities are treated with dignity and respect is also a duty of the 182 countries who ratified the treaty [4]. Although the majority of literature focused on understanding disability stigma has been carried out in high-income settings [5,6,7], in the last decade, an increasing number of scholars have conducted studies looking at the negative stereotypes, prejudices and inaccurate beliefs that shape disability stigma in the Global South [3,8,9,10]. Most of these studies have described how these stigmatizing beliefs are often driven by a combination of personal and societal factors, ranging from misconceptions concerning the causes of different impairments (e.g., disability to be seen as a form of curse or punishment); assumptions about the lack of capabilities of people with disabilities; or discriminatory practices that actively endorse separation between people with and without disabilities [3,9,11,12]. Yet, there is a dearth of comparative studies that examine the perspectives of both people with and without disabilities of disability stigma and discrimination, including how the use of assistive technology may shape stigmatizing interactions.
International Journal of Environmental Research and Public Health; 2021
Abstract
“When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya
Disability stigma in many low- and middle-income countries represents one of the most pervasive barriers preventing people with disabilities from accessing equal rights and opportunities, including the uptake of available assistive technology (AT). Previous studies have rarely examined how disability stigma may be shaped through factors endemic to social interactions, including how the use of assistive technology itself may precipitate or alleviate disability stigma. Through two strands of work, we address this gap. Via a series of focus groups with Kenyans without disabilities (Study 1) and secondary data analysis of consultations with Kenyans with disabilities and their allies (Study 2), we identify shared and divergent understandings of what shapes disability stigma and discrimination. Specifically, Kenyans with and without disabilities were cognizant of how religious/spiritual interpretations of disability, conceptions of impairments as “different” from the norm, and social stereotypes about (dis)ability shaped the experience of stigma and discrimination. Moreover, both groups highlighted assistive technology as an influential factor that served to identify or “mark” someone as having a disability. However, whereas participants without disabilities saw assistive technology purely as an enabler to overcome stigma, participants with disabilities also noted that, in some cases, use of assistive technologies would attract stigma from others.
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“When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya
Barbareschi G, Carew MT, Johnson EA, Kopi N, Holloway C. “When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya. International Journal of Environmental Research and Public Health. 2021; 18(8):4272.https://doi.org/10.3390/ijerph...
“When They See a Wheelchair, They’ve Not Even Seen Me”—Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya
Type
Journal Paper
Themes
Inclusive Design
Culture and Participation
Research Group
Disability Interactions
Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement
Giulia Barbareschi,Ben Oldfrey, Long Xin, Grace N. Magomere, Wyclife A. Wetende, Carol Wanjira, Joyce Olenja,Victoria Austin, andCatherine Holloway
The World Health Organisation estimate that there are approximately a billion people with disabilities who require access to appropriate assistive technology and this number is set to double by 2050 [82]. Assistive technologies (ATs) play a crucial role in the lives of people with disabilities and are necessary to be able to access essential services and participate in family and community life according to one’s aspirations [40, 62, 68, 81]. Although this is not often specifcally mentioned, the large majority of people with disabilities will routinely use more than one assistive device in their everyday lives [25, 26]. For example a person with a visual impairment is likely to use a white cane to navigate from their house to the office where they work and have a screen-reader, or an equivalent accessibility software, on their computer to be able to do their work once in the office [17].
ASSETS '20: Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility; 2020
Abstract
Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement
Living in informality is challenging. It is even harder when you have a mobility impairment. Traditional assistive products such as wheelchairs are essential to enable people to travel. Wheelchairs are considered a Human Right. However, they are difficult to access. On the other hand, mobile phones are becoming ubiquitous and are increasingly seen as an assistive technology. Should therefore a mobile phone be considered a Human Right? To help understand the role of the mobile phone in contrast of a more traditional assistive technology – the wheelchair, we conducted contextual interviews with eight mobility impaired people who live in Kibera, a large informal settlement in Nairobi. Our findings show mobile phones act as an accessibility bridge when physical accessibility becomes too challenging. We explore our findings from two perspective – human infrastructure and interdependence, contributing an understanding of the role supported interactions play in enabling both the wheelchair and the mobile phone to be used. This further demonstrates the critical nature of designing for context and understanding the social fabric that characterizes informal settlements. It is this social fabric which enables the technology to be useable.
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Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement
Giulia Barbareschi, Ben Oldfrey, Long Xin, Grace Nyachomba Magomere, Wycliffe Ambeyi Wetende, Carol Wanjira, Joyce Olenja, Victoria Austin, and Catherine Holloway. 2020. Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal settlement. In Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility (ASSETS '20). Association for Computing Machinery, New York, NY, USA, Article 50, 1–13.https://doi.org/10.1145/337362...
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Bridging the Divide: Exploring the use of digital and physical technology to aid mobility impaired people living in an informal setlement
Type
Editorial
Themes
Assistive & Accessible Technology
Culture and Participation
Research Group
Social Justice
Critical Junctures in Assistive Technology and Disability Inclusion
Dr Maria Kett,Catherine Holloway,Vicki Austin,Dr Maria Kett
It is clear from the events of the last 18 months that while technology has a huge potential for transforming the way we live and work, the entire ecosystem—from manufacturing to the supply chain—is vulnerable to the vagaries of that ecosystem, as well as having the potential to exacerbate new and existing inequalities [1]. Nowhere has this been more apparent than in the lives of people with disabilities, who make up around 15% of the world’s population and already face barriers to accessing education, employment, healthcare and other services [2]. Some of these barriers are a result of unequal access and opportunities. However, there is a growing movement to better understand how assistive technology systems and services can be designed to enable more robust and equitable access for all. As part of this growing movement, the Paralympic Games in Tokyo this autumn saw the launch of a new global campaign to transform the lives of the world’s 1.2 bn persons with disabilities: the ‘WeThe15’ campaign reached more than 4.5 billion people through its marketing and stands ready to be the biggest of its kind in history. Next year, the World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF), AT scale and GDI Hub will publish the first World Report on Access to Assistive Technology, which will include research from the £20 million, UK Aid funded, GDI Hub-led, programme, AT2030. Ahead of that, in this Special Issue, we focus on how some events and situations—as diverse as the coronavirus pandemic and the Paralympics—can act as ‘critical junctures’ that can enable a rethink of the status quo to facilitate and promote change.
Sustainability; 2021
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Critical Junctures in Assistive Technology and Disability Inclusion
Kett, M.; Holloway, C.; Austin, V. Critical Junctures in Assistive Technology and Disability Inclusion. Sustainability2021, 13, 12744.https://doi.org/10.3390/su1322...
Critical Junctures in Assistive Technology and Disability Inclusion
Type
Editorial
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Introduction to the companion papers to the global report on assistive technology
Johan Borg, Wei Zhang, Emma M. Smith,Cathy Holloway
GReAT, but do we care?
If accessible, assistive technology would be life changing for a billion people across the world today – and two billion people in 2050 (WHO,2018). It would make the difference between independence and dependence, inclusion and exclusion, life and death. It holds the potential to improve and transform health, education, livelihood and social participation; fundamental human rights everyone is entitled to. And if we are lucky to grow old, the chances are that we all would use assistive technology by then. But do we care?
Assistive Technology, The Official Journal of RESNA; 2021
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Introduction to the companion papers to the global report on assistive technology
Johan Borg, Wei Zhang, Emma M. Smith & Cathy Holloway (2021) Introduction to the companion papers to the global report on assistive technology, Assistive Technology, 33:sup1, 1-2, DOI:10.1080/10400435.2021.2003658
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Introduction to the companion papers to the global report on assistive technology
Type
Journal Paper
Themes
Assistive & Accessible Technology
Climate & Crisis Resilience
Research Group
Disability Interactions
Measuring assistive technology supply and demand: A scoping review
Jamie Danemayer,Dorothy Boggs, Emma M. Smith, Vinicius Delgado Ramos, Linamara Rizzo Battistella,Cathy Holloway,and Sarah Polack
An assistive product (AP) is defined as a product used exter-nally to the human body, whose primary purpose is to main-tain or improve an individual’s functioning and independence and thereby promote his or her well-being (WHO, 2016). Global population aging forecasts a rise in the need for solu-tions that support participation and independence, including APs. In this paper, we review current population-level AP supply and demand estimation methods for five priority APs and provide recommendations for improving national and global AP market evaluation.
Assistive Technology The Official Journal of RESNA; 2021
Abstract
Measuring assistive technology supply and demand: A scoping review
The supply of and market demand for assistive products (APs) are complex and influenced by diverse stakeholders. The methods used to collect AP population-level market data are similarly varied. In this paper, we review current population-level AP supply and demand estimation methods for five priority APs and provide recommendations for improving national and global AP market evaluation. Abstracts resulting from a systematic search were double-screened. Extracted data include WHO world region, publication year, age-groups, AP domain(s), study method, and individual assessment approach.497 records were identified. Vision-related APs comprised 65% (n = 321 studies) of the body of literature; hearing (n = 59), mobility (n = 24), cognitive (n = 2), and studies measuring multiple domains (n = 92) were proportionately underrepresented. To assess individual AP need, 4 unique approaches were identified among 392 abstracts; 45% (n = 177) used self-report and 84% (n = 334) used clinical evaluation. Study methods were categorized among 431 abstracts; Cross-sectional studies (n = 312, 72%) and secondary analyses of cross-sectional data (n = 61, 14%) were most common. Case studies illustrating all methods are provided. Employing approaches and methods in the contexts where they are most well-suited to generate standardized AP indicators will be critical to further develop comparable population-level research informing supply and demand, ultimately expanding sustainable access to APs.
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Measuring assistive technology supply and demand: A scoping review
Jamie Danemayer, Dorothy Boggs, Emma M. Smith, Vinicius Delgado Ramos, Linamara Rizzo Battistella, Cathy Holloway & Sarah Polack (2021) Measuring assistive technology supply and demand: A scoping review, Assistive Technology, 33:sup1, S35-S49, DOI: 10.1080/10400435.2021.1957039
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Measuring assistive technology supply and demand: A scoping review
Type
Journal Paper
Themes
Assistive & Accessible Technology
Research Group
Humanitarian & Disasters
Meeting AT needs in humanitarian crises: The current state of provision
Golnaz Whittaker, Gavin Adam Wood, Giulia Oggero,Maria Kett, Kirstin Lange
This paper discusses the evidence available in the literature for the scale and quality of AT provision interventions in crises, and what is known about the challenges and facilitators of provision. We conducted a search of the academic literature and retained literature that reported on any form of AT provision following crisis, where international humanitarian response was in place, published in English between January 2010 and June 2020.
Assistive Technology The Official Journal of RESNA; 2021
Abstract
Meeting AT needs in humanitarian crises: The current state of provision
Humanitarian coordination systems increasingly recognize and aim to respond to the needs of people with disabilities within populations affected by crises, spurred on by the UN Convention on the Rights of Persons with Disabilities (CRPD) which was adopted in 2006. Many agencies state their aim to meet the requirements of the CRPD using a “twin track” approach: ensuring the inclusion of people with disabilities in mainstream provision, alongside targeted support for their needs, which may include the need for Assistive Technology (AT). However, there is very little evidence of AT provision in humanitarian settings, which is a specific and urgent need for many people including the elderly and people with disabilities, and an implicit requirement of Article 11 of the CRPD and World Health Assembly resolution on improving access to assistive technology. There is also little evidence of effective mechanisms for AT provision in humanitarian settings. This is despite high and growing levels of unmet AT need in crises, and despite the legally binding requirement in the CRPD to provide AT for those who need it. AT provision faces unique challenges in humanitarian settings. This paper discusses the evidence available in the literature for the scale and quality of AT provision interventions in crises, and what is known about the challenges and facilitators of provision. We conducted a search of the academic literature and retained literature that reported on any form of AT provision following crisis, where international humanitarian response was in place, published in English between January 2010 and June 2020. We found very few examples in that academic literature of systematic and coordinated AT provision at the acute stage of crisis, and even less in the preparedness and post-acute stages. However, it is difficult to assess whether this is the result of insufficient academic attention or reflects a lack of provision. The small body of academic literature that describes AT provision in humanitarian settings paints a picture of small-scale provision, specialized to single types of impairments, and delivered by predominantly by NGOs. We also conducted a search of the gray literature, using the same inclusion criteria, in two countries: Afghanistan and South Sudan (case studies forthcoming). This gray literature provided supplementary evidence of the types of AT providers and AT provision available in those protracted crises. There are very few examples of how AT services can be scaled up (from a very low baseline) and maintained sustainably within a strengthened health system. The literature also describes more examples of provision of assistive products for mobility over assistive products for other impairments. If the paucity of literature on AT provision in humanitarian settings is a reflection of the scale of provision, this implies a deficiency in humanitarian response when it comes to providing people with AT needs with the essential products and services to which they have a right, and which will enable their access to basic, life-saving assistance. We conclude by providing recommendations for urgent actions that the AT and humanitarian community must take to fill this critical gap in the provision of essential products and services for a potentially marginalized and excluded group.
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Meeting AT needs in humanitarian crises: The current state of provision
Golnaz Whittaker, Gavin Adam Wood, Giulia Oggero, Maria Kett & Kirstin Lange (2021) Meeting AT needs in humanitarian crises: The current state of provision, Assistive Technology, 33:sup1, S3-S16, DOI: 10.1080/10400435.2021.1934612
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Meeting AT needs in humanitarian crises: The current state of provision
Type
Journal Paper
Themes
Assistive & Accessible Technology
Research Group
Local Productions
Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World?
Ben Oldfrey,Giulia Barbareschi, Priya Morjaria, Tamara Giltsoff, Jessica Massie, Mark Miodownik andCatherine Holloway
From multiple studies conducted through the FCDO AT2030 Programme, as well as key literature, we examine whether Assistive Technology (AT) provision models could look towards more sustainable approaches, and by doing this benefit not only the environment, but also address the problems that the current provision systems have.
Sustainability
Abstract
Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World?
From multiple studies conducted through the FCDO AT2030 Programme, as well as key literature, we examine whether Assistive Technology (AT) provision models could look towards more sustainable approaches, and by doing this benefit not only the environment, but also address the problems that the current provision systems have. We show the intrinsic links between disability inclusion and the climate crisis, and the particular vulnerability people with disabilities face in its wake. In particular, we discuss how localised circular models of production could be beneficial, facilitating context driven solutions and much needed service elements such as repair and maintenance. Key discussion areas include systems approaches, digital fabrication, repair and reuse, and material recovery. Finally, we look at what needs be done in order to enable these approaches to be implemented. In conclusion, we find that there are distinct parallels between what AT provision models require to improve equitable reliable access, and strategies that could reduce environmental impact and bring economic benefit to local communities. This could allow future AT ecosystems to be key demonstrators of circular models, however further exploration of these ideas is required to make sense of the correct next steps. What is key in all respects, moving forward, is aligning AT provision with sustainability interventions.
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Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World?
Oldfrey, B.; Barbareschi, G.; Morjaria, P.; Giltsoff, T.; Massie, J.; Miodownik, M.; Holloway, C. Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World? Sustainability2021, 13, 10867.https://doi.org/10.3390/su1319...
Could Assistive Technology Provision Models Help Pave the Way for More Environmentally Sustainable Models of Product Design, Manufacture and Service in a Post-COVID World?
Type
Journal Paper
Themes
Assistive & Accessible Technology
Research Group
Local Productions
A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems
Catherine Holloway, Dafne Zuleima Morgado Ramirez,Tigmanshu Bhatnagar,Ben Oldfrey, Priya Morjaria, Soikat Ghosh Moulic, Ikenna D. Ebuenyi,Giulia Barbareschi,Fiona Meeks, Jessica Massie, Felipe Ramos-Barajas, Joanne McVeigh, Kyle Keane, George Torrens, P. V.M. Rao, Malcolm MacLachlan,Victoria Austin, Rainer Kattel, Cheryl D Metcalf & Srinivasan Sujatha
It is essential to understand the strategies and processes which are deployed currently across the Assistive Technology (AT) space toward measuring innovation. The main aim of this paper is to identify functional innovation strategies and processes which are being or can be deployed in the AT space to increase access to AT globally.
Assistive Technology The Official Journal of RESNA
Abstract
A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems
It is essential to understand the strategies and processes which are deployed currently across the Assistive Technology (AT) space toward measuring innovation. The main aim of this paper is to identify functional innovation strategies and processes which are being or can be deployed in the AT space to increase access to AT globally. We conducted a scoping review of innovation strategies and processes in peer-reviewed literature databases and complemented this by identifying case studies demonstrating innovation strategies. The review includes WHO world region, publication year, AT type and a sector analysis against the Systems-Market for Assistive and Related Technologies Framework. We analyzed the case studies and interviews using thematic analysis. We included 91 papers out of 3,127 after review along with 72 case studies. Our results showed that product innovations were more prevalent than provision or supply innovations across papers and case studies. Case studies yielded two themes: open innovation (OI); radical and disruptive innovation. Financial instruments which encourage OI are needed and we recommend pursuing OI for AT innovation. Embedding AT within larger societal missions will be key to success governments and investors need to understand what AT is and their translational socioeconomic value.
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A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems
Catherine Holloway, Dafne Zuleima Morgado Ramirez, Tigmanshu Bhatnagar, Ben Oldfrey, Priya Morjaria, Soikat Ghosh Moulic, Ikenna D. Ebuenyi, Giulia Barbareschi, Fiona Meeks, Jessica Massie, Felipe Ramos-Barajas, Joanne McVeigh, Kyle Keane, George Torrens, P. V.M. Rao, Malcolm MacLachlan, Victoria Austin, Rainer Kattel, Cheryl D Metcalf & Srinivasan Sujatha (2021) A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems, Assistive Technology, 33:sup1, 68-86, DOI:10.1080/10400435.2021.1970653
A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems
Type
Journal Paper
Themes
Inclusive Design
Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities
Mikaela Patrick,Iain McKinnon
Public spaces, including recreational and social spaces, are often not prioritised. Inclusive public spaces are fundamental to participation and inclusive in society. Including persons with disabilities in the design and planning of the built environment supports equal rights and helps identify people’s aspirations for inclusive environments. Four city case studies will be discussed in this paper: Ulaanbaatar, Mongolia; Varanasi, India; Surakarta, Indonesia; and Nairobi, Kenya.
The Journal of Public Space
Abstract
Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities
This paper presents some of the findings from a global research study on inclusive infrastructure and city design and will focus on inclusive public spaces. Persons with disabilities can experience multi-dimensional exclusion from urban life, including but not limited to physical, attitudinal and social barriers. Public spaces, including recreational and social spaces, are often not prioritised. Inclusive public spaces are fundamental to participation and inclusive in society. Including persons with disabilities in the design and planning of the built environment supports equal rights and helps identify people’s aspirations for inclusive environments.Four city case studies will be discussed in this paper: Ulaanbaatar, Mongolia; Varanasi, India; Surakarta, Indonesia; and Nairobi, Kenya. Research participants and objectives are organised by three stakeholder groups:
People- first-hand experiences of persons with disabilities living in the city and their aspirations for a more inclusive city
Policy- the awareness and understanding of inclusive design among policy-makers
Practice- the awareness and understanding of inclusive design among practitioners including barriers to implementation, opportunities and the relationship with assistive technology
Methods include document reviews, interviews, photo diaries and co-design workshops with participatory and inclusive engagement of persons with disabilities throughout. Findings on public spaces are discussed in three ways:
The types of public spaces valued by participants in each of the four cities.
The barriers and challenges experienced by persons with disabilities in the public realm.
Aspirations for more inclusive public spaces and opportunities for inclusive design
The paper concludes by discussing how the targeted stakeholder groups of people, policy and practice also help represent three essential dimensions of inclusive city design and forming a framework for successful implementation and delivery and supporting targets set out through the UNCRPD and Sustainable Development Goals (SDGs).
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Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities
Patrick, M. and McKinnon, I. (2022) “Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities”, The Journal of Public Space, 7(2), pp. 93–116. doi: 10.32891/jps.v7i2.1500.
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Co-creating Inclusive Public Spaces: Learnings from Four Global Case Studies on inclusive Cities
Type
Journal Paper
Themes
Culture and Participation
Research Group
Social Justice
Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change
Jessica Noske-Turner, Emma Pullen, Mufunanji Magalasi, Damian Haslett, Jo Tacchi
Communication & Sport
Abstract
Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change
The purpose of this commentary is to discuss how Paralympic coverage in sub-Saharan Africa can be effectively mobilised to stimulate discursive and structural change around disability. Paralympic coverage has demonstrated its pedagogical power to engage public(s) and challenge stigma toward disability. Yet, the Global picture of Paralympic broadcasting is deeply uneven, with audiences in parts of the Global South afforded limited opportunities to watch the Games. Considering this, the International Paralympic Committee has begun to broadcast Paralympic coverage across sub-Saharan Africa with an explicit aim to challenge stigma toward disability. In this article, we draw on examples from research to argue that ideas from the field of Communication for Social Change (CfSC) can add value towards this aim. We begin by providing a brief overview of CfSC before critically examining one of the field’s key concepts – Communicative (E)ecologies. Following this, we critically reflect on the potential of Paralympic broadcasting as a vehicle for social change and disability rights agendas in sub-Saharan Africa. We argue that thinking with CfSC concepts show the importance of a ‘decentred’ media approach that engages with disability community advocacy groups, localised communication activities and practices, and culturally specific disability narratives.
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Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change
Noske-Turner, J., Pullen, E., Magalasi, M., Haslett, D., & Tacchi, J. (2022). Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change. Communication & Sport, 10(5), 1001–1015.https://doi.org/10.1177/216747...
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Paralympic Broadcasting in Sub-Saharan Africa: Sport, Media and Communication for Social Change
Type
Journal Paper
Themes
Culture and Participation
Research Group
Social Justice
This Is the Story of Community Leadership with Political Backing. (PM1)" Critical Junctures in Paralympic Legacy: Framing the London 2012 Disability Inclusion Model for New Global Challenges ?"
Victoria Austin,Kate Mattick, andCathy Holloway
Disability inclusion necessitates proactive efforts to ensure everybody has an independent and equitable opportunity to meaningfully participate in the activities of their choosing [1,2,3]. Furthermore, disability justice is not a minority concern. There are more than a billion disabled people worldwide, and impairment is something which affects most people’s family right now and will impact all of us over our lifetime. The United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) enshrines human rights of all disabled people [4], and in 2015 the Sustainable Development Goals (SDG’s) recognised disability inclusion for the first time with the call to ‘leave no-one behind’. Increasingly, governments, non-governmental agencies and businesses alike are seeking to develop and implement policy and practice which enables greater social inclusion for disabled people (In this paper, Disabled People is used in line with the Social Model of Disability in the UK, though please note the UN uses ‘Persons with Disabilities’ as is common in North America) [5]. Eighty percent of the disabled people in the world live in low resource settings in the Global South [3] with a projected growth of this number due to an increase in population age, there is the ever-pressing need to critically evaluate how best to approach disability inclusion to build a societies where we all can flourish. Despite this, we lack case studies of how disability inclusion can be done well—in the literature and in practice. For this reason, we set out to undertake this research using one the most recognised cases of ‘disability inclusion done well’.
Sustainability
Abstract
This Is the Story of Community Leadership with Political Backing. (PM1)" Critical Junctures in Paralympic Legacy: Framing the London 2012 Disability Inclusion Model for New Global Challenges ?"
The London 2012 Paralympic Games was called “the most successful Paralympic Games ever” (by the then-President of the IPC), and it saw more athletes from more countries than ever before compete and become global heroes for the first time in a redeveloped part of East London which also hosted “the most accessible Olympic Games ever” that summer. However, the model used to design and deliver disability inclusion for London 2012, and its legacy, has never been explicitly written up. This paper presents new primary evidence from first-hand research from those who were involved; retrospectively framing the London 2012 Disability Inclusion Model such that it might be usable and developed for other global disability challenges. We used an adapted Delphi methodology, through four rounds: beginning with an initial hypothesis and testing through semi-structured interviews with ten key players in the London 2012 disability inclusion approach. Using thematic analysis with consensus building surveys and workshops we came to a settled unanimous agreement on the 12-step London 2012 Disability Inclusion Modelcomprising three parts: (Get ready) community-led mission setting, (Get set) essential building blocksand (Go) enabling a culture of success. The model is presented here, alongside a narrative on its uniqueness and replicability to other major programs, as a public good. We welcome its active use, testing and adaption by others in service of disability innovation for a fairer world.
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This Is the Story of Community Leadership with Political Backing. (PM1)" Critical Junctures in Paralympic Legacy: Framing the London 2012 Disability Inclusion Model for New Global Challenges ?"
Victoria Austin, Kate Mattick, and Cathy Holloway. 2021. "“This Is the Story of Community Leadership with Political Backing. (PM1)” Critical Junctures in Paralympic Legacy: Framing the London 2012 Disability Inclusion Model for New Global Challenges" Sustainability13, no. 16: 9253.https://doi.org/10.3390/su13169253
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This Is the Story of Community Leadership with Political Backing. (PM1)" Critical Junctures in Paralympic Legacy: Framing the London 2012 Disability Inclusion Model for New Global Challenges ?"
Type
Workshop
Themes
Assistive & Accessible Technology
Culture and Participation
Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions
Maryam Bandukda, Aneesha Singh,Catherine Holloway,Nadia Berthouze, Emeline Brulé, Ana Tajadura-Jiménez, Oussama Metatla, Ana Javornik, and Anja Thieme
The emerging possibilities of multisensory interactions provide an exciting space for disability and open up opportunities to explore new experiences for perceiving one's own body, it's interactions with the environment and also to explore the environment itself. In addition, dynamic aspects of living with disability, life transitions, including ageing, psychological distress, long-term conditions such as chronic pain and new conditions such as long-COVID further affect people's abilities. Interactions with this diversity of embodiments can be enriched, empowered and augmented through using multisensory and cross-sensory modalities to create more inclusive technologies and experiences. To explore this, in this workshop we will explore three related sub-domains: immersive multi-sensory experiences, embodied experiences, and disability interactions and design.
CHI EA '21: Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems
Abstract
Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions
The emerging possibilities of multisensory interactions provide an exciting space for disability and open up opportunities to explore new experiences for perceiving one's own body, it's interactions with the environment and also to explore the environment itself. In addition, dynamic aspects of living with disability, life transitions, including ageing, psychological distress, long-term conditions such as chronic pain and new conditions such as long-COVID further affect people's abilities. Interactions with this diversity of embodiments can be enriched, empowered and augmented through using multisensory and cross-sensory modalities to create more inclusive technologies and experiences. To explore this, in this workshop we will explore three related sub-domains: immersive multi-sensory experiences, embodied experiences, and disability interactions and design. The aim is to better understand how we can re-think the senses in technology design for disability interactions and the dynamic self, constructed through continuously changing sensing capabilities either because of changing ability or because of the empowering technology. This workshop will: (i) bring together HCI researchers from different areas, (ii) discuss tools, frameworks and methods, and (iii) form a multidisciplinary community to build synergies for further collaboration.
Cite
Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions
Maryam Bandukda, Aneesha Singh, Catherine Holloway, Nadia Berthouze, Emeline Brulé, Ana Tajadura-Jiménez, Oussama Metatla, Ana Javornik, and Anja Thieme. 2021. Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions. Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems. Association for Computing Machinery, New York, NY, USA, Article 118, 1–5. DOI:https://doi.org/10.1145/341176...
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Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions
Type
Editorial
Themes
Assistive & Accessible Technology
A right to the frivolous? Renegotiating a wellbeing agenda for AT research
Giulia Barbareschi& Tom Shakespeare
Assistive products (APs) are broadly defined as “ any product (including devices, equipment, instruments, and software), either specially designed and produced or generally available, whose primary purpose is to maintain or improve an individual’s functioning and independence and thereby promote their wellbeing” (Khasnabis et al.,2015). Although the concept of wellbeing is extremely slippery and researchers have yet to agree on a single definition for it, as individuals we instinctively develop mental models about what does, and does not, promote our happiness and wellbeing. Considerations about values, wellbeing and happiness are extremely personal and are shaped by a variety of factors ranging from our age and socio-cultural background to our life experiences (Schwartz & Bardi,2001).
RESNA
Abstract
A right to the frivolous? Renegotiating a wellbeing agenda for AT research
Assistive products (APs) are broadly defined as “ any product (including devices, equipment, instruments, and software), either specially designed and produced or generally available, whose primary purpose is to maintain or improve an individual’s functioning and independence and thereby promote their wellbeing” (Khasnabis et al.,2015). Although the concept of wellbeing is extremely slippery and researchers have yet to agree on a single definition for it, as individuals we instinctively develop mental models about what does, and does not, promote our happiness and wellbeing. Considerations about values, wellbeing and happiness are extremely personal and are shaped by a variety of factors ranging from our age and socio-cultural background to our life experiences (Schwartz & Bardi,2001).
However, when it comes to assistive technology (AT) research, our focus seems to be primarily geared toward values and activities in the domains of education, employment, transport or health, often framed according to an outcome driven perspective that is heavily influenced by what is seen as useful (often what is measurable), vs what is frivolous (less tangible social or emotional aspects).
This disparity parallels the priorities of the disability rights movement and disability studies research that have helped to shape the research agenda around disability and AT. Often influenced by labor movement politics, or feminism, there appears to have been more concern with public and practical aspects of social life as opposed to the more private and sensitive ones (Shakespeare,2014). The focus on the public utilitarian function of AT becomes even more evident when we consider AT research carried out in the Global South. In this context the success of an intervention is usually assessed using measures of outcome and impact which can be somehow linked to economic improvement (Alkire,2016).
In this editorial, we are not suggesting that enabling people with disabilities to gain a good education, obtain a fulfilling job or be able to vote are not important goals for the APs we develop and research. But are those the only worthwhile goals? Should we not also enquire whether existing and future APs could help people with disabilities to develop meaningful friendships, enjoy fulfilling sex lives with their partners of choice, cook sociable dinners, or engage in their favorite hobbies? Although sporadic publications focus on the role of APs in the context of personal relationships, sexuality, or fun and play for people with disabilities do exist, these are rare, and often framed around utilitarian goals. For example, research around AT and play is largely focused on children and often examined in connection to learning outcomes. Similarly, sex and sexuality are often explored solely in connection to dysfunction, abuse or sexual health (Shakespeare & Richardson,2018).
These unbalanced narratives show how the AT research agenda is dictated by a set of universal priorities that are largely focused on global measurable goals that do not necessarily match the everyday values of people with disabilities. We invite researchers and practitioners to consider ways to find a better balance between public and private aspects of life, and between utilitarian and emotional values. Both approaches have a significant impact on the lives of people with disabilities.
Ultimately, as AT researchers we need to actively engage with people with disabilities to uncover their priorities, understand what different people with disabilities most value in life, and identify how current and future APs might help to make a positive impact on wellbeing. Aspects of life such as friendship, socialization, sexuality, love and play might indeed be more frivolous than practical ones such as education, health, employment and civil rights, but they are inherent to our shared humanity and fundamental to our happiness.
Cite
A right to the frivolous? Renegotiating a wellbeing agenda for AT research
Giulia Barbareschi & Tom Shakespeare (2021) A right to the frivolous? Renegotiating a wellbeing agenda for AT research, Assistive Technology, 33:5, 237, DOI:10.1080/10400435.2021.1984112
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A right to the frivolous? Renegotiating a wellbeing agenda for AT research
Type
Workshop
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Disability Design and Innovation in Low Resource Settings: Addressing Inequality Through HCI.
Giulia Barbareschi,Dafne Zuleima Morgado-Ramirez,Catherine Holloway, Swami Manohar Swaminathan, Aditya Vashistha, and Edward Cutrell.
Approximately 15% of the world's population has a disability and 80% live in low resource-settings, often in situations of severe social isolation. Technology is often inaccessible or inappropriately designed, hence unable to fully respond to the needs of people with disabilities living in low resource settings. Also lack of awareness of technology contributes to limited access. This workshop will be a call to arms for researchers in HCI to engage with people with disabilities in low resourced settings to understand their needs and design technology that is both accessible and culturally appropriate.
Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems.
Abstract
Disability Design and Innovation in Low Resource Settings: Addressing Inequality Through HCI.
Approximately 15% of the world's population has a disability and 80% live in low resource-settings, often in situations of severe social isolation. Technology is often inaccessible or inappropriately designed, hence unable to fully respond to the needs of people with disabilities living in low resource settings. Also lack of awareness of technology contributes to limited access. This workshop will be a call to arms for researchers in HCI to engage with people with disabilities in low resourced settings to understand their needs and design technology that is both accessible and culturally appropriate. We will achieve this through sharing of research experiences, and exploration of challenges encountered when planning HCI4D studies featuring participants with disabilities. Thanks to the contributions of all attendees, we will build a roadmap to support researchers aiming to leverage post-colonial and participatory approaches for the development of accessible and empowering technology with truly global ambitions.
Cite
Disability Design and Innovation in Low Resource Settings: Addressing Inequality Through HCI.
Giulia Barbareschi, Dafne Zuleima Morgado-Ramirez, Catherine Holloway, Swami Manohar Swaminathan, Aditya Vashistha, and Edward Cutrell. 2021. Disability Design and Innovation in Low Resource Settings: Addressing Inequality Through HCI. Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems. Association for Computing Machinery, New York, NY, USA, Article 124, 1–5. DOI:https://doi.org/10.1145/3411763.3441340
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Disability Design and Innovation in Low Resource Settings: Addressing Inequality Through HCI.
Type
Journal Paper
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Physiological Computing
STEP-UP: Enabling Low-Cost IMU Sensors to Predict the Type of Dementia During Everyday Stair Climbing
Catherine Holloway, William Bhot, Keir X. X. Yong, Ian McCarthy, Tatsuto Suzuki, Amelia Carton, Biao Yang, Robin Serougne, Derrick Boampong, Nick Tyler, Sebastian J. Crutch, Nadia Berthouze andYoungjun Cho
Posterior Cortical Atrophy is a rare but significant form of dementia which affects people's visual ability before their memory. This is often misdiagnosed as an eyesight rather than brain sight problem. This paper aims to address the frequent, initial misdiagnosis of this disease as a vision problem through the use of an intelligent, cost-effective, wearable system, alongside diagnosis of the more typical Alzheimer's Disease.
Frontiers in Computer Science
Abstract
STEP-UP: Enabling Low-Cost IMU Sensors to Predict the Type of Dementia During Everyday Stair Climbing
Posterior Cortical Atrophy is a rare but significant form of dementia which affects people's visual ability before their memory. This is often misdiagnosed as an eyesight rather than brain sight problem. This paper aims to address the frequent, initial misdiagnosis of this disease as a vision problem through the use of an intelligent, cost-effective, wearable system, alongside diagnosis of the more typical Alzheimer's Disease. We propose low-level features constructed from the IMU data gathered from 35 participants, while they performed a stair climbing and descending task in a real-world simulated environment. We demonstrate that with these features the machine learning models predict dementia with 87.02% accuracy. Furthermore, we investigate how system parameters, such as number of sensors, affect the prediction accuracy. This lays the groundwork for a simple clinical test to enable detection of dementia which can be carried out in the wild.
STEP-UP: Enabling Low-Cost IMU Sensors to Predict the Type of Dementia During Everyday Stair Climbing
| https://www.disabilityinnovation.com/publications?page=7&type=editorial+journal-paper+report+workshop |
World War II Servicemen's Correspondence Collection, 1941-1945 | SDSUnbound
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Collection Description
A collection of approximately 5,000 original letters sent by San Diego State students on active duty in the armed forces during World War II, or their families, to Professor Lauren Post who compiled and distributed the Aztec News Letter.
Immediately after Pearl Harbor and as the War progressed, Aztec students were soon scattered all over the globe, disconnected and separated from their college, their friends, their loved ones, and their former lives. In the spring of 1942, Dr. Post, professor of geography from 1937-69 and a veteran of World War I, decided to try a "news service experiment" intended to provide information about the locations of current and former Aztecs dispersed around the world. The Aztec News Letter thus became a crucial lifeline throughout the War for Aztec servicemen and women facing difficulty and danger wherever they were stationed. Lauded as one of the first of its kind in the nation, the Aztec News Letter premiered in May of 1942 and was released monthly until its 48th issue in March of 1946. By then, The Aztec News Letter circulated to more than 3,000 service and home front readers. The project and the letters that made it possible would forever characterize the Aztec spirit during wartime. Not only are the letters historically significant; they also offer a unique perspective about San Diego State during a global crisis.
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Letter from Ben L. Parker, 1942 Letter from Ben L. Parker, 1943-03 Letter from Ben L. Parker, 1943-06
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Letter from Ben Siegel, 1945-04
Letter from Ben Siegel, 1945-07
Letter from Ben Siegel, 1945-08
Letter from Ben W. Long, 1943 Letter from Ben W. Stanley, 1943
Letter from Ben W. Stanley, 1944-01
Letter from Ben W. Stanley, 1944-05 Letter from Benjamin D. Shoemaker, Jr., 1942
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Can the BMI-based dose regimen be used to reduce injection activity and to obtain a constant image quality in oncological patients by 18F-FDG total-body PET/CT imaging? | Request PDF
Request PDF | Can the BMI-based dose regimen be used to reduce injection activity and to obtain a constant image quality in oncological patients by 18F-FDG total-body PET/CT imaging? | Purpose PET image quality is influenced by the patient size according to the current guideline. The study aimed to propose an optimized dose... | Find, read and cite all the research you need on ResearchGate
Can the BMI-based dose regimen be used to reduce injection activity and to obtain a constant image quality in oncological patients by 18F-FDG total-body PET/CT imaging?
December 2021
European Journal of Nuclear Medicine and Molecular Imaging 49(4)
DOI: 10.1007/s00259-021-05462-5
Authors:
Sui Xiuli
Fudan University
Abstract and Figures
Purpose
PET image quality is influenced by the patient size according to the current guideline. The study aimed to propose an optimized dose regimen to yield a constant image quality independent of patient habitus to meet the clinical needs.
Methods
A first patient cohort of 78 consecutive oncological patients (59.7 ± 13.7 years) who underwent a total-body PET/CT scan were retrospectively enrolled to develop the regimen. The patients were randomly distributed in four body mass index (BMI) groups according to the World Health Organization (WHO) criteria. The liver SNR (signal-to-noise ratio, SNRL) was obtained by manually drawing regions of interest (ROIs) and normalized (SNRnorm) by the product of injected activity and acquisition time. Fits of SNRnorm against different patient-dependent parameters were performed to determine the best correlating parameter and fit method. A qualitative assessment on image quality was performed using a 5-point Likert scale to determine the acceptable threshold of SNRL. Thus, an optimized regimen was proposed and validated by a second patient cohort consisted of prospectively enrolled 38 oncological patients.
Results
The linear fit showed SNRnorm had the strongest correlation (R² = 0.69) with the BMI than other patient-dependent parameters and fit method. The qualitative assessment indicated a SNRL value of 14.0 as an acceptable threshold to achieve sufficient image quality. The optimized dose regimen was determined as a quadratic relation with BMI: injected activity (MBq) = 39.2 (MBq)/(− 0.03*BMI + 1.49)². In the validation study, the SNRL no longer decreased with the increase of BMI. There was no significant difference of the image quality regarding the value of SNRL between different BMI groups (p > 0.05). In addition, the injected activity was reduced by 75.6 ± 2.9%, 72.1 ± 4.0%, 67.1 ± 4.4%, and 64.8 ± 3.5% compared with the first cohort for the four BMI groups, respectively.
Conclusion
The study proposed a quadratic relation between the ¹⁸F-FDG injected activity and the patient’s BMI for total-body ¹⁸F-FDG PET imaging. In this regimen, the image quality can maintain in a constant level independent of patient habitus and meet the clinical requirement with a reduced injected activity.
Reference images of the scores from 1 to 5 (from left to right). Image quality was assessed based on the maximum intensity projection (MIP) images (upper row) and the transverse images (lower row) …
Boxplots of the SNRL(a) against acquisition durations. According to Whiskers specify Tukey plot, a significant difference compared with G300 (grey box) is indicated with **** (p < 0.0001) …
The linear fits (a-g) and non-linear fits (a1-g1) of the SNRnorm against the patient-dependent parameters, including height (a, a1), BM (body mass, b, b1), body mass per height (BM/H, c, c1), lean body weight (LBW, d, d1), fat mass (FM, e, e1), body surface area (BSA, f, f1) and body mass index (BMI, g, g1). Note: SNRnorm, normalized signal-to-noise ratio …
Qualitative scores of different BMI groups in the validation cohort. There was no significant difference between the BMI groups. Note: ns, no significant difference …
Comparison of patient images in a linear weight-based (a, b) and the proposed BMI-based dose regimen (c, d). Compared with the linear weight-based regimen, MIP and transverse images of the total-body ¹⁸F-FDG PET images showed an improved image quality for patients with a BMI = 25 kg/m² (subfigure a vs. c) and 30 kg/m² (subfigure b vs. d) …
Figures - available from: European Journal of Nuclear Medicine and Molecular Imaging
Vol.:(0123456789)
1 3
https://doi.or g/10.1007/s00259-021-05462-5
ORIGINAL ARTICLE
Can theBMI‑based dose regimen be used toreduce injection activity
andtoobtain aconstant image quality inoncological patients
by 18 F‑FDG total‑body PET/CT imaging?
JieXiao 1,2,3 · HaojunY u 1,2,3 · XiuliSui 1,2,3 · Y anHu 1,2,3 · Yan yanCao 1,2,3 · GuobingLiu 1,2,3 · YiqiuZhang 1,2,3,4 ·
PengchengHu 1,2,3 · Ying Wang 5 · ChenweiLi 5 · BaixuanXu 6 · HongchengShi 1,2,3,4
Received: 6 April 2021 / Accepted: 10 June 2021
© The Author(s), under exclusive lic ence to Springer-Verlag GmbH Germany, part of Springer Nature 2021
Abstract
Purpose PET image quality is influenced by the patient size according to the current guideline. The study aimed to propose
an optimized dose regimen to yield a constant image quality independent of patient habitus to meet the clinical needs.
Methods A first patient cohort of 78 consecutiv e oncological patients (59.7 ± 13.7years) who under went a to tal-body PET/
CT scan were retrospectivel y enrolled to develop the regimen. The patients were randomly distributed in four body mass
index (BMI) groups according to the W orld Health Organization (WHO) criteria. The liver SNR (signal-to-noise ratio, SNR L )
was obtained by manually dra wing regions of interest (ROIs) and normalized (SNR norm ) by the product of injected activity
and acquisition time. Fits of SNR norm against different patient-dependent parame ters were performed to determine the best
correlating parameter and fit method. A qualitative assessment on image quality was perf ormed using a 5-point Likert scale
to determine the acceptable threshold of SNR L . Thus, an optimized regimen was proposed and validated by a second patient
cohort consisted of prospectively enrolled 38 oncological patients.
Results The linear fit showed SNR norm had the strongest correlation (R 2 = 0.69) with the BMI than other patient-dependent
parameters and fit method. The qualitative assessment indicated a SNR L v alue of 14.0 as an acceptable threshold to achieve
sufficient image quality . The optimized dose regimen was determined as a quadratic relation with BMI: injected activity
(MBq) = 39.2 (MBq)/(− 0.03*BMI + 1.49) 2 . In the validation study , the SNR L no longer decreased with the increase of BMI.
There was no significant difference of the image quality regarding the v alue of SNR L between different BMI groups ( p > 0.05).
In addition, the injected activity was reduced by 75.6 ± 2.9%, 72.1 ± 4.0%, 67.1 ± 4.4%, and 64.8 ± 3.5% compared with the
first cohort for the four BMI groups, respectivel y.
Conclusion The study proposed a quadratic relation between the 18 F-FDG injected activity and the patient’ s BMI for total-
body 18 F-FDG PET imaging. In this regimen, the image quality can maintain in a constant level independent of patient
habitus and meet the clinical requirement with a reduced injected activity .
Keywords Image quality· Dose optimization· Patient habitus· T otal-body PET· FDG· PET/CT imaging
This article is part of the Topical Collection on Technology
* Baixuan Xu
xbx301@163.com
* Hongcheng Shi
Shi.hongcheng@zs-hospital.sh.cn
1 Department ofNuclear Medicine, Zhongshan Hospital
affiliated Fudan University , 180 Fenglin Road,
Shanghai200032, China
2 Institute ofNuclear Medicine, Fudan University ,
Shanghai200032, China
3 Shanghai Institute ofMedical Imaging, Shanghai200032,
China
4 Collaborative Innovation Center f orMolecular Imaging
Precision Medicine, Shanxi Medical University , Taiyuan,
Shanxi030001, People’sR epublicofChina
5 Central Research Institute, United Imaging Healthcare,
Shanghai201807, China
6 Department ofNuclear Medicine, Chinese PLA General
Hospital, Beijing100853, China
/ Published online: 29 June 2021
European Journal of Nuclear Medicine and Molecular Imaging (2021) 49:269–278
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... It is also worth to be mentioned that most of the articles used several injected doses, which led to one or several optimized doses. In the summary Table 1, explore the studies that had utilized very highly sensitive PET devices in their studies (>170 cps/MBq), all of which were using the Time of flight (TOF) and Point Spread Function (PSF) options together (17)(18)
(19)
(20)(21)(22). In addition, almost more than half of the PET scanners that were included in our literature were utilizing both the Time of flight and Point Spread Function technology for positron emission tomographic images reconstruction (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). ...
... In the summary Table 1, explore the studies that had utilized very highly sensitive PET devices in their studies (>170 cps/MBq), all of which were using the Time of flight (TOF) and Point Spread Function (PSF) options together (17)(18)(19)(20)(21)(22). In addition, almost more than half of the PET scanners that were included in our literature were utilizing both the Time of flight and Point Spread Function technology for positron emission tomographic images reconstruction (17)(18)
(19)
(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). Also optimization of reconstruction algorithm, using of using new Bayesian penalized-likelihood reconstruction algorithm (Q.clear) (1, 16-22, 24-27, 31-40) could show their effect on injection dose optimization. ...
... we have found that most of the PET scanner's sensitivity values mentioned in our study were between 9 and 16 cps/kBq (1, 18, 20, 23-25, 30-32, 34, 36, 39-41). However, the new generated scanner sensitivity was about 176 cps/kBq (17)(18)
(19)
(20)(21)(22)26). It was also demonstrated that all of the studies used scanners with a large axial field of view, beginning at 153 mm and including 24 out of 31 PET scanners with a longer FOV greater than 190 mm. ...
18F-FDG PET Adults Whole-Body Scan Injected Dose Optimization: A Mini Review
Full-text available
Mar 2023
Murtadha Al-Fatlawi
Hayder Jasim Taher
Farideh Pak
Peyman Sheikhzadeh
While there is a necessity to have guidelines in order to control the 18 F-FDG usage in PET-CT scan exams to protect the patient and the clinical staff, there is another necessity to keep these guidelines up-to-date and according to the recent advances and adaptations of the new PET-CT scanner modalities. Regarding SNMMI, a fixed range of 18 F-FDG activity administered to the Whole-body scans in adult patients was established, yet the last update of these guidelines was in 2006. By the same token, the EANM last updated guidelines were in 2015. In this review 27 articles were successfully optimized the FDG injected dose using different techniques after 2015. These articles were analyzed and sorted to check the most common facilities that have been used to reach the optimized amount of FDG. As a result, most of the articles have very common features and each of them had an optimized rate that is under the lower limits the EANM injection guidelines. And due to the common advance techniques, that has been used in these scanners we concluded that its utterly possible to have an exam using a DTP below the guidelines while maintain a reportable image quality. Therefore, international guidelines need to take in count these advance facilities in the upcoming version of their recommendations.
... Regarding constant and acceptable image quality, we previously investigated the influence of patient size on image quality, and proposed a dose regimen based on body mass index (BMI, kg/m 2 ), demonstrating the feasibility of constant image quality for 18 F-FDG total-body PET/CT
[11]
. In addition, adjusting the duration time per bed based on scanner sensitivity and patient-specific attenuation might acquire uniform image noise or homogenous image [12]. ...
... The image quality was scored from 3 perspectives: the overall impression of the image quality, the image noise, and the lesion detectability. Score were based on a 5-point Likert scale, as follows: Score 1, image with non-diagnostic quality, excessive noise, or unfavorable lesion contrast; Score 2, acceptable image but with sub-optimal noise and lesion depiction leading to impaired diagnostic confidence; Score 3, image with quality equivalent to those used in clinical practice; Score 4, image with quality superior to the average image quality; Score 5, image with excellent quality, optimal noise, sharp lesion depiction, and free of artifact, providing diagnosis with full confidence
[11]
. A score of 3 was deemed as acceptable image quality in routine clinical practice in our center. ...
... The difference was consistent with a previous study in which the acceptable SNR L was 6.2 for whole-body 68 Ga-DOTATATE PET/CT, but 18 F-FDG studies have revealed a higher SNR of 10 [19]. Compared with 18 F-FDG with liver SUVmean of 2.6, the accumulation degree of 68 Ga-DOTATATE in liver was higher with liver SUVmean of 8.4
[11]
. We hypothesize that difference might be related to the percentage of biological distribution in the liver. ...
A personal acquisition time regimen of 68Ga-DOTATATE total-body PET/CT in patients with neuroendocrine tumor (NET): a feasibility study
Jie Xiao
Haojun Yu
Sui Xiuli
Hongcheng Shi
Background
The injection activity of tracer, acquisition time, patient-specific photon attenuation, and large body mass, can influence on image quality. Fixed acquisition time and body mass related injection activity in clinical practice results in a large difference in image quality. Thus, this study proposes a patient-specific acquisition time regimen of ⁶⁸ Ga-DOTATATE total-body positron emission tomography-computed tomography (PET/CT) to counteract the influence of body mass (BM, kg) on image quality, and acquire an acceptable and constant image of patients with neuroendocrine tumors (NETs).
Methods
The development cohort consisting of 19 consecutive patients with full activity (88.7–204.9 MBq, 2.0 ± 0.1 MBq/kg) was to establish the acquisition time regimen. The liver SNR (signal-to-noise ratio, SNR L ) was normalized (SNR norm ) by the product of injected activity (MBq) and acquisition time (min). Fitting of SNR norm against body mass (BM, kg) in linear correlation was performed. Subjective assessment of image quality was performed using a 5-point Likert scale to determine the acceptable threshold of SNR L , and an optimized acquisition regimen based on BM was proposed, and validated its feasibility through the validation cohort of 57 consecutive NET patients with half activity (66.9 ± 11.3 MBq, 1.0 ± 0.1 MBq/kg) and a fixed acquisition time regimen.
Results
The linear correlation ( R 2 = 0.63) between SNR norm and BM (kg) was SNR norm = -0.01*BM + 1.50. The threshold SNR L of acceptable image quality was 11.2. The patient-specific variable acquisition time regimen was determined as: t (min) = 125.4/(injective activity)*(-0.01*BM + 1.50) ² . Based on that proposed regimen, the average acquisition time for acceptable image quality in the validation cohort was 2.99 ± 0.91 min, ranging from 2.18 to 6.35 min, which was reduced by 36.50% ~ 78.20% compared with the fixed acquisition time of 10 min. Subjective evaluation showed that acceptable image quality could be obtained at 3.00 min in the validation group, with an average subjective score of 3.44 ± 0.53 (kappa = 0.97, 95% CI: 0.96 ~ 0.98). Bland–Altman analysis revealed good agreement between the proposed regimen and the fixed acquisition time cohort.
Conclusion
A patient-specific acquisition time regimen was proposed in NET patients in development cohort and validated its feasibility in patients with NETs in validation cohort by ⁶⁸ Ga-DOTATATE total-body PET/CT imaging. Based on the proposed regimen, the homogenous image quality with optimal acquisition time was available independent of body mass.
... As reported by several papers [13][14][15][16][17][18]
[19]
, the performances guaranteed by tbPET/CT systems may determine the reduction of acquisition times and injected activities, still providing performant imaging in oncological patients. Zhang et al. [13] investigated if a shorter acquisition time (180 s, 120 s, 60 s, 30 s and 18 s) had an impact on the image quality and lesion detectability in 19 oncological patients performing [ 18 F]-FDG PET/CT on a LAFOV scanner with a standard injected activity. ...
... Indeed, 10% of standard activity (0.37 MBq/Kg) allowed to obtain diagnostic images on a uEXPLORER PET/CT scanner with a dynamic acquisition protocol in non-obese patients. The relationship between body mass index (BMI) and the amount of injected activity in LAFOV PET/CT systems was assessed by Xiao et al.
[19]
. The authors divided 78 oncological patients performing [ 18 F]-FDG PET/CT on a uEXPLORER scanner into the 4 corresponding BMI well-balanced subgroups defined by the World Health Organization guidelines [20], aiming to offer PET imaging with a validated personalized dose regimen. ...
Clinical applications of long axial field-of-view PET/CT scanners in oncology
Giuseppe De Vincentis
PurposeTo provide a comprehensive overview of the current main applications of long axial field-of-view (LAFOV) PET/CT in oncology.Methods
Relevant studies published from 2017 up to September 2022 were selected by searching Scopus, PubMed, and Web of Science. The following data were extracted: characteristics of studies and patients, technical aspects, and usefulness of the LAFOV PET/CT in the oncological setting. Selected imaging studies were analyzed using a modified version of the Critical Appraisal Skills Programme (CASP).ResultsSeventeen papers were finally selected: 12 (70.6%) were retrospective, while 5 (29.4%) were prospective, with an overall number of 877 included patients. Most of the studies (14/17, 82.4%) employed [18F]-FDG as a radiopharmaceutical agent, 2 papers used [68Ga]-PSMA-11 and 1 employed mixed tracers. Eleven studies were focused on protocols at low/ultra-low activity or with fast/ultra-fast scanning time, 3 papers compared the performance of LAFOV PET/CT scanners with that of conventional (standard axial field-of-view/SAFOV) devices, 4 were total-body PET dynamic studies.ConclusionsLAFOV PET/CT showed superior diagnostic performance than traditional SAFOV devices, allowing reduced activity/time and dynamic protocols. The applications of this novel technology in some clinical settings, mainly the pediatric population, are promising but should be a topic of future investigations.
... Recently, the total-body PET/CT, uEXPLORER (United Imaging Healthcare, Shanghai, China) with the 194-cmlong Field of View (FOV), has ultrahigh system sensitivity and spatial resolution. Thus, it dramatically improves image quality and ability to detect small lesions and distant metastases (14,
15)
. Regarding semiquantitative parameters, several studies have found that the standard uptake value ratio (SUR) is a better predictive index than tumor maximum standard uptake value (SUVmax) (16)(17)(18)(19). ...
... The newest total-body PET/CT can achieve lower injection dose, faster scanning speed, and higher resolution than the others
(15,
40,41). Therefore, it is more valuable in clinical application. ...
The predictive value of total-body PET/CT in non-small cell lung cancer for the PD-L1 high expression
Purpose
Total-body positron emission tomography/computed tomography (PET/CT) provides faster scanning speed, higher image quality, and lower injected dose. To compensate for the shortcomings of the maximum standard uptake value (SUVmax), we aimed to normalize the values of PET parameters using liver and blood pool SUV (SUR-L and SUR-BP) to predict programmed cell death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) patients.
Materials and methods
A total of 138 (104 adenocarcinoma and 34 squamous cell carcinoma) primary diagnosed NSCLC patients who underwent ¹⁸ F-FDG-PET/CT imaging were analyzed retrospectively. Immunohistochemistry (IHC) analysis was performed for PD-L1 expression on tumor cells and tumor-infiltrating immune cells with 22C3 antibody. Positive PD-L1 expression was defined as tumor cells no less than 50% or tumor-infiltrating immune cells no less than 10%. The relationships between PD-L1 expression and PET parameters (SUVmax, SUR-L, and SUR-BP) and clinical variables were analyzed. Statistical analysis included χ ² test, receiver operating characteristic (ROC), and binary logistic regression.
Results
There were 36 patients (26%) expressing PD-L1 positively. Gender, smoking history, Ki-67, and histologic subtype were related factors. SUVmax, SUR-L, and SUR-BP were significantly higher in the positive subset than those in the negative subset. Among them, the area under the curve (AUC) of SUR-L on the ROC curve was the biggest one. In NSCLC patients, the best cutoff value of SUR-L for PD-L1-positive expression was 4.84 (AUC = 0.702, P = 0.000, sensitivity = 83.3%, specificity = 54.9%). Multivariate analysis confirmed that age and SUR-L were correlated factors in adenocarcinoma (ADC) patients.
Conclusion
SUVmax, SUR-L, and SUR-BP had utility in predicting PD-L1 high expression, and SUR-L was the most reliable parameter. PET/CT can offer reference to screen patients for first-line atezolizumab therapy.
... Previous studies have shown changes in SNR over a range of patient weights, especially in obese patients with a significant amount of body fat, and despite prescribing weight-based injected activity for them, the accumulation of radiopharmaceuticals and the resulting SNR are still low, which affect the quality of PET images.
21
Therefore, it can be helpful to compare liver SNR for different ROIs and VOIs from the PET acquisition data over a wide range of patient weights. ...
Impact of Region-of-Interest Delineation on Stability and Reproducibility of Liver SNR Measurements in 68Ga-PSMA PET/CT
Masoomeh Fooladi
Objective This study aims to assess the impact of various regions of interest (ROIs) and volumes of interest (VOIs) delineations on the reproducibility of liver signal-to-noise-ratio (SNRliver) measurements, as well as to find the most reproducible way to estimate it in gallium-68 positron emission tomography (68Ga-PET) imaging. We also investigated the SNRliver-weight relationship for these ROIs and VOIs delineations.
Methods A cohort of 40 patients (40 males; mean weight: 76.5 kg [58–115 kg]) with prostate cancer were included. 68Ga-PET/CT imaging (mean injected activity: 91.4 MBq [51.2 MBq to 134.1 MBq] was performed on a 5-ring bismuth germanium oxide-based Discovery IQ PET/CT using ordered subset expectation maximization image reconstruction algorithm. Afterward, circular ROIs and spherical VOIs with two different diameters of 30 and 40 mm were drawn on the right lobe of the livers. The performance of the various defined regions was evaluated by the average standardized uptake value (SUVmean), standard deviation (SD) of the SUV (SUVSD), SNRliver, and SD of the SNRliver metrics.
Results There were no significant differences in SUVmean among the various ROIs and VOIs (p > 0.05). On the other hand, the lower SUVSD was obtained by spherical VOI with diameter of 30 mm. The largest SNRliver was obtained by ROI (30 mm). The SD of SNRliver with ROI (30 mm) was also the largest, while the lowest SD of SNRliver was observed for VOI (40 mm). There is a higher correlation coefficient between the patient-dependent parameter of weight and the image quality parameter of SNRliver for both VOI (30 mm) and VOI (40 mm) compared to the ROIs.
Conclusion Our results indicate that SNRliver measurements are affected by the size and shape of the respective ROIs and VOIs. The spherical VOI with a 40 mm diameter leads to more stable and reproducible SNR measurement in the liver.
... The advent of the total-body or long axial FOV PET scanners has made a breakthrough in the system sensitivity, which has been proven its ability in reducing the administered activity [20][21]
[22]
[23][24]. However, up to now, there are only a limited number of total-body PET/CT scanners available worldwide. ...
Deep progressive learning achieves whole-body low-dose F-FDG PET imaging
Objectives
To validate a total-body PET-guided deep progressive learning reconstruction method (DPR) for low-dose ¹⁸F-FDG PET imaging.
Methods
List-mode data from the retrospective study (n = 26) were rebinned into short-duration scans and reconstructed with DPR. The standard uptake value (SUV) and tumor-to-liver ratio (TLR) in lesions and coefficient of variation (COV) in the liver in the DPR images were compared to the reference (OSEM images with full-duration data). In the prospective study, another 41 patients were injected with 1/3 of the activity based on the retrospective results. The DPR images (DPR_1/3(p)) were generated and compared with the reference (OSEM images with extended acquisition time). The SUV and COV were evaluated in three selected organs: liver, blood pool and muscle. Quantitative analyses were performed with lesion SUV and TLR, furthermore on small lesions (≤ 10 mm in diameter). Additionally, a 5-point Likert scale visual analysis was performed on the following perspectives: contrast, noise and diagnostic confidence.
Results
In the retrospective study, the DPR with one-third duration can maintain the image quality as the reference. In the prospective study, good agreement among the SUVs was observed in all selected organs. The quantitative results showed that there was no significant difference in COV between the DPR_1/3(p) group and the reference, while the visual analysis showed no significant differences in image contrast, noise and diagnostic confidence. The lesion SUVs and TLRs in the DPR_1/3(p) group were significantly enhanced compared with the reference, even for small lesions.
Conclusions
The proposed DPR method can reduce the administered activity of ¹⁸F-FDG by up to 2/3 in a real-world deployment while maintaining image quality.
... Although preliminary data suggest that fast-scan or lowactivity protocols result as accurate as the standard 15/20-min or full-activity scans for lesions' detection, the majority of the studies carried out until now included relatively small cohorts of subjects and presented a retrospective design, thus being hampered by possible selection bias. Furthermore, it has still to be defined how much inter-individual heterogeneity in body mass index (BMI) might impact on TB-PET/CT protocols
[37]
. However, it is clear that LAFOV scanners provide a higher sensitivity and allow low dose imaging. ...
Long axial field-of-view PET/CT devices: are we ready for the technological revolution?
Impact of patient's habitus on image quality and quantitative metrics in 18F-FDG PET/CT images
Purpose:
To study how the quantitative parameters of 18F-FDG PET imaging change with the emission scan duration (ESD) and the body-mass-index (BMI) in phantom and patients on a time-of-flight (TOF)-PET/CT system.
Methods:
The image-quality phantom with (b-NEMA-IQ, BMI = 29.2 kg/m2) and without (NEMA-IEC, BMI = 21.4 kg/m2) a 'belt' of water-bags was filled with 18F-FDG activities to obtain nominal standardized uptake values (SUV) of 19, 8 and 5. Patients with BMI ≤ 25 kg/m2 (L-BMI) and BMI > 25 kg/m2 (H-BMI) were enrolled in this study. Phantom and patients underwent list-mode PET acquisition at 120 s/bed-position. Images reconstructed with clinical protocol and different ESD (120, 90, 75, 60, 45, 30 s) were analysed for comparison of maximum SUV (SUVmax), maximum standardized uptake value lean-body-mass corrected (SULmax) and noise.
Results:
79 oncologic patients (45 L-BMI, 44 H-BMI) were analysed. From 90 s to 30 s, an increasing variation of SUVmax and SULmax with respect to the reference 120 s time was observed, from 18% to 60% and from 16% to 37% for phantom and patients, respectively. SUVmax values were significantly higher (+50%) in b-NEMA-IQ than NEMA-IQ phantom and in H-BMI (+33%) than L-BMI patients. No significant difference was found in SULmax for the two BMI categories in both phantom and patients. CV values decreased when increasing ESD, being higher in H-BMI patients (0.13-0.25) and b-NEMA-IQ phantom (0.15-0.28) than in L-BMI patients (0.11-0.21) and NEMA-IQ phantom (0.11-0.20).
Conclusions:
Reduction of ESD may severely impact on the variations of SUVmax and SULmax in 18F-FDG PET/CT imaging. This study confirms recommendations of using SUL for lesion uptake quantification, being unaffected by BMI variation.
The feasibility of ultralow-activity 18F-FDG dynamic PET imaging in lung adenocarcinoma patients through total-body PET/CT scanner
Jul 2022
Jing Lv
Objective:
To explore the feasibility of ultralow-activity 18F-FDG total-body dynamic PET imaging for clinical practice in patients with lung adenocarcinoma.
Methods:
Eight of 18 patients were randomly injected with 18F-FDG with full activity (3.7 MBq/kg) for total-body dynamic PET imaging, while 10 received one-tenth activity (0.37 MBq/kg). The generated time-to-activity curves (TACs) according to the regions of interest (ROIs) were processed by PMOD through standard FDG two-tissue compartment model fitting. The kinetic constant rates (K1, K2, K3, and Ki), radiation dose, prompt counts, and data storage size were analysed between the full- and ultralow-activity groups. The SUVmax-Tumour/SUVmax-Liver and SUVmax-Tumour/SUVmax-Muscle on static PET images were also assessed.
Results:
Each of the fitted models has a satisfactory goodness-of-fit with R2 greater than 0.9 except 3 (3/234) in ultralow-activity group, where one in pancreas (R2 = 0.851), another one in muscle (R2 = 0.868), and the third one in bone marrow (R2 = 0.895). All the fitted models in the full-activity group had a better goodness-of-fit than those in the ultralow-activity group. However, no significant differences were found in any of the kinetic metrics or image quality between the two groups except in the reduction of radiation dose and data storage size.
Conclusions:
The 10 × reduction of injected 18F-FDG could achieve comparable kinetic metrics and T/N ratios by total-body dynamic PET imaging in lung adenocarcinoma patients. Ultralow-activity total-body PET imaging is feasible for clinical practice in oncological patients without obesity, especially in dynamic PET scanning.
Expert consensus on oncological [18F]FDG total-body PET/CT imaging (version 1)
Background:
[18F]FDG imaging on total-body PET/CT (TB PET/CT) scanners, with improved sensitivity, offers new potentials for cancer diagnosis, staging, and radiation treatment planning. This consensus provides the protocols for clinical practices with a goal of paving the way for future studies with the total-body scanners in oncological [18F]FDG TB PET/CT imaging.
Methods:
The consensus was summarized based on the published guidelines and peer-reviewed articles of TB PET/CT in the literature, along with the opinions of the experts from major research institutions with a total of 40,000 cases performed on the TB PET/CT scanners.
Results:
This consensus describes the protocols for routine and dynamic [18F]FDG TB PET/CT scanning focusing on the reduction of imaging acquisition time and FDG injected activity, which may serve as a reference for research and clinic oncological PET/CT studies.
Conclusion:
This expert consensus focuses on the reduction of acquisition time and FDG injected activity with a TB PET/CT scanner, which may improve the patient throughput or reduce the radiation exposure in daily clinical oncologic imaging.
Key points:
• [18F]FDG-imaging protocols for oncological total-body PET/CT with reduced acquisition time or with different FDG activity levels have been summarized from multicenter studies. • Total-body PET/CT provides better image quality and improved diagnostic insights. • Clinical workflow and patient management have been improved.
Ultra-low-activity total-body dynamic PET imaging allows equal performance to full-activity PET imaging for investigating kinetic metrics of 18F-FDG in healthy volunteers
| https://www.researchgate.net/publication/352829708_Can_the_BMI-based_dose_regimen_be_used_to_reduce_injection_activity_and_to_obtain_a_constant_image_quality_in_oncological_patients_by_18F-FDG_total-body_PETCT_imaging |
(PDF) 7 Å resolution in protein twodimensional-crystal X-ray diffraction at Linac Coherent Light Source
PDF | Membrane proteins arranged as two-dimensional crystals in the lipid environment provide close-to-physiological structural information, which is... | Find, read and cite all the research you need on ResearchGate
Article
PDF Available
7 Å resolution in protein twodimensional-crystal X-ray diffraction at Linac Coherent Light Source
<here is a image 233da97462cb218f-db18f30570b08be9>
July 2014
Philosophical Transactions of The Royal Society B Biological Sciences369(1647)
DOI: 10.1098/rstb.2013.0500
Source
PubMed
Authors:
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe>
Bill Pedrini
Paul Scherrer Institut
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Ching-Ju Tsai
Ching-Ju Tsai
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Guido Capitani
Guido Capitani
<here is a image 245167084d3aef68-aef66848951311bf>
Celestino Padeste
Paul Scherrer Institut
Abstract and Figures
Membrane proteins arranged as two-dimensional crystals in the lipid environment provide close-to-physiological structural information, which is essential for understanding the molecular mechanisms of protein function. Previously, X-ray diffraction from individual two-dimensional crystals did not represent a suitable investigational tool because of radiation damage. The recent availability of ultrashort pulses from X-ray free-electron lasers (XFELs) has now provided a means to outrun the damage. Here, we report on measurements performed at the Linac Coherent Light Source XFEL on bacteriorhodopsin two-dimensional crystals mounted on a solid support and kept at room temperature. By merging data from about a dozen single crystal diffraction images, we unambiguously identified the diffraction peaks to a resolution of 7 Å, thus improving the observable resolution with respect to that achievable from a single pattern alone. This indicates that a larger dataset will allow for reliable quantification of peak intensities, and in turn a corresponding increase in the resolution. The presented results pave the way for further XFEL studies on two-dimensional crystals, which may include pump-probe experiments at subpicosecond time resolution.
<here is a image fcc75533e3970c02-6689d7823f692f96>
Example of a diffraction image from a single bR two-dimensional crystal. The dashed ring corresponds to 10 A ˚ resolution. The circles mark the positions of expected diffraction peaks at lower than 7 A ˚ resolution. The precise orientation of the peak lattice was derived from the positions of the prominent, easily identifiable peaks encircled in red. The basis vectors (a * , b * ) of the two-dimensional reciprocal space lattice are shown as green arrows. The small arrows mark the position of peaks in the classes ((7, 1)) (black), ((1, 7)) (magenta), ((27, 21)) (orange) and ((21, 27)) (cyan), each class consisting of three equivalent peaks. rstb.royalsocietypublishing.org Phil. Trans. R. Soc. B 369: 20130500 …
Figures - uploaded by
rstb.royalsocietypublishing.org
Research
Citethisarticle: PedriniB etal .20147A
˚
resolutioninproteintwo-dimensional-crystal
X-raydiffractionatLinacCoherentLightSource.
Phil.Trans.R.Soc.B 369 :20130500.
http://dx.doi.org/10.1098/rstb.2013.0500
Onecontributionof27toaDiscussionMeeting
Issue‘Biologywithfree-electronX-raylasers’.
SubjectAreas:
structuralbiology
Keywords:
two-dimensionalproteincrystal,X-ray
diffraction,X-rayfree-electronlaser,
crystallographicdataanalysis,
bacteriorhodopsin
Authorsforcorrespondence:
BillPedrini
e-mail:bill.pedrini@psi.ch
MatthiasFrank
e-mail:frank1@llnl.gov
Xiao-DanLi
e-mail:xiao.li@psi.ch
7A
˚
resolutioninproteintwo-
dimensional-crystalX-raydiffraction
atLinacCoherentLightSource
BillPedrini 1 ,Ching-JuTsai 1 ,GuidoCapitani 1 ,CelestinoPadeste 1,
MarkS.Hunter 2 ,NadiaA.Zatsepin 4,AntonBarty 5 ,W.HenryBenner 2,
Se
´ bastienBoutet 6 ,GeoffreyK.Feld 2,StefanP.Hau-Riege 2,RichardA.Kirian 5,
ChristopherKupitz 4 ,MarcMesserschmitt 6 ,JohnI.Ogren 7 ,TommasoPardini 2,
BrentSegelke 2 ,GarthJ.Williams 6 ,JohnC.H.Spence 4 ,RafaelAbela 1,
MatthewColeman 2 ,JamesE.Evans 3,GebhardF.X.Schertler 1,
MatthiasFrank 2 andXiao-DanLi 1
1
PaulScherrerInstitute,5232VilligenPSI,Switzerland
2
LawrenceLivermoreNationalLaboratory,7000EastAvenue,Livermore,CA94550,USA
3
EnvironmentalMolecularSciencesLaboratory,PacificNorthwestNationalLaboratory,3335Innovation
Boulevard,Richland,WA99354,USA
4
DepartmentofPhysics,ArizonaStateUniversity,300E.UniversityDrive,Tempe,AZ85287,USA
5
CenterforFree-ElectronLaserScience,DESY,Notkestrasse85,22607Hamburg,Germany
6
LinacCoherentLightSource,2575SandHillRoad,MenloPark,CA94025,USA
7
PhysicsDepartment,BostonUniversity,590CommonwealthAvenue,Boston,MA02215,USA
Membraneproteinsarrangedastwo-dimensionalcrystalsinthelipidenviron-
mentprovideclose-to-physiologicalstructuralinformation,whichisessential
forunderstandingthemolecularmechanismsofproteinfunction.Previously,
X-raydiffractionfromindividualtwo-dimensionalcrystalsdidnotrepresent
asuitableinvestigationaltoolbecauseofradiationdamage.Therecentavail-
abilityofultrashortpulsesfromX-rayfree-electronlasers(XFELs)hasnow
providedameanstooutrunthedamage.Here,wereportonmeasurements
performedattheLinacCoherentLightSourceXFELonbacteriorhodopsin
two-dimensionalcrystalsmountedonasolidsupportandkeptatroomtemp-
erature.Bymergingdatafromaboutadozensinglecrystaldiffractionimages,
weunambiguouslyidentifiedthediffractionpeakstoaresolutionof7A
˚
,thus
improvingtheobservableresolutionwithrespecttothatachievablefroma
singlepatternalone.Thisindicatesthatalargerdatasetwillallowforreliable
quantificationofpeakintensities,andinturnacorrespondingincreaseinthe
resolution.ThepresentedresultspavethewayforfurtherXFELstudieson
two-dimensionalcrystals,whichmayincludepump–probeexperimentsat
subpicosecondtimeresolution.
1.Introduction
Knowledgeoftheatomicstructureofmembraneproteins,especiallythestructural
changestriggeredbyexternalstimuli[1,2],isofkeeninterest.Atwo-dimensional
proteincrystalisatwo-dimensionalperiodicarrayofthesamemotif,forminga
singlelayerofmolecules.Thisisafavourablearrangementformembraneproteins,
becausethelipidiccomponentbetweentheproteinscloselymimicsthenatural
environmentinthecellmembrane[3].Moreover,itcanbeassumedthatthestruc-
tureinthetwo-dimensionalcrystalenvironmentisalmostthesameasinthe
naturalstate,andthatpotentialstructuralchangesarenotasrestrictedasmay
happeninthree-dimensionalcrystals[4].
Sincethe1970s,electronmicroscopy(EM)hasexploitedthesignalenhance-
mentbroughtaboutbythetwo-dimensionalperiodicstructureandprovideda
fewdozenuniquestructureswithresolutionlessthan1nm[5–7].Thekeyof
thatsuccessisthat,unlikeindiffraction-typeexperiments,bothamplitude
& 2014TheAuthor(s)PublishedbytheRoyalSociety.Allrightsreserved.
on March 22, 2015 http://rstb.royalsocietypublishing.org/ Downloaded from
andphaseoftheBraggreflectionsareexperimentallyaccessi-
ble[8].Continuousmethodologicalimprovements[9–11]
thatinclude,inparticular,cryo-coolingofthesample[12]
haveledtostructuresatatomicresolution[13].However,a
realbreakthroughintermsofhigh-throughputhasalways
beenhamperedbyradiationdamage.
ThesituationisevenmorecriticalwithX-rays,forwhichthe
ratiobetweenusefuldiffractionanddamagingabsorptionevents
isfarworse[14].UntiltheadventofX-rayfree-electronlasers
(XFELs)[15,16],theexperimentswerelimitedtopowderdiffrac-
tionintransmissionfrompelletedbacteriorhodopsin(bR)
two-dimensionalcrystals[17],andtograzing-incidencedif-
fractionfrombRtwo-dimensionalcrystalsfloatingatthe
water–airinterface[18].WhileX-raydiffractionfromasingle
two-dimensionalcrystalwouldofferremarkableadvantages,
synchrotronsourcesarelimiting,inthatradiationdamage
destroysthesamplefasterthantheaccumulationofsufficient
signalintheBraggpeaks.AtXFELs,thesituationisradically
different:diffract-before-destroyexperimentsintheframework
ofserialfemtosecondcrystallography[19]onsubmicrometre-
sizedthree-dimensionalcrystalshaverecentlyprovedthatthe
femtosecondXFELpulsesoutrunthedamage,andthatthey
areofsufficientintensitytogeneratemeaningfulBraggpeaksig-
nals.Theaboveresultspromptedustoextendtheapplicationof
thediffract-before-destroyconcepttotwo-dimensionalprotein
crystalsunderclose-to-physiologicalconditionsofhydration
andtemperature,thusavoidingthedeleteriouseffectsof
cryogeniccooling.Furtherconsiderationsinsupportofthis
approachwererelatedtothestrongerpenetrationpowerof
X-rays,whichpossiblyallowstheacquisitionofdiffraction
dataatlargertiltanglesthanfeasiblewithcryo-EM,aswell
astotheperspectiveofexploitingthefinitesizeofthetwo-
dimensionalcrystalinthedirectionperpendiculartothecrystal
planefordirectphaseretrieval[20],notpossibleinstandard
three-dimensionalcrystallography.
Eventhoughthesingle-layerarrangementstronglyreduces
thescatteringpoweroftwo-dimensionalcrystals,thefeasibility
ofdiffract-before-destroyexperimentswasdemonstrated
duringaLinacCoherentLightSource(LCLS)beamtimeatthe
coherentdiffractionimaging(CXI)stationinMay2012,where
wecapturedsubnanometreBraggdiffractionfromindividual
two-dimensionalcrystals[21].Thesubmicrometre-sized
X-rayfocusavailableatCXIenhancedtheprobabilityof
simultaneouslyilluminatingonlyasmallnumberoftwo-dimen-
sionalcrystals.However,duringthisinitialbeamtime,thesingle-
crystalhitratewassolowthataveragingdataforacomplete
samplingofallBraggpeakswasimpossible.Thus,theattainable
resolutionremainedsignal-to-n oiselimited,whichaffectedthe
overallinterpretabilityoftheachievedresults.
Here,wedescribealargerdatasetacquiredinMay2013,
andshowthatakeypointistomergedatafromdifferentcrys-
talstoenhancethesignal-to-noiseratioofthemeasurable
Braggreflections.Althoughlimitedbythesmallnumberof
analysablediffractionimages,ourapproachledustoconclude
thatthepreparedsamplediffractstoatleast7A
˚
,andindi-
catesthatreliabledeterminationofthereflectionintensities
justrequiresmorediffractionpatterns.
2.Methods
(a)X-raydiffractionmeasurements
Themeasurementswereperformedatthe0.1 m mfocusenviron-
mentoftheCXIexperimentalstationoftheLCLSXFEL[22],at
anX-raywavelengthof8.8keV(1.4A
˚
)andwithnominalpulse
energiesofabout2mJ.
Thesamplewassupportedbyasolidsiliconwafer,shaped
withanextendedarrayof100 100 mm
2
thinwindowscon-
sistingofa5nmcarbonfilmwitha40nmpoly(methyl
methacrylate)layer.About2.2 m gbRtwo-dimensionalcrystals,
withatypicalsizeof0.5–1.0 m m,weresuspendedin15 m lof
0.5%w/vglucosesolution.Thiswaspaintedonthebackside
partofthewafer,sothatitcouldadheretothecarbonfaceof
thewindows.Afterdrying,theremaininglayerofglucose
actedasprotectionagainstdehydrationinthevacuumchamber.
TheXFELwasrunin‘burstmode’,andthewaferwasmoved
transverselytothebeam,sothateveryX-raypulsehitanew,
undamagedwindow.Inthisway,theeffectiverateof
diffractionimageacquisitionwasabout1Hz.
(b)Diffractionimageanalysis
Foratwo-dimensionalcrystal,theX-raycrosssectionismarkedly
differentfromzeroonlyaroundtheBraggrods.Thesearelinesper-
pendiculartothetwo-dimensionalcrystalplane.Theirprojection
ontothisplanecorrespondstothereciprocallatticeofthetwo-
dimensionalcrystallattice.Eachrodisthereforelabelledbyindices
( h , k )correspondingtothetworeciprocalunitcellvectors( a
*
, b
*
).
Peaksintwo-dimensionalcrystaldiffractionimagesoriginate
fromtheintersectionoftheEwaldspherewiththeBraggrods,
andthustheyarelabelledwiththesamepairofindices.Inthesim-
plestapproach,weconsideredonlytheimageswhichexhibiteda
cleardiffractionpatternfromasingletwo-dimensionalcrystal,
withthecrystalplanealmostperpendiculartotheincoming
beam.Suchimagesweretaggedbecauseofthecharacteristicdif-
fractionpeakpositions(‘peaklattice’).Inanindividualimage,
onlythemostprominentpeaksarevisible.Toevaluatethepotential
completenessofthemeasurablepeaks,weenhancedthesignal-to-
noiseratiobyaveragingtheintensitiesofsmallsectorsofdiffraction
images,withthesectorscentredatthepositionofequivalentpeaks.
a *
b *
(1, 7)
(–1, 8)
(7, –8) (8, –7)
(–8, 1)
(–7, –1)
(1, –8)
(–1, –7)
(8, –1)
(7, 1)
(–7, 8)
(–8,7)
Figure1. ExampleofadiffractionimagefromasinglebRtwo-dimensional
crystal.Thedashedringcorrespondsto10A
˚
resolution.Thecirclesmarkthe
positionsofexpecteddiffractionpeaksatlowerthan7A
˚
resolution.Thepre-
ciseorientationofthepeaklatticewasderivedfromthepositionsofthe
prominent,easilyidentifiablepeaksencircledinred.Thebasisvectors( a
*
,
b
*
)ofthetwo-dimensionalreciprocalspacelatticeareshownasgreen
arrows.Thesmallarrowsmarkthepositionofpeaksintheclasses((7,
1))(black),((1,7))(magenta),(( 2 7, 21))(orange)and(( 2 1, 27))
(cyan),eachclassconsistingofthreeequivalentpeaks.
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Thisallowedusinparticulartomergedatafromdifferentimages.
Todothat,however,weneeded(i)todeterminepreciselytheorien-
tationofeachpeaklattice,whichwaspossiblebasedonthe
positionsofthemostprominentpeaks,and(ii)toindexeachlattice,
whichrequiredtheintensitiesofthoseprominentpeaksasinput,
andwhichincludes,amongvariousaspects,theassessmentof
thefaceofthetwo-dimensionalcrystalexposedtothebeam.The
detailsoftheprotocolwillbepresentedinafuturepublication.
3.Resultsanddiscussion
Theconsidereddatasetconsistedof324diffractionimages,
acquiredwithinabout6minofbeamtime.Amongthese,
15exhibitedcleardiffractionpatternsoriginatingfroma
singlebRtwo-dimensionalcrystal,outofwhich11wereun-
ambiguouslyindexed.Figure1showsatypicalexample.The
peaksareindeedpositionedonaneasilyrecognizablesixfold
symmetricpattern,originatingfromthetworeciprocalunit
cellvectors( a
*
, b
*
)showningreen,whichinthecaseofthe
particularbRsampleusedareknowntohaveequallength
2
p
/62.45A
˚
andtoformanangleof60 8 [5,10].Theredcircles
markthepositionsofprominentpeaksthatwereusedtofind
theexactorientationofthepeaklatticewithrespecttothe
beamaxis,perpendiculartothefigure.
BecauseofFriedel’slaw,forperpendicularincidence,the
p
3
-symmetryofthetwo-dimensionalcrystalwouldresultina
sixfoldsymmetricdiffractionintensityforshortincoming
X-raywavelength.Thislimitisnotachievedwithinthe
actualexperimentalset-up.Owingtothecurvatureofthe
Ewaldsphere,the( h , k )and( 2 h , 2 k )peaksarenolonger
Friedelpairs,whichismanifestinthatthesymmetryofthe
observedpeakintensitiesisclearlyreducedfromsix-tothree-
fold.Crystallographicallyequivalentpeaksarerelatedonly
bya120 8 rotation,meaningthatpeaks( h , k ),( 2 h 2 k , h)
and( k , 2 h2 k )belongtothesameequivalenceclass,which
welabelby(( h , k )).Figure2displaysthepeaksobserved
forclasses((7,1)),(( 2 7, 21)),((1,7))and(( 2 1, 2 7)),allat
7.2A
˚
resolution,asmagnificationsofthediffractionimage
offigure1aroundtheconcernedpeakpositions.Thepeak
intensityvariationswithinaclassareinpartrecognizable
byeye,andcanbeexplainedasthejointeffectofPoissonstat-
isticswithsmalltiltsoftheindividualtwo-dimensional
crystals.Indeed,tiltsoflessthan25 8 canhardlybeassessed
fromthepeakpositionsalone[23].
The11indexableimageswerefurtherusedforenhancing
thepeaksignals.Figure3displaysimagesectorsumsforthe
equivalenceclassesoffigure2.Eachplotarisesfromtheinten-
sitysumofatleast20imagesectors.Inthisway,almostall
(1, 7)(7, –8)(–8, 1)
((1, 7))
(7, 1)(1, –8)(–8, 7)
(–7, –1)(–1, 8)(8, –7)
((7, 1))
((–7, –1))
(–1, –7)(–7, 8)(8, –1)
((–1, –7))
Figure2. Magnificationsofthediffractionimageoffigure1aroundpeakpositionsinclasses((7,1)),(( 2 7, 2 1)),((1,7))and(( 2 1, 2 7)).Thecolourcoding
givenbythearrowsontheleftisthesameasinfigure1.
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peaksuptoaresolutionofabout7A
˚
becameobservable.
Peaksintheclass((1,7))areclearlyvisibleinmostoftheindi-
vidualpatterns,andthereforealsoemergeasprominent
featuresintheimagesectorsum.Bycontrast,the(( 2 7, 2 1))
and(( 2 1, 2 7))reflectionsrepresenttypicalpeaksthatcan
hardlybeidentifiedinasinglediffractionimage(figure2),
yetappearasaclearpeaksinthesum.Finally,((7,1))exempli-
fiesthefewreflectionsbeingsoweakthattheydonotemerge
fromnoiseevenafterthesummingprocedure,althoughone
canguessthatapeak-likefeatureispresent.
Atthispoint,wenotethattwooverallindexingambiguities
areintrinsicandcanbefixedarbitrarily.Theycorrespondto
anarbitrarychoiceofthereferenceorientationofthetwo-
dimensionalcrystal.First,exchanging(( h , k ))and(( k , h))results
inreversingthefaceofthetwo-dimensionalcrystalexposedto
thepositiveout-of-planedirection.Wefixedthisfreedomin
ordertobeconsistentwiththeconventionsusedinreference
[24].Second,swapping(( h ,k ))with(( 2h , 2k ))corresponds
toa180 8rotation(equivalenttoa60 8 rotation)ofthecrystal.
Fromthedescribedresults,weconcludethattheprepared
two-dimensionalcrystalsdiffracttoatleast7A
˚
.Aproper,com-
pletemeasurementofthepeakintensitieswillbenefitfrom
mergingdatafromalargerdiffractionimageset.Wearework-
ingtowardsusingimagesarisingfromtheilluminationofafew
two-dimensionalcrystallinedomains,wherediffractionspots
stillremainwellseparatedandthereforeindexable;indeed,
about30%ofthe324imagesinthedatasetdiscussedinthis
paperbelongedtothiscategory.Fromthesamplepreparation
pointofview,theaimistoincreasethepercentageofindexable
images,andespeciallytoavoidpowder-likerings,bytuning
theproteinconcentrationinthesolutiontobepaintedonthe
wafer.WealsoplantooptimizetheshapeoftheX-rayfocus
bycuttingtailsinthetransversedirectionthatweaklyillumin-
ateneighbouringtwo-dimensionalcrystals,givingrisetoa
spotty,ring-likebackground.Finally,weexpecttoincrease
theimageacquisitionratebyreducingthetranslational
motionofthestagebetweentwosubsequentimageacqui-
sitions.Thismaybepossiblebyusingwaferswitheither
smallerandcloserwindows,orwithrectangularwindows
withanextendeddimension,tobescannedatthefullrepe-
titionrateoftheFEL.Insummary,webelievethatsimple
andstraightforwardmodificationswilldrasticallyimprove
theoutput,potentiallyprovidingvaluablescientificreturns
totheongoingeffortsontwo-dimensionalcrystalsnapshot
diffractionatXFELs.
4.Conclusion
Acquisitionofdiffractiondatafromsingletwo-dimensional
crystalsofproteinsmountedonasolidsupportwaspreviously
showntobefeasibleatXFELsindiffract-before-destroymode.
Here,wedemonstratedthatexploitingthecurrentlyavailable
X-raypulseenergiesofabout2mJandmergingdatafrom
multipleimagesmakesitpossibleunambiguouslytoidentify
diffractionpeakstoaresolutionofatleast7A
˚
.Multiple
samplingofthesamediffractionpeakenhancesthesignal-
to-noiseratio,whichleadstoenhancedresolutioncompared
withtheprocessingofsinglediffractionpatterns.Theabove
resultsreliedonalimitednumberofsingle-crystaldiffraction
images,whichleavesamplespaceforprogress.Theexperi-
mentswereperformedatroomtemperature,offeringan
obviousadvantagewithrespecttotechniquesthatneedcryo-
coolingtoreduceradiationdamagetothesample.Theset-up
canbeextendedtopump–probeexperiments,pavingthe
wayforstructuraldynamicsstudiesofmembraneproteins.
Acknowledgements. TheX-raymeasurementswerecarriedoutattheLinac
CoherentLightSource(LCLS)atSLACNationalAcceleratorLabora-
tory.LCLSisanOfficeofScienceUserFacilityoperatedfortheUS
DepartmentofEnergyOfficeofSciencebyStanfordUniversity.
Fundingstatement. C.J.T.,X.D.L.andG.F.X.S.acknowledgetheFemtose-
condandAttosecondScienceandTechnology(ETH-FAST)Initiative
inSwitzerland.Partoftheworkwasperformedundertheauspicesof
theUSDepartmentofEnergybyLawrenceLivermoreNational
Laboratoryundercontractno.DE-AC52-07NA27344andPacific
NorthwestNationalLaboratory(operatedbyBattelleMemorial
Institute)undercontractno.DE-AC05–76RL01830.Supportwaspro-
videdbytheUCOPLabFeeProgramme(awardno.118036),NIH
grantnumbers5RC1GM091755andGM095583,NSFawardMCB-
1021557andNSFSTCaward1231306,LLNLLab-DirectedResearch
andDevelopmentProject012-ERD-031andthePNNLChemicalIma-
gingInitiative.PartoftheworkwasalsosupportedbytheCenterfor
BiophotonicsScienceandTechnology,adesignatedNSFScience
andTechnologyCentermanagedbytheUniversityofCalifornia,
Davis,CAunderCooperativeagreementno.PHY0120999.
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[47]
. The X-ray nanocrystallography, so far, has been realized predominantly with the X-ray free-electron lasers and significant developments in sample delivery and data analysis have been made to support this development [48,49]. ...
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<here is a image 404bb1a1dd401abd-675bb4b4dc0366cb> Thomas Grant
<here is a image 1979bcf00817ad89-2c77a56148850b98> Matthew A Coleman
Nanolipoprotein particles (NLPs), also called “nanodiscs”, are discoidal particles with a patch of lipid bilayer corralled by apolipoproteins. NLPs have long been of interest due to both their utility as membrane-model systems into which membrane proteins can be inserted and solubilized and their physiological role in lipid and cholesterol transport via high-density lipoprotein (HDL) and low-density lipoprotein (LDL) maturation, which are important for human health. Serial femtosecond crystallography (SFX) at X-ray free electron lasers (XFELs) is a powerful approach for structural biology of membrane proteins, which are traditionally difficult to crystallize as large single crystals capable of producing high-quality diffraction suitable for structure determination. To facilitate understanding of the specific role of two apolipoprotein/lipid complexes, ApoA1 and ApoE4, in lipid binding and HDL/LDL particle maturation dynamics, and to develop new SFX methods involving NLP membrane protein encapsulation, we have prepared and crystallized homogeneous populations of ApoA1 and ApoE4 NLPs. Crystallization of empty NLPs yields semi-ordered objects that appear crystalline and give highly anisotropic and diffuse X-ray diffraction, similar to fiber diffraction. Several unit cell parameters were approximately determined for both NLPs from these measurements. Thus, low-background, sample conservative methods of delivery are critical. Here we implemented a fixed target sample delivery scheme utilizing the Roadrunner fast-scanning system and ultra-thin polymer/graphene support films, providing a low-volume, low-background approach to membrane protein SFX. This study represents initial steps in obtaining structural information for ApoA1 and ApoE4 NLPs and developing this system as a supporting scaffold for future structural studies of membrane proteins crystalized in a native lipid environment.
... Another challenge for structural studies is recording the dynamics of proteins, which would only be possible with classical X-ray techniques when using large crystals. All of these challenges are being addressed by diffraction experiments at X-ray free electron lasers (XFELs) [3]
[4]
[5][6]. These large-scale facilities can produce femtosecond X-ray pulses with much higher intensities compared to synchrotrons, enabling structure determination based on a diffract-before-destroy principle using a method commonly described as serial femtosecond crystallography (SFX). ...
Microfabricated silicon chip as lipid membrane sample holder for serial protein crystallography
Article
Full-text available
May 2019
M.Ł. Górzny
<here is a image 459944cb432e8945-7f9fd3ce17d59d42> Nadia Lengweiler -Opara
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Vitaliy A. Guzenko
Celestino Padeste
Rapid progress in protein crystallography techniques at X-ray free electron lasers (X-FELs) requires the development of new methods for sample delivery. Recording dynamic changes in protein structures is one of the aims. To assess protein dynamics, sample holders for crystallography need to become active devices, providing possibilities to induce in situ changes of the protein conformation during the experiments. We propose an integrated device for crystallographic studies on 2D crystals of membrane proteins. The conceptual device can support physiological conditions and provide a platform for electrophysiological measurements, as well as for electrical stimulation during the diffraction experiments at X-FELs. This allows for triggering conformational changes in membrane proteins, ultimately permitting to take series of crystallographic snapshots of the dynamic behavior of proteins. The device integrates a microfabricated silicon chip between two microfluidic transport layers. We demonstrate the fabrication of the device, describe its key components and show the method of sample loading and lipid bilayer formation with the use of the microfluidic delivery system. Electrochemical impedance spectroscopy (EIS) has been used to characterize the properties of lipid bilayers formed in the microfabricated silicon nitride support. Minimizing the sample consumption, mimicking physiological conditions during crystallographic data collection and an interface for electrochemical characterization and addressing protein 2D crystals are the key properties of the proposed device.
... The fundamental ingredient is therefore the coherence of the X-rays source, only available at third generation synchrotron facilities [192][193][194][195][196][197], and fourth generation synchrotron facilities [212][213][214] or from free electron lasers (FEL) [198][199][200][201][202][203]215,216]. In cases when dose related problems can be overcame [217], interesting crystallographic results have been achieved so far with X-ray coherent beam to solve the structure solution of protein nanocrystals
[218]
[219][220]. ...
Watching nanomaterials with X-Ray eyes: probing different length scales by combining scattering with spectroscopy
Everybody dreams to have X-ray eyes and discover the most invisible secrets of the world around us. X-rays can probe matter (depth resolved) down to atomic resolution, if relying on diffraction-based techniques. An X-ray diffraction pattern may contain information over many length scales (atomic structure, microstructure, mesostructure). This peculiarity justifies the well-recognized impact of several X-ray diffraction-based techniques to diverse fields of research. On the other hand, X-ray spectroscopies (both in absorption and in emission) provide insights on the electronic structure and, exploiting element selectivity and local environment, can complement or even replace scattering techniques for diluted systems and amorphous materials. Herein, we provide a theoretical foundation which spans from very basic concepts, through well-known techniques, with applications to nanomaterials research. An increasing level of material complexity is explored: size and shape analysis of nanoparticles dispersed in solution or single nanostructures localized onto surfaces; local morphology/strain analysis of nanostructured surfaces; average defects analysis of stacking faulted nanocrystals; regular 2D and 3D lattices of self-assembled nanocrystals; clusters of nanocrystals without any nanoscale lattice order, standing alone as isolated objects or embedded in tenths-of-µm-thick polymers (here coherent and focused X-rays were mandatory to explore the spatial inhomogeneity and lattice (in)coherence of the materials).
... GPCRs are the family of membrane proteins, regulating most cellular responses to hormones and neurotransmitters. Based on their sequence and structural similarity, GPCRs are generally classified into five families, including rhodopsin, secretin, glutamate, adhesion, and Frizzled/Taste2
[30]
. These proteins have strongly hydrophobic transmembrane helix structures. ...
Oncogenic Signaling Pathways in Cancer: An Overview
Cancer is a leading cause of death worldwide. It is theorized that underlying genetic and epigenetic changes enable cells to proliferate out of control by escaping regulatory mechanisms. The progression of cancer is associated with increased cell proliferation, metabolic modifications, resistance to apoptosis, genetic instability, induction of angiogenesis and augmented migratory capability. Recent developments in DNA and RNA analysis have made it possible to study these genetic changes systematically. These advances have enabled us to possess a deeper knowledge of the signaling pathways and involved processes. In-depth studies of the pathways involved in carcinogenesis have led to the identification of pathways that may be targeted for therapeutic purposes. In this review, we provide an overview of the relevant mechanisms and pathways involved in the development and progression of cancer.
... Moreover, the material or design should minimize background scattering, generated when X-rays are transmitted through the sample holder 29,31 . Currently, various sample holders, such as silicon nitride 11,
18,
24 , silicon chips 26 , microfluidic chips 21 , and microgrids 17,19 are being used for the development of serial crystallography and are successfully implemented in FT-SFX. However, the processes of precise chip fabrication for silicon nitride, silicon chip, and microfluidic chip are challenging and time-consuming 15,21 . ...
Nylon mesh-based sample holder for fixed-target serial femtosecond crystallography
Fixed-target serial femtosecond crystallography (FT-SFX) was an important advance in crystallography by dramatically reducing sample consumption, while maintaining the benefits of SFX for obtaining crystal structures at room temperature without radiation damage. Despite a number of advantages, preparation of a sample holder for the sample delivery in FT-SFX with the use of many crystals in a single mount at ambient temperature is challenging as it can be complicated and costly, and thus, development of an efficient sample holder is essential. In this study, we introduced a nylon mesh-based sample holder enclosed by a polyimide film. This sample holder can be rapidly manufactured using a commercially available nylon mesh with pores of a desired size at a low cost without challenging technology. Furthermore, this simple device is highly efficient in data acquisition. We performed FT-SFX using a nylon mesh-based sample holder and collected over 130,000 images on a single sample holder using a 30 Hz X-ray pulse for 1.2 h. We determined the crystal structures of lysozyme and glucose isomerase using the nylon mesh at 1.65 and 1.75 Å, respectively. The nylon mesh exposed to X-rays produced very low levels of background scattering at 3.75 and 4.30 Å, which are negligible for data analysis. Our method provides a simple and rapid but highly efficient way to deliver samples for FT-SFX.
A fixed-target platform for serial femtosecond crystallography in a hydrated environment
For serial femtosecond crystallography at X-ray free-electron lasers, which entails collection of single-pulse diffraction patterns from a constantly refreshed supply of microcrystalline sample, delivery of the sample into the X-ray beam path while maintaining low background remains a technical challenge for some experiments, especially where this methodology is applied to relatively low-ordered samples or those difficult to purify and crystallize in large quantities. This work demonstrates a scheme to encapsulate biological samples using polymer thin films and graphene to maintain sample hydration in vacuum conditions. The encapsulated sample is delivered into the X-ray beam on fixed targets for rapid scanning using the Roadrunner fixed-target system towards a long-term goal of low-background measurements on weakly diffracting samples. As a proof of principle, we used microcrystals of the 24 kDa rapid encystment protein (REP24) to provide a benchmark for polymer/graphene sandwich performance. The REP24 microcrystal unit cell obtained from our sandwiched in-vacuum sample was consistent with previously established unit-cell parameters and with those measured by us without encapsulation in humidified helium, indicating that the platform is robust against evaporative losses. While significant scattering from water was observed because of the sample-deposition method, the polymer/graphene sandwich itself was shown to contribute minimally to background scattering.
Strategies for sample delivery for femtosecond crystallography
Highly efficient data-collection methods are required for successful macromolecular crystallography (MX) experiments at X-ray free-electron lasers (XFELs). XFEL beamtime is scarce, and the high peak brightness of each XFEL pulse destroys the exposed crystal volume. It is therefore necessary to combine diffraction images from a large number of crystals (hundreds to hundreds of thousands) to obtain a final data set, bringing about sample-refreshment challenges that have previously been unknown to the MX synchrotron community. In view of this experimental complexity, a number of sample delivery methods have emerged, each with specific requirements, drawbacks and advantages. To provide useful selection criteria for future experiments, this review summarizes the currently available sample delivery methods, emphasising the basic principles and the specific sample requirements. Two main approaches to sample delivery are first covered: (i) injector methods with liquid or viscous media and (ii) fixed-target methods using large crystals or using microcrystals inside multi-crystal holders or chips. Additionally, hybrid methods such as acoustic droplet ejection and crystal extraction are covered, which combine the advantages of both fixed-target and injector approaches.
X-Ray Free-Electron Lasers for the Structure and Dynamics of Macromolecules
X-ray free-electron lasers provide femtosecond-duration pulses of hard X-rays with a peak brightness approximately one billion times greater than is available at synchrotron radiation facilities. One motivation for the development of such X-ray sources was the proposal to obtain structures of macromolecules, macromolecular complexes, and virus particles, without the need for crystallization, through diffraction measurements of single noncrystalline objects. Initial explorations of this idea and of outrunning radiation damage with femtosecond pulses led to the development of serial crystallography and the ability to obtain high-resolution structures of small crystals without the need for cryogenic cooling. This technique allows the understanding of conformational dynamics and enzymatics and the resolution of intermediate states in reactions over timescales of 100 fs to minutes. The promise of more photons per atom recorded in a diffraction pattern than electrons per atom contributing to an electron micrograph may enable diffraction measurements of single molecules, although challenges remain. Expected final online publication date for the Annual Review of Biochemistry Volume 88 is June 20, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Femtosecond X-ray diffraction from two-dimensional protein crystals
X-ray diffraction patterns from two-dimensional (2-D) protein crystals obtained using femtosecond X-ray pulses from an X-ray free-electron laser (XFEL) are presented. To date, it has not been possible to acquire transmission X-ray diffraction patterns from individual 2-D protein crystals due to radiation damage. However, the intense and ultrafast pulses generated by an XFEL permit a new method of collecting diffraction data before the sample is destroyed. Utilizing a diffract-before-destroy approach at the Linac Coherent Light Source, Bragg diffraction was acquired to better than 8.5 Å resolution for two different 2-D protein crystal samples each less than 10 nm thick and maintained at room temperature. These proof-of-principle results show promise for structural analysis of both soluble and membrane proteins arranged as 2-D crystals without requiring cryogenic conditions or the formation of three-dimensional crystals.
First lasing and operation of an Ångstrom-wavelength free-electron laser
The recently commissioned Linac Coherent Light Source is an X-ray free-electron laser at the SLAC National Accelerator Laboratory. It produces coherent soft and hard X-rays with peak brightness nearly ten orders of magnitude beyond conventional synchrotron sources and a range of pulse durations from 500 to <10 fs (10−15 s). With these beam characteristics this light source is capable of imaging the structure and dynamics of matter at atomic size and timescales. The facility is now operating at X-ray wavelengths from 22 to 1.2 Å and is presently delivering this high-brilliance beam to a growing array of scientific researchers. We describe the operation and performance of this new ‘fourth-generation light source’.
Analysis of Conformational Variation in Macromolecular Structural Models
| https://www.researchgate.net/publication/262979483_7_A_resolution_in_protein_twodimensional-crystal_X-ray_diffraction_at_Linac_Coherent_Light_Source |
Facts about "Casablanca" : Classic Movie Hub (CMH)
Browse Fun Facts and Trivia about at Classic Movie Hub (CMH).
<here is a image bf78f8e36794dad7-ec58925fe0d64af1>
Casablanca
"As Time Goes By" was written by lifelong bachelorHerman Hupfeldand debuted in 1931's Broadway show "Everybody's Welcome", sung byFrances Williams, It had been a personal favorite of playwright and high school teacherMurray Burnettwho, seven years later, visited Vienna just after the Nazis had entered. Later, after visiting a café in south France where a black pianist had entertained a mixed crowd of Nazis, French and refugees, Burnett was inspired to write the melodrama "Everybody Comes to Rick's", which was optioned for production byMartin GabelandCarly Wharton, and later, Warners. After the film's release, "As Time Goes By" stayed on radio's "Hit Parade" for 21 weeks. However, because of the coincidental musicians' union recording ban, the 1931Rudy Valleeversion became the smash hit. (It contains the rarely-sung introductory verse, not heard in the film.)Max Steiner, in a 1943 interview, admitted that the song "must have had something to attract so much attention".
"Here's looking at you, kid" was improvised by
Humphrey Bogart
in the Parisian scenes and worked so well that it was used later on again in the film. He originally used the same line in
Midnight
. It is also rumored that during breaks,
Ingrid Bergman
would play poker with other cast members. Since she was still learning English, Bogart would occasionally watch the game, and he added "Here's looking at you" to her poker repertoire.
"Rick's Café Américain" was modeled after Hotel El Minzah in Tangiers.
Humphrey Bogarthad to wear platform shoes to play alongsideIngrid Bergman.
Humphrey Bogart
,
Ingrid Bergman
and
Paul Henreid
later reprised their roles for a radio performance of on the CBS radio program "The Screen Guild Players", a war benefit show on April 26, 1943.
Humphrey Bogart
's wife
Mayo Methot
continually accused him of having an affair with
Ingrid Bergman
, often confronting him in his dressing room before a shot. Bogart would come onto the set in a rage. In fact, despite the undeniable on-screen chemistry between Bogart and Bergman, they hardly spoke, and the only time they bonded was when the two had lunch with
Geraldine Fitzgerald
. According to Fitzgerald, "the whole subject at lunch was how they could get out of that movie. They thought the dialogue was ridiculous and the situations were unbelievable... I knew Bogart very well, and I think he wanted to join forces with Bergman, to make sure they both said the same things." For whatever reasons, Bogart and Bergman rarely spoke after that.
S.Z. Sakall, who plays the maitre d' at Rick's Cafe, actually has more screen time thanPeter LorreorSydney Greenstreet.
Madeleine Lebeau
, who plays Yvonne, and
Marcel Dalio
, who plays croupier Emil, were husband and wife at the time of filming. They had not long before escaped the Nazis by fleeing their native France.
Dooley Wilson
(Sam) was a professional drummer who faked playing the piano. As the music was recorded at the same time as the film, the piano playing was actually a recording of a performance by
Elliot Carpenter
who was playing behind a curtain but who was positioned such that Dooley could watch, and copy, his hand movements.
Dooley Wilsonwas borrowed from Paramount at $500 a week.
Dooley Wilsonwas, in fact, the only member of the cast to have ever actually visited the city of Casablanca.
Joy Page
, who played the young Bulgarian wife, was the stepdaughter of studio head
Jack L. Warner
. She,
Humphrey Bogart
and
Dooley Wilson
were the only American-born people in the credited cast. This film was her debut.
Hal B. Wallisdidn't wantHumphrey Bogartwearing a hat too often in the film, as he thought it made Bogart look like a gangster.
Hal B. Wallis's first choice for director wasWilliam Wyler.
Sydney Greenstreet
wanted to wear something more ethnic to show that his character had assimilated into the Moroccan lifestyle. This idea was nixed by producer
Hal B. Wallis
who insisted that he wear his now-iconic white suit.
Ingrid BergmanandPaul Henreidmake their first appearance 24 minutes into the film.
Ingrid Bergman
considered her left side as her better side, and to the extent possible that was the side photographed throughout the film, so she is almost always on the right side of the screen looking towards the left regardless of who is in the shot with her. However, there are several shots where she is to the left and
Humphrey Bogart
is on the right, including the flashbacks to the street scene in Paris (0:41:50) and the scene at the window (0:43:40). There are also several scenes where Bergman is centered between
Paul Henreid
and Bogart, suggesting the triangle nature of their relationship; in these shots Henreid is usually to the left and Bogart is usually on the right, including the scene where she and Henreid enter the café at just before the famous "Battle of the Anthems" (1:07:40); the scene where Captain Renault arrests Victor Laszlo (1:34:00); and at the end of the final airport scene (1:39:00).
Ingrid Bergman's contract was owned by producerDavid O. Selznick, and producerHal B. Wallissent the film's writers,Philip G. EpsteinandJulius J. Epstein, to persuade Selznick to loan her to Warner Bros. for the picture. After 20 minutes of describing the plot to Selznick, Julius gave up and said, "Oh, what the hell! It's a lot of shit likeAlgiers!" Selznick nodded and agreed to the loan.
Ingrid Bergman
's line "Victor Laszlo is my husband, and was, even when I knew you in Paris" was almost cut from the film because during that time it was deemed inappropriate for a film to depict or suggest a woman romancing with another man if she were already married. However, it was pointed out that later in the film she explains that she had thought Laszlo was dead at the time, and the censors allowed the line to stay in.
Howard Hawks
had said in interviews that he was supposed to direct
Casablanca
and
Michael Curtiz
was supposed to direct
Sergeant York
. The directors had lunch together, where Hawks said he didn't know how to make this "musical comedy", while Curtiz didn't know anything about "those hill people." They switched projects. Hawks struggled on how to direct the scenes that involved singing, namely the "La Marseillaise" scene. It is ironic to note that most of his other films involved at least one singing scene.
| https://www.classicmoviehub.com/facts-and-trivia/film/casablanca-1942/?lv=true%2Fpage%2F6%2F%2Fpage%2F3%2F%2Fpage%2F4%2F%2Fpage%2F4%2F%2Fpage%2F2%2F%2Fpage%2F5%2F%2Fpage%2F4%2F |
Human Gene CYP1B1 (ENST00000494864.1) from GENCODE V43
Human Gene CYP1B1 (ENST00000494864.1) from GENCODE V43 Description: cytochrome P450 family 1 subfamily B member 1 (from HGNC CYP1B1) RefSeq Summary (NM_000104): This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The enzyme encoded by this gene localizes to the endoplasmic reticulum and metabolizes procarcinogens such as polycyclic aromatic hydrocarbons and 17beta-estradiol. Mutations in this gene have been associated with primary congenital glaucoma; therefore it is thought that the enzyme also metabolizes a signaling molecule involved in eye development, possibly a steroid. [provided by RefSeq, Jul 2008]. ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000610745.5/ ENSP00000478561.1 RefSeq Select criteria :: based on single protein-coding transcript regulatory uORF :: PMID: 19908239 ##RefSeq-Attributes-END## Gencode Transcript: ENST00000494864.1 Gencode Gene: ENSG00000138061.12 Transcript (Including UTRs) Position: hg38 chr2:38,070,066-38,109,902 Size: 39,837 Total Exon Count: 2 Strand: - Coding Region Position: hg38 chr2:38,070,722-38,071,240 Size: 519 Coding Exon Count: 1 Page Index Sequence and Links Primers MalaCards CTD Microarray Expression RNA Structure Other Species mRNA Descriptions Pathways Other Names GeneReviews Methods Data last updated at UCSC: 2023-02-17 13:02:02
Sequence and Links to Tools and Databases Genomic Sequence (chr2:38,070,066-38,109,902) mRNA (may differ from genome) Protein (172 aa) Gene Sorter Genome Browser Other Species FASTA VisiGene Gene interactions Table Schema AlphaFold BioGPS Ensembl ExonPrimer Gencode GeneCards HGNC Lynx MGI PubMed UniProtKB Wikipedia
Primer design for this transcript Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.Click here to load the transcript sequence and exon structure into Primer3Plus Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.Click here to open Exonprimer with this transcript To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3
MalaCards Disease Associations MalaCards Gene Search: CYP1B1 Diseases sorted by gene-association score: glaucoma 3a, primary open angle, congenital, juvenile, or adult onset * (1578), anterior segment dysgenesis 6, multiple subtypes * (900), peters-plus syndrome * (505), anterior segment dysgenesis 5, multiple subtypes * (283), glaucoma 1a, primary open angle * (212), glaucoma 1, open angle, e * (188), cyp1b1-related primary congenital glaucoma * (100), juvenile glaucoma * (42), primary congenital glaucoma (36), open-angle glaucoma (22), axenfeld-rieger syndrome (19), corneal edema (16), adamantinoma of long bones (13), aniridia (12), early-onset glaucoma (12), hydrophthalmos (12), primary angle-closure glaucoma (11), gastrointestinal adenoma (11), breast disease (9), acrofrontofacionasal dysostosis (8), excessive tearing (7), weber syndrome (7), mycetoma (7), iris hypoplasia (6), eye disease (5), pulmonary immaturity (5), endometrial cancer (3), breast cancer (2) * = Manually curated disease association
Comparative Toxicogenomics Database (CTD) The following chemicals interact with this gene C023035 3,4,5,3',4'-pentachlorobiphenyl D013749 Tetrachlorodibenzodioxin D001564 Benzo(a)pyrene D008748 Methylcholanthrene C042881 1-ethynylpyrene C014024 2,4,5,2',4',5'-hexachlorobiphenyl D015127 9,10-Dimethyl-1,2-benzanthracene D004958 Estradiol C011512 alpha-naphthoflavone D019324 beta-Naphthoflavone more ... click here to view the complete list
Microarray Expression Data Press "+" in the title bar above to open this section.
mRNA Secondary Structure of 3' and 5' UTRs Region Fold Energy Bases Energy/Base Display As 5' UTR -81.70 304 -0.269 Picture PostScript Text 3' UTR -171.30 656 -0.261 Picture PostScript Text The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Orthologous Genes in Other Species Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene. Mouse Rat Zebrafish D. melanogaster C. elegans S. cerevisiae Genome Browser Genome Browser No ortholog No ortholog No ortholog No ortholog Gene Details Gene Sorter MGI RGD Protein Sequence Protein Sequence Alignment Alignment
Descriptions from all associated GenBank mRNAs LF210932 - JP 2014500723-A/18435: Polycomb-Associated Non-Coding RNAs. MA446509 - JP 2018138019-A/18435: Polycomb-Associated Non-Coding RNAs. LP895403 - Sequence 267 from Patent EP3253886. U03688 - Human dioxin-inducible cytochrome P450 (CYP1B1) mRNA, complete cds. FW340004 - Screening. BC012049 - Homo sapiens cytochrome P450, family 1, subfamily B, polypeptide 1, mRNA (cDNA clone MGC:19842 IMAGE:4662252), complete cds. JD047292 - Sequence 28316 from Patent EP1572962. JD522010 - Sequence 503034 from Patent EP1572962. JD093590 - Sequence 74614 from Patent EP1572962. JD530143 - Sequence 511167 from Patent EP1572962. JD501124 - Sequence 482148 from Patent EP1572962. JD089032 - Sequence 70056 from Patent EP1572962. AK297039 - Homo sapiens cDNA FLJ51600 complete cds, highly similar to Cytochrome P450 1B1 (EC 1.14.14.1). LF342215 - JP 2014500723-A/149718: Polycomb-Associated Non-Coding RNAs. MA577792 - JP 2018138019-A/149718: Polycomb-Associated Non-Coding RNAs. JD225848 - Sequence 206872 from Patent EP1572962. JD082418 - Sequence 63442 from Patent EP1572962. AK303862 - Homo sapiens cDNA FLJ51599 complete cds, highly similar to Cytochrome P450 1B1 (EC 1.14.14.1). AK312686 - Homo sapiens cDNA, FLJ93081, Homo sapiens cytochrome P450, family 1, subfamily B, polypeptide 1(CYP1B1), mRNA. BT019979 - Homo sapiens cytochrome P450, family 1, subfamily B, polypeptide 1 mRNA, complete cds. BT020001 - Homo sapiens cytochrome P450, family 1, subfamily B, polypeptide 1 mRNA, complete cds. JF432813 - Synthetic construct Homo sapiens clone IMAGE:100074131 cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) gene, encodes complete protein. KJ904445 - Synthetic construct Homo sapiens clone ccsbBroadEn_13839 CYP1B1 gene, encodes complete protein. LF342216 - JP 2014500723-A/149719: Polycomb-Associated Non-Coding RNAs. MA577793 - JP 2018138019-A/149719: Polycomb-Associated Non-Coding RNAs. LF342217 - JP 2014500723-A/149720: Polycomb-Associated Non-Coding RNAs. MA577794 - JP 2018138019-A/149720: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways KEGG - Kyoto Encyclopedia of Genes and Genomes hsa00140 - Steroid hormone biosynthesis hsa00380 - Tryptophan metabolism hsa00980 - Metabolism of xenobiotics by cytochrome P450
Other Names for This Gene Alternate Gene Symbols: A0A087WW26, BC012049, uc061ifw.1 UCSC ID: ENST00000494864.1 RefSeq Accession: NM_000104
| https://genome.ucsc.edu/cgi-bin/hgGene?hgg_chrom=chr2&hgg_gene=ENST00000494864.1 |
Nature (PR) | Ciencia Puerto Rico
Nature (PR)
A list of scientific jobs from Naturejobs.com
URL:
http://www.nature.com/naturejobs/science/jobs?escape=false&location=PR%2C+US&order_by=created_on&order_direction=desc&precision=2
Doctoral student in PET Radiochemistry
The Department of Clinical Neuroscience (CNS) conducts research and education in the field of neuroscience from the molecular level to the society level. The clinical research and education is conducted in collaboration with other research groups from the Karolinska Institutet, with other universities as well as the Stockholm County Council.Please visit our website for more information: ki.se/en/cns
A doctoral position is an available doctoral education project to which a PhD student is to …
Associate Professor/Full Professor in Computational materials science (tenure track)
Lappeenranta University of Technology, LUT. LUT’s Trailblazer strategy is searching for answers to four key questions: Are we going to burn up everything? Is humanity condemned to suffer from the water it has polluted? Will waste be the grave of our future? Will we let Europe degenerate to the world’s back yard? No. We will lead the way with a trailblazer spirit. We are the best young university in the Nordic countries (Times Higher Education 100 Under 50 Ranking, 2015). We are compact by size…
Independent Group Leaders
The Center of Regenerative Medicine in Barcelona (CMR[B]) is an internationally recognized center for research in pluripotent stem cell biology and applications. The CMR[B] was co-founded in 2004 by the Catalan Government's Ministry of Health and the Carlos III Healthcare institute (ISC IIII) of the Spanish Ministry of Science and Innovation. The CMR[B] mission is to conduct fundamental research of excellence for advancing the clinical translation of strategies of regenerative medicine. For this…
Head of Production
BioMed Central is the leading open access publisher of STM (Science, Technology and Medicine) research. Since it was founded in 2000, BioMed Central has successfully pioneered the open access publishing model and brought open access to the mainstream. With offices in London, North America and Asia, the company employs over 290 people across a range of operations including editorial, production, IT and business. BioMed Central is a vibrant and innovative company. It operates in a fast-paced and …
Lecturer in Neurobiology of Paediatric Pain
UCL Institute of Child Health – IIIP
Lecturer in Neurobiology of Paediatric Pain
The appointment will be full time on UCL Grade 8. The salary range will be £41,844 – £43,030 per annum depending on skills and experience, inclusive of London Allowance.
The Paediatric Pain Research Group at UCL Institute of Child Health and Great Ormond Street Hospital conducts laboratory and clinical research investigating the mechanisms, assessment, and management of pain throughout early development an…
CIMED announces Junior and Senior Investigator grants within medical research
Research at the Center for Innovative Medicine (CIMED) focuses on basic and medical research aiming towards greater understanding and improved treatments of important healthproblems and diseases. Interplay between the Stockholm County Council, Karolinska Institutet and industry ensures a stimulating research environment for modern medical research and drug development.
*Applications are now welcome for CIMED 5-year (2017-21) Junior and Senior Investigator grants in basic, translational or …
Senior Scientist, Immunology Research
Senior Scientist, Immunology Research
Bavarian Nordic is a biopharmaceutical company focused on the development and manufacturing of cancer immunotherapies and vaccines for infectious diseases.With a focus on the immunobiology of viral vectors and vaccines, the Immunology Research department strives for bridging basic and applied science. In order to strengthen the department’s efforts in moving forward novel ideas for prophylactic and therapeutic vaccines in the fields of cancer and infe…
Research Assistant in Digital Literacy and PBL (Level 1) - Specific Purpose Contract
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Crucial, Up-to-date Data for ASSISI HEALTHCARE OF CLARE OAKS, Review & Ratings
The most comprehensive and up to date information on ASSISI HEALTHCARE OF CLARE OAKS. Find general information about ASSISI HEALTHCARE OF CLARE OAKS along with detailed ratings, trend analysis, deficiencies, and ownership. Updated Monthly.
ASSISI HEALTHCARE OF CLARE OAKS: Data Analysis and Ratings
CMS Five Star Rating(5 out of 5):
829 CARILLON DRIVE BARTLETT, IL 60103
630-483-3905
Data date:April 01, 2021
This is not the most recent data for ASSISI HEALTHCARE OF CLARE OAKS. For the most recent information,click here.
The Most Important Data about ASSISI HEALTHCARE OF CLARE OAKS
We've looked at a lot of nursing homes, this is what we think you need to see first and if you don't want to spend a lot of time. (It's the tl;dr section.)
There is no indication of abuse occuring at ASSISI HEALTHCARE OF CLARE OAKS. (CMS flags facilities where abuse has either happened or is very likely.)
CMS 5-Star Overall Rating:
(5 out of 5):(The national average overall star rating is 3 stars.)
Current Trend:Worsening
Total Nursing Hours Spent Per Resident Per Day: 5.29(The national average is 3.74 )
Best Nursing Homes in IL
According to our analysis, ASSISI HEALTHCARE OF CLARE OAKS is ranked #31 out of 211 skilled nursing homes within a 25 mile radius. See detailed information from recent inspection reports, nursing hours analysis, surverys, and information on owners and operators.Click here to view the ranked list of nursing homes near ASSISI HEALTHCARE OF CLARE OAKS.
What is this page all about?
Below is everything shred of information that we can find about ASSISI HEALTHCARE OF CLARE OAKS, along with our best effort to make sense of the data. Our purpose here is to help you to make good decisions when picking a nursing home and to keep you informed once you have chosen a home. We know from personal experience that choosing a nursing home is not something you do once and then you forget about it. In fact, it gets worse. Once you select a nursing home and get through the initial steps of figuring out how to pay for it, then the real worries start. Are they taking good care of me or my loved one? This is the question that will keep you up at night: Can I really trust these people? We wish we could answer this question, we can't. What he can do is churn through the tons of data and try and help you to make sense of it. We hope it helps.
General Data Card
These are the basic data points for the facility.
Data date:April 01, 2021
Address:829 CARILLON DRIVE, BARTLETT, IL 60103
Phone:630-483-3905
Ranking:ASSISI HEALTHCARE OF CLARE OAKS is ranked #6 out of 39 facilities within a 10 mile radius and #31 out of 211 facilities within a 25 mile radius.
Medicare Provider Number:146125
Participating in Medicare Since:July 10, 2008
No. of Certified Beds:60
No. of Residents:53
Occupancy:88.33 % (as of
06/18/2023 )
Amount fined in recent period:$975.00
Complaints filed:0
Ratings History for ASSISI HEALTHCARE OF CLARE OAKS
Review of ASSISI HEALTHCARE OF CLARE OAKS Ratings and Inspection Scores
CMS regularly inspects every skilled nursing facility. (The timing is supposed to be annually, but since the beginning of the Covid pandemic, these inspections have not occured as frequently.) The results of the multi-day inspection is reduced to a series of scores which are then translated into the star ratings. The health inspection scores are an absolute value, so you can compare one facility's score directly to another. The Overall Star rating is based on the facility's performance as compared to other facilities in the same state, so you cannot easily compare one facility's Overall star rating to a facility in another state.
Ratings
<table><tbody><tr><td> Overall Rating</td><td> 5:</td></tr><tr><td> Health Inspection Rating</td><td> 4:</td></tr><tr><td> Quality Rating</td><td> 3:</td></tr><tr><td> Staffing Rating</td><td> 5:</td></tr></tbody></table>
Inspection Scores
<table><tbody><tr><td> Cycle 1 Score (as of October 01, 2020)</td><td> 24</td></tr><tr><td> Cycle 2 Score (as of March 06, 2019)</td><td> 12</td></tr><tr><td> Cycle 3 Score (as of April 19, 2018)</td><td> 20</td></tr><tr><td> Weighted All Cycles Score</td><td> 19</td></tr></tbody></table>
It has been 6 months since the most recent inspection.
What Goes Into the Nursing Home's 5-Star Rating
CMS has put a lot of effort into creating its very elaborate 5-Star Quality Rating System specifically to provide a quick way for residents and family members to easily understand how well a nursing home is performing and to make comparing nursing homes easier. The rating system allows people to easily compare facilities across numerous dimensions with the express purpose of identifying the best and best performing nursing homes. The rating system was initially developed in 2008 and the methodologies are regularly reviewed and updated.
The rating system has five separate ratings including:
Overall rating
Health Inspection rating
Staff rating
RN Staffing rating
Quality Measures rating
Nursing homes are rated from 1-star to 5-stars with 1-star being the best rating and 5-star being the best rating. For the Health Inspection Rating the nursing homes in each state are ranked based on their weighted three year inspection score. The top 10 percent of nursing homes (those with the lowest scores) are awarded a 5-star rating; the bottom 20 percent (those with the highest scores) are awarded a 1-star rating. In between 1-star and 5-star, the remaining homes are divided equally into three tranches which correspond with the stars 2 to 4. The staff ratings and quality measure ratings follow a similar process but the divisions are based on a national ranking. The division between star ratings is called the “cut-rate”. Cut-rates are redefined periodically and are published by CMS.See the latest cut rates on this table.
Calculating the Overall Star Rating is done differently. According to CMS, the reason for adopting a different system is to give the Health Inspection Rating higher weight in the Overall Rating. So, since there are FIVE ratings and FIVE stars for each rating, there must also be a FIVE step process to calculate the Overall Rating (so symetrical!) :
Begin with the Health Inspection Rating
Add one star to the Health Inspection Rating if the Staffing Rating is at least four-stars and is higher than the Health Inspection Rating. (We will call this the "Adjusted Rating".)
Subtract one star from the Health Inspection Rating if the Staffing Rating is one-star.
Add a star to the Adjusted Rating if the Quality Measure Rating is 5-stars.
Subtract one star from the Adjusted Rating if the Quality Measure Rating is 1-star.
Throughout the calculation of the Overall Rating, the rating cannot exceed 5-stars. The Overall Rating is capped at 2-stars if the Health Inspection rating is 1-star. No Overall Rating is awarded if the nursing home does not have a Health Inspection Rating (This effectively means that a nursing home is not rated until the home has been operating for more than two years.)
Changes in a nursing homes star rating can be due to the results of a new health inspection report, the processing of new complaints, the aging of older complaints, a new inspection control survey, a revisit, or the resolution of disputes that change the scope and or severity of deficiencies.
Most Recent Nursing Home Inspections
CMS is required to inspect each senior nursing facility at least annually. These inspections take several days. Additional follow-up inspections as conducted as needed or for certain purposes. Inspections stopped for more than seven months in 2020 due to the Covid pandemic. That stoppage has caused all inspections to be delayed as the inspectors continue to deal with a backlog. The table below shows the latest inspections for ASSISI HEALTHCARE OF CLARE OAKS including health, fire, and inspection control inspections:
Inspection Type Inspection Date
Fire Safety Standard October 09, 2020
Fire Safety Standard March 06, 2019
Fire Safety Standard April 18, 2018
Health Standard October 01, 2020
Health Standard March 06, 2019
Health Standard April 19, 2018
Infection Control June 02, 2020
Owner and Operator Information for ASSISI HEALTHCARE OF CLARE OAKS
Our database of owners and operators shows all direct owners of the nursing nurse, any managers and directors, and the most adjacent indirect owners of the facility (that is, if the direct owner is company, then the owners of that company.) Lists of nursing home owners are available and you cansearch for nursing home owners and operatorson our site.
Business Entity Name:
CLARE OAKS
Owners:
Managers and Directors:
BRIAN DOWD(OPERATIONAL/MANAGERIAL CONTROL)
BRIAN DOWD(OFFICER)
BRIAN DOWD(MANAGING EMPLOYEE)
ER SENIOR MANAGEMENT IL LLC(OPERATIONAL/MANAGERIAL CONTROL)
KATHY MEISINGER(DIRECTOR)
AARON REINKE(DIRECTOR)
JEANNENE WALKER(OFFICER)
JEANNENE WALKER(MANAGING EMPLOYEE)
Analysis of Nursing Hours Spent Per Patient
CMS provides detailed information about how long nursing staff spends with residents. This data includes nursing subcategories of Registered Nurse, Licensed Practical Nurse, and non-nursing Certified Nursing Assistants. More hours spend per patient should can indicate a better facility or it could indicate more complicated situations.
The nursing staff of ASSISI HEALTHCARE OF CLARE OAKS spends MORE time on average with its residents than the state average for total nursing homes spent per resident and
MORE time than the national average for total nursing homes spent per resident.
Type Facility State / National Avg
Registered Nurse (RN)
Hours 1.63 0.73 /
0.65
Case Mix 0.36 0.41 /
0.39
Adjusted 1.83 NA /
NA
Licensed Practical Nurse (LPN)
Hours 1.33 0.66 /
0.88
Case Mix 0.72 NA /
NA
Adjusted 1.37 NA /
NA
Certified Nursing Assistants (CNA)
Hours 2.33 2.02 /
2.21
Case Mix 2.09 NA /
NA
Adjusted 2.29 NA /
NA
Total Licensed Staff
Hours 2.96 1.38 /
1.52
Physical Therapist (PT)
Hours 0.00 0.06 /
0.07
Total Nursing Homes Spent per Resident on Average
Hours 5.29 3.40 /
3.74
Case Mix 3.17 3.29 /
3.16
Adjusted 5.34 NA /
NA
Quality Measures
Quality measures are based both on patient survey information and on the results of actual claims that are filed with CMS. It is not clear what period is covered in the measures.
Desc. Perc. State Avg. / Comparison
Percentage of short-stay residents who were rehospitalized after a nursing home admission (qm521) 20.0% 23.0%
Better
Percentage of short-stay residents who had an outpatient emergency department visit (qm522) 7.9% 9.4%
Better
Number of hospitalizations per 1000 long-stay resident days (qm551) 1.4% 1.7%
Better
Number of outpatient emergency department visits per 1000 long-stay resident days (qm552) 0.7% 0.8%
Better
Percentage of long-stay residents whose need for help with daily activities has increased (qm401) 12.0% 15.8%
Better
Percentage of long-stay residents who lose too much weight (qm404) 6.1% 8.0%
Better
Percentage of low risk long-stay residents who lose control of their bowels or bladder (qm405) 63.3% 45.3%
Worse
Percentage of long-stay residents with a catheter inserted and left in their bladder (qm406) 1.9% 1.8%
Worse
Percentage of long-stay residents with a urinary tract infection (qm407) 7.0% 2.8%
Worse
Percentage of long-stay residents who have depressive symptoms (qm408) 0.8% 28.2%
Better
Percentage of long-stay residents who were physically restrained (qm409) 0.0% 0.2%
Better
Percentage of long-stay residents experiencing one or more falls with major injury (qm410) 6.7% 3.3%
Worse
Percentage of long-stay residents assessed and appropriately given the pneumococcal vaccine (qm415) 97.0% 89.3%
Better
Percentage of long-stay residents who received an antipsychotic medication (qm419) 7.0% 18.4%
Better
Percentage of short-stay residents assessed and appropriately given the pneumococcal vaccine (qm430) 93.4% 72.9%
Better
Percentage of short-stay residents who newly received an antipsychotic medication (qm434) 2.3% 2.1%
Worse
Percentage of long-stay residents whose ability to move independently worsened (qm451) 20.1% 23.1%
Better
Percentage of long-stay residents who received an antianxiety or hypnotic medication (qm452) 8.3% 19.6%
Better
Percentage of high risk long-stay residents with pressure ulcers (qm453) 13.6% 8.7%
Worse
Percentage of long-stay residents assessed and appropriately given the seasonal influenza vaccine (qm454) 97.5% 94.0%
Better
Percentage of short-stay residents who made improvements in function (qm471) 56.5% 65.1%
Worse
Percentage of short-stay residents who were assessed and appropriately given the seasonal influenza vaccine (qm472) 90.3% 73.3%
Better
ASSISI HEALTHCARE OF CLARE OAKS Violations, Complaints and Fines
These are complaints and fines that are reported by CMS. Some of the data is not very recent, but we have decided to include it here so that you have as much information as possible.
Amount fined in recent period:$975.00, Complaints filed:0
Deficiency Deficiency Date / Date Corrected
Inspect, test, and maintain automatic sprinkler systems.
(Fire Safety) 04-18-2018 /
05-11-2018
Install corridor and hallway doors that block smoke.
(Fire Safety) 04-18-2018 /
05-18-2018
Ensure smoke barriers are constructed to a 1 hour fire resistance rating.
(Fire Safety) 04-18-2018 /
05-04-2018
Ensure precautions for handling oxygen cylinders and equipment are correctly followed.
(Fire Safety) 04-18-2018 /
05-04-2018
Provide appropriate pressure ulcer care and prevent new ulcers from developing.
(Health) 04-19-2018 /
05-29-2018
Add doors in an exit area that do not require the use of a key from the exit side unless in case of special locking arrangements.
(Fire Safety) 03-06-2019 /
03-22-2019
Have an enclosure around a vertical opening shaft.
(Fire Safety) 03-06-2019 /
03-22-2019
Properly select, install, inspect, or maintain portable fire extinguishes.
(Fire Safety) 03-06-2019 /
03-22-2019
Install corridor and hallway doors that block smoke.
(Fire Safety) 03-06-2019 /
03-22-2019
Provide care and assistance to perform activities of daily living for any resident who is unable.
(Health) 03-06-2019 /
03-25-2019
Provide appropriate care for residents who are continent or incontinent of bowel/bladder, appropriate catheter care, and appropriate care to prevent urinary tract infections.
(Health) 03-06-2019 /
03-25-2019
Ensure that a nursing home area is free from accident hazards and provides adequate supervision to prevent accidents.
(Health) 10-01-2020 /
11-09-2020
Provide appropriate care for residents who are continent or incontinent of bowel/bladder, appropriate catheter care, and appropriate care to prevent urinary tract infections.
(Health) 10-01-2020 /
11-09-2020
Ensure that feeding tubes are not used unless there is a medical reason and the resident agrees; and provide appropriate care for a resident with a feeding tube.
(Health) 10-01-2020 /
11-09-2020
Provide and implement an infection prevention and control program.
(Health) 10-01-2020 /
11-09-2020
Conduct risk assessment and an All-Hazards approach.
(Fire Safety) 10-09-2020 /
11-23-2020
Develop Emergency Preparedness policies and procedures.
(Fire Safety) 10-09-2020 /
10-29-2020
Address subsistence needs for staff and patients.
(Fire Safety) 10-09-2020 /
10-29-2020
Develop a communication plan.
(Fire Safety) 10-09-2020 /
10-29-2020
Provide a means of sharing information on occupancy/needs.
(Fire Safety) 10-09-2020 /
10-29-2020
Conduct testing and exercise requirements.
(Fire Safety) 10-09-2020 /
11-23-2020
Implement emergency and standby power systems.
(Fire Safety) 10-09-2020 /
11-23-2020
Install a two-hour-resistant firewall separation.
(Fire Safety) 10-09-2020 /
10-29-2020
Have properly located and lighted "Exit" signs.
(Fire Safety) 10-09-2020 /
10-29-2020
Inspect, test, and maintain automatic sprinkler systems.
(Fire Safety) 10-09-2020 /
10-29-2020
Install corridor and hallway doors that block smoke.
(Fire Safety) 10-09-2020 /
10-29-2020
Ensure receptacles at patient bed locations and where general anesthesia is administered, are tested after initial installation, replacement or servicing.
(Fire Safety) 10-09-2020 /
11-23-2020
Have generator or other power source capable of supplying service within 10 seconds.
(Fire Safety) 10-09-2020 /
11-23-2020
Ensure proper usage of power strips and extension cords.
(Fire Safety) 10-09-2020 /
10-29-2020
Have proper medical gas storage and administration areas.
(Fire Safety) 10-09-2020 /
10-29-2020
Hospitals Near ASSISI HEALTHCARE OF CLARE OAKS
Quite often skilled nursing facilities and hospitals work closely together to help patients recover or manage a terminal illness. Hospitals deals with acute care while nursing homes treat patients for a longer period of time. New residents at skilled nursing homes typically come from a hospital and nursing home residents may be readmitted to a hospital if their recovery does not proceed well. (Hospital readmission rates are closely monitored by CMS.) Consequently it is important that you consider which hospitals are near a nursing home which choosing one. Below is a list of hospitals near ASSISI HEALTHCARE OF CLARE OAKS.
This information is based on the most recent Hospital data. Historical data is not available.
Hospital 5-Star Overall Rating
MT SINAI HOSPITAL MEDICAL CENTER
1500 S FAIRFIELD AVE
CHICAGO, IL 60608 1
MACNEAL HOSPITAL
3249 SOUTH OAK PARK AVENUE
BERWYN, IL 60402 2
PRESENCE SAINT JOSEPH HOSPITAL - ELGIN
77 N AIRLITE STREET
ELGIN, IL 60123 2
ADVOCATE CHRIST HOSPITAL & MEDICAL CENTER
4440 W 95TH STREET
OAK LAWN, IL 60453 2
LOYOLA UNIVERSITY MEDICAL CENTER
2160 S 1ST AVENUE
MAYWOOD, IL 60153 2
COMMUNITY FIRST MEDICAL CENTER
5645 W ADDISON STREET
CHICAGO, IL 60634 2
WEST SUBURBAN MEDICAL CENTER
3 ERIE COURT
OAK PARK, IL 60302 2
ADVENTHEALTH BOLINGBROOK
500 REMINGTON BOULEVARD
BOLINGBROOK, IL 60440 3
ST ALEXIUS MEDICAL CENTER
1555 N BARRINGTON RD
HOFFMAN ESTATES, IL 60169 3
NORTHWESTERN LAKE FOREST HOSPITAL
1000 N WESTMORELAND ROAD
LAKE FOREST, IL 60045 3
ADVOCATE CONDELL MEDICAL CENTER
801 S MILWAUKEE AVE
LIBERTYVILLE, IL 60048 4
NORTHWESTERN MEDICINE CENTRAL DUPAGE HOSPITAL
25 NORTH WINFIELD ROAD
WINFIELD, IL 60190 4
NORTHWEST COMMUNITY HOSPITAL 1
800 W CENTRAL ROAD
ARLINGTON HEIGHTS, IL 60005 4
ADVOCATE SHERMAN HOSPITAL
1425 NORTH RANDALL ROAD
ELGIN, IL 60123 4
ALEXIAN BROTHERS MEDICAL CENTER 1
800 W BIESTERFIELD RD
ELK GROVE VILLAGE, IL 60007 4
ADVOCATE LUTHERAN GENERAL HOSPITAL
1775 DEMPSTER ST
PARK RIDGE, IL 60068 4
LOYOLA GOTTLIEB MEMORIAL HOSPITAL
701 WEST NORTH AVE
MELROSE PARK, IL 60160 4
ADVOCATE GOOD SAMARITAN HOSPITAL
3815 HIGHLAND AVENUE
DOWNERS GROVE, IL 60515 4
COPLEY MEMORIAL HOSPITAL
2000 OGDEN AVENUE
AURORA, IL 60504 4
AMITA HEALTH RESURRECTION MEDICAL CENTER
7435 W TALCOTT AVENUE
CHICAGO, IL 60631 4
Medical Professionals Associated with ASSISI HEALTHCARE OF CLARE OAKS
These are the doctors who are affiliated with ASSISI HEALTHCARE OF CLARE OAKS. The data is from the most recent period. Historical data is not available.
PERCIVAL BIGOL( INTERNAL MEDICINE )
SANA CHAUDHRY( HOSPITALIST - DUPAGE MEDICAL GROUP LTD )
JOHN BORN( FAMILY PRACTICE - EDWARD HEALTH VENTURES )
RAJIV SOOD( INTERNAL MEDICINE - ADVANCE MIDWEST MEDICAL SC )
ALEX SANCHEZ( GERIATRIC MEDICINE - MIDWEST PROFESSIONAL MEDICAL CARE INC )
Detailed Analysis Pages:
Depending on the nursing home, this page can get really long. So, we have also broken up the data onto separate pages to allow you to find what you want more easily. We will keep adding to these pages as we continue to analyze the nursing home database.
CMS Five Star Ratings and Quality Measures for ASSISI HEALTHCARE OF CLARE OAKS
Five different rating results plus detailed inspection numbers and quality measures for ASSISI HEALTHCARE OF CLARE OAKS.
Covid Infections at ASSISI HEALTHCARE OF CLARE OAKS
This report is updated weekly and shows new and historical infection levels.
Nursing Hours Analysis for ASSISI HEALTHCARE OF CLARE OAKS
How long a nurse spends with a resident can be an important factor in their recovery. This page shows the average nursing hours spent per resident for RNs, LPNs, CNAs, PTs and all licensed staff.
Ownership Details for ASSISI HEALTHCARE OF CLARE OAKS
A list of all of the registered owners for ASSISI HEALTHCARE OF CLARE OAKS. This includes direct and indirect owners and managers.
Noted Deficiencies for ASSISI HEALTHCARE OF CLARE OAKS
A list of all of the deficiencies for the facility. This includes a description, type of deficiency, incident date and when the facility reports that the incident was corrected.
Comparison Ranking of Nearby Skilled Nursing Facilities
How does ASSISI HEALTHCARE OF CLARE OAKS compare to other skilled nursing facilities? This list shows the competitive set within a 25 mile radius.
Best Nursing Homes in BARTLETT, IL
Homes that you should consider. A list ranking the best skilled nursing facilities in BARTLETT based on their weighted inspection score as of April 01, 2021.
Worst Nursing Homes in BARTLETT, IL
Homes that you avoid if possible. A list ranking the worst skilled nursing facilities in BARTLETT based on their weighted inspection score as of April 01, 2021.
Other Data Periods:
Data on ASSISI HEALTHCARE OF CLARE OAKS is available for the following periods:
| https://www.nursinghomedatabase.com/home/IL/BARTLETT/60103/assisi-healthcare-of-clare-oaks/2021-04-01 |
Psychological implications of traumatic brain damage on the patient's family
Download Citation | Psychological implications of traumatic brain damage on the patient's family | Discusses counseling to help families adapt to the behavioral and personality disturbances accompanying moderate to severe brain damage, namely... | Find, read and cite all the research you need on ResearchGate
Psychological implications of traumatic brain damage on the patient's family
January 1986
Rehabilitation Psychology 31(4):241-250
DOI: 10.1037/h0091551
Authors:
Abstract
Discusses counseling to help families adapt to the behavioral and personality disturbances accompanying moderate to severe brain damage, namely those incurred in motor vehicle accidents. Families of brain-damaged patients often do not understand the nature and behavioral sequelae of the injury. Stresses in the family created by the patient's altered behavior can be compounded by unrealistically optimistic expectations. Family reactions to the sequelae go through 6 stages, as pleasure at the patient's return home is replaced by bewilderment and anxiety when energy and optimism wear thin; this stage is often followed by guilt, depression, despair, mourning, and reorganization and emotional disengagement. Psychological intervention can help families negotiate these stages by helping them to understand the nature and effects of the injury, facilitating more realistic expectations, and helping them work through the conflicts and pain engendered by the injury. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
... Sbordone, Seyranian and Ruff, 1998). Disadvantages include potential bias through: denial (particularly in the early stages;
Lezak, 1986
); levels of stress and fatigue; and personality style (e.g. neuroticism; ...
... Family members after brain injury -theoretical models
Lezak (1986)
, in her model o f loss and bereavement, outlines of a series of stages that family members pass though as they adjust to the changes in the head injured person and life after ABI: initially they feel happiness and relief that the patient is home and alive; this is followed by anxious bewilderment, discouragement, guilt and depression as they realize things ...
... Wood and Yurdakul, 1997;Peters et al. 1990;Gosling and Oddy, 1999;Peters et al., 1992), loss and grief (e.g.
Lezak, 1986)
and stress, burden and psychopathology (e.g. Linn et al., 1994;Kreutzer et al., 1994a;Livingston et al., 1985a;1985b). ...
An exploration of the psychological well-being and relationship quality of partners and spouses after acquired brain injury
Thesis
Jan 2004
Anne Whelan
Historically, the acquired brain injury (ABI) literature has tended to address the negative outcomes of spouses and caregivers. As a result, the area of positive functioning, or 'flourishing', has been neglected. The field has also tended to focus on psychological outcomes to the exclusion of understanding relationships, particularly between spouses or partners, after ABI. The effect of 'awareness of deficit', a common consequence of ABI, on partners or spouses is also relatively unexplored. This study was intended to bridge these gaps. It aimed to explore the positive Psychological Well-Being (PWB) of partners of persons with ABI; the nature of the couple relationship; and what factors affect these outcomes. The sample consisted of 46 partners of patients with acquired non-progressive brain injury (traumatic brain injury, 50%; cerebrovascular accident, 37%; anoxia, 7%; infection, 4%; other, 2%) in the chronic phase of injury. Contacted through a neurorehabilitation unit and a charity, couples were required to complete postal questionnaires and partners, a follow up semi-structured telephone interview. Using three scales of Psychological Well-Being (e.g. Ryff, 1989), partners appeared able to achieve PWB in certain dimensions ('Personal Growth', PG; 'Positive Relations with Others', PR) but not others ('Environmental Mastery', EM). On the Dyadic Adjustment Scale (DAS; Spanier, 1976), certain relationship dynamics were also found to be preserved (cohesion, expression of affection) whilst others suffered (overall adjustment, consensus, satisfaction). About a third of the couple relationships were considered 'poorly adjusted' by commonly used cut-offs. The trend was for partners to be less satisfied with their relationship with the injured person now compared to before the injury, although a minority was more satisfied. Lower patient current functioning (particularly in activities of daily living; Patient Competency Rating Scale, PCRS) emerged as predictive of better partner PWB in one dimension (EM) although no brain injury factor was predictive of other dimensions (PG, PR). Similarly, more severe patient neurobehavioural symptoms (Neurobehavioural Rating Scale, NRS; Levin et al, 1979; particularly 'somatic/anxiety' symptoms) and lower satisfaction with preinjury relationship were predictive of poorer current relationship quality. Awareness of deficit, length of time since injury and injury severity were predictive neither of PWB nor relationship quality. Those with children/adolescents at home had greater relationship cohesion but were no different in other aspects of the relationship and partner PWB. Length of time in relationship preinjury had no association with outcomes. In exploring impaired awareness of deficit, patients rated themselves as having significantly fewer deficits than partners rated them, and 'awareness' was more impaired for cognitive and behavioural than physical deficits. Awareness was not associated with time since injury or severity. The strengths and limitations of the study and the implications for theory, research, professional and clinical practice are discussed.
... Earlier works outlined the importance of considering models of bereavement and loss in work with families of post-TBI adults
(Lezak, 1986;
Oddy & Herbert, 2003;Roundhill et al., 2007) or post-pABI parents (A. Clark et al., 2008). ...
... Prior to the ABI, all the children had developed typically with no brain injury, chronic illness, physical disability, or psychiatric condition. We were interested in interviewing parents at least 1 year following pABI as it takes from 9 months to 2 years to realize post-injury loss
(Lezak, 1986)
. ...
“Concurrent Ropes and Ladders”: Mapping and Conceptualizing the Emotional Loss Experience of Parents Following Pediatric Acquired Brain Injury
This grounded theory study aims to map, conceptualize, and theorize the emotional loss experienced by parents following their child’s pediatric acquired brain injury (pABI). Data were obtained from 47 semi-structured interviews conducted with parents (72% mothers) at least 1 year following pABI. The study’s theory of “concurrent ropes and ladders” emerged from a process of initial in vivo coding followed by focused and thematic coding. Codes were consolidated into five thematic categories capturing parents’ emotional continuous loss experience: (a) comparing life before and after, (b) struggling to construct new realities, (c) recognizing instability and permanency, (d) adjusting and readjusting, and (e) grieving as an emotional shadow. These categories are at work simultaneously in parents’ accounts, thus supporting a model of dynamic concurrency within and across their lived experiences. Recommendations for practitioners were derived from the theory to support parents’ emotional coping with living loss throughout the chronic stage.
... Phase four is considered chronic phase consisting of further rehabilitation or maintenance training, if any ( Figure 2). If needed rehabilitation/ maintenance Murial Lezak was one of the first in the brain injury literature to describe the process of family reactions throughout the rehabilitation process
(39)
. She described specific family reactions seen at different time points throughout rehabilitation phases. ...
... This description was linear, outlining how the patient progressed simultaneously with the process of the family and how the different reactions followed one another in phases. According to the model, the reactions within the family evolve from initial happiness due to the survival of the patient to mourning and reorganization from 15 months and onward
(39)
. This is in opposition to a later model proposed by Stroebe & Schut (40) . ...
Family matters in neurorehabilitation: why, when, who, and how?
The objective of this clinical paper is to describe the different types of family matters that professionals deal with every day when working in rehabilitation. This paper emphasizes WHY and WHEN it is important to work with the whole family and summarizes family reactions throughout the rehabilitation process. Furthermore, it is examined WHO in the family is more at risk of poor caregiver outcomes. Lastly, the paper identifies the needs of the family following brain injury and HOW it is possible to work with the family throughout the different phases of rehabilitation.
... Symptoms of fatigue and irritability in particular have been found to affect TBI survivors across all levels of injury severity (Belmont, et al., 2006;Juengst et al., 2013). While symptoms relating to mild head injury diminish and typically resolve within three months, those individuals sustaining moderate to severe or very severe injury are likely to experience neurological damage which contributes, directly or indirectly, to some level of longer-term or lifelong disability
(Lezak, 1985;
Ponsford, 1995a). level of burden and distress they may carry (Allen et al., 1994;Livingston et al., 1985;Norman, 2016;Oddy, Humphrey & Uttley, 1978;Oder et al., 1992;Wade et al., 2001;). ...
... The themes identified in this study represent previous literature surrounding the experience of TBI more generally. The theme of discontinuity and continuity of the TBI survivor in highlighted by
Lezak (1985)
who observes that the familiar appearance and mannerisms of the person may make it difficult for those close to the TBI survivor to appreciate that often profound changes have taken place at less immediately obvious levels. ...
The Secondary Impact of Traumatic Brain Injury: An Interpretative Phenomenological Analysis of the Experiences of Family and Friends
Jane Townshend
This study seeks to contribute to our understanding of the lived experiences of family members and friends of individuals with traumatic brain injury (TBI). The study employed an interpretative phenomenological approach, enabling family members and friends to identify and reflect upon the factors they themselves considered most significant about the impact of TBI on someone close to them, and how this experience has affected their own lives and their relationship with the TBI survivor. Eleven participants, two males and nine females aged 22-79, were from the UK. Several strong and interconnected themes emerged from the interviews, clustering into four superordinate themes: ‘Continuity and discontinuity’; ‘Damage, loss and grief’; ‘Roles and responsibility’; and ‘Coping and not coping’. The study findings identify the importance of support and information provision for family members and friends of those with TBI to help them manage the long term impact of TBI.
... Loss and grieving models.
Lezak (1986)
provided a bereavement model of family adaptation following TBI. She proposed that families need to go through a similar process of accommodation to loss after a TBI, as after a death, that is, as in Kubler-Ross's (1969) linear model of grief in which individuals proceed through a series of stages of denial, anger, bargaining, depression and acceptance. ...
... In terms of emotional functioning, life cycle transitions are significant triggers to feelings of loss, grief, anxiety and depression
(Lezak, 1986;
Rolland, 1994;Silverberg, 1996). Simon's parents had frequent reminders of what Simon should be doing as part of the transition from adolescence to young adulthood -for example, studying for A-levels, making plans to go to university, having a girlfriend. ...
A Contextual, Systemic Perspective in Child Neuropsychological Rehabilitation
Chapter
The variable, somewhat idiosyncratic long-term cognitive, physical, social, emotional and behavioural outcomes for children with brain injury, especially if the injury is severe, are well-documented (Stancin et al., 2002; Schwartz et al., 2003; Anderson et al, 2011). In addition, families of children with brain injury report high rates of psychological distress, enduring burden, social isolation, changes in family relationships and loss of income as they care for their child and adjust to the effects of brain injury (Rivara et al., 1992; Wade et al, 2001, 2002, 2004; Gan et al., 2006; Anderson et al., 2011).
... Even with a mild or moderate trau-matic brain injury, it is known that patients demonstrated emotional impairment. For example, post-traumatic emotional changes included impaired capacity for social activity
[6]
, impaired interpretation of non-verbal communication and increased auditory processing time, a lack of emotional attachment and empathy, lack of warmth in social interactions, or chronic social and emotional deficits [7][8][9][10]. For comas caused by severe traumatic brain injury, we could expect a significantly impaired perception of charged emotional stimuli. ...
Acoustic and Subjective Basis of Emotional Perception in Comatose Patients: A Comparative Study
Article
Jun 2023
... Journal of Emotion and Psychopathology (Alderman, 2003;Burke et al., 1988;Demark & Gemeinhardt, 2002;Eames & Wood, 2003;Felmingham et al., 2001;Harris, 1997;Khan et al., 2003;
Lezak, 1987;
Lezak & O'Brien, 1988;Oddy et al., 1985;Prigatano, 1987;Sansone et al., 2012;Slaughter et al., 2003;Winkler, 2006). Considering the prevalence and negative impact of anger and aggression on outcomes after TBI, it is critical to have clinically relevant evidence-based treatments for these issues. ...
Intervention to Change Attributions that are Negative (ICAN): A Feasibility Study on Reducing Anger After Brain Injury
Article
Full-text available
Jeong Hoon Jang
Dawn Neumann
Objectives: Explore the early efficacy of a treatment to modify anger, aggression, negative attributions, and perspective-taking in participants with traumatic brain injury (TBI). Design: Randomized waitlist-controlled trial. Participants: Twenty-four adults with a TBI (≥ 1-year post-injury) who had above average aggression and either negative attribution bias or poor perspective-taking. Intervention: Intervention to Change Attributions that are Negative (ICAN). Measures: Epps Scenarios (attributions of intent, hostility, blame; anger and aggression responses); Aggression Questionnaire (AQ); PROMIS-Anger; Interpersonal Reactivity Index Perspective-taking; and Participant Global Impression of Change (PGIC) for anger and perspective-taking. Results: Twenty-one participants completed the study (ICAN = 8; Waitlist control [WLC] = 13). Post-treatment, ICAN participants had lower anger responses to Epps Scenarios (p = 0.03) compared to WLC participants who had not yet received treatment. Other between-group comparisons were not significant. Analyses comparing pre/post-intervention changes in the pooled sample (n=21), revealed reduced attributions of intent (p < 0.01) and blame (p = 0.05), and anger (p = 0.01) and aggression responses to Epps scenarios (p < 0.01) after receiving treatment. Post-intervention scores on the AQ and PROMIS-Anger were also significantly reduced (p < 0.01). On the PGIC, 83% and 45% reported noticeable changes in perspective-taking and anger, respectively. Discussion: ICAN may reduce anger and negative attributions after TBI and merits further investigation.
... Parents had to be with no psychiatric or substance abuse history. We were interested in recruiting parents for at least 1 year following pABI as it takes from 9 months to 2 years to realize postinjury loss
(Lezak, 1986)
. pABI included: traumatic brain injury (TBI): motor vehicle accident (55.8%) and fall (7.7%); ...
Parental narcissistic injury following child acquired brain injury (ABI): Exploring self-object needs and emotional experience.
Michal Ben-Asher
Einat Yehene
Maya Gerner
... The changes that occur in higher functions have to be identified, measured, and described in certain areas. These abilities include the following areas: visuospatial, language, memory, intellectual processes, and attention [12]
[13]
[14]. On the other hand, the Luria-DNA battery is selective, so that it makes it possible to explore the higher psychological processes in a short period of time and meets the criteria of being sensitive to offer a neuropsychological profile with multiple possibilities of comparison, being its strengths and weaknesses interpretable from Luria's neuropsychological theory [11]. ...
Mental Health in Women Victims of Gender Violence: Descriptive and Multivariate Analysis of Neuropsychological Functions and Depressive Symptomatology
Article
Full-text available
María-Concepción Vega-Hernández
Concha Antón
Female victims of abuse, as well as suffering from psychopathological disorders such as depression, can have neuropsychological sequelae affecting memory and attention, with serious consequences, both physical and psychological, in their daily lives. Therefore, the objective of this study is to analyse these sequelae that affect attention and memory, as well as the possible association of these sequelae to depression. A total of 68 women, victims of gender-based violence, between the ages of 15 and 62 participated in this study. The Luria DNA Battery (Neuropsychological Diagnosis of Adults) by Manga and Ramos (2000); and the Beck Depression Inventory (2011) were applied. It is shown that female victims of gender-based violence present poor short-term memory, attentional control, and score low on the Luria-DNA battery. Of these women, 60% suffer from some relevant type of depression. Through HJ-Biplot analysis, a direct relationship was found between memory and attentional control with the total score of the Luria battery. However, an inverse relationship was found between short-term memory and depression. In addition, three well-differentiated clusters of female victims of gender-based violence were identified. It is concluded that a lower rate of depression is observed in female victims of abuse when they have a more intact short-term memory.
... Lezak's work in the 1980s focused specifi cally on reactions of family members during inpatient rehabilitation with six stages identifi ed: helping families observe the patient accurately amid denial, families becoming more receptive to incomplete recovery, families pulling back as coping mechanisms develop, families seeing the person as different than before the injury, families actively mourning despite the person's survival, and emotional detachment to preserve the family.
27
However, Lezak's model was developed during a time when inpatient adult rehabilitation stays were much longer than those now available under managed care and insurance caps. Again, this model does not address the unique aspects of grief and mourning for families with a child who has ABI. ...
Family Assessment and Intervention After Pediatric Acquired Brain Injury
Chapter
Full-text available
... Responses can be written or given orally. It assesses the ability to learn by repetition, short-term visual memory, visual motor skills and psychomotor speed, qualities which are necessary for sustained attention, focus, concentration, learning ability, coordination, speed of reaction and mental flexibility (Groth-Marnat, 2000;
Lezak, 1986)
. (c) Controlled Oral Word Association Test (COWAT) (Benton and Hamsher, 1976) (also known as Test of Verbal Fluency). ...
Neurocognitive and emotional status after one- year of mindfulness-based intervention in patients with relapsing-remitting multiple sclerosis Neurocognitive and emotional status after one-year of mindfulness-based intervention in patients with relapsing-remitting multiple sclerosis
Article
Full-text available
Isabel Mato
Sandra Doval
Veronica Hidalgo Hernández
Multiple sclerosis (MS) is the most common disabling neurological disease among young adults. The diagnosis of this disease usually leads to uncertainty, stress, and anxiety, which in turn can lead to negative outcomes. Consequently, the development of healthy lifestyle strategies can lead to better emotional management of perceived stress. Due to the importance of the patient's emotional response during the development and management of the disease and the repercussions of the cognitive deficits, the objective of this study is to develop a mindfulness-based intervention to provide to patients a tool for stress management. This study offers data on neuropsychological, functional and emotional outcomes in a sample of 30 patients with remitting relapsing form of MS after one year of intervention compared to 30 controls. We tested a model of intervention with a program of Mindfulness-Based Cognitive Therapy, based on an adapted Jon Kabat-Zinn's MBSR program. Results showed cognitive and emotional benefits after one year following this program. Discussion about the opportunities of these types of intervention in neurological diseases is provided in light of results obtained. This study represents pioneering research in MS and psychological treatment of this neurological autoimmune disease and it offers positive results of applying mindfulness-based intervention in this population.
... The finding showing that the more time elapsed since injury, the less parents reported adequate BF, indicates the adverse impact of long-term caregiving, marked by fatigue, resource depletion, while grasping the permanency of the injury with its unforeseen end (Roos, 2002;Jordan & Linden, 2013). Such findings corroborate earlier propositions suggesting that parents' loss experience accentuates with time as they realize their need to adjust the full impact of injury across the lifespan
(Lezak, 1986;
Collins, 2007). Accordingly, relative to the comparison group, parents reported significantly more health problems and feelings of depression. ...
Factors associated with parental grief reaction following pediatric acquired brain injury
The present study investigated factors associated with parental grief reaction (PGR) following pediatric acquired brain injury (ABI), and compared PGR to the one exhibited following child death. Fifty-seven parents of 51 children (aged 3–18) whose ABI occurred 1–14 years before participation, completed the multi-scale Two-Track Bereavement Questionnaire; a socio-demographic questionnaire; and a scale assessing perceived behavioural changes in the child. Results from regression analysis indicated that time since injury had no impact on parents’ grief other than having an adverse impact on their overall coping and functioning; A higher amount of weekly caring hours predicted only a greater traumatic perception of the loss; Older children’s ages but mostly greater parental-perceived behavioural changes, predicted greater PGR on most scales. PGR was compared with the pre-existing data of bereaved parents who completed the same grief questionnaire. Although grief response patterns and intensity were similar in both groups, significant differences were found on scales assessing the continuing bond with the child: relational active grief, close and positive relationship, and conflictual relationship. Our findings indicate that parental grief is multi-dimensional following pediatric ABI and illuminate the interplay between elements characterizing parents’ nonfinite vs. finite loss experience.
... With respect to loss, a period of grief for the person that has been lost was a feature of the stage models of family adaptation to traumatic brain injury that were developed in the 1980s (e.g. Groveman & Brown, 1985;
Lezak, 1986)
. Feelings of loss and grief have also been reported by some spousal carers in more recent qualitative studies (e.g. ...
Partners’ experiences of relationship continuity in acquired brain injury
Background: Research in dementia suggests that spousal carers differ in terms of whether they perceive their relationship with the person with dementia as continuous with the pre-morbid relationship or as radically changed, and that these differences may be associated with how spouses respond to the challenges of care-giving. The aim of this study was to explore whether the conceptual framework of relationship continuity (which comprises five dimensions) may also be applicable to understanding the experience of spousal carers in acquired brain injury. Method: Five spouses were interviewed about their relationship, and the data were analysed using Template Analysis. The applicability of the framework was evaluated by assessing (1) whether the accounts of each participant provided material relevant to each of the five dimensions of relationship continuity, and (2) whether the accounts suggested a close link between the dimensions (i.e. whether participants who showed continuity on one dimension tended to show continuity on the other dimensions). The association between continuity/discontinuity and responses to the challenges of care-giving was also explored. Findings: Findings suggested that the two criteria were met and that the framework may be useful in understanding the experience of spousal carers in brain injury. Furthermore, those who perceived discontinuity drew on medical models for making sense of changes in their partner, experienced greater subjective burden, and expressed doubts about remaining within the relationship. Those who perceived discontinuity also reported experiencing less warmth and affection from their partner. © 2017 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license.
... b Cohabitant status means married/cohabiting in general and includes both caregivers married to the patient and married to others.
(Lezak, 1986)
. This last stage is often followed 462 by anxiety, depression, mourning, and emotional dis- Oddy et al., 1985). ...
Patterns of change and stability in caregiver burden and life satisfaction from 1 to 2 years after severe traumatic brain injury: A Norwegian longitudinal study
NEUROREHABILITATION
Objective:
To assess burden and life satisfaction in family members of patients with severe traumatic brain injury (sTBI) at 1 and 2 years post-injury, examine if change in burden can be predicted by family member and patient demographics, patient's functional status, family members social network or level of burden at 1 year.
Methods:
Prospective national multicenter study. Self-report from family members, patient data collected from a national cohort study on patients with sTBI. 80 family members participated.
Main outcome measure:
The Caregiver Burden Scale (CBS), life satisfaction.
Results:
Total burden increased between years 1 and 2 post-injury (P = 0.04). Thirty percent of the family members reported an increased burden, 55% were stable, and 15% had a decrease in burden between the two follow-up times. Logistic regression analyses revealed that experiencing loneliness was an independent predictor of increased burden from 1 to 2 years post-injury (OR = 4.35, P < 0.05). Life Satisfaction was lower at the 2 year follow-up than at 1 year (p = 0.03).
Conclusions:
The results demonstrate a need for long-term follow-up of patients and family members that focuses on professional support to relieve burden and risk of loneliness or social isolation. This group may benefit from additional follow-up interventions tailored to their needs.
... Problems refer to loss of interest, feeling down, sleep, fatigue, poor appetite, feeling bad about oneself, difficulty concentrating, moving slower, and thoughts of suicide. The total score is used to determine depression severity, which is further divided into the following categories: severe (20)(21)(22)(23)(24)(25)(26)(27), moderately severe (15)(16)
(17)
(18)(19), moderate (10-15), mild (5)(6)(7)(8)(9), and none (0-4). ...
The Relations of Self-Reported Aggression to Alexithymia, Depression, and Anxiety After Traumatic Brain Injury
James Malec
Flora M. Hammond
Objectives: To compare self-reported aggression in people with and without traumatic brain injury (TBI) and examine the relations of aggression to alexithymia (poor emotional insight), depression, and anxiety.
Setting: Rehabilitation hospital.
Participants: Forty-six adults with moderate to severe TBI who were at least 3 months postinjury; 49 healthy controls (HCs); groups were frequency matched for age and gender.
Design: Cross-sectional study using a quasi-experimental design.
Main Measures: Aggression (Buss-Perry Aggression Questionnaire); alexithymia (Toronto Alexithymia Scale-20); depression (Patient Health Questionnaire-9); and trait anxiety (State-Trait Anxiety Inventory).
Results: Participants with TBI had significantly higher aggression scores than HCs. For participants with TBI, 34.2% of the adjusted variance of aggression was significantly explained by alexithymia, depression, and anxiety; alexithymia accounted for the largest unique portion of the variance in this model (16.2%). Alexithymia, depression, and anxiety explained 46% of the adjusted variance of aggression in HCs; in contrast to participants with TBI, depression was the largest unique contributor to aggression (15.9%).
Conclusion: This was the first empirical study showing that poor emotional insight (alexithymia) significantly contributes to aggression after TBI. This relation, and the potential clinical implications it may have for the treatment of aggression, warrants further investigation.
Copyright
... Problems refer to loss of interest, feeling down, sleep, fatigue, poor appetite, feeling bad about oneself, difficulty concentrating, moving slower, and thoughts of suicide. The total score is used to determine depression severity, which is further divided into the following categories: severe (20)(21)(22)(23)(24)(25)(26)(27), moderately severe (15)(16)
(17)
(18)(19), moderate (10-15), mild (5)(6)(7)(8)(9), and none (0-4). ...
The Influence of Personal Emotional Awareness on Aggression After Brain Injury
... The family adaptation process has also been described as families needing to undertake four tasks: the task of grieving, the task of restructuring, the task of developing a new identity, and the task of growing through adversity (Perlesz, Furlong, & McLachlan, 1992). Other conceptual frameworks include the family system recovery process moving through six stages: optimism during the hospitalization; bewilderment and anxiety when the family returns home with the injured member; feelings of guilt; depression, despair, and mourning; reorganization; and emotional disengagement
(Lezak, 1986)
. ...
Family Forward: Promoting Family Adaptation Following Pediatric Acquired Brain Injury
Lyndal Hickey
Vicki Anderson
This article describes a new and innovative social work intervention, Family Forward, designed to promote early adaptation of the family system after the onset of a child's acquired brain injury. Family Forward is integrated into inpatient rehabilitation services provided to the injured child and recognizes the important role of family in child rehabilitation outcomes and the parallel process of recovery for the child and family following an injury. Family Forward is informed by clinical practice, existing research in family adaptation after pediatric acquired brain injury, the resiliency model of family adjustment and adaptation, and family therapy theories and approaches.
... can also negatively affect the family of the patient significantly, which may inhibit their ability to be support systems
(Lezak, 1986)
. ...
Neuropathic Pain Treatment: A Biopsychosocial Approach
Research
The aims of this study were to assess individual opinion on psychological intervention in chronic pain treatment, namely neuropathic pain, given key points of what neuropathic pain actually is. After receiving doctor education of the ineffectiveness of pharmacotherapy in neuropathic pain; would they put more time and effort into their rehabilitation without pharmacotherapy? This study also assessed two additional questions: why is psychological intervention not a primary treatment option for neuropathic pain patients? Also; what is the greatest predictor of why patients may decline psychological intervention as a primary treatment option for neuropathic pain? Those tested predictors will be age, gender, level of education, and lack of knowledge from doctor.
A population of at least 25 people was selected. The survey questioned participants from a hypothetical standpoint…“If they suffered from neuropathic pain”, If they decline psychological intervention, they were surveyed on why. Responses shed light about why psychological intervention in neuropathic pain, or chronic pain as a whole, is not a primary treatment option. Patient choice and perception on psychological intervention plays a big role in this.
This study was a quantitative, correlational, and a between subjects pretest-posttest design. The population answered the same set of questions before AND after the presentation of adequate information that may affect their decision to opt into psychological intervention for neuropathic pain treatment. An ANOVA was used to treat each hypothesis individually, to assess significant differences between groups, and to determine predictors.
For more depth about statistical methods used:
Descriptive Statistics and Frequencies: Frequencies of all answer choices from the survey were recorded, and bar graphs were used to illustrate and compare participant choices within groups and between groups.
ANOVA: ANOVAs were used to calculate significant differences between predictor variables and responses, as well as significant differences.
Statistical Significance: High statistical significance of the alternate hypotheses is predicted, p < .05, thus rejecting the null hypotheses.
(Henry, 2015)
... Emotion dysregulation manifested by increased anger/aggression is not only one of the most common consequences of acquired brain injury (ABI), but also one that has a powerful impact on survivors and their relationships with others (Baguley, 2006;Draper, Ponsford, & Schönberger, 2007;
Lezak, 1987;
Rao et al., 2009;R. L. Wood, Liossi, & Wood, 2005;Wood & Thomas, 2013). ...
Perspective training to treat anger problems after brain injury: Two case studies
NEUROREHABILITATION
Jill Winegardner
Clare Keohane
Leyla Alexis Prince
Dawn Neumann
Background:
People with acquired brain injury (ABI) often show increased anger and aggression. Anger after ABI has been linked to attributions of hostile intent. The more intentional and hostile the judgments of other's behaviours are, the angrier the responses become. People with ABI make harsher attributions than healthy controls (negative attribution bias). Poor perspective-taking may distort assessment of others' intentions, thereby contributing to this bias and subsequent anger responses.
Objective:
Examine changes in anger and perspective-taking after a Perspectives Group in two participants with ABI.
Methods:
This study is a case report exploring observational changes in anger, hostility, verbal and physical aggression and perspective-taking in two males with ABI and severe emotion dysregulation. Participants and their spouses also provided qualitative feedback through a semi-structured interview following perspectives training. The six-week "Perspectives Group" used hypothetical and real-life situations to teach participants to consider the perspectives of others when determining their intentions.
Results:
Both participants showed post-treatment declines in aggression. Although only minimal changes occurred on the perspective-taking measure, spouses described important behavioural changes in their partners that indicated both decreased aggression and better perspective taking.
Conclusions:
These preliminary findings support further investigation of perspectives training for reducing anger after ABI.
... Personality and behavioral changes are often judged by family members, employers, friends, and others to be the most problematic consequence of brain in-jury
[11,
12]. For some individuals with brain injuries, their behavior contributes to a life where supports and opportunities disappear, resulting in loneliness and isolation [15,22]. ...
Neurobehavioral Complications of Brain Injury
Christina Peters
Christopher Schaub
MJ Schmidt
Factors that support and hinder recovery and adjustment after traumatic brain injury: a qualitative multiple case study
Lauren Woods
Anne H Zachry
Background/Aims
The numbers of individuals acquiring brain injuries in childhood is increasing. The deficits caused by brain injury can often have long-term implications that require support from caregivers, friends and the community. This study was conducted to gain an understanding of the shared perspectives of parental caregivers and their adolescent children as to what factors supported and hindered recovery and adjustment after traumatic brain injury.
Methods
In this qualitative multiple case study, semi-structured interviews were conducted with a purposive sample of four individuals with traumatic brain injury and their five parental caregivers. A thematic, cross-case analysis was used to identify factors that support and hinder recovery and adjustment.
Results
Seven themes were identified from the interviews: lack of educational resources about traumatic brain injury; poor consistency of care; caregiver stress and guilt; disconnection and isolation; connection, empathy and social support; being high achieving and resourceful; and authentic relationships between adolescents with traumatic brain injury and their parents.
Conclusions
The findings highlight the need for improved access to follow-up or community-based services for adolescents with traumatic brain injury who do not experience a hospital or inpatient rehabilitation stay. Additionally, healthcare providers should capitalise on the relationships between adolescents with traumatic brain injury and their parents to support recovery. The information gained from this study can be used to inform allied health professionals when developing and implementing interventions to support recovery in adolescents with traumatic brain injury and their parental caregivers.
Christian and Faith-based Counseling for Brain Injury: Techniques for Survivors and Families
Deana Adams
Developing a conceptual framework to identify and classify sources of parental stress following pediatric concussion
Elizabeth F Teel
Jeff Caron
Isabelle Gagnon
Objectives:
To create a conceptual framework that classifies the various stresses parents experience following their child's concussion.
Methods:
Twelve parents of children with concussion completed a semi-structured interview with the lead author. Questions broadly focused on post-concussion stress, with specific probes for caregiving responsibilities, concussion knowledge, and athletic participation. Data were analyzed using thematic analysis.
Results:
Ten mothers and 2 fathers participated. Five themes stemmed from our analysis: 1) Concussion Knowledge (central theme): stressors related to sources of concussion information; 2) Child Health Factors: stressors related to injury and illness, including concussion; 3) Activity Factors: stressors related to academic and athletic performance; 4) Parent-Injured Child Relationship Factors: stressors related to providing care to the child; and 5) Personal Factors: stressors unrelated to the concussion (e.g. family, social, career, etc.). Child Health Factors was most frequently identified as the primary stressor (n = 9).
Conclusions:
Sources of parental stress were varied following pediatric concussion. Issues relating to the child's post-injury dysfunction and the uncertain recovery from concussion were key stressors identified by parents. Moving forward, this framework can be used to ground the development of specific parental stress screening tools and interventions, which may benefit the parent's mental health and the child's clinical recovery.
Humanising health and social care: What do family members of people with a severe acquired brain injury value most in service provision
Caroline Ellis-Hill
Introduction
Family members living with relatives with severe acquired brain injury (ABI) face many challenges. Although this is recognised, service provision in the UK is poor and needs development.
Method
In order to support innovative service delivery for family members, we reflect on the research carried out by the first author using a new perspective – a lifeworld humanising approach in order to consider (a) the dehumanising existential challenges facing family members of people living with severe ABI and (b) what family members most value in service delivery presented in humanising terms.
Findings
Following ABI, family members may enter a parallel lifeworld (feeling separate from ‘usual’ life as it flows by) and face fundamental existential challenges of isolation, loss of agency, dislocation, loss of meaning and loss of personal journey. Family members have reported that service providers who are highly valued are those who act as ‘expert companions’. This role involves supporting families in some, if not all of the following (a) reaching across into the lifeworld of the family member and appreciating and validating what they are facing, (b) helping them make sense of their situation in terms which are meaningful to them and which they can explain to others, (c) through ABI expertise, supporting their relative through knowing their interests and needs and adapting the environment to suit these to help their relative to ‘settle’ and flourish, (d) supporting family members to share their life experiences – developing safe and trusting relationships, (e) having a humane, positive, creative and for some, a humorous approach, (f) being responsive to changing situations, (g) being available to call during times of worry or crisis and (h) help link with others and helpful networks.
Discussion
It is suggested that the role and approach of companion may help family members regain some sense of their own life and their well-being.
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Negative Attribution Bias and Related Risk Factors After Brain Injury
J HEAD TRAUMA REHAB
Susan M Perkins
Dawn Neumann
Angelle Sander
Flora M. Hammond
Objective:
In participants with traumatic brain injury (TBI) and peer controls, examine (1) differences in negative attributions (interpret ambiguous behaviors negatively); (2) cognitive and emotional factors associated with negative attributions; and (3) negative attribution associations with anger responses, life satisfaction, and participation.
Setting:
Two TBI outpatient rehabilitation centers.
Participants:
Participants with complicated mild to severe TBI (n = 105) and peer controls (n = 105).
Design:
Cross-sectional survey study.
Main measures:
Hypothetical scenarios describing ambiguous behaviors were used to assess situational anger and attributions of intent, hostility, and blame. Executive functioning, perspective taking, emotion perception and social inference, alexithymia, aggression, anxiety, depression, participation, and life satisfaction were also assessed.
Results:
Compared with peer controls, participants with TBI rated behaviors significantly more intentional, hostile, and blameworthy. Regression models explained a significant amount of attribution variance (25%-43%). Aggression was a significant predictor in all models; social inference was also a significant predictor of intent and hostility attributions. Negative attributions were associated with anger responses and lower life satisfaction.
Conclusion:
People with TBI who have higher trait aggression and poor social inferencing skills may be prone to negative interpretations of people's ambiguous actions. Negative attributions and social inferencing skills should be considered when treating anger problems after TBI.
ПРОСТРАНСТВА ЭЭГ ДЛЯ ИССЛЕДОВАНИЯ ПСИХИЧЕСКИХ ПРОЦЕССОВ В НОРМЕ И ПРИ ПАТОЛОГИИ
Galina Portnova
Изменения ЭЭГ при различных психических состояниях
имеют как минимум две составляющие: частотно-амплитудную и пространственную (а именно локализацию этих
изменений). Для оценки качественных и количественных
изменений ЭЭГ при любой мыслительной деятельности, восприятии, актуализации воспоминаний, переживании эмоций, а также других психических процессов необходим учёт
обеих вышеуказанных составляющих ЭЭГ. В частности, как
было показано, решение в уме вербально-логических и пространственно-образных задач сопровождается появлением
на ЭЭГ человека характерных ритмических паттернов, соответствующих характеру мыслительного процесса [Иваницкий, 1997; Иваницкий, 2007; Ivanitsky et al., 2010]. Более того,
ранее исследователями были выделены частотные характеристики ритмов ЭЭГ, ответственные за определенную когнитивную функцию, в частности, рабочую память [Griesmayr
et al., 2010; Sauseng et al., 2010], внимание [Orekhova, 2001], поиск вербальных ассоциаций [Abdullaev, 1998, Nikolaev et al.,
2001], подавление непроизвольного движения [Rougeul-Buser,
1997]. Переживание эмоций также сопровождалось специфическими изменениями ритмов ЭЭГ [Портнова, 2012; Portnova,
2014; Ильюченок, 2001], что позволило ряду исследователей
выделить специфические характеристики ритмов ЭЭГ при
восприятии приятных и неприятных картинок [Iosilevich
et al., 2012]. В частности, было показано, что мощность дельтаи тета-ритма была больше выражена для неприятных стимулов, в то время как для приятных стимулов характерна более
высокая частота альфа-ритма [Tumyalis et al., 2010]. Обобщая
полученные многочисленные данные, можно сделать вывод о нерациональности исследования изменений отдельных ритмов ЭЭГ в отрыве их пространственной локализации
и от изменений на других частотах. В то же время, изменения частотно-пространственных характеристик ЭЭГ при том
или ином состоянии необходимо воспринимать и исследовать как нечто целое, «целостный конструкт», по выражению
А.Я. Каплана [Fingelkurts, 2003], который соответствует тому
или иному психическому процессу.
Выделение «целостного конструкта» изменений электрической активности мозга важно не только для исследования
психических процессов, но и для выявления специфики их нарушений при различных видах психической и неврологической патологии, при которых изменяется работа когнитивных
функций, появляются эмоционально-личностные особенности
психики. В частности, у пациентов, перенесших легкую и средне-тяжелую ЧМТ, наблюдаются специфические изменения
личности и эмоциональной сферы, сопровождающиеся эмоциональной лабильностью, снижением эмпатии [Lezak, 1986]
и теплоты при социальных взаимодействиях [Williams, 2010;
Hynes et al., 2011]. У детей с расстройствами аутистического
спектра (РАС) отмечаются специфические нарушения восприятия, касающиеся, прежде всего, трудностей при распознавании эмоций других людей [Brewer R., 2016], а также при восприятии социальных и эмоциональных аспектов интонации
голоса и мимики [Downs & Smith, 2004; Gross, 2004]. Восприятие
информации у лиц с РАС характеризуется еще одной аномалией, а именно, неспособностью подавлять нерелевантную информацию от стимулов и гиперреактивностью по отношению
к сенсорным стимулам [Tavassoli et al., 2014; Lane et al., 2014;
Takahashi et al., 2014], которая проявляется даже при сохранном
интеллекте (синдром Аспергера) и сопровождается усилением
представленности высокочастотного альфа-ритма.
200 201
Успехи современной нейробиологии: достижения, закономерности, проблемы Глава 6
Отношение к изменениям частоты и локализации ЭЭГ
как к чему-то целостному позволит выявить не только отсутствие или наличие реакции, как например, у пациентов
в коме, где изменение электрической активности на частотах бета- и тета-ритма [Portnova, 2014] было выявлено при
предъявлении эмоционально значимой стимуляции, а при
предъявлении нейтральной стимуляции – отсутствовало
[Sisson, 1990; Puggina et al., 2005; Cheng et al., 2014], но и выявить общее и различное в психических процессах как
в норме, так и при патологии. В частности, восприятие
эмоционально значимых стимулов в различных модальностях имеют свою специфику изменений электрической
активности мозга [Wu et al., 2018]. Тем не менее, для каждой сенсорной модальности выделяются приятные, неприятные и нейтральные стимулы, которые сопровождаются
схожими эмоциональными ощущениями [Grabenhorst et al.,
2007], что и позволило ряду исследователей предположить
общие механизмы в оценке эмоциональных стимулов разных модальностей [Delplanque et al., 2008]. В качестве таких
механизмов были выделены два: участие лимбической системы в обработке эмоционально значимой информации
[Lévesque et al., 2017; Diao et al., 2017; McGlone et al., 2014]
и специфические функции правого и левого полушария мозга, ответственные за различные эмоциональные тональности [Coan and Allen, 2004; Fernandez-Carriba et al., 2002]. Общее
и различное психических процессов может быть выявлено
и визуализировано при помощи пространств ЭЭГ, как было
показано Г.А. Иваницким и А.О. Роик на примере решения
пространственных и вербальных задач с различной степенью выраженности вербального и пространственного компонентов [Роик & Иваницкий, 2011; Роик и др., 2012].
Применение метода построения когнитивных пространств, впервые предложенного Г.А. Иваницким и А.О.
Роик [Роик & Иваницкий, 2011; Роик и др., 2012], позволило
получить качественную и количественную меру различения
психических процессов друг от друга, а также между различными субъектами. Эффективность применения метода
для визуализации различных процессов мышления, восприятия и эмоциональных состояний у здоровых испытуемых,
а также изменения этих процессов у пациентов с различной
психической и неврологической патологией, продемонстрирована в данной главе. В частности, нами были исследованы когнитивные процессы при решении пространственных
и вербальных задач, восприятии зрительных и слуховых
стимулов, предъявляемых с различной частотой, а также
эмоциональные состояния при предъявлении эмоционально значимых стимулов в четырех сенсорных модальностях:
зрительной, слуховой, тактильной и обонятельной. Результатом использования методики Иваницкого и Роик стало
построение когнитивных, эмоциональных, музыкальных,
мультимодальных и ритмических пространств у пациентов
с расстройствами аутистического спектра, пациентов перенесших ЧМТ различной степени тяжести и здоровых добровольцев различных возрастных групп.
revis-neuro-1-240118
Poster
Full-text available
Luis Ruiz-Domínguez
Relacionar la habilidad intelectual no verbal del alumno de secundaria con el bajo desempeño académico para elaborar estrategias de intervención. No existe ningún tipo de relación entre las variables y el bajo desempeño académico. Hipotesis: existe una correlación positiva alta entre el CI no verbal y el bajo desempeño académico. El enfoque de la investigación que se propone es de carácter cuantitativo. Esta
investigación utiliza la recolección de datos para probar hipótesis, con base en la medición numérica y el análisis estadístico, para establecer patrones de comportamiento y probar teorías.
Page: 118
EEG of patients in coma after traumatic brain injury reflects physical parameters of auditory stimulation but not its emotional content
Galina Portnova
Mikhail Atanov
Primary Objective: We aimed to investigate the origin of EEG response of patients in coma and after moderate TBI to emotional stimulation, whether they distinguish emotional content or only react to the physical features of an audio signal.
Research Design: We registered EEG during continuous pleasant and unpleasant non-verbal stimulation and in rest. A total of 69 subjects participated in our study: healthy adults, conscious patients after moderate TBI and patients in coma after severe TBI. We analysed the distances between the stimuli according to EEG data and applied correlation analysis to the distances, acoustic parameters of stimuli, subjects’ emotional assessment of the stimuli, GCS score and Doppler ultrasound data.
Main Outcomes and Results: The EEG response to the stimulation in patients in coma mostly reflects the physical parameters of the stimuli, and correlated with Doppler ultrasound data. The EEG of healthy adults reflects their psychological assessment of the stimuli. Patients after moderate TBI differentiate unpleasant stimuli well and pleasant stimuli poorly, they mainly consider pitch to cope with this task like healthy adults do.
Conclusions: The reactivity to the acoustic features of emotional stimulation in patients in coma should be investigated further as a marker of patients’ recovery.
Abbreviations: TBI: traumatic brain injurym; TBI: moderate TBI; MCA: middle cerebral artery; GCS: Glasgow Coma Scale; M: mean; SD: standard deviation
Understanding Health-related Quality of Life in Caregivers of Civilians and Service Members/Veterans With Traumatic Brain Injury: Establishing the Reliability and Validity of PROMIS Mental Health Measures
ARCH PHYS MED REHAB
Noelle Carlozzi
Robin Ann Hanks
Rael T Lange
Angelle Sander
Objective:
To provide important reliability and validity data to support the use of the PROMIS Mental Health measures in caregivers of civilians or service members/veterans with traumatic brain injury (TBI).
Design:
Patient-reported outcomes surveys administered through an electronic data collection platform.
Setting:
Three TBI Model Systems rehabilitation hospitals, an academic medical center, and a military medical treatment facility.
Participants:
560 caregivers of individuals with a documented TBI (344 civilians and 216 military) INTERVENTION: Not Applicable MAIN OUTCOME MEASURES: PROMIS Anxiety, Depression, and Anger Item Banks RESULTS: Internal consistency for all of the PROMIS Mental Health item banks was very good (all α > .86) and three-week test retest reliability was good to adequate (ranged from .65 to .85). Convergent validity and discriminant validity of the PROMIS measures was also supported. Caregivers of individuals that were low functioning had worse emotional HRQOL (as measured by the three PROMIS measures) than caregivers of high functioning individuals, supporting known groups validity. Finally, levels of distress, as measured by the PROMIS measures, were elevated for those caring for low-functioning individuals in both samples (rates ranged from 26.2% to 43.6% for caregivers of low-functioning individuals).
Conclusions:
Results support the reliability and validity of the PROMIS Anxiety, Depression, and Anger item banks in caregivers of civilians and service members/veterans with TBI. Ultimately, these measures can be used to provide a standardized assessment of HRQOL as it relates to mental health in these caregivers.
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Coping strategies used by parents of children with traumatic brain injury: A cross-sectional study of Palestinians and Israelis
Article
Aug 2017
Wedad Masalha
Gail K Auslander
This study examined the use and helpfulness of coping strategies and patterns among parents of children with traumatic brain injury (TBI). Participants were 122 Arab-Israeli, Jewish-Israeli, and Palestinian parents of 65 children with TBI following their discharge from pediatric rehabilitation hospital. Family-focused strategies were highly prevalent and most helpful among both mothers and fathers. Jewish mothers reported that support coping pattern (but not medical or family) was more helpful than did Arab-Israeli and Palestinian mothers. The findings highlight the need to promote effective coping among mothers of children with TBI with low levels of income and education and underscore the need for continuous long-term professional support to parents of children with TBI after hospital discharge.
Neuropsychological issues in litigation following traumatic brain injury.
Article
Oct 1990
Jeffrey Kreutzer
Jennifer Harris Marwitz
Stefanie L. Myers
Provides information about issues confronting neuropsychologists involved in brain injury litigation. Neuropsychologists are often involved as experts in the litigation process because of their unique role in assessment and treatment of brain injury sequelae. Focus is on evaluation, preparation of reports, testimony, professional credibility, ethics, and responsibilities to the patient. Criteria for evaluating the expertise and credentials of psychologists hired by attorneys are presented.
A national service: coma to community
Chapter
Jan 1995
Zeev Groswasser
Until recently, the fate of patients with traumatic brain injury (TBI) was gloomy. It was assumed, that once they survived the acute state, nothing more could be done, despite their normal estimated life expectancy, especially in cases of penetrating brain lesions [1–4] uncomplicated by post-traumatic epilepsy. Conroy and Kraus [4] summarized their experience by stating that ‘people [with TBI] who are discharged alive from the hospital have survival comparable to that of the population they came from’.
Enactive Approach and Dual-Tasks for the Treatment of Severe Behavioral and Cognitive Impairment in a Person with Acquired Brain Injury: A Case Study
Article
Full-text available
Nov 2016
David Martínez-Pernía
David Huepe
Daniela Huepe-Artigas
María Beitia
One of the most important sequela in persons who suffer from acquired brain injury (ABI) is a behavioural disorder. To date, the primary approaches for the rehabilitation of this sequela are Applied Behaviour Analysis, Cognitive-Behaviour Therapy, and Comprehensive-Holistic Rehabilitation Programs. Despite this theoretical plurality, none of these approaches focuses on rehabilitating behavioural disorders considering the relation between affordance and environmental adaptation. To introduce this therapeutic view to neurorehabilitation, we apply the theoretical tenets of the enactive paradigm to the rehabilitation of a woman with severe behavioural and cognitive impairment. Over seventeen sessions, her behavioural and cognitive performance was assessed in relation to two seated affordances (seated on a chair and seated on a ball 65 cm in diameter) and the environmental adaptation while she was working on various cognitive tasks. These two seated affordances allowed to incorporate the theoretical assumptions of the enactive approach and to know how the behavior and the cognition were modified based on these two postural settings and the environmental adaptation. The findings indicate that the subject exhibited better behavioural (physical and verbal) and cognitive (matching success and complex task) performances when the woman worked on the therapeutic ball than when the woman was on the chair. The enactive paradigm applied in neurorehabilitation introduces a level of treatment that precedes behaviour and cognition. This theoretical consideration allowed the discovery of a better relation between a seated affordance and the environmental adaptation for the improvement behavioural and cognitive performance in our case study.
Coping and adaptive strategies of traumatic brain injury survivors and primary caregivers
Article
Jun 2016
NEUROREHABILITATION
Deana Adams
D Dahdah
Background:
Qualitative research methods allowed the investigator to contribute to the development of new theories and to examine change in processes over time, which added rich detail to existing knowledge of the use of coping and adaptive strategies by traumatic brain injury survivors and their primary caregivers (Ponsford, Sloan, & Snow, 2013). The advantages of phenomenological study were that it allows flexibility to explore and understand meanings attached by people to well-studied concepts such as coping, resiliency, and adaptation or compensation. Phenomenological study was sensitive to contextual factors. It also permitted the study of in-depth dynamics of coping and adaptive strategies of TBI survivors and primary caregivers, while understanding the social and psychological implications of the phenomenon.
Objective:
To explore the needs and deficits of adult traumatic brain injury (TBI) survivors and primary caregivers; and to identify their self-initiated coping and adaptive strategies. Significant to this study was the development of coping and adaptive strategies by the participants after their discharge from inpatient and rehabilitation treatment. The compensatory skills taught in treatment settings did not transfer to the home environment. Therefore, these strategies developed independently from previous treatment recommendations contributed to the development of theory related to rehabilitation and counseling. Distinctive to this study was the similarity of coping and adaptive strategies developed from both mild and severe traumatic brain injury survivors.
Methods:
This study consisted of eleven with TBI and six primary caregivers (N = 17), who participated in a series of semi-structured interviews aimed at discovering the coping and adaptive strategies utilized in dealing with the effects of brain injury. A Qualitative Phenomenological design was employed.
Results:
Patience and understanding, support, and professional help were identified by TBI survivors and caregivers as being their most relevant needs. Self-reported deficits included short-term memory loss (STM), fatigue, anger, and personality changes, and the strategies that TBI survivors and caregivers identified tended to address their problems with these specific day-to-day deficits. Problem focused, emotion focused, and avoidant coping were utilized to some degree in their adjustment to home life and activities of daily living. Participants offered suggestions for mental health professionals addressing how to more effectively work with brain injury survivors and their primary caregivers.
Conclusion:
TBI survivors and caregivers had multiple self-reported unaddressed needs following their discharge from facility-based treatment. They reported spontaneously engaging in various coping and adaptive strategies to address their needs and deficits. However, further education regarding potential post-TBI challenges and strategies for addressing them are needed, including a need for community and mental health resources.
Family Adjustment to Minor Traumatic Brain Injury
Chapter
Full-text available
Jan 1993
Paul R. Sachs
Families are recognized as an important part of the rehabilitation process for the survivor of severe traumatic brain injury (TBI). With this importance in mind, rehabilitation professionals have developed specific treatment approaches for families of these survivors (1–4).
Long-Term Family Intervention
Chapter
Jan 1989
Harvey E Jacobs
The effects of persisting sequelae of traumatic brain injury (TBI) on patients and family members have been well documented. A number of studies have identified a broad range of effects on family relationships relative to the time since injury, age and sex of the survivor, premorbid life style, family composition, level of recovery, behavior problems, family resources, and a host of other factors [1–8]. These findings indicate that there is no one course of adaptation and reaction on the part of family members, but rather a multitude of individualized circumstances and effects that may shape family functioning.
Organic Mental Disorders
Chapter
Jan 1994
Gerald Goldstein
Individuals sometimes begin engaging in aggressive behaviors following brain injury or during the development of a degenerative brain disease. Perhaps this phenomenon was first noted clinically in children with encephalitis. Jervis (1959) made the following comment: “Of great diagnostic importance is a certain pattern of behavior which is often observed in postencephalitic children. It is marked by episodes of overactivity, restlessness, impulsiveness, assaultiveness, and wanton destruction” (p. 1305). Another neurological disorder in which aggressive behavior is a commonly observed feature is Huntington’s disease. Patients with this disorder are frequently described as “irritable and quarrelsome,” “violent,” or “excitable.” The psychopathology of Huntington’s disease has been studied in some detail (Whittier, 1977). Whittier suggests that the aggressive behaviors result from dyscontrol arising from progressive loss of capacity to inhibit.
Neurologische Erkrankungen
Chapter
Jan 2003
Bernd Leplow
Kerstin Paetow
Bei mindestens 500000 neurologischen Neuerkrankungen pro Jahr und einer Jahresprävalenz von über 1,7 Mio. Betroffenen ist die Versorgung neurologischer Patienten auch von erheblicher volkswirtschaftlicher Bedeutung. Neurologische Krankheitsbilder zeigen sich in einer Fülle unterschiedlicher Formen und Ausprägungen mit ganz verschiedenen psychischen, kognitiven und behavioralen Veränderungen. Diese stellen nicht selten erhebliche Anforderungen an die Therapeuten. Inzwischen wurden eine Fülle verhaltensmedizinischer Verfahren entwickelt, welche in der Praxis jedoch kaum bekannt sind und entsprechend selten zur Anwendung kommen. Deswegen sollen in diesem Kapitel wichtige neurologische Erkrankungen nach Maßgabe psychologischer Modellvorstellungen zur Aufrechterhaltung und Verschlechterung körperlicher Zustandsbilder gegliedert und die auf diesen Modellen aufbauenden verhaltensmedizinischen Interventionsmöglichkeiten dargestellt werden.
Pathophysiologische Grundlagen
Chapter
Jan 2002
Tilman Wetterling
In diesem Kapitel werden die pathophysiologischen Grundlagen der den organischen Psychosyndromen zu Grunde liegenden Erkrankungen, Schädigungen oder Funktionsstörungen dargestellt. Dabei wird besonders auf die neuropathologischen und die biochemischen Veränderungen eingegangen. Der genaue Zusammenhang zwischen der neuropathologisch nachweisbaren Schädigung und der Ausbildung einer organisch bedingten psychischen Störung (OPS) ist häufig noch unklar, da die Schädigungen auf sehr verschiedenden Ebenen erfolgen bzw. erkennbar werden (Abb.2.1). Ähnliches gilt für die biochemischen Veränderungen.
Erkrankungen, die zu einer organischen psychischen Störung führen können
Chapter
Jan 2002
Tilman Wetterling
In diesem Kapitel werden Erkrankungen, die häufig zu einer organisch bedingten psychischen Störung führen können, ausführlich dargestellt. Dabei wird auch darauf eingegangen, ob und inwieweit psychische Symptome Frühsymptome oder gar die Erstmanifestation dieser Erkrankungen sein können. Da bei einer Reihe der in Frage kommenden Störungen verschiedene OPS auftreten können und daher die Differenzialdiagnose erschwert ist, sind in einer tabellarischen Übersicht (Tabelle 5.1) die am häufigsten vorkommenden zusammengestellt.
Nichtmedikamentöse Therapien
Chapter
Jan 2002
Tilman Wetterling
Neben den medikamentösen Therapien, die in den Kap. 4 bis 6 eingehend dargestellt sind, und den spezifischen neuropsychologischen Rehabilitationsmaßnahmen, die in Kap. 8 erwähnt werden, sind bei Patienten mit einer organischen psychischen Störung häufig nichtmedikamentöse Therapien, v. a. psychotherapeutische Interventionen, indiziert, da diese Patienten oft große Schwierigkeiten in der Bewältigung der krankheitsbedingten Beeinträchtigungen haben [18, 40] (→ Kap. 4.4.5) und/oder Verhaltensauffälligkeiten zeigen (→ Kap. 6). Verhaltensauffälligkeiten sind auch ein häufiger Grund für eine Heimeinweisung von OPS-Patienten [59].
Neurosystémique
Chapter
Dec 2011
J.-M. Destaillats
Antoinette Prouteau
C. Belio
J.-M. Mazaux
Families’ Early Sessions, Emotional Status, and Treatment Themes
Chapter
Apr 2014
Pamela S. Klonoff
This chapter describes the initial consultation with a psychotherapist who is incorporating family members into the neurorehabilitation process for their loved one. The role of family as a critical adjunct to the treatment of the patient is clarified, also including the limits of a doctor–patient relationship. Factors and considerations in early sessions are provided, encompassing important and common emotional and behavioral presentations by family members, which influence early working hypotheses. A semi-structured interview approach is presented to assist the psychotherapist in obtaining germane aspects of the family’s prior social history as well as their current functional and psychological status. Criteria to establish a baseline of the family’s level of awareness, acceptance, and realism are offered, and are divided into patient-related inquiries and caregiver/support network topics. Later in the chapter, an overview of prominent emotional reactions and psychosocial changes in families after brain injury are provided. These include depression, anxiety, and demoralization; anger and frustration; grief and loss; denial; guilt; identity and social role changes; subjective care burden; and shattering of the assumptive world and loss of sense of self. Lastly, global factors for psychotherapists working effectively with families as well as pervasive treatment themes are described.
Family Psychotherapy After Moderate to Severe Traumatic Brain Injury
Chapter
Apr 2014
Pamela S. Klonoff
This chapter provides a comprehensive overview of the effects of moderate to severe traumatic brain injury as a way to educate and support family members. First, the neuropathology is reviewed. Then through a series of family scenarios, the loved one’s alterations in the areas of memory; executive functions; organic unawareness; mood, behavior, and communication; and physical functioning are described. This will capture the universal themes related to the global consequences of moderate to severe traumatic brain injuries. For each domain, a series of psychotherapeutic “helpful hints” and tools are presented to assist the caregiver and tier supports to better understand and cope with their loved one’s postinjury sequelae. The chapter also describes techniques learned in psychotherapy for families to manage their personal distress, depression, anxiety, and dismay emanating from the pervasive limitations related to the brain injury. Lastly, an integrative case study is presented, illustrating the amalgamation of the initial consultation and early sessions (from Chap. 2) and key content from this chapter.
Loved Ones’ End-of-Life and Existential Considerations as a Caregiver
Chapter
Apr 2014
Pamela S. Klonoff
This chapter explores end-of-life and existential considerations about illness, injury, or death and provides “helpful hints” and coping tools for the family system. It is divided into several subsections. First, using brain tumors as a prototype, the relatives’ practical and emotional preparation for the loved one’s impending death is delved into. Specific topics include advance directives, hospice care, anticipatory grief, denial, emotional preparedness, and presencing. Positive aspects of caregiving are appraised. Following this, grief reactions and coping techniques after the death of the loved one are examined in family members, including children. The mourning (or emotional reconstitution) and adjustment process after the death of a loved one is then discussed. The concept of “complicated grief” is touched upon. Fundamental existential constructs for caregivers and the family are derived from positive psychology and existential psychology and include: restructuring the assumptive world and lifestyles; integrating ambiguous loss and chronic sorrow; posttraumatic growth; new meaning in life; spirituality; hope; resiliency; learned optimism; as well as personal and family morale. A case study illustrates the therapeutic process and principles. The chapter also incorporates a number of multimedia resources to exemplify the constructs, including websites, songs, books, stories, plays, poetry, broadcasts, and films.
The Forensic Psychological Evaluation of Traumatic Brain Injury
Chapter
Mar 2000
Joseph Yedid
Pediatric Brain Injury
Chapter
Jan 1997
Thomas Boll
Lisa Stanford
The purpose of this chapter is not to provide a comprehensive review of the literature in the area of pediatric brain injury in neuropsychology. This has been accomplished multiple times, most recently by Ryan, LaMarche, Barth, and Boll (1995). Reviews of specific neurobehavioral recovery issues cited individually in this chapter are also available in reasonably recent form (Levin, Grafman & Eisenberg, 1987). The purpose of this chapter is to engage in a series of discussions about the issues that influence the outcome of pediatric brain injury, including those issues or mechanisms that predate the injury itself. Such mechanisms include the premorbid psychological characteristics of the patient (not just the injury the brain sustains, but the brain that sustains the injury) as well as the epidemiologic mechanisms that contribute to the nature of the injury and the specific characteristics of the individuals who sustain that injury. Amelioration of the injury, which has in many reviews been focused largely on rehabilitative techniques of a formal nature, are discussed in the broader context of psychological interventions, educational interventions, and family-based activities. One of the purposes of this chapter will be to enhance understanding of the importance of the individual who has the accident, and the context in which that individual lives, and will continue to live. The chapter begins with a discussion of the physiological, epidemiological, and psychological mechanisms that characterize a brain injury, and/or characterize the patient who suffers the brain injury. Discussion then proceeds to multifactorial influences on outcome, including those that make outcome in certain instances so perplexing when to initial glance, “dose and response” seems hopelessly out of proportion. The emphasis of the final portion on school and family once again suggests the unique role in children’s lives of those institutions, and the individuals who come into contact with children who have had a head injury, as well as the children who come into contact with the children who have had a head injury. Because considerable data have already been amassed on specific tests, treatment technologies, complicating factors such as bleeding and seizures, and developmental influences, this chapter can enjoy the luxury of going somewhat further afield in discussing those day-to-day and somewhat more mundane issues that cross the clinician’s desk, and confront the treating doctor, be it psychologist, psychiatrist, neurologist, or other health professional.
View
Show abstract
Psychosocial Aspects of Neurological Impairments in Children
Chapter
Jan 1999
Margaret Semrud-Clikeman Ph.D.
With the advent of new technological methods, the assessment of brain tumors, head injury, and neurological impairments through neuropsychological techniques has moved beyond diagnosis to determining educational needs and intervention strategies. It has become apparent that efforts now need to be directed at investigating and understanding the psychosocial needs accompanying these disorders. Many clients are provided with sufficient information about their intellectual and medical needs, but social and emotional areas are not as clearly explained nor targeted for interventions.
Closed Head Injury and Family Structure
Chapter
Jan 1992
Bobby G. Greer
Mary Anne Knack
Rob Roberts
Considerable attention has been given in the literature to the impact of closed head injury on the family (Brooks, 1984; Brown & McCormick, 1988). Stressors, as well as other factors, contributing to posttrauma family adjustment have been delineated (Braciszeski, 1987). This chapter will review this other work and will propose another perspective from which to view family restructuring after closed head injury.
Traumatic Brain Injury
Chapter
Jan 1995
Eleanor B. Callon
Warren T Jackson
Medical scientists recognized and described traumatic brain injury (TBI) as early as 3000 B.C. (Walsh, 1978). Over the past two decades, advances in trauma evaluation (Collicott, 1991), neuroimaging (Bigler, Yeo, & Turkheimer, 1989), and neurosurgery (Adams & Victor, 1989) have greatly increased survival rates for TBI patients. Rehabilitation utilizing combined knowledge and cooperative efforts of medicine, physical therapy, occupational therapy, speech pathology, therapeutic recreation, rehabilitation psychology, neuropsychology, and social work has improved quality of lives of those survivors. Yet, our understanding of the brain and how it recovers is still in early development, and we have much to learn.
View
Stresses upon the Relatives of Head-Injured Patients
Article
Full-text available
Jan 1979
Michael Oddy
Michael Humphrey
David Uttley
As part of a prospective study of closed head injury, 54 relatives were interviewed within a month of the patient's accident and again six and twelve months later.
The degree of stress on the relatives was measured by means of the Wakefield Depression Scale and by interview questions.
The worst period of stress for the majority of relatives appeared to be during the first month after the accident. However, the degree of stress appeared to level off by the sixth month and no further diminution was found at twelve months.
Stress was apparently mediated by the relatives' perception of personality changes and subjective defects. It was not affected by the severity of the head injury or associated disabilities, nor by whether the patient had resumed work and leisure activities.
The nature of the stress is analysed and methods of alleviating it discussed.
Neuropsychological rehabilitation after closed head injury in adults
Article
Full-text available
Jun 1984
George Prigatano
David J. Fordyce
Harriet Zeiner
B C Wood
Cognitive and personality disturbances following severe closed head injury in young adults are associated with poor rehabilitation outcome. Yet systematic programmes for dealing with these disturbances have generally not appeared. The present report briefly describes the Neuropsychological Rehabilitation Program (NRP) at Presbyterian Hospital in Oklahoma City and the initial outcome data on eighteen closed head injury patients and seventeen untreated controls. Greater improvement in neuropsychological functioning occurred in the NRP patient group on selected variables, but generally the effects were modest. Emotional distress, however, substantially decreased in treated patients. Fifty percent of the NRP patients maintained productivity 75% of the time or more following rehabilitation, compared to 36% of the controls. Treatment successes showed less personality disturbances than treatment failures and better learning and memory scores post-treatment.
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Show abstract
| https://www.researchgate.net/publication/232522485_Psychological_implications_of_traumatic_brain_damage_on_the_patient%27s_family |
68199bbd340a71a554c8a96b8b013029183b11c19562c379d70e2ba7ac64d61a_optim.pdf
User Manual for USB-DI models including: USB-DI, Project Series, UDI-5004-101, USB, Digital to Analog, Convertor, with, Isolated Outputs
USB-DI PS manual MJD2-27-19 V3
USB-DI PS manual MJD2-27-19 V3 - ART Pro Audio
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USB-DI-PS-manual-MJD2-27-19-V3
USB-DI
USB Digital to Analog Convertor with Isolated Outputs
Project Series
User's Manual
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IMPORTANT SAFETY INSTRUCTION READ FIRST
This symbol, whenever it appears, er it appears, alerts you
alerts you to the presence of uninsulated ing and maintenance
dangerous voltage inside the enclosure-voltage accompanying literature.
that may be sufficient to constitute a risk of shock. manual.
This symbol, wherevto important operatinstructions in the Please read the
Read instructions: Retain these safety and operating instructions for future reference. Heed all warnings printed here and on the equipment. Follow the operating instructions printed in this user manual.
Do not open: There are no user serviceable parts inside. Refer any service work to qualified technical personnel only.
Moisture: To reduce the risk of fire or electrical shock do not expose the unit to moisture or use in damp or wet conditions. Do not place container of liquid on unit.
Heat: Do not locate the unit close to excessive heat or direct sunlight, as this could cause a fire hazard. Locate the unit away from any equipment, which produces heat such as: power supplies, power amplifiers and heaters.
Environment: Protect from excessive dirt, dust, heat, and vibration when operating and storing. Avoid tobacco ash, drink spillage and smoke, especially that associated with smoke machines.
Handling: Protect the controls from damage during transit. Use adequate padding if you need to ship the unit. To avoid injury to yourself or damage to the equipment, take care when lifting, moving, or carrying the unit.
Servicing: Unplug power immediately if equipment is exposed to moisture, the power supply becomes damaged during a lightning storm or if smoke odor or noise is noted. Refer servicing to qualified technical personnel only.
Installation: Install the unit in accordance with the instructions printed in the user manual.
Table of Contents:
TOC \O "1-3" \H \Z HYPERLINK \L "_TOC1135573" INTRODUCTION
PAGEREF _TOC1135573 \H 1 HYPERLINK \L "_TOC1135574" Key Features Include
PAGEREF _TOC1135574 \H 1 HYPERLINK \L "_TOC1135575" CONTROLS and OPERATION
PAGEREF _TOC1135575 \H 3 HYPERLINK \L "_TOC1135576" FRONT PANEL
PAGEREF _TOC1135576 \H 3 HYPERLINK \l "_Toc1135577" MAIN OUTPUTS FIXED/VARIABLE
PAGEREF _Toc1135577 \h 3 HYPERLINK \L "_TOC1135578" REAR PANEL
PAGEREF _TOC1135578 \H 3 HYPERLINK \l "_Toc1135579" USB Connection
PAGEREF _Toc1135579 \h 3 HYPERLINK \l "_Toc1135580" LEFT and RIGHT OUTPUTS
PAGEREF _Toc1135580 \h 3 HYPERLINK \l "_Toc1135581" GROUND LIFT
PAGEREF _Toc1135581 \h 3 HYPERLINK \L "_TOC1135582" OPERATION WITH A COMPUTER
PAGEREF _TOC1135582 \H 4
HYPERLINK \L "_TOC1135583" APPLICATIONS
PAGEREF _TOC1135583 \H 4 HYPERLINK \l "_Toc1135584" Audio interfaces
PAGEREF _Toc1135584 \h 4 HYPERLINK \l "_Toc1135585" When to use the Fixed versus the variable switch
PAGEREF _Toc1135585 \h 4
HYPERLINK \L "_TOC1135586" WARRANTY INFORMATION
PAGEREF _TOC1135586 \H 5 HYPERLINK \L "_TOC1135587" Limited Warranty
PAGEREF _TOC1135587 \H 5 HYPERLINK \L "_TOC1135588" Online Registration
PAGEREF _TOC1135588 \H 5 HYPERLINK \L "_TOC1135589" Exclusions
PAGEREF _TOC1135589 \H 5 HYPERLINK \L "_TOC1135590" SERVICE
PAGEREF _TOC1135590 \H 6 HYPERLINK \L "_TOC1135591" SPECIFICATIONS
PAGEREF _TOC1135591 \H 7
INTRODUCTION
The USB-DI Project Series is a high quality Digital to Analog Convertor for connecting a computer to a stereo or PA system. It takes in USB audio, converts it to analog audio and then isolates the output using custom transformers. The output isolation is key to removing ground loops and other system noise between the digital and analog audio systems. A large knob on the front panel allows quick, precise control over the output level. A separate headphone output allows you to monitor the system. The front panel Main Outputs switch allows you to keep the isolated outputs at a fixed level while controlling level of the Headphones output. The line level XLR outputs are available for connecting to all sorts of systems. The Main outputs are always isolated but allow you to control the ground reference to reduce noise. The USB-DI Project Series is powered by USB, drawing less than 200mA and eliminating the need for an external power.
Key Features Include
USB Connectivity to Desktop and Laptop Computers High Quality D to A Convertor Sample rates from 32kHz to 48kHz Switchable Transformer isolated outputs Front panel Volume control Front panel 1/8-inch Headphone Monitor output USB powered Compact rugged package all Aluminum chassis Stackable chassis Perfect for connecting computers to any Audio System Three Year Warranty
The USB-DI Project Series has been designed with a set of isolation transformers to eliminate the hum and buzz that may be caused by stray voltages and ground loops. Depending on your application, computers, optical projectors and many other consumer types of equipment can induce noise in your audio paths. The USB-DI Project Series is equipped to cover these problem areas and give you a great clean audio path.
CONNECTIONS
The 1/8-inch MONITOR HEADPHONES is stereo TRS jack. It can accommodate a wide variety of headphone models. Maximum output level is 150mW.
The USB port is USB 2.0 compliant and should be used to connect directly to one of the USB connections on your computer. This connection also powers the USB circuitry inside the USB-DI Project Series. To your computer this connection looks like a "USB Audio DAC" and your computer then controls the sample rate.
Since the USB connection will be carrying high quality digital audio to and from your computer as well as bus powering the USB interface, we suggest that you use a high quality shielded USB cable for best performance. Ideally you should connect directly to one of the USB ports on your computer. Connecting through a shared hub can reduce power and bandwidth that is available for each USB device and should be avoided when possible. Though the USB-DI Project Series is compatible with USB 1.1 and 2.0 interfaces, USB 2.0 is preferred for the cabling and computer connection as it allows for more system bandwidth.
The XLR LEFT and RIGHT analog Outputs can be connected to a variety of line level input products a few examples would be a mixers, receivers, or powered speakers.
NOTE: Before connecting the USB-DI box XLR OUTPUTS, make sure all audio levels are turned down or the system is not powered on. This helps to prevent any popping issues that would damage more sensitive equipment. It also helps to be in Variable output mode with the volume control fully CCW before powering up if connected to an audio system.
CONTROLS and OPERATION
FRONT PANEL
MAIN OUTPUTS FIXED/VARIABLE
Using the FIXED switch position. When the MAIN OUTPUTS switch of the USBDI is set to FIXED (switch is engaged) the switch will light Blue. The outputs are fixed and will not vary with the LEVEL pot. The LEVEL pot will only adjust the signal level of the MONITOR HEADPHONES. The output of the USB-DI will default to 650mV RMS (-1.5dBu) max output.
Using the VARIABLE switch position. When the MAIN OUTPUTS switch of the of the UDB-DI is set to VARIABLE (switch is released) the switch will light Red. This function allows you to control the LEFT and Right OUTPUTS and the MONITOR HEADPHONES by varying the LEVEL pot from Min to Max.
NOTE: The LED function also doubles as a power indicator. The lit LED shows that there is a valid power connection thru the USB cable. If this LED is not lit the unit is not powered.
REAR PANEL
USB Connection Connect the USB cable to the appropriate computer (digital USB) device and then to the USB connector on the USB-DI Project Series. Once the USB connection is made and your computer is on, the unit will automatically connect and try to set your computer "Default Audio Device" to be "USB Audio DAC". Usually the computer will do this automatically whenever a USB device is first connected, but it is sometimes necessary to make the selection manually. The same settings may need to be made in your particular audio application as well (Check your application instructions). These settings should be made while the USB-DI Project Series and computer are connected.
LEFT and RIGHT OUTPUTS Connect the line level XLR OUTPUT jacks to all sorts of systems using analog inputs.
GROUND LIFT
Ground Lift switch eliminates grounding loop hum. The switch adds another level of hum protection. It lifts pin-1 on the XLR jacks. Computers sometimes are a source for noise issues in audio setups.
OPERATION WITH A COMPUTER
Once the USB connection is made and your computer is on, your computer will power the USB interfaces circuitry over the USB bus and the unit will automatically connect and try to set your computer "Default Audio Device" to be "USB Audio DAC". Usually the computer will do this automatically whenever a USB device is first connected, but it is sometimes necessary to make the selection manually. The same settings may need to be made in your particular audio application as well (Check your application instructions). These settings should be made while the USB-DI Project Series and computer are connected and powered on.
Your computer audio output "Speaker" is now set to be the "USB Audio DAC" and playback audio is routed to the USB-DI Project Series. This must be done while the USB-DI Project Series is connected to the computer and powered on. After the above settings are made, your computer will automatically reconfigure itself back to these settings every time the USB-DI Project Series is reconnected to the computer. Your recording software may also select which inputs or outputs are being used.
NOTE: The USB-DI Project Series interface uses the standard "USB Audio DAC". This driver is built into most modern operating systems, including most current versions of Linux. Since some details of how the audio interface is set vary with different versions of Linux, the setup is beyond the scope of this document. The main key in setup is to look for "USB Audio DAC" as the recording source or playback monitor output while the USB-DI Project Series is connected.
APPLICATIONS
Audio interfaces Audio sources from computers, Audio projectors and any other USB audio source to an analog audio interface, receivers, mixers and powered speakers.
When to use the Fixed versus the Variable switch Monitoring the source signal. A separate headphone output allows you to monitor the input signal, in the FIXED mode. This will allow you to vary the output signal for the headphones without changing the gain out the Main outputs.
In the FIXED mode the signal gain will not vary and can be adjusted from the preamp section or mixer that the USB-DI has been connected to. In the VARIABLE mode you will be able to adjust the output signal to the preamp or mixer from the USB-DI.
WARRANTY INFORMATION
Limited Warranty
Applied Research and Technology will provide warranty and service for this unit in accordance with the following warrants:
Applied Research and Technology (A R T) warrants to the original purchaser that this product and the components thereof will be free from defects in workmanship and materials for a period of three years from the date of purchase. Applied Research and Technology will, without charge, repair or replace, at its option, defective product or component parts upon prepaid delivery to the factory service department or authorized service center, accompanied by proof of purchase date in the form of a valid sales receipt.
Online Registration
We recommend that you register your product online to insure prompt warranty repair servicing on any repair issues. Please go to www.artproaudio.com. Select "Support", then "Product Registration". Then input your information here.
Exclusions
This warranty does not apply in the event of misuse or abuse of the product or as a result of unauthorized alterations or repairs. This warranty is void if the serial number is altered, defaced, or removed.
A R T reserves the right to make changes in design or make additions to or improvements upon this product without any obligation to install the same on products previously manufactured.
A R T shall not be liable for any consequential damages, including without limitation damages resulting from loss of use. Some states do not allow limitations of incidental or consequential damages, so the above limitation or exclusion may not apply to you. This warranty gives you specific rights and you may have other rights, which vary from state to state.
For units purchased outside the United States, an authorized distributor of Applied Research and Technology will provide service.
SERVICE
The following information is provided in the unlikely event that your unit requires service.
Be sure that the unit is the cause of the problem. Check to make sure the unit has power, all cables are connected correctly, and the cables themselves are in working condition. You may want to consult with your dealer for assistance in troubleshooting or testing your particular configuration.
If you believe that the ART unit is at fault, go to www.artproaudio.com.
Select "Support", then "Return Authorization Request" to request a return authorization number.
If you are returning the unit for service, pack the unit in its original carton or a reasonable substitute. The original packaging may not be suitable as a shipping carton, so consider putting the packaged unit in another box for shipping. Print the RA number clearly on the outside of the shipping box. Print your return shipping address on the outside of the box.
Include, with your unit, a note with the RA number and your contact information, including a return shipping address (we cannot ship to a P.O. box) and a daytime phone number, and a description of the problem, preferably attached to the top of the unit. Also include a copy of your purchase receipt.
Fill in the following information for your reference:
Date of purchase ___________________
Purchased from ___________________
Serial number
___________________
SPECIFICATIONS
Input Connections: Output Connections: Max XLR output level:
Headphone output: Frequency Response: THD: Dynamic Range: Supported Sample rates: Chassis Type: rubber sides Power Requirements:
USB 2.0 Balanced XLR and 1/8-inch Headphone output +7.5dBu. Balanced line, Variable output mode. -1.5dBu Balanced Line, Fixed output mode 150mW / channel max. @16 Ohms load. 20 Hz to 20 kHz +/- 1dB <0.020% [typical] 96dB "A" wtd. typ. 32kHz, 44.1kHz, 48kHz All aluminum black anodized with integral
USB bus powered, 500mA Max
Dimensions(HWD): Weight:
1.87-inch x 4.61-inch x 4.27-inch 47.5mm x 117mm x 108mm 1.89 lbs. (0.86 kg) with packaging
Note: 0 dBu = 0.775Vrms
ART maintains a policy of constant product improvement. Therefore, specifications are subject to change without notice.
Go to HYPERLINK http://www.artproaudio.com www.artproaudio.com for the latest information and support on the USB-DI Project Series.
www.artproaudio.com E-mail: support@artproaudio.com
2019 Applied Research & Technology/ Yorkville Sound
USB - DI Project Series UDI-5004-101
PAGE 12 PAGE 8
EMBED Word.Picture.8 EMBED Word.Picture.8
| https://manuals.plus/m/68199bbd340a71a554c8a96b8b013029183b11c19562c379d70e2ba7ac64d61a_doc |
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Remote Sensing | Free Full-Text | Evaluation of Pre-Earthquake Anomalies of Borehole Strain Network by Using Receiver Operating Characteristic Curve
In order to monitor temporal and spatial crustal activities associated with earthquakes, ground- and satellite-based monitoring systems have been installed in China since the 1990s. In recent years, the correlation between monitoring strain anomalies and local major earthquakes has been verified. In this study, we further evaluate the possibility of strain anomalies containing earthquake precursors by using Receiver Operating Characteristic (ROC) prediction. First, strain network anomalies were extracted in the borehole strain data recorded in Western China during 2010–2017. Then, we proposed a new prediction strategy characterized by the number of network anomalies in an anomaly window, Nano, and the length of alarm window, Talm. We assumed that clusters of network anomalies indicate a probability increase of an impending earthquake, and consequently, the alarm window would be the duration during which a possible earthquake would occur. The Area Under the ROC Curve (AUC) between true predicted rate, tpr, and false alarm rate, fpr, is measured to evaluate the efficiency of the prediction strategies. We found that the optimal strategy of short-term forecasts was established by setting the number of anomalies greater than 7 within 14 days and the alarm window at one day. The results further show the prediction strategy performs significantly better when there are frequent enhanced network anomalies prior to the larger earthquakes surrounding the strain network region. The ROC detection indicates that strain data possibly contain the precursory information associated with major earthquakes and highlights the potential for short-term earthquake forecasting.
Background:
Evaluation of Pre-Earthquake Anomalies of Borehole Strain Network by Using Receiver Operating Characteristic Curve
Katsumi Hattori 3,4 ,
Kaiguang Zhu 1,2,* ,
Mengxuan Fan 1,2 ,
Dedalo Marchetti 2,5 ,
Xiaodan He 1,2 and
Chengquan Chi 6
*
Author to whom correspondence should be addressed.
Remote Sens. 2021 , 13 (3), 515; https://doi.org/10.3390/rs13030515
Received: 2 December 2020 / Revised: 24 January 2021 / Accepted: 29 January 2021 / Published: 1 February 2021
(This article belongs to the Special Issue Advances in Remote Sensing Systems for Disaster Management and Risk Mitigation )
Abstract
:
In order to monitor temporal and spatial crustal activities associated with earthquakes, ground- and satellite-based monitoring systems have been installed in China since the 1990s. In recent years, the correlation between monitoring strain anomalies and local major earthquakes has been verified. In this study, we further evaluate the possibility of strain anomalies containing earthquake precursors by using Receiver Operating Characteristic (ROC) prediction. First, strain network anomalies were extracted in the borehole strain data recorded in Western China during 2010–2017. Then, we proposed a new prediction strategy characterized by the number of network anomalies in an anomaly window,
N
a
n
o
, and the length of alarm window,
T
a
l
m
. We assumed that clusters of network anomalies indicate a probability increase of an impending earthquake, and consequently, the alarm window would be the duration during which a possible earthquake would occur. The Area Under the ROC Curve (AUC) between true predicted rate,
t
p
r
, and false alarm rate,
f
p
r
, is measured to evaluate the efficiency of the prediction strategies. We found that the optimal strategy of short-term forecasts was established by setting the number of anomalies greater than 7 within 14 days and the alarm window at one day. The results further show the prediction strategy performs significantly better when there are frequent enhanced network anomalies prior to the larger earthquakes surrounding the strain network region. The ROC detection indicates that strain data possibly contain the precursory information associated with major earthquakes and highlights the potential for short-term earthquake forecasting.
Keywords:
receiver operating characteristic
;
a new prediction strategy
;
frequent network anomalies
;
prediction efficiency
;
short-term earthquake forecasting
Graphical Abstract
1. Introduction
It has been observed that the preparatory process and the occurrence of shallow earthquakes are usually accompanied by crustal deformation. Precise observations of surface displacement, using data from GNSS satellites, strainmeters and seismographs all over the world, allow the investigation of complex tectonic structures [ 1 , 2 , 3 ] and the prediction of short- and medium-term earthquakes [ 4 , 5 ]. However, earthquakes have complicated changing spatio-temporal distribution characteristics, which makes the evaluation of earthquake-related deformation data highly challenging. In recent years, various studies have attempted to understand the interactions and relationships between strain data and earthquakes [ 6 , 7 , 8 , 9 ], including those related to the 2008 Wenchuan earthquake in China [ 10 , 11 ] and the 2011 Tohoku earthquake in Japan [ 12 , 13 , 14 ]. Deformation data represented by borehole strain measurements are also considered to contribute to the estimation of crustal changes. These measurements also play an important role in analysing geodynamic processes, such as those related to volcanic activity [ 15 ], slow earthquakes [ 16 , 17 ], and moreover precursory activity [ 6 , 18 , 19 , 20 ].
Although borehole strain have been considered to record some pre-earthquake anomalies [ 8 , 9 , 21 ], whether these anomalies contain precursory information and their use in forecasting of major earthquakes were not evaluated. Receiver Operating Characteristic (ROC) analysis has previously been employed for short-term forecasting to explore whether earthquake precursor information can be obtained from geophysical observations of precursor anomalies [ 22 , 23 ]. Prediction strategies are based on an alarm model that detects and classifies the extracted anomalies extracted and targets earthquake events, thereby evaluating whether measurements contain precursory information for large earthquakes. Recently, various geophysical measurements have indicated the potential for earthquake forecasting [ 24 , 25 , 26 ], through GPS data [ 27 ] and electromagnetic measurements [ 28 , 29 , 30 , 31 ]. However, current alarm models only focus on a single anomaly and underestimate the clustering of earthquake anomalies [ 32 , 33 ], which may increase the risk of inaccurate results from short-term forecasting.
In this study, we employ complex networks to jointly investigate borehole strain observations from multiple stations, using seven YRY-4 borehole strainmeter measurements in Western China from 2010 to 2017. We then propose a new prediction strategy to test enhanced networks clustering and earthquake occurrences using ROC analysis and assess its significance related to earthquakes. Furthermore, we discuss the efficiency of the strategy under the influence of different factors. Also, by comparing with GNSS geodetic data, we found that the prediction strategy performs more significantly when there are frequent enhanced network anomalies prior to the earthquakes.
2. Data and Observations
2.1. Borehole Strain Observations
More than 40 YRY-4 borehole strainmeters have been installed in China with the aim of coordinating with satellite-based measurement systems and monitoring surface deformation associated with earthquakes. Surrounding the north and south sides of active fault zones, such as the Longmenshan fault zone and Haiyuan fault zone, we selected the following monitoring sights: YC, HY, LX, GZ, ZT, YS, and TC, all of which yield fairly good data with long-term continuity. Table 1 lists the detailed information of the seven stations, and Figure 1 shows their locations and the regional tectonic settings.
YRY-4 borehole strainmeters sample every minute with a resolution of nearly one-billionth strain changes. The strainmeters can test the quality and reliability of the observations through a self-consistency function, because of their four gauges arranged at
45
∘
intervals. Consequently, the arrangement produces four components [
21
]. In this study, the strain data were collected from 1 January 2010 to 10 August 2017, and we applied the areal strain,
S a
, which is transformed by half of the sum of the four observed components and describes the subsurface strain state [
21
].
2.2. Studied Earthquakes
In this study, we employed the
E
s
parameter, which considers the magnitude of the earthquake and the epicentral distance to identify earthquake events. The
E
s
index is the daily sum of the local earthquake energy, whereas
E
s
′
is the local energy of an earthquake in the borehole strain network defined by the following equation and the local energy of a single station is shown by the multiplier in the root sign [
28
,
34
]:
E
s
=
∑
1
d
a
y
E
s
′
(1)
E
s
′
=
∏
i
=
1
M
10
4.8
+
1.5
m
r
i
2
M
(2)
Here,
m
and
r
i
are the magnitude of the earthquake and the epicentral distance of each site, respectively, and
M
is the number of sites. We selected the earthquakes in the area
24
∘
–
39
∘
N,
98
∘
–
106
∘
E during 1 January 2010 to 10 August 2017. It should be noted that all the events occurred within the study area during the study period are shallow earthquakes (less than 60 km, mostly less than 30 km), and the earthquakes with magnitude greater than 1.0 were taken into account. To avoid repeated detection of the same process, we have declustered the earthquake catalog by the traditional Reasenberg declustering algorithm, obtained from the Zmap toolbox [
35
,
36
]. The completeness of the declustering earthquake catalog is around 1.5, and there are 162 earthquakes of
M
s
≥
4.0
, 30 earthquakes of
M
s
≥
5.0
, 9 earthquakes of
M
s
≥
5.7
and 2 earthquakes of
M
s
≥
7.0
. The local seismicity and the daily
E
s
are shown in
Figure 2
. First, we considered that an earthquake occurred if the
E
s
index on a given day exceeded
10
7
J/km
2
. There are 26 target earthquakes, and their detailed information is presented in
Table 2
. If
10
7
is converted to magnitude, when the average epicentral distance in the network is about 440 km, generally an earthquake should be greater than Ms5.0. We only listed the type of fault of an earthquake when the seismic moment tensors are available.
2.3. Tectonic Settings in Brief
The Longmenshan, the Xianshuihe and the Anninghe fault reflect the structural characteristics of the compression of the Yangtze block by the Qinghai Tibet Plateau, as shown in Figure 1 . After a long period of geological development, these three fault zones have become the primary zonal faults of Bayan Har Block, Sichuan Basin and Sichuan-Yunnan Block. The total regional stress in this area comes from the compression of the Qinghai Tibet Plateau in the northwest direction [ 37 ]. However, the fault structure in this area is diversified, because of the complex geological environments. The Longmenshan fault, which shows a thrust motion from south to north, can be divided into three main faults: the Maoxian-Wenchuan fault (southern segment), the Beichuan-Yingxiu fault (central segment) and the Anxian-Guanxian fault (northern segment) [ 38 ]. These three faults are imbricate and all dip northwestward. At the depth of 20–24 km, they converge and merge into a gently inclined reverse fault, which becomes the dominant structure of the Qinghai Tibet Plateau napping over the Sichuan Basin [ 39 , 40 ]. The southernmost end of Xianshuihe fault is the approximately north-south striking Anninghe fault, also known as the Xianshuihe-Anninghe fault zone; it is a large left-lateral strike-slip shear zone [ 39 , 41 ]. The Haiyuan fault is an important active fault zone in the northeastern border of the Qinghai Tibet Plateau, which separates the Bayan Har Block of Qinghai Tibet Plateau from the relatively stable Ordos plate. Its present movement mode is mainly left-lateral strike-slip with thrust component [ 42 ].
3. Data Analysis
3.1. Extracting Network Anomalies of Borehole Strain
Complex networks can be used as an abstraction of strain monitoring systems to express concealed interactions or relationships between spatial and temporal characteristics [
43
,
44
,
45
,
46
,
47
,
48
,
49
]. we defined a borehole strain network by a graph consisting of
M
nodes and a set of edges between nodes.
M
nodes are on behalf of
M
borehole stations, while edges are defined by significant relationship between two nodes [
50
]. An adjacency matrix is applied to describe the graph;
A
=
a
i
j
,
i
,
j
∈
V
. The correlation between the sequences of length n from two nodes,
P
=
P
i
and
Q
=
Q
j
,
i
,
j
∈
V
, is defined as
R
P
Q
=
∑
t
=
1
n
(
p
t
−
p
¯
)
(
q
t
−
q
¯
)
∑
t
=
1
n
(
p
t
−
p
¯
)
2
∑
t
=
1
n
(
q
t
−
q
¯
)
2
.
(3)
Here,
p
¯
and
q
¯
are the means of
P
and
Q
, respectively, and
P
and
Q
are the strain components of each observation site [
50
]. The adjacency matrix
A
=
a
i
j
,
i
,
j
∈
V
acquires the components that were assigned as “one” if the absolute value of
R
P
Q
was greater than 0.8, and as “zero” if
R
P
Q
was less than 0.8, indicating whether nodes
i
and
j
were connected or not connected. To monitor the changes in the borehole strain network connection, the network degree is used based on the adjacency matrix
A
. The degree
k
i
of a node is defined as the total number of edges connected to that node in a borehole strain network:
k
i
=
∑
j
=
1
M
a
i
j
.
(4)
Then, the network degree is calculated as the mean value of the
k
i
, (
i
=
1
,
…
,
M
) in the network, which is expressed as follows:
k
¯
=
1
M
∑
i
=
1
M
k
i
.
(5)
The greater the network degree, the stronger the connection between networks; otherwise, the nodes are considered to be weakly connected, indicating a disordered network. Figure 3 shows an example of the strain network result of 2017 Ms7.0 Jiuzhaigou earthquake, Sichuan. The green lines represent the connections between two stations. It is a fully connected network of that day. The red star shows the epicenter of the earthquake. The daily network degree together with the seismicity and the daily Es are shown in Figure 2 for the complete period of 2010–2017.
3.2. Evaluation of Strain Network Anomalies and Earthquake Occurrence
Due to an increase in the spatiotemporal coherence during earthquake precursory activity [
31
,
50
,
51
], we assumed that the network would be highly connected during such activities. In order to explore the correlations between strain network connection and earthquakes, we proposed a prediction model to test their relationship through a Receiver Operating Characteristic (ROC) curve. The prediction strategy is shown in
Figure 4
. We analysed how many anomalies of the strain network degree,
N
a
n
o
, are in an anomaly window,
T
a
n
o
, where the first day and last day of an anomaly window are required to be anomalous. An alarm window,
T
a
l
m
, is described as the period in which an impending earthquake would occur. First, we select a threshold to define the anomalies in the strain network degrees. An anomaly is detected when the network degree exceeds the threshold. Next, if the anomalies (
N
a
n
o
) in the alarm window (
T
a
n
o
) account for more than half (as shown in
Figure 4
, the length of the anomaly window is 6 and the number of anomalies exceeds 3), we assume that a target earthquake with
E
s
≥
10
7
will occur in the following alarm window,
T
a
l
m
.
A target earthquake is labelled as predicted if it falls in the alarm window, or as missed if it falls outside the window. The selected threshold is set to vary from the maximum to the minimum network degree. Consequently, the number of anomalies changes from 0 to the length of the sequence. As a result,
t
p
r
and
f
p
r
change from 0.0 to 1.0. Thus, the confusion matrix shown in
Figure 4
b can be used to estimate the true positive rates,
t
p
r
, and false positive rates,
f
p
r
. We set
t
p
r
=
T
P
/
(
T
P
+
F
N
)
and
f
p
r
=
F
P
/
(
F
P
+
T
N
)
[
31
,
52
].
Figure 5
shows an ROC detection result with
t
p
r
against
f
p
r
. For a given alarm rate,
t
p
r
, the probability of
n
1
predictions in
n
target earthquakes is subject to a binomial distribution [
28
]:
B
(
n
1
|
n
,
t
p
r
)
=
C
n
n
1
(
t
p
r
)
n
1
(
1
−
t
p
r
)
(
n
−
n
1
)
.
(6)
As a result, the diagonal line in the ROC diagram indicates a prediction by random guessing [
24
,
53
,
54
], and the confidence interval of the true positive rate at each alarm rate can be computed. Any prediction above the diagonal line shows that the number of predicted earthquakes is better than that of false alarm days. Next, the Area Under the Curve (AUC) is introduced to evaluate the efficiency of the prediction. The expected area of random prediction is 0.5, where an area greater than 0.5 indicates that the strain network anomalies may contain precursory earthquake information. The result in
Figure 5
shows that the prediction for
N
a
n
o
=
7
and
T
a
l
m
=
1
days is obviously better than random guess with AUC = 0.81.
4. Results
To reduce the contingency of ROC detection, we performed statistical studies based on Superposed Epoch Analysis (SEA) of the strain network during 2010–2017 preferentially. SEA is a statistical method to highlight typical features of a special event by reducing random noise by superposition [
55
,
56
,
57
]. First, if there is a network anomaly, we count one for that corresponding day for the whole dataset. Here, we set the threshold of the network degree to 4. Then, for each target earthquake, we extracted a data set of 45 days before and 30 days after its occurrence day. We repeated this procedure for the 26 target earthquakes, and then superposed the counts for all data sets. We performed the SEA results of 1-day count and 5-day counts as shown in
Figure 6
, respectively. To evaluate statistical significance, we randomly selected 26 days instead of studied earthquakes in the whole dataset, and conducted the same procedure. We repeated such random SEA tests 10,000 times to calculate the random_mean and the random standard deviation (
σ
) [
54
,
57
].
Generally, if the earthquake events and the network anomalies are not correlated, the count distribution probably is random. In other words, if the 1-day or 5-day counts exceed the random_mean+
1.5
σ
level, it is indicative of a statistically significant correlation between the earthquakes and the network anomalies. In
Figure 6
, the most anomalies occurred on the earthquake day inferring that coseismic anomalies were recorded by each station. Before an earthquake, there are clearly higher probabilities of network anomalies than after. We found, about 20 days before, the results of 1-day counts are mostly significant. The results of 5-day counts are also clearly significant during the periods 1–20 days before the earthquake. We backtracked
Figure 5
, and found when
f
p
r
was surrounding 0.1–0.2,
t
p
r
was more significant. The corresponding threshold is 3–5 at that time, which is consistent with that in the above SEA analysis results. These results highly suggested the correlation between the local earthquakes (
E
s
≥
10
7
) and strain network anomalies.
Moreover, we performed a comparative analysis with shuffled target earthquakes [
58
]. The SEA analysis and the ROC detection results are shown in
Figure 7
. The counts of network anomalies corresponding to the shuffled target earthquakes are random and not significant. And the ROC result indicates that the network anomalies do not contain precursory information, with AUC being 0.42. Therefore, the above results further suggest a possible relationship between the network anomalies and earthquakes (
E
s
≥
10
7
).
Next, their correlation was further discussed using the ROC prediction. Regarding the prediction model, there are two variables related to the efficiency of detection: the number of network anomalies in an anomaly window,
N
a
n
o
, and the length of the alarm window,
T
a
l
m
. Thus, we first repeated the detections for the earthquakes (
E
s
≥
10
7
) with different variable lengths.
N
a
n
o
and
T
a
l
m
were varied from 1 to 30 days as shown in
Figure 8
a.
We found that an optimal efficiency of predictability exists for
N
a
n
o
and
T
a
l
m
, as shown in
Figure 8
a. When there were within 20 anomalies in the anomaly window and the alarm window length was 1–25, the AUC was greater than 0.5, indicating the effectiveness of the prediction strategy. Next, we extracted the row and column of the maximum AUC (0.81), i.e.,
T
a
l
m
=
1
when
N
a
n
o
=
7
, and a detailed optimal area as shown in
Figure 8
b. The AUC value exceeded the upper boundary of the 90% confidence interval when
N
a
n
o
was between 1 and 15 and
T
a
l
m
was 1–12. Especially in
Figure 5
, the prediction of strain network is clearly better than the random prediction when
N
a
n
o
=
7
and
T
a
l
m
=
1
days. These results further suggested the statistical efficiency of short-term forecasts and indicate that the network tends to be highly connected prior to the earthquakes (
E
s
≥
10
7
).
Moreover, with regard to the prediction model in
Figure 4
, three other factors should be discussed: different
E
s
thresholds, different proportions of the anomalies in an anomaly window, and local earthquake region. In the following, we further investigate the impact of these three factors on ROC prediction efficiency. First, target earthquakes with different
E
s
values were selected, consisting of 8, 26, 75, and 184 earthquakes with
E
s
thresholds of
10
8
,
10
7
,
10
6
, and
10
5
, respectively. With fixed values of
N
a
n
o
=
7
and
T
a
l
m
=
1
, we performed ROC analysis for these different target earthquakes as shown in
Figure 9
. The detection efficiency increases when the threshold of
E
s
was
10
7
and
10
8
, with AUC values of 0.81 and 0.76, respectively. However, the ROC curves are not significant when the threshold was
10
5
and
10
6
. This illustrates the higher efficiency of ROC analysis for the earthquakes with larger energy.
Second, we tested the influence of different proportions of anomalies in an anomaly window, as shown in
Figure 10
. This test also shows the ROC curves with fixed values of
N
a
n
o
=
7
and
T
a
l
m
=
1
. We found that, when there were more than half (
2
N
) or a third (
3
N
) of network degree anomalies in an anomaly window, the detection efficiency was more significant and stable. When there were few anomalies in an anomaly window, the detection efficiency was low and especially when
T
a
n
o
=
8
N
a
n
o
, the result seems to be accidental and irregular. This result shows that clusters of anomalies indicate an increased probability of an earthquake, which is also consistent with the physical assumption [
32
].
Third, we selected the local seismicity for other two larger region, that is,
23
∘
–
40
∘
N,
97
∘
–
107
∘
E, and
22
∘
–
41
∘
N,
96
∘
–
108
∘
E, respectively. The condition of this ROC prediction is that
E
s
≥
10
7
,
N
a
n
o
≥
T
a
n
o
/
2
,
N
a
n
o
=
7
and
T
a
l
m
=
1
. The results are shown in
Figure 11
. The AUC values decrease as the detection range increases, which also indicates the network anomalies are related with local earthquakes. Earthquake selection within a larger region may bring irrelevant events, thereby increasing the missing rate. Thus, ROC prediction for earthquakes surrounding the network may be a good choice. In summary, we consider that clusters of highly connected network anomalies may contain precursory information related to local earthquakes (
E
s
5. Discussion
By using the ROC prediction, we proved that the pre-earthquake strain-network anomalies are significant, which consequently suggests a possible correlation between the borehole strain data recorded in Western China the and local earthquakes (
E
s
≥
10
7
). This research supports the understanding of pre-earthquake processes, and the fault network can be regard as a big seismogenic system in Mainland China [
59
]. In certain subsystems, multiple ‘potential sources’ appear because of fault activities and fault blocks, crustal movement and stress accumulation. The space-time evolution of the interaction between ‘potential sources’ and subsystems is considered as a self-organizing process. Regardless of the expression of the measurements, the dimensionality and disorder will decrease before reaching a new steady state [
59
]. Consequently, earthquake precursors are the dynamic behavior in the self-organizing evolution of the seismogenic system. With regard to borehole strain data, network anomalies before the target earthquakes probably indicate that the steady state started to weaken due to the crustal movements. Meanwhile, a new steady state is established through the recovery of the network after an earthquake. If we think of this self-organization process as the entropy reduction of a seismic system, then the unknown external energy that flows in may be related to impending earthquakes [
50
,
60
,
61
].
The crustal deformation before earthquakes is an important factor in integrated seismological research. To examine whether borehole strain measurements are useful crustal information before earthquakes, statistical tests were performed for the aligned GNSS-azimuths related to earthquakes with magnitudes greater than 5 during 2012–2015 in similar areas [ 24 , 62 ]. The ROC diagram of the optimal prediction strategy shows the prediction is obviously better than the random prediction, indicating the correlation between aligned GNSS-azimuths and earthquakes. Precursor patterns recorded several days before major earthquakes in the seismicity have also been found through the measurement of other remote sensing data, which may be helpful for earthquake prediction [ 63 , 64 , 65 ]. Sarlis et al. [ 64 ] used the natural time analysis to study the electric signal activity and found that changes of the order parameter appeared minima a few days before a mainshock. [ 64 ]. The statistical significance of this study has recently been verified through the ROC technique by focusing on the AUC [ 31 ] and event coincidence analysis [ 66 ].
From the 29 target earthquakes (
Table 2
), the 2013 Lushan Ms7.0 earthquake, 2014 Ms6.6 Ludian earthquake, and 2017 Ms7.0 Jiuzhaigou earthquake were the most remarkable. During the Lushan earthquake, the deformation signal was extracted by analysing the change of the GNSS geometry net-form, integrating the location, baseline length, and direction information of all GNSS stations in the seismic source area [
67
]. A significant pre-seismic deformation anomaly with locked status and deceleration in the first shear strain and direction were found in the GNSS time series, implying the occurrence of strong sinistral shear tectonic forces. Before the Ludian earthquake, the temporal evolution of the GNSS-derived orientation exhibited a unique disorder-alignment-disorder sequence that corresponded well with the four stages of an earthquake preparation [
68
]. This region of stress accumulation was generally consistent with the earthquake preparation zones estimated through numerical models [
62
]. And before the Jiuzhaigou earthquake, GNSS data were usually used to study the long-term strain accumulation of 3–8 years [
2
,
69
]. With regard to short-term anomalies, the seismo-conductivity anomalies could be observed by the geomagnetic data with epicentral distance from 63 to 385 km approximately 17 days before the earthquake, which matched the results of our predictive model. These anomalies are considered to be created by earthquake-related stress that accumulates in the crust [
70
]. Meanwhile, the rest target earthquakes with
M
s
≥
5
were also occasionally accompanied by multiple types of pre-earthquake anomalies [
71
,
72
]. The pre-earthquake anomalies of seismo-crustal deformation are also proved to contain precursory information in New Zealand, California, Japan and Taiwan [
27
,
28
,
73
].
These results suggest that surface deformation provides useful crustal displacement information before relatively large earthquakes. However, it is still far from the practical application for short-term earthquake forecasts. Since mechanisms and preparation phases of earthquake events and the time lags between anomalies and earthquakes generally are different from case to case, we were still unable to deal with accurate prediction [ 53 ]. Moreover, actual earthquake processes are more complicated than this prediction model. In future studies, we will improve the model by including additional factors combined with physical backgrounds and utilise more types of data, such as a combination of satellite and ground-based measurements.
6. Conclusions
Strainmeters provide precise observation of surface deformation that permits to capture strain anomalies related to earthquakes. However, whether these anomalies contain precursory information and their use for forecasting earthquakes were not evaluated before. In this study, we used ROC prediction to study the borehole strain data observed in Western China from 2010–2017. Initially, daily connections between multiple stations of borehole strain network were detected. The correlation between the network anomalies and local earthquakes (
E
s
≥
10
7
) was verified by Superposed Epoch Approach. Then, we proposed a new prediction strategy based on an assumption that clusters of network anomalies indicate an increased probability of an earthquake and discussed how it can be used in short-term forecasting. We further demonstrated the influences of
N
a
n
o
and
T
a
l
m
on short-term earthquake forecasting using AUC values. Furthermore, on comparing with GNSS geodetic data, the ROC prediction results indicate that the detection of borehole strain networks has a higher significance for forecasting. We found the optimal strategy for short-term forecast: that is to evaluate anomalies greater than 7 within 14 days and to set the alarm window at 1 day. After discussing three other influences on the prediction strategy, i.e., different
E
s
thresholds, different proportions of anomalies in an anomaly window, and local earthquake selection, we consider that clusters of enhanced network connections may contain precursory information related to the earthquakes (
E
s
≥
10
7
) surrounding the strain network. The methodology proposed in this study could help evaluate prediction strategies and investigate the possibility of using different measurements for short-term earthquake forecasting.
Author Contributions
Conceptualization, Z.Y., K.H. and K.Z.; methodology, Z.Y.; software, Z.Y.; validation, Z.Y., K.H. and K.Z; formal analysis, Z.Y., M.F., C.C. and X.H.; investigation, Z.Y.; resources, K.Z.; data curation, Z.Y., C.C. and K.Z.; writing—original draft preparation, Z.Y., D.M. and K.H.; writing—review and editing, Z.Y., K.H. and K.Z.; supervision, K.H., D.M. and K.Z. All authors have read and agreed to the published version of the manuscript.
Funding
This work was supported by the National Natural Science Foundation of China under Grant 41974084 (Zhu K. G.) and the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, under its observation and Research Program for Prediction of Earthquakes and Volcanic Eruptions.
Acknowledgments
The borehole strain data can be acquired at National Earthquake Precursor Network Centre ( http://qzweb.seis.ac.cn/twzx , last access: 9 October 2017). The authors would like to thank Wang X. Y., Yang D. H. and Yu H. C. from the China Earthquake Administration for giving essential help in accessing the website and downloading the strain data. The authors are also grateful to the China Earthquake Network for earthquake catalogues data ( http://data.earthquake.cn/ , last access: 13 October 2020) and the United States Geological Survey for moment tensors data ( https:www.usgs.gov/ , last access: 7 January 2021). Moreover, the authors thank Qiu Z. H. for his helpful suggestions and guidance.
Conflicts of Interest
The authors declare no conflict of interest.
References
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Figure 1.
Map showing the tectonic settings of the Western China and the locations of seven borehole strain staioins (green triangles). The thin Black curves indicate faults. The bold black curves indicate the main faults. The red circles show the epicenters of 26 earthquakes (
E
s
≥
10
7
) in the study area.
Figure 1.
Map showing the tectonic settings of the Western China and the locations of seven borehole strain staioins (green triangles). The thin Black curves indicate faults. The bold black curves indicate the main faults. The red circles show the epicenters of 26 earthquakes (
E
s
≥
10
7
) in the study area.
Figure 2.
From top to bottom are variations of the seismicity, the
E
s
parameter and daily network degree during 2010-2017, respectively. The pink horizontal line indicates
E
s
=
10
7
.
Figure 2.
From top to bottom are variations of the seismicity, the
E
s
parameter and daily network degree during 2010-2017, respectively. The pink horizontal line indicates
E
s
=
10
7
.
Figure 3. An example of the strain network result for a fully connected network on 8 August 2017, Ms7.0 Jiuzhaogou earthquake. The green lines represent the connections between two stations. The red star shows the epicenter of the earthquake.
Figure 3. An example of the strain network result for a fully connected network on 8 August 2017, Ms7.0 Jiuzhaogou earthquake. The green lines represent the connections between two stations. The red star shows the epicenter of the earthquake.
Figure 4.
(
a
) Schematic diagram of the prediction strategy of the borehole strain network. We assume that a target earthquake with
E
s
≥
10
7
will occur in an alarm window,
T
a
l
m
, if
N
a
n
o
≥
T
a
n
o
/
2
. (
b
) Confusion matrix of the prediction results.
Figure 4.
(
a
) Schematic diagram of the prediction strategy of the borehole strain network. We assume that a target earthquake with
E
s
≥
10
7
will occur in an alarm window,
T
a
l
m
, if
N
a
n
o
≥
T
a
n
o
/
2
. (
b
) Confusion matrix of the prediction results.
Figure 5.
Receiver operating characteristic (ROC) curve used to detect the relationship between the network degree and the earthquakes with
E
s
≥
10
7
. The black diagonal line shows prediction by random guessing, whereas the blue steps provide 90% confidence intervals for the random prediction. The red solid line indicates the prediction result for
N
a
n
o
=
7
and
T
a
l
m
=
1
days. For this prediction, the AUC (Area Under the ROC Curve) was 0.81.
Figure 5.
Receiver operating characteristic (ROC) curve used to detect the relationship between the network degree and the earthquakes with
E
s
≥
10
7
. The black diagonal line shows prediction by random guessing, whereas the blue steps provide 90% confidence intervals for the random prediction. The red solid line indicates the prediction result for
N
a
n
o
=
7
and
T
a
l
m
=
1
days. For this prediction, the AUC (Area Under the ROC Curve) was 0.81.
Figure 6.
The Superposed Epoch Analysis (SEA) results of strain network anomalies. The blue, the black, and the red lines indicate the counts of 1-day count, random_mean, and random_mean+
1.5
σ
, respectively. The grey bars and the pink line demonstrate 5-day counts and corresponding random_mean+
1.5
σ
. The “0 day” indicates the day when
E
s
≥
10
7
.
Figure 6.
The Superposed Epoch Analysis (SEA) results of strain network anomalies. The blue, the black, and the red lines indicate the counts of 1-day count, random_mean, and random_mean+
1.5
σ
, respectively. The grey bars and the pink line demonstrate 5-day counts and corresponding random_mean+
1.5
σ
. The “0 day” indicates the day when
E
s
≥
10
7
.
Figure 7.
(
a
) The SEA results of strain network anomalies for shuffled earthquakes with
E
s
≥
10
7
. The blue, the black, and the red lines indicate the counts of 1-day count, random_mean, and random_mean+
σ
, respectively. The grey bars and the pink line demonstrate 5-day counts and corresponding random_mean+
σ
. (
b
) The pink line shows the ROC prediction between the network degree and the shuffled earthquakes, under the condition of
N
a
n
o
=
7
and
T
a
l
m
=
1
days. The black diagonal line indicates prediction by random guessing, whereas the blue steps provide 90% confidence intervals for the random prediction. For this prediction, the AUC was 0.42.
Figure 7.
(
a
) The SEA results of strain network anomalies for shuffled earthquakes with
E
s
≥
10
7
. The blue, the black, and the red lines indicate the counts of 1-day count, random_mean, and random_mean+
σ
, respectively. The grey bars and the pink line demonstrate 5-day counts and corresponding random_mean+
σ
. (
b
) The pink line shows the ROC prediction between the network degree and the shuffled earthquakes, under the condition of
N
a
n
o
=
7
and
T
a
l
m
=
1
days. The black diagonal line indicates prediction by random guessing, whereas the blue steps provide 90% confidence intervals for the random prediction. For this prediction, the AUC was 0.42.
Figure 8.
(
a
) AUC for the condition of
E
s
≥
10
7
for different numbers in an anomaly window and different lengths of the alarm window. (
b
) Two typical AUC changes. The pink line indicates AUC changes with
N
a
n
o
when
T
a
l
m
=
1
, whereas the blue line indicates AUC changes with
T
a
l
m
when
N
a
n
o
=
7
. The horizontal line is the threshold, which is the AUC of the upper boundary of the 90% confidence interval for random prediction. The AUC of the upper boundary curve is 0.64.
Figure 8.
(
a
) AUC for the condition of
E
s
≥
10
7
for different numbers in an anomaly window and different lengths of the alarm window. (
b
) Two typical AUC changes. The pink line indicates AUC changes with
N
a
n
o
when
T
a
l
m
=
1
, whereas the blue line indicates AUC changes with
T
a
l
m
when
N
a
n
o
=
7
. The horizontal line is the threshold, which is the AUC of the upper boundary of the 90% confidence interval for random prediction. The AUC of the upper boundary curve is 0.64.
Figure 9.
ROC prediction of earthquake events selected according to different
E
s
values.
Figure 9.
ROC prediction of earthquake events selected according to different
E
s
values.
Figure 10.
ROC prediction of different proportions of
N
a
n
o
to
T
a
n
o
.
Figure 10.
ROC prediction of different proportions of
N
a
n
o
to
T
a
n
o
.
Figure 11.
ROC prediction of different earthquake selection regions. Region A:
24
∘
–
39
∘
N,
98
∘
–
106
∘
E, Region B:
23
∘
–
40
∘
N,
97
∘
–
107
∘
E and Region C:
22
∘
–
41
∘
N,
96
∘
–
108
∘
E.
Figure 11.
ROC prediction of different earthquake selection regions. Region A:
24
∘
–
39
∘
N,
98
∘
E.
Table 1. Specifications of borehole strain stations used in this study.
Table 1. Specifications of borehole strain stations used in this study.
Station Name Locations Depth (m) YC 38.61°N, 105.61°E 50.00 HY 36.51°N, 105.93°E 60.37 LX 35.60°N, 103.20°E 44.70 GZ 30.11°N, 102.17°E 41.00 ZT 27.32°N, 103.73°E 45.00 YS 26.69°N, 100.76°E 43.00 TC 25.02°N, 98.54°E 45.00
Table 2.
List of earthquakes with
E
s
≥
10
7
in the study area.
Table 2.
List of earthquakes with
E
s
7
in the study area.
No. Date a Locations Depth (km) Magnitude ( Ms ) b Es (lg) Type of Fault 1 25 February 2010 25.42°N, 101.94°E 20 5.2 7.1 right-lateral strike-slip 2 10 April 2011 31.28°N, 100.80°E 10 5.4 7.4 left-lateral strike-slip 3 20 June 2011 25.05°N, 98.69°E 10 5.3 7.4 4 9 August 2011 25.00°N, 98.70°E 11 5.2 7.3 5 1 November 2011 32.60°N, 105.30°E 6 5.2 7.1 reverse 6 24 June 2012 27.71°N, 100.69°E 11 5.7 8.0 normal 7 7 September 2012 27.51°N, 103.97°E 14 5.7 8.3 strike-slip 8 18 January 2013 30.95°N, 99.40°E 15 5.5 7.4 left-lateral strike-slip 9 19 February 2013 27.10°N, 103.10°E 10 4.9 7.1 10 3 March 2013 25.93°N, 99.72°E 9 5.5 7.6 normal 11 17 April 2013 25.90°N, 99.75°E 10 5.1 7.0 12 20 April 2013 30.30°N, 102.90°E 17 7.0 10.0 reverse 13 22 July 2013 34.54°N, 104.21°E 15 6.7 9.4 reverse 14 31 August 2013 28.15°N, 99.35°E 10 5.9 8.2 normal 15 20 September 2013 37.73°N, 101.53°E 15 5.3 7.1 16 5 April 2014 28.14°N, 103.57°E 13 5.1 7.1 17 3 August 2014 27.11°N, 103.33°E 10 6.6 9.4 left-lateral strike-slip 18 17 August 2014 28.12°N, 103.51°E 7 5.2 7.3 19 1 October 2014 28.38°N, 102.74°E 10 5.2 7.3 20 22 November 2014 30.29°N, 101.68°E 20 6.4 9.1 strike-slip 21 12 October 2015 34.36°N, 98.20°E 10 5.3 7.0 22 21 January 2016 37.66°N, 101.65°E 10 6.4 8.7 reverse 23 18 May 2016 26.08°N, 99.58°E 17 5.1 7.1 24 23 September 2016 30.11°N, 99.61°E 16 5.2 7.4 25 27 March 2017 25.89°N, 99.80°E 12 5.1 7.2 26 8 August 2017 33.20°N, 103.82°E 10 7.0 9.8 left-lateral strike-slip a The date refers to UTC+8 time. b M s is the largest magnitude on one day.
| https://www.mdpi.com/2072-4292/13/3/515/xml |
Materials | Free Full-Text | Modelling the Thermal Energy Storage of Cementitious Mortars Made with PCM-Recycled Brick Aggregates
This paper reports a numerical approach for modelling the thermal behavior and heat accumulation/liberation of sustainable cementitious composites made with Recycled Brick Aggregates (RBAs) employed as carriers for Phase-Change Materials (PCMs). In the framework of the further development of the fixed grid modelling method, classically employed for solving the well-known Stefan problem, an enthalpy-based approach and an apparent calorific capacity method have been proposed and validated. More specifically, the results of an experimental program, following an advanced incorporation and immobilization technique, developed at the Institut für Werkstoffe im Bauwesen for investigating the thermal responses of various combinations of PCM-RBAs, have been considered as the benchmark to calibrate/validate the numerical results. Promising numerical results have been obtained, and temperature simulations showed good agreement with the experimental data of the analyzed mixtures.
Modelling the Thermal Energy Storage of Cementitious Mortars Made with PCM-Recycled Brick Aggregates
Christoph Mankel 1 ,
Antonio Caggiano 1,2,* ,
Andreas König 3 ,
Diego Said Schicchi 1 ,
Mona Nazari Sam 1 and
Institut für Werkstoffe im Bauwesen, Technische Universität Darmstadt, Franziska-Braun-Straße 3, 64287 Darmstadt, Germany
2
CONICET, LMNI, INTECIN, Facultad de Ingeniería, Universidad de Buenos Aires, C1053 Buenos Aires, Argentina
3
Department of Prosthodontics and Dental Materials Science, Leipzig University, 04109 Leipzig, Germany
*
Author to whom correspondence should be addressed.
Materials 2020 , 13 (5), 1064; https://doi.org/10.3390/ma13051064
Received: 8 January 2020 / Revised: 14 February 2020 / Accepted: 17 February 2020 / Published: 27 February 2020
(This article belongs to the Special Issue Energy in Construction and Building Materials )
Abstract
This paper reports a numerical approach for modelling the thermal behavior and heat accumulation/liberation of sustainable cementitious composites made with Recycled Brick Aggregates (RBAs) employed as carriers for Phase-Change Materials (PCMs). In the framework of the further development of the fixed grid modelling method, classically employed for solving the well-known Stefan problem, an enthalpy-based approach and an apparent calorific capacity method have been proposed and validated. More specifically, the results of an experimental program, following an advanced incorporation and immobilization technique, developed at the
Institut für Werkstoffe im Bauwesen
for investigating the thermal responses of various combinations of PCM-RBAs, have been considered as the benchmark to calibrate/validate the numerical results. Promising numerical results have been obtained, and temperature simulations showed good agreement with the experimental data of the analyzed mixtures.
Keywords:
thermal-energy storage
;
enthalpy method
;
apparent calorific capacity method
;
recycled brick aggregates
;
meso-scale
;
;
paraffin waxes
;
1. Introduction
The energy demand for heating and cooling the global building stock represents a massive part of the total energy consumption around the world (≈ 40%) [ 1 ]. In the EU, it accounts for about half of all energy consumption [ 2 ]. To attenuate this number, thermal efficiency of construction and building elements, like walls, roofs, and floors, has become the most important measure to enhance energy savings of the new and existing building stock. Recently, with the introduction of the 2019/2021 EU Buildings Directive, it has been additionally emphasized that new buildings of the EU-Member States have to be designed as “Nearly-Zero-Energy Buildings” from the beginning of 2021 onward [ 3 ]. For public non-residential buildings, this obligation should become active in 2019 and will be permanently anchored in future building legislation. Moreover, the German Energy Saving Regulation (EnEV) 2014 has proclaimed 25% stricter requirements for energy savings in their 2016 issue, which affects the set of most important regulations of new and existing German buildings. These regulations define the maximum annual primary energy demand and the maximum permissible loss of transmission heat through the building envelope, on the basis of a reference building. In order to comply with the European targets on energy savings, the German federal government will merge the rules that currently apply in parallel—(i) the Energy Saving Act (EnEG) [ 4 ], (ii) the Energy Saving Regulation (EnEV) [ 5 ], and (iii) the Renewable Energy Heat Act (EEWärmeG) [ 6 ]—into a new Building Energy Act (GEG) [ 7 ].
Possible innovative solutions include the potential of materials to embody large amounts of thermal energy, which would stabilize the inner thermal comfort of either residential or non-residential buildings. Particularly, this can be achieved through an effective use of Phase Change Materials (PCMs), which minimizes the additional need of primary energy for heating/cooling [ 8 , 9 ]. Numerous articles on PCMs have been reported in literature and in several fields of applications. The experimental-based research is predominantly addressing the thermo-hydro-chemo-mechanical properties of cementitious materials with PCMs [ 10 , 11 , 12 ]. In those works, the investigated PCMs are characterized by a melting temperature that varies between 19 °C and 26 °C, which corresponds to a standard temperature range for comfortable living [ 13 ]. According to their chemical compositions, PCMs can be categorized as organic, inorganic and eutectics [ 14 ], while according to their phase transition mode as liquid–gas, solid–gas, solid–liquid, and solid–solid. Solid–liquid is the most preferred mode for energy and building applications [ 15 , 16 ].
A large number of review studies are already available in literature, which are very helpful for understanding the State of the Art (SoA) of the current research, and also to evaluate the potential directions for future investigations. In a very recent review paper, performed at TU-Darmstadt [
17
], the authors reviewed the various numerical tools that are used for modelling phase change phenomena in problems of materials science and engineering. The available modelling strategies for PCM-based cementitious composites, at different scale levels (micro-, meso-, macro-, and multiscale [
18
]), have been deeply explored, evaluated and discussed.
Numerical tools and theoretical approaches, available in scientific literature for modelling Thermal Energy Storage (TES) and heat accumulation/liberation of PCM-based applications, deal with solving the so-called Stefan problem [ 19 ] or an extended version of it. The Stefan problem assumes the existence of two different domains, one representing the solid phase ( Ω S ) and another representing the liquid phase ( Ω L ). These are separated by a sharp front, identified as a moving interface ( Γ ), which is the location where the phase transformation takes place. Such sharp surface front is characterized by a temperature field that equals the melting temperature T m . Several authors, under simplified assumptions (like 1D conduction-only heat problem in both the solid and liquid phase), have proposed analytical solutions for this problem [ 20 ]. While, more complex models can be taken into account for further evaluation of the classical Stefan problem: e.g., by introducing a so-called “mushy zone” representing non-isothermal conditions and dealing with a finite thickness of this moving interface zone, where the liquid and solid phases may coexist [ 21 ]. The solution method of the Stefan problem and/or its extended formulation, can generally be subdivided into three different categories [ 22 ]: (i) the fixed grid method, where the grid of spatial nodes, used for discretizing the problem, remains fixed during time, thus the phase change is traced through auxiliary constitutive formulations and state functions; (ii) the deformed grid method, where the nodes forming the grid may move to explicitly follow the moving sharp front that occurs during the melting and/or solidification; (iii) and hybrid methods, which are a combination of (i) and (ii). Most classical examples are those based on a further development of the fixed grid method through following the enthalpy-based approach (EA) [ 23 ], which mainly boils down into two alternative solutions: (i) the apparent calorific capacity method (ACCM) [ 24 ] and (ii) the heat source method (HSM) [ 25 ].
In this context, the present study investigated the TES of mortars made of Recycled Brick Aggregates containing PCMs. The main scope was to assess a numerical procedure for simulating the effects of paraffin waxes on the thermal energy responses of mortars produced with different types and amounts of PCM-RBAs. The results of a wide series of thermal tests [
26
] (DSC measurements, thermal conductivity and special spherical tests, labelled DKK—
Dynamische Kugel Kalorimetrie
), carried out on PCM, aggregates, plain mortars, and PCM-RBA mortars are summarized. The aforementioned experimental results are employed in an inverse identification procedure for unveiling the key parameters that drive the TES of the mixtures.
Following this short introductive literature review, the paper is structured as follows. Section 2 addresses the enthalpy-based model and the ACCM resolution of it, employed for simulating the phase transformation phenomena of the PCM-RBA mortars. Experimental results, outlined in terms of TES results, are shown in Section 3 . Section 4 outlines the spherical-based solution and numerical implementation of the model procedure described in Section 2 . In Section 5 , numerical results and comparisons against the experimental data are reported and discussed to demonstrate the soundness and capability of the numerical procedure. Concluding remarks and future research outlook are addressed in Section 6 .
2. The Enthalpy-Based Model and Apparent Calorific Capacity
This section reports the enthalpy-based model that will be employed for predicting the phase transformation phenomena of PCM-RBA mortars.
2.1. Basic Principles: Thermodynamics and Thermal Energy Storages
The enthalpy
H
of a thermodynamic system can be defined as
H = U + p V
(1)
with
U
the internal energy,
p
the pressure and
V
the volume of the system.
Then, by introducing the first law of thermodynamics, for closed systems and an infinitesimal process, the following equation can be stated as
d U = δ Q − δ W
(2)
i.e., the variation of the internal system energy (
dU
) is equal to an infinitesimal amount of heat added (
δ Q
) minus an infinitesimal amount of work performed (
δ W
).
Under the hypothesis that only p and V spend work (quasi-static process), δ W = p d V .
It follows that
d U = δ Q − p d V .
(3)
Now, by evaluating
dH
from Equation (1) and using Equation (3), the following equation will be achieved:
d H = d U + d ( p V ) = d U + d p V + p d V = δ Q − p d V + d p V + p d V = δ Q + d p V .
(4)
For a constant pressure, which represents most cases of PCM-concrete systems of construction and building applications, it can be assumed that a small variation of enthalpy is equal to a small amount of heat added:
d H = δ Q .
(5)
2.2. Enthalpy Description and Apparent Calorific Capacity Method (ACCM)
In accordance with the fixed grid modelling method and with its discretization through the ACCM approach (see reference [
17
]), the classical equation for describing a heat conduction problem can written as follows:
∂ Q ∂ t = ∇ . ( λ ∇ T ) + q ˙ v ∀ x ∈ Ω
(6)
where
Q
is the heat of the system,
t
the time,
λ = λ ( T , x )
the thermal conductivity of the material, which depends on the temperature
T
and position vector
x
(of the considered body
Ω
),
q ˙ v
is the possible source term, while
∇ .
and
∇
are the divergence and gradient tensorial operators.
Substituting Equation (5) into Equation (6) leads to the following equation:
∂ H ∂ t = ∇ . ( λ ∇ T ) + q ˙ v ∀ x ∈ Ω
(7)
which is the mostly adopted equation for solving phase changes in simulations for construction and building applications, and it is known in literature as the enthalpy-based method.
Applying the chain rule to
∂ H ∂ t
of Equation (7),
∂ H ∂ t = ∂ H ∂ T ∂ T ∂ t
(8)
and by introducing the concept of the Apparent Calorific Capacity Method (ACCM), the following temperature-dependent (apparent of effective) heat capacity expression can be written [
17
]:
∂ H ∂ T = ρ C e f f ( T )
(9)
Thus, Equation (7) modifies into the following heat transfer equation.
ρ C e f f ( T ) d T d t = ∇ . ( λ ∇ T ) + q ˙ v ∀ x ∈ Ω
(10)
Finally, the following initial condition (IC) and boundary conditions (BCs) complete the description of the phase change problem:
IC : T ( x , t = 0 ) = T 0 ( x ) ∀ x ∈ Ω
(11)
BCs : T ( x , t ) = T D ∀ x ∈ Γ T ( λ ∇ T ) ⋅ n = q ∀ x ∈ Γ q ( λ ∇ T ) ⋅ n = h ( T e n v − T ) ∀ x ∈ Γ c ( λ ∇ T ) ⋅ n = κ ( T r a d − T ) ∀ x ∈ Γ r
(12)
where
Γ T , Γ q , Γ c and Γ r
are the essential and natural (flux, convection and radiation) boundary conditions of the domain
Ω
.
T D
is the specified temperature imposed at the essential boundary,
q
the heat flux,
h
the heat convection and
κ
the radiation coefficients, respectively,
T e n v
the environmental temperature, and, finally,
T rad
the external radiation source temperature.
3. Overview of the Experimental Test Data
This section reports the results of an experimental program performed for characterizing the thermal-energy response of PCM-RBA mortar mixtures and their components. The experimental data are used for validation of the numerical simulations discussed in Section 5 .
Six mixtures were considered, having a w/c ratio of 0.5 and various amounts of PCM-RBA volume fractions ( Table 1 ). All mixtures were prepared according to EN 196-1 [ 27 ]. Recycled bricks (labelled “SB”) and high porosity Poroton® fired-clay blocks (labelled “PB”) have been considered [ 28 ]. These building materials, processed in the form of medium/coarse aggregates and provided by a local company (SHW GmbH, Messel, Germany), were used as carriers (containers) for storing a predefined volume of PCM.
Table 1. Overview of the six PCM-RBA mortars.
RT 25 HC [
29
] paraffin waxes were used as PCM. They are characterized by a high crystallinity and possess an excellent heat store capacity during phase changes, from solid to liquid and vice versa. The thermo-physical properties of the paraffin wax, considered in this research, are a melting temperature of 25 °C, a storage capacity of approximately 230 kJ/kg, a latent heat capacity of almost 200 kJ/kg, thermal conductivity (in both phases) of 0.20 W/m × K, and densities of 880 (liquid)/770 (solid) kg/m³. The PCM-RBAs were thus produced following an advanced encapsulation technique, proposed and patented by the
Institut für Werkstoffe im Bauwesen
of TU-Darmstadt (Darmstadt, Germany) [
30
].
The mixture names (labels) in Table 1 aim at providing the key information on the amount of PCM, filling the RBA’s open porosity (expressed in volume fraction of the open capillary pore space), and the type of RBAs considered in the mixture. For example, the label ‘‘REF-SB’’ refers to the reference mixture (without PCM) using SB type of bricks; or “SB-65” indicates a mixture using SB-bricks and a filling degree of PCM of 65 V.-% of the total SB-RBA open capillary porosity. The complete description (materials, methods, results and discussion) of the experimental campaign is available in Mankel et al. [ 28 ].
3.1. DSC Measurements: Aggregates, Paste, and PCMs
Differential Scanning Calorimetry (DSC) tests were performed for each component used in the investigated PCM-RBA mortar mixtures. Their heat storage capacity has been expressed in terms of bulk density times the specific heat capacity, i.e. ρ × C
p
. Three samples per each component were analyzed and the mean value for each of them was presented in this section. Particularly, the DSC thermograms under either heating or cooling, for the cement paste with a w/c of 0.50 and for both SB- and PB-RBAs, have been shown in
Figure 1
a. They were done within the temperature range of 10 °C to 40 °C and using a heating/cooling rate of 10 K × min
−1
. From these results, it can be observed that the sensible behavior of both RBAs is almost similar, whereby a slightly higher sensible heat storage capacity can be detected for the cement paste.
Figure 1. ρ × C p results of DSC measurements of ( a ) w/c = 0.50 cement pastes, SB and PB obtained with a heating/cooling rate of 10 K × min −1 and ( b ) Paraffin RT25HC with a heating/cooling rate of 0.25 K × min −1 .
In Figure 1 b, the DSC results of the used paraffin wax (Rubitherm® RT25HC, Rubitherm Technologies GmbH, Berlin, Germany) is shown. The test procedure was conducted in accordance with the IEA DSC 4229 PCM Standard [ 31 ] to determine the final heating/cooling rate for the considered dynamic DSC measurements. The adopted heating/cooling rate was 0.25 K × min −1 on the final measured results. This value represented a compromise between accuracy of the results and acceptable mitigation of heating rate measurements, fulfilling the IEA DSC 4229 requirements [ 31 ].
DSC curves of the considered PCM, in Figure 1 b, shows a sensible heat storage character of the material in those temperature ranges, far from the phase change responses (e.g., in the solid and liquid stages), and shows a pronounced latent peak in the region close to the temperature where the phase change occurs (T m = 24.5 °C for heating and T m = 22.95 °C for cooling).
3.2. Thermal Conductivity of the PCM-RBA Mortars
The thermal conductivity of PCM-RBA mortar mixtures was determined using the Hot-Disk transient plane source method [
28
]. For this aim, three samples of 150 mm × 150 mm × 80 mm cuboids were tested. The measurements were done with a 9.9 mm diameter sensor, in three different specimen sides. Steady-state conditions with a temperature of 20 °C were considered. In
Figure 2
, it can be observed that all mixtures have quite comparable thermal conductivities, which range between 0.696 (min. value) and 0.846 (max. value) W/mK. As a general trend, it can be observed that the mixtures with PB RBAs deal with slightly lower conductivities than the SB RBA ones. This can be attributed to the higher porosity of the SB RBAs, which affect the overall conductivity of the composites. It could also be observed that for higher PCM contents, the thermal conductivity is lower.
Figure 2. Thermal conductivity of the SB- and PB-RBA mortars, with and without PCMs.
Moreover, it can be also observed that the thermal conductivities are only slightly affected by the different PCM volume fractions. A little increase of the thermal conductivity was measured for those mixtures with a higher pore filling ratio (i.e. PB-80 in comparison with PB-65). This could be the result of the allocation of paraffin wax into the capillary pore space of the composites, which leads to a slight increase in heat conductivity of the PCM-RBAs since the considered PCMs are more conductive than air. However, it can finally be concluded that immobilizing PCMs into the RBA porous structure does basically not (e.g. SB-80 vs. SB-65), or only slightly (see, PB-80 vs. PB-65), modify the overall thermal conductivity of RBA mortars.
3.3. Thermal-Energy Storage DKK Tests in Spherical Samples
Spherical-shaped specimens were used to monitor the time-dependent temperature evolution of the PCM-RBA mortars. The adopted and patented non-conventional testing technique (namely
Dynamische Kugel Kalorimetrie
), DKK [
26
]) was followed by the authors for the TES identification of the composite materials under investigation. For each considered mixture, three spherical samples were produced, and two thermocouples were positioned in the center of each sphere and at its outer surface, respectively. Heating tests were done by using an isothermal conditioned oven with a fixed temperature of 49 °C. Cooling tests were done with a climatic chamber fixing the temperature at ca. 9 °C.
The graphs of
Figure 3
show the average results (from three independent spherical specimens) of the measured temperature evolution, in the center of the spherical samples, versus time. Heating and cooling results are plotted for both PCM SB-brick and PB-brick mixtures. It can be seen that, for the mortar mixtures casted with either SB or PB bricks, a delay of the temperature development takes place when PCM-RBAs, with PCM filling degrees of 65 V.-% and 80 V.-%, are analyzed. The presence of PCM and their melting/solidification behavior actually shifts the temperature curve into the right/down direction for heating response (
Figure 3
a,c) and up/left for cooling (
Figure 3
b,d). Particularly, a quasi-horizontal plateau of the temperature evolution data can be appreciated during both temperature rise (heating) or temperature decrease (cooling), i.e. in the range between 21 and 26 °C the PCM and vice versa. By taking into consideration the effect of PCM volume fractions, it appeared that almost no thermal differences between the considered RBAs and PCM additions, i.e., 65 and 80%, exist. Comparison of the temperature evolutions SB-65 with SB-80 or PB-65 with PB-80 show an almost equal response. For each mixture and/or sample, the complete phase change of the paraffin was always fully occurring, meaning that all PCMs were in their final state at the end of each heating or cooling test. This is also shown in
Figure 3
where the center of the spheres at the end of each cooling test has a temperature less than 10 °C and under heating close to 50 °C, while the melting points range between 21–26 °C.
Figure 3. Temperature evolutions of the DKK tests: ( a ) heating and ( b ) cooling of PCM-RBA mortars with SB bricks, ( c ) heating and ( d ) cooling of PCM-RBA mortars with PB bricks. These results represent the average of three measurements in the center of the spherical samples.
For a thorough discussion on the present experimental data, with emphasis on the DSC analyses, conductivity measurements and DKK tests, reference is made to Mankel et al. 2019 [ 28 ].
4. Numerical Implementation and Spherical-based Solution
4.1. D Spherical-Based Solution for the ACCM
Equation (10) is now transferred into spherical coordinates for predicting the thermal energy storage behavior and temperature evolution in the tested specimens presented in Section 3.3 .
From this, the following relation can be derived:
ρ C e f f ( T ) d T d t = 1 r 2 ∂ ∂ r ( λ r 2 ∂ T ∂ r ) + 1 r 2 sin 2 θ ∂ ∂ ϕ ( λ ∂ T ∂ ϕ ) + 1 r 2 sin θ ∂ ∂ θ ( λ sin θ ∂ T ∂ θ ) + q ˙ v
(13)
where
( r , θ , ϕ )
are the radial distance and polar and azimuthal angles. Making use of the spherical symmetry, the previous relationship can be significantly simplified as follows:
ρ C e f f ( T ) d T d t = 1 r 2 ∂ ∂ r ( λ r 2 ∂ T ∂ r ) + q ˙ v .
(14)
4.2. Schematization and Discretization
The ACCM model, under the assumptions of spherical geometry and symmetry, was solved by means of the finite difference method. The heat-diffusion through the PCM-RBA mortar systems was calculated by solving the differential equation previously described in Equation (14), having a 1D spherical-based hypothesis and by adopting heat convection (Robin) boundary conditions for describing the environmental surface conditions of either a furnace or a climate chamber.
Thus, the boundary condition for the sample core at node “1” ( Figure 4 ) was adiabatic, meaning that the heat flux, q 1 , is null.
Figure 4. ( a ) Finite difference (FD) space discretization scheme of a 1D-heat transfer in spherical specimens; ( b ) FD molecule for implicit time using the Backward Euler Method and the Space Central Method.
Sample core : q 1 = − λ ( ∂ T ∂ r ) | r = 0 = 0
(15)
while the Robin boundary condition is applied at the outer surface (node “
n s
”)
Ambient condition : q n s = − λ ( ∂ T ∂ r ) | r = R = h ( T f − T r )
(16)
where
T f
is the ambient temperature (fixed by the oven or climatic chamber),
T r
is the surface temperature at
r = R
, while
h
is the heat transfer coefficient.
In this context, the Finite Difference (FD) space domain was discretized into
n s
spaces (namely Finite Differences), leading to
n s
+ 1 nodes and
n t
time discretization steps. Furthermore, a fully implicit Euler Method for the transient problem was applied.
The differential equation shown in Equation (14), within a space domain with a length of R between the node 1 to
n s
(see
Figure 4
a), can be solved as shown in the following scheme:
ρ C e f f ( T ) d T d t = 2 λ r ∂ T ∂ r + λ ∂ 2 T ∂ r 2 with r = ( i − 1 ) Δ r
(17)
By using the implicit backward Euler Method for time (
j
) and central for space (
i
) (see
Figure 4
b), Equation (17) can be discretized to
ρ C e f f ( T i j + 1 ) T i j + 1 − T i j Δ t = λ T i + 1 j + 1 − T i − 1 j + 1 ( i − 1 ) Δ r 2 + λ T i − 1 j + 1 + 2 T i j + 1 + T i + 1 j + 1 Δ r 2 .
(18)
The boundary condition, for the sample core at
r = 0
(
i
= 1), has been further developed. The right-hand side of Equation (17) can be simplified as follows [
32
]
lim r → 0 ( 2 λ r ∂ T ∂ r + λ ∂ 2 T ∂ r 2 ) = 3 λ ∂ 2 T ∂ r 2
(19)
Then, by adopting the central difference approximation of the adiabatic boundary condition expressed of Equation (15) and by using one ghost node (namely node “0”), the following expression can be stated:
− λ ( ∂ T ∂ r ) | r = 0 = − λ T 2 j + 1 − T 0 j + 1 2 Δ r = 0
(20)
It follows that
T 2 j + 1 = T 0 j + 1
and combining it into Equations (18) and (19), it can be easily achieved the following expression of the adiabatic boundary condition:
ρ C e f f ( T 1 j + 1 ) T 1 j + 1 − T 1 j Δ t = 6 λ T 2 j + 1 + T 1 j + 1 Δ r 2
(21)
For the implementation of the Robin boundary condition at the outer surface of the specimens, e.g. node
r = R
(
i = n
s
), Equation (15) can be discretized in the following way:
− λ T n s − 1 j + 1 − T n s + 1 j + 1 2 Δ r = h ( T f j + 1 − T r j + 1 )
(22)
In Equation (22), the temperature at the ghost node
r = R
+ 1 (
i = n s
+ 1) is known,
T n s + 1 j + 1 = T f
, thus the following expression can be rewritten:
T n s + 1 j + 1 = 2 Δ r h λ ( T n s j + 1 − T f j + 1 ) + T n s − 1 j + 1
(23)
Thus, Equation (16) can be easily written as
ρ C e f f ( T n s j + 1 ) T n s j + 1 − T n s j Δ t = λ ( 2 Δ r h λ ( T n s j + 1 − T f j + 1 ) + T n s − 1 j + 1 ) − T n s − 1 j + 1 ( i − 1 ) Δ r 2 + λ T n s − 1 j + 1 + 2 T n s j + 1 ( 2 Δ r h λ ( T n s j + 1 − T f j + 1 ) + T n s − 1 j + 1 ) Δ r 2
and after some mathematical elaborations, the following expression can be achieved for the Robin natural boundary condition:
ρ C e f f ( T n s j + 1 ) T n s j + 1 − T n s j Δ t = 2 [ h ( T n s j + 1 − T f j + 1 ( i − 1 ) Δ r + T n s j + 1 − T f j + 1 Δ r ) + λ ( T n s − 1 j + 1 + T n s j + 1 Δ r 2 ) ]
(25)
5. Numerical Results and Comparisons
This section reports the description of the numerical results and shows their comparisons against the experimental data, which has been briefly outlined in Section 3 . The numerical simulations are based on the assumption that the PCM-RBA mortars can be considered as a continuum and homogenous media. In this context, homogenized (meso-scale based) parameters were considered in the selection of the input data for the numerical prediction.
5.1. Homogenized Macroscopic C eff Model for the PCM-RBA Mixtures
A homogenization technique was employed for evaluating the effective specific heat capacity
C eff
of the PCM-RBA mortars. It is based on the mixture theory by using the volume percentages of each individual component such as RBAs, cement paste and PCMs. More precisely, the model smears out the specific heat capacity of the RBA
C RBA (T)
, cement paste
C paste (T)
and the apparent specific heat capacity of the PCM
C app,PCM (T)
through adopting the volume fraction of each component as the smeared out (weighting) factor
χ
.
The specific heat capacities of each component were experimentally determined with DSC measurements (see Section 3.1 ) and are shortly summarized in Table 2 .
Table 2. Overview of the six PCM-RBA mortars.
RBAs and cement pastes have only the sensible heat storage part ( Figure 1 a), while the PCMs have an apparent specific heat capacity C app,PCM (T) that incorporates the additional latent behavior within the temperature range of the phase change (during melting and solidification, as shown in Figure 1 b).
The evaluation of the specific heat capacities was determined in two consecutive steps. First, at aggregate level, where the PCM-RBAs were considered as lumped components of RBAs (
C RBA (T)
) plus PCM (
C app,PCM (T)
) and weighting their volume fractions χ to achieve the smeared
C eff,PCM-RBA (T):
PCM-RBAs : C e f f , P C M − R B A ( T ) = χ R B A × C R B A ( T ) + χ P C M × C a p p , P C M ( T )
(26)
where
χ RBA
and
χ PCM
are the volume fraction of the recycled bricks and the filled PCMs, respectively.
Then, at a composite level (i.e., PCM-RBA mortar) a homogenized overall system of the effective specific heat capacity,
C eff
, was determined by weighting the heat capacities
C eff,PCM-RBA (θ)
, evaluated through Equation (26), and
C paste (θ)
of the individual material components by their volume fractions
ψ:
PCM-RBA mixtures : C e f f ( T ) = ψ p a s t e × C p a s t e ( T ) + ψ P C M − R B A × C e f f , P C M − R B A ( T )
(27)
The exact volume fraction ratio between PCM-RBAs and cement paste, of the investigated mixtures, were investigated by performing μ3D-XCT-scans [
33
] of the spherical specimens. Nine 2D-slices were extracted from each 3D body of the scanned spherical specimens (
Figure 5
) and mean volume fractions of PCM-RBAs and cement paste were accurately determined by image analyses. An average area ratio was evaluated for each slice by applying a recoloring of the surface area through white and red pictures (
Figure 5
). The results of these analyses are shown in
Figure 6
where the volume fractions of paste and PCM-RBA were determined in both PCM.RBA mortars SB and PB.
Figure 5. μ3D-XCT-scans setup ( a , b ) and slices cross including image-segmentation ( c , d ) of the spherical specimens.
Figure 6. Volume fractions of paste and PCM-RBA determined by image-analysis.
The effective specific heat capacity of the composite systems, C eff (T) , were thus modelled using Equations (26) and (27) by taking into account the determined volume fractions between cement paste (including air voids) and PCM-RBAs (shown in Figure 6 ) and considering the specific heat capacities of each component as summarized in Table 2 .
Figure 7 and Figure 8 shows the afore described C eff (T) further multiplied by the bulk density ρ of the PCM-RBA mortar systems ( ρ = 1829.6 kg/m³ for REF-SB, 1710.37 kg/m³ for SB-65, 1671.6 kg/m³ for SB-80, 1853.5 kg/m³ for REF-PB, 1767.25 kg/m³ for PB-65 and 1739.8 kg/m³ for PB-80).
Figure 7. ρ × Ceff of PCM-RBA mortar systems with SB bricks: ( a ) heating and ( b ) cooling.
Figure 8. ρ × Ceff of PCM-RBA mortar systems with PB bricks: ( a ) heating and ( b ) cooling.
5.2. Numerical Prediction and Comparison
By implementing the ACCM procedure described in Section 2 and Section 4 , temperature evolutions were simulated and compared with the experimental data reported in Section 3 . More in detail, the spherical samples made of RBA mortars (with and without PCMs) were simulated with the proposed heat flow model. The input values were obtained from the conducted experimental measurements, as well as from the C eff (T) curves described in Section 5.1 . All input parameters employed in the aforementioned simulations are summarized in Table 3 and Table 4 .
Table 3. Overview of the numerical parameters assumed for the SB mixtures.
Table 4. Overview of the numerical parameters assumed for the PB mixtures.
The thermal conductivities were assumed as temperature-independent and measured through Hot-Disk tests, as outlined in Section 3.2 . Then, the effective specific heat capacity C eff (T) was modelled by using the homogenized model as described before in this section. The number of FD space discretization was chosen 100 while the number of time steps selected was 1000, in all simulations. Moreover, the calibrated Robin heat transfer coefficient (h), representing the heat transfer conditioning coefficient was the same for each mixture and reported in Table 3 and Table 4 .
The numerical simulations, based on the input parameters above mentioned, have been compared against the experimental data of Section 3.3 . In Figure 9 , the six graphs show the temperature evolutions for the control mixtures ( Figure 9 a,b), and for that one having PCM: i.e., SB-65 ( Figure 9 c), SB-80 ( Figure 9 e), PB-65 ( Figure 9 d), and PB-80 ( Figure 9 f). The experimental scatter of the result data for each mixture have been also plotted in grey.
Figure 9. Experimental “DKK” vs. numerical results: ( a , c , e ) SB brick type mixtures and ( b , d , f ) PB brick type mixtures.
It can be observed that the modeling approach was able to simulate the experimental temperature evolutions very accurately. In particular, the simulations of the reference mixtures represented in
Figure 9
a,b show a very good agreement with the experimental results. Then, the simulations of the mixtures TES enhanced with PCM also show good comparisons and trends as the experimental values. A slightly overestimated latent effect can be observed, which results in a slightly amplified shoulder in the temperature evolution (see
Figure 9
c–f). A reason for this effect can be attributed to micro- and/or meso-structural effect, which can influence the effective thermal conductivity and the melting/solidification activations of the integrated PCMs. This could lead to a slight deviation of the latent effects.
In this context, it may be important to remark that almost all input parameters were chosen from the characterizations of the thermal tests as well as from the homogenized C
eff
model, which is actually represented by the experimentally determined heat capacities of the individual material components weighted by their volume fractions (see
Section 5.1
). Thus, with this set of input parameters, a sound numerical prediction, for all six PCM-RBA mortar systems, could be achieved, without the need of applying re-calibration and/or optimizations. The results also show that, with a unique heat transfer coefficient, described as the
h
(Robin) parameter, the simulations for the reference PCM-RBA mortar systems, REF-SB and REF-PB, are almost in perfect agreement with the corresponding experiments. This supports the assumption that both the spherical symmetry and the hypothesis that the composite PCM-RBA mortar systems could be considered by a homogeneous medium, were both effectively correct.
6. Conclusions
Based on the results shown in this paper, the following conclusions can be drawn:
An enthalpy-based model, formulated for spherical coordinates and symmetry, was proposed for predicting the thermal energy storage in the tested PCM-RBA specimens.
Thermal measurements, obtained from dynamic DSC and steady-state Hot Disk tests, were employed for calibrating the model of the numerical activities.
A mixture theory, based on volume fractions deduced from 3D micro μX-ray computer tomography measurements, was used for generating the resulting meso-composite thermal parameters adopted in the numerical analysis. Particularly the C eff (T) curves have been based on this approach.
The numerical simulations for the temperature evolution, compared with the experimental DKK results, showed accurate and consistent agreement. It may be important to highlight that these numerical results were just based on input parameters obtained from the experimental characterizations of the mortar components.
No fitting adjustments, re-calibrations, or numerical adaptions were necessary for reaching good agreement between numerical to experimental data. This can confirm that on the one hand the experimental activities were performed in an accurate way, and on the other hand, that the numerical assumptions and procedures are very accurate to model TES responses in cementitious materials.
Future numerical developments, which follow this research, will include micro-to-meso scale analysis taking into considerations local effects like inclusions (PCM-RBAs), air bubbles, porosity, and interface effects. These further steps will lead to optimizing the “best” recipe for achieving the most performing energy-saving and sustainable cementitious composite.
Author Contributions
Conceptualization, C.M. and A.C.; methodology: materials, methods and processing C.M., A.K. and M.N.S.; data curation, C.M. and A.C.; numerical simulations and comparisons, C.M., A.C. and D.S.S.; writing—original draft preparation, C.M. and A.C.; writing—review and editing, everybody; supervision, A.C. and E.K.; project administration, E.K.; funding acquisition, E.K. All authors have read and agreed to the published version of the manuscript.
Funding
The second author acknowledge the Alexander von Humboldt-Foundation ( www.humboldt-foundation.de/ ) for funding his position at the WiB – TU Darmstadt under the research grant ITA-1185040-HFST-P (2CENERGY project). The support to networking activities provided by the PoroPCM Project (part of the EIG CONCERT-Japan funding, http://concert-japan.eu/ ) is also gratefully acknowledged.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. ρ × C p results of DSC measurements of ( a ) w/c = 0.50 cement pastes, SB and PB obtained with a heating/cooling rate of 10 K × min −1 and ( b ) Paraffin RT25HC with a heating/cooling rate of 0.25 K × min −1 .
Figure 2. Thermal conductivity of the SB- and PB-RBA mortars, with and without PCMs.
Figure 3. Temperature evolutions of the DKK tests: ( a ) heating and ( b ) cooling of PCM-RBA mortars with SB bricks, ( c ) heating and ( d ) cooling of PCM-RBA mortars with PB bricks. These results represent the average of three measurements in the center of the spherical samples.
Figure 4. ( a ) Finite difference (FD) space discretization scheme of a 1D-heat transfer in spherical specimens; ( b ) FD molecule for implicit time using the Backward Euler Method and the Space Central Method.
Figure 5. μ3D-XCT-scans setup ( a , b ) and slices cross including image-segmentation ( c , d ) of the spherical specimens.
Figure 6. Volume fractions of paste and PCM-RBA determined by image-analysis.
Figure 7. ρ × Ceff of PCM-RBA mortar systems with SB bricks: ( a ) heating and ( b ) cooling.
Figure 8. ρ × Ceff of PCM-RBA mortar systems with PB bricks: ( a ) heating and ( b ) cooling.
Figure 9. Experimental “DKK” vs. numerical results: ( a , c , e ) SB brick type mixtures and ( b , d , f ) PB brick type mixtures.
Table 1. Overview of the six PCM-RBA mortars.
Labels REF-SB SB-65 SB-80 REF-PB PB-65 PB-80 Cement [kg/m 3 ] 701.5 694.2 692.9 700.2 691.7 691.7 Water [kg/m 3 ] 350.8 347.1 346.5 350.1 345.9 345.9 PCM-RBA [kg/m 3 ] 655.2 719.3 734.0 664.0 728.9 743.9 Air cont. [V.-%] 2.3 2.9 3.0 2.4 3.1 3.1 w/c ratio [-] 0.50
Table 2. Overview of the six PCM-RBA mortars.
Cement Paste RBA PCM C paste Solid phase C RBA Solid phase C app,PCM Liquid phase Phase change Solid phase Figure 1 a Figure 1 a Figure 1 b
Table 3. Overview of the numerical parameters assumed for the SB mixtures.
Numerical Parameters REF-SB SB-65 SB-80 ρ C eff (J cm −3 K −1 ) Figure 7 λ (W/m K) ( Figure 2 ) 0.846 0.768 0.768 h (W m −2 K −1 ) 25.0
Table 4. Overview of the numerical parameters assumed for the PB mixtures.
Numerical Parameters REF-PB PB-65 PB-80 ρ C eff (J cm −3 K −1 ) Figure 8 λ (W/m K) ( Figure 2 ) 0.712 0.696 0.725 h (W m −2 K −1 ) 25.0
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/ ).
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Constance Tom Noguchi's research works | National Institutes of Health, MD (NIH) and other places
Constance Tom Noguchi's 261 research works with 10,276 citations and 13,719 reads, including: Vascular P-Selectin Modulation of Microvascular Flow in a Mouse Model of Sickle Cell Disease
while affiliated with University of California, San Francisco
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Publications (261)
Vascular P-Selectin Modulation of Microvascular Flow in a Mouse Model of Sickle Cell Disease
Article
May 2023
N.M. Matsui S. Ramanujam C.K. Seto [...] Stephen Embury
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Neuronal nitric oxide synthase is required for erythropoietin stimulated erythropoiesis in mice
Article Full-text available
Feb 2023
Jeeyoung Lee Soumyadeep Dey
Praveen K. Rajvanshi [...] Constance T. Noguchi
Introduction: Erythropoietin (EPO), produced in the kidney in a hypoxia responsive manner, is required for red blood cell production. In non-erythroid tissue, EPO increases endothelial cell production of nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) that regulates vascular tone to improve oxygen delivery. This contributes to EPO ca...
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1402-P: Endogenous Erythropoietin Is Protective in Mice during High-Fat Diet to Obesity and Cardiac Function while Exogenous Erythropoietin Exacerbates Cardiac Function
Article
Jun 2022
JEEYOUNG LEE HEATHER ROGERS
CONSTANCE T. NOGUCHI
Endogenous Erythropoietin (EPO) provides protection against obesity and heart function. Mice with EPO receptor restricted to erythroid tissue (ΔEPORE mice) become obese, glucose intolerant and insulin resistant. In male mice at 4 months of age, after three weeks of high fat diet feeding, ΔEPORE mice showed an increase in fat mass from to 13 grams c...
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238-LB: Erythropoietin Receptor–Mediated Erythropoietin Regulation of Energy Metabolism in Mice
Article
Jun 2022
WEIQIN YIN HEATHER ROGERS
PRAVEEN K. RAJVANSHI [...] CONSTANCE T. NOGUCHI
EPO receptor (EPOR) expression in white adipose tissue (WAT) mediates EPO metabolic activity and mitochondrial biogenesis. Mice that lack EPOR in adipose tissue have increase fat mass accumulation, increased susceptibility to diet induced obesity and decreased WAT mitochondrial activity. Here we assess the potential for EPO to promote a metabolic r...
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Erythropoietin Non-hematopoietic Tissue Response and Regulation of Metabolism During Diet Induced Obesity
Article Full-text available
Sep 2021
Soumyadeep Dey Jeeyoung Lee
Constance T. Noguchi
Erythropoietin (EPO) receptor (EPOR) determines EPO response. High level EPOR on erythroid progenitor cells gives rise to EPO regulated production of red blood cells. Animal models provide evidence for EPO activity in non-hematopoietic tissue mediated by EPOR expression. Beyond erythropoiesis, EPO activity includes neuroprotection in brain ischemia...
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1203-P: High-Dose Erythropoietin and Cardiac Function in Mice
Article
Jun 2021
JEEYOUNG LEE CONSTANCE T. NOGUCHI
Erythropoietin (EPO) is the cytokine required for erythropoiesis. EPO stimulated increase in hematocrit elevates blood viscosity that may cause hemodynamic risks in the cardiovascular system, promote ischemic heart disease, and stroke. Herein, we studied the physiological effect of high dose exogenous EPO (i.p. 3000 U/kg, 3 times/week for three wee...
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218-LB: Age, Sex, and Fat Mass Affects Erythropoietin Metabolic Response in Mice
Article
Jun 2021
HEATHER ROGERS CONSTANCE T. NOGUCHI
Erythropoietin (EPO) is required for erythrocyte production. However, EPO receptor (EpoR) extends beyond erythroid tissue and ΔEpoR mice with EpoR restricted to hematopoietic tissue show an increase in fat mass. At 3 months of age, ΔEpoR mice show no difference in body weight compared with wild type (WT, C57BL/6) mice. By 6 months of age, male body...
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Erythropoietin treatment and the risk of hip fractures in hemodialysis patients
Article Full-text available
Apr 2021
Sukanya Suresh Elizabeth C. Wright
Daniel G. Wright [...] Constance T. Noguchi
Erythropoietin (EPO) is the primary regulator of bone marrow erythropoiesis. Mouse models have provided evidence that EPO also promotes bone remodeling and that EPO‐stimulated erythropoiesis is accompanied by bone loss independent of increased red blood cell production. EPO has been used clinically for three decades to treat anemia in end‐stage ren...
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+2
Oxygen in Red Blood Cell Concentrates: Influence of Donors' Characteristics and Blood Processing
Article Full-text available
Dec 2020
Alan Schechter David Wood
Constance Tom Noguchi [...] Tatsuro Yoshida
Objective: Unexpectedly wide distribution (<10 to >90%) of hemoglobin oxygen saturation (sO 2 ) within red cell concentrates (RCCs) has recently been observed. Causes of such variability are not yet completely explained whereas the roles of oxygen and oxidative lesions during the storage of RCCs are known. The objectives of the present study are to...
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Commentary on Winzeler et al ‘Low arginine vasopressin levels in patients with diabetes insipidus are not associated with anaemia’
Article
Dec 2020
Balázs Mayer Krisztian Nemeth
Miklós Krepuska [...] Eva Mezey
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Erythropoietin reduces fat mass in female mice lacking estrogen receptor alpha
Article Full-text available
Dec 2020
Jeeyoung Lee Mary F. Walter
Kenneth S Korach Constance Tom Noguchi
Objective
Erythropoietin (EPO), the cytokine required for erythropoiesis, contributes to metabolic regulation of fat mass and glycemic control. EPO treatment in mice on high fat diet (HFD) improved glucose tolerance and decreased body weight gain via reduced fat mass in males and ovariectomized females. The decreased fat accumulation with EPO treat...
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Effects of Erythropoietin in White Adipose Tissue and Bone Microenvironment
Article Full-text available
Nov 2020
Sukanya Suresh Jeeyoung Lee
Constance Tom Noguchi
Erythropoietin (EPO) is expressed primarily in fetal liver and adult kidney to stimulate red blood cell production. Erythropoietin receptor expression is not restricted to erythroid progenitor cells, and non-erythroid EPO activity includes immune response and bone remodeling. In bone fracture models, EPO administration promotes bone formation and a...
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Erythropoietin regulates metabolic response in mice via receptor expression in adipose tissue, brain and bone
Article
Sep 2020
Constance Tom Noguchi
Erythropoietin (EPO) acts by binding to erythroid progenitor cells to regulate red blood cell production. While EPO receptor (Epor) expression is highest on erythroid tissue, animal models demonstrate EPO activity in non-hematopoietic tissues is mediated, in part, via tissue specific Epor expression. This review describes the metabolic response in...
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Erythropoietin signaling in osteoblasts is required for normal bone formation and for bone loss during erythropoietin‐stimulated erythropoiesis
Article
Jul 2020
Sukanya Suresh Jeeyoung Lee
Constance T. Noguchi
Erythropoietin (EPO) regulates erythropoiesis by binding to erythropoietin receptor (Epor) on erythroid progenitor cells. Epor is also expressed on bone forming osteoblasts and bone loss accompanies EPO‐stimulated erythropoiesis in mice. Mice with Epor restricted to erythroid tissue exhibit reduced bone and increased marrow adipocytes; in contrast,...
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1950-P: Fat Mass Affects Metabolic Response to Erythropoietin in Mice
Article
Jun 2020
HEATHER ROGERS CONSTANCE T. NOGUCHI
Erythropoietin (EPO) is required for erythrocyte production. However, EPO receptor (EpoR) expression extends beyond erythroid tissue. To assess EPO activity on glucose homeostasis and fat mass accumulation, wild type (WT, C57BL/6) mice, ΔEpoRE mice with EpoR restricted to hematopoietic tissue and ΔEpoRWAT mice with targeted EpoR deletion in fat tis...
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1939-P: Sex Dimorphism in Erythropoietin Regulation of Fat Mass
Article
Jun 2020
JEEYOUNG LEE HEATHER ROGERS
CONSTANCE T. NOGUCHI
Erythropoietin (EPO), the cytokine required for erythropoiesis, contributes to metabolic regulation of fat mass and glycemic control. In male mice and ovariectomized female mice on high fat diet (HFD), EPO treatment increased hematocrit, improved glucose tolerance and attenuated body weight gain via reduced fat mass. Estradiol supplementation abrog...
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+1
Erythropoietin-Induced Changes in Bone and Bone Marrow in Mouse Models of Diet-Induced Obesity
Article Full-text available
Feb 2020
Sukanya Suresh Josue Caban Alvarez
Soumyadeep Dey Constance Tom Noguchi
Obesity remodels bone and increases bone marrow adipocytes (BMAT), which negatively regulate hematopoiesis and bone. Reduced BMAT could restore altered hematopoiesis and bone features. We analyzed the potential of erythropoietin (EPO), the cytokine required for erythropoiesis, to inhibit BMAT in C57BL6/J mice fed four weeks of a high-fat diet (HFD)...
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Sex-specific brain erythropoietin regulation of mouse metabolism and hypothalamic inflammation
Article
Feb 2020
Soumyadeep Dey Zhenzhong Cui
Oksana Gavrilova [...] Constance T. Noguchi
The blood hormone erythropoietin (EPO), upon binding to its receptor (EpoR), modulates high fat-diet (HFD)-induced obesity in mice, improves glucose tolerance, and prevents white adipose tissue inflammation. Transgenic mice with constitutive over-expression of human EPO solely in brain (Tg21) were used to assess the neuro-endocrine EPO effect witho...
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The Many Facets of Erythropoietin Physiologic and Metabolic Response
Article Full-text available
Jan 2020
Sukanya Suresh Praveen Kumarn Rajvanshi Constance T. Noguchi
In mammals, erythropoietin (EPO), produced in the kidney, is essential for bone marrow erythropoiesis, and hypoxia induction of EPO production provides for the important erythropoietic response to ischemic stress, such as during blood loss and at high altitude. Erythropoietin acts by binding to its cell surface receptor which is expressed at the hi...
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Erythropoietin modulates bone marrow stromal cell differentiation
Article Full-text available
Dec 2019
Sukanya Suresh Luis Fernández De Castro Soumyadeep Dey [...]
Constance Tom Noguchi
Erythropoietin is essential for bone marrow erythropoiesis and erythropoietin receptor on non-erythroid cells including bone marrow stromal cells suggests systemic effects of erythropoietin. Tg6 mice with chronic erythropoietin overexpression have a high hematocrit, reduced trabecular and cortical bone and bone marrow adipocytes, and decreased bone...
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Neutropenia in Myelosuppressed Cancer Patients Treated with Recombinant Human Erythropoietin (EPO)
Article
Nov 2019
Daniel G. Wright Elizabeth C. Wright
Constance Tom Noguchi
Recombinant human erythropoietin (EPO) has been used extensively for 3 decades to treat various forms of anemia, including anemia associated with cancer treatment. Multiple randomized, placebo controlled clinical trials conducted since the late 1980's found that EPO treatment ameliorated anemia, reduced transfusion requirements, and improved qualit...
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UFMylation of RPL26 links translocation-associated quality control to endoplasmic reticulum protein homeostasis
Article
Oct 2019
Lihui Wang Yue Xu Heather Rogers [...] Yihong Ye
Protein biogenesis at the endoplasmic reticulum (ER) in eukaryotic cells is monitored by a protein quality control system named ER-associated protein degradation (ERAD). While there has been substantial progress in understanding how ERAD eliminates defective polypeptides generated from erroneous folding, how cells remove nascent chains stalled in t...
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UFMylation of RPL26 links translocation-associated quality control to endoplasmic reticulum protein homeostasis
Article Full-text available
Oct 2019
Lihui Wang Yue Xu Heather Rogers [...] Yihong Ye
Protein biogenesis at the endoplasmic reticulum (ER) in eukaryotic cells is monitored by a protein quality control system named ER-associated protein degradation (ERAD). While there has been substantial progress in understanding how ERAD eliminates defective polypeptides generated from erroneous folding, how cells remove nascent chains stalled in t...
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1997-P: Cross Talk between EPO and Estrogen Signaling in Regulation of Fat Mass
Article
Jun 2019
JEEYOUNG LEE HEATHER ROGERS
CONSTANCE T. NOGUCHI
Erythropoietin (EPO), the cytokine that regulates erythropoiesis, contributes to metabolic regulation in rodents. The increase in red blood cell production with EPO treatment in mice was accompanied by improved glycemic control, and by attenuated body weight gain via reducing fat mass in male mice. No change in body weight was observed in mice with...
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2007-P: Age-Dependent Metabolic Response to Erythropoietin in Mice
Article
Jun 2019
HEATHER ROGERS CONSTANCE T. NOGUCHI
Erythropoietin (EPO), the cytokine required for erythrocyte production, regulates glucose homeostasis and fat mass accumulation in animal models. For example, young (5-6 weeks) mice on high fat diet (HFD) treated with EPO for 5 weeks show a dose dependent increase in hematocrit and reduction in fat mass accumulation/weight gain. To assess potential...
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Compensatory mechanisms in myoglobin deficient mice preserve NO homeostasis
Article
Jun 2019
Ji Won Park Barbora Piknova
Soumyadeep Dey [...] Alan Schechter
The mechanism for nitric oxide (NO) generation from reduction of nitrate (NO3-) and nitrite (NO2-) has gained increasing attention due to the potential beneficial effects of NO in cardiovascular diseases and exercise performance. We have previously shown in rodents that skeletal muscle is the major nitrate reservoir in the body and that exercise en...
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IL-6 stimulation of DNA replication is JAK1/2 mediated in cross-talk with hyperactivated ERK1/2 signaling: IL6 stimulation of JAK1/2 in MPN
Article
Dec 2018
Tijana Subotički Olivera Mitrović Ajtić
Bojana B Beleslin-Cokic [...] Vladan P Cokic
Myeloproliferative neoplasms (MPNs) are developing resistance to therapy by JAK1/2 inhibitor ruxolitinib. To explore the mechanism of ruxolitinib's limited effect, we examined the JAK1/2 mediated induction of proliferation related ERK1/2 and AKT signaling by proinflammatory interleukin‐6 (IL‐6) in MPN granulocytes and JAK2V617F mutated human erythr...
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Inhibiting Glycogen Synthase Kinase 3 Reverses Obesity-Induced White Adipose Tissue Inflammation by Regulating Apoptosis Inhibitor of Macrophage/CD5L-Mediated Macrophage Migration
Article
Jul 2018
Li Wang Yuan Wang Chao Zhang
[...] Lijun Di
Objective:
Obesity-induced inflammation in white adipose tissue, characterized by increased macrophage infiltration and associated with macrophage population shift from anti-inflammatory M2 to proinflammatory M1 macrophages, largely contributes to obesity-induced insulin resistance and influences type 2 diabetes mellitus pathogenesis. GSK3 (glycog...
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The Metabolic Effect of Chronic Elevated Erythropoietin in Tg6 Mice
Article
May 2018
HEATHER ROGERS OKSANA GAVRILOVA CONSTANCE T. NOGUCHI
Erythropoietin (EPO) is the cytokine required for erythrocyte production. However, EPO receptor (EpoR) expression is not restricted to erythroid tissue and non-hematopoietic EPO action has been associated with the regulation of glucose homeostasis and fat mass accumulation in animal models. The hemizygous transgenic tg6 mouse (PDGF- promoter/human...
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Gender-Dependent EPO Action in Adipose Tissue
Article
May 2018
JEEYOUNG LEE CONSTANCE T. NOGUCHI
Erythropoietin (EPO) is a glycoprotein that stimulates the production of red blood cells. Recent studies have shown the nonerythroid effect of EPO involved in metabolic regulation. EPO treatment attenuated body weight gain in male mice on normal chow, high fat diet induced obese mice and ob/ob mice. EPO regulation of body weight is concomitant with...
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Vasopressin stimulates the proliferation and differentiation of red blood cell precursors and improves recovery from anemia
Article Full-text available
Nov 2017
Balázs Mayer Krisztian Nemeth
Miklós Krepuska [...] Eva Mezey
Arginine vasopressin (AVP) made by hypothalamic neurons is released into the circulation to stimulate water resorption by the kidneys and restore water balance after blood loss. Patients who lack this antidiuretic hormone suffer from central diabetes insipidus. We observed that many of these patients were anemic and asked whether AVP might play a r...
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Erythropoietin and Hypothalamic–Pituitary Axis
Chapter
Mar 2017
Soumyadeep Dey Constance T. Noguchi
Erythropoietin (EPO), known primarily for its erythropoietic activity, is commonly used clinically to treat anemia of chronic kidney disease. However, the expression of EPO receptor (EpoR) beyond erythroid tissue provides for potential extrahematopoietic effects of EPO, including EPO regulation of metabolic homeostasis ( Zhang et al., 2014 ). Small...
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Sex difference in mouse metabolic response to erythropoietin
Article
Mar 2017
Yuanyuan Zhang Heather M. Rogers
Xiaojie Zhang Constance Tom Noguchi
Erythropoietin (EPO) is the cytokine that regulates red blood cell production. Less understood is the nonerythroid action of EPO, including metabolic regulation of fat accumulation and glucose homeostasis. Although EPO treatment increased hematocrit and improved glucose tolerance in male and female mice, we observed a gender difference in EPO effec...
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Metabolic Burden of Erythropoietin Stimulated Erythropoiesis in Mice
Article
Dec 2016
Constance Tom Noguchi Heather Marie Rogers
Erythropoietin (EPO) promotes erythroid differentiation and increases glucose uptake in erythroid progenitor cells in culture. The metabolic burden associated with EPO treatment in adult mice is suggested by a decrease in body weight concomitant with increased hematocrit. Wild type male mice (C57Bl/6, age 8 months) treated with EPO showed the expec...
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Angiogenic factors are increased in circulating granulocytes and CD34(+) cells of myeloproliferative neoplasms
Article
Jun 2016
Tijana Subotički Olivera Mitrović Ajtić
Bojana B Beleslin-Cokic [...] Vladan P Cokic
It has been shown that angiogenesis and inflammation play an important role in development of most hematological malignancies including the myeloproliferative neoplasm (MPN). The aim of this study was to investigate and correlate the levels of key angiogenic molecules such as hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor...
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Non-hematopoietic effects of endogenous erythropoietin on lean mass and body weight regulation: Erythropoietin and Body Weight in Men and Women
Article
May 2016
Martin Reinhardt Soumyadeep Dey
Constance Tom Noguchi [...] Marie S. Thearle
Objective:
To investigate the concurrent relationships between human plasma erythropoietin concentrations and energy expenditure (EE), body composition, plasma leptin concentrations, and associations with weight change.
Methods:
Plasma to measure erythropoietin and leptin; data for body composition; 24-h EE measured in a whole-room calorimeter;...
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Erythropoietin regulates POMC expression via STAT3 and potentiates leptin response
Article
Nov 2015
Soumyadeep Dey Xiaoxia Li
Ruifeng Teng [...] Constance Tom Noguchi
The arcuate-nucleus of the hypothalamus is essential for metabolic-homeostasis and responds to leptin by producing several neuropeptides including proopiomelanocortin (POMC). We previously reported that high-dose erythropoietin (Epo)-treatment in mice while increasing hematocrit, reduced body-weight, fat-mass, and food intake, and increased energy-...
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Association of Erythropoietin Dose and Route of Administration with Clinical Outcomes for Patients on Hemodialysis in the United States
Article
Sep 2015
Daniel G Wright Elizabeth C Wright
Andrew S Narva [...] Paul W Eggers
Background and objectives:
Recombinant human erythropoietin (epoetin) is used routinely to increase blood hemoglobin levels in patients with ESRD and anemia. Although lower doses of epoetin are required to achieve equivalent hemoglobin responses when administered subcutaneously rather than intravenously, standard practice has been to administer ep...
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+4
Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway
Article Full-text available
Aug 2015
Vladan P Cokic Pascal Mossuz Jing Han [...] Alan Schechter
The gene and protein expression profiles in myeloproliferative neoplasms (MPNs) may reveal gene and protein markers of a potential clinical relevance in diagnosis, treatment and prediction of response to therapy. Using cDNA microarray analysis of 25,100 unique genes, we studied the gene expression profile of CD34+ cells and granulocytes obtained fr...
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Erythropoietin and Metabolic Response
Article
Aug 2015
Constance Tom Noguchi Yuanyuan Zhang Heather M Rogers [...]
Mawadda Alnaeeli
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Erythropoietin negatively regulates pituitary ACTH secretion
Article Full-text available
Mar 2015
Soumyadeep Dey Tyler Scullen
Constance Tom Noguchi
Erythropoietin (Epo) and Epo-receptor (EpoR) signaling, in addition to its classical role in erythropoiesis, exhibit a protective response in non-hematopoietic tissues. Mice with EpoR expression restricted to only hematopoietic tissues (ΔEpoRE), become obese, have low energy expenditure, and are glucose intolerant and insulin resistant. In the arcu...
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Skeletal Muscle as an Endogenous Nitrate Reservoir
Article Full-text available
Feb 2015
Barbora Piknova Ji Won Park
Kathryn M Swanson [...] Alan Schechter
The nitric oxide synthase (NOS) family of enzymes form nitric oxide (NO) from arginine in the presence of oxygen. At reduced oxygen availability NO is also generated from nitrate in a two step process by bacterial and mammalian molybdopterin proteins, and also directly from nitrite by a variety of five-coordinated ferrous hemoproteins. The mammalia...
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Erythropoietin's inhibiting impact on hepcidin expression occurs indirectly
Article Full-text available
Dec 2014
Elena Gammella Victor Diaz
Stefania Recalcati [...] Gaetano Cairo
Under conditions of accelerated erythropoiesis, elevated erythropoietin (Epo) levels are associated to inhibition of hepcidin synthesis, a response that ultimately increases iron availability to meet the enhanced iron needs of erythropoietic cells. In the search for erythroid regulators of hepcidin many candidates have been proposed, including Epo...
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Erythropoietin and obesity-induced white adipose tissue inflammation: Redefining the boundaries of the immunometabolism territory
Article
Dec 2014
Mawadda Alnaeeli Constance Tom Noguchi
The adipose tissue represents a critical and predominant site for the interaction between metabolic and inflammatory responses during health and disease. In the white adipose tissue microenvironment, macrophages/adipocytes cross-talk have been shown to influence the metabolic and inflammatory states of both cell types, and contribute to the develop...
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Erythropoietin, a Novel Versatile Player Regulating Energy Metabolism beyond the Erythroid System
Article Full-text available
Aug 2014
Li Wang Lijun Di Constance Tom Noguchi
Erythropoietin (EPO), the required cytokine for promoting the proliferation and differentiation of erythroid cells to stimulate erythropoiesis, has been reported to act as a pleiotropic cytokine beyond hematopoietic system. The various activities of EPO are determined by the widespread distribution of its cell surface EPO receptor (EpoR) in multipl...
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AMPK is Involved in Mediation of Erythropoietin Influence on Metabolic Activity and Reactive Oxygen Species Production in White Adipocytes
Article
Jun 2014
Li Wang Lijun Di Constance Tom Noguchi
Erythropoietin, discovered for its indispensable role during erythropoiesis, has been used in the therapy for selected red blood cell disorders in erythropoietin-deficient patients. The biological activities of erythropoietin have been found to extend to non-erythroid tissues due to the expression of erythropoietin receptor. We previously demonstra...
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Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Kruppel-like factor
Article Full-text available
Jun 2014
Xunde Wang Laurel Mendelsohn
Heather M Rogers [...] Gregory James Kato
In adults with sickle cell disease (SCD), markers of iron burden are associated with excessive production of the angiogenic protein placenta growth factor (PlGF) and high estimated pulmonary artery pressure. Enforced PlGF expression in mice stimulates production of the potent vasoconstrictor endothelin-1, producing pulmonary hypertension. We now de...
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Erythropoietin Action in Stress Response, Tissue Maintenance and Metabolism
Article Full-text available
Jun 2014
Yuanyuan Zhang Li Wang
Soumyadeep Dey [...] Constance Tom Noguchi
Erythropoietin (EPO) regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia for two and half decades and has facilitated studies of EPO action. Re...
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Erythropoietin Signaling: A Novel Regulator of White Adipose Tissue Inflammation During Diet-Induced Obesity
Article Full-text available
Mar 2014
Mawadda Alnaeeli Bruce M Raaka
Oksana Gavrilova [...] Constance Tom Noguchi
Obesity-induced white adipose tissue (WAT) inflammation and insulin resistance are associated with macrophage (Mô) infiltration and phenotypic shift from "anti-inflammatory" M2-like to predominantly "pro-inflammatory" M1-like cells. Erythropoietin (EPO), a glycoprotein hormone indispensable for erythropoiesis, has biological activities that extend...
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Nitric oxide and hypoxia stimulate erythropoietin receptor via MAPK kinase in endothelial cells
Article Full-text available
Mar 2014
Bojana B Beleslin-Cokic Vladan P Cokic Sukanya Suresh [...]
Constance Tom Noguchi
Erythropoietin receptor (EPOR) expression level determines the extent of erythropoietin (EPO) response. Previously we showed that EPOR expression in endothelial cells is increased at low oxygen tension and that EPO stimulation of endothelial cells during hypoxia can increase endothelial nitric oxide (NO) synthase (eNOS) expression and activation as...
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Supplementary Data
Data
Nov 2013
Li Wang Ruifeng Teng Lijun Di
[...] Constance Tom Noguchi
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Placenta Growth Factor Is Regulated By Heme-Bound Iron Via Erythroid Krüppel-Like Factor In Erythroid Cells and Is Linked To Iron Status In Vivo In Sickle Cell Disease and Hereditary Hemochromatosis
Article
Nov 2013
Xunde Wang Laurel G. Mendelsohn
Heather Marie Rogers [...] Gregory James Kato
Iron is a critical element for erythroid development and the function of many proteins, but is toxic in excessive amounts, most often by inducing oxidative stress that may play a role in vasculopathy. We have shown that markers of high iron burden such as serum ferritin have been associated with excessive production of the angiogenic factor placent...
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Erythropoietin Increases Erythropoiesis, Metabolism and Weight Loss In Mice
Article
Nov 2013
Constance Tom Noguchi Heather Marie Rogers Li Wang Ruifeng Teng
Erythropoietin is required for erythroid progenitor cell survival, proliferation and differentiation. Increasing evidence suggests that erythropoietin treatment in mice can stimulate erythropoiesis and also affect metabolic processes in a dose dependent manner. For example, medium to high dose erythropoietin treatment (600 U/kg or 3000 U/kg) in lep...
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PPAR and Sirt1 Mediate Erythropoietin Action in Increasing Metabolic Activity and Browning of White Adipocytes to Protect Against Obesity and Metabolic Disorders
Article Full-text available
Aug 2013
Li Wang Ruifeng Teng Lijun Di
[...] Constance Tom Noguchi
Erythropoietin (EPO) has shown beneficial effects in the regulation of obesity and metabolic syndrome. However, detailed mechanism is still largely unknown. Here, we created the mice with adipocyte specific deletion of EPO receptor (EpoR). These mice exhibited obesity and decreased glucose tolerance and insulin sensitivity especially on high fat di...
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+3
Erythropoietin contributes to slow oxidative muscle fiber specification via PGC-1α and AMPK activation
Article Full-text available
Mar 2013
Li Wang Yi Jia Heather M Rogers
[...] Constance Tom Noguchi
Erythropoietin activity, required for erythropoiesis, is not restricted to the erythroid lineage. In light of reports on the metabolic effects of erythropoietin, we examined the effect of erythropoietin signaling on skeletal muscle fiber type development. Skeletal muscles that are rich in slow twitch fibers are associated with increased mitochondri...
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+2
Globin gene expression in correlation with G protein-related genes during erythroid differentiation
Article Full-text available
Feb 2013
Vladan P Oki Reginald D Smith
Angélique Biancotto [...] Alan Schechter
Background
The guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs) regulate cell growth, proliferation and differentiation. G proteins are also implicated in erythroid differentiation, and some of them are expressed principally in hematopoietic cells. GPCRs-linked NO/cGMP and p38 MAPK signaling pathways already demonstrated pot...
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+1
Effect of Blood Nitrite and Nitrate Levels on Murine Platelet Function
Article Full-text available
Feb 2013
Ji Won Park Barbora Piknova Paul Huang [...] Alan N Schechter
Nitric oxide (NO) appears to play an important role in the regulation of thrombosis and hemostasis by inhibiting platelet function. The discovery of NO generation by reduction of nitrite (NO(2) (-)) and nitrate (NO(3) (-)) in mammals has led to increased attention to these anions with respect to potential beneficial effects in cardiovascular diseas...
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Nitric oxide and hypoxia stimulate and regulate erythropoietin receptor in endothelial cells
Article
Oct 2012
Bojana B Beleslin-Cokic Vladan P Cokic Constance T. Noguchi
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Metabolic activity associated with erythropoietin
Article
Oct 2012
Constance Tom Noguchi Ruifeng Teng
Mawadda AlNaeeli
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+2
Acetylation of Histone Deacetylase 1 Regulates NuRD Corepressor Complex Activity
Article Full-text available
Sep 2012
Tao Yang Wei Jian Yi Luo [...]
Yi Qiu
Background:
HDAC1-containing NuRD complex is required for GATA-1-mediated repression and activation.
Results:
GATA-1 associated with acetylated HDAC1-containing NuRD complex, which has no deacetylase activity, for gene activation.
Conclusion:
Acetylated HDAC1 converts NuRD complex from a repressor to an activator during GATA-1-directed erythro...
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+1
T-cell Acute Leukemia 1 (TAL1) Regulation of Erythropoietin Receptor and Association with Excessive Erythrocytosis
Article Full-text available
Sep 2012
Heather M Rogers Li Wang
Xiaobing Yu [...] Constance Tom Noguchi
During erythropoiesis, erythropoietin stimulates induction of erythroid transcription factors that activate expression of
erythroid genes including the erythropoietin receptor (EPO-R) that results in increased sensitivity to erythropoietin. DNA binding of the basic helix-loop-helix transcription factor,
TAL1/SCL, is required for normal erythropoies...
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+2
GATA-binding Protein 4 (GATA-4) and T-cell Acute Leukemia 1 (TAL1) Regulate Myogenic Differentiation and Erythropoietin Response via Cross-talk with Sirtuin1 (Sirt1)
Article Full-text available
Jul 2012
Li Wang Yi Jia Heather M Rogers
[...] Constance Tom Noguchi
Erythropoietin (EPO), the cytokine required for erythrocyte production, contributes to muscle progenitor cell proliferation and delay myogenic differentiation. However, the underlying mechanism is not yet fully understood. Here, we report that EPO changes the skeletal myogenic regulatory factor expression program and delays differentiation via indu...
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Additional file 3
Data
Jun 2012
Vladan P Cokic Bhaskar Bhattacharya
Bojana B Beleslin-Cokic [...] Alan Schechter
Statistically significant by t-test genes down-/up-regulated vs. HuURNA among examined cells.
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JAK-STAT and AKT pathway-coupled genes in erythroid progenitor cells through ontogeny
Article Full-text available
Jun 2012
Vladan P Cokic Bhaskar Bhattacharya
Bojana B Beleslin-Cokic [...] Alan Schechter
It has been reported that the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway regulates erythropoietin (EPO)-induced survival, proliferation, and maturation of early erythroid progenitors. Erythroid cell proliferation and survival have also been related to activation of the JAK-STAT pathway. The goal of this study was to observe the func...
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Additional file 2
Data
Jun 2012
Vladan P Cokic Bhaskar Bhattacharya
Bojana B Beleslin-Cokic [...] Alan Schechter
Statistically significant by t-test genes down-regulated vs. HuURNA among examined cells.
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Additional file 4
Data
Jun 2012
Vladan P Cokic Bhaskar Bhattacharya
Bojana B Beleslin-Cokic [...] Alan Schechter
Statistically significant genes by ANOVA down-/up-regulated vs. HuURNA among examined cells. p < 0.01 (shadow box), p < 0.05 (open box).
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Additional file 1
Data
Jun 2012
Vladan P Cokic Bhaskar Bhattacharya
Bojana B Beleslin-Cokic [...] Alan Schechter
Statistically significant by t-test genes up-regulated vs. HuURNA among examined cells.
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Endogenous erythropoietin signaling facilitates skeletal muscle repair and recovery following pharmacologically induced damage
Article
Apr 2012
Yi Jia Norio Suzuki Masayuki Yamamoto [...] Constance Tom Noguchi
Erythropoietin acts by binding to its cell surface receptor on erythroid progenitor cells to stimulate erythrocyte production. Erythropoietin receptor expression in nonhematopoietic tissue, including skeletal muscle progenitor cells, raises the possibility of a role for erythropoietin beyond erythropoiesis. Mice with erythropoietin receptor restric...
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Erythropoietin in Brain Development and Beyond
Article Full-text available
Feb 2012
Mawadda Alnaeeli Li Wang
Barbora Piknova [...] Constance Tom Noguchi
Erythropoietin is known as the requisite cytokine for red blood cell production. Its receptor, expressed at a high level on erythroid progenitor/precursor cells, is also found on endothelial, neural, and other cell types. Erythropoietin and erythropoietin receptor expression in the developing and adult brain suggest their possible involvement in ne...
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Angiogenic factors eNOS and VEGF have increased expression in granulocytes of JAK2V617F homozygous forms of Polycythemia Vera
Conference Paper
Dec 2011
Vladan P Cokic Dragana Marković
Olivera Mitrović Ajtić [...] Schechter A.
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Angiogenic Factors eNOS and VEGF Have Increased Expression in Granulocytes of JAK2V617F Homozygous Forms of Polycythemia Vera
Article
Nov 2011
Vladan P Cokic Dragana Marković
Olivera Mitrovic [...] Alan Schechter
3847
The microvessel density of bone marrow is increased in myeloproliferative neoplasms (MPN) parallel with vascular endothelial growth factor (VEGF). VEGF-mediated angiogenesis requires nitric oxide (NO) production from activated endothelial NO synthase (eNOS). NO as well as hypoxia stimulate the VEGF gene expression and angiogenesis by enhancing...
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Microarray and Proteomic Analysis of Myeloproliferative Neoplasms
Article
Nov 2011
Vladan P Cokic Pascal Mossuz Jing Han [...] Alan Schechter
3856
The gene and protein expression profiles in myeloproliferative neoplasms (MPN) may reveal gene markers of a potential clinical function in diagnosis and prediction of response to therapy. Using cDNA microarray analysis, involving 25,100 unique genes, we studied the gene expression profile of hematopoietic CD34+ progenitor cells and granulocyte...
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Supplementary Material 2
Data
Nov 2011
Ruifeng Teng Oksana Gavrilova
Norio Suzuki [...] Constance Tom Noguchi
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+3
Disrupted erythropoietin signaling promotes obesity and alters hypothalamus proopiomelanocortin production
Article Full-text available
Nov 2011
Ruifeng Teng Oksana Gavrilova
Norio Suzuki [...] Constance Tom Noguchi
Although erythropoietin (Epo) is the cytokine known to regulate erythropoiesis, erythropoietin receptor (EpoR) expression and associated activity beyond haematopoietic tissue remain uncertain. Here we show that mice with EpoR expression restricted to haematopoietic tissues (Tg) develop obesity and insulin resistance. Tg-mice exhibit a decrease in e...
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Supplementary Material 1
Data
Nov 2011
Ruifeng Teng Oksana Gavrilova
Norio Suzuki [...] Constance Tom Noguchi
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Supplementary material 1
Data
May 2011
Ruifeng Teng John W. Calvert
Nathawut Sibmooh [...] Constance Tom Noguchi
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P53. Endothelial response in acute erythropoietin treatment for cardioprotection
Article
May 2011
Ruifeng Teng Nathawut Sibmooh
Barbora Piknova [...] Constance Tom Noguchi
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Acute erythropoietin cardioprotection is mediated by endothelial response
Article Full-text available
Feb 2011
Ruifeng Teng John W Calvert
Nathawut Sibmooh [...] Constance Tom Noguchi
Increasing evidence indicates that high levels of serum erythropoietin (Epo) can lessen ischemia-reperfusion injury in the heart and multiple cardiac cell types have been suggested to play a role in this Epo effect. To clarify the mechanisms underlying this cardioprotection, we explored Epo treatment of coronary artery endothelial cells and Epo car...
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Erythropoietin and hypoxia increase erythropoietin receptor and nitric oxide levels in lung microvascular endothelial cells
Article
Feb 2011
Bojana B Beleslin-Cokic Vladan P Cokic Li Wang [...] Constance T Noguchi
Acute lung exposure to low oxygen results in pulmonary vasoconstriction and redistribution of blood flow. We used human microvascular endothelial cells from lung (HMVEC-L) to study the acute response to oxygen stress. We observed that hypoxia and erythropoietin (EPO) increased erythropoietin receptor (EPOR) gene expression and protein level in HMVE...
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The Effects of Erythropoietin Dose Titration during High-Fat Diet-Induced Obesity
Article Full-text available
Jan 2011
Amanda Foskett Mawadda Alnaeeli
Li Wang [...] Constance T Noguchi
Erythropoietin (Epo) is a pleotropic cytokine with several nonhematopoietic tissue effects. High-dose Epo treatment-mediated effects on body weight, fat mass and glucose tolerance have recently been reported, thus extending its pleotropic effects to fat and glucose metabolism. However, the exact dose range of Epo treatment required for such effects...
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Regulation of HDAC1 Histone Deacetylase Activity During Hematopoesis
Article
Nov 2010
Tao Yang Yi Lou Wei Jian [...]
Yi Qiu
3869
Histone deacetylases (HDACs) play important roles in transcriptional regulation in eukaryotic cells. HDAC1 has been implicated in diverse cellular processes, such as developmental programming, gene expression and cell cycle progression, which are often linked to epigenetic repression. However, emerging evidence also suggests that histone deace...
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Glucose Metabolism and Erythropoietin Stimulation of Erythroid Progenitor Cells
Article
Nov 2010
Heather Marie Rogers Ruifeng Teng
Constance Tom Noguchi
4232
Erythropoietin (EPO) is known for its activity in stimulating erythroid progenitor cell survival, proliferation and differentiation. EPO is produced in the interstitial cells of the kidney in a hypoxic responsive manner and is used in treatment of anemia in patients with chronic kidney disease. Suggestions that EPO may affect metabolic paramet...
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Lineage Specific Erythropoietin Receptor Expression Regulation
Article
Nov 2010
Li Wang Heather Marie Rogers
Constance Tom Noguchi
4779
Erythropoietin receptor (EpoR) is a member of the cytokine receptor superfamily. During erythroid differentiation of hematopoietic stem cells, Epo acts through binding of EpoR on the surface of early erythroid progenitor cells to promote cell survival, proliferation and differentiation down the erythroid lineage. The extent of Epo response is...
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Up-regulation of erythropoietin receptor by nitric oxide mediates hypoxia preconditioning
Article
Nov 2010
Zhi-Yong Chen Li Wang Pundit Asavaritkrai Constance Tom Noguchi
Erythropoietin (Epo), known to stimulate erythroid progenitor cell survival, proliferation, and differentiation, has been shown to be neuroprotective against brain ischemia in animal models. Both Epo and Epo receptor (EpoR) are expressed in the brain and are up-regulated by hypoxia. Brain Epo signaling can stimulate neural cell survival and prevent...
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GLOBIN GENES VERSUS COMMON GENES EXPRESSION PROFILING IN ERYTHROID CELLS DURING ONTOGENY
Conference Paper
Sep 2010
Vladan P Cokic B. Bhattacharya
Bojana B Beleslin-Cokic [...] A. Schechter
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Apoliprotein A-I Mimetic Peptide and Sickle Vasculopathy: Mouse Model Study of Acute Administration.
Article
Nov 2009
Lewis L Hsu Valeriani Bead Lita Freeman [...] Marcelo Amar
1521
Poster Board I-544
Epidemiologic observations associate low levels of Apolipoprotein A-1 (ApoA-I) and low high density lipoprotein (HDL) with greater prevalence of pulmonary hypertension in sickle cell patients. Sickle cell mice with knockout of apoliproteins have greater pulmonary hypertension and endothelial dysfunction than sickle cell mice...
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Liver Hypoxia and Tissue Injury Are Specific to Sickle Cell Mice in An Experimental Model of Sickle Cell Vaso-Occlusion.
Article
Nov 2009
Lewis L Hsu Audrey C Noguchi
Constance Noguchi [...] Bhalchandra Diwan
2569
Poster Board II-546
Sickle cell vaso-occlusion causes tissue ischemia, injury, and severe pain in patients with sickle cell disease (SCD). Investigations of the pathophysiology of vaso-occlusion have largely focused on the mechanisms for microcirculatory obstruction, rather than the tissue damage. The liver is frequently involved in human SCD...
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+1
Erythropoietin Improves Histological and Functional Outcomes after Traumatic Brain Injury in Mice in the Absence of the Neural Erythropoietin Receptor
Article Full-text available
Sep 2009
Ye Xiong Asim Mahmood
Changsheng Qu [...] Michael Chopp
Erythropoietin (EPO), essential for erythropoiesis, provides neuroprotection. The EPO receptor (EPOR) is expressed in both neural and non-neural cells in the brain. This study was designed to test the hypothesis that EPO provides beneficial therapeutic effects, even in the absence of the neural EPOR. In this study, EPOR-null mice were rescued with...
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Stimulated stromal cells induce γ-globin gene expression in erythroid cells via nitric oxide production
Article
Aug 2009
Vladan P Cokic Bojana B Beleslin-Cokic Reginald D Smith [...] Alan Schechter
We have previously shown that nitric oxide (NO) is involved in the hydroxyurea-induced increase of gamma-globin gene expression in cultured human erythroid progenitor cells and that hydroxyurea increases NO production in endothelial cells via endothelial NO synthase (NOS). We have now expanded those studies to demonstrate that stimulation of gamma-...
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LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis
Article Full-text available
Jul 2009
Xin Hu Xingguo Li Kristell Valverde [...] Suming Huang
TAL1 is a critical transcription factor required for hematopoiesis. However, perturbation of its activity often leads to T cell leukemia. Whether and how its transcriptional activities are regulated during hematopoiesis remains to be addressed. Here, we show that TAL1 is associated with histone demethylase complexes containing lysine-specific demet...
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Erythropoietin signaling promotes transplanted progenitor cell survival
Article
Jun 2009
Yi Jia Renaud F Warin Xiaobing Yu
[...] Constance Tom Noguchi
We examine the potential for erythropoietin signaling to promote donor cell survival in a model of myoblast transplantation. Expression of a truncated erythropoietin receptor in hematopoietic stem cells has been shown to promote selective engraftment in mice. We previously demonstrated expression of endogenous erythropoietin receptor on murine myob...
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Erythropoietin expression and myoblasts survival
Article
Apr 2009
yi jia Max Gassmann Constance Tom Noguchi
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P96. Globin gene stimulation by nitric oxide produced by the hematopoietic microenvironment
Article
Dec 2008
Vladan P Cokic B BELESLINCOKIC
Constance T. Noguchi Alan N. Schechter
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Erythropoietin Receptor Expression: A Role for the Tal1/SCL and GATA-1 Complex
Article
Nov 2008
Heather Marie Rogers Li Wang
Xiaobing Yu Constance Tom Noguchi
Tal1/SCL is required for hematopoietic stem cell development and is essential for normal erythropoiesis. Although Tal1-DNA binding is not required for hematopoietic development, Tal1 participates in a complex with other binding partners GATA-1, LMO2, Ldb1 and possibly Sp1. During erythropoiesis, Tal1 can activate expression via direct association w...
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LSD1-Mediated Epigenetic Modification Is Important for TAL1 Function
Article
Nov 2008
Xin Hu Xingguo Li River Saenz
[...] Suming Huang
TAL1/SCL is critical for normal and abnormal hematopoiesis by regulating hematopoietic stem/progenitor cell growth and differentiation. However, it is still unclear how its transcriptional activities are controlled during hematopoiesis. Here, we undertook the biochemical isolation of TAL1-associated protein complexes in erythroleukemia cells and sh...
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Histological and functional outcomes after traumatic brain injury in mice null for the erythropoietin receptor in the central nervous system
Article
Sep 2008
Ye Xiong Asim Mahmood Dunyue Lu [...] Michael Chopp
Erythropoietin (EPO) and its receptor (EPOR), essential for erythropoiesis, are expressed in the nervous system. Recombinant human EPO treatment promotes functional outcome after traumatic brain injury (TBI) and stroke, suggesting that the endogenous EPO/EPOR system plays an important role in neuroprotection and neurorestoration. This study was des...
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Where the Epo cells are
Article
Jun 2008
Constance Tom Noguchi
In this issue of Blood, Obara and colleagues report on their use of a GFP transgene to mark kidney Epo-producing cells in mice. These cells in the interstitial space express neuronal markers, and their number correlates with plasma Epo levels and increases with hypoxic induction.
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Erythropoietin in myoblast maintenance and muscle regeneration
Article
Apr 2008
yi Jia Norio Suzuki Masayuki Yamamoto [...] Constance Tom Noguchi
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Hydroxyurea nitrosylates and activates soluble guanylyl cyclase in human erythroid cells
Article Full-text available
Mar 2008
Vladan P Cokic Silvana Andric
Stanko S Stojilkovic [...] Alan Schechter
Hydroxyurea, a drug widely used for treating myeloproliferative diseases, has also been approved for the treatment of sickle cell disease by raising fetal hemoglobin (HbF). We have shown that nitric oxide (NO) and the soluble guanylyl cyclase (sGC) pathways are involved in hydroxyurea induction of HbF levels in erythroid progenitor cells (EPCs). We...
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Survival and proliferative roles of erythropoietin beyond the erythroid lineage
Article Full-text available
Feb 2008
Constance Tom Noguchi Li Wang
Heather M Rogers [...] Yi Jia
Since the isolation and purification of erythropoietin (EPO) in 1977, the essential role of EPO for mature red blood cell production has been well established. The cloning of the EPO gene and production of recombinant human EPO led to the widespread use of EPO in treating patients with anaemia. However, the biological activity of EPO is not restric...
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1 2 3
Citations
... EPO, a pleiotropic factor, can affects the occurrence and progression of many diseases (32, 33)
. EPO was reported that expressed in the lung to respond to Hypoxia by promoting erythropoiesis and neovascularization (13,(34)(35)(36) . ...
Reference: EPO rs1617640 A>C is a protective factor for chronic obstructive pulmonary disease: a case control study
Erythropoietin Non-hematopoietic Tissue Response and Regulation of Metabolism During Diet Induced Obesity
Citing article
Sep 2021
Soumyadeep Dey Jeeyoung Lee
Constance Tom Noguchi
View full-text
... The following mechanisms might explain this association: First, anti-EPOR antibodies may inhibit the action of EPO binding to EPOR in cardiac tissues as well as bone marrow erythroid precursors. EPORs have been reported to be expressed not only on immature erythrocyte membranes but also on cardiomyocytes [15, 32,
33], and ESA administration has been shown to protect cardiac function through EPORs on cardiomyocytes after a cardiac injury [33]. In experimental mouse models in which EPOR is lacking in non-hematopoietic cells, left ventricular myocardial stress was found to lead to significantly greater left ventricular mass and less cardiac contractility than those in control mice, concomitant with decreased signal transducer and activator of transcription 3 (STAT3) signaling required for cardioprotection [15]. ...
Reference: Association between Anti-Erythropoietin Receptor Antibodies and Cardiac Function in Patients on Hemodialysis: A Multicenter Cross-Sectional Study
Erythropoietin treatment and the risk of hip fractures in hemodialysis patients
Citing article
Apr 2021
Sukanya Suresh Elizabeth C Wright Daniel G. Wright Kevin C Abbott Constance Tom Noguchi
View full-text
... Estrogen receptor 1 knockout (Esr1 −/− ) mice are widely used in research to study aspects of estrogen receptors and their functions [8,10]. Sex-specific differences and estrogen receptor signaling are the subject of ongoing investigation [7, 35]
. To validate global deletion of Esr1 in the used mouse model (B6N(Cg)-Esr1 tm4.2Ksk /J), DNA was isolated from ear punches and subjected to genotyping. ...
Reference: Expression Analysis of Lipocalin 2 (LCN2) in Reproductive and Non-Reproductive Tissues of Esr1-Deficient Mice
Erythropoietin reduces fat mass in female mice lacking estrogen receptor alpha
Citing article
Dec 2020
Jeeyoung Lee Mary Walter Kenneth S. Korach Constance Tom Noguchi
View full-text
... The initial ATP difference before and at the beginning of incubation on day two may just be a relic of physiological blood nature, independent of the incubation conditions ( Figure 5). Women's blood products are characterized by a lower oxygen saturation [47]
. It may favor the liberation of the glycolytic enzymes from band 3 and hence, boost glycolysis and ATP production compared to male-derived RBCs [48,49]. ...
Reference: The Effect of the Donor’s and Recipient’s Sex on Red Blood Cells Evaluated Using Transfusion Simulations
Oxygen in Red Blood Cell Concentrates: Influence of Donors' Characteristics and Blood Processing
Citing article
Dec 2020
Alan N. Schechter David Wood
Constance Tom Noguchi Michel Prudent
Tatsuro Yoshida
View full-text
... 57 Hence, these properties of EPO can be used to treat anemias associated with chronic kidney diseases and blood disorders such as anemia. 62, 63
EPO affect osteoblast and osteoclast activity during EPO-stimulated erythropoietic response stimulate the debate on the relative efficacy and safety of EPO vs hypoxia inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) for patients who require long-term treatment for anemia. 62 ...
Reference: Role of hormones in bone remodeling in the craniofacial complex: A review
Effects of Erythropoietin in White Adipose Tissue and Bone Microenvironment
Citing article
Nov 2020
Sukanya Suresh Jeeyoung Lee Constance Tom Noguchi
View full-text
... Their administration led to downregulation of proteins involved in the synthesis of lipids in the liver, such as fatty acid synthase, acetyl-CoA carboxylase, and sterol regulatory element-binding protein 1. They additionally led to upregulation of proteins involved in the lipolysis of visceral white adipose tissue, such as anti-adipose triglyceride lipase and hormone sensitive lipase [83, 84]
. In the brown fat tissue of young male mice, EPO therapy regulated differentiation of brown adipocyte, STAT3 activation, secretion of FGF21, and improved insulin sensitivity and glucose tolerance via upregulation of master transcriptional coregulator PRDM16 [84]. ...
Reference: Molecular Sciences STAT5 as a Key Protein of Erythropoietin Signalization
Erythropoietin regulates metabolic response in mice via receptor expression in adipose tissue, brain and bone
Citing article
Sep 2020
Constance Tom Noguchi
View
... While in fetuses and neonates, the liver as well as the kidney are Epo producers, a rapid shift is observed after birth toward the peritubular cells of the kidneys as major producers [32]. However, in mouse models, it was shown that local production of Epo in osteoblasts as well as macrophages is also important for physiological bone and hematopoietic metabolism [33]
[34]
[35][36]. In addition, VEGF-induced upregulation of Epo production has been extensively described in the literature as the other major regulatory mechanism. ...
Reference: Local YB-1, Epo, and EpoR concentrations in fractured bones: results from a porcine model of multiple trauma
Erythropoietin signaling in osteoblasts is required for normal bone formation and for bone loss during erythropoietin‐stimulated erythropoiesis
Citing article
Jul 2020
Sukanya Suresh Jeeyoung Lee Constance Tom Noguchi
View
... We identified 5193 records in the initial search and then removed 1930 duplicates. After the screening based on titles, abstracts, and full-texts, 80 articles 16, were finally included in systematic review and 60 articles 16,[19][20][21][22][23][24]26,27,[29][30][31][32][33][34][35][36][37][38][40][41][42][44][45][46]48,[50][51][52][53]55,56,59,60,64,66,68,[70][71][72][73][74][76][77][78][79][81][82] [83]
[84]86,[88][89][90][92][93][94][95][96][97] with data of μCT or bone mechanical properties assessment were included in the meta-analysis ( Figure 1). ...
Reference: How high‐fat diet affects bone in mice: A systematic review and meta‐analysis
Erythropoietin-Induced Changes in Bone and Bone Marrow in Mouse Models of Diet-Induced Obesity
Citing article
Feb 2020
Sukanya Suresh Josue Caban Alvarez
Soumyadeep Dey Constance Tom Noguchi
View full-text
... Herein, as reported by two recent studies [21,22], female animals exhibited better protection from EPO-induced bone loss than males. In addition, the sex-differential EPO phenotypes seen in other tissues [64]
[65][66][67] suggest the involvement of sex hormones. Although no sex-specific differences in the plasma concentration of EPO were detected [68], estrogen has been shown to affect EPO response and mediate gender-specific EPO actions [69]. ...
Reference: Erythropoietin Receptor (EPOR) Signaling in the Osteoclast Lineage Contributes to EPO-Induced Bone Loss in Mice
Sex-specific brain erythropoietin regulation of mouse metabolism and hypothalamic inflammation
Citing article
Feb 2020
Soumyadeep Dey Zhenzhong Cui
Oksana Gavrilova XiaoJie Zhang
Constance Tom Noguchi
View
... Erythropoietin (EPO) is a U.S. Food and Drug Administration (FDA) approved drug for the treatment of anemia associated with chronic kidney disease. The functional role of EPO via EPO receptors (EPOR) has been reported in many other tissues including the intestine [8] [9]
[10]. Our recent study has shown a novel beneficial effect of EPO against POI by reducing oxidative stress and inflammatory insults in wild-type mice [11]. ...
Reference: A critical role for erythropoietin on vagus nerve Schwann cells in intestinal motility
The Many Facets of Erythropoietin Physiologic and Metabolic Response
Citing article
Jan 2020
Sukanya Suresh Praveen Kumarn Rajvanshi
Constance Tom Noguchi
View full-text
Top co-authors (50)
Alan Schechter
National Institutes of Health
Griffin P Rodgers
Vladan P Cokic
Institute for Medical Research - Belgrade
Bojana B Beleslin-Cokic
Clinic for Endocrinology, Diabetes and Metabolic Diseases, University of Belgrade, Belgrade, Serbia
Li Wang
University of Macau
Ruifeng Teng
National Institutes of Health
Soumyadeep Dey
National Institutes of Health
Heather M Rogers
National Institutes of Health
HEATHER ROGERS
Xiaobing Yu
Top journals
Blood (63)
Journal of Biological Chemistry (16)
Diabetes (12)
Blood Cells Molecules and Diseases (12)
Experimental Hematology (8)
Affiliations
National Institutes of Health
Department
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of California, San Francisco
The National Institute of Diabetes and Digestive and Kidney Diseases
Disciplines
Medicine
Topic
Cardiology Diabetology Internal Medicine (General Medicine) Nephrology Nutrition and Dietetics Nutritional Biochemistry Clinical Chemistry Toxicology
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Fuzzy Surfaces in GIS and Geographical Analysis: Theory, Analytical Methods, Algorithms and Applications [1st edition] 9780849363955, 0849363950 - EBIN.PUB
This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with pe...
Fuzzy Surfaces in GIS and Geographical Analysis: Theory, Analytical Methods, Algorithms and Applications [1st edition]
9780849363955, 0849363950
This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with pe
311 31 3MB
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Weldon Lodwick
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Fuzzy Surfaces in GIS and Geographical Analysis Theory, Analytical Methods, Algorithms, and Applications© 2008 by Taylor & Francis Group, LLCFuzzy Surfaces in GIS and Geographical Analysis Theory, Analytical Methods, Algorithms, and ApplicationsEdited byWeldon LodwickBoca Raton London New YorkCRC Press is an imprint of the Taylor & Francis Group, an informa business© 2008 by Taylor & Francis Group, LLCCRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2008 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number-13: 978-0-8493-6395-5 (Hardcover) This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www. copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging-in-Publication Data Lodwick, Weldon A. Fuzzy surfaces in GIS and geographical analysis : theory, analytical methods, algorithms, and applications / Weldon Lodwick. p. cm. Includes bibliographical references and index. ISBN 978-0-8493-6395-5 (alk. paper) 1. Geographic information systems--Mathematics. 2. Fuzzy mathematics. 3. Surfaces. I. Title. G70.23.L63 2008 526.0285--dc22 Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com© 2008 by Taylor & Francis Group, LLC2007032995Dedication This book is dedicated to Professor Angelo Marcello Anile, who is not only the inspiration for this book, but, in many ways, its main author. Beyond his individual professional creativity, he has guided and mentored so many, and has always been willing to share his knowledge in the seeds he has planted among young and seasoned colleagues alike.© 2008 by Taylor & Francis Group, LLCContents Chapter 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Weldon Lodwick, Marcelo Anile, and Salvatore Spinella Chapter 2 Interpolation with Data Containing Interval, Fuzzy, and Possibilistic Uncertainty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Marcello Anile and Salvatore Spinella Chapter 3 Introduction to Geographical Information Systems . . . . . . . . . . . . 55 Cid´alia Fonte, Jorge Santos, and Gil Gonc¸alves Chapter 4 Geographical Entities as Surfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Cid´alia Fonte Chapter 5 Surface Modeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 Jorge Santos Chapter 6 Visualization and Analysis on Surfaces . . . . . . . . . . . . . . . . . . . . . . . 105 Giovanni Gallo Chapter 7 Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 Cid´alia Fonte, Jorge Santos, Gil Gonc¸alves, Salvatore Spinella, and Marcelo Anile Chapter 8 Algorithms — Pseudo Code . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 Cid´alia Fonte, Jorge Santos, and Salvatore Spinella Chapter 9 Appendices — Fuzzy Arithmetic and Fuzzy Query C++ Source. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .137 Salvatore Spinella References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159© 2008 by Taylor & Francis Group, LLCPreface Surfaces are a major component of geographical information systems (GISs). When surfaces are used to model geographical entities, they inherently contain uncertainty in terms of both position and attribute. This book presents the requisite framework for surfaces where uncertainty is an explicit part of the process, from the data input stage to the conceptualization of its storage as fuzzy geographical entities, to its display and to its analyses. The reader will find the pseudo code of the computer programs that are requisite for actualizing what is presented in the book, while the associated code itself may be run utilizing the accompanying CD. The applications that are presented illustrate the concepts and indicate the relevance, richness, breadth, and depth of analyses that are possible with fuzzy surfaces. We trust that the reader will find what is presented to be useful.© 2008 by Taylor & Francis Group, LLCThe Editor I was born and raised in S˜ao Paulo, Brazil, where I lived until the end of high school. I came to the United States and attended Muskingum College in New Concord, Ohio, where I graduated in 1967 with a major in mathematics (honors), a minor in physics, and an emphasis in philosophy. I obtained my master’s degree from the University of Cincinnati in 1969 and a Ph.D. in mathematics from Oregon State University. In between my master’s and Ph.D., I taught junior high and high school mathematics in rural Georgia from 1969 to 1973. I left Oregon State University in 1977 to begin work at Michigan State University as a systems analyst on an international project analyzing food production potential working in the Dominican Republic, Costa Rica, Nicaragua, Honduras, and Jamaica. In addition, I helped to develop software for food production analysis for Syria. My job consisted of developing software, geographical information systems, statistical models, linear programming models, analysis, and training for transfer to various countries. While in Costa Rica, I worked directly with the Organization of American States (IICA) on Nicaraguan and Honduran projects that were similar to those I worked on while at Michigan State. In 1982, I was hired by the Department of Mathematics of the University of Colorado at Denver where I am a full professor of mathematics. Weldon A. Lodwick© 2008 by Taylor & Francis Group, LLCContributors Marcello Anile University of Catania Dipartimento di Matematica e Informatica Citt`a Universitaria Catania, Italy Cid´alia Fonte Universidade de Coimbra Departamento de Matematica Coimbra, Portugal Giovanni Galo University of Catania Dipartimento di Matematica e Informatica Citt`a Universitaria Catania, Italy© 2008 by Taylor & Francis Group, LLCGil Gon¸calves Universidade de Coimbra Departamento de Matematica Coimbra, Portugal Jorge Santos Universidade de Coimbra Departamento de Matematica Coimbra, Portugal Salvatore Spinella University of Catania Dipartimento di Matematica e Informatica Citt`a Universitaria Catania, Italy1 Introduction Weldon Lodwick, Marcello Anile, and Salvatore Spinella CONTENTS 1.11.21.3Interval Arithmetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.1.1 Intervals and Operations Among Intervals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.1.2 Examples: The Malthus Law . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 1.1.3 Functions of Intervals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 1.1.4 The Vertex Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Fuzzy Arithmetic. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 1.2.1 Introduction to Fuzzy Sets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 1.2.1.1 Fuzzy Sets. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 1.2.1.2 Examples and Interpretations of the Membership Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 1.2.1.3 The Mountain Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 1.2.1.4 The Median Construction of the Membership Function . . . 25 1.2.1.5 Operations with Fuzzy Sets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 1.2.2 Operations Among Fuzzy Numbers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 1.2.2.1 Definition of Fuzzy Numbers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 1.2.3 Comparing Fuzzy Numbers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 1.2.3.1 The Center of Mass . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 1.2.3.2 The Mean Interval . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 1.2.3.3 Distances Between Fuzzy Numbers . . . . . . . . . . . . . . . . . . . . . . . . 31 1.2.3.4 Distance Between Intervals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 1.2.3.5 Comparison of Statistical and Fuzzy Descriptions. . . . . . . . . 37 1.2.3.6 Arithmetic Operations. Examples . . . . . . . . . . . . . . . . . . . . . . . . . . 38 1.2.3.7 The Malthus Law Revisited . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 1.2.4 Functions of Fuzzy Numbers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 Semantics of Interval, Fuzzy, and Possibilistic Entities . . . . . . . . . . . . . . . . . . . . . . . 44Surfaces are central to geographical analysis and their generation and manipulation a key component of geographical information systems (GISs). Geographical surface data are often not precise (errorless) since uncertainty is inherent in what is obtained — measurement uncertainty (position, instrument accuracy), method of data collection (satellite, sonar, LIDAR, altimeter, air photographs), the surface itself (ocean bottom, steep slope, terrain, wetlands, landforms — categories whose meanings combine several definitions or ideas), and methods of classification (dense forest, land cover/use — classifications, for example, defined via clustering algorithms). The uncertainty types 1 © 2008 by Taylor & Francis Group, LLC2Fuzzy Surfaces in GIS and Geographical Analysisof interest to this presentation are: (i) finite ranges or intervals, for example, slope data are often given in 10-degree increments; (ii) transitional boundaries or fuzzy sets, for example, ocean to shore, grassland to shrubland; (iii) possibilistic values which are values that are known to exist, such as a 2000-meter isoline, but whose precise location is not since it is based on evidence arising from measurement and knowledge of the area, for example; and (iv) frequency or probability, for example, the daily temperature distribution over the last 100 years. It is emphasized that these four types of uncertainty are distinct from each other and must be handled correctly semantically and analytically. Data of types (i), (ii), (iii), and (iv) will be called in this study uncertainty data. This book presents the theory, methods, algorithms, and applications that directly model and analyze surfaces that are derived from uncertainty data. The focus is on the uncertainty that arises from transitional boundaries (intervals or fuzzy sets) and possibility distributions. We do not deal with statistical methods and probabilistic uncertainties since these are well known. That is, the uncertainties that are studied herein and the ways to deal with these uncertainties within the framework of a GIS and geographical analysis of surfaces are limited to three types — intervals, fuzzy sets, and possibility distributions. In the sequel, these are clearly described; the associated mathematics, as it pertains to surfaces defined; the algorithms developed; and the applications illustrated. The book sets out the process to identify the uncertainty in the geographical entity being studied, obtain the associated data, model, and analyze the data, display, and interpret results all within the context of a GIS. The book’s development takes the reader from the foundations of uncertainty relevant to the type of data encountered in surface analysis, its representation, storage and manipulation to analysis and display. The thesis set forward here is that much, if not most, of the uncertainty in geographical surface analysis is typically interval, fuzzy, and/or possibilistic. Second, when these data do contain one of these three types of uncertainty, the most faithful, useful, and natural way to model surfaces is to incorporate (represent and store), analyze, and display explicitly using interval, fuzzy, and/or possibilistic entities. To this end, the theory, methods, and applications are presented that clearly demonstrate the way to do this. A reader interested in understanding how to create, analyze, and display surfaces with inherent interval, fuzzy, or possibilistic uncertainties will find help herein to perform the task via the software and applications presented in the book. Moreover, the reader will develop a deeper knowledge of uncertainty itself as related to geographical analysis of surfaces containing interval, fuzzy, and possibilistic uncertainties so that the applications of these theories to problems that arise yield solutions that are more closely allied to the inherent reality, which is usually and most often undeniably imprecise and fuzzy. Since the three aspects of uncertainty that are the focus of this book (interval, fuzzy, and possibility) are relatively new fields of study, a few paragraphs introducing their development follow, much of which is a summary of [68]. Fuzzy set and possibility theory were defined and developed by L. Zadeh beginning with [103] and subsequently [104], [105], [106], and [107]. As is now well known, the idea was to mathematize and develop analytical tools to solve problems whose© 2008 by Taylor & Francis Group, LLCIntroduction3uncertainty was more ample in scope than probability theory. Classical mathematical sets, for example, a set A, have the property that either an element x ∈ A or x ∈ / A, but not both. There are no other possibilities for classical sets, which are also called crisp sets. An interval is a classical set. Zadeh’s idea was to relax this “all-or-nothing” membership in a set to allow for grades of belonging to a set. When grades of belong˜ Zadeh associated a real-valued ing are used, a fuzzy set ensues. To each fuzzy set A, function μ A˜ (x), called a membership function, for all x in the domain of interest, the universe , whose range is in the interval [0, 1] that describes and quantifies the ˜ For example, if A ˜ is the fuzzy set “warm day,” then degree to which x belongs to A. a 0◦ C day has a membership value of 0 while a 20◦ C day might have a membership value of 1, and a 10◦ C day might have a membership value of one half. That is, a fuzzy set is a set for which membership in the set is defined by its membership function μ A˜ (x) : → [0, 1] where a value of 0 means that an element does not belong to the ˜ with certainty and a value of 1 means that the element belongs to the set A ˜ with set A certainty. Intermediate values indicate the degree to which an element belongs to the set. Using this definition, a classical (so-called crisp) set A is a set whose membership function has a range which is binary, that is, μ A (x) : → {0, 1}, where μ A (x) = 0 means that x ∈ / A, and μ A (x) = 1 means x ∈ A. This membership function for a crisp set A is, of course, the characteristic function. So a fuzzy set can be thought of as being one which has a generalized characteristic function that admits values in [0, 1] and not just two values {0, 1} and is uniquely defined by its membership function. Another way of looking at a fuzzy set is as a set in R2 as follows. DEFINITION 1.1˜ as a crisp set in R2 , is the set of ordered pairs A fuzzy set A, A˜ = {(x, μ A˜ (x))} ⊆ {(−∞, ∞) × [0, 1]}.(1.1)Much has been written about fuzzy sets that can be found in standard textbooks (see, for example, [62]) and will not be repeated here. We present only the ideas that are pertinent to the areas in the interfaces between interval and fuzzy analysis of interest. The use of fuzzy sets in geographical analysis is relatively new (see [5], [41], [44], [46], [48], [66], [69], [71], [88], and [99]). Its application to geographical surfaces is even more recent ([5], [69], and [88]). Fuzzy surfaces will be studied in detail in subsequent chapters. An interval may be represented as a fuzzy set and consequently as a possibility distribution, as we will see below. Given this fact, we will concentrate on fuzzy set and possibilistic uncertainties. However, it will be via intervals that we will develop our analytical and numerical techniques associated with fuzzy sets. Since interval numbers are easier to manipulate than fuzzy sets, intervals and their applications to surfaces will be developed separately. Possibility theory was also developed by Zadeh [108] and extended by many authors, notably by Dubois and Prade (see [27], [32]), to model uncertainties to allow for a more general theory of uncertainty than probability theory models. There is often confusion in the semantics of uncertainty pertaining to probability, interval, fuzzy, and possibility. This is clarified below. GIS applications have seldom, if ever, used possibilistic geographical analysis. There are many reasons for this. Perhaps the© 2008 by Taylor & Francis Group, LLC4Fuzzy Surfaces in GIS and Geographical Analysisgreatest reason is that fuzzy set theory, as distinguished from possibility theory, is not always clear. Second, since geographical entities are often fuzzy (boundaries are gradual or transitional in nature between geographical entities) the use of possibilistic entities is frequently omitted. Third, since Zadeh develops possibility theory via fuzzy set theory [108], most authors do not make a distinction and consider possibility distributions the same as fuzzy membership functions. The distinction between fuzzy set theory and possibility theory is most important in its semantics so that a section dealing with the semantics is included below. The first research papers in fuzzy set theory appeared in the early 1960s, and while fuzzy “logic” (which can be related to mathematical analysis) can be thought of being developed in the early 1920s, the area of fuzzy set theory as a separate field of study dates from the mid-1960s. On the other hand, the first research “paper” in interval analysis can be considered to be Archimedes’ computation of circumference of a circle [83]. More recently Burkhill [13] in 1924 can be considered as the second research paper in the field. However, interval analysis as a separate field of study began in the early 1960s. While there are five known direct and clear precursors to Moore’s version of interval arithmetic and interval analysis beginning in 1924 (see [13], [35], [91], [97], and [102]), Moore was the one who worked out rounded computer arithmetic and fully developed the mathematical analysis of intervals, called interval analysis. As developed by R. E. Moore (see [78], [81], and [82]), interval analysis arose from the attempt to compute error bounds of numerical solutions on a finite state machine that accounted for all numerical and truncation errors, including roundoff error, automatically (by the computer itself). This led in a natural way to the investigation of computations with intervals as the entity, data type, that enabled automatic error analysis. R. E. Moore and his colleagues are responsible for developing the early theory, extensions, vision, and wide applications of interval analysis and the actual implementation of these ideas to computers. E. R. Hansen writes (see [53]): R. E. Moore (see [80]) states that he conceived of interval arithmetic and some of its ramifications in the spring of 1958. By January of 1959, he had published [78] a report on how interval arithmetic could be implemented on a computer. A 1959 report [82] showed that interval computations could bound the range of rational functions and integrals of rational functions. Theoretical and practical interval arithmetic were differentiated. Reference [77] discusses interval valued functions, interval contractions, a metric topology for interval numbers, interval integrals, and contains an extensive discussion of Moore’s use of interval analysis to bound the solution of ordinary differential equations.The methods for handling interval uncertainty and arithmetic of fuzzy sets, thus, can be traced to R. E. Moore’s technical reports in 1959 and 1960, and his Ph.D. thesis in 1962 (see [78], [79], [81], and [82]). On the real number line, with the usual meaning of the order relation, an interval [a, b] is the set of all real numbers {x|a ≤ x ≤ b}. Moreover, intervals can be considered as a number with two parameters (the left endpoint and the right endpoint). These two natures of intervals, numbers and sets, lead to interval arithmetic and interval analysis. What follows will develop the methods required to represent, store, manipulate, and analyze interval entities. While interval analysis is over 40 years old, the application of interval analysis to geographical surfaces is recent (see [66], [69], [71], and [88]).© 2008 by Taylor & Francis Group, LLCIntroduction5Intersections and unions of intervals also have an algebra and are computed in a straightforward manner. These definitions, unlike those of fuzzy set theory found in the sequel, come from classical set theory. Intersections and unions, of course, are crucial in defining what we mean by solutions to simultaneous equations and inequalities as well as the fundamental building blocks of logical statements. For a given interval [a, b] and a given real number x, the statement x ∈ [a, b] is either true or false. There is no vagueness or ambiguity except for roundoff when the statement is implemented on a computer. For two intervals A1 and A2 , if we know that x ∈ A1 and x ∈ A2 , then we also know with certainty that x ∈ A1 ∩ A2 . These statements have certainty except when one accounts for implementations on the computer and roundoff error comes into play unlike statements of this type in fuzzy set theory. Interval arithmetic and the interval analysis developed from it do not assign any measure of possibility or probability to parts of an interval. A number x is either in an interval A, or it is not. By introducing probability distributions or possibility distributions on an interval, and using level sets, integrals, or other measures, a connection between intervals and fuzzy sets can be made. Intervals are sets, and they are a (new type of) number. This dual role is exploited ¯ has a in the arithmetic and analysis. As a fuzzy set, an interval number U = [u, u] membership function ¯ 1 for u ≤ x ≤ u, μU (x) = 0 otherwise Thus, interval analysis can be considered as a subset of fuzzy set theory. As a probability distribution, an interval number can be considered as one of two probability density functions: 1. An interval may be considered to be the uniform distribution ¯ u < u¯ 1/(u¯ − u) for u ≤ x ≤ u, p(x) = 0 otherwise 2. An interval may represent the fact that all we know is the support so that ¯ is in the interval. every distribution p(x) with support supp{ p(x)} = [u, u] The first distribution may be appropriate when an approximation to the distribution is needed in the presence of no information about how the uncertainty is distributed as a “best” guess. Most researchers, however, consider the second probabilistic interpretation the most faithful probabilistic meaning of an interval as an uncertainty entity. There are excellent introductions to interval analysis beginning with R. E. Moore’s book [77] (also see other texts listed in the bibliography). A more recent introduction can be found in [21] and downloaded from: http://www.eng.mu.edu/corlissg/ PARA04/READ ME.html. Moreover, there are introductions that can be downloaded from the interval analysis website http://www.cs.utep.edu/interval-comp. On the interval analysis website, a list of languages that support interval data types is given. See http://www.cs.utep.edu/interval-comp/intlang.html. In particular, a MATLABTM system called INTLAB that supports the interval data types and interval linear algebraic analysis can be found and downloaded from: http://www.ti3.tu-harburg.de/∼© 2008 by Taylor & Francis Group, LLC6Fuzzy Surfaces in GIS and Geographical Analysisrump/intlab/index.html. INTLAB was used to develop the fuzzy interval arithmetic systems and analyses associated with this book (also see [86]).1.1INTERVAL ARITHMETIC1.1.1 INTERVALS AND OPERATIONS AMONG INTERVALS An interval [a, b] is an ordered pair of real numbers a, b with a < b. In a computer, in order to obtain exact lower and upper bounds on interval arithmetic operations, it is necessary to use the conservative form representation, which consists in representing a with the largest machine number a L such that a L ≤ a and b with the lowest machine number b R such that b R ≥ b [54]. An interval X = [a, b] is positive if a ≥ 0, and strictly positive if a > 0, negative if b ≤ 0, and strictly negative if b < 0. Two intervals X = [a, b], Y = [c, d] are equal if a = c and b = d. Among intervals, it is possible to define a partial ordering: [a, b] < [c, d] ⇔ b < c(1.2)Arithmetic operations among intervals are defined as follows. Let op be any arithmetic operation among reals, op = +, −, ∗, /. If X, Y are two intervals, op between the two intervals is defined as: X op Y = {x op y|x ∈ X, y ∈ Y }(1.3)Explicitly: [a, b] + [c, d] = [a + c, b + d](1.4)[a, b] − [c, d] = [a − d, b − c](1.5)[a, b] ∗ [c, d] = [min(ac, ad, bc, bd), max(ac, ad, bc, bd)](1.6)If the interval Y does not contain 0, the inverse 1/Y is defined by: 1/Y = [1/d, 1/c](1.7)X/Y = X ∗ (1/Y )(1.8)and the division of X by Y is:Among the elementary operations, it is convenient to introduce the following: Power, defined by the following rules [54]: ⎧ [1, 1] if n = 0 ⎪ ⎪ ⎪ ⎨[a n , bn ] if a ≥ 0 ∨ (a ≤ 0 ≤ b ∧ n is odd) [a, b]n = n n ⎪ [b , a ] if b ≤ 0 ⎪ ⎪ ⎩ n n [0, max(a , b )] if a ≤ 0 ≤ b ∧ n is even © 2008 by Taylor & Francis Group, LLC(1.9)Introduction7For the square root and the logarithm, we have when [a, b] is strictly positive [60], √ √ [a, b] = [ a, b] (1.10) log([a, b]) = [log(a), log(b)] (1.11) and for the exponential exp([a, b]) = [exp(a), exp(b)](1.12)First we notice that the commutative and distributive laws hold also for intervals X = [a, b], Y = [c, d], and Z = [e, f ]. X +Y = Y + X X ∗Y = Y ∗ XX + (Y + Z ) = (X + Y ) + Z X ∗ (Y ∗ Z ) = (X ∗ Y ) ∗ Z(1.13) (1.14) (1.15) (1.16)Furthermore, defining 0 = [0, 0] and 1 = [1, 1], one has 0+ X = X +0= X 1∗ X = X ∗1= X(1.17) (1.18)Now we give some examples. The distributive law between product and difference does not hold as shown by the following example: [1, 2] ∗ ([1, 2] − [1, 2]) = [−2, 2] and [1, 2] ∗ [1, 2] − [1, 2] ∗ [1, 2] = [−3, 3] Also the difference between two intervals is not zero: [2, 5] − [2, 5] = [−3, 3] The ratio X/ X is not 1 as shown by [2, 5]/[2, 5] = [2/5, 5/2] This causes what is called the redundancy problem: X ∗Y = X Y as an example: [1, 3] ∗ [2, 4]/[2, 4] = [1/2, 6] and the resulting interval [1/2, 6] is much larger than x = [1, 3]. © 2008 by Taylor & Francis Group, LLC8Fuzzy Surfaces in GIS and Geographical AnalysisTherefore, whenever in an expression a variable is repeated several times, the interval domain grows in an uncontrollable way, and furthermore, this makes it impossible to adopt the standard cancellation laws when performing algebraic calculations. This redundancy problem implies that, for the general problem of estimating the final uncertainty of a complex calculation, it is not practical to utilize interval arithmetic because there is no general way to control the growth of the uncertainty interval at each step of the calculation. There are ways to remedy this drawback [54] by taking appropriate precautions, such as automatically analyzing the individual steps of a complex calculation in order to detect redundancies and correct them. A rather interesting approach is that of affine arithmetic, see [90], which has been applied to several problems in computer graphics. Another relevant approach is that of constrained interval arithmetic, see [67]. However, in the interval literature, there seems to be no generally accepted methodology and accompanying efficient software for achieving this. In this book, we shall not utilize this general form of interval arithmetic (i.e., breaking a calculation into a sequence of interval operations and then applying the interval arithmetic rules) in order to treat uncertainty in interesting environmental problems. Instead, we shall adopt a more ad hoc approach, in the sense that, for a large class of functions that are encountered in interesting environmental problems, we shall utilize special algorithms, which estimate the final uncertainty interval with sufficient accuracy and efficiency.1.1.2 EXAMPLES: THE MALTHUS LAW One of the simplest examples is population dynamics as described by the discrete form of Malthus law: X (t + 1) = X (t) (1.19) with the growth constant. This constant (as well as other parameters that appear in population dynamics models, in epidemiological studies, etc.) can be interpreted as a transition probability in a Markov process. Usually, the data are not sufficient to determine the parameters with sufficient accuracy, and therefore the incorporation of the uncertainty of the constant in the model is an important aspect of the model building. Recent work on modeling and forecasting tuberculosis in the United States with Markov processes has represented the uncertainty in the parameters using triangular fuzzy numbers [23], and as a consequence, also the predictions are represented in terms of fuzzy numbers. In this chapter, we shall perform uncertainty analysis for the discrete Malthus law in Equation (1.19) with interval analysis and then we shall compare the results with those obtained via the probabilistic simulation approach. The fuzzy number analysis (which is in a sense an extension of the interval analysis, as will be shown later) will be performed in the next chapter. Let us assume that the initial value of X lies in the range between 3 and 6 and therefore can be represented by the interval X (0) = [3, 6] © 2008 by Taylor & Francis Group, LLCIntroduction9and that the growth constant lies in the range between 0.95 and 1.05 and is represented by the interval = [0.95, 1.05] What will be the uncertainty if the population be at the 20th iteration? The answer X (20) = [1.0754, 15.9198] can be obtained with the MATLAB program imalthus.m: clear; x0=infsup(3,6); lambda=infsup(0.95,1.05); x=x0; mm=20; for i=1:mm, x=lambda*x; end infsup(x) y=(lambda^mm)*x0; infsup(y) In the probabilistic simulation approach, X (0) and are treated as uniform random variables in the ranges [3, 6] and [0.95,1.25], respectively. A naive application of Monte Carlo simulation through the MATLAB program rmalthus.m yields the histogram of the simulated data, and from this, the empirical probability density is calculated. clear; n=20; m=2000000; for j=1:m, x(1,j)=3+3*rand; end hist(x,20); figure; mean=1.; for j=1:m, for i=2:n, lambda=0.95+0.1*rand; x(i,j)=x(i-1,j)*lambda; end end xx=1:m; for j=1:m, yy(j)=x(n,j); end min(yy) max(yy) hist(yy,100); figure; zz=1:n; Nx=hist(yy,zz);© 2008 by Taylor & Francis Group, LLC10Fuzzy Surfaces in GIS and Geographical Analysiszn=max(Nx); for j=1:n, Nx(j)=Nx(j)/zn; end plot(zz,Nx); z=0; for j=1:m, z=z+x(n,j); end z=z/m With m = 100 simulation, one finds that the range of the values after 20 iterations is: X (20) = [2.7719, 7.5400] and one can see that the range is smaller than that obtained with interval arithmetic. By increasing the number of simulations to m = 1000, one obtains: X (20) = [2.1289, 7.4606] and for 10,000 simulations: X (20) = [2.1181, 8.8219] Finally, for 1,000,000 simulations, one has the histogram in Figure 1.1: X (20) = [1.7384, 9.2908] 300025002000150010005000123456FIGURE 1.1 Histogram after 1,000,000 simulations.© 2008 by Taylor & Francis Group, LLC78910Introduction11which starts to approach the interval result. To approach more closely the interval arithmetic results, more Monte Carlo simulations are needed and, with the present naive approach, this would lead to incredible computing time. Obviously, for the simple problem at hand, the probabilistic approach could be done in a much more efficient way by computing an integral. However, the scope of the exercise was to show the potential of the interval arithmetic approach over the probabilistic-simulation one, at least when the calculations could be done exactly (or almost exactly). In this case, the interval obtained with interval calculations is exact because it expresses simply X (n) = λn · X (0) (1.20)and λn is calculated exactly according to the definition of power of an interval. The result is also consistent with the observation that the real function λn is monotonic. We notice that the largest interval obtained with the probabilistic approach requires 1,000,000 simulations, which is very demanding computationally. To obtain 1,000,000 function evaluations for functions that are not as simple as the Malthus law might be prohibitively expensive for the computational resources.1.1.3 FUNCTIONS OF INTERVALS It is convenient to introduce the subject with an example. Let us compute the average of two interval quantities: Y = (C1 ∗ X 1 + C2 ∗ X 2 )/(X 1 + X 2 ) where X 1 = [6, 8],X 2 = [10, 12]and the weights are also intervals: C1 = [600, 1500],C2 = [500, 1200].Then using interval arithmetic, we obtain Y = [430, 1650] through the MATLAB program average.m c1=infsup(600,1500); c2=infsup(500,1200); x1=infsup(6,8); x2=infsup(10,12); y1=(c1*x1+c2*x2)/(x1+x2); y=infsup(y1) This result is awkward because one expects that the average should be included in the interval [500, 1500]. In fact, a probabilistic simulation with n = 10,000 runs done with the MATLAB program rmediau.m© 2008 by Taylor & Francis Group, LLC12Fuzzy Surfaces in GIS and Geographical Analysisclear all; n=50000; x1l=6; x1r=8; c1l=600; c1r=1500; x2l=10; x2r=12; c2l=500; c2r=1200; x1sig=(x1r-x1l); x2sig=(x2r-x2l); c1sig=(c1r-c1l); c2sig=(c2r-c2l); for i=1:n, x1(i)=x1l+x1sig*rand; end for i=1:n, x2(i)=x2l+x2sig*rand; end for i=1:n, c1(i)=c1l+c1sig*rand; end for i=1:n, c2(i)=c2l+c2sig*rand; end for i=1:n, c(i)=(x1(i)*c1(i)+x2(i)*c2(i))/(x1(i)+x2(i)); end xx1=mean(x1) x1va=var(x1) hist(x1,20) figure; xx2=mean(x2) x2va=var(x2) hist(x2,20) figure; cc1=mean(c1) c1va=var(c1) hist(c1,20) figure; cc2=mean(c2) c2va=var(c2) hist(c2,20) figure; cc=mean(c)© 2008 by Taylor & Francis Group, LLCIntroduction13vc=var(c) hist(c,20) min(c) max(c) gives: Y = [563, 1310] which instead is well within the expected range [500,1500]. If we repeat the simulation with n = 20,000 runs we obtain Y = [543, 1321] Again, with n = 30,000 runs, we have Y = [562, 1316] and with n = 40,000 runsY = [536, 1326]and the range seems to converge as it is shown by increasing n (however, at the cost of long CPU times). The result obtained with a naive application of interval arithmetic is an example of the redundancy problem, i.e., a consequence of the repeated occurrence of the variables in the formula and indicates the need for a different algorithm. One of the most popular approaches is that of interval weighted averages also called the vertex method and this will be the subject of the next section.1.1.4 THE VERTEX METHOD First let us introduce functions of interval variables. Starting from a function of real variables one can introduce a function of interval variables: DEFINITION 1.2(Functions of interval variables) Let f (x1 , . . . , xn ) be a function of n real variables. Let F(X 1 , . . . , X n ) be a function of n intervals X 1 , . . . , X n . The function F is an interval extension of f if f (x1 , . . . , xn ) ∈ F(x1 , . . . , xn )(1.21)whenever the intervals X 1 , . . . , X n reduce to the real numbers x1 , . . . , xn . DEFINITION 1.3(Inclusion monotone function) An interval function F is inclusion monotonic if X i ⊂ Yi ,i = 1, . . . , n ⇒ F(X 1 , . . . , X n ) ⊂ F(Y1 , . . . , Yn )The interval arithmetic operations are inclusion monotonic.© 2008 by Taylor & Francis Group, LLC(1.22)14Fuzzy Surfaces in GIS and Geographical AnalysisNow we can introduce the IWA algorithm of Dong and Wong [26] (also called the vertex method ) in order to evaluate a large class of interval functions. Let the function to evaluate be Y = f (X 1 , . . . , X n ) (1.23) with X 1 = [a1 , b1 ], . . . , X n = [an , bn ]. We assume that f has no extreme in the interior of the polyinterval [a1 , b1 ] × . . . × [an , bn ]. Let us consider the M = 2n permutations of the endpoints, each represented by a vector with components βi , i = 1, . . . , M = 2n : β1 = (a1 , a2 , . . . , an )β2 = (b1 , a2 , . . . , an ) ... β M = (b1 , b2 , . . . , bn ) Then the interval value of the function f is: Y = [c, d] = [min f (i), max f (i)] ii(1.24)where f (1) = f (a1 , a2 , . . . , an ), etc. The MATLAB program iwaff.m performs such algorithm. function y=iwaff(m,x,handle); %implements the iwa algorithm with a general function; %m is the number of arguments; %x is the vector of arguments; %to change the function one has to type first from the %command windowhandle=@functionname; for h=1:m; con(h)=0; t(h)=0; end for r=1:m, xl(r)=inf(x(r)); xr(r)=sup(x(r)); end for j=1:2^m, for i=1:m, if con(i)==2^(i-1); t(i)=mod(t(i)+1,2); con(i)=0; end xx(j,i)=(1-t(i))*xl(i)+t(i)*xr(i); con(i)=con(i)+1; end end for k=1:2^m,© 2008 by Taylor & Francis Group, LLCIntroduction15v=xx(k,:); ou(k)=feval(handle,v); end vv1=min(ou); vv2=max(ou); cc=infsup(vv1,vv2); y=infsup(cc); For the example we have considered, the result is the interval [533.33, 1333.33], which is the correct value. The IWA algorithm gives the correct result if the function has its extreme only on the boundary of the domain where it is defined. For the function under consideration in the example, this is the case, as can be verified by computing the derivatives and noticing that they do not vanish.1.2FUZZY ARITHMETIC1.2.1 INTRODUCTION TO FUZZY SETS 1.2.1.1 Fuzzy SetsFuzzy sets represent a mathematical concept in order to describe mathematically nonstochastic uncertainty, for example, deriving from subjective judgments or from imprecise knowledge of parameters. A fuzzy set is a generalization of the classical concept of set. A fuzzy set A is an assembly of objects of the universe of discourse U that share some common property. The fuzzy set A is characterized by a membership function μ : U → [0, 1](1.25)which associates to each element x of U a real number belonging to the interval [0, 1], representing the degree of belonging to A [62]. In this way, the concept of characteristic function of a set A is generalized. The concept of degree of belonging can be interpreted also in the framework of possibility theory as the degree of possibility that the event corresponding to x belongs to the class of events described by A [62]. The set of elements of U for which the membership function is positive is called the support of A. A singleton is a fuzzy set whose support consists of a single point of U . In the following paragraphs, we shall give examples of membership function constructions from observed data. 1.2.1.2 Examples and Interpretations of the Membership FunctionsMeasurements in a Vague Environment: The Interpretation of Klawonn Klawonn [61] introduces the membership function of a fuzzy set as a way of representing imprecision in a vague environment. It is better to start with an example. Let us consider the temperature in a room in order to control it. For most purposes, a temperature difference less than 0.001◦ C is completely irrelevant for conditioning. Therefore, we can identify two temperature values that differ by less of 0.001◦ C.© 2008 by Taylor & Francis Group, LLC16Fuzzy Surfaces in GIS and Geographical AnalysisMore generally, once a tolerance threshold ǫ has been chosen (and this choice depends on the type of application), we can identify values of a variable whose distance (measured in an appropriate metric) s is less than ǫ. As an example, consider the temperature in a room that is assumed to vary in the interval [0, 35] centigrades [61]. For the purpose of controlling the temperature, the region of most interest is that between 19 and 23◦ C, because human beings are rather sensitive to small variations within this range. Instead, the temperatures within the region 15–19 can be lumped in the concept of cold and that between 23 and 27 as hot, and from the viewpoint of the human sensations, it is not important to discriminate very accurately within those regions. Also, for temperatures in the ranges [0, 15] or [27, 35] there is no interest in fine-tuning the control because the only sensible choice would be either to heat up in the first case or to cool down in the second one. In order to take this into account, it is convenient to distinguish the various scales by introducing a scale factor c(x) and the operation defines a vague environment. Returning to the example of the temperature, a reasonable scale factor could be (see Figure 1.2): ⎧ 0 if 0 ≤ x < 15 ⎪ ⎪ ⎪ ⎪ ⎪ 0.25 if 15 ≤ x < 19 ⎪ ⎨ if 19 ≤ x < 23 c(x) = 1.5 ⎪ ⎪ ⎪ 0.25 if 23 ≤ x < 27 ⎪ ⎪ ⎪ ⎩ 0 if 27 ≤ x < 35 Scale factor for the temperature vague environment 1.5Membership10.50051015 20 TemperatureFIGURE 1.2 Scale factor for the temperature environment.© 2008 by Taylor & Francis Group, LLC253035Introduction17We shall consider two values x1 , x2 ǫ-indistinguishable if their distance measured by the scale factor c (whose choice depends on the variability of x) is less than ǫ. Formally, we proceed as follows: Let X = [a, b] be an interval of the real line and c(x), a scale factor (the only requirement on c(x) is that it must be integrable). We can define a weighted distance between the two points x1 , x2 belonging to the interval [a, b] x2 c(s) ds (1.26) δc (x1 , x2 ) = x1The two points x1 , x2 are considered ǫ-distinguishable with respect to the scale factor c if their transformed distance δc (x1 , x2 ) ≥ ǫ. Now let us consider x0 ∈ X . We associate to x0 all other x that are not ǫdistinguishable from x0 (with respect to the scale factor c) and for ǫ varying between 0 and 1, that is, the set Sx0 , ǫ = {x ∈ X : δc (x, x0 ) ≤ ǫ}(1.27)We let ǫ vary between 0 and 1; different values can be taken into account by a suitable redefinition of the scale factor. This set can be described through the mapμx0 : X → [0, 1](1.28)x → 1 − min (δc (x, x0 ), 1)(1.29)Sx0 , ǫ = {x ∈ X : μx0 (x) ≥ 1 − ǫ}(1.30)whence We can interpret μx0 as the membership function of the fuzzy set of those values which are ǫ-indistinguishable from x0 ; ǫ vary between 0 and 1. The interpretation of the membership function is then the following. The interval corresponding to the α-level α is the set of points that are indistinguishable from x0 for ǫ = 1−α. Example: Let us assume c(x) to be constant. Then δc (x1 , x2 ) = c(x2 − x1 ), whence μx0 (x) = 1 − min{c(x − x0 ), 1} is a linear function that assumes its maximum at x0 and the sides of the triangle have slope c. The MATLAB program klawonnplot.m found in the accompanying CD gives Figure 1.3. Another example is obtained with the scale factor (x − x0 ) exp c(x) = s2−(x − x0 )2 2s 2which yields, with s = 0.1, Figure 1.4. For the scale factor of 1.2, the membership functions corresponding to the nominal values 15, 19, 21, 23, 27 degree celsius are given in Figures 1.5, 1.6, 1.7, 1.8, and 1.9.© 2008 by Taylor & Francis Group, LLC18Fuzzy Surfaces in GIS and Geographical AnalysisKlawonn construction of membership function 1 0.9Membership function0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 000.511.522.5 x33.544.55FIGURE 1.3 Membership function of almost 2 in a vague environment with a constant scale factor.Klawonn construction of membership function 1 0.9Membership function0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 000.511.522.5 x33.544.55FIGURE 1.4 Membership function of almost 2 in a vague environment with a Gaussian scale factor.© 2008 by Taylor & Francis Group, LLCIntroduction19 Klawonn construction of membership function1 0.9Membership function0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 005101520253035xFIGURE 1.5 Membership function of 15 degrees in the vague environment defined by the temperature scale factor.Klawonn construction of membership function 1 0.9Membership function0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 005101520253035xFIGURE 1.6 Membership function of 19 degrees in the vague environment defined by the temperature scale factor.© 2008 by Taylor & Francis Group, LLC20Fuzzy Surfaces in GIS and Geographical AnalysisKlawonn construction of membership function1 0.9Membership function0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0051015x20253035FIGURE 1.7 Membership function of 21 degrees in the vague environment defined by the temperature scale factor.Klawonn construction of membership function1 0.9Membership function0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 005101520253035xFIGURE 1.8 Membership function of 23 degrees in the vague environment defined by the temperature scale factor.© 2008 by Taylor & Francis Group, LLCIntroduction21 Klawonn construction of membership function1 0.9Membership function0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 005101520253035xFIGURE 1.9 Membership function of 27 degrees in the vague environment defined by the temperature scale factor.Membership Function as Degree of Preference for Design Parameters According to the context, there could be several interpretations of the membership function. An interesting interpretation is due to Wood, Otto, and Antonsson [100]. In the design process, there could be several parameters, which could be imprecisely known, that is, they vary within some ranges. Therefore, a first step would be to treat them as intervals. However, the designer might have some preference for some of the parameters, and this could be quantified by introducing the degree of preference μ. This function could then be interpreted as the membership function of a fuzzy set.Membership Function from Histograms: The Interpretation of Dubois and Prade This method is better explained in the case of the definition of the fuzzy set concept of tall. The universe of discourse U consists of all the possible heights, for example, in centimeters. The interval U = [linf , lsup ], where, for example, linf = 0.5, lsup = 2.5 in meters. A sample of people are asked at which height in the range U = [linf , lsup ] they consider a person tall. If somebody answers, say, s = 1.75, this means that this person considers all individuals with height in the range S = [s, lsup ] as tall. One can then discretize the set U in subsets of the kind Si = [si , lsup ], and the histogram of the numerical answers is given in Figure 1.10. The sets Si form a nested sequence covering the set U . If the number of answers is considerably large, one can assign probabilities P(Si ) to the sets Si from the normalized histogram. Then a fuzzy set could© 2008 by Taylor & Francis Group, LLC22Fuzzy Surfaces in GIS and Geographical Analysis 250200150100500 1.51.61.71.81.922.12.22.3FIGURE 1.10 Histogram corresponding to the height distribution for the concept of tall.be constructed by defining the membership function μ(s) on the set U as follows: (1.31) μ(s) = P(Si )over si ≤ s. The interpretation of this choice is that we assign to s the degree of belonging to the fuzzy set tall given by the sum of all probabilities that s lies in the intervals [si , lsup ], which coincides with the cumulative distribution function of the probability measure defined by P(Si ). This interpretation is quite intuitive and a formal justification in the framework of evidence theory can also be given [28]. With the MATLAB programs DP1, DP1a, and DP1b found in the accompanying CD, one obtains the graph of the membership function in Figure 1.11. The Probabilistic Interpretation of Jamison and Lodwick For a critical investigation of the relationship between membership function and probability, see Hisdal and Jamison and Lodwick [58]. 1.2.1.3 The Mountain FunctionThe mountain function method aims at summarizing a set of data described with a single fuzzy number. Let the data set consist of the points: DS = {z 1 , . . . , z N }(1.32)then the mountain function is defined by M(c) =© 2008 by Taylor & Francis Group, LLCN j=1ex p(− αd(z j , c))(1.33)Introduction231 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0.511.522.5FIGURE 1.11 Membership function for the concept of tall.where N is the number of data points, α is a positive constant, and d(x j , c) a distance, for example, of the kind d(x j , ci ) = (x j − c)2 (1.34) and c represents the modal point of the resulting fuzzy number. Then c is chosen as to maximizing the mountain function M(c). The method has been extended and modified in order to treat the case of imprecise data, described by triangular fuzzy numbers. For the sake of concreteness, let us represent the data as a set of quintuples of the kind: D j = (x j , y j , z jmin , z jmax , z jcenter )z jmin < z jcenter < z jmax(1.35)For each quintuple, xi and yi represent the spatial coordinates, assumed to be precisely known, whereas [z jmin , z jmax , z jcenter ] represents a fuzzy triangular number. In the particular case, when the three values of [z jmin , z jmax , z jcenter ] coincide, we have a crisp number. Our aim is to construct a fuzzy number that, in a sense, is a summary of the N fuzzy triangular numbers [z jmin , z jmax , z jcenter ] located at (x j , y j ). The construction proceeds as follows: Find a fuzzy number S with membership function m S such that: i support(m S ) = [a, b] where a = min z jmin , b = max z jmax ii there exists a unique element z S such that m S (z S ) = 1 iii m S is monotone increasing to the left of z S and decreasing to the right of z S© 2008 by Taylor & Francis Group, LLC24Fuzzy Surfaces in GIS and Geographical AnalysisIn the case of imprecise data, we must take into account the spread of each datum in the definition of the mountain function. In particular, following [48] we shall weigh less the data that have a larger spread. The definition we use for the mountain function is the following: M(c) =Nexp(− d(z j , c))(1.36)j=1where now the distance is given by d(z j , c) = (c − z jcenter )2 α j1d(z j , c) = (c − z jcenter )2 α j2c < z jcenter(1.37)c ≥ z jcenter(1.38)with α j1 = α j2 =(z jcenter − z jmin )2 2(z jcenter − a)2 (z jmax − z jmin )2 (z jcenter − z jmin )2 2(z jcenter − b)2 (z jmax − z jmin )2(1.39) (1.40)The modal point of the resulting fuzzy number is identified with the maximum of the mountain function. To construct the full membership function, one proceeds by utilizing a six–control point linear spline as follows: The control points P0 and P5 are, respectively, the points (a, 0) and (b, 0), implying that the support of the membership function is the interval [a, b]. The control point P3 is chosen in such a way that the requirement ii is satisfied. The other control points P1 , P2 , and P4 are chosen for the sake of simplicity, according to the following rules: If (a − c) > (z − b), P1 is taken to be:3 (1.41) P1 = c − (b − c), h 4 9(b − c)2 k h= 2(3c − 2a − b)(5b − 4a − c) (b − c)2 k= 2(c − a)2 P2 is taken to be:P4 is taken to be:1 c − (b − c), k 2(1.42)1 c + (b − c), k 2(1.43)Similar formulae apply in the case (a − c) ≤ (z − b). As a simple example, let us consider the following artificial data set: D1 = (x1, y1, 109, 125, 144); D2 = (x2, y2, 102, 125, 149); © 2008 by Taylor & Francis Group, LLC(1.44) (1.45)Introduction25Mountain function reconstruction1Prototype 0.9Membership function0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 100110120130140 150 160 x coordinate170180190200FIGURE 1.12 Mountain function reconstruction of a set of fuzzy data.D3 = (x3, y3, 107, 125, 146); D4 = (x4, y4, 152, 175, 186); D5 = (x5, y5, 163, 175, 191); D6 = (x6, y6, 167, 175, 183).(1.46) (1.47) (1.48) (1.49)The spatial coordinates of the data are irrelevant for our purpose, because they are assumed to belong to the same cell. The disc that accompanies this book contains the MATLAB programs distm.m, prototype.m,mountain.m, which lead to the membership function represented in Figure 1.12. 1.2.1.4 The Median Construction of the Membership FunctionAn overly simplistic method for constructing a membership function from a set of data is that of fitting a triangular membership function to the reduced data set consisting of the minimum, the maximum, and the median. The median is taken to correspond to the peak value for α = 1, and the minimum and maximum define the range of the triangular fuzzy number. A better interval-based construction can be envisaged in which the support of the membership function is defined by the interval of the minimum and maximum of the data and the interval corresponding to the α-level α is obtained by deleting from the ordered data set, in a symmetric way from the median, a fraction α of the data from the range starting from the extremes. As an example consider the data consisting of the hourly measurements of the pollutant P M10 (dust) at a given site© 2008 by Taylor & Francis Group, LLC26Fuzzy Surfaces in GIS and Geographical Analysis 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 00100200300400500600700FIGURE 1.13 Triangular fuzzy number from a set of pollutant PM10 concentration data during the first 2 months of 1999 at a site near a petrochemical factory in Sicily.near a petrochemical factory in Sicily, taken for the first 2 months of 1999. First we summarize the data with a triangular fuzzy number and obtain Figure 1.13. Next we apply the median method and obtain the much more satisfactory membership function of Figure 1.14. We consider also the yearly data from another station and obtain the triangular fuzzy number (Figure 1.15) and the median reconstruction (Figure 1.16). In this latter example, one sees clearly that the median reconstruction gives results that are much more satisfctory than the triangular fuzzy number representation. In particular, the effect of outliers is insignificant in the median reconstruction. 1.2.1.5 Operations with Fuzzy Sets DEFINITION 1.4(Union) Given two fuzzy subsets A, B of the universe of discourse U, defined by the membership functions μ A and μ B , their union is defined as the fuzzy subset of U whose membership function is μ A∪B (x) = max(μ A (x), μ B (x))(1.50)DEFINITION 1.5(Intersection) Likewise the intersection of the two fuzzy subsets A, B is defined by the membership function μ A∩B (x) = min(μ A(x) , μ B(x) ) © 2008 by Taylor & Francis Group, LLC(1.51)Introduction271 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 00100200300400500600700FIGURE 1.14 Median membership function construction from a set of pollutant PM10 concentration data during the first 2 months of 1999 at a site near a petrochemical factory in Sicily.1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 001002003004005006007008009001000FIGURE 1.15 Triangular fuzzy number from a set of pollutant PM10 concentration data during the year 1999 at a site near a petrochemical factory in Sicily.© 2008 by Taylor & Francis Group, LLC28Fuzzy Surfaces in GIS and Geographical Analysis 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 001002003004005006007008009001000FIGURE 1.16 Median membership function construction from a set of pollutant PM10 concentration data during the year 1999 at a site near a petrochemical factory in Sicily. DEFINITION 1.6(Complement) The complement of the fuzzy subset A is defined by the membership function μC A (x) = 1 − μ A(x)(1.52)DEFINITION 1.7(Equivalence) Two fuzzy subsets A and B are equivalent if their membership functions are equal: A = B ⇔ ∀x ∈ U μ A (x) = μ B (x)(1.53)1 0.8 0.6 0.4 0.21234FIGURE 1.17 Triangular fuzzy number for l = 1, m = 2, r = 3 is “almost 2.” © 2008 by Taylor & Francis Group, LLCIntroduction29 1 0.8 0.6 0.4 0.21234FIGURE 1.18 Triangular fuzzy number for l = 2, m = 3, r = 4 is “almost 3.” DEFINITION 1.8(Inclusion) The fuzzy subset A is included in the fuzzy subset B iff A ⊆ B ⇔ ∀x ∈ U μ A (x) ≤ μ B (x)(1.54)REMARK 1.1(Identities) It is easy to prove the following identities: C(C A) = A(1.55)C(A ∪ B) = C A ∩ C B(1.56)C(A ∩ B) = C A ∪ C B(1.57)In fact one has: μCC A (x) = 1 − μC A (x)= 1 − (1 − μ A (x))= μ A (x) andμC(A ∪ B) (x) = 1 − μ A ∪ B (x) = 1 − max(μ A (x), μ B (x)) = min(1 − μ A (x), 1 − μ B (x)) = μCA ∩ CB (x)(1.58) (1.59) (1.60)analogously for the other identity. REMARK 1.2(Tertium non datur) The law of “tertium non datur” does not hold; in fact A ∪ CA = U because© 2008 by Taylor & Francis Group, LLCmax(μ A (x), 1 − μ A (x)) = 1(1.61)30Fuzzy Surfaces in GIS and Geographical Analysisand likewise A ∩ CA = ∅because(1.62)min(μ A (x), 1 − μ A (x)) = 0 DEFINITION 1.9(Fuzzy normal subset) A fuzzy subset A of U (universe of discourse) is said to be normal if its membership function reaches its maximum at a point, that is, max μ A (x) = 1 x∈U(1.63)DEFINITION 1.10(Fuzzy convex subset) A fuzzy subset A of the universe of discourse U is said to be convex if ∀x, y ∈ [a, b] μ A (λx + (1 − λ)y) ≥ min(μ A (x), μ A (y))(1.64)DEFINITION 1.11(Direct product of fuzzy sets) Let U, V be universes of discourse and A, B fuzzy subsets of U, V, respectively. The direct product A × B is the fuzzy subset of the Cartesian product U × V, defined by the membership function μ A×B (x, y) = min(μ A (x), μ B (y))(1.65)1.2.2 OPERATIONS AMONG FUZZY NUMBERS 1.2.2.1 Definition of Fuzzy Numbers DEFINITION 1.12(Fuzzy number) A fuzzy number is a convex and normal fuzzy with compact support and piecewise continuous membership function. The set of fuzzy numbers on the real line R will be denoted by F(R). DEFINITION 1.13(α-levels) For a fuzzy subset A of the universe of discourse U , we introduce the α-levels Aα defined as follows for 0 ≤ α ≤ 1 Aα = {x : μ A (x) ≥ α}(1.66)PROPOSITION 1.1 (Resolution principle)Let χ Aα (x) be the characteristic function of the α-level Aα , then μ A (x) = sup min(α, χ Aα (x))(1.67)α∈[0,1]An example of α-level representation of the membership function with MATLAB is the m-file atrian.m included in the CD that accompanies this book.© 2008 by Taylor & Francis Group, LLCIntroduction31As an example, we plot the triangular fuzzy number with l = 1, m = 2, r = 3, which could be interpreted as almost 2, Figure 1.17.1.2.3 COMPARING FUZZY NUMBERS The problem of comparing fuzzy numbers has been amply studied in the literature [29]. The simplest way of comparing two fuzzy numbers is to defuzzify the two numbers, obtaining two crisp numbers representing in a sense typical values of the two quantities, and then to compare these two crisp numbers in the usual way. 1.2.3.1 The Center of MassThe simplest defuzzification procedure is that of taking the center of mass [111]: b xμ(x) dx g = a b (1.68) a μ(x) dxwhere μ(x) is the fuzzy number membership function. The program MATLAB centermass.m found in the accompanying CD computes the center of mass for a fuzzy number given by the matrix of its α-levels.1.2.3.2 The Mean IntervalA very interesting concept is that of mean interval, which in a sense summarizes both the expected value and the spread of a fuzzy number [29]. Its definition for a fuzzy number described by the α-levels z α = [zlα , zrα ] is 1 1 zrα d α (1.69) zlα d α, M(z) = 00The program MATLAB meanint.m found in the accompanying CD computes the mean interval for a fuzzy number given by the matrix of its α-levels. 1.2.3.3 Distances Between Fuzzy NumbersA simple way of constructing distances for fuzzy numbers is to use any of defuzzifying scalars and defining a distance between two fuzzy numbers u, v in terms of the absolute distance between the corresponding defuzzifying scalars, for example: dist 1 (u, v) = Abs[M M[u] − M M[v]](1.70)where M M[u] represents the scalar that defuzzifies u. Other distances could be defined on fuzzy numbers starting from distances on intervals. 1.2.3.4 Distance Between IntervalsA classical example of a distance between intervals is the Hausdorff distance d H (A, B) = max[sup inf |x − y|, sup inf |y − x|] (Hausdorff) x∈A y∈B© 2008 by Taylor & Francis Group, LLCy∈B x∈A(1.71)32Fuzzy Surfaces in GIS and Geographical AnalysisAnother widely used distance [29] starts from a function φ p (x) = x p and two intervals A = [a, b] and B = [c, d]. The distance is then: dist(A, B) = φ −1 p (0.5(φ p (| a − c |) + φ p (| b − d |)))(1.72)where p ≥ 1. Then given two fuzzy numbers in terms of their α-levels u α , vα , an induced distance can be defined by [29]: 1 dist(u α , vα ) dα (1.73) dist2 (u, v) = 0The program MATLAB fdist.m found in the accompanying CD computes the distance dist2 for two fuzzy numbers given by the matrices of their α-levels. However, both distances introduced above suffer from the drawbacks that they do not enjoy some desirable properties of distance between intervals, as discussed by Bertoluzza et al. [10]. To remedy these drawbacks arising from the fact that only the endpoints of the intervals are taken into account in the interval distance definition, a new class of distances with interesting properties has been introduced in [10] as follows. DEFINITION 1.14(Distance between intervals) Let g be a normalized and integrable weight function on [0, 1]. The squared distance d 2 between two intervals A = [a, b] and B = [c, d] is given by 1 2 [t · a − b + (1 − t)c − d]2 dg(t) (1.74) d (A, B) = 0In this class, a particular distance that corresponds to concentrated weights at the endpoints and at the midpoints of the intervals and is easily implemented is [10]: d 2 (A, B) = k(a − b)2 + h(A G − BG )2 + k(c − d)2 with A G = a + b/2, BG = c + d/2, and the weights h, k are such that 2k + h = 1. Another distance based on similar concepts has been introduced by Tran and Duckstein ([72] and [94]) and applied to fuzzy regression: 2 1 1 dt (a + b) + t(b − a) − (c + d) + t(d − c) d (A, B) = 2 2 − 212 21 1 1 1 1 = (a + b) − (c + d) + (b − a) − (c − d) (1.74a) 2 2 3 2 2 21 2As an example, the distance dist2 between the intervals A = [0, 0] (a crisp number) and B = [−1, 3] is the same as between A and C = [1, 3] and equal to © 2008 by Taylor & Francis Group, LLCIntroduction332.2361, although A is inside B and outside C. Instead, with the distance introduced by Tran and Duckstein [72], the distance between A and B is 1.5275 and that between A and C is 2.0817. By utilizing either of the previously defined distances between intervals, one can define distances between fuzzy numbers as follows. DEFINITION 1.15(Distance between fuzzy numbers) Given an integrable weight function w, [0, 1] → R such that: w(α) ≥ 0α ′ < α ′′ =⇒ w(α ′ ) < w(α ′′ ) 1 w(α) dα = 1(1.75)0 ∈ F(R) is a function d : F(R)2 → R the distance between fuzzy numbers A, B defined by 1 α )w(α) dα d( A, B) = d 2 ([ A]α , [ B] (1.76) 0This definition is consistent with the fact that intervals with a higher presumption level α should have a higher weight in determining the distance. Furthermore, this definition reduces to the Euclidean one for real numbers. The MATLAB programs fdistbert.m and fdistduck found in the accompanying CD compute the above defined distances for two fuzzy numbers given by the matrices of their α-levels in terms of the interval distances given by Equations (1.75) and (1.76), respectively. As an example let us consider the two couples of triangular fuzzy numbers: A = (−2, 0, 2), B = (−1, 0, 1), A1 = (−2, 0, 1), B1 = (−1, 0, 2). The two couples are represented in Figures 1.19 and 1.20, respectively. From the figures, it is intuitive that the distance between A1 and B1 should be greater than that between A and B because in A1 and B1 there are points that are farther away than between A and B. Now with the first distance we have introduced in Equation (1.73), one finds: fdist(A, B) = 0.5(1.77)fdist(A1 , B1 ) = 0.5 which shows that such a distance is not able to discriminate between the two cases. Instead, for the other distances we have introduced: fdistbert(A, B) = 0.4472 fdistbert(A1 , B1 ) = 0.5774© 2008 by Taylor & Francis Group, LLC(1.78)34Fuzzy Surfaces in GIS and Geographical Analysis 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 –3–2–1012323FIGURE 1.19 Triangular fuzzy numbers (–2, 0, 2) and (–1, 0, 1).1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 –3–2–101FIGURE 1.20 Triangular fuzzy numbers (–2, 0, 1) and (–1, 0, 2).© 2008 by Taylor & Francis Group, LLCIntroduction35 CBDA –3–2–101234567FIGURE 1.21 Interval A overtakes B by 0, B overtakes C by 3/5 and finally D overtakes C by 1.and also fdistduck (A, B) = 0.333(1.79)fdistduck (A1 , B1 ) = 0.5774 which shows that these distances are more sensitive to the shapes of the fuzzy numbers. With the introduced distance, one can obtain a consistent ordering for fuzzy numbers that is adequate for most practical applications. Given any distance between fuzzy numbers, we can give the following definition of equivalence between fuzzy numbers. DEFINITION 1.16 a real number ε > 0 and a (Fuzzy equivalence) Given two fuzzy numbers A and B, 2 < ε, that fuzzy distance d : F(R) → R, then A and B are ε-equivalent if d( A, B) is, ⇐⇒ d( B l ∧ Al ≤ B l ⎪ ⎩ l l 1 A >B where width(A) is the width of interval A.Figure 1.22 clarifies the above definition. The overtaking of A with respect to B is 0, and of B with respect to C is 3/5 while of D with respect to C is 1. The program MATLAB intover.m included in the CD that accompanies this book computes the above defined overtaking between two intervals.© 2008 by Taylor & Francis Group, LLC36Fuzzy Surfaces in GIS and Geographical Analysis 1 A B C D0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 –6–4–202468FIGURE 1.22 Triangular fuzzy numbers (−4, −2.2, −1), (−1, 0.5, 2), (0, 2, 4), and (4.5, 5.5,6.5).From this definition, one can define the δ-overtaking operator as: DEFINITION 1.18(δ-overtaking operator between intervals) Given two intervals A, B and a real number δ ∈ [0, 1], then A overtakes B by δ if σ (A, B) ≥ δ, that is, A ≥δ B ⇐⇒ σ (A, B) ≥ δ(1.82)Likewise we can define the overtaking between fuzzy numbers as follows: DEFINITION 1.19(Overtaking between fuzzy numbers) One defines overtaking of the fuzzy number A as the real function σ : F(R)2 → R defined as with respect to the fuzzy number B 1 α )w(α) dα σ ( A, B) = σ ([ A]α , [ B] (1.83) 0where for w : [0, 1] → R, one assumes the definitions in Equation (1.75).Figure 1.21 clarifies the above definition. The overtaking of A with respect to B is 0, and of B with respect to C is about 0.2430 while of D with respect to C is 1. The program MATLAB over.m included in the CD that accompanies this book computes the above-defined overtaking for two fuzzy numbers given by the matrices of their α-levels. Likewise one can define the operator of δ-overtaking between fuzzy numbers as follows:© 2008 by Taylor & Francis Group, LLCIntroduction37 1400 1200 1000 800 600 400 200 0050100150200250300FIGURE 1.23 Histogram of the hourly PM10 data detected by a sensor for a whole year. DEFINITION 1.20 ∈ F(R) and a real num(δ-overtaking operator between fuzzy numbers) Given A, B by δ if σ ( ≥ δ, that is, ber δ ∈ [0, 1], then A overtakes B A, B) ⇐⇒ σ ( ≥δ A, B) A ≥δ B(1.84)1.2.3.5 Comparison of Statistical and Fuzzy DescriptionsA comparison with a statistical approach has been made as follows: We consider the yearly pollution data previously introduced (see Figure 1.16). From an analysis of the data histogram, it is seen that they are reasonably well represented by a Gamma(a, b) distribution (Figure 1.23). Having computed the mean and standard deviation of the data (see Table 1.1), one has proceeded to fit such a distribution to a Gamma(a, b) distribution. A possible way to compare the fuzzy number membership function with the statistical distribution is to calculate the probability of observing values of the distribution greater than t and the overtaking of the fuzzy number representing the data with respect to the threshold t of a typical quantity, for example, δ = 0.66. Table 1.2 suggests a possible comparison.TABLE 1.1 Statistical Parameters Obtained from the Data Detected by the Environmental Sensor No. ElementsAverageStandard DeviationMinimumMedianMaximum731425.1029.630.118.3954.2© 2008 by Taylor & Francis Group, LLC38Fuzzy Surfaces in GIS and Geographical AnalysisTABLE 1.2 Relationship between Thresholds and Probability for the Chosen Distribution Model and Comparison with the Fuzzy-Overtaking Method Threshold t1.27 3.45 6.37 10.10 14.82 20.93 29.16 41.22 62.64P(X ≥ t) 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Z ≥0.66 tTrue True True True True False False False FalseThe third column in the table considers the comparison between fuzzy number overtaking the threshold t by δ = 0.66 and the probability representing the data Z of the random variable with the Ŵ distribution function to be greater than t. Notice the precise correspondence between probabilities and truth values. We are confident therefore that the rough membership function construction matches reasonably the statistical distribution function. However, a detailed statistical data analysis is required in order to guess the distribution function whereas the fuzzy number membership construction does not require any prior data analysis. We remark that the mean interval of the median-reconstructed fuzzy number is [5.8719, 40.7382]. 1.2.3.6 Arithmetic Operations. ExamplesLet us consider the function of two variables g : X × Y → Z and let A, B be fuzzy subsets of X, Y , respectively. Then, on the basis of the extension principle, one has μg(A,B) (z) = sup[μ A (x), μ B (y)](1.85)where z = g(x, y) and in terms of α-levels, g(A, B)α = g(Aα , Bα ). Therefore, the result is the same as by applying the interval arithmetic extension of the function g. The MATLAB m-files sum.m, product.m, difference.m, and quotient.m given found in the CD that accompanies this book perform the four basic operations. As an example, we consider the operations with triangular fuzzy numbers. Let x = atrian(1, 2, 3) and y = atrian(2, 3, 4) be two triangular fuzzy numbers (in this case, they are centered at m = 2 and m = 3, respectively, and could be interpreted as “almost 2” and “almost 3”) given in Figures 1.17 and 1.18. Their sum is then given by the fuzzy number z = x + y in terms of α-levels, represented in Figure 1.24. Likewise we have for the product of the previous two fuzzy numbers z = x ∗ y, represented in Figure 1.25.© 2008 by Taylor & Francis Group, LLCIntroduction391 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 02345678FIGURE 1.24 Sum of the TFN (triangular fuzzy numbers) [1, 2, 3] and [2, 3, 4].For the inverse operations, we have the difference z = y − x, represented in Figure 1.26 and for their division z = y/x (x = 0), represented in Figure 1.27. √ Also the elementary functions x α , exp(x), log(x), and x of MATLAB are overloaded for treating fuzzy numbers as a list of intervals. Figures 1.28, 1.29, 1.30, and 1.31 list some examples. 1.2.3.7 The Malthus Law RevisitedAs an application, we consider the same discrete Malthus law, which was considered for the interval case. We represent the initial value as a triangular fuzzy number 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 02345678910111213FIGURE 1.25 Product of the TFN (triangular fuzzy numbers) [1, 2, 3] and [2, 3, 4].© 2008 by Taylor & Francis Group, LLC40Fuzzy Surfaces in GIS and Geographical Analysis 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 −2−101234FIGURE 1.26 Difference of the TFN (triangular fuzzy numbers) [2, 3, 4] and [1, 2, 3].X 0 comprised between 3 and 6 with peak value 4.5 and the growth constant (see Figure 1.32) λ as a triangular fuzzy number comprised between 0.95 and 1.05 with peak value 1. With the MATLAB program fmalthus.m, we obtain, after 20 iterations, Figure 1.33.1.2.4 FUNCTIONS OF FUZZY NUMBERS Let us consider a function f : X ⇒ Y assumed to be bounded and continuous, with X = X1 × . . . × Xn. 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 000.511.522.533.544.5FIGURE 1.27 Division of the TFN (triangular fuzzy numbers) [2, 3, 4] and [1, 2, 3].© 2008 by Taylor & Francis Group, LLCIntroduction411 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0012345678910FIGURE 1.28 Square of the TFN [1, 2, 3].Let A1 , A2 , . . . , An be fuzzy sets belonging to X 1 , . . . , X n , respectively. If the fuzzy sets A1 , A2 , . . . , An are normal and convex, and the function f has some appropriate properties, then also the set B, the range in Y of the function f , will be normal and convex, and therefore a fuzzy number. For a general α-level, the problem is to compute the real interval: Bα = f (A1α , . . . , Anα ) = [y L , y R ](1.86)for each level α in [0, 1], where y L , y R represent the global minimum and maximum of f in the space X α = X 1α × · · · × X nα (1.87) 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0.911.11.21.3FIGURE 1.29 Square root of the TFN [1, 2, 3].© 2008 by Taylor & Francis Group, LLC1.41.51.61.71.842Fuzzy Surfaces in GIS and Geographical Analysis1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0246810121416182022FIGURE 1.30 Exponential of the TFN [1, 2, 3].It is obvious that the number of α-levels used in the discretization of the interval [0, 1] affects the accuracy of the approximation of the resulting fuzzy number. From the above properties, it is apparent that the calculation of a fuzzy function can be reduced to the calculation of an interval function for the given number of α-levels. Therefore, the same problems of redundancy arise as with the interval arithmetic. These could be avoided if one utilizes the (computationally costly) global optimization algorithms. One of the most popular algorithms is the extension to the fuzzy case (i.e., for each α-level) of the interval weighted average, IWA, algorithm, which in this case is called fuzzy weighted algorithm, FWA in short. In order to be applicable, as in the interval case, it requires the function f to be monotonic in each argument. 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 000.20.40.6FIGURE 1.31 Logarithm of the TFN [1, 2, 3].© 2008 by Taylor & Francis Group, LLC0.811.21.4Introduction431 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 002468101214161820161820FIGURE 1.32 Initial value for X 0 in the discrete Malthus law.1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 002468101214FIGURE 1.33 Malthus law with fuzzy numbers; X 0 = TFN(3, 4.5, 6), λ = TFN(0.95, 1, 1.05), after 20 iterations.© 2008 by Taylor & Francis Group, LLC44Fuzzy Surfaces in GIS and Geographical AnalysisOther cases are covered by the algorithm of Yang et al. [101], which depends on the structure of the domain X of the function f : X ⇒ Y . The domains are classified as uniform (or quasi-uniform) and nonuniform [101]: X is a uniform space if X α has no subspaces in which all the first partial derivatives of the function (assumed to be differentiable) vanish. In this case, one can apply the IWA algorithm to each α-level, that is, the FWA algorithm. X is quasi-uniform if X α has subspaces where the first partial derivatives of the function, ∂i f , vanish but ∂i f do not depend on the variable xi , i = 1, . . . , n. Also in this case, the function f takes its extremal values at the corner points. Therefore, also in this case, one can apply the FWA algorithm as follows. One evaluates the n partial derivatives ∂i f , and for each variable, one chooses xiL if ∂i f > 0, otherwise xiR as a basis for evaluating y L . In this way, one obtains y L and y R, respectively minimum and maximum of the function on the chosen xi . Notice that it is sufficient to determine the sign of the derivatives only at the lowest α-level because then, the space being quasi-uniform, the sign of each derivative will remain the same at all the other α-levels. X is a nonuniform space if the function can have extremal points within the domain. The algorithm then finds a list of points, called poles, which are candidates to be the extremal points of the function. In the end, it is equivalent to solving a nonlinear optimization problem. All these algorithms can be easily parallelized on the basis of assigning the computation at each α-level to a different processor [19].1.3SEMANTICS OF INTERVAL, FUZZY, AND POSSIBILISTIC ENTITIESThere is often confusion about the differences between fuzzy and possibilistic entities. Fuzzy and possibilistic entities have a different development from first principles. Fuzzy set and possibility theory were defined and developed by L. Zadeh, beginning with [103] and subsequently [104], [105], [106], [107], and [108]. Associated with fuzzy sets, measures and membership functions are two other types of measures and ensuing distributions — possibility and necessity measures and distributions. Whereas fuzzy measures quantify the uncertainty of gradualness, possibility and necessity measures are ways to quantify uncertainty of lack of information. Books and articles are available that develop possibility theory (see, for example, [31], [27], [96], [62]). What is of interest here for fuzzy and possibilistic mathematical analysis that is developed, is what is called quantitative possibility theory [30]. In particular, possibility theory may be derived in any one of the following ways: 1. via normalized fuzzy sets (see [105], [106], and [107] ), 2. axiomatically from fuzzy measures g that satisfy g(A∪B) = max{g(A), g(B)} (see [32] and [63], for example),© 2008 by Taylor & Francis Group, LLCIntroduction453. via belief functions of Dempster-Shafer theory whose focal elements are normalized and nested (see [62]), or 4. by construction via nested sets with normalization, for example, nested α-level sets (see [58]). Of special interest are the third and fourth approaches since they lead directly into a quantitative possibility theory, though the first points the way and lays the foundation. It will be assumed that the possibilistic/necessity measures and distributions that are used herein are constructed according to third or fourth approaches. Fuzzy and possibilistic entities have different meanings, semantics. Fuzzy and possibility uncertainty model different entities and the associated solution methods are different as will be seen. Fuzzy entities, as is well known, are sets with nonsharp boundaries in which there is a transition between elements that belong and elements that do not belong to the set. Possibilistic entities are those that exist but the evidence associated with whether or not a particular element is that entity is incomplete, missing, or not available. Quantitative possibility distributions constructed from first principles require nested sets (see, for example, [58]) and normalization. Possibility distributions are normalized since their semantics are tied to existent entities. Normalization is not required of fuzzy membership functions. Thus, not all fuzzy sets can give rise to possibility distributions. That is, even though Zadeh’s original development of possibility theory was derived from fuzzy sets, possibility theory is different from fuzzy set theory. Possibilistic distributions (of fuzzy numbers, for example) encapsulate the best estimate of the possible values of an entity, given the available information. Fuzzy membership function values (of fuzzy numbers) describe the degree to which an entity is that value. Note that if the possibility distribution at x is 1, this signifies that the best evidence available indicates x is the entity that the distribution describes. On the other hand, if the fuzzy membership function value at x is 1, x is certainly the value of the entity that the fuzzy set describes. Thus, the nature of mathematical analysis in the presence of fuzzy and possibilistic uncertainties is quite different in semantics. The most general form of possibility theory sets up an order among variables with respect to their being an entity. The magnitudes associated with this ordering have no significance other than an indication of order. Thus, if possibility A (x ) = 0 .75 and possibility A (y) = 0 .25 , all that can be said is that the evidence is stronger that x is the entity A than y. One cannot conclude that x is three times more likely to be A than y is. This means that for mathematical analysis, if the possibility distributions were constructed using the most general assumptions, comparisons among several distributions are restricted (to merely order). For the most general possibility theory, setting the possibility level to be greater than or equal to a certain fixed value α, 0 ≤ α ≤ 1, does not have the same meaning as setting a probability to be at least α. In the former case, the α has no inherent meaning (other than if one has a β > α, one prefers the decision that generated β to that which generated α) whereas for the case of probability or quantitative possibility, the value of α is meaningful. The third and fourth derivations of possibility theory lead to quantitative possibility theory.© 2008 by Taylor & Francis Group, LLC46Fuzzy Surfaces in GIS and Geographical AnalysisAn alternative approach to possibility theory is as a system of upper and lower distributions bounding a given, yet unknown probability. That is, given a measurable set A, N ec(A) ≤ pr ob(A) ≤ Pos(A) bounds the unknown probability of the event A so that Pos(A) ≤ α guarantees that pr ob(A) ≤ α. If the possibilistic entities are constructed from this perspective, then their α-levels are numerically meaningful beyond simply being an ordering. This is the method developed in [58].© 2008 by Taylor & Francis Group, LLCwith Data 2 Interpolation Containing Interval, Fuzzy, and Possibilistic Uncertainty Marcello Anile and Salvatore Spinella CONTENTS 2.12.3General Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 2.1.1 Modeling Observations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 2.1.2 Real B-Splines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 2.1.3 Interval B-Splines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 2.1.4 Fuzzy B-Splines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 Constructing Fuzzy B-Spline Surfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 2.2.1 Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 Fuzzy Kriging and Boundary Condition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 522.1GENERAL DEFINITIONS2.22.1.1 MODELING OBSERVATIONS Let O be a sequence of n observational data in a domain X ⊆ R 2 in the form O = {(x1 , y1 , Z 1 ), . . . , (xi , yi , Z i ), . . . , (xn , yn , Z n )}(2.1)with (xi , yi ) ∈ XZ i = {z i,1 , . . . , z i,m i }(2.2)where z i, j ∈ R represents the jth observation at the point (xi , yi ). As previously discussed in the introduction, a first approach to data reduction is to model the observation set Z i with the interval Ii defined by the minimum and maximum values of the observations at the point (xi , yi ) [40]: I O = {(x1 , y1 , I1 ), . . . , (xi , yi , Ii ), . . . , (xn , yn , In )}(2.3)where Ii is the interval Iil = min z i, j 1≤ j≤m iIiu = max z i, j 1≤ j≤m i47 © 2008 by Taylor & Francis Group, LLC48Fuzzy Surfaces in GIS and Geographical AnalysisFor some applications, this reduction is too coarse because it does not take into account the distribution and the quality of the data Z i at (xi , yi ). If the data set Z i comprises a large number of observations z i, j , a representation of Z i in terms of a probability density can be achieved and then a stochastic model can be fitted to the data in the form of a stochastic surface. However, in general, this approach requires special assumptions on the joint probability density of the data distribution, which are difficult to check from the data themselves. Furthermore, the interrogation of the stochastic surface model can be done, in general, only through Monte Carlo simulation, which is both noisy and computationally very expensive. Finally, this approach cannot be pursued when the data set contains only few data and the data quality is judged subjectively from the observer. For all these reasons, another approach has been introduced [3, 72] that represents the datum Z i with an appropriately constructed fuzzy number that reflects both the data distribution and their quality. Here, fuzzy numbers [60] are defined as maps that associate to each presumption level α ∈ [0, 1] a real interval Aα such that α ′′ > α ′ ⇒ Aα′′ ⊆ Aα′(2.4)and the latter property is formally called convex hull property. A regularity property such as upper semicontinuity is usually also invoked. The core of a fuzzy number is the set of values with membership equal to 1. When the core has only one element, the latter is called modal value. The support of the fuzzy number is an interval where the membership function is positive. In this representation, fuzzy numbers are viewed as the natural generalization of intervals and intervals can be viewed as fuzzy numbers whose core equals its support. By utilizing one of several methods for constructing fuzzy set membership functions ([61], [48]) from Z i , one can represent the n observational data as FO = {(x1 , y1 , z 1 ), . . . , (xi , yi , z i ), . . . , (xn , yn , z n )}(2.5)where z i ∈ F(R) is the fuzzy number representing the observations at the point (xi , yi ). Arithmetic operations among reals are extended to operations among fuzzy numbers by utilizing first the extension principle of interval arithmetic [54]. DEFINITION 2.1(Operation ⊗ between intervals). Given two intervals [a, b] and [c, d], the operation [a, b] ⊗ [c, d] is defined formally by [a, b] ⊗ [c, d] = min({x ⊗ y|x ∈ [a, b], y ∈ [c, d]} ⊆ [e, f ]) [e, f ](2.6)Likewise, the operations among fuzzy numbers are introduced by the following definition ([60], [2]). DEFINITION 2.2(Operation ⊗ between fuzzy numbers). The operation F1 ⊗ F2 associates with the fuzzy numbers F1 = {Aα }α∈[0,1] and F2 = {Bα }α∈[0,1] ; the fuzzy number F = {Cα }α∈[0,1] such that ∀α ∈ [0, 1] one has Cα = Aα ⊗ Bα© 2008 by Taylor & Francis Group, LLCInterpolation with Data Containing Interval, Fuzzy, and Possibilistic Uncertainty49Fuzzy arithmetic, which is based on interval arithmetic, is conservative with respect to the uncertainty of the data in the sense that, by utilizing the min-max operations, it yields under/overestimation for each α-cut.2.1.2 REAL B-SPLINES For an introduction to the theory of B-splines, see the book by Lancaster and Saskaulas [63]. A B-spline function of order h is a piecewise polynomial function f (t) : [t0 , tm ] → R of degree at most h − 1. The sequence of knots of a B-spline is a nondecreasing sequence of real numbers: (t0 , . . . , ti , . . . , tm ). Let k = m − (2h − 1) where h is the order of the B-spline. The knots of the subsequence (th−1 ,. . . , tk+h−1 ) are the inner knots of the B-spline. f (t) is C ∞ in [t0 , tm ], but at a knot of multiplicity p, f (t) is only C h− p−1 . A B-spline of order h on a sequence of m = k + 2h − 1 knots is a linear combination k+h−1 f (t) = ci Bi,h (t) (2.7) i =0where ci are the control coefficients, or control points, and Bi,h (t) are the basis functions of the B-splines of order h defined recursively by [24] 1 if ti ≤ t ≤ ti+1 Bi,1 (t) = 0 otherwise ti+h − t t − ti Bi,h−1 (t) + Bi+1,h−1 (t) for h > 1 (2.8) Bi,h (t) = ti+h−1 − ti ti+h − ti+1 A real B-spline surface is a tensor product of B-splines defined on a rectangular domain of M × N control points {ci, j }i=0,...,M−1, j=0,...,N −1 : f (u, v) =N −1 M−1 ci, j Bi,h (u)B j,h (v)(2.9)i =0 j =0The basis functions of real B-splines are all positive and guarantee, among other things, the convex hull property, that is, that f (t) is contained, for all t in the convex envelope of the control points.2.1.3 INTERVAL B-SPLINES The concept of real B-spline can be easily extended to the space I (R) of real intervals [40]. DEFINITION 2.3(Interval B-spline). An interval B-spline F(t) relative to the knot sequence (t0 , t1 , . . . , tm ), m = k + 2(h − 1), is a function of the kind F(t) : R → I (R) defined as h+h−1 F(t) = Ii Bi,h (t) (2.10) i =0© 2008 by Taylor & Francis Group, LLC50Fuzzy Surfaces in GIS and Geographical Analysiswhere the control coefficients Ii are real intervals and Bi,h (t) real B-spline basis functions. The generalization in 2D of an interval B-spline relative to a rectangular grid of M × N knots is M−1 N −1 Ii, j Bi,h (u)B j,h (v) (2.11) f (u, v) = i =0 j =0The construction of an interval B-spline will be considered under the more general case of a fuzzy B-spline, since intervals can be considered as a special case of fuzzy numbers.2.1.4 FUZZY B-SPLINES Similar to what is done for intervals in [40], we introduce fuzzy B-spline as follows [3]: DEFINITION 2.4(B-spline fuzzy) A fuzzy B-spline F(t) relative to the knot sequence (t0 , t1 , . . . , tm ), m = k + 2(h − 1) is a function of the kind F(t) : R → F(R) defined as F(t) =h+h−1 Fi Bi,h (t)(2.12)i =0where the control coefficients Fi are fuzzy numbers and Bi,h (t) real B-spline basis functions. Notice that Definition 2.4 is consistent with the previous definitions and more precisely for any t, F(t) is a fuzzy number, that is, it verifies the convex hull property given by Equation (2.4): α ′′ > α ′ ⇒ F(t)α′′ ⊆ F(t)α′ because the B-spline basis functions are nonnegative. The generalization in 2D of a fuzzy B-spline relative to a rectangular grid of M × N knots is N −1 M−1 Fi, j Bi,h (u)B j,h (v) (2.13) f (u, v) = i =0 j =0with the same properties as described above. Similar considerations in the more general framework of fuzzy interpolation can be found in [71].2.2CONSTRUCTING FUZZY B-SPLINE SURFACESLet us consider a sequence of fuzzy numbers representing the observations in Equation (2.5). If a fuzzy B-spline F(u, v) on a rectangular grid G ⊇ X of M × N knots© 2008 by Taylor & Francis Group, LLCInterpolation with Data Containing Interval, Fuzzy, and Possibilistic Uncertainty51approximates FO given by Equation (2.5) then ∀α ∈ [0, 1] [z i ]α ⊆ [F(xi , yi )]αi = 1, . . . , n(2.14)and furthermore, one must also have M−1 N −1 G i =0 j =0≤Fi,u j M−1 N −1 G i =0 j =0αYi,u j − Fi,l j α Bi,h (u)B j,h (v) dudv − Yi,l j α Bi,h (u)B j,h (v) dudvα∀{Yi, j }i=0,...,N −1, j=0,...,M−1 ∈ F(R) ∀α ∈ [0, 1](2.15)where [F l ]α and [F u ]α indicate, respectively, the lower and upper bounds of the interval representing the fuzzy number α-level. More precisely, for each presumption α-level, the volume encompassed by the upper and lower surfaces of the fuzzy B-spline is the smallest. These definitions are the generalization to the fuzzy case of the corresponding interval ones [40]. Notice that the integral in a rectangular domain of a real B-spline is the following linear expression: M−1 N −1 Pi, j Bi,h (u)B j,h (v) dudv =D i =0 j =0N −1 M−1 Pi, ji =0 j =0(ti+h − ti )(s j+h − s j ) h2(2.16)where obviously {(ti , s j )}i=0,...,M+h−1, j=0,...,N +h−1 are the grid knots. Therefore, given the set FO of observations in Equation (2.5) and a finite number P +1 of presumption levels α0 > α1 > · · · > α P , the construction of a fuzzy B-spline requires the solution of the following constrained optimization problem: ⎧ (t −t )(s −s ) P M−1 N −1 u ⎪ min k=0 Fi, j αk − Fi,l j αk i+h i h 2 j+h j ⎪ j =0 i =0 ⎪ ⎪ l l l u ⎪ ⎪ ⎪ F ≤ F ≤ · · · ≤ F ≤ Fi, j α P ≤ · · · ⎪ i, j i, j i, j α α α ⎪ 0 1 P ⎨ u u · · · ≤ Fi, j α1 ≤ Fi, j α0 i = 0 . . . M − 1 j = 0 . . . N − 1 ⎪ ⎪ u M−1 N −1 u ⎪ ⎪ r = 1, . . . , n k = 0, . . . , P ⎪ j = 0 Fi, j αk Bi,h (xr )B j,h (yr ) ≥ z r αk i =0 ⎪ ⎪ ⎪ ⎪ N −1 M−1 l ⎩ l r = 1, . . . , n k = 0, . . . , P j = 0 Fi, j αk Bi,h (xr )B j,h (yr ) ≤ z r αk i =0(2.17)With the variable transformation llFi,l j = F i, j − F i, juuFi,u j = F i, j − F i, jand the further constraints lF i, j ≥ 0lF i, j ≥ 0uF i, j ≥ 0uF i, j ≥ 0such a problem can be treated as a linear programming problem.© 2008 by Taylor & Francis Group, LLC52Fuzzy Surfaces in GIS and Geographical Analysis2.2.1 REMARKS For the problem in Equation (2.17), one notices that 1. The objective function minimizes the uncertainty of the representation. 2. The first group of constraints represents the convex hull property. 3. The second group of constraints is a consistency requirement for the upper bounds of the intervals to be greater than the upper bounds of the data at the data points. 4. The third group of constraints is a consistency requirement for the lower bounds of the intervals to be lower than the lower bounds of the data at the data points. By considering a grid of size M × N , T fuzzy observations, and P presumption levels, the dimensions of the problem are of 4M N P variables and 2(P − 1)M N + 2T constraints [70].2.3FUZZY KRIGING AND BOUNDARY CONDITIONIn the previous paragraph, we expounded the method for constructing a fuzzy surface approximating, in a well defined way, the fuzzy numbers representing the data sets. The quality of this approximation will deteriorate the farther one is from the sites of the data sets. Therefore, one expects the constructed approximation not to be very satisfactory at the border of the domain within which the data sites are comprised. To remedy such drawbacks, one has to introduce further information regarding the decay of the quantity of interest away from the domain. A simple approach would be to assume that the quantity of interest decays to zero outside the boundary but this is hardly justifiable. However, a better treatment would be to construct fictitious observation data just outside the boundary by utilizing statistical kriging. The latter approach is more realistic because, in some sense, it amounts to an extrapolation driven by the data. By ordinary spatially distributed data and with stationary hypothesis of the distribution, the kriging combines the available data by weights in order to construct an unbiased estimator with minimum variance. Likewise, such approach is extended to the fuzzy case [25]. Given N spatially distributed fuzzy data {(x1 , y1 , z 1 ), . . . , (xi , yi , z i ), . . . , (xn , yn , z n )}, one looks for an estimator constructed by a linear combination of weights λi to evaluate the distribution at the point (x, y) like ∗ = ZN i=1λi z i(2.18) ∗ like random fuzzy Notice that the above interprets fuzzy data z i and estimator Z number. In order to construct this estimator, the following hypothesis must be satisfied ∗ ) = E( Z ) = E( Z (x + h, y + k) = r (K1) E( Z ∗, Z )2 must be minimized (K2) Ed( Z(K3) λi ≥ 0,© 2008 by Taylor & Francis Group, LLCi = 1, . . . , N(2.19)Interpolation with Data Containing Interval, Fuzzy, and Possibilistic Uncertainty53N The first condition (K1) implies i=1 λi = 1; instead, the last one (K3) guarantees the estimator stands in the cone of random fuzzy number generated by the data. It can be proved that ∗, Z )2 = Ed( ZNi, j=1λi λ jNαCα (xi , yi , x j , y j )−2 i=1 λi α Cα (xi , yi , x, y) + α Cα (x, y, x, y)(2.20)where Cα is a positive defined function that represents a covariance. The minimization of such function together to the hypotheses (K1) and (K3) leads to a constrained minimization problem. It is solvable formulating everything in terms of Kuhn-Tucker conditions by the following theorem. THEOREM 2.1 ∗ be an estimator for Z of the form Z ∗ = N λi z i . Suppose the conditions Let Z i=1 (K1) and (K3) are satisfied and the matrix defined by Ŵi j = α Cα (xi , yi , x j , y j ), i, j = 1, . . . , N is strictly positive defined. Then there exists a unique linear unbiased ∗ satisfying the (K2) condition. Moreover, the weight satisfies the following estimator Z system N α C α (x i , yi , x, y) i=1 Ŵi j λi j − L j − μ = N i=1 λi = 1 (2.21) N i=1 L i λi = 0 L i , λi ≥ 0, i = 1, . . . , NThe residual is σ2 =Cα (x, y, x, y) + μ −αN i=1λiCα (xi , yi , x, y)(2.22)αThe above problem defines the weights λi and it can be solved using a method to manipulate the constraints in Equation (2.21) like the active set method [42].© 2008 by Taylor & Francis Group, LLCto 3 Introduction Geographical Information Systems Cid´alia Fonte, Jorge Santos, and Gil Gonc¸alves CONTENTS 3.1Geographical Information Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 3.1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 3.1.1.1 Data Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 3.1.1.2 Data Structures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 3.1.1.3 Analysis in GIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 3.1.2 The Object Data Model — Geographical Entities . . . . . . . . . . . . . . . . . . . . 59 3.1.3 The Field Data Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 3.1.3.1 The Field Data Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 3.1.3.2 Map Algebra Operations on Fields . . . . . . . . . . . . . . . . . . . . . . . . . 613.1GEOGRAPHICAL INFORMATION SYSTEMS3.1.1 INTRODUCTION Geographical information system (GIS) is an information system where the geographical locations of the phenomena are stored, enabling the retrieval and processing of geographical information. 3.1.1.1 Data ModelsTraditionally, the geographical information is modeled considering the object data model or the field data model. The phenomena that exist only on a limited region of the geographical space are represented by objects whose position in the geographical space represents their location. Depending on the type of phenomena to be represented, they may be modeled as points, lines, or areas (see Figure 3.1). This data model is known as the object data model and is appropriate to represent, for example, roads, administrative regions, or crops. When the phenomenon to be represented exists in all geographical space, and what is to be represented is its variation over the geographical space, the phenomenon is modeled using a surface z = f (x, y), where the coordinates x and y represent the 55 © 2008 by Taylor & Francis Group, LLC56Fuzzy Surfaces in GIS and Geographical AnalysisAB D1 D2CD3D4FIGURE 3.1 Representation of phenomena using the object data model. Objects A, D1, D2, D3, and D4 represent areal entities; object B represents a linear entity and object C a point entity.geographical planimetric position and z the value of the phenomenon at that location (see Figure 3.2). This data model is known as the field data model and is appropriate to represent phenomena such as altitude, atmospheric pressure, or rainfall. In addition to these traditional data models, a hybrid model may be considered, based on the use of fuzzy geographical entities (FGEs). This approach enables the representation of objects with surfaces, gathering therefore the important characteristics of both traditional data models. It may be used, for example, to represent GEs with ill-defined boundaries or whose position varies continuously in the geographical space. Further details about the construction and processing of FGEs are given in chapter 4. 3.1.1.2 Data StructuresFor the digital representation of the phenomena, two data structures are traditionally considered: the vector data structure and the raster data structure. The vector data zyxFIGURE 3.2 Representation of a phenomenon using the surface data model. The coordinates x and y represent the geographical position and coordinate z the value and concentration of amplitude of the phenomenon.© 2008 by Taylor & Francis Group, LLCIntroduction to Geographical Information Systems57structure uses primitives as points, lines, and areas, and the geographical space is considered continuous. A point is represented by its coordinates (x, y); a line is represented by a sequence of points, which are usually connected by straight segments, or, less frequently, by curves; and an area is represented by a closed line corresponding to its boundary. The vector data structure is usually associated to the representation of objects, but it can also be used to represent surfaces, using, for example, contours, profiles, or a tessellation of regions such as the Delaunay triangles or the Voronoi polygons (see Figure 3.3). The raster data structure is characterized by a grid of cells, usually square, known as pixels. Since only a value of each phenomenon is associated to each cell, in the raster(xR1, yR1)(xP , yP) (xR2, yR2)P(xS1, yS1)(xR3, yR3) R(xS2, yS2)(xS7, yS7) S(xR4, yR4)(xS6, yS6)(xS3, yS3) (xS5, yS5)(xR5, yR5) (xR6, yR6)(xS4, yS4) (xR7, yR7) (a)(b)(c)(d)FIGURE 3.3 (a) Representation of entities using the vector data structure. Representation of surfaces using the vector data structure: with (b) contours; (c) Delaunay triangles; (d) Voronoi polygons.© 2008 by Taylor & Francis Group, LLC58Fuzzy Surfaces in GIS and Geographical Analysis(a)(b)FIGURE 3.4 (a) A surface represented with the raster data structure. (b) Entities (objects) represented with the raster data structure.data structure, the geographical space is considered discrete. This type of structure adapts well to the representation of surfaces, even though its resolution is conditioned to the dimension of the cells. The raster data structure may also be used to represent objects. Each object is represented explicitly by a set of contiguous cells, corresponding to the same attribute value, such as soil type or slope classes (see Figure 3.4). A tessellation is a representation where the geographical space is partitioned into a finite number of contiguous elementary regions, which may be regular or irregular. To each elementary region, a value of the phenomenon to be represented is associated. The raster data structure is a particular case of a tessellation. 3.1.1.3 Analysis in GISAn important characteristic of GISs is their capability of incorporating functions to perform operations with the stored geographical information, providing analysis capabilities. A great variety of operations may be executed, which can be grouped into two types: operations with attributes and spatial operations [18]. The operations with attributes involve only the nonspatial attributes of the stored geographical information. Examples of these operations are querying the database about the owner or soil type of a parcel identified by the parcel number. These queries do not involve information about the spatial location of the parcel. The spatial operations use the data about the geographical location of the information, and the analysis performed with these operations is called spatial analysis. Among this type of operation are, for example, the computation of areas or the identification of the parcels located within 500 meters of a road. Spatial analysis often requires the consecutive use of several operators, which may process the information initially stored in the GIS or information generated through the previous application of other operators. Some operators just retrieve information from the GIS, such as the identification of the parcels with certain characteristics, although many operators generate new attributes and new geographical information ([6], [18], [93]).© 2008 by Taylor & Francis Group, LLCIntroduction to Geographical Information Systems593.1.2 THE OBJECT DATA MODEL — GEOGRAPHICAL ENTITIES In object-based GISs, the geographical information is represented by GEs. These entities are characterized by an attribute and a spatial location. The attribute specifies the phenomenon represented by the entity, such as building, forest, parcel, or more complex attributes, such as rural region with a slope between 10 and 20 percent, good solar exposure, and high levels of humidity. The spatial location of a geographical entity is specified by a point, a line, or a region and may be represented either in the vector or in the raster data structure. A group of GEs characterized by the same attribute is a class of GEs, or simply a class. Construction of GE Geographical entities may be built using several methods and with several types of data. The sources of geographical data may be grouped into primary and secondary [57]. The primary sources correspond to the cases where the data are collected directly from the geographical space, such as with topographic or photogrammetric surveys. The secondary methods correspond to the use of information already collected and processed, eventually for other aims, which may be in digital or analog format. Basically two approaches may be considered to construct GEs: Attribute-location approach This approach consists in identifying the attribute that characterizes the geographical entity, and determining its geographical location, that is, identifying the regions of the geographical space where that attribute can be found. One way to determine the geographical location is to identify the attribute in the terrain, aerial photos, remote sensing images, or even paper maps, and determine the position of the point, line, area, pixels, or cells corresponding to that attribute. The information may be collected in the vector data structure, as in the case of topographic surveys, vectorization of paper maps, or aerial photos, or in the raster data structure, for example, when paper maps are digitized to the raster data structure using a scanner. However, in most cases, the construction of GE in the raster data structure results from processing of information already in the raster data structure, such as the classification of remote sensing images. This last case may be included in a more vast procedure, named here classification of tessellations, which consists in classifying tessellations representing one or several phenomena or attributes, named base attributes, generating new attributes, named derived attributes. The tessellations are formed by elementary regions ri , which may be cells in a raster data structure or any other regions, such as, for example, irregular polygons corresponding to classes of slope. Each derived attribute corresponds to a set of values of the base attribute and characterizes a class of GEs. For example, the attribute “forest” may correspond to a set of levels of radiance in a multispectral image obtained by sensors installed in artificial satellites, or the attribute “mountain”© 2008 by Taylor & Francis Group, LLC60Fuzzy Surfaces in GIS and Geographical Analysis Values of the base attributes Derived attributes{1, 2, 3, 4, 5, 6, 7, 8, 9, 10} ABCFIGURE 3.5 Correspondence between the values of the base attributes and the values of the derived attributes.to a set of values of terrain altitude. In these cases, the GEs are obtained aggregating contiguous elementary regions to which the same derived attribute was assigned during the classification. For example, in Figure 3.6, the derived attributes were defined as a function of the base attributes, where derived attribute A corresponds to the interval [1, 3] of the base attributes, attribute B to the interval [4, 7], and attribute C to the interval [8, 10] (see Figure 3.5). Location-attribute approach The reverse of the previous approach may also be used to build GE. In this case homogeneous regions are identified in the geographical space. When their position is determined, the attribute characterizing them will be identified. The location-attribute approach may also be used either with the vector data structure or the raster data structure. In the former, regions are identified, for example, in aerial photos or high resolution remote sensing images, and the subsequent identification of the corresponding phenomena is done. In the raster data structure, the classification of remote sensing images with the unsupervised classification method is an example of this approach.3.1.3 THE FIELD DATA MODEL 3.1.3.1 The Field Data ModelThe field-based approach conceptualizes the geographic space as a collection of fields. Each field defines the spatial variation of an attribute of interest as a mathematicalACB(a) Base attribute(b) Derived attribute(c) Geographical entities corresponding to the derived attributesFIGURE 3.6 Geographical entities obtained aggregating contiguous cells to which the same derived attribute was assigned during the classification of the base attribute.© 2008 by Taylor & Francis Group, LLCIntroduction to Geographical Information Systems61function Z = f (x, y). This function is defined on a given region of the geographic space and assigns to every element of that region a corresponding field attribute value from the attribute domain. The field model usually assumes a partition of the geographic space into a finite tessellation of spatial entities. The tessellation can be regular, such as a grid of squares, or irregular, such as a network of triangles or Voronoi polygons. The values of the attribute domain are commonly classified using four scales of measurement: nominal, ordinal, interval, and ratio. Categorical or qualitative attributes are often expressed in nominal and ordinal scales. Quantitative attributes are reported in interval or ratio scales. The fields may be continuous, differentiable, discrete, and isotropic or anisotropic, with positive or negative autocorrelation. The basic mathematical model Z = f (x, y) can be generalized to allow tridimensional spatial coordinates x = (x, y, z), time parameter t, and multivalued fields Z = (Z 1 , Z 2 , ..., Z n ), taking the form Z = f ( x, t). 3.1.3.2 Map Algebra Operations on FieldsMap algebra describes a set of field operations that are typically classified into local, focal, and zonal types [93]. These operations take as input one or more fields and generate a separate field as an output data layer. In a local operation, the value of the new field at any location x is dependent only on the values of the input field functions at that location. In focal operations, the value of the new field at a location x depends not only on the attribute of the input field but also on the attributes of these functions in a neighborhood of x. Zonal operations take as input a value field and a zone field, and aggregate the values of the field over each zone.© 2008 by Taylor & Francis Group, LLCEntities 4 Geographical as Surfaces Cid´alia Fonte CONTENTS 4.1 4.24.34.1Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Fuzzy Geographical Entities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 4.2.1 Construction of Fuzzy Geographical Entities . . . . . . . . . . . . . . . . . . . . . . . . . 64 4.2.1.1 Attribute Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 4.2.1.2 Positioning an Attribute . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 4.2.1.3 Identifying Homogeneous Regions . . . . . . . . . . . . . . . . . . . . . . . . . 71 4.2.1.4 Choosing an Attribute . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 Processing Fuzzy Geographical Entities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 4.3.1 Complement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 4.3.2 Union and Intersection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 4.3.3 Buffers Generation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 4.3.4 Distances and Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 4.3.5 Area . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 4.3.5.1 Rosenfeld Area . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 4.3.5.2 Fuzzy Area . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 4.3.6 Perimeter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 4.3.6.1 Rosenfeld Perimeter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 4.3.6.2 Fuzzy Perimeter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81INTRODUCTIONThe construction of geographical entities (GEs) may be influenced by several types of errors and uncertainty that generate errors and uncertainty in the attributes and/or the geographical location of the entities. In other situations, the need to choose between the object data model and the field data model is a source of error, since some phenomena have characteristics of both data models and therefore are not adequately represented by either of them. Fuzzy set theory incorporates some concepts that can be used to overcome some of the problems described above, modeling some types of uncertainty associated to geographical information as well as its heterogeneity. They enable the development of an alternative data model that integrates characteristics of the object and the field data models, where the geographical information is represented with fuzzy geographical entities (FGEs), which are geographical entities (objects) represented with surfaces. 63 © 2008 by Taylor & Francis Group, LLC64Fuzzy Surfaces in GIS and Geographical AnalysisAn overview of the several sources of uncertainties and/or errors associated with GEs is presented in this chapter as well as methods to model their uncertainty or heterogeneity using fuzzy sets. FGEs are an efficient way to represent the positional uncertainty of GEs, or a gradual variation between them, but their inclusion in geographical information systems (GISs) requires not only their construction but also the development of operators capable of processing them. Some basic operators that process FGEs have already been developed and are briefly reviewed in this chapter.4.2FUZZY GEOGRAPHICAL ENTITIESSince this chapter addresses the representation of GEs as surfaces that represent the uncertainty or heterogeneity of the entities using fuzzy sets, through the construction of FGEs, only the types of errors and uncertainty that can be modeled with this approach are considered. A GE is characterized by an attribute and a geographical location. These two components of the GEs are intimately related, and therefore the errors and uncertainty associated to each of them are also related. A FGE E A , characterized by attribute “A,” is a GE whose position in the geographical space is defined by the fuzzy set E A = {(x, y) : (x, y) belongs to the GE characterized by attribute “A”} with membership function μ E A (x, y) ∈ [0, 1] defined for every location in the space of interest. The membership value 1 represents full membership. The membership value 0 represents no membership, and the values in between correspond to membership grades to E A , decreasing from 1 to 0. The construction of FGEs is based on the construction of the membership function μ E A (x, y), so its construction is of prime importance, but it is also one of the main difficulties of using fuzzy sets ([37], [95], [110]). Since the grades of membership to a fuzzy set may have several semantic interpretations, they may be used in several contexts with different meanings and therefore their semantic interpretation should be identified. Some methods to build FGEs are presented in the next section, and a semantic interpretation of the grades of membership is given for each case.4.2.1 CONSTRUCTION OF FUZZY GEOGRAPHICAL ENTITIES In chapter 3, section 3.1.2, two main approaches were presented to build GEs, the attribute-location approach and the location-attribute approach. In both approaches, several sources of uncertainty may be considered. 4.2.1.1 Attribute DefinitionIn the attribute-location approach, the first step is the definition of the attribute that characterizes the GE. This definition may just consist in the choice of a concept easily identified by humans on the ground, aerial photographs, or satellite images, such as buildings, roads, or rivers, or may depend upon a group of measurable characteristics© 2008 by Taylor & Francis Group, LLCGeographical Entities as Surfaces65Characteristic function(taking values on a scale Z ), such as, for example, radiance levels, altitude, or slope. In this case, the attribute definition involves a series of choices to identify the appropriate characteristics, which, in some cases, may not be easily determined. For example, suppose the regions suitable to construct an infrastructure are the GEs characterized by slopes between 10 and 20 percent and good solar exposure. Why choose slopes between 10 and 20 percent and not 9 and 21 percent? What is a good solar exposure? Since these choices are sometimes subjective and/or difficult to define, it may be considered that, in some situations, there is uncertainty associated to the definition of the attributes that characterize the GEs. When the attribute definition is just based on the choice of a concept, it is assumed that humans are able to identify it without any measured values. The attribute definition may be more or less precise, giving some instructions regarding, for example, what types of constructions are considered as buildings. With this approach, most difficulties will be encountered in the second phase of the construction of the GEs, that is, in the identification of the locations on the ground that correspond to the attribute, since the process is subjective. The location of the GE will depend upon the identification of the regions where the attribute occurs, and therefore any misinterpretation of its meaning will generate uncertainty in the position of the GE. So, the attributes should be defined with some detail to reduce any doubts that might occur during its identification on the terrain. Where the attribute is defined by a group of values within one or several characteristics chosen to identify the attribute, the values z of scale Z that correspond to the attribute have to be chosen for each characteristic considered in the definition of the attribute. In most situations, these values correspond to an interval Z A = [z, z] (see Figure 4.1), and therefore, z and z have to be identified for each attribute. One source of uncertainty in this case is that the transition between the set of values that correspond to the attribute and the ones that do not may not be clear, and therefore the attribute may be more accurately defined if, instead of choosing a crisp set Z A , a gradual transition between membership and nonmembership is allowed, using a A (see Figure 4.2). fuzzy set Z A requires the assignment to every value z of a The construction of fuzzy set Z grade of membership to the set, that is, the definition of a membership function of the z values to the set.1ZA0zFIGURE 4.1 Set of Z values that define attribute A.© 2008 by Taylor & Francis Group, LLCzZFuzzy Surfaces in GIS and Geographical AnalysisMembership function661~ ZA0 Core of z~AZ A. FIGURE 4.2 Fuzzy set ZThe semantic import approach used frequently to build membership functions (e.g., [14], [16], [74], [75], and [95]) considers this approach. Within this method, the grades of membership represent degrees of similarity. A method to build the membership functions based on this semantic interpretation is presented in [46]. The similarity view interprets grades of membership as a quantification of the similarity between the observed characteristics and the ideal ones [92]. The first step to build the membership function is to identity the values that ideally correspond to the attribute, that is, to identity the core Z Aid = [z id , z id ] of the fuzzy set. The second step corresponds to the computation of the degrees of similarity between the other z values and the ideal ones. These may be quantified considering the distance between those values and the extreme points of interval Z Aid . The distance A (see Figure 4.3) is given by between value z and the core of fuzzy set Z d(z, Z Aid ) =/ [z id , z id ] min[d(z, z id ), d(z, z id )] ⇐= z ∈ 0 z ∈ [z id , z id ](4.1)where d(z, z id ) and d(z, z id ) are, respectively, the Euclidean distance between z and the extreme points of interval Z Aid (see Figure 4.4). A are computed considering a The degrees of membership of the z values to Z (z) = f [d(z, Z )]. Function f is application dependent function f such that μ Aid ZA and translates the degree of variation of the membership grades with the distance.d(z1, ZAid ) z1zidZAidd(z2, ZAid ) zid z2ZFIGURE 4.3 Distances d(z 1 , Z Aid )and d(z 2 , Z Aid ) are, respectively, the distances of values z 1 and z 2 to the set of ideal values corresponding to attribute A, that is, to Z Aid = [z id , z id ].© 2008 by Taylor & Francis Group, LLCGeographical Entities as Surfaces67 d(z, zid)d(z, zid) zZAzididzidZFIGURE 4.4 Distances d(z, z id ) and d(z, z id ) are, respectively, the Euclidean distance of z to the extreme points of interval Z Aid .It must be a decreasing function such that f (0) = 1lim d(z,Z Aid )→+∞f [d(z, Z Aid )] = 0(4.2)In most applications, positive memberships are considered only for distances smaller than a predefined value dmax . This generates a fuzzy set with a bounded support, and therefore function f is such that f (0) = 1 d(z, Z Aid ) ≥ dmax =⇒ f [d(z, Z Aid )] = 0(4.3)Any function with these characteristics may be used, including functions with different branches for both sides of the core of the fuzzy set, generating asymmetric fuzzy sets. (Figure 4.2 shows an asymmetric fuzzy set.) Linear and sinusoidal functions are the most used. Another source of uncertainty in the definition of the attributes characterizing the GEs occurs when there are several versions of the set Z A that defines the attribute [46]. This type of uncertainty occurs, for example, when the interval Z A is determined by experts and several experts have different opinions about its amplitude, or when Z A is estimated using several methods and different methods determine different intervals, such as in the supervised classification of multispectral remote sensing images, where different classification methods produce different results. Therefore, as illustrated in Figure 4.5, for some z values, the classification is ambiguous, since, depending on the version used, it may belong or not to Z A . To model this type of uncertainty, as in the previous case, attribute A may be A . Although, in this case, the interpretation of grades of represented by a fuzzy set Z membership as random sets (see [33] or [92]) will be used to compute the grades of A ([46]). membership of the z values to Z Let us consider the random set A = {(Z A j , m j ) : j = 1, . . . , n}, where the sets Z A j are the several versions of the set Z A , and the values m j are weights assigned to the sets such that n j=1© 2008 by Taylor & Francis Group, LLCm j = 1.68Fuzzy Surfaces in GIS and Geographical AnalysisZ A1ZA2ZA310 ZzFIGURE 4.5 Three versions of Z A : Z A1 , Z A2 , and Z A3 . The inclusion of z in set Z A is then ambiguous.Then, according to the procedure to compute degrees of membership based on random A is given by sets, the membership function of every value z to the fuzzy set Z mj (4.4) μ Z A (z) = z∈Z A j4.2.1.2 Positioning an AttributeIn the second phase of the attribute-location approach to build GEs, the geographical location of the attribute chosen in the first phase is determined. In the cases presented in the previous section where the attribute definition is based on measurable quantities and the uncertainty of the attribute definition is modeled using fuzzy sets, for each location (xi , yi ) where the measurable quantities Z are known, that is, where a value z i is known, the uncertainty in the attribute space may be transposed to the geographical space considering μ E A (xi , yi ) = μ Z A (z i )(4.5)Therefore, whenever z values are known for a tessellation or in every point of the geographical space (when the geographical space is considered continuous), for each location (xi , yi ) of the geographical space, a degree of membership to the FGE E A , characterized by attribute A, is obtained. When no uncertainty is associated to the attribute definition, several sources of errors and uncertainty may be considered in the next step: •The predefined attribute may be difficult to identify, and therefore it will be difficult to determine its location on the geographical space. For example, the attribute is a certain land cover class, and in some regions, the available data leave doubts about which land cover class is present.© 2008 by Taylor & Francis Group, LLCGeographical Entities as Surfaces••• ••69The attribute definition is not accurate enough, raising doubts about whether entities with some characteristics belong or not to that attribute. For example, if the attribute is buildings, what is exactly considered to be a building? Is a hut a building? There is not an abrupt transition between the predefined attribute and other attributes, making the identification of its exact location difficult. For example, if the attribute is forest, it may be difficult to identify the limits of the forest, since there may be a gradual transition between the forest and the surrounding regions. The geographical location of the attribute changes with time, and therefore it is difficult to determine its position, such as the coastline or dunes. There are errors associated to the measurements made to determine the geographical location of the attributes, for example, observation errors in topographic measurements. There are several versions for the entities’ position, such as digitalizations made by several operators.To model the uncertainty or errors regarding the positioning of an attribute, two cases may be considered. One is when the attribute is defined using only a concept such as buildings, forest, or rivers, and the other case is when the attribute definition is based on measurable quantities. In the first case, the difficulty to position the attributes on the ground will depend upon the details given on its definition and upon the heterogeneity of those attributes on the region under study. The details used in the attribute definition should be such that it is clear what the attribute represents, but note that if too many details are given, the identification of all those details in the ground may complicate the operator’s work, since it may be difficult to identify, for example, in an aerial photograph, if a hut is made of wood or brick. So, the attribute definition should be adapted to the methods and sources of information available to identify the entities. Whenever the operator has some difficulties in the classification, he may always assign a degree of uncertainty to the entity. For example, if there is some uncertainty whether a certain entity should be considered a building or not, a degree of uncertainty may be assigned to it. These degrees of uncertainty are subjective and only indicative that some difficulties in the classification were found. They are assigned to the entity as a whole, since it is an indivisible object. Note that, in this case, the grade of membership represents uncertainty in the attribute that should be assigned to all the region. The outcome of this process is then a GE with a constant grade of membership to an attribute. These grades of membership translate degrees of membership to the attribute defining the GE and not uncertainty on the geographical space. They result from lack of data to assign the correct attribute or lack of attribute definition. In other situations, the uncertainty is not in the identification of the attribute corresponding to a certain GE, but in the identification of its exact location. In this case, a fuzzy set may be used to express the entities’ location in the geographical space. For example, if the attribute is forest and the operator has some difficulties in the identification of its limits, he may define a core where the attribute forest applies for sure and then a surrounding region where there is some transition between forest© 2008 by Taylor & Francis Group, LLC70Fuzzy Surfaces in GIS and Geographical AnalysisInteriorExteriorFrontierFIGURE 4.6 Egg-yolk approach to represent GEs.and nonforest. This corresponds to the identification of the core of the fuzzy set and its support, and therefore all the region between the support and the core belongs to the uncertainty region. If it is possible to differentiate further inside the uncertainty region, then α-levels may be identified, if not, only an uncertainty region may be used. This process generates FGEs, which correspond to the “egg-yolk” approach used, for example, in [20] or [38]. This approach considers that the GEs are formed by three regions: the interior, the frontier, and the exterior, where the frontier is represented not by lines, but by a region with any dimension or shape (see Figure 4.6), and that may be considered homogeneous or heterogeneous. The “egg-yolk” representation is a simplified representation of FGEs and is convenient when the GEs are to be represented using the vector data structure and to establish neighborhood relations between GEs with uncertain or fuzzy geographical position. It is important to stress that, in any of these cases, the grades of membership are subjective and translate human reasoning. When the attribute definition is based on measurable quantities and no uncertainty in the attribute definition is considered, the attributes are defined by intervals Z A . The attributes positioning on the geographical space corresponds to determine whether the values z i measured at location (xi , yi ) belong or not to interval Z A . Two sources of uncertainty may be identified in this case: • •There are errors affecting measured values z i . There are several measurements of z i made at different times.When there are errors affecting values z i , they influence the attribute assigned to that location, and therefore the geographical extent of the GEs. When these errors are modeled using a probability distribution function, a fuzzy set, a fuzzy number, or only an interval, the influence of these errors on the classification may be modeled using a method similar to the method proposed by Hisdal to simulate human language (see [55]), where the interpretation of the grades of membership is based on likelihoods. Denoting by EF (z i ) the function modeling the error in value z i , when EF (z i ) is a probability distribution function, the degree of membership of (xi , yi ) to the FGEs characterized by attribute A, defined by Z A = [z, z], is given by (see [46]). z EF (z i )dz i (4.6) μ E A (xi , yi ) = z© 2008 by Taylor & Francis Group, LLCGeographical Entities as Surfaces71µ 1ZA0 ziminzizzimaxzZFIGURE 4.7 The area of the shaded region is the grade of membership of location (xi , yi ) to the FGEs characterized by attribute A, defined by set Z A , where the uncertainty in the z i value is modeled with a triangular fuzzy number.When the error is modeled using fuzzy sets, fuzzy numbers, or intervals, the grades of membership are computed using zz EF (z i )dz i μ E A (xi , yi ) = zmax z min EF (z i )dz i(4.7)where z min and z max are, respectively, the smaller and larger values that z i can take according to the error estimation. This value corresponds to the normalized area of the EF (z i ) that is inside set Z A (see Figure 4.7). When there are several measurements of z i , made at different times, these measurements may reflect a changing geographical reality. That is, these measurements reflect a variation over time of what exists in that location. This time variation may be represented using FGEs. In this case, the random set view of fuzzy sets [33] may be used to compute the grades of membership [46]. If n observations are made of the z i values at all locations, then n versions of the GEs are obtained. The random set E A = {(E A j , m j )| j = 1, . . . , n} may be considered, where E A j , with j = 1, . . . , n, represents the n versions of the GE, and the values m j are weights assigned to each set of observations and therefore to each version, such that nj=1 m j = 1. The membership grades of each region to the FGE corresponding to attribute A are given by: μ E A (xi , yi ) = mj (4.8) (xi ,yi )∈A j4.2.1.3 Identifying Homogeneous RegionsIn the location-attribute approach to build GEs, two phases can also be considered: 1. identification of homogeneous regions in the geographical space; 2. determination of the attribute characterizing those regions. Errors and uncertainty may be found in both phases. The identification of homogeneous regions is subject to error and uncertainty, since it is necessary to determine© 2008 by Taylor & Francis Group, LLC72Fuzzy Surfaces in GIS and Geographical Analysisthe degree to which observed characteristics are considered similar, and may therefore be considered to belong to the same region. The resulting regions are supposed to be homogeneous, but a certain degree of heterogeneity will always be present. This heterogeneity may be modeled using fuzzy sets. The most used method to model the heterogeneity is the fuzzy k-means or fuzzy c-means (see, e.g., [16], [56], or [62]). The method enables the clustering of values in k fuzzy classes whose limits are not previously defined. It requires the choice of: 1. the number of classes to be defined; 2. a distance that is used to measure the degree of similarity between the elements of the class; 3. a number m ∈ [1, ∞], which determines the degree of diversity acceptable within each class (higher values correspond to higher heterogeneity); 4. a positive integer, which determines the degree of similarity required between the elements of the same class, which is usually used as a stop criterion. This method is usually started choosing a membership grade of each point to each class. Then, the mean of the degrees of membership of the elements that belong to the same class is computed. The next step is to recompute the value of the membership function of each element to each class, minimizing the weighted sum of the distances between each class mean and the degree of membership of the element to each class. With the obtained results, new means are computed for each class and the process is repeated iteratively until the degree of similarity between the elements of each class defined in step 4 is achieved. Note that, in this case, the degrees of membership to each class are degrees of similarity between each value and an ideal value, which, in each iteration, is the mean of all grades of membership to that class. Note also that, in this method, the membership of each location to the several classes adds up to 1, which means that the classes are not independent of each other [14]. This method has been frequently used to classify several types of phenomena, such as soil types, landforms, and pollution concentration (e.g., [15], [47], [75], and [109]). 4.2.1.4 Choosing an AttributeThe second phase of the classification procedure involves the identification of the attribute corresponding to each of the classes identified in the previous step, which is also subject to uncertainty and error. The fuzzy k-mean clustering method requires the number of classes to be identified a´ priori, which means that some knowledge about the terrain characteristics is necessary in advance. It may, however, happen that the classes obtained with the fuzzy k-mean approach do not describe the terrain adequately, and therefore it may not be easy to choose the attributes that correspond to each of the obtained classes since, on one hand, there may be some heterogeneity in the regions and, on the other hand, there may be doubts in the identification of that attribute. So the previous step may have to be repeated until a realistic classification is obtained.© 2008 by Taylor & Francis Group, LLCGeographical Entities as Surfaces4.373PROCESSING FUZZY GEOGRAPHICAL ENTITIESThe use of FGEs in a GIS environment requires operators capable of processing this type of entity. The immediate approach to process FGEs is to convert them into crisp entities and use the usual operators to perform the necessary operations. Since the α-levels of fuzzy sets are crisp sets, the easiest way to convert FGEs to crisp GEs is to substitute the entity by one of its α-levels. With this approach, different versions of the FGE may be obtained according to the needs of each application, choosing different α-levels to represent it. This versatility may be an advantage over the use of common crisp GEs, since different versions of the FGE may be considered according to the needs, but it has also the disadvantage of having different GEs representing the same characteristic in different contexts, which may become confusing if not properly explained in the metadata. This approach, however, does not use the full capabilities of FGEs, since their conversion to crisp entities implies a loss of information regarding their positional uncertainty. Therefore, it is useful to develop operators capable of processing the FGEs without defuzzifying them. These operators work with fuzzy inputs and may have crisp or fuzzy outputs. The operators with fuzzy outputs propagate the fuzziness in the input data to the results of the analysis operations. Since what characterizes a FGE is the representation of its position in the geographical space, only spatial operators will be considered, that is, operators that process the position of the entity in the geographical space. Some of these operators only generate attributes, which may be crisp or fuzzy, and others generate new entities. Some examples are shown in Table 4.1. Since the geographical extent of FGEs is represented by fuzzy sets, some operators developed within fuzzy set theory may be used to process FGEs.4.3.1 COMPLEMENT The complement of a GE is its exterior, that is, the region that does not belong to it, and therefore is the complement of the set representing the GE. Then, the complementTABLE 4.1 Some Spatial Operations OperatorsInputBufferOne entityComplement Intersection ReunionSeveral entitiesArea PerimeterNew entitiesOne entityShapeNew attributesDistance Direction Neighborhood© 2008 by Taylor & Francis Group, LLCOutputSeveral entities74Fuzzy Surfaces in GIS and Geographical AnalysisFIGURE 4.8 Fuzzy geographical entity.of a FGE is the complement of the fuzzy set representing the entity. The standard complement of a fuzzy set A is the set indicated in Definition 1.6. Therefore, the standard complement of a FGE E is the FGE CE, such that, for all the space under consideration, μCE (x, y) = 1 − μ E (x, y) Figure 4.9 shows the standard complement of the FGE shown in Figure 4.8.4.3.2 UNION AND INTERSECTION Some authors suggested the use of the standard fuzzy operators of union and intersection to determine the union and intersection of FGEs ([16], [59], [75]). The standard union of two fuzzy sets A and B is given by Definition 1.4. Then, the union of two FGEs E and F is the FGE, such that, for every point (x, y) of the geographical space (see Figure 4.10), μ E∪F (x, y) = max[μ E (x, y), μ F (x, y)]FIGURE 4.9 Complement of fuzzy geographical entity shown in Figure 4.8.© 2008 by Taylor & Francis Group, LLCGeographical Entities as Surfaces751 0.90.7 0.6 (a) Fuzzy geographical entity E1(b) Fuzzy geographical entity E20.5 0.4 0.3Membership function values0.80.2 0.1 0 (c) Intersection of E1 and E2(d) Union of E1 and E2FIGURE 4.10 (a) FGE E 1 , (b) FGE E 2 , (c) intersection of FGEs E 1 and E 2 , and (d) union of FGEs E 1 and E 2 .A similar approach may be considered for the intersection. The standard intersection of two fuzzy sets is given by Definition 1.5. Then, the standard intersection of two FGEs E and F is the FGE, that, for every point (x, y) of the geographical space, satisfies (see Figure 4.10), μ E∩F (x, y) = min[μ E (x, y), μ F (x, y)]4.3.3 BUFFERS GENERATION Operators to generate buffers around FGEs proposed, for example, by [34] and by [59]. Katinsky proposes that a buffer around FGEs be obtained considering traditional buffers around each α-level of the FGE. In this way, each α-level will generate a region and its degree of membership to the buffer is α (the grade of membership of the αlevel that generated it). Fuzzy buffers are also proposed, which introduce another source of uncertainty, since a fixed distance is not used. A more complex approach is presented by [34] and [52], which present several algorithms to generate fuzzy buffers, including iterative methods, global methods, and methods based on the use of graphical software.© 2008 by Taylor & Francis Group, LLC76Fuzzy Surfaces in GIS and Geographical Analysis4.3.4 DISTANCES AND DIRECTIONS Altman [1] developed a metric to compute distances between FGEs and directions defined by two FGEs. This approach considers that the distance between two fuzzy sets, represented by discrete points, is a fuzzy set whose elements are the values of the distance between the points of both FGEs. That is, dist(E, F) = {di : di = d[(x1 , y1 ), (x2 , y2 )], (x1 , y1 ) ∈ E ∧ (x2 , y2 ) ∈ F} where d[(x1 , y1 ), (x2 , y2 )] represents the distance between points (x1 , y1 ) and (x2 , y2 ). The Euclidean distance can be used, as well as any other distance of interest. The grade of membership of each value di to the fuzzy distance is given by μdist(E,F) (di ) = max{min[μ E (x1 , y1 ), μ F (x2 , y2 )]} diThe metric developed by Altman [1] for directions is similar to the one developed for distances, replacing the computation of the distance between the points of both sets by the computation of the bearing defined by them.4.3.5 AREA The computation of areas of GEs is a basic operation in a GIS. Several approaches have been considered to compute the area of FGEs, generating crisp and fuzzy results. According to Katinsky [59], unambiguous areas of FGEs can only be computed if the FGEs are defuzzified, and no further developments are made. Erwig and Schneider [39] point out that the areas of fuzzy regions are intervals. Their lower limit is the area of the region’s core and the upper limit the area of the region’s support. Since the use of intervals requires new operators, they proposed considering only minimum and maximum area values corresponding to the lower and upper limits of the intervals. 4.3.5.1 Rosenfeld AreaRosenfeld [87] proposed an operator to compute the area of a fuzzy set. Since the geographical location of FGEs is represented by a fuzzy set, this operator can be applied to compute the area of FGEs. The Rosenfeld operator to compute areas (expressed here as the Rosenfeld area R A) considers that the area of a fuzzy set E, formed by n regions ri , with area A(ri ) and membership function μ E (ri ) is given by: RA(E) =n μ E (ri )A(ri )i=1This operator returns a positive real number and therefore generates a crisp value for the area. Considering the standard fuzzy intersection, union, and complement operators and establishing a comparison with the three following well-known properties of areas of crisp regions:© 2008 by Taylor & Francis Group, LLCGeographical Entities as Surfaces771. ∀E Area(E) ≥ 0 2. ∀E, F Area(E ∪ F) = Area(E) + Area(F) − Area(E ∩ F) 3. ∀E, F : F ⊆ E Area(E − F) = Area(E) − Area(F) where E − F = E ∩ C F, denoting C F the complement of set F, the Rosenfeld area has the properties listed below. Proofs and further explanations of other characteristics of the Rosenfeld area can be found in [44]. Property RA1: For any FGE E, R A(E) ≥ 0. Property RA2: Let E and F be two FGEs, then RA(E ∪ F) = RA(E) + RA(F) − RA(E ∩ F) Property RA3: If E ∩ F = φ, that is, ∃/ ri : µ E (ri ) > 0 ∧ µ F (ri ) > 0, then RA(E ∪ F) = RA(E) + RA(F)(4.9)Property RA4: Let E and F be two FGEs such that F ⊆ E. If ∀ri ∈ support(F), µ E (ri ) = 1, that is, support (F) ⊆ core(E), then RA(E − F) = RA(E) − RA(F) Property RA5: For any FGEs E and F such that F ⊆ E, RA(E − F) ≥ RA(E) − RA(F)(4.10)As shown in the previous properties, some care must be taken when making operations with Rosenfeld areas, since the Rosenfeld area of the difference of two FGEs may not be equal to the difference of the Rosenfeld areas of both entities. The method proposed by Rosenfeld to compute the area of a FGE considers that the contribution of the area of each elementary region to the total area is proportional to the degree of membership of the elementary region to the entity. Then, this operator is appropriate to determine the area of a FGE, when the degrees of membership represent the proportion of the area of the elementary region occupied by the attribute characterizing the entity. These FGEs may, for example, be obtained converting GEs from the vector data structure to the raster data structure (for more details, see [43]). However, when the degrees of membership to the FGE represent the uncertainty of whether the elementary regions belong to the GE or not, the spatial extension of the GE is not known and, consequently, its area is also not known. In this case, the value of the area of the FGE obtained with the Rosenfeld operator is just an approximate value of the area, and does not give any other information about the other values it may take. For example, consider a FGE that represents the risk of atmospheric pollution with a certain pollutant, where the degrees of membership of each elementary region to the FGE represent the possibility that the region is affected by the pollutant. Usery presents a simple method to build such a membership function using the semantic import approach [95]. Since any region with µ > 0 may belong to the affected zone, the area of this entity may vary between the areas of the support and the core of the fuzzy set representing the FGE. Note that the degrees of membership of interest may© 2008 by Taylor & Francis Group, LLC78Fuzzy Surfaces in GIS and Geographical Analysisvary with the application. If, for example, the objective is to determine the area of all regions that may be affected by the pollutant, or if only the area which has a possibility of being affected larger than 0.4 is of interest, the Rosenfeld area operator is not useful. The Rosenfeld area operator does not give also any information about the possible variation of the area with the different degrees of membership to the entity. If the degrees of membership translate degrees of similarity to the attribute characterizing the FGE, the area of the GE depends on the degrees of similarity acceptable for a certain application. For example, if the degrees of membership represent degrees of similarity to the attribute “pine forest,” based on the percentage of pine trees observed on the terrain and on the percentage of pine trees considered typical of a pine forest, the area of the entity may, once again, take values between the area of the support and the area of the core of the fuzzy set that represents the FGE. If the objective of a certain application is to determine the area of all regions where pine trees can be found, all degrees of membership are acceptable and the wanted area is the area of the support of the FGE. On the opposite direction, if the objective is to determine the area of the regions where there are only pine trees, only the degrees of membership equal to 1 are of interest. All intermediate situations can be considered, and the Rosenfeld area operator is not useful in either of them. The previous examples show that the information given by the Rosenfeld area operator is limited and insufficient for many applications. 4.3.5.2 Fuzzy AreaTo overcome some of the limitations of the previous operator, a new operator was proposed, called the fuzzy area operator [44]. The spatial location of a FGE is represented by a fuzzy set, which is uniquely represented by a family of α-levels, for α ∈ [0, 1]. Since an α-level is a crisp set such that E α = {ri : µ E (ri ) ≥ α}, its area, denoted by Area(E α ), is the sum of the areas of elementary regions ri , forming a tessellation, that belong to it. Let us consider the function Area E : [0, 1] → R+ 0 α → Area E (α) = Area(E α ) = z and denote by z i , i = 1, . . . , n, a set of values of R+ 0 such that ∃αi : z i = Area E (αi ), where 0 < αi < αi+1 ≤ 1. DEFINITION 4.1The fuzzy area of a FGE is the fuzzy set FA(E) = {(z, µ FA(E) (z))} with µ FA(E) (z) : R+ 0 → [0, 1] and ⎧ max αi if ∃i : z = z i ⎪ ⎪ ⎨zi =Area E (αi ) z−z k (αk+1 − αk ) + αk if ∃ / i : z = z i ∧ z ∈ [ Area E (1), Area E (0)] µ FA(E) (z) = zk+1 −z k ⎪ ⎪ ⎩ 0 if z ∈ / [ Area E (1), Area E (0)] (4.11) min (αi ). where z k = max(z i ) and αk = z i ≤z© 2008 by Taylor & Francis Group, LLCz k = Area E (αi )Geographical Entities as Surfaces790000000000000000 0.1 00000 0.1 0.2 0 0.3 0.2 0000 0.1 0.3 0.4 0.8 0.5 0.3 0.2 0.1 0 0 0.3 0.4 0.7 1 0.6 0.4 0.3 0.2 0 0 0.2 0.3 11 0.8 0.5 0.4 000 0.1 0.2 11 0.9 0.6 0.5 0.3 000 0.1 0.6 0.6 1 0.8 0.5 0.2 0000 0.3 0.7 0.8 0.7 0.8 0.1 00000000000FIGURE 4.11 Fuzzy geographical entity E.To compute the fuzzy area of the FGE represented in Figure 4.11, some α-levels αi have to be considered and their areas computed. Table 4.2 shows the areas z i obtained for the α-levels αi . Figure 4.12 shows a plot of the fuzzy area of E obtained using the values of Table 4.2. A MATLAB routine to compute fuzzy areas of FGEs can be found in the attached CD (routine fuzzyarea.m). The fuzzy area has some properties corresponding to the area properties indicated in the previous section. These properties are listed below. The proofs and some additional explanations about the fuzzy area may be found in [44]. Property FA1: ∀E, the support of FA (E) is a subset of R+ 0. Property FA2: ∀E, µFA(E) (z) is a decreasing left-continuous function over z ∈ [ Area E (1), Area E (0)].TABLE 4.2 Area of the α-Levels of E© 2008 by Taylor & Francis Group, LLCiαiz i = Area(Eαi )1 2 3 4 5 6 7 8 9 10 110.001 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 168 68 58 47 36 30 23 19 15 11 780Fuzzy Surfaces in GIS and Geographical Analysis1 0.9 Membership function0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 00510152025 30 Area35404550FIGURE 4.12 Fuzzy area of FGE E.Property FA3: If E is a normal FGE, then FA(E) is a fuzzy number. Property FA4: If ∃/ ri : µ E (ri ) > 0 ∧ µ F (ri ) > 0 (that is, E ∩ F = φ), then FA(E ∪ F) = FA(E) + FA(F)(4.12)The notation used in the following properties is such that, for a fuzzy set S with α-levels Sα = [sα− , sα+ ], Sα+ = sα+ and Sα− = sα− . Property FA5: Let E and F be two FGEs, such that ∃ri : µ E (ri ) = 1 ∧ µ F (ri ) = 1. Then, + + + FA(E ∪ F)+ α = FA(E)α + FA(F)α − FA(E ∩ F)α ≤ [FA(E) + FA(E) − FA(E ∩ F)]+ α(4.13)Property FA6: Let E and F be two FGEs, such that ∃ri : µ E (ri ) = 1 ∧ µ F (ri ) = 1. Then, − − − FA(E ∪ F)− α = FA(E)α + FA(F)α − FA(E ∩ F)α ≥ [FA(E) + FA(E) − FA(E ∩ F)]− α(4.14)Note that properties FA5 and FA6 show that FA(E ∪ F) ⊆ FA(E) + FA(F) − FA(E ∩ F)(4.15)Property FA7: If E and F are FGEs such that F ⊆ E, then + FA(E − F)+ α ≤ [FA(E) − FA(F)]α(4.16)Property FA8: If E and F are FGEs such that F ⊆ cor e(E) and E − F is a normal FGE, then − + − FA(E − F)− α = min[FA(E) − FA(F)]α = FA(E)1 − FA(F)0+whereFA(F)+ 0+represents the largest value of the support of FA(F).© 2008 by Taylor & Francis Group, LLC(4.17)Geographical Entities as Surfaces81As shown above, the fuzzy area operator generates a fuzzy number, but, even though some properties similar to the area of classic regions hold, in some cases, care must be taken when making operations with the fuzzy areas, since the results of the operations (mainly the difference) may have a behavior different from the expected.4.3.6 PERIMETER The perimeter computation of GEs is also a basic operator of a GIS. 4.3.6.1 Rosenfeld PerimeterRosenfeld [87] proposed an operator to compute the perimeter of a fuzzy set formed by a finite set of contiguous and homogeneous regions. This operator, herein designated by Rosenfeld perimeter (RP), may be applied to FGE represented by a tessellation. The Rosenfeld perimeter is given by: RP(E) =ni j n i, j=1i< jk=1|µ E (ri ) − µ E (r j )|l(ai jk )(4.18)where n is the number of elementary regions forming the FGE, n i j is the number of arcs separating regions ri and r j and l(ai jk ) is the length of k arc ai jk of contact between regions ri and r j . This operator considers that each arc separating contiguous elementary regions has a degree of belonging to the perimeter equal to the difference of the membership grades associated to the elementary regions that it separates. Therefore, as for the Rosenfeld area operator, the Rosenfeld perimeter operator generates an approximate real value for the perimeter of the FGE, giving no other information about the other values it can take, or about its variability with the grades of membership to the FGE. To overcome these limitations a fuzzy perimeter operator was proposed. 4.3.6.2 Fuzzy PerimeterA level cut of a FGE E is a classical set. Let P (E α ) be the perimeter of the α-level cut of the fuzzy set representing the FGE. Let us now consider for each FGE E a function PE such that PE : [0, 1] −→ R+ 0 α −→ PE (α) = P(E α ) = p(4.19)and denote by pi , i = 1, . . . , n, a set of values of R+ 0 such that ∃αi : pi = PE (αi ), where 0 < αi < αi+1 < 1. DEFINITION 4.2The fuzzy perimeter of a FGE E is the fuzzy set FP(E) = {(z, µ F P(E) (z))} where µFP(E) : R+ 0 −→ [0, 1] p −→ µ F P(E) ( p)© 2008 by Taylor & Francis Group, LLC(4.20)82Fuzzy Surfaces in GIS and Geographical AnalysisTABLE 4.3 Perimeter of the α-Levels of E αipi = P(Eαi )0.001 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 136 36 34 30 24 22 22 24 24 14 14i 1 2 3 4 5 6 7 8 9 10 11andµFP(E) ( p) =⎧ ⎪ ⎪ ⎪ ⎪ ⎨ (p ⎪ ⎪ ⎪ ⎪ ⎩maxpk , pk+1 : k ≤ p≤ pk+1 ∨ pk+1 ≤ p≤ pk ) ∧ pk = pk+10p− pk pk+1 − pk (αk+1 − αk ) + αk ifp ∈ [min pi , max pi ](4.21)if p ∈ / [min pi , max pi ]The perimeter values pi corresponding to the α-levels αi of the FGE represented in Figure 4.12 are shown in Table 4.3. Figure 4.13 shows the plot of the pi values shown 1 Crisp perimeter values Fuzzy perimeter0.9Membership function0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 005101520 25 Perimeter3035FIGURE 4.13 Fuzzy perimeter of fuzzy geographical entity E.© 2008 by Taylor & Francis Group, LLC4045Geographical Entities as Surfaces83in Table 4.3 and the fuzzy perimeter of FGE E. A MATLAB routine to compute fuzzy perimeters of FGEs can be found in the attached CD (routine fuzzyperimeter.m). Note that the perimeter-levels 0.5 and 0.6 of α are smaller than the perimeter values of α-level 0.7 (which has a larger area, as can be seen in Table 4.2). Therefore, the fuzzy perimeter is not built in the same way the fuzzy area is because, otherwise in some cases, the output would not be a fuzzy set. The fuzzy perimeter operator satisfies the following properties. Proofs can be found in [45]. Property FP1: For all FGE E, the support of PF(E) is a subset of R+ 0. Property FP2: If E is a normal FGE, then PF(E) is a fuzzy number. Such as with the fuzzy area operator, the support of the fuzzy perimeter shows the set of values the perimeter of the FGE can take and each α-level cut of the fuzzy perimeter is the set of all values the perimeter can take when level cuts of the FGE corresponding to values larger than or equal to α are considered. Therefore, the fuzzy perimeter operator, as the fuzzy area operator, incorporates more information than the crisp operators. Since the fuzzy perimeter operator generates a fuzzy number, it is possible to perform operations with it, such as the addition of perimeters or the computation of the shape of a FGE, where a fuzzy area may also be used. For more details see [45].© 2008 by Taylor & Francis Group, LLC5 Surface Modeling Jorge Santos CONTENTS 5.1 5.2 5.3Introduction — Data Uncertainty in Surface Models . . . . . . . . . . . . . . . . . . . . . . . . . 85 Univariate Case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 Bivariate Case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 5.3.1 Non-Gridded Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 5.3.1.1 Fuzzy TIN Interpolator . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 5.3.1.2 Fuzzy Interpolators Based on Weighted Average . . . . . . . . . . 92 5.3.1.3 Fuzzy Interpolators Based on Radial Functions. . . . . . . . . . . . 93 5.3.2 Gridded Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 5.3.2.1 Bivariate Lagrange Polynomial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 5.3.2.2 Bilinear Fuzzy Splines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 5.3.2.3 Bicubic Fuzzy Splines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 5.3.3 Fuzzy Geostatistic Interpolator (Kriging) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 5.3.3.1 Estimation of Fuzzy Variogram . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 5.3.3.2 Kriging Fuzzy Data. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1035.1INTRODUCTION — DATA UNCERTAINTY IN SURFACE MODELSTo model a continuous geographic phenomenon, first a set of data points needs to be collected from the geographical space. There are two stages in this process: sampling and measurement. Sampling refers to the distribution of measurement places, in order to have a representative sample data set of the phenomena. In this context, the uncertainty arises not only from the inaccuracy of measurements but also from the lack of representativity of sample points and from the choice of the model to be used. The uncertainty will be included in membership functions of fuzzy numbers, which will be used to express attribute values (see Figure 5.1). Therefore, the sample set will by given by f (xi , z˜ i ), i = 1, 2, . . . , N , (5.1) where f (xi ) ∈ Rn is the position of sample z˜ i ∈ F(R). Mathematical interpolators will be used as models for continuous geographic phenomena. The first condition for those interpolators is that they should assume the sampled values in the sampled sites. ˜f (xi ) = z˜ i ,i = 1, 2, . . . , N .(5.2) 85© 2008 by Taylor & Francis Group, LLC86Fuzzy Surfaces in GIS and Geographical Analysisz+ z1 z– YZ X y xFIGURE 5.1 Triangular fuzzy sample.Therefore, when sample values are fuzzy numbers, we will have fuzzy interpolators. The fuzzy interpolator can be defined by its α-levels [ f (x)]α = [ f α− ( x), f α+ ( x)],α ∈ [0, 1],(5.3)α, α ′ ∈ [0, 1].(5.4)with, α < α ′ ⇒ [ f (x)]α′ ⊂ [ f (x))]α ,The type of function to be used will have the general formula ˜f (x) =n ζ˜ j φ j (x),(5.5)j=1where φ j (x) are the basis functions, which set the interpolator type. Using α-levels, we get n [ζ j ]α φ j (x), α ∈ [0, 1], (5.6) [ f (x)]α = j=1and, expressing intervals in radius/midpoint format, we have [ f (x)]α =n ζˇ j,α φ j (x) +j=1n ρ j,α |φ j (x)|[−1, 1],α ∈ [0, 1],(5.7)j=1where ζˇ j,α and ρ j,α are, respectively, the midpoint and the radius of the interval [ζ j ]α . Another important condition is that the surfaces generated by those interpolators should behave in the same way as the phenomena that they model. For example, smoothness should be similar. There are several well-known crisp interpolators usually used in geographic modeling. The generalization from crisp to fuzzy interpolators will be done in the way to keep the same properties, namely, smoothness. Consequently, we introduce the notion of consistent fuzzy interpolator, which is a fuzzy interpolator whose α-levels’ limits are still functions of the same type of the original crisp ones. We will see that this additional condition will force us to relax the conditions in Equation (5.2) to ˜f (xi ) ⊇ z˜ i ,© 2008 by Taylor & Francis Group, LLCi = 1, 2, . . . , N ,(5.8)Surface Modeling87or [ f (x)]α =n ζˇ j,α φ j (x) +n ρ j,α φ j (x)[−1, 1] ⊇ [z i ]α ,α ∈ [0, 1],(5.9)j=1j=1where the radius ρ j,α should be minimal.5.2UNIVARIATE CASEIn the univariate case, we will represent the sampling set by {(xi , z˜ i ), i = 1, 2, . . . , N }, with the partition a = x1 < x2 < · · · < xN = b. The problem here is to find a mathematical function ˜f that will model the geographical phenomena within the interval [a, b] ⊂ R, following the N conditions ˜f (xi ) = z˜ i ,i = 1, 2, . . . , N˜f (xi ) ⊇ z i ,i = 1, 2, . . . , N .or, at least, The type of function to be used will have the general formula ˜f (x) =N ζ˜ j φ j (x),j=1or, using α-levels, [ f (x)]α =N [ζ j ]α φ j (x),α ∈ [0, 1],j=1and, expressing intervals in radius/midpoint format, [ f (x)]α =N ζˇ j,α φ j (x) +N ρ j,α |φ j (x)|[−1, 1],α ∈ [0, 1].(5.10)j=1j=1Let us start by the particular example of Lagrange interpolation polynomial, where the basis functions are φ j (x) = L j (x) ≡N (x − xi ) , (x j − xi ) i=1j = 1, 2, . . . , N .(5.11)i= jIn a first approach, the α-levels of Lagrange fuzzy interpolator will be given by [ p(x)]α =N zˇ j,α L j (x) +j=1N r j,α |L j (x)|[−1, 1],α ∈ [0, 1],(5.12)j=1where zˇ j,α and r j,α are, respectively, the midpoint and the radius of a sample α-level.© 2008 by Taylor & Francis Group, LLC88Fuzzy Surfaces in GIS and Geographical Analysis50 45 40 35 30 25 20 15 135140145150155160165170175180FIGURE 5.2 Triangular fuzzy Lagrange polynomial (support limits in dash, modal curve in continuous, and consistent support limits in dot).Originally, Lagrange polynomial is infinitely differentiable. However, the fuzzy generalization in Equation (5.12) does not have that property, since the α-levels’ limits are pα− (x) =N zˇ j,α L j (x) −j=1=N N r j,α |L j (x)|and pα+ (x)j=1zˇ j,α L j (x) +j=1N r j,α |L j (x)|.(5.13)j=1The presence of absolute values |L j (x)| generates nondifferentiable functions (see Figure 5.2). This leads to an inconsistent fuzzy interpolator. To achieve consistency, a Lagrange polynomial with the same degree should approximate the α-levels’ limits given by Equation (5.13). To solve this problem, we have to find the consistent interpolator ˜f with α-levels [ f (x)]α =N ζˇ j,α L j (x) +N ρ j,α L j (x)[−1, 1],α ∈ [0, 1],(5.14)j=1j=1such that [ p(x)]α ⊆ [ f (x)]α =N ζˇ j,α L j (x) +j=1N ρ j,α L j (x)[−1, 1],α ∈ [0, 1], (5.15)j=1where the radii ρ j,α are minimal. This generates a constrained optimization problem min ρα , subject to ραραt L(x)− rαt© 2008 by Taylor & Francis Group, LLC|L(x)| ≥ 0,∀x ∈ [a, b], α ∈ [0, 1],(5.16)Surface Modeling89where ρα , rα , L(x), and |L(x)| are vectors with components ρ j,α , r j,α , L j (x) and |L j (x)|, respectively. The above optimization problem has an infinite number of conditions (semiinfinite programming). A simple approach to this is to subdivide the interval [a, b], approximating the infinite conditions by a finite number. Other known interpolators can be fuzzified using the same approach. We will see now the case of other popular interpolators like splines. Linear splines are a simple case of those interpolators. The fuzzy linear splines s˜1 will be given by its following α-levels [s1 (x)]α =N zˇ j,α s1, j (x) +j=1N j=1where (x j+1 − x) , (x j+1 − x j ) r j,α s1, j (x) [−1, 1] ,α ∈ [0, 1],(5.17)(x − x j ) , x ∈ [x j , x j+1 ]. (x j+1 − x j ) Since x j < x j+1 , we have always s1, j (x) = s1, j (x), s1, j+1 (x) = s1, j+1 (x), and s1, j (x) =[s1 (x)]α =N and s1, j+1 (x) =zˇ j,α s1, j (x) +j=1N r j,α s1, j (x)[−1, 1],α ∈ [0, 1].(5.18)j=1Consequently, fuzzy linear splines are inherently consistent (see Figure 5.3). The most used splines are the cubic ones, which can be given by s3 (x) =N z j s3, j (x),j=145 40 35 30 25 20 15 10 5 0 –5020406080100120140160180200FIGURE 5.3 Triangular fuzzy linear spline (support limits in dash and modal curve in continuous).© 2008 by Taylor & Francis Group, LLC90Fuzzy Surfaces in GIS and Geographical Analysis38 36 34 32 30 28 26 145150155160165170175180185FIGURE 5.4 Triangular fuzzy cubic spline (support limits in dash, modal curve in continuous, and consistent support limits in dot).where the base functions s3, j are cubic splines interpolating the data points {(x j , δi, j ), 1, i = j j = 1, 2, . . . , N }, with δi. j = , i = 1, 2, . . . , N . Following the same 0, i = j procedure, a first approach for fuzzy cubic splines will have the α-levels [s3 (x)]α =N zˇ j,α s3, j (x) +j=1N r j,α |s3, j (x)|[−1, 1],α ∈ [0, 1].j=1As in the Lagrange polynomial, the consistency is lost here (see Figure 5.4). To achieve consistency, we follow the same strategy of Lagrange case, getting [ f (x)]α =N zˇ j,α s3, j (x) +j=15.3N ζ j,α s3, j (x)[−1, 1],α ∈ [0, 1].j=1BIVARIATE CASEThe natural extension from the univariate to the bivariate case is to use the tensor product, but data have to be arranged in a grid format. However, in most of the practical problems, the sampling set is given by {(xi , yi , z i ), i = 1, 2, . . . , N },in a region D ⊂ R2 ,where the positions (xi , yi ) have nongrid distribution. Therefore, first we will study the general case of irregular-spaced data.© 2008 by Taylor & Francis Group, LLCSurface Modeling91The problem now is to find a mathematical function ˜f that will model the geographical phenomena, following the N conditions ˜f (xi , yi ) = z i ,or, at least,˜f (xi , yi ) ⊇ z i ,i = 1, 2, . . . , N i = 1, 2, . . . , N .The type of function to be used will have the general formula ˜f (x, y) =N ζ˜ j φ j (x, y),j=1with α-levels given by [ f (x, y)]α =N zˇ j,α φ j (x, y) +N ζ j,α |φ j (x, y)|[−1, 1],α ∈ [0, 1].(5.19)j=1j=15.3.1 NON-GRIDDED DATA In this subsection, the data will be considered spatially irregularly distributed over a region (see Figure 5.5). There are several interpolators able to solve this type of problem. These interpolators are usually local, depending only on the existing data in a neighborhood of the interpolation position. The well-known Delaunay triangulation is usually used to find these neighborhoods, as we will see later on. 5.3.1.1 Fuzzy TIN InterpolatorAs the name suggests, the triangular irregular network (TIN) interpolator is defined over a triangulation of data positions. Inside every triangle Tk , the interpolator is defined by a plane passing through the triangle’s vertex, which is given by f (x, y) = ak x + bk y + ck , (x, y) ∈ Tk ,k = 1, 2, . . . , Nt ,(5.20)50 40 30 0200 15050 100100 15050 2000FIGURE 5.5 Example of a fuzzy triangular nongridded data set.© 2008 by Taylor & Francis Group, LLC92Fuzzy Surfaces in GIS and Geographical Analysis25 20 15 0200 50150 100100 15050 2000FIGURE 5.6 Fuzzy TIN surface for fuzzy triangular data in Figure 5.5.where Nt is the number of triangles and ak , bk , ck are the solution of the following linear system of equations ⎡ ⎤ ⎤ ⎡ ⎡ ⎤ ak xk,1 yk,1 1 z k,1 ⎢ ⎥ ⎥ ⎢ ⎢ ⎥ (5.21) Ak xk = z k , withAk = ⎣ xk,2 yk,2 1 ⎦, xk = ⎣ bk ⎦, z k = ⎣ z k,2 ⎦. xk,3 yk,3 1 ck z k,3Therefore, the resulting surface is a set of contiguous, nonoverlapping triangular facets. The fuzzy TIN interpolator ˜f (x, y) is defined by its α-levels [ f (x, y)]α for which limits f α− (x, y) and f α+ (x, y) are TINs. For every triangle Tk and for every α-level, the limits f α− (x, y) and f α+ (x, y) are planes determined by solving two linear systems like in Equation (5.21). The only difference is in the right members of equation, which are − − − − + + + + z k,α = [z k,α,1 z k,α,2 z k,α,3 ]t and z k,α = [z k,α,1 z k,α,2 z k,α,3 ]t , respectively. Consequently, the resulting fuzzy TIN surface will be like in Figure 5.6. 5.3.1.2 Fuzzy Interpolators Based on Weighted AverageWeighted averages can be written in the form f (x, y) =Nk z j ω j (x, y), withj=1Nk ω j (x, y) = 1,(x, y) ∈ Vk ,j=1where Vk is a neighborhood of (x, y) containing points {(xi , yi ) ∈ Vk , i = 1, 2, . . . , Nk }. The functions ω j are called weights and usually depend on the position (x, y). A common case is to define those weights based on the inverse of the distances di (x, y) between the position (x, y) where the interpolation takes place and the neighborhood points in Vk Nk −p −p di (x, y), ω j (x, y) = d j (x, y)/ i=1with di (x, y) = (x − xi )2 + (y − yi )2 , p ∈ N, i = 1, 2, . . . , Nk . © 2008 by Taylor & Francis Group, LLCSurface Modeling9330 20 10 0200 50150 100100 15050 2000FIGURE 5.7 Fuzzy surface resulting from the fuzzy Shepard method ( p = 2) for fuzzy triangular data in Figure 5.5.This choice of weights generates the so-called Shepard method or inverse distance weighting (IDW) of interpolation, which is a simple approach to model geographical phenomena, where usually dependency is inversely proportional to distance (see Figure 5.7). Since the weight functions ω j are always non-negative, the generalization to fuzzy Shepard method is straightforward. The fuzzy interpolator will be given by ˜f (x, y) =Nk z˜ j ω j (x, y),(x, y) ∈ Vk ,j=1with α-levels expressed by [ f (x, y)]α =Nk zˇ j,α ω j (x, y)j=1+Nk r j,α ω j (x, y)[−1, 1],α ∈ [0, 1],(x, y) ∈ Vk . (5.22)j=15.3.1.3 Fuzzy Interpolators Based on Radial FunctionsWeighted functions are an example of radial functions, since they do not depend on the direction but only a distance. Another interpolator based on radial functions is the thin-plate splines (see Figure 5.8). This interpolator is defined by M a j κ j (x, y) + a M+1 + a M+2 x + a M+3 y, (5.23) S(x, y) = j=1whereκ j (x, y) =1 2 d (x, y) ln[d j (x, y)], 8π j© 2008 by Taylor & Francis Group, LLCd 2j (x, y) = (x − x j )2 + (y − y j )2 . (5.24)94Fuzzy Surfaces in GIS and Geographical Analysis40 20 0200 50150 100100 15050 2000FIGURE 5.8 Fuzzy surface resulting from the fuzzy thin-plate spline interpolator for fuzzy triangular data in Figure 5.5.The coeficients a j ( j = 1, 2, . . . , M + 3) are found by solving the linear system of equations Aa = z, (5.25) whereA= K P , Pt 0⎤ a1 ⎢ . ⎥ ⎢ .. ⎥ ⎥ ⎢ ⎥ ⎢ ⎢ aM ⎥ a=⎢ ⎥, ⎥ ⎢a ⎢ M+1 ⎥ ⎢ ⎥ ⎣a M+2 ⎦ ⎡a M+3with⎤ κ1 (x1 , y1 ) · · · κ M (x1 , y1 ) ⎥ ⎢ .. .. .. ⎥, K =⎢ . . . ⎦ ⎣ κ1 (x M , y M ) · · · κ M (x M , y M ) ⎡⎤ z1 ⎢ . ⎥ ⎢ .. ⎥ ⎢ ⎥ ⎢ ⎥ ⎢ ⎥ z = ⎢z M ⎥, ⎢0⎥ ⎢ ⎥ ⎢ ⎥ ⎣0⎦ ⎡0⎡ 1 ⎢. P=⎢ ⎣ ..1x1 .. . xMTherefore, this interpolator can also be written in the form N (5.26)⎤ y1 .. ⎥ ⎥ . ⎦. yM(5.27)z j φ j (x, y),(5.28)φ(x, y) = (A−1 )t κ(x, y),(5.29)S(x, y) =j=1where N = M + 3 and twith φ(x, y)=[φ1 (x, y) · · · φ N (x, y)] and κ(x, y) = [ κ1 (x, y) · · · κ M (x, y) 1 x y ]t .© 2008 by Taylor & Francis Group, LLCSurface Modeling95Three zero-attribute values (z M+1 = z M+2 = z M+3 = 0) were added to keep the general interpolation formula in Equation (5.28). Now we can derive the fuzzy version for this interpolator, getting ˜ S(x, y) =Nk z˜ j φ j (x, y),j=1with α-levels expressed by [S(x, y)]α =Nk zˇ j,α φ j (x, y) +Nk r j,α |φ j (x, y)|[−1, 1],α ∈ [0, 1].(5.30)j=1j=1Here we have, again, the problem of lack of consistency because the basis functions φ j (x, y) do not have constant sign. To have consistent fuzzy thin-plate splines, we have to follow the same procedure we did for Lagrange polynomial and cubic splines, getting [ f (x, y)]α =Nk zˇ j,α φ j (x, y) +Nk ζ j,α φ j (x, y)[−1, 1],α ∈ [0, 1].(5.31)j=1j=1As it was noticed in the begining of this subsection, these interpolators use most of the time only the neighbor data values, especially when there is a large amount of data to interpolate.5.3.2 GRIDDED DATA Now we will consider that the sample data are distributed over a rectangular grid (see Figure 5.9). There are interpolators that can be applied only in this context.50 40 30 0200 50150 100100 15050 2000FIGURE 5.9 Example of a fuzzy triangular gridded data set.© 2008 by Taylor & Francis Group, LLC96Fuzzy Surfaces in GIS and Geographical AnalysisTherefore, before applying an interpolator of this type to a set of samples distributed irregularly, first an interpolator for nongridded data has to be used to generate a gridded distribution. The grid is defined by partitions over a rectangular region D = [a, b] × [c, d] ⊂ R2 a = x1 < x2 < · · · < x N = b, c = y1 < y2 < · · · < y M = d. As it was mentioned before, bivariate interpolators can be derived from univariate ones by using the tensor product. Taking the general interpolator formula ˜f (x, y) =N M ζ˜i j φi j (x, y),(5.32)i=1 j=1we write the basis functions as a tensor product φi j (x, y) = φi (x)φ j (y).(5.33)This allows us to build bivariate fuzzy interpolators from univariate ones. 5.3.2.1 Bivariate Lagrange PolynomialThe bivariate Lagrange polynomial is usually written in the form f (x, y) =M N z i j L i j (x, y),(5.34)i=1 j=1where the bivariate basis functions are written as a tensor product L i j (x, y) = L i (x)L j (y),(5.35)with L i (x) ≡N (x − xk ) , (x i − xk ) k=1i = 1, 2, . . . , N andk=iM (y − yk ) L j (y) ≡ , (y j − yk ) k=1j = 1, 2, . . . , M.(5.36)k= jThe first approach for fuzzy bivariate Lagrange interpolator will be given by ˜f (x, y) =N M z˜ i j L i j (x, y),(5.37)i=1 j=1with the following α-levels [ f (x, y)]α =N M zˇ i j,α L i j (x, y)i=1 j=1+N M i=1 j=1© 2008 by Taylor & Francis Group, LLCri j,α |L i j (x, y)|[−1, 1],α ∈ [0, 1].(5.38)Surface Modeling97As in the univariate case, consistency is lost here. Therefore, the consistent bivariate fuzzy Lagrange polynomial, defined by the α-levels M N [ f (x, y)]α =zˇ i j,α L i j (x, y)i=1 j=1M N +ζi j,α L i j (x, y)[−1, 1],α ∈ [0, 1],(5.39)i=1 j=1has to be found using a similar procedure. 5.3.2.2 Bilinear Fuzzy SplinesThe fuzzy bilinear spline will be given by its α-levels [ f (x, y)]α =M N zˇ i j,α s1,i j (x, y)i=1 j=1+M N ri j,α |s1,i j (x, y)|[−1, 1],α ∈ [0, 1].(5.40)(i = 1, 2, . . . , N ), ( j = 1, 2, . . . , M),(5.41)i=1 j=1Using again the tensor product, we have s1,i j (x, y) = s1,i (x)s1, j (y),where the only nonzero basis functions are (x − xi ) , (xi+1 − xi )s1,i (x) =(xi+1 − x) , (xi+1 − xi )s1, j (y) =(y j+1 − y) (y − y j ) and s1, j+1 (y) = , (y j+1 − y j ) (y j+1 − y j )s1,i+1 (x) =with (x, y) ∈ [xi , xi+1 ] × [y j , y j+1 ]. Since xi < xi+1 and y j < y j+1 , we have always |s1,i j (x, y)| = s1,i j (x, y). Therefore, as in the univariate case, consistency is maintained. The α-levels for bilinear fuzzy splines are [ f (x, y)]α =N M zˇ i j,α s1,i j (x, y)i=1 j=1+N M i=1 j=1© 2008 by Taylor & Francis Group, LLCri j,α s1,i j (x, y) [−1, 1] , α ∈ [0, 1].(5.42)98Fuzzy Surfaces in GIS and Geographical Analysis5.3.2.3 Bicubic Fuzzy SplinesFollowing the same method, in a first approach, the bicubic fuzzy splines have the following α-levels [ f (x, y)]α =N M zˇ i j,α s3,i j (x, y)i=1 j=1+N M i=1 j=1 ri j,α s3,i j (x, y) [−1, 1] , α ∈ [0, 1].(5.43)The tensor product allows us once more to express the bivariate basis functions using the univariate ones. The result is s3,i j (x, y) = s3,i (x) s3, j (y),(5.44), δi, j ), i = where s3,i and s3, j are cubic splines interpolating the data points {(xi 1, i = j 1, 2, . . . , N , } and {(y j , δi, j ), j = 1, 2, . . . , M}, respectively, with δi. j = . 0, i = j As in the Lagrange polynomial, the consistency is lost in this case. Therefore, the consistent bicubic spline should be redefined by the following α-levels (see Figure 5.10) [ f (x, y)]α =M N zˇ i j,α s3,i j (x, y)i=1 j=1+M N ζi j,α s3,i j (x, y)[−1, 1], α ∈ [0, 1].(5.45)i=1 j=150 40 30 0200 50150 100100 15050 2000FIGURE 5.10 Fuzzy surface resulting from the fuzzy bicubic spline interpolator for fuzzy triangular data in Figure 5.9.© 2008 by Taylor & Francis Group, LLCSurface Modeling99As in the other cases, the consistent interpolator has to be found using an approximation procedure as described before.5.3.3 FUZZY GEOSTATISTIC INTERPOLATOR (KRIGING) Geostatistics was developed by the French mathematician Georges Matheron in the early sixties, from the seminal work of its inventor, Daniel G. Krige, a South African mining engineer, from whom the name kriging is derived [36]. The geostatistic interpolation is often used to model geographical phenomena. Often, the sampled data used in the interpolation have uncertainty that can be expressed by fuzzy numbers ([8], [7], [25]). In this section, the geostatistic tools will be extended to deal with samples expressed by triangular fuzzy numbers in the form z˜ = z˜ (x, y) = (z − (x, y)/z 1 (x, y)/z + (x, y)),(x, y) ∈ D ⊂ R2 .(5.46)The geographical phenomena will be modeled by a triangular fuzzy random field { Z˜ (x, y) = (Z − (x, y)/Z 1 (x, y)/Z + (x, y)),(x, y) ∈ D} −(5.47) 1and the sample set of triangular fuzzy numbers {˜z (xi , yi ) = (z (xi , yi )/z (xi , yi )/ z + (xi , yi )), i = 1, 2, . . . , N } will be a set of realizations of the random field. Using the Hausdorff metric η between the α-levels, a metric d∗ can be defined over the set of fuzzy numbers F, given by d∗ (˜z 1 , z˜ 2 ) = sup η([z 1 ]α , [z 2 ]α ).(5.48)α∈(0,1]For triangular fuzzy numbers, an equivalent metric can be defined by 2 d(˜z 1 , z˜ 2 )2 = (z 1− − z 2− )2 + z 11 − z 21 + (z 1+ − z 2+ )2 .(5.49)Generalizing last metric for any fuzzy number defined by its α-levels, we have − − 2 + + 2 d(˜z 1 , z˜ 2 )2 = [(z 1,α − z 2,α ) + (z 1,α − z 2,α ) ]. αDiamond [25] proved that the expectation E Z˜ (x, y) exists if and only if Ed ˜ 2 , where 0˜ = (0/0/0), exists and is a triangular fuzzy number given by ˜ ( Z (x, y), 0) E Z˜ (x, y) = (E Z − (x, y)/E Z 1 (x, y)/E Z + (x, y)); Besides the variance Var Z˜ is defined by Var Z˜ (x, y) = Ed( Z˜ (x, y), E Z˜ (x, y))2(5.50)and it is a real number. To express spatial variability, the so-called stationary covariance or covariagram ˜ which is defined by the covariance between Z˜ (xi , yi ) and Z˜ (x j , y j ), is function C, used. ˜ i − x j , yi − y j ) = cov( Z˜ (xi , yi ), Z˜ (x j , yi )). C(x We say that the random variable Z˜ (x, y) is second order stationary if the expected value exists and is independent of location (x, y), that is, E Z˜ (x, y) = m˜ = (m − /m 1 /m + ),© 2008 by Taylor & Francis Group, LLC∀(x, y) ∈ D,(5.51)100Fuzzy Surfaces in GIS and Geographical Analysisand there exist lower, C − , modal, C 1 , and upper covariance, C + , that are functions of the lag vector h i j between positions (xi , yi ) and (x j , y j ) such that C − (h i j ) = E[Z − (xi , yi )Z − (x j , y j )] − (m − )2 , C 1 (h i j ) = E[Z 1 (xi , yi )Z 1 (x j , y j )] − (m 1 )2 , C + (h i j ) = E[Z + (xi , yi )Z + (x j , y j )] − (m + )2 .(5.52) (5.53) (5.54)The assumption of second order stationarity is common in geostatistics. It represents physical homogeneity and the existence of the first two moments, which are independent of location. In practical situations, the observations may show a systematic trend, and it cannot be assumed that the mean is constant. Universal kriging takes this into account, or then a small “moving window” of adjacent points can be used to take a moving average, where the constancy of E Z˜ (x, y) = m˜ is not a bad approximation. Traditionally, the variogram has been used for modeling spatial variability rather than covariance. It is an alternative to the covariance and is defined as the variance of the increment Z (xi , yi ) − Z (x j , y j ). If both exist, they are related by γ (h ij ) = C(0) − C(h ij ).(5.55)Let γ˜ (h) = (γ − (h)/γ 1 (h)/γ + (h)) represent the fuzzy triangular variogram. Assuming the existence of lower, γ − , modal, γ 1 , and upper semivariogram, γ + , independent of (x, y), the stationarity condition may be expressed by 2γ − (h i j ) = E[Z − (xi , yi ) − Z − (x j , y j )]2 , 2γ 1 (h i j ) = E[Z 1 (xi , yi ) − Z 1 (x j , y j )]2 , 2γ + (h i j ) = E[Z + (xi , yi ) − Z + (x j , y j )]2 .(5.56) (5.57) (5.58)5.3.3.1 Estimation of Fuzzy VariogramIn crisp kriging, the experimental variogram is given by γˆ (h ij ) =n(h)− Z (x j , y j )]2 2n(h ij )i=1 [Z (x i , yi )(5.59)where n(h) is the number of data pairs separated by the same h; under isotropy conditions only, magnitude h is considered. If data Z˜ (x1 ), Z˜ (x2 ), . . . , Z˜ (xn ) are fuzzy numbers, then fuzzy arithmetic operations [2] can be used to evaluate experimental variogram γˆ (h) =n(h)˜i=1 [( Z (x i , yi )⊖ Z˜ (x j , y j )) ⊗ ( Z˜ (xi , yi ) ⊖ Z˜ (x j , y j ))] . 2n(h ij )(5.60)After the experimental variogram has been calculated, a theoretical variogram has to be chosen and fitted to it (see Figures 5.11 and 5.12). The classical method to fit© 2008 by Taylor & Francis Group, LLCSurface Modeling101γ h µFIGURE 5.11 Fuzzy experimental variogram.a model γ to a finite set of data (h i , γi ), (i = 1, 2, . . . , N (h)) is based on the least squares method. Extending that method to fit a fuzzy model γ˜ to fuzzy data (h i , γ˜i ), we have to minimize F( p˜ 1 , p˜ 2 , . . . , p˜ q ) =N (h) d(γ˜i , γ˜ ∗ (h i ))2 ,(5.61)i=1where ( p˜ 1 , p˜ 2 , . . . , p˜ q ) are the fuzzy parameters of γ˜ ∗ .0.1 40.05 0 1.23.5 3 12.5 0.82 0.6Distance h1.5 0.410.20.50 –0.20FIGURE 5.12 Fuzzy theoretical variogram fitted to experimental fuzzy values.© 2008 by Taylor & Francis Group, LLC102Fuzzy Surfaces in GIS and Geographical AnalysisA distance d between fuzzy numbers has to be defined. Taking the metric in Equation (5.49), we have F( p˜ 1 , p˜ 2 , . . . , p˜ q ) =N (h) i=1 (γi− − γ − (h i ))2 + γi1 − γ 1 (h i )2 + (γi+ − γ + (h i ))2 .(5.62)Using, for example, a fuzzy spherical theoretical variogram model ⎧˜ 0, ⎪ ⎪ ⎨ γ˜ ∗ (h) = C˜ 0 ⊕ C˜ 1 ⊗ 3h − 2a ⎪ ⎪ ⎩˜ ˜ C0 ⊕ C1 ,h=0 h3 , 0 < h ≤ a, 2a 3(5.63)h>awhere the variogram parameters are the range a, the nugget effect C˜ 0 , and the sill C˜ 0 ⊕ C˜ 1 . Since a is a distance, it will be considered as a real value. Taking C˜ 0 and C˜ 1 as triangular fuzzy numbers, we have C˜ 0 = (C0− /C01 /C0+ ) and C˜ 1 = (C1− /C11 /C1+ ). So, the variogram can be written as ⎧ (0/0/0), h=0 ⎪ ⎪ ⎨ h3 γ˜ ∗ (h) = C0− /C01 /C0+ ⊕ C1− /C11 /C1+ ⊗ 3h , 0a ⎧ (0/0/0), h=0 ⎪ ⎪ ⎪ ⎪ 3 3 + − − 3h h h 3h ⎪ 1 1 ⎨ C0 + C1 2a − 2a 3 /C0 + C1 2a − 2a 3 /C0 = . h3 ⎪ ⎪ +C1+ 3h , 0a (5.64) Substituting in Equation (5.62), using ηi (a) = F(a, C˜ 0 , C˜ 1 ) =N (h≤a) i=1h i3 2a 3+γi13h i 2ato simplify, it turns out 2 (γi− + C0− + C1− ηi (a))2 + γi1 + C01 + C11 ηi (a) 2 + γi+ + C0+ + C1+ ηi (a) + −−C01−2 C11+(γi+N (h>a)N (0 F(x, y)Require: a threshold t (real or fuzzy), a fuzzy surface F(x, y), a δ ∈ [0, 1] if Overtake(t, F(x, y)) > δ then return TRUE else return FALSE end if© 2008 by Taylor & Francis Group, LLCAlgorithms — Pseudo Code131The algorithm for interrogation in section 8.1.2 is a predicate that returns “true” if there is an overtake of δ between fuzzy numbers. A global interrogation on a map can be done with one of the many algorithms of scan line.8.2PSEUDO CODE FOR FUZZY INTERPOLATORS8.2.1 CONSTRUCTION OF FUZZY UNIVARIATE LINEAR SPLINES The construction of a fuzzy univariate linear spline is based on crisp linear splines. Every α-level limit is a crisp linear spline (see routine flspline in f uzinter p MATLAB toolbox). Algorithm 5Fuzzy univariate linear splineRequire: (xd, z˜ d) and evaluation positions x for i ← 1 to NumOfPositions do for α ← 0 to 1 do FuzLinSpi (α) ← [ LinearSpline(xd, z − (α); xi ), LinearSpline (xd, z + (α); xi )] end for end for return Fuz LinSp(x)8.2.2 CONSTRUCTION OF FUZZY UNIVARIATE CUBIC SPLINES The construction of a fuzzy univariate cubic spline is based on basis cubic splines. Since these functions can be negative, consistency is to be achieved by solving a semi-infinite optimization problem. However, for computational reasons, it is much easier to find an approximation. Therefore, we suggest to use crisp cubic splines to approximate the α-levels’ limits of the inconsistent fuzzy cubic splines (see routine cfuzpline in fuzinterp MATLAB toolbox).Algorithm 6Fuzzy univariate cubic splineRequire: (xd, z˜ d) and evaluation positions x for i ← 1 to NumOfPositions do for α ← 0 to 1 do FuzCubSpi (α) ← | BasisCubicSplines(xd; xi )| ∗ z˜ d(α) end for end for for α ← 0 to 1 ConsistFuzCubSp(α) ← [ FittedCubSp(x, FuzCubSp − (α)), FittedCubSp(x, FuzCubSp + (α))] end for© 2008 by Taylor & Francis Group, LLC132Fuzzy Surfaces in GIS and Geographical Analysisfor i ← 1 to NumOfPositions do for α ← 0 to 1 do ConsistFuzCubSpi (α) ← ConsistFuzCubSp(α; xi ) end for end for return Consist FuzCubSp(x)8.2.3 CONSTRUCTION OF FUZZY TINS The construction of a fuzzy TIN just needs to triangulate the data points and find the planes that are the α-levels’ limits for every triangle (see routine ftin in fuzinterp MATLAB toolbox). Algorithm 7Fuzzy TINRequire: (xd, yd, z˜ d) and evaluation positions (x, y) tri ← triangulation(xd, yd) for i ← 1 to NumOfPositions do T ← Find Triangle in tri containing (xi , yi ) for α ← 0 to 1 do + planeT (α) ← [ plane(x T , yT , z − T (α)), plane(x T , yT , z T (α))] FuzT I Ni (α) ← planeT (α, xi , yi ) end for end for return FuzT I N (x, y)8.2.4 CONSTRUCTION OF FUZZY SHEPARD METHOD The construction of fuzzy Shepard method needs to find a neighborhood of interpolation positions to data points and the distances between them, to calculate the weights (see routine fshep in fuzinterp MATLAB toolbox).Algorithm 8Fuzzy Shepard methodRequire: (xd, yd, z˜ d) and evaluation positions (x, y) for i ← 1 to NumOfPositions do neighs ← neighbors(xd, yd) of (xi , yi ) weights ← distances of (xi , yi ) to neighs for α ← 0 to 1 do FuzShepi (α) ← weights ∗ z˜ (α, neighs) end for end for return FuzShep(x, y)© 2008 by Taylor & Francis Group, LLCAlgorithms — Pseudo Code1338.2.5 CONSTRUCTION OF FUZZY THIN-PLATE SPLINES The construction of fuzzy thin-plate splines also needs to find a neighborhood of interpolation positions to data points. The weights here are determined from the solution of a linear system of radial functions. Since weights can be negative here, consistency is to be achieved also by solving a semi-infinite optimization problem. As in Algorithm 6, it is much easier and more efficient to find an approximation. Therefore, we suggest to use crisp thin-plate splines to approximate the α-levels’ limits of the inconsistent fuzzy thin-plate splines (see routine cftps in fuzinterp MATLAB toolbox).Algorithm 9Fuzzy thin-plate splinesRequire: (xd, yd, z˜ d) and evaluation positions (x, y) for i ← 1 to NumOfPositions do neighs ← neighbors(xd, yd) of (xi , yi ) weights ← SolveLin((xi , yi ), neighs for α ← 0 to 1 do FuzTPSi (α) ← weights ∗ z˜ (α, neighs) end for end for return FuzTPS(x, y)8.2.6 CONSTRUCTION OF FUZZY CUBIC SPLINES The construction of a fuzzy cubic spline surface is based on tensor product of basis cubic splines in x and y. Again, the consistency is to be achieved by solving a semiinfinite optimization problem, but the best approach is also to find an approximation using crisp cubic splines to approximate the α-levels’ limits of the inconsistent fuzzy cubic splines (see routine cfuzpline2 in fuzinterp MATLAB toolbox).Algorithm 10Fuzzy cubic splineRequire: (xd, yd, z˜ d) and evaluation positions (x, y) for i ← 1 to NumOfPositions do for α ← 0 to 1 do FuzCubSpi (α) ← | BasisCubicSplines(xd, yd; xi , yi )| ∗ z˜ d(α) end for end for for α ← 0 to 1 do ConsistFuzCubSp(α) ← [FitCubSp(x, y, FuzCubSp − (α)), FitCubSp(x, y, FuzCubSp + (α))] end for© 2008 by Taylor & Francis Group, LLC134Fuzzy Surfaces in GIS and Geographical Analysisfor i ← 1 to NumOfPositions do for α ← 0 to 1 do ConsistFuzCubSpi (α) ← ConsistFuzCubSp(α; xi , yi ) end for end for return ConsistFuzCubSp(x, y)8.3PSEUDO CODE FOR THE CONSTRUCTION OF FUZZY GEOGRAPHICAL ENTITIESAs explained in chapter 4, several approaches can be used to construct FGEs, depending on what they represent and the information available. Algorithms to build FGEs over a tessellation are presented below, considering the four possible sources of uncertainty mentioned in chapter 4. For all cases, a tessellation of the geographical space is considered, and the value z of the characteristic used to define the attribute is known in each elementary region of the tessellation.8.3.1 UNCERTAINTYIN THEATTRIBUTE DEFINITIONThis algorithm can be used to construct FGEs when there is uncertainty in the definition of the attribute characterizing the GEs. Algorithm 11Uncertain attributeRequire: z j values for all elementary regions r j of the tessellation and membership function μ A (z) characterizing attribute A for all z j values do μFGE A (r j ) ← μ A (z j ) end for8.3.2 SEVERAL VERSIONS OF THE ATTRIBUTE This algorithm applies when there are several versions of the attribute characterizing a GE, resulting in uncertainty in the attribute definition. Algorithm 12Several versions of the attributeRequire: z j values for all elementary regions r j of the tessellation, i sets (Z A )i corresponding to all versions (Z A and the degree of confidence of each version i of A) for each elementary region r j do counter ← 0 for each version i do if z j belongs to (Z A )i then© 2008 by Taylor & Francis Group, LLCAlgorithms — Pseudo Code135counter ← counter + degree of confidence of version i end if end for μ A (z j ) ← counter μFGE A (r j ) ← μ A (z j ) end for The degrees of confidence assigned to each version of the attribute must be a value between 0 and 1, and the sum of the degrees of confidence assigned to all versions of the same attribute must add up to 1.8.3.3 ERRORS IN THE BASE ATTRIBUTE VALUES This algorithm applies when the values of the base attribute at the elementary regions are affected by errors. These errors can be used to construct FGEs.Algorithm 13Uncertainty in z valuesRequire: z j values for all elementary regions r j of the tessellation, the attribute values Z A = [z, z] defining attribute A, the error function of each z j : EF(z j ) and the maximum and minimum values z j can take z max and z min z z EF(z j )dz j μFGE A (r j ) ← zmax z min EF(z j ) dz j8.3.4 EVOLUTION OVER TIME This algorithm applies when the geographical locations of the GEs change over time. The information about the position of the entities in different epochs can be used to construct FGEs.Algorithm 14Evolution over timeRequire: all versions of the geographical entity characterized by A and the degree of confidence of each version for each elementary region r j do counter ← 0 for each version do if region belongs to version then counter ← counter + degree of confidence of version end if end for μFGE A (r j ) ← counter end for© 2008 by Taylor & Francis Group, LLC1368.4Fuzzy Surfaces in GIS and Geographical AnalysisPSEUDO CODE FOR OPERATIONS WITH FUZZY GEOGRAPHICAL ENTITIES8.4.1 FUZZY AREA COMPUTATION The fuzzy area determination requires the computation of the crisp area of several αlevels of the FGEs. The α-levels may be chosen by the user according to the needs and the variation of the FGEs grades of membership. In Matlab routine fuzzyarea.m found in the attached CD, default values α are 0.001, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 and 1. The pseudo code algorithm 15 shows the basic steps of the fuzzy area routine. Algorithm 15Fuzzy area computationRequire FGE E, set of values α ∈ [0, 1], cell size for all α-levels do A (α) ←area of α-level α E end for for i ← 1 to number of α values do slope(i) ← slope of the segment defined by points [A{α(i)}, α(i)] and [A{α(i + 1)}, α(i + 1)] y − intersect (i) ← y − intersect of the segment defined by points [A{α(i)}, α(i)] and [A{α(i + 1)}, α(i + 1)] end for eliminate unnecessary branches of membership function return slope, y-intersect and points (A, α)defining each branch of the fuzzy area8.4.2 FUZZY PERIMETER COMPUTATION Pseudo code algorithm 16 shows the basic steps of the computation of the fuzzy perimeter of FGEs. Such as with the fuzzy area algorithm, the fuzzy perimeter determination also requires the computation of the crisp perimeter of several α-levels of the FGE. In Matlab routine fuzzyperimter.m found in the attached CD, default values of α are 0.001, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 and 1. Algorithm 16Fuzzy perimeter computationRequire FGE E, set of values α ∈ [0, 1], cell size for all α-levels do P(α) ← perimeter of α-level α E end for for i ← 1 to number of α values-1 do slope (i) ← slope of the segment defined by points [P{α(i)}, α(i)] and [P{α(i + 1)}, α(i + 1)] y − intersect (i) ← y-intersect of the segment defined by points [P{α(i)}, α(i)] and [P{α(i + 1)}, α(i + 1)] end for fuzzyperimeter(P) = max (grade of membership considering all branches defined by points [P{α(i)}, α(i)] and [P{α(i + 1)}, α(i + 1)] to which P may belong ) return slope, y-intersect and points (P, α) defining each branch of the fuzzy perimeter© 2008 by Taylor & Francis Group, LLC— Fuzzy 9 Appendices Arithmetic and Fuzzy Query C++ Source Salvatore Spinella CONTENTS 9.1 9.2A Fuzzy Number Implementation in C++ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 Fuzzy Query System. C++ Code . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156DISCLAIMER OF WARRANTY We make no warranties, expressed or implied, that the programs contained in this volume are free of error, or are consistent with any particular standard of merchantability, or that they will meet your requirements for any particular application. They should not be relied on for solving a problem whose incorrect solution could result in injury to a person or loss of property. If you do use the programs in such a manner, it is at your own risk. The authors and publisher disclaim all liability for direct or consequential damages resulting from your use of the programs.9.1A FUZZY NUMBER IMPLEMENTATION IN C++This section introduces a base of C++ code for fuzzy number implementation. The implementation is based on a class named FuzzyNumber, which includes constructors and arithmetic operators. The member of this class is a map that implements the functional relation between α-level and interval. Many other operators (like inserter and extractor for input–output operations) and fuzzy function are listed in the code. Notice that all code is written as template with respect to a T type, which can assume integer type or floating point type. /* Name: Fuzzy.h Description: A collection of templates to define in C++ the fuzzy arithmetic. */ #include "Interval.h" #include #include 137 © 2008 by Taylor & Francis Group, LLC138Fuzzy Surfaces in GIS and Geographical Analysis#include #include /* Definition of Fuzzy Number */ template class FuzzyNumber{ public: typedef T valuetype; FuzzyNumber(vector&, vector&); // Constructors FuzzyNumber(); FuzzyNumber(T&); bool Insert(T&, Interval&); // Insert of an interval of level alpha FuzzyNumber& // Operators FuzzyNumber& FuzzyNumber& FuzzyNumber&operator+=(const FuzzyNumber&); operator-=(const FuzzyNumber&); operator*=(const FuzzyNumber&); operator/=(const FuzzyNumber&);pair operator()(const T&) const; // Map operator FuzzyNumber& operator=(const T& a); // Real assignment FuzzyNumber& operator+=(const T& a); // unary operator FuzzyNumber& operator-=(const T& a); FuzzyNumber& operator*=(const T& a); FuzzyNumber& operator/=(const T& a);};map A; // Map representation of a // Fuzzy Number/* Constructor of the fuzzy number zero at alpha-level zero */ template FuzzyNumber::FuzzyNumber(){ T zero=T(); A[zero]=zero; };© 2008 by Taylor & Francis Group, LLCAppendices — Fuzzy Arithmetic and Fuzzy Query C++ Source139/* Constructor from real data of a fuzzy number given a vector of data and a vector of levels. It constructs an alpha-level representation of the data. Data are ordered and for each alpha level a median interval, which envelops a portion (1-alpha) of data. This choice supposes data are representative of the uncertainty. */ templateFuzzyNumber::FuzzyNumber(vector& data, vector & level) { T zero=T(), uno=T(1), l; unsigned n=data.size(),k; sort(data.begin(),data.end(),less()); A[zero] = Interval(data[0], data[n-1]); for (unsigned i=0; isecond.in(bins.first-> second)){ A.erase(bins.first); return false; } return true; }/* Definition of operation "+=" between fuzzy numbers. This operator evaluates the representation of two fuzzy numbers and updates a result that represents the sum of the fuzzy numbers. */ template inline FuzzyNumber& FuzzyNumber :: operator+=(constFuzzyNumber& a) { typedef map::const_iterator CI; CI f1_end = a.A.end(), f1 = a.A.begin(), f_end = A.end(), f = A.begin(); Interval i=f->second, i1=f1->second; T alpha=f->first, alpha1=f1->first; for(;;){ if(f->first > f1->first){ if(f1!=f1_end){ A[alpha1] = i+i1; if(++f1!=f1_end) {alpha1=f1->first; i1=f1->second;} else{ f++; A.erase(alpha); if(f==f_end)break; else{i=f->second; alpha=f->first;} } }else {© 2008 by Taylor & Francis Group, LLCAppendices — Fuzzy Arithmetic and Fuzzy Query C++ Source141A[alpha] = i+i1; if(f!=f_end && ++f!=f_end){i=f-> second; alpha=f->first; } else break; } } else if(f->first < f1->first){ if(f!=f_end){ A[alpha] = i+i1; if(++f!=f_end){i=f-> second; alpha=f->first;} else{ f1++; A.erase(alpha1); if(f1==f1_end)break; else {alpha1=f1->first; i1=f1-> second;} } }else { A[alpha1] = i+i1; if(f1!=f1_end && ++f1! =f1_end) {alpha1=f1->first; i1=f1->second;} else break; } }else { A[alpha] = i + i1; if(f1!=f1_end && ++f1!=f1_end){alpha1=f1-> first; i1=f1->second;} if(f!=f_end && ++f!=f_end){ alpha=f->first; i=f->second; } if(f1==f1_end && f==f_end)break; } } return * this; } /* Definition of operation "-=" between fuzzy numbers. This operator evaluates the representation of two fuzzy numbers and updates a result that represents the sum of the fuzzy numbers. */ template inline FuzzyNumber& FuzzyNumber ::operator-=(constFuzzyNumber& a) { typedef map::const_iterator CI; CI f1_end = a.A.end(), f1 = a.A.begin(), f_end = A.end(), f = A.begin();© 2008 by Taylor & Francis Group, LLC142Fuzzy Surfaces in GIS and Geographical AnalysisInterval i=f->second, i1=f1->second; T alpha=f->first, alpha1=f1->first; for(;;){ if(f->first > f1->first){ if(f1!=f1_end){ A[alpha1] = i-i1; if(++f1!=f1_end) {alpha1=f1->first; i1=f1->second;} else{ f++; A.erase(alpha); if(f==f_end)break; else{i=f->second; alpha=f->first;} } }else { A[alpha] = i-i1; if(f!=f_end && ++f!=f_end) { i=f->second; alpha=f->first; } elsebreak; } }else if(f->first < f1->first){ if(f!=f_end){ A[alpha] = i-i1; if(++f!=f_end) { i=f->second; alpha=f->first;} else{ f1++; A.erase(alpha1); if(f1==f1_end)break; else {alpha1=f1->first; i1=f1->second;} } }else { A[alpha1] = i-i1; if(f1!=f1_end && ++f1! =f1_end){alpha1=f1->first; i1=f1->second;} else break; } } else { A[alpha] = i - i1; if(f1!=f1_end && ++f1!=f1_end){alpha1=f1-> first; i1=f1->second;} if(f!=f_end && ++f!=f_end){ alpha=f->first; i=f->second; } if(f1==f1_end && f==f_end)break; } } return * this; }© 2008 by Taylor & Francis Group, LLCAppendices — Fuzzy Arithmetic and Fuzzy Query C++ Source143/* Definition of operation "*=" between fuzzy numbers. This operator evaluates the representation of two fuzzy numbers and updates a result that represents the sum of the fuzzy numbers. */ template inline FuzzyNumber& FuzzyNumber:: operator*=(constFuzzyNumber& a) { typedef map::const_iterator CI; CI f1_end = a.A.end(), f1 = a.A.begin(), f_end = A.end(), f = A.begin(); Interval i=f->second, i1=f1->second; T alpha=f->first, alpha1=f1->first; for(;;){ if(f->first > f1->first){ if(f1!=f1_end){ A[alpha1] = i*i1; if(++f1!=f1_end) {alpha1=f1->first; i1=f1->second;} else{ f++; A.erase(alpha); if(f==f_end)break; else{i=f->second; alpha=f->first;} } }else { A[alpha] = i*i1; if(f!=f_end && ++f!=f_end){ i=f-> second; alpha=f->first; } elsebreak; } }elseif(f->first < f1->first){ if(f!=f_end){ A[alpha] = i*i1; if(++f!=f_end) { i=f->second; alpha=f->first;} else{ f1++; A.erase(alpha1); if(f1==f1_end)break; else {alpha1=f1->first; i1=f1->second;} } }else { A[alpha1] = i*i1; if(f1!=f1_end &&© 2008 by Taylor & Francis Group, LLC144Fuzzy Surfaces in GIS and Geographical Analysis++f1!=f1_end){alpha1=f1->first; i1=f1->second;} elsebreak; } }else { A[alpha] = i * i1; if(f1!=f1_end && ++f1!=f1_end){alpha1=f1-> first; i1=f1->second;} if(f!=f_end && ++f!=f_end){ alpha=f->first; i=f->second; } if(f1==f1_end && f==f_end)break; } } return * this; } /* Definition of operation "/=" between fuzzy numbers. This operator evaluates the representation of two fuzzy numbers and updates a result that represents the sum of the fuzzy numbers. */ template inline FuzzyNumber& FuzzyNumber :: operator/=(const Fuzzy Number& a) { typedef map::const_iterator CI; CI f1_end = a.A.end(), f1 = a.A.begin(), f_end = A.end(), f = A.begin(); Interval i=f->second, i1=f1->second; T alpha=f->first, alpha1=f1->first; for(;;){ if(f->first > f1->first){ if(f1!=f1_end){ A[alpha1] = i/i1; if(++f1!=f1_end) {alpha1=f1->first; i1=f1->second;} else{ f++; A.erase(alpha); if(f==f_end)break; else{i=f->second; alpha=f->first;} } }else { A[alpha] = i/i1; if(f!=f_end && ++f!=f_end){ i=f-> second; alpha=f->first; }© 2008 by Taylor & Francis Group, LLCAppendices — Fuzzy Arithmetic and Fuzzy Query C++ Source145elsebreak; } }elseif(f->first < f1->first){ if(f!=f_end){ A[alpha] = i/i1; if(++f!=f_end) { i=f->second; alpha=f->first;} else{ f1++; A.erase(alpha1); if(f1==f1_end)break; else {alpha1=f1->first; i1=f1->second;} } }else { A[alpha1] = i/i1; if(f1!=f1_end && ++f1!=f1_end){alpha1=f1->first; i1=f1->second;} elsebreak; } }else { A[alpha] = i / i1; if(f1!=f1_end && ++f1!=f1_end){alpha1=f1-> first; i1=f1->second;} if(f!=f_end && ++f!=f_end){ alpha=f->first; i=f->second; } if(f1==f1_end && f==f_end)break; } } return * this; }/* Definition of binary operator "+" between fuzzy numbers. This operator evaluates the representation of two fuzzy numbers and returns a result that represents the sum of the fuzzy numbers. */ template FuzzyNumber operator+(const FuzzyNumber& a, constFuzzyNumber& b) { FuzzyNumber r = a; return r+=b; }© 2008 by Taylor & Francis Group, LLC146Fuzzy Surfaces in GIS and Geographical Analysis/* Definition of binary operator "-" between fuzzy numbers. This operator evaluates the representation of two fuzzy numbers and returns a result that represents the sum of the fuzzy numbers. */ template FuzzyNumber operator-(const FuzzyNumber& a, const FuzzyNumber& b) { FuzzyNumber r = a; return r-=b; } /* Definition of binary operator "*" between fuzzy numbers. This operator evaluates the representation of two fuzzy numbers and returns a result that represents the sum of the fuzzy numbers. */ template FuzzyNumber operator*(const FuzzyNumber& a, const FuzzyNumber& b) { FuzzyNumber r = a; return r*=b; } /* Definition of binary operator "/" between fuzzy numbers. This operator evaluates the representation of two fuzzy numbers and returns a result that represents the sum of the fuzzy numbers. */ template FuzzyNumber operator/(const FuzzyNumber& a, const FuzzyNumber& b) { FuzzyNumber r = a; return r/=b; } /* Functional representation. Given an alpha-level x, this operator returns a pair (alpha-level, interval) whose alpha-level is the superior extreme of the alpha-level set less than x. */© 2008 by Taylor & Francis Group, LLCAppendices — Fuzzy Arithmetic and Fuzzy Query C++ Source147template pair FuzzyNumber:: operator()(const T& x) const { map::const_iterator p=A.lowerbound(x); if(p->first==x){ pair f(p->first,p->second); return f; }else{ p--; pair f(p->first,p->second); return f; } } /* Definition of the operator ">". It gets formatted input from a channel. */ template istream& operator >> (istream& s, FuzzyNumber& x) { FuzzyNumber z; Interval Int; char c=0; T lev; z.A.clear();© 2008 by Taylor & Francis Group, LLC148Fuzzy Surfaces in GIS and Geographical Analysiss >> c; if (c == '{') while ((s>>c) && c!=`}'){ if (c==`('){ s >> lev >> c; if (c==`,'){ s >> Int >> c; if (c!=`)' || !z.Insert(lev,Int)) {s.clear(ios::badbit);break;} else continue; }else{ s.clear(ios::badbit);break;} }else{ s.clear(ios::badbit);break;} } else s.clear(ios::badbit); if (s && c==`}') x=z; else s.clear(ios::badbit); return s; } /* Constructor to transform a scalar in a fuzzy number. It links algebraic arithmetic and fuzzy arithemetic. */ template FuzzyNumber::FuzzyNumber(T& x){ T zero=T(); A[zero]=x; } /* Scalar assignment to a fuzzy number. This operator links algebraic arithmetic and fuzzy number arithmetic. */ template FuzzyNumber& FuzzyNumber:: operator=(const T& a) { typedef map::const_iterator CI; CI f=A.begin(),f_end = A.end(); T zero=T(); A.erase(f,f_end); A[zero]=a;© 2008 by Taylor & Francis Group, LLCAppendices — Fuzzy Arithmetic and Fuzzy Query C++ Source149return * this; } /* Definition of the operator "+=" between a fuzzy number and a scalar. */ template FuzzyNumber& FuzzyNumber:: operator+=(const T& a) { typedef map:: iterator CI; CI f,f_end = A.end(); for(f=A.begin(); f!=f_end; f++) f->second+=a; return * this; }/* Definition of the operator "-=" between a fuzzy number and a scalar. */ template FuzzyNumber& FuzzyNumber:: operator-=(const T& a) { typedef map::const_iterator CI; CI f,f_end = A.end(); for(f=A.begin(); f!=f_end; f++) f->second-=a; return * this; } /* Definition of the operator "*=" between a fuzzy number and a scalar. NOTA: OPERAZIONE NON CONSERVATIVA. */ template FuzzyNumber& FuzzyNumber:: operator*=(const T& a) { typedef map::iterator CI; CI f,f_end = A.end();© 2008 by Taylor & Francis Group, LLC150Fuzzy Surfaces in GIS and Geographical Analysisfor(f=A.begin(); f!=f_end; f++) f->second*=a; return * this; } /* Definition of operator "/=" between a fuzzy number and a scalar. */ template FuzzyNumber& FuzzyNumber:: operator/=(const T& a) { typedef map::const_iterator CI; CI f,f_end = A.end(); for(f=A.begin(); f!=f_end; f++) f->second/=a; return * this; } /* Definition of the operator "+" between a fuzzy number and a scalar. */ template FuzzyNumber operator+(const FuzzyNumber& a, constT& b) { FuzzyNumber r = a; return r+=b; } /* Definition of the operator "-" between a fuzzy number and a scalar. */ template FuzzyNumber operator-(const FuzzyNumber& a, const T& b) { FuzzyNumber r = a; return r-=b; } /* Definition of the operator "-" between a fuzzy number and a scalar. */© 2008 by Taylor & Francis Group, LLCAppendices — Fuzzy Arithmetic and Fuzzy Query C++ Source151template FuzzyNumber operator*(const FuzzyNumber& a, constT& b) { FuzzyNumber r = a; return r*=b; } /* Definition of the operator "/" between a fuzzy number and a scalar. */ template FuzzyNumber operator/(const FuzzyNumber& a, constT& b) { FuzzyNumber r = a; return r/=b; } /* Definition of the operator "+" between a scalar and a fuzzy number. */ template inline FuzzyNumber operator+(const T& b, const FuzzyNumber& a) { return a + b; } /* Definition of the operator "-" between a scalar and a fuzzy number. */ template inline FuzzyNumber operator-(const T& b, const FuzzyNumber& a) { typedef map::const_iterator CI; CI f,f_end = a.A.end(); FuzzyNumber r; for(f=a.A.begin(); f!=f_end; f++) r.A[f->first] = b - f->second;© 2008 by Taylor & Francis Group, LLC152Fuzzy Surfaces in GIS and Geographical Analysisreturn r; } /* Definition of the operator "*" between a scalar and a fuzzy number. */ template inline FuzzyNumber operator*(const T& b, const FuzzyNumber& a) { return a * b; } /* Definition of the operator "/" between a scalar and a fuzzy number. */ template inline FuzzyNumber operator/(const T& b,constFuzzyNumber& a) { typedef map::const_iterator CI; CI f,f_end = a.A.end(); FuzzyNumber r; for(f=a.A.begin(); f!=f_end; f++) r.A[f->first] =b/f->second; return r; } /* A weighting function for summation of intervals with respect to their alpha-levels. */ double g( double alpha){ return alpha+.5; } /* Definition of fuzzy distance. */ template T FuzzyDist(const FuzzyNumber& a, const FuzzyNumber& b){ typedef map::const_iterator CI;© 2008 by Taylor & Francis Group, LLCAppendices — Fuzzy Arithmetic and Fuzzy Query C++ SourceCI f1_end = b.A.end(), f_end = a.A.end(), f1 = b.A.begin(), f = a.A.begin(); stack d; // < level,distance> pair dtmp; T fdist=T(); double tmpg,tmph; while(f!=f_end && f1!=f1_end) { if(f->first > f1->first) { d.push(pair(f1->first,dist(f->second, f1->second))); if(f1!=f1_end) f1++; } else if(f->first < f1->first) { d.push(pair(f->first,dist(f->second, f1->second))); if(f!=f_end) f++; } else { d.push(pair(f->first,dist(f->second, f1->second))); if(f1!=f1_end) f1++; if(f!=f_end) f++; } } dtmp=d.top(); fdist += pow(dtmp.second,2.)* (g(1.) + (tmpg=g(dtmp.first))) * (1.-(tmph=dtmp.first))/2.; d.pop(); while (d.size()){ dtmp=d.top(); fdist+= pow(dtmp.second,2.)* (tmpg+g(dtmp.first))*(tmph-dtmp.first)/2.; tmpg=g(dtmp.first); tmph=dtmp.first; d.pop(); }© 2008 by Taylor & Francis Group, LLC153154Fuzzy Surfaces in GIS and Geographical Analysisreturn sqrt(fdist); } /* Overtaking between fuzzy numbers. "f1 > f2" */ template T FuzzyOver(const FuzzyNumber& a, const FuzzyNumber& b){ typedef map::const_iterator CI; CI f=a.A.begin(),f_end = a.A.end(); stack o; // pair stmp; T s,h1,h2; while (f!=f_end){ s = (f->second.upper()-b(f->first). second.lower()) / (f->second.upper()-f->second.lower()); if(s>1.) s=1.; if (s>.0) { o.push(pair(f->first,s)); f++;} else{break;} } if (f==f_end) o.push(pair(1.,.0)); else if (sfirst,.0)); s=T(); stmp=o.top(); h1=stmp.first; while (o.size()){ stmp=o.top(); h2=stmp.first; s+=stmp.second*(h1-h2)*(g(h1) +g(h2))*.5; h1=h2; o.pop(); } return s; } /* Definition of mean interval of a fuzzy number. */ template Interval meanint(FuzzyNumber a){ typedef map::const_iterator CI; CI f,f_end = a.A.end(); T l=T(), r=T(), prevl=T(), prevu=T(), preva=T();© 2008 by Taylor & Francis Group, LLCAppendices — Fuzzy Arithmetic and Fuzzy Query C++ Source155for(f=a.A.begin()++; f!=f_end; f++){ l+=((f->second.lower()+prevl)* (f->first-preva)); r+=((f->second.upper()+prevu)* (f->first-preva)); prevl=f->second.lower(); prevu=f->second.upper(); preva=f->first; } l+=(prevu-prevl)*(1-preva); r+=(prevu-prevl)*(1-preva); Interval i(l/2.,r/2.); return i; } /* Definition of centroid for a fuzzy number. */ template double centroid(FuzzyNumber a){ typedef map::const_iterator CI; CI f,f_end = a.A.end(); T l=T(), r=T(), prevl=T(), prevu=T(), preva=T(), l=T(), u=T(); for(f=a.A.begin()++; f!=f_end; f++){ l+=(f->second.lower()*f->first +prevl*preva)*(f->second.lower() - prevl); l+=(f->first+preva)*(f->second.lower() - prevl); r+=(f->second.up()*f->first+prevu*preva) *(prevu - f->second.up()); r+=(f->first+preva)*(prevu - f->second.up());prevl=f->second.lower(); prevu=f->second.upper(); preva=f->first; }© 2008 by Taylor & Francis Group, LLC156Fuzzy Surfaces in GIS and Geographical Analysisl+=((prevl+prevu)/2.+prevl*preva)*(prevu-prevl)/2.; l+=(1-preva)*(prevu-prevl)/2.; r+=((prevl+prevu)/2.+prevl*preva)*(prevl-prevu)/2.; r+=(1-preva)*(prevl-prevu)/2.; return (l+r)/(l+r); }9.2FUZZY QUERY SYSTEM. C++ CODE#include #include #include #include #include"BSplineFuzzy.h" int main( int argc, char *argv[]) { //Definition of variables, input...try{ BSplineFuzzy< double> B(grado,xg,yg,vliv,x,y,f,EPS); B.write(st);double l[2],u[2], xgs, ygs,lvl; l[0]=(*(*B).u)[1]; l[1]=(*(*B).v)[1]; u[0]=(*(*B).u)[(*(*B).u).size()-(*B).M]; u[1]=(*(*B).v)[(*(*B).v).size()-(*B).M];// Writing down a map at level lvl lvl = ... for(xx=l[0]; xx
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