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β-Hydride elimination is a reaction in which a metal- alkyl centre is converted into the corresponding metal- hydride - alkene . [ 1 ] β-Hydride elimination can also occur for many alkoxide complexes as well. The main requirements are that the alkyl group possess a C-H bond β to the metal and that the metal be coordinatively unsaturated. Thus, metal- butyl complexes are susceptible to this reaction whereas metal- methyl complexes are not. The complex must have an empty (or vacant) site cis to the alkyl group for this reaction to occur. β-Hydride elimination, which can be desirable or undesirable, affects the behavior of many organometallic complexes .
Moreover, for facile cleavage of the C–H bond, a d electron pair is needed for donation into the σ* orbital of the C–H bond. Thus, d 0 metals alkyls are generally more stable to β-hydride elimination than d 2 and higher metal alkyls and may form isolable agostic complexes , even if an empty coordination site is available. [ 2 ]
The Shell higher olefin process relies on β-hydride elimination to produce α- olefins which are used to produce detergents.
β-Hydride elimination interferes with the Ziegler–Natta polymerization , leading to decreased molecular weight. [ 3 ] The production of branched polymers from ethylene relies on chain walking , a key step of which is β-hydride elimination.
Nickel - and palladium -catalyzed couplings mainly focus on aryl-aryl couplings. Aryl-alkyl and especially alkyl-alkyl couplings are less successful because of β-hydride elimination can lower the yield.
In Hydroformylation , β-hydride elimination can act as a side reaction that influences product regioselectivity . [ 4 ] For example, in the hydroformylation of open chain unsaturated ethers, it reverses the formation of branched metal-alkyl intermediates at high temperatures, leading to a greater yield of linear products. [ 5 ]
β-Hydride elimination is one step in the synthesis of some metal hydrides. For instance in the synthesis of RuHCl(CO)(PPh 3 ) 3 from ruthenium trichloride , triphenylphosphine and 2-methoxyethanol , an intermediate alkoxide complex undergoes a β-hydride elimination to form the hydride ligand and the pi-bonded aldehyde which then is later converted into the carbonyl ( carbon monoxide ) ligand.
β-Hydride elimination transforms a metal-alkyl complex into an metal-hydrido-alkene complex. [ 6 ] Starting with an unsaturated complex, the transformation proceeds in stages:
1) Dissociation of a ligand from a metal alkyl complex, yielding a coordinatively unsaturated derivative.
2) Alignment of the beta hydrogen. In this step, a vacant site on the metal forms an agostic complex by binding a C-H bond of the alkyl (or alkoxide). [ 7 ] [ 8 ] [ 9 ] 3) Hydride Transfer/Alkene Formation. In this step, the M-H bond forms concomitant with cleavage of a C-H bond and the development of a double bond in what was once an alkyl (or alkoxide) ligand. [ 9 ] The resulting metal hydride can eliminate the alkene ligand. The transition state for this β-hydride elimination involves a 4-membered ring. [ 10 ] [ 9 ]
Especially for Pt(II) complexes, β-hydride eliminations may occur without the dissociation of an ancillary ligand. [ 11 ] [ 12 ] [ 13 ] [ 14 ] This was suggested primarily based on the observed order of the L-type ligand in the rate law derived from kinetic studies. This mechanism appears to be operative for the minority of reactions studied.
Relative to an arbitrary reference complex, β-hydride elimination is faster in a complex with the following characteristics:
Several strategies exist for avoiding β-hydride elimination. The most common strategy is to employ alkyl ligands that lack hydrogen atoms at the β position. Common substituents include methyl and neopentyl . β-Hydride elimination is also inhibited when the reaction would produce a strained alkene. This situation is illustrated by the stability of metal complexes containing norbornyl ligands, where the β-hydride elimination product would violate Bredt's rule . [ 20 ]
Dissociation-induced β-hydride eliminations. [ 21 ] [ 22 ] [ 23 ] [ 24 ]
β-Hydride elimination involving metal alkoxide and amido complexes. [ 25 ] [ 26 ] [ 27 ] [ 28 ] [ 29 ] [ 30 ]
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β-Hydroxy β-methylbutyryl-coenzyme A ( HMB-CoA ), also known as 3-hydroxyisovaleryl-CoA , is a metabolite of L -leucine that is produced in the human body. [ 1 ] [ 2 ] Its immediate precursors are β-hydroxy β-methylbutyric acid (HMB) and β-methylcrotonoyl-CoA (MC-CoA). It can be metabolized into HMB, MC-CoA, and HMG-CoA in humans.
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β-Hydroxybutyric acid , also known as 3-hydroxybutyric acid or BHB , is an organic compound and a beta hydroxy acid with the chemical formula CH 3 CH(OH)CH 2 CO 2 H; its conjugate base is β-hydroxybutyrate , also known as 3-hydroxybutyrate . β-Hydroxybutyric acid is a chiral compound with two enantiomers : D -β-hydroxybutyric acid and L -β-hydroxybutyric acid. Its oxidized and polymeric derivatives occur widely in nature. In humans, D -β-hydroxybutyric acid is one of two primary endogenous agonists of hydroxycarboxylic acid receptor 2 (HCA 2 ), a G i/o -coupled G protein-coupled receptor (GPCR). [ 1 ] [ 2 ]
In humans, D -β-hydroxybutyrate can be synthesized in the liver via the metabolism of fatty acids (e.g., butyrate ), β-hydroxy β-methylbutyrate , and ketogenic amino acids through a series of reactions that metabolize these compounds into acetoacetate , which is the first ketone body that is produced in the fasting state. The biosynthesis of D -β-hydroxybutyrate from acetoacetate is catalyzed by the β-hydroxybutyrate dehydrogenase enzyme .
Butyrate can also be metabolized into D -β-hydroxybutyrate via a second metabolic pathway that does not involve acetoacetate as a metabolic intermediate. This metabolic pathway is as follows: [ 3 ]
The last reaction in this metabolic pathway, which involves the conversion of D -β- ( D -β-hydroxybutyryloxy ) -butyrate into D -β-hydroxybutyrate , is catalyzed by the hydroxybutyrate-dimer hydrolase enzyme. [ 3 ]
The concentration of β-hydroxybutyrate in human blood plasma, as with other ketone bodies , increases through ketosis . [ 4 ] This elevated β-hydroxybutyrate level is naturally expected, as β-hydroxybutyrate is formed from acetoacetate. The compound can be used as an energy source by the brain and skeletal muscle when blood glucose is low. [ 5 ] [ 6 ] [ 7 ] [ 8 ] Diabetic patients can have their ketone levels tested via urine or blood to indicate diabetic ketoacidosis . In alcoholic ketoacidosis , this ketone body is produced in greatest concentration. Ketogenesis occurs if oxaloacetate in the liver cells is depleted, a circumstance created by reduced carbohydrate intake (through diet or starvation); prolonged, excessive alcohol consumption; and/or insulin deficiency. Because oxaloacetate is crucial for entry of acetyl-CoA into the TCA cycle, the rapid production of acetyl-CoA from fatty acid oxidation in the absence of ample oxaloacetate overwhelms the decreased capacity of the TCA cycle, and the resultant excess of acetyl-CoA is shunted towards ketone body production. [ citation needed ]
D -β-Hydroxybutyric acid, along with butyric acid , are the two primary endogenous agonists of hydroxycarboxylic acid receptor 2 (HCA 2 ), a G i/o -coupled GPCR . [ 1 ] [ 2 ] [ 12 ]
β-Hydroxybutyric acid is able to cross the blood-brain-barrier into the central nervous system . [ 13 ] Levels of β-hydroxybutyric acid increase in the liver , heart , muscle , brain , and other tissues with exercise , calorie restriction , fasting , and ketogenic diets . [ 13 ] The compound has been found to act as a histone deacetylase (HDAC) inhibitor . [ 13 ] Through inhibition of the HDAC class I isoenzymes HDAC2 and HDAC3 , β-hydroxybutyric acid has been found to increase brain-derived neurotrophic factor (BDNF) levels and TrkB signaling in the hippocampus . [ 13 ] Moreover, a rodent study found that prolonged exercise increases plasma β-hydroxybutyrate concentrations, which induces promoters of the BDNF gene in the hippocampus. [ 13 ] These findings may have clinical relevance in the treatment of depression , anxiety , and cognitive impairment . [ 13 ]
In epilepsy patients on the ketogenic diet, blood β-hydroxybutyrate levels correlate best with degree of seizure control. The threshold for optimal anticonvulsant effect appears to be approximately 4 mmol/L . [ 14 ]
β-Hydroxybutyric acid is the precursor to polyesters, which are biodegradable plastics . This polymer, poly(3-hydroxybutyrate) , is also naturally produced by the bacteria Alcaligenes eutrophus . [ 15 ]
β-Hydroxybutyrate can be extracted from poly(3-hydroxybutyrate) by acid hydrolysis . [ 16 ]
The concentration of β-hydroxybutyrate in blood plasma is measured through a test that uses β-hydroxybutyrate dehydrogenase , with NAD + as an electron-accepting cofactor . The conversion of β-hydroxybutyrate to acetoacetate, which is catalyzed by this enzyme, reduces the NAD + to NADH , generating an electrical change; the magnitude of this change can then be used to extrapolate the amount of β-hydroxybutyrate in the sample.
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β-Hydroxybutyryl-CoA (or 3-hydroxybutyryl-coenzyme A ) is an intermediate in the fermentation of butyric acid , and in the metabolism of lysine and tryptophan . [ 1 ] [ 2 ] The L-3-hydroxybutyl-CoA (or (S)-3-hydroxybutanoyl-CoA) enantiomer is also the second to last intermediate in beta oxidation of even-numbered, straight chain, and saturated fatty acids. [ 3 ]
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β-Leucine ( beta -leucine ) is a beta amino acid and positional isomer of L -leucine which is naturally produced in humans via the metabolism of L -leucine by the enzyme leucine 2,3-aminomutase . [ 1 ] [ 2 ] [ 3 ] In cobalamin (vitamin B 12 ) deficient individuals, plasma concentrations of β-leucine are elevated. [ 3 ]
A small fraction of L -leucine metabolism – less than 5% in all tissues except the testes where it accounts for about 33% – is initially catalyzed by leucine aminomutase , producing β-leucine, which is subsequently metabolized into β-ketoisocaproate (β-KIC), β-ketoisocaproyl-CoA , and then acetyl-CoA by a series of uncharacterized enzymes. [ 1 ] [ 2 ]
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β-Lysine (3,6-diaminohexanoic acid [ 1 ] ) is an amino acid produced by platelets during coagulation and is directly antibacterial by causing lysis of many Gram positive bacteria by acting as a cationic detergent. [ 2 ]
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β-Melanocyte-stimulating hormone ( β-MSH ) is an endogenous peptide hormone and neuropeptide . [ 1 ] It is a melanocortin , specifically, one of the three types of melanocyte-stimulating hormone (MSH), and is produced from proopiomelanocortin (POMC). [ 1 ] It is an agonist of the MC 1 , MC 3 , MC 4 , and MC 5 receptors . [ 1 ] It contains 23 amino acid residues.
β-MSH is also known to decrease food intake in animals such as rats, chicken due to the effect of proopiomelanocortin (POMC). [ 2 ] Research was performed to see the effect β-MSH has on chicks, and it has been found that chicks responded with a decrease in food and water intake when treated with β-MSH. The experiment showed that β-MSH causes anorexigenic effects in chicks. [ 3 ]
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β-Neoendorphin is an endogenous opioid peptide with a nonapeptide structure and the amino acid sequence Tyr - Gly -Gly- Phe - Leu - Arg - Lys -Tyr- Pro (YGGFLRKYP). [ 1 ]
β-Neoendorphins (β-NEP) have the capability to stimulate wound healing by accelerating keratinocyte migration. This is achieved by β-NEP's activation of mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases 1 and 2 (ERK 1 and ERK 2); along with the upregulation of matrix metalloproteinase 2 and 9 ( MMP-2 and MMP-9 ). Wound healing by β-NEP results in migration without consequences on proliferation in human keratinocytes. [ 2 ]
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β-Thromboglobulin ( β-TG ), or beta-thromboglobulin , is a chemokine protein secreted by platelets . [ 1 ] [ 2 ] It is a type of chemokine (C-X-C motif) ligand 7 . [ 3 ] Along with platelet factor 4 (PF4), β-TG is one of the best-characterized platelet-specific proteins. [ 4 ] β-TG and PF4 are stored in platelet alpha granules and are released during platelet activation . [ 1 ] [ 4 ] [ 5 ] As a result, they are useful markers of platelet activation. [ 1 ] [ 4 ] β-TG also has multiple biological activities , for instance being involved in maturation of megakaryocytes . [ 6 ]
β-TG is a chemoattractant , strongly for fibroblasts and weakly for neutrophils . It is a stimulator of mitogenesis , extracellular matrix synthesis, glucose metabolism , and plasminogen activator synthesis in human fibroblasts. [ 5 ]
β-TG also affects megakaryocyte maturation, and thus helps in regulating platelet production. [ 5 ]
Levels of β-TG is used to index platelet activation. It is measured by ELISA in blood plasma or urine, and often in conjunction with PF4. [ 5 ]
β-TG levels may increase with age. [ 7 ] It is elevated in diabetes mellitus . [ 8 ]
β-TG levels have been found to be increased by treatment with the synthetic estrogen ethinylestradiol , though were not significantly increased by the natural estrogen estradiol valerate . [ 9 ] [ 10 ] [ 11 ] [ 12 ] Levels of β-TG have also been found to be increased or unchanged during normal pregnancy . [ 13 ]
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γ-Melanocyte-stimulating hormone ( γ-MSH ) is an endogenous peptide hormone and neuropeptide . [ 1 ] It is a melanocortin , specifically, one of the three types of melanocyte-stimulating hormone (MSH), and is produced from proopiomelanocortin (POMC). [ 1 ] It is an agonist of the MC 1 , MC 3 , MC 4 , and MC 5 receptors . [ 1 ] It exists in three forms, γ 1 -MSH, γ 2 -MSH, and γ 3 -MSH. [ 2 ]
γ-MSH regulated cardiovascular functions. γ-MSH effects are measured through the effects it has on the central neural pathway dispersed throughout the kidney. [ 3 ] It is not moderated based on tubular sodium transport. Gamma-MSH activates MC3R in renal tubular cells by limiting sodium absorption by inhibiting the central neural pathway. [ 3 ] This regulates sodium balance and blood pressure. If MC3R is absent then there is resistance in γ-MSH which results in hypertension on HSD. [ 4 ]
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12-20-34(4)23-16-27-37(7)29-30-39-38(8)28-17-31-40(39,9)10/h11-12,14-16,
18-20,22-30,39H,13,17,21,31H2,1-10H3/b12-11+,22-14+,23-16+,26-15+,
δ-Carotene ( delta -carotene) or ε,ψ-carotene is a form of carotene with an ε-ring at one end, and the other uncyclized , labelled ψ ( psi ). It is an intermediate synthesis product in some photosynthetic plants between lycopene and α-carotene (β,ε-carotene) or ε-carotene (ε,ε-carotene). [ 1 ] δ-Carotene is fat soluble. Delta-carotene contains an alpha-ionone instead of a beta-ionone ring; [ 2 ] this conversion is carried out by the gene Del which shifts the position of the double bond in the ring structure. The formation delta-carotene under the presence of the Del gene is sensitive to high temperatures. [ 3 ]
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In geochemistry , paleoclimatology , and paleoceanography δ 13 C (pronounced "delta thirteen c") is an isotopic signature , a measure of the ratio of the two stable isotopes of carbon — 13 C and 12 C —reported in parts per thousand (per mil, ‰). [ 1 ] The measure is also widely used in archaeology for the reconstruction of past diets, particularly to see if marine foods or certain types of plants were consumed. [ 2 ]
The definition is, in per mille :
where the standard is an established reference material .
δ 13 C varies in time as a function of productivity, the signature of the inorganic source, organic carbon burial , and vegetation type. Biological processes preferentially take up the lower mass isotope through kinetic fractionation . However some abiotic processes do the same. For example, methane from hydrothermal vents can be depleted by up to 50‰. [ 3 ]
The standard established for carbon-13 work was the Pee Dee Belemnite (PDB) and was based on a Cretaceous marine fossil, Belemnitella americana , which was from the Peedee Formation in South Carolina . This material had an anomalously high 13 C: 12 C ratio (0.0112372 [ 4 ] ), and was established as δ 13 C value of zero.
Since the original PDB specimen is no longer available, its 13 C: 12 C ratio can be back-calculated from a widely measured carbonate standard NBS-19, which has a δ 13 C value of +1.95‰. [ 5 ] The 13 C: 12 C ratio of NBS-19 was reported as 0.011078 / 0.988922 = 0.011202 {\displaystyle 0.011078/0.988922=0.011202} . [ 6 ] Therefore, one could calculate the 13 C: 12 C ratio of PDB derived from NBS-19 as 0.011202 / ( 1.95 / 1000 + 1 ) = 0.011202 / 1.00195 = 0.01118 {\displaystyle 0.011202/(1.95/1000+1)=0.011202/1.00195=0.01118} .
Note that this value differs from the widely used PDB 13 C: 12 C ratio of 0.0112372 used in isotope forensics [ 7 ] and environmental scientists; [ 8 ] this discrepancy was previously attributed by a Wikipedia author to a sign error in the interconversion between standards, but no citation was provided. Use of the PDB standard gives most natural material a negative δ 13 C. [ 9 ] A material with a ratio of 0.010743 for example would have a δ 13 C value of −44‰ from ( 0.010743 ÷ 0.01124 − 1 ) × 1000 {\displaystyle (0.010743\div 0.01124-1)\times 1000} .
The standards are used for verifying the accuracy of mass spectroscopy ; as isotope studies became more common, the demand for the standard exhausted the supply. Other standards calibrated to the same ratio, including one known as VPDB (for "Vienna PDB"), have replaced the original. [ 10 ] The 13 C: 12 C ratio for VPDB, which the International Atomic Energy Agency (IAEA) defines as a δ 13 C value of zero is 0.01123720. [ 11 ]
Methane has a very light δ 13 C signature: biogenic methane of −60‰, thermogenic methane −40‰. The release of large amounts of methane clathrate can affect global δ 13 C values, as at the Paleocene–Eocene Thermal Maximum . [ 12 ]
More commonly, the ratio is affected by variations in primary productivity and organic burial. Organisms preferentially take up light 12 C, and have a δ 13 C signature of about −25‰, depending on their metabolic pathway . Therefore, an increase in δ 13 C in marine fossils is indicative of an increase in the abundance of vegetation. [ citation needed ]
An increase in primary productivity causes a corresponding rise in δ 13 C values as more 12 C is locked up in plants. This signal is also a function of the amount of carbon burial; when organic carbon is buried, more 12 C is locked out of the system in sediments than the background ratio.
C 3 and C 4 plants have different signatures, allowing the abundance of C 4 grasses to be detected through time in the δ 13 C record. [ 13 ] Whereas C 4 plants have a δ 13 C of −16 to −10‰, C 3 plants have a δ 13 C of −33 to −24‰. [ 14 ]
Positive δ 13 C excursions are interpreted as an increase in burial of organic carbon in sedimentary rocks following either a spike in primary productivity, a drop in decomposition under anoxic ocean conditions or both. [ 15 ] For example, the evolution of large land plants in the late Devonian led to increased organic carbon burial and consequently a rise in δ 13 C. [ 16 ]
Negative δ 13 C anomalies, which are thought to represent a decrease in primary productivity and release of plant-based carbon, often mark mass extinctions .
Other important applications of δ 13 C involves understanding its signatures from soft sediments especially in lacustrine environments. This depends on the system from which it is extracted (open system, closed system, etc.). Temporal variations in δ 13 C in organic matter are influenced by diverse internal and external processes: [ 17 ]
Understanding these processes is crucial for interpreting δ 13 C variations in lake sediments and reconstructing paleoenvironmental conditions.
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In geochemistry , hydrology , paleoclimatology and paleoceanography , δ 15 N (pronounced " delta fifteen n") or delta-N-15 is a measure of the ratio of the two stable isotopes of nitrogen , 15 N : 14 N . [ 1 ]
Two very similar expressions for δ 15 N are in wide use in hydrology . [ 2 ] Both have the form 1000 ⋅ s − a a {\displaystyle 1000\cdot {\frac {s-a}{a}}} ‰ (‰ = permil or parts per thousand) where s and a are the relative abundances of 15 N in respectively the sample and the atmosphere. The difference is whether the relative abundance is with respect to all the nitrogen, i.e. 14 N plus 15 N, or just to 14 N. Since the atmosphere is 99.6337% 14 N and 0.3663% 15 N, a is 0.003663 in the former case and 0.003663/0.996337 = 0.003676 in the latter. However s varies similarly; for example if in the sample 15 N is 0.385% and 14 N is 99.615%, s is 0.003850 in the former case and 0.00385/0.99615 = 0.003865 in the latter. The value of 1000 ⋅ s − a a {\displaystyle 1000\cdot {\frac {s-a}{a}}} is then 51.05‰ in the former case and 51.38‰ in the latter, an insignificant difference in practice given the typical range of −20 to 80 for δ 15 N .
The ratio of 15 N to 14 N is of relevance because in most biological contexts, 14 N is preferentially uptaken as the lighter isotope. As a result, samples enriched in 15 N can often be introduced through a non-biological context.
One use of 15 N is as a tracer to determine the path taken by fertilizers applied to anything from pots to landscapes. [ 2 ] Fertilizer enriched in 15 N to an extent significantly different from that prevailing in the soil (which may be different from the atmospheric standard a ) is applied at a point and other points are then monitored for variations in δ 15 N . [ 3 ]
Another application is the assessment of human waste water discharge into bodies of water. [ 4 ] The abundance of 15 N is greater in human waste water than in natural water sources. Hence δ 15 N in benthic sediment gives an indication of the contribution of human waste to the total nitrogen in the sediment. Sediment cores analyzed for δ 15 N yield an historical record of such waste, with older samples at greater depths.
δ 15 N is also used to measure food chain length and the trophic level of a given organism; high δ 15 N values are positively correlated with higher trophic levels; likewise, organisms low on the food chain generally exhibit lower δ 15 N values. Higher δ 15 N values in apex predators generally indicate longer food chains. [ 5 ]
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In geochemistry , paleoclimatology and paleoceanography δ 18 O or delta-O-18 is a measure of the deviation in ratio of stable isotopes oxygen-18 ( 18 O) and oxygen-16 ( 16 O).
It is commonly used as a measure of the temperature of precipitation , as a measure of groundwater/mineral interactions, and as an indicator of processes that show isotopic fractionation , like methanogenesis .
In paleosciences, 18 O: 16 O data from corals , foraminifera and ice cores are used as a proxy for temperature.
It is defined as the deviation in "per mil" (‰, parts per thousand) between a sample and a standard:
where the standard has a known isotopic composition, such as Vienna Standard Mean Ocean Water (VSMOW). [ 1 ] The fractionation can arise from kinetic , equilibrium , or mass-independent fractionation .
Foraminifera shells are composed of calcium carbonate (CaCO 3 ) and are found in many common geological environments. The ratio of 18 O to 16 O in the shell is used to indirectly determine the temperature of the surrounding water at the time the shell was formed. The ratio varies slightly depending on the temperature of the surrounding water, as well as other factors such as the water's salinity, and the volume of water locked up in ice sheets.
δ 18 O also reflects local evaporation and freshwater input, as rainwater is 16 O-enriched—a result of the preferential evaporation of the lighter 16 O from seawater. Consequently, the surface ocean contains greater proportions of 18 O around the subtropics and tropics where there is more evaporation, and lesser proportions of 18 O in the mid-latitudes where it rains more.
Similarly, when water vapor condenses, heavier water molecules holding 18 O atoms tend to condense and precipitate first. The water vapor gradient heading from the tropics to the poles gradually becomes more and more depleted of 18 O. Snow falling in Canada has much less H 2 18 O than rain in Florida ; similarly, snow falling in the center of ice sheets has a lighter δ 18 O signature than that at its margins, since heavier 18 O precipitates first.
Changes in climate that alter global patterns of evaporation and precipitation therefore change the background δ 18 O ratio.
Solid samples (organic and inorganic) for oxygen isotope analysis are usually stored in silver cups and measured with pyrolysis and mass spectrometry . [ 2 ] Researchers need to avoid improper or prolonged storage of the samples for accurate measurements. [ 2 ]
Based on the simplifying assumption that the signal can be attributed to temperature change alone, with the effects of salinity and ice volume change ignored, Epstein et al. (1953) estimated that
a δ 18 O increase of 0.22‰ is equivalent to a cooling of 1 °C (or 1.8 °F). [ 3 ] More precisely, Epstein et al. (1953) give a quadratic extrapolation for the temperature, as
where T is the temperature in °C (based on a least-squares fit for a range of temperature values between 9 °C and 29 °C, with a standard deviation of ±0.6 °C, and δ is δ 18 O for a calcium carbonate sample).
Recent research proposes that early ocean temperatures have been overestimated due to powerful carbonatization and silicification processes in the oceanic crust which consumed oxygen-18 . [ 4 ]
δ 18 O can be used with ice cores to determine the temperature from when the ice was formed.
Lisiecki and Raymo (2005) used measurements of δ 18 O in benthic foraminifera from 57 globally distributed deep sea sediment cores, taken as a proxy for the total global mass of glacial ice sheets, to reconstruct the climate for the past five million years. [ 5 ]
The stacked record of the 57 cores was orbitally tuned to an orbitally driven ice model, the Milankovitch cycles of 41 ky ( obliquity ), 26 ky ( precession ) and 100 ky ( eccentricity ), which are all assumed to cause orbital forcing of global ice volume. Over the past million years, there have been a number of very strong glacial maxima and minima, spaced by roughly 100 ky.
As the observed isotope variations are similar in shape to the temperature variations recorded for the past 420 ky at Vostok Station , the figure shown on the right aligns the values of δ 18 O (right scale) with the reported temperature variations from the Vostok ice core (left scale), following Petit et al. (1999). [ clarification needed ]
δ 18 O from biomineralized tissues may also be used in reconstructing past environmental conditions. In vertebrates, apatite from bone mineral , tooth enamel and dentin contains phosphate [PO 4 ] 3− groups which may preserve the oxygen isotope ratios of environmental water. [ 6 ] [ 7 ] Fractionation of oxygen isotopes in these tissues may be affected by biological factors such as body temperature and diet. [ 8 ]
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The δ 34 S (pronounced delta 34 S ) value is a standardized method for reporting measurements of the ratio of two stable isotopes of sulfur , 34 S: 32 S, in a sample against the equivalent ratio in a known reference standard. The most commonly used standard is Vienna-Canyon Diablo Troilite (VCDT). Results are reported as variations from the standard ratio in parts per thousand, per mil or per mille , using the ‰ symbol. Heavy and light sulfur isotopes fractionate at different rates and the resulting δ 34 S values, recorded in marine sulfate or sedimentary sulfides , have been studied and interpreted as records of the changing sulfur cycle throughout the earth's history.
Of the 25 known isotopes of sulfur , four are stable . [ 1 ] In order of their abundance, those isotopes are 32 S (94.93%), 34 S (4.29%), 33 S (0.76%), and 36 S (0.02%). [ 2 ] The δ 34 S value refers to a measure of the ratio of the two most common stable sulfur isotopes, 34 S: 32 S, as measured in a sample against that same ratio as measured in a known reference standard. The lowercase delta character is used by convention, to be consistent with use in other areas of stable isotope chemistry . [ 3 ] That value can be calculated in per mil (‰, parts per thousand) as: [ 4 ]
Less commonly, if the appropriate isotope abundances are measured, similar formulae can be used to quantify ratio variations between 33 S and 32 S, and 36 S and 32 S, reported as δ 33 S and δ 36 S, respectively. [ 5 ]
Sulfur from meteorites was determined in the early 1950s to be an adequate reference standard because it exhibited a small variability in isotopic ratios. [ 6 ] It was also believed that because of their extraterrestrial provenances, meteors represented primordial terrestrial isotopic conditions. [ 7 ] During a meeting of the National Science Foundation in April 1962, troilite from the Canyon Diablo meteorite found in Arizona, US, was established as the standard with which δ 34 S values (and other sulfur stable isotopic ratios) could be calculated. [ 6 ] [ 8 ] Known as Canyon Diablo Troilite (CDT), the standard was established as having a 32 S: 34 S ratio of 22.220 and was used for around three decades. [ 6 ] In 1993, the International Atomic Energy Agency (IAEA) established a new standard, Vienna-CDT (VCDT), based on artificially prepared silver sulfide (IAEA-S-1) that was defined to have a δ 34 S VCDT value of −0.3‰. [ 8 ] In 1994, the original CDT material was found not to be isotopically homogeneous, with internal variations as great as 0.4‰, confirming its unsuitability as a reference standard. [ 6 ]
Two mechanisms of fractionation occur that alter sulfur stable isotope ratios: kinetic effects, especially due to the metabolism of sulfate-reducing bacteria , and isotope exchange reactions that occur between sulfide phases based on temperature. [ 9 ] With VCDT as the reference standard, natural δ 34 S value variations have been recorded between −72‰ and +147‰. [ 10 ] [ 11 ]
The presence of sulfate-reducing bacteria, which reduce sulfate ( SO 2− 4 ) to hydrogen sulfide (H 2 S), has played a significant role in the oceanic δ 34 S value throughout the earth's history. Sulfate-reducing bacteria metabolize 32 S more readily than 34 S, resulting in an increase in the value of the δ 34 S in the remaining sulfate in the seawater. [ 7 ] Archean pyrite found in barite in the Warrawoona Group , Western Australia, with sulfur fractionations as great as 21.1‰ hint at the presence of sulfate-reducers as early as 3,470 million years ago . [ 12 ]
It is now better known that the degree of isotope fractionation during microbial sulfate reduction depends on the cell-specific sulfate reduction rate of the sulfate-reducing microorganism. [ 13 ] [ 14 ] The relative extent of sulfur isotope fractionating activities, including sulfate reduction, sulfide reoxidation and disproportionation, determines the isotopic compositions of the minerals or fluid measured. [ 15 ] Other than microbial activities and environmental conditions, isotopic compositions also change due to diffusion, accumulation and mixing after burial. [ 16 ] [ 17 ] [ 15 ]
The δ 34 S value, recorded by sulfate in marine evaporites , can be used to chart the sulfur cycle throughout earth's history. [ 7 ] [ 4 ] The Great Oxygenation Event around 2,400 million years ago altered the sulfur cycle radically, as increased atmospheric oxygen permitted an increase in the mechanisms that could fractionate sulfur isotopes, leading to an increase in the δ 34 S value from ~0‰ pre-oxygenation. Approximately 700 million years ago , the δ 34 S values in seawater sulfates began to vary more and those in sedimentary sulfates grew more negative. Researchers have interpreted this excursion as indicative of an increase in water column oxygenation with continued periods of anoxia in the deepest waters. Modern seawater sulfate δ 34 S values are consistently 21.0 ± 0.2‰ across the world's oceans, while sedimentary sulfides vary widely. Seawater sulfate δ 34 S and δ 18 O values exhibit similar trends not seen in sedimentary sulfide minerals. [ 7 ]
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ΔP ( Delta P ) is a mathematical term symbolizing a change (Δ) in pressure (P).
Given that the head loss h f expresses the pressure loss Δp as the height of a column of fluid,
where ρ is the density of the fluid. The Darcy–Weisbach equation can also be written in terms of pressure loss:
In general, compliance is defined by the change in volume (Δ V ) versus the associated change in pressure (Δ P ), or Δ V /Δ P :
During mechanical ventilation , compliance is influenced by three main physiologic factors:
Lung compliance is influenced by a variety of primary abnormalities of lung parenchyma , both chronic and acute. Airway resistance is typically increased by bronchospasm and airway secretions. Chest wall compliance can be decreased by fixed abnormalities (e.g. kyphoscoliosis , morbid obesity ) or more variable problems driven by patient agitation while intubated. [ 1 ]
Calculating compliance on minute volume (V E : Δ V is always defined by tidal volume (V T ), but Δ P is different for the measurement of dynamic vs. static compliance.
where PIP = peak inspiratory pressure (the maximum pressure during inspiration), and PEEP = positive end expiratory pressure . Alterations in airway resistance, lung compliance and chest wall compliance influence C dyn .
where P plat = plateau pressure. P plat is measured at the end of inhalation and prior to exhalation using an inspiratory hold maneuver. During this maneuver, airflow is transiently (~0.5 sec) discontinued, which eliminates the effects of airway resistance. P plat is never > PIP and is typically < 3-5 cmH 2 O lower than PIP when airway resistance is normal.
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ζ-Carotene ( zeta -carotene) is a carotenoid . It is different from α-carotene and β-carotene because it is acyclic. [ 1 ] ζ-Carotene is similar in structure to lycopene , but has an additional 4 hydrogen atoms. ζ-carotene can be used as an intermediate in forming β-carotene. [ 2 ] A dehydrogenation reaction converts ζ-carotene into lycopene, which then can be transformed into β-carotene through the action of lycopene beta-cyclase . [ 3 ] [ 4 ] ζ-Carotene is a natural product found in Lonicera japonica and Rhodospirillum rubrum .
ζ-carotene is formed in plants as an intermediate in the carotenoid biosynthetic pathway . It is produced through sequential desaturation of phytoene by phytoene desaturase and ζ-carotene desaturase enzymes ζ-Carotene occupies a key position in the pathway, serving as a precursor to lycopene , which is further converted into essential carotenoids such as β-carotene . These downstream carotenoids are vital for plant functions, including photosynthesis , photoprotection , and hormone synthesis. [ 5 ] Thus, ζ-carotene plays an important regulatory and biosynthetic role in plant metabolism.
Zeta-carotene has gained attention in plant biotechnology due to its role as an intermediate in carotenoid biosynthesis . Advances in synthetic biology have enabled targeted manipulation of carotenoid pathways, with zeta-carotene serving as a key point for regulating the production of downstream compounds such as lycopene and β-carotene. These strategies aim to optimize carotenoid composition in plants to enhance nutritional value , improve stress tolerance, and increase pigment content for industrial uses. [ 6 ] As such, zeta-carotene has become an important focus in efforts to engineer plant metabolism for agricultural and commercial benefits.
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In mathematics, an η set ( eta set ) is a type of totally ordered set introduced by Hausdorff ( 1907 , p. 126, 1914 , chapter 6 section 8) that generalizes the order type η of the rational numbers.
If α {\displaystyle \alpha } is an ordinal then an η α {\displaystyle \eta _{\alpha }} set is a totally ordered set in which for any two subsets X {\displaystyle X} and Y {\displaystyle Y} of cardinality less than ℵ α {\displaystyle \aleph _{\alpha }} , if every element of X {\displaystyle X} is less than every element of Y {\displaystyle Y} then there is some element greater than all elements of X {\displaystyle X} and less than all elements of Y {\displaystyle Y} .
The only non-empty countable η 0 set (up to isomorphism) is the ordered set of rational numbers.
Suppose that κ = ℵ α is a regular cardinal and let X be the set of all functions f from κ to {−1,0,1} such that if f ( α ) = 0 then f ( β ) = 0 for all β > α , ordered lexicographically. Then X is a η α set. The union of all these sets is the class of surreal numbers .
A dense totally ordered set without endpoints is an η α set if and only if it is ℵ α saturated .
Any η α set X is universal for totally ordered sets of cardinality at most ℵ α , meaning that any such set can be embedded into X .
For any given ordinal α , any two η α sets of cardinality ℵ α are isomorphic (as ordered sets). An η α set of cardinality ℵ α exists if ℵ α is regular and Σ β < α 2 ℵ β ≤ ℵ α .
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The μ-law algorithm (sometimes written mu -law , often abbreviated as u-law ) is a companding algorithm, primarily used in 8-bit PCM digital telecommunications systems in North America and Japan . It is one of the two companding algorithms in the G.711 standard from ITU-T , the other being the similar A-law . A-law is used in regions where digital telecommunication signals are carried on E-1 circuits, e.g. Europe.
The terms PCMU , G711u or G711MU are used for G711 μ-law. [ 1 ]
Companding algorithms reduce the dynamic range of an audio signal . In analog systems, this can increase the signal-to-noise ratio (SNR) achieved during transmission; in the digital domain, it can reduce the quantization error (hence increasing the signal-to-quantization-noise ratio). These SNR increases can be traded instead for reduced bandwidth for equivalent SNR.
At the cost of a reduced peak SNR, it can be mathematically shown that μ-law's non-linear quantization effectively increases dynamic range by 33 dB or 5 + 1 ⁄ 2 bits over a linearly-quantized signal, hence 13.5 bits (which rounds up to 14 bits) is the most resolution required for an input digital signal to be compressed for 8-bit μ-law. [ 2 ]
The μ-law algorithm may be described in an analog form and in a quantized digital form.
For a given input x , the equation for μ-law encoding is [ 3 ] F ( x ) = sgn ( x ) ln ( 1 + μ | x | ) ln ( 1 + μ ) , − 1 ≤ x ≤ 1 , {\displaystyle F(x)=\operatorname {sgn}(x){\dfrac {\ln(1+\mu |x|)}{\ln(1+\mu )}},\quad -1\leq x\leq 1,}
where μ = 255 in the North American and Japanese standards, and sgn( x ) is the sign function . The range of this function is −1 to 1.
μ-law expansion is then given by the inverse equation: [ 3 ] F − 1 ( y ) = sgn ( y ) ( 1 + μ ) | y | − 1 μ , − 1 ≤ y ≤ 1. {\displaystyle F^{-1}(y)=\operatorname {sgn}(y){\dfrac {(1+\mu )^{|y|}-1}{\mu }},\quad -1\leq y\leq 1.}
The discrete form is defined in ITU-T Recommendation G.711 . [ 4 ]
G.711 is unclear about how to code the values at the limit of a range (e.g. whether +31 codes to 0xEF or 0xF0). [ citation needed ] However, G.191 provides example code in the C language for a μ-law encoder. [ 5 ] The difference between the positive and negative ranges, e.g. the negative range corresponding to +30 to +1 is −31 to −2. This is accounted for by the use of 1's complement (simple bit inversion) rather than 2's complement to convert a negative value to a positive value during encoding.
The μ-law algorithm may be implemented in several ways:
μ-law encoding is used because speech has a wide dynamic range . In analog signal transmission, in the presence of relatively constant background noise, the finer detail is lost. Given that the precision of the detail is compromised anyway, and assuming that the signal is to be perceived as audio by a human, one can take advantage of the fact that the perceived acoustic intensity level or loudness is logarithmic by compressing the signal using a logarithmic-response operational amplifier ( Weber–Fechner law ). In telecommunications circuits, most of the noise is injected on the lines, thus after the compressor, the intended signal is perceived as significantly louder than the static, compared to an uncompressed source. This became a common solution, and thus, prior to common digital usage, the μ-law specification was developed to define an interoperable standard.
This pre-existing algorithm had the effect of significantly lowering the amount of bits required to encode a recognizable human voice in digital systems. A sample could be effectively encoded using μ-law in as little as 8 bits, which conveniently matched the symbol size of the majority of common computers.
μ-law encoding effectively reduced the dynamic range of the signal, thereby increasing the coding efficiency while biasing the signal in a way that results in a signal-to- distortion ratio that is greater than that obtained by linear encoding for a given number of bits.
The μ-law algorithm is also used in the .au format , which dates back at least to the SPARCstation 1 by Sun Microsystems as the native method used by the /dev/audio interface, widely used as a de facto standard for sound on Unix systems. The au format is also used in various common audio APIs such as the classes in the sun.audio Java package in Java 1.1 and in some C# methods.
This plot illustrates how μ-law concentrates sampling in the smaller (softer) values. The horizontal axis represents the byte values 0-255 and the vertical axis is the 16-bit linear decoded value of μ-law encoding.
The μ-law algorithm provides a slightly larger dynamic range than the A-law at the cost of worse proportional distortions for small signals. By convention, A-law is used for an international connection if at least one country uses it.
This article incorporates public domain material from Federal Standard 1037C . General Services Administration . Archived from the original on 22 January 2022.
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In organic chemistry , aromaticity is a chemical property describing the way in which a conjugated ring of unsaturated bonds , lone pairs , or empty orbitals exhibits a stabilization stronger than would be expected from conjugation alone. The earliest use of the term was in an article by August Wilhelm Hofmann in 1855. [ 1 ] There is no general relationship between aromaticity as a chemical property and the olfactory properties of such compounds.
Aromaticity can also be considered a manifestation of cyclic delocalization and of resonance . [ 2 ] [ 3 ] [ 4 ] This is usually considered to be because electrons are free to cycle around circular arrangements of atoms that are alternately single- and double- bonded to one another. This commonly seen model of aromatic rings, namely the idea that benzene was formed from a six-membered carbon ring with alternating single and double bonds (cyclohexatriene), was developed by Kekulé (see History section below). Each bond may be seen as a hybrid of a single bond and a double bond, every bond in the ring identical to every other. The model for benzene consists of two resonance forms, which corresponds to the double and single bonds superimposing to give rise to six one-and-a-half bonds. Benzene is a more stable molecule than would be expected without accounting for charge delocalization.
As is standard for resonance diagrams , a double-headed arrow is used to indicate that the two structures are not distinct entities, but merely hypothetical possibilities. Neither is an accurate representation of the actual compound, which is best represented by a hybrid (average) of these structures, which can be seen at right. A C=C bond is shorter than a C−C bond, but benzene is perfectly hexagonal—all six carbon-carbon bonds have the same length , intermediate between that of a single and that of a double bond .
A better representation is that of the circular π bond (Armstrong's inner cycle ), in which the electron density is evenly distributed through a π-bond above and below the ring. This model more correctly represents the location of electron density within the aromatic ring.
The single bonds are formed with electrons in line between the carbon nuclei — these are called σ-bonds . Double bonds consist of a σ-bond and a π-bond. The π-bonds are formed from overlap of atomic p-orbitals above and below the plane of the ring. The following diagram shows the positions of these p-orbitals:
Since they are out of the plane of the atoms, these orbitals can interact with each other freely, and become delocalized. This means that, instead of being tied to one atom of carbon, each electron is shared by all six in the ring. Thus, there are not enough electrons to form double bonds on all the carbon atoms, but the "extra" electrons strengthen all of the bonds on the ring equally. The resulting molecular orbital has π symmetry.
The first known use of the word "aromatic" as a chemical term — namely, to apply to compounds that contain the phenyl radical — occurs in an article by August Wilhelm Hofmann in 1855. [ 1 ] If this is indeed the earliest introduction of the term, it is curious that Hofmann says nothing about why he introduced an adjective indicating olfactory character to apply to a group of chemical substances only some of which have notable aromas . Also, many of the most odoriferous organic substances known are terpenes , which are not aromatic in the chemical sense. But terpenes and benzenoid substances do have a chemical characteristic in common, namely higher unsaturation indices than many aliphatic compounds , and Hofmann may not have been making a distinction between the two categories.
In the 19th century, chemists found it puzzling that benzene could be so unreactive toward addition reactions, given its presumed high degree of unsaturation. The cyclohexatriene structure for benzene was first proposed by August Kekulé in 1865. Over the next few decades, most chemists readily accepted this structure, since it accounted for most of the known isomeric relationships of aromatic chemistry.
Between 1897 and 1906, J. J. Thomson , the discoverer of the electron, proposed three equivalent electrons between each carbon atom in benzene.
An explanation for the exceptional stability of benzene is conventionally attributed to Sir Robert Robinson , who was apparently the first (in 1925) [ 6 ] to coin the term aromatic sextet as a group of six electrons that resists disruption.
In fact, this concept can be traced further back, via Ernest Crocker in 1922, [ 7 ] to Henry Edward Armstrong , who in 1890 wrote "the (six) centric affinities act within a cycle ... benzene may be represented by a double ring ( sic ) ... and when an additive compound is formed, the inner cycle of affinity suffers disruption, the contiguous carbon-atoms to which nothing has been attached of necessity acquire the ethylenic condition". [ 8 ] [ verification needed ]
Here, Armstrong is describing at least four modern concepts. First, his "affinity" is better known nowadays as the electron , which was to be discovered only seven years later by J. J. Thomson. Second, he is describing electrophilic aromatic substitution , proceeding (third) through a Wheland intermediate , in which (fourth) the conjugation of the ring is broken. He introduced the symbol C centered on the ring as a shorthand for the inner cycle , thus anticipating Erich Clar 's notation. It is argued that he also anticipated the nature of wave mechanics , since he recognized that his affinities had direction, not merely being point particles, and collectively having a distribution that could be altered by introducing substituents onto the benzene ring ( much as the distribution of the electric charge in a body is altered by bringing it near to another body ).
The quantum mechanical origins of this stability, or aromaticity, were first modelled by Hückel in 1931. He was the first to separate the bonding electrons into sigma and pi electrons.
An aromatic (or aryl ) compound contains a set of covalently bound atoms with specific characteristics:
Whereas benzene is aromatic (6 electrons, from 3 double bonds), cyclobutadiene is not, since the number of π delocalized electrons is 4, which of course is a multiple of 4. The cyclobutadienide (2−) ion, however, is aromatic (6 electrons). An atom in an aromatic system can have other electrons that are not part of the system, and are therefore ignored for the 4n + 2 rule. In furan , the oxygen atom is sp² hybridized. One lone pair is in the π system and the other in the plane of the ring (analogous to C-H bond on the other positions). There are 6 π electrons, so furan is aromatic.
Aromatic molecules typically display enhanced chemical stability, compared to similar non-aromatic molecules. A molecule that can be aromatic will tend to alter its electronic or conformational structure to be in this situation. This extra stability changes the chemistry of the molecule. Aromatic compounds undergo electrophilic aromatic substitution and nucleophilic aromatic substitution reactions, but not electrophilic addition reactions as happens with carbon-carbon double bonds.
Many of the earliest-known examples of aromatic compounds, such as benzene and toluene, have distinctive pleasant smells. This property led to the term "aromatic" for this class of compounds, and hence the term "aromaticity" for the eventually discovered electronic property.
The circulating π electrons in an aromatic molecule produce ring currents that oppose the applied magnetic field in NMR . [ 9 ] The NMR signal of protons in the plane of an aromatic ring are shifted substantially further down-field than those on non-aromatic sp² carbons. This is an important way of detecting aromaticity. By the same mechanism, the signals of protons located near the ring axis are shifted up-field.
Aromatic molecules are able to interact with each other in so-called π-π stacking : The π systems form two parallel rings overlap in a "face-to-face" orientation. Aromatic molecules are also able to interact with each other in an "edge-to-face" orientation: The slight positive charge of the substituents on the ring atoms of one molecule are attracted to the slight negative charge of the aromatic system on another molecule.
Planar monocyclic molecules containing 4n π electrons are called antiaromatic and are, in general, destabilized. Molecules that could be antiaromatic will tend to alter their electronic or conformational structure to avoid this situation, thereby becoming non-aromatic. For example, cyclooctatetraene (COT) distorts itself out of planarity, breaking π overlap between adjacent double bonds. Relatively recently, cyclobutadiene was discovered to adopt an asymmetric, rectangular configuration in which single and double bonds indeed alternate; there is no resonance and the single bonds are markedly longer than the double bonds, reducing unfavorable p-orbital overlap. This reduction of symmetry lifts the degeneracy of the two formerly non-bonding molecular orbitals, which by Hund's rule forces the two unpaired electrons into a new, weakly bonding orbital (and also creates a weakly antibonding orbital). Hence, cyclobutadiene is non-aromatic; the strain of the asymmetric configuration outweighs the anti-aromatic destabilization that would afflict the symmetric, square configuration.
Aromatic compounds play key roles in the biochemistry of all living things. The four aromatic amino acids histidine , phenylalanine , tryptophan , and tyrosine each serve as one of the 20 basic building-blocks of proteins. Further, all 5 nucleotides ( adenine , thymine , cytosine , guanine , and uracil ) that make up the sequence of the genetic code in DNA and RNA are aromatic purines or pyrimidines . The molecule heme contains an aromatic system with 22 π electrons. Chlorophyll also has a similar aromatic system.
Aromatic compounds are important in industry. Key aromatic hydrocarbons of commercial interest are benzene , toluene , ortho -xylene and para -xylene . About 35 million tonnes are produced worldwide every year. They are extracted from complex mixtures obtained by the refining of oil or by distillation of coal tar, and are used to produce a range of important chemicals and polymers, including styrene , phenol , aniline , polyester and nylon .
The overwhelming majority of aromatic compounds are compounds of carbon, but they need not be hydrocarbons.
Benzene , as well as most other annulenes ( cyclodecapentaene excepted) with the formula C n H n where n ≥ 4 and is an even number, such as cyclotetradecaheptaene .
In heterocyclic aromatics ( heteroaromats ), one or more of the atoms in the aromatic ring is of an element other than carbon. This can lessen the ring's aromaticity, and thus (as in the case of furan ) increase its reactivity. Other examples include pyridine , pyrazine , imidazole , pyrazole , oxazole , thiazole , thiophene , and their benzannulated analogs ( benzimidazole , for example).
Polycyclic aromatic hydrocarbons are molecules containing two or more simple aromatic rings fused together by sharing two neighboring carbon atoms (see also simple aromatic rings ). Examples are naphthalene , anthracene , and phenanthrene .
Many chemical compounds are aromatic rings with other functional groups attached. Examples include trinitrotoluene (TNT), acetylsalicylic acid (aspirin), paracetamol , and the nucleotides of DNA .
Aromaticity is found in ions as well: the cyclopropenyl cation (2e system), the cyclopentadienyl anion (6e system), the tropylium ion (6e), and the cyclooctatetraene dianion (10e). Aromatic properties have been attributed to non-benzenoid compounds such as tropone . Aromatic properties are tested to the limit in a class of compounds called cyclophanes .
A special case of aromaticity is found in homoaromaticity where conjugation is interrupted by a single sp ³ hybridized carbon atom.
When carbon in benzene is replaced by other elements in borabenzene , silabenzene , germanabenzene , stannabenzene , phosphorine or pyrylium salts the aromaticity is still retained. Aromaticity also occurs in compounds that are not carbon-based at all. Inorganic 6-membered-ring compounds analogous to benzene have been synthesized. Hexasilabenzene (Si 6 H 6 ) and borazine (B 3 N 3 H 6 ) are structurally analogous to benzene, with the carbon atoms replaced by another element or elements. In borazine, the boron and nitrogen atoms alternate around the ring. Quite recently, the aromaticity of planar Si 5 6- rings occurring in the Zintl phase Li 12 Si 7 was experimentally evidenced by Li solid state NMR. [ 10 ]
Metal aromaticity is believed to exist in certain metal clusters of aluminium. [ citation needed ]
Möbius aromaticity occurs when a cyclic system of molecular orbitals, formed from p π atomic orbitals and populated in a closed shell by 4n (n is an integer) electrons, is given a single half-twist to correspond to a Möbius strip . A π system with 4n electrons in a flat (non-twisted) ring would be anti-aromatic, and therefore highly unstable, due to the symmetry of the combinations of p atomic orbitals. By twisting the ring, the symmetry of the system changes and becomes allowed (see also Möbius–Hückel concept for details). Because the twist can be left-handed or right-handed , the resulting Möbius aromatics are dissymmetric or chiral .
As of 2012, there is no proof that a Möbius aromatic molecule was synthesized. [ 11 ] [ 12 ] Aromatics with two half-twists corresponding to the paradromic topologies were first suggested by Johann Listing . [ 13 ] In carbo-benzene the ring bonds are extended with alkyne and allene groups.
Y-aromaticity is a concept which was developed to explain the extraordinary stability and high basicity of the guanidinium cation. Guanidinium does not have a ring structure but has six π-electrons which are delocalized over the molecule. However, this concept is controversial and some authors have stressed different effects. [ 14 ] [ 15 ] [ 16 ]
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Horst Prinzbach (20 July 1931 in Haslach im Kinzigtal – 18 September 2012 in Freiburg im Breisgau ) was a German chemist and professor emeritus.
Prinzbach studied chemistry at the University of Freiburg and received his PhD under Arthur Lüttringhaus. He joined William von Eggers Doering at Yale University for postdoctoral work. In 1962 he completed his habilitation at Freiburg with a dissertation on sesquifulvalenes. In 1965 he became a professor of organic chemistry at the University of Lausanne , Switzerland, and in 1969 he became a full professor in organic chemistry at Freiburg.
Of his many research interests in organic chemistry, including photochemistry with unusual chromophores, synthesis of new carba-/hetera cages, radical cations, dications, total synthesis of aminoglycosid antibiotics, and enzymes, Prinzbach was probably best known for the pagodane route towards dodecahedrane . [ citation needed ] In the course of his research, the phenomenon of σ-bishomoaromaticity was discovered as an extreme case of chemical bonding. The final landmark the development of dodecahedrane chemistry over many years was the preparation and characterisation of C20 fullerene in the gas phase based on bromination-elimination reactions of dodecahedrane. [ 1 ] [ 2 ]
σ-Bishomoaromaticity is an extreme case of the chemical bond and the aromaticity . It was found by the Prinzbach when they synthesized dodecahedrane via the Pagodane route [ 3 ] [ 4 ] [ 5 ]
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In mathematical logic , an ω-consistent (or omega-consistent , also called numerically segregative ) [ 1 ] theory is a theory (collection of sentences ) that is not only (syntactically) consistent [ 2 ] (that is, does not prove a contradiction ), but also avoids proving certain infinite combinations of sentences that are intuitively contradictory. The name is due to Kurt Gödel , who introduced the concept in the course of proving the incompleteness theorem . [ 3 ]
A theory T is said to interpret the language of arithmetic if there is a translation of formulas of arithmetic into the language of T so that T is able to prove the basic axioms of the natural numbers under this translation.
A T that interprets arithmetic is ω-inconsistent if, for some property P of natural numbers (defined by a formula in the language of T ), T proves P (0), P (1), P (2), and so on (that is, for every standard natural number n , T proves that P ( n ) holds), but T also proves that there is some natural number n such that P ( n ) fails . [ 2 ] This may not generate a contradiction within T because T may not be able to prove for any specific value of n that P ( n ) fails, only that there is such an n . In particular, such n is necessarily a nonstandard integer in any model for T (Quine has thus called such theories "numerically insegregative"). [ 4 ]
T is ω-consistent if it is not ω-inconsistent.
There is a weaker but closely related property of Σ 1 -soundness. A theory T is Σ 1 -sound (or 1-consistent , in another terminology) [ 5 ] if every Σ 0 1 -sentence [ 6 ] provable in T is true in the standard model of arithmetic N (i.e., the structure of the usual natural numbers with addition and multiplication).
If T is strong enough to formalize a reasonable model of computation , Σ 1 -soundness is equivalent to demanding that whenever T proves that a Turing machine C halts, then C actually halts. Every ω-consistent theory is Σ 1 -sound, but not vice versa.
More generally, we can define an analogous concept for higher levels of the arithmetical hierarchy . If Γ is a set of arithmetical sentences (typically Σ 0 n for some n ), a theory T is Γ-sound if every Γ-sentence provable in T is true in the standard model. When Γ is the set of all arithmetical formulas, Γ-soundness is called just (arithmetical) soundness .
If the language of T consists only of the language of arithmetic (as opposed to, for example, set theory ), then a sound system is one whose model can be thought of as the set ω, the usual set of mathematical natural numbers. The case of general T is different, see ω-logic below.
Σ n -soundness has the following computational interpretation: if the theory proves that a program C using a Σ n −1 - oracle halts, then C actually halts.
Write PA for the theory Peano arithmetic , and Con(PA) for the statement of arithmetic that formalizes the claim "PA is consistent". Con(PA) could be of the form "No natural number n is the Gödel number of a proof in PA that 0=1". [ 7 ] Now, the consistency of PA implies the consistency of PA + ¬Con(PA). Indeed, if PA + ¬Con(PA) was inconsistent, then PA alone would prove ¬Con(PA)→0=1, and a reductio ad absurdum in PA would produce a proof of Con(PA). By Gödel's second incompleteness theorem , PA would be inconsistent.
Therefore, assuming that PA is consistent, PA + ¬Con(PA) is consistent too. However, it would not be ω-consistent. This is because, for any particular n , PA, and hence PA + ¬Con(PA), proves that n is not the Gödel number of a proof that 0=1. However, PA + ¬Con(PA) proves that, for some natural number n , n is the Gödel number of such a proof (this is just a direct restatement of the claim ¬Con(PA)).
In this example, the axiom ¬Con(PA) is Σ 1 , hence the system PA + ¬Con(PA) is in fact Σ 1 -unsound, not just ω-inconsistent.
Let T be PA together with the axioms c ≠ n for each natural number n , where c is a new constant added to the language. Then T is arithmetically sound (as any nonstandard model of PA can be expanded to a model of T ), but ω-inconsistent (as it proves ∃ x c = x {\displaystyle \exists x\,c=x} , and c ≠ n for every number n ).
Σ 1 -sound ω-inconsistent theories using only the language of arithmetic can be constructed as follows. Let I Σ n be the subtheory of PA with the induction schema restricted to Σ n -formulas, for any n > 0. The theory I Σ n + 1 is finitely axiomatizable, let thus A be its single axiom, and consider the theory T = I Σ n + ¬ A . We can assume that A is an instance of the induction schema, which has the form
If we denote the formula
by P ( n ), then for every natural number n , the theory T (actually, even the pure predicate calculus) proves P ( n ). On the other hand, T proves the formula ∃ x ¬ P ( x ) {\displaystyle \exists x\,\neg P(x)} , because it is logically equivalent to the axiom ¬ A . Therefore, T is ω-inconsistent.
It is possible to show that T is Π n + 3 -sound. In fact, it is Π n + 3 - conservative over the (obviously sound) theory I Σ n . The argument is more complicated (it relies on the provability of the Σ n + 2 - reflection principle for I Σ n in I Σ n + 1 ).
Let ω-Con(PA) be the arithmetical sentence formalizing the statement "PA is ω-consistent". Then the theory PA + ¬ω-Con(PA) is unsound (Σ 3 -unsound, to be precise), but ω-consistent. The argument is similar to the first example: a suitable version of the Hilbert – Bernays – Löb derivability conditions holds for the "provability predicate" ω-Prov( A ) = ¬ω-Con(PA + ¬ A ), hence it satisfies an analogue of Gödel's second incompleteness theorem.
The concept of theories of arithmetic whose integers are the true mathematical integers is captured by ω-logic . [ 8 ] Let T be a theory in a countable language that includes a unary predicate symbol N intended to hold just of the natural numbers, as well as specified names 0, 1, 2, ..., one for each (standard) natural number (which may be separate constants, or constant terms such as 0, 1, 1+1, 1+1+1, ..., etc.). Note that T itself could be referring to more general objects, such as real numbers or sets; thus in a model of T the objects satisfying N ( x ) are those that T interprets as natural numbers, not all of which need be named by one of the specified names.
The system of ω-logic includes all axioms and rules of the usual first-order predicate logic, together with, for each T -formula P ( x ) with a specified free variable x , an infinitary ω-rule of the form:
That is, if the theory asserts (i.e. proves) P ( n ) separately for each natural number n given by its specified name, then it also asserts P collectively for all natural numbers at once via the evident finite universally quantified counterpart of the infinitely many antecedents of the rule. For a theory of arithmetic, meaning one with intended domain the natural numbers such as Peano arithmetic , the predicate N is redundant and may be omitted from the language, with the consequent of the rule for each P simplifying to ∀ x P ( x ) {\displaystyle \forall x\,P(x)} .
An ω-model of T is a model of T whose domain includes the natural numbers and whose specified names and symbol N are standardly interpreted, respectively as those numbers and the predicate having just those numbers as its domain (whence there are no nonstandard numbers). If N is absent from the language then what would have been the domain of N is required to be that of the model, i.e. the model contains only the natural numbers. (Other models of T may interpret these symbols nonstandardly; the domain of N need not even be countable, for example.) These requirements make the ω-rule sound in every ω-model. As a corollary to the omitting types theorem , the converse also holds: the theory T has an ω-model if and only if it is consistent in ω-logic.
There is a close connection of ω-logic to ω-consistency. A theory consistent in ω-logic is also ω-consistent (and arithmetically sound). The converse is false, as consistency in ω-logic is a much stronger notion than ω-consistency. However, the following characterization holds: a theory is ω-consistent if and only if its closure under unnested applications of the ω-rule is consistent.
If the theory T is recursively axiomatizable , ω-consistency has the following characterization, due to Craig Smoryński : [ 9 ]
Here, T h Π 2 0 ( N ) {\displaystyle \mathrm {Th} _{\Pi _{2}^{0}}(\mathbb {N} )} is the set of all Π 0 2 -sentences valid in the standard model of arithmetic, and R F N T {\displaystyle \mathrm {RFN} _{T}} is the uniform reflection principle for T , which consists of the axioms
for every formula φ {\displaystyle \varphi } with one free variable. In particular, a finitely axiomatizable theory T in the language of arithmetic is ω-consistent if and only if T + PA is Σ 2 0 {\displaystyle \Sigma _{2}^{0}} -sound.
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https://en.wikipedia.org/wiki/Ω-consistent_theory
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In set theory , Ω-logic is an infinitary logic and deductive system proposed by W. Hugh Woodin ( 1999 ) as part of an attempt to generalize the theory of determinacy of pointclasses to cover the structure H ℵ 2 {\displaystyle H_{\aleph _{2}}} . Just as the axiom of projective determinacy yields a canonical theory of H ℵ 1 {\displaystyle H_{\aleph _{1}}} , he sought to find axioms that would give a canonical theory for the larger structure. The theory he developed involves a controversial argument that the continuum hypothesis is false.
Woodin's Ω-conjecture asserts that if there is a proper class of Woodin cardinals (for technical reasons, most results in the theory are most easily stated under this assumption), then Ω-logic satisfies an analogue of the completeness theorem . From this conjecture, it can be shown that, if there is any single axiom which is comprehensive over H ℵ 2 {\displaystyle H_{\aleph _{2}}} (in Ω-logic), it must imply that the continuum is not ℵ 1 {\displaystyle \aleph _{1}} . Woodin also isolated a specific axiom, a variation of Martin's maximum , which states that any Ω-consistent Π 2 {\displaystyle \Pi _{2}} (over H ℵ 2 {\displaystyle H_{\aleph _{2}}} ) sentence is true; this axiom implies that the continuum is ℵ 2 {\displaystyle \aleph _{2}} .
Woodin also related his Ω-conjecture to a proposed abstract definition of large cardinals: he took a "large cardinal property" to be a Σ 2 {\displaystyle \Sigma _{2}} property P ( α ) {\displaystyle P(\alpha )} of ordinals which implies that α is a strong inaccessible , and which is invariant under forcing by sets of cardinal less than α. Then the Ω-conjecture implies that if there are arbitrarily large models containing a large cardinal, this fact will be provable in Ω-logic.
The theory involves a definition of Ω-validity : a statement is an Ω-valid consequence of a set theory T if it holds in every model of T having the form V α B {\displaystyle V_{\alpha }^{\mathbb {B} }} for some ordinal α {\displaystyle \alpha } and some forcing notion B {\displaystyle \mathbb {B} } . This notion is clearly preserved under forcing, and in the presence of a proper class of Woodin cardinals it will also be invariant under forcing (in other words, Ω-satisfiability is preserved under forcing as well). There is also a notion of Ω-provability ; [ 1 ] here the "proofs" consist of universally Baire sets and are checked by verifying that for every countable transitive model of the theory, and every forcing notion in the model, the generic extension of the model (as calculated in V ) contains the "proof", restricted its own reals. For a proof-set A the condition to be checked here is called " A -closed". A complexity measure can be given on the proofs by their ranks in the Wadge hierarchy . Woodin showed that this notion of "provability" implies Ω-validity for sentences which are Π 2 {\displaystyle \Pi _{2}} over V . The Ω-conjecture states that the converse of this result also holds. In all currently known core models , it is known to be true; moreover the consistency strength of the large cardinals corresponds to the least proof-rank required to "prove" the existence of the cardinals.
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https://en.wikipedia.org/wiki/Ω-logic
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Dinitrogen tetroxide Dinitrogen trioxide Nitrogen dioxide Nitrous oxide Nitroxyl (reduced form) Hydroxylamine (hydrogenated form)
Nitric oxide ( nitrogen oxide or nitrogen monoxide [ 1 ] ) is a colorless gas with the formula NO . It is one of the principal oxides of nitrogen . Nitric oxide is a free radical : it has an unpaired electron , which is sometimes denoted by a dot in its chemical formula ( • N=O or • NO). Nitric oxide is also a heteronuclear diatomic molecule , a class of molecules whose study spawned early modern theories of chemical bonding . [ 6 ]
An important intermediate in industrial chemistry , nitric oxide forms in combustion systems and can be generated by lightning in thunderstorms. In mammals, including humans, nitric oxide is a signaling molecule in many physiological and pathological processes. [ 7 ] It was proclaimed the " Molecule of the Year " in 1992. [ 8 ] The 1998 Nobel Prize in Physiology or Medicine was awarded for discovering nitric oxide's role as a cardiovascular signalling molecule. [ 9 ] Its impact extends beyond biology, with applications in medicine, such as the development of sildenafil (Viagra), and in industry, including semiconductor manufacturing. [ 10 ] [ 11 ]
Nitric oxide should not be confused with nitrogen dioxide (NO 2 ), a brown gas and major air pollutant , or with nitrous oxide (N 2 O), an anesthetic gas. [ 6 ]
Nitric oxide (NO) was first identified by Joseph Priestley in the late 18th century, originally seen as merely a toxic byproduct of combustion and an environmental pollutant. [ 12 ] Its biological significance was later uncovered in the 1980s when researchers Robert F. Furchgott , Louis J. Ignarro , and Ferid Murad discovered its critical role as a vasodilator in the cardiovascular system, a breakthrough that earned them the 1998 Nobel Prize in Physiology or Medicine. [ 13 ]
The ground state electronic configuration of NO is, in united atom notation: [ 14 ]
( 1 σ ) 2 ( 2 σ ) 2 ( 3 σ ) 2 ( 4 σ ∗ ) 2 ( 5 σ ) 2 ( 1 π ) 4 ( 2 π ∗ ) 1 {\displaystyle (1\sigma )^{2}(2\sigma )^{2}(3\sigma )^{2}(4\sigma ^{*})^{2}(5\sigma )^{2}(1\pi )^{4}(2\pi ^{*})^{1}}
The first two orbitals are actually pure atomic 1 s O and 1 s N from oxygen and nitrogen respectively and therefore are usually not noted in the united atom notation. Orbitals noted with an asterisk are antibonding. The ordering of 5σ and 1π according to their binding energies is subject to discussion. Removal of a 1π electron leads to 6 states whose energies span over a range starting at a lower level than a 5σ electron an extending to a higher level. This is due to the different orbital momentum couplings between a 1π and a 2π electron.
The lone electron in the 2π orbital makes NO a doublet (X ²Π) in its ground state whose degeneracy is split in the fine structure from spin-orbit coupling with a total momentum J = 3 ⁄ 2 or J = 1 ⁄ 2 .
The dipole of NO has been measured experimentally to 0.15740 D and is oriented from O to N (⁻NO⁺) due to the transfer of negative electronic charge from oxygen to nitrogen. [ 15 ]
Upon condensing to a neat liquid, nitric oxide dimerizes to colorless dinitrogen dioxide (O=N–N=O), but the association is weak and reversible. The N–N distance in crystalline NO is 218 pm, nearly twice the N–O distance. Condensation in a highly polar environment instead gives the red alternant isomer O=N–O + =N − . [ 6 ]
Since the heat of formation of • NO is endothermic , NO can be decomposed to the elements. Catalytic converters in cars exploit this reaction:
When exposed to oxygen , nitric oxide converts into nitrogen dioxide :
This reaction is thought to occur via the intermediates ONOO • and the red compound ONOONO. [ 16 ]
In water, nitric oxide reacts with oxygen to form nitrous acid (HNO 2 ). The reaction is thought to proceed via the following stoichiometry :
Nitric oxide reacts with fluorine , chlorine , and bromine to form the nitrosyl halides, such as nitrosyl chloride :
With NO 2 , also a radical, NO combines to form the intensely blue dinitrogen trioxide : [ 6 ]
Nitric oxide rarely sees organic chemistry use. Most reactions with it produce complex mixtures of salts, separable only through careful recrystallization . [ 17 ]
The addition of a nitric oxide moiety to another molecule is often referred to as nitrosylation . The Traube reaction is the addition of a two equivalents of nitric oxide onto an enolate , giving a diazeniumdiolate (also called a nitrosohydroxylamine ). [ 18 ] The product can undergo a subsequent retro- aldol reaction , giving an overall process similar to the haloform reaction . For example, nitric oxide reacts with acetone and an alkoxide to form a diazeniumdiolate on each α position , with subsequent loss of methyl acetate as a by-product : [ 19 ]
This reaction, which was discovered around 1898, remains of interest in nitric oxide prodrug research. Nitric oxide can also react directly with sodium methoxide , ultimately forming sodium formate and nitrous oxide by way of an N -methoxydiazeniumdiolate. [ 20 ]
Sufficiently basic secondary amines undergo a Traube-like reaction to give NONOates . [ 21 ] However, very few nucleophiles undergo the Traube reaction, either failing to adduce NO or immediately decomposing with nitrous oxide release. [ 17 ]
Nitric oxide reacts with transition metals to give complexes called metal nitrosyls . The most common bonding mode of nitric oxide is the terminal linear type (M−NO). [ 6 ] Alternatively, nitric oxide can serve as a one-electron pseudohalide. In such complexes, the M−N−O group is characterized by an angle between 120° and 140°. The NO group can also bridge between metal centers through the nitrogen atom in a variety of geometries.
In commercial settings, nitric oxide is produced by the oxidation of ammonia at 750–900 °C (normally at 850 °C) with platinum as catalyst in the Ostwald process :
The uncatalyzed endothermic reaction of oxygen (O 2 ) and nitrogen (N 2 ), which is effected at high temperature (>2000 °C) by lightning has not been developed into a practical commercial synthesis (see Birkeland–Eyde process ):
In the laboratory, nitric oxide is conveniently generated by reduction of dilute nitric acid with copper :
An alternative route involves the reduction of nitrous acid in the form of sodium nitrite or potassium nitrite :
The iron(II) sulfate route is simple and has been used in undergraduate laboratory experiments.
So-called NONOate compounds are also used for nitric oxide generation, especially in biological laboratories. However, other Traube adducts may decompose to instead give nitrous oxide . [ 22 ]
Nitric oxide concentration can be determined using a chemiluminescent reaction involving ozone . [ 23 ] A sample containing nitric oxide is mixed with a large quantity of ozone. The nitric oxide reacts with the ozone to produce oxygen and nitrogen dioxide , accompanied with emission of light ( chemiluminescence ):
which can be measured with a photodetector . The amount of light produced is proportional to the amount of nitric oxide in the sample.
Other methods of testing include electroanalysis (amperometric approach), where ·NO reacts with an electrode to induce a current or voltage change. The detection of NO radicals in biological tissues is particularly difficult due to the short lifetime and concentration of these radicals in tissues. One of the few practical methods is spin trapping of nitric oxide with iron- dithiocarbamate complexes and subsequent detection of the mono-nitrosyl-iron complex with electron paramagnetic resonance (EPR). [ 24 ] [ 25 ]
A group of fluorescent dye indicators that are also available in acetylated form for intracellular measurements exist. The most common compound is 4,5-diaminofluorescein (DAF-2). [ 26 ]
Nitric oxide reacts with the hydroperoxyl radical ( HO • 2 ) to form nitrogen dioxide (NO 2 ), which then can react with a hydroxyl radical (HO • ) to produce nitric acid (HNO 3 ):
Nitric acid, along with sulfuric acid , contributes to acid rain deposition.
• NO participates in ozone layer depletion . Nitric oxide reacts with stratospheric ozone to form O 2 and nitrogen dioxide:
This reaction is also utilized to measure concentrations of • NO in control volumes.
As seen in the acid deposition section, nitric oxide can transform into nitrogen dioxide (this can happen with the hydroperoxy radical, HO • 2 , or diatomic oxygen, O 2 ). Symptoms of short-term nitrogen dioxide exposure include nausea, dyspnea and headache. Long-term effects could include impaired immune and respiratory function. [ 27 ]
NO is a gaseous signaling molecule . [ 28 ] It is a key vertebrate biological messenger , playing a role in a variety of biological processes. [ 29 ] It is a bioproduct in almost all types of organisms, including bacteria, plants, fungi, and animal cells. [ 30 ]
Nitric oxide, an endothelium-derived relaxing factor (EDRF), is biosynthesized endogenously from L -arginine , oxygen , and NADPH by various nitric oxide synthase (NOS) enzymes . [ 31 ] Reduction of inorganic nitrate may also make nitric oxide. [ 32 ] One of the main enzymatic targets of nitric oxide is guanylyl cyclase . [ 33 ] The binding of nitric oxide to the heme region of the enzyme leads to activation, in the presence of iron. [ 33 ] Nitric oxide is highly reactive (having a lifetime of a few seconds), yet diffuses freely across membranes. These attributes make nitric oxide ideal for a transient paracrine (between adjacent cells) and autocrine (within a single cell) signaling molecule. [ 32 ] Once nitric oxide is converted to nitrates and nitrites by oxygen and water, cell signaling is deactivated. [ 33 ]
The endothelium (inner lining) of blood vessels uses nitric oxide to signal the surrounding smooth muscle to relax, resulting in vasodilation and increasing blood flow. [ 32 ] Sildenafil (Viagra) is a drug that uses the nitric oxide pathway. Sildenafil does not produce nitric oxide, but enhances the signals that are downstream of the nitric oxide pathway by protecting cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum , allowing for the signal to be enhanced, and thus vasodilation . [ 31 ] Another endogenous gaseous transmitter, hydrogen sulfide (H 2 S) works with NO to induce vasodilation and angiogenesis in a cooperative manner. [ 34 ] [ 35 ]
Nasal breathing produces nitric oxide within the body, while oral breathing does not. [ 36 ] [ 37 ]
In the U.S., the Occupational Safety and Health Administration (OSHA) has set the legal limit ( permissible exposure limit ) for nitric oxide exposure in the workplace as 25 ppm (30 mg/m 3 ) over an 8-hour workday. The National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit (REL) of 25 ppm (30 mg/m 3 ) over an 8-hour workday. At levels of 100 ppm, nitric oxide is immediately dangerous to life and health . [ 38 ]
Liquid nitrogen oxide is very sensitive to detonation even in the absence of fuel, and can be initiated as readily as nitroglycerin. Detonation of the endothermic liquid oxide close to its boiling point (−152 °C or −241.6 °F or 121.1 K) generated a 100 kbar pulse and fragmented the test equipment. It is the simplest molecule that is capable of detonation in all three phases. The liquid oxide is sensitive and may explode during distillation, and this has been the cause of industrial accidents. [ 39 ] Gaseous nitric oxide detonates at about 2,300 metres per second (8,300 km/h; 5,100 mph), but as a solid it can reach a detonation velocity of 6,100 metres per second (22,000 km/h; 13,600 mph). [ 40 ]
Notes
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https://en.wikipedia.org/wiki/•N=O
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Dinitrogen tetroxide Dinitrogen trioxide Nitrogen dioxide Nitrous oxide Nitroxyl (reduced form) Hydroxylamine (hydrogenated form)
Nitric oxide ( nitrogen oxide or nitrogen monoxide [ 1 ] ) is a colorless gas with the formula NO . It is one of the principal oxides of nitrogen . Nitric oxide is a free radical : it has an unpaired electron , which is sometimes denoted by a dot in its chemical formula ( • N=O or • NO). Nitric oxide is also a heteronuclear diatomic molecule , a class of molecules whose study spawned early modern theories of chemical bonding . [ 6 ]
An important intermediate in industrial chemistry , nitric oxide forms in combustion systems and can be generated by lightning in thunderstorms. In mammals, including humans, nitric oxide is a signaling molecule in many physiological and pathological processes. [ 7 ] It was proclaimed the " Molecule of the Year " in 1992. [ 8 ] The 1998 Nobel Prize in Physiology or Medicine was awarded for discovering nitric oxide's role as a cardiovascular signalling molecule. [ 9 ] Its impact extends beyond biology, with applications in medicine, such as the development of sildenafil (Viagra), and in industry, including semiconductor manufacturing. [ 10 ] [ 11 ]
Nitric oxide should not be confused with nitrogen dioxide (NO 2 ), a brown gas and major air pollutant , or with nitrous oxide (N 2 O), an anesthetic gas. [ 6 ]
Nitric oxide (NO) was first identified by Joseph Priestley in the late 18th century, originally seen as merely a toxic byproduct of combustion and an environmental pollutant. [ 12 ] Its biological significance was later uncovered in the 1980s when researchers Robert F. Furchgott , Louis J. Ignarro , and Ferid Murad discovered its critical role as a vasodilator in the cardiovascular system, a breakthrough that earned them the 1998 Nobel Prize in Physiology or Medicine. [ 13 ]
The ground state electronic configuration of NO is, in united atom notation: [ 14 ]
( 1 σ ) 2 ( 2 σ ) 2 ( 3 σ ) 2 ( 4 σ ∗ ) 2 ( 5 σ ) 2 ( 1 π ) 4 ( 2 π ∗ ) 1 {\displaystyle (1\sigma )^{2}(2\sigma )^{2}(3\sigma )^{2}(4\sigma ^{*})^{2}(5\sigma )^{2}(1\pi )^{4}(2\pi ^{*})^{1}}
The first two orbitals are actually pure atomic 1 s O and 1 s N from oxygen and nitrogen respectively and therefore are usually not noted in the united atom notation. Orbitals noted with an asterisk are antibonding. The ordering of 5σ and 1π according to their binding energies is subject to discussion. Removal of a 1π electron leads to 6 states whose energies span over a range starting at a lower level than a 5σ electron an extending to a higher level. This is due to the different orbital momentum couplings between a 1π and a 2π electron.
The lone electron in the 2π orbital makes NO a doublet (X ²Π) in its ground state whose degeneracy is split in the fine structure from spin-orbit coupling with a total momentum J = 3 ⁄ 2 or J = 1 ⁄ 2 .
The dipole of NO has been measured experimentally to 0.15740 D and is oriented from O to N (⁻NO⁺) due to the transfer of negative electronic charge from oxygen to nitrogen. [ 15 ]
Upon condensing to a neat liquid, nitric oxide dimerizes to colorless dinitrogen dioxide (O=N–N=O), but the association is weak and reversible. The N–N distance in crystalline NO is 218 pm, nearly twice the N–O distance. Condensation in a highly polar environment instead gives the red alternant isomer O=N–O + =N − . [ 6 ]
Since the heat of formation of • NO is endothermic , NO can be decomposed to the elements. Catalytic converters in cars exploit this reaction:
When exposed to oxygen , nitric oxide converts into nitrogen dioxide :
This reaction is thought to occur via the intermediates ONOO • and the red compound ONOONO. [ 16 ]
In water, nitric oxide reacts with oxygen to form nitrous acid (HNO 2 ). The reaction is thought to proceed via the following stoichiometry :
Nitric oxide reacts with fluorine , chlorine , and bromine to form the nitrosyl halides, such as nitrosyl chloride :
With NO 2 , also a radical, NO combines to form the intensely blue dinitrogen trioxide : [ 6 ]
Nitric oxide rarely sees organic chemistry use. Most reactions with it produce complex mixtures of salts, separable only through careful recrystallization . [ 17 ]
The addition of a nitric oxide moiety to another molecule is often referred to as nitrosylation . The Traube reaction is the addition of a two equivalents of nitric oxide onto an enolate , giving a diazeniumdiolate (also called a nitrosohydroxylamine ). [ 18 ] The product can undergo a subsequent retro- aldol reaction , giving an overall process similar to the haloform reaction . For example, nitric oxide reacts with acetone and an alkoxide to form a diazeniumdiolate on each α position , with subsequent loss of methyl acetate as a by-product : [ 19 ]
This reaction, which was discovered around 1898, remains of interest in nitric oxide prodrug research. Nitric oxide can also react directly with sodium methoxide , ultimately forming sodium formate and nitrous oxide by way of an N -methoxydiazeniumdiolate. [ 20 ]
Sufficiently basic secondary amines undergo a Traube-like reaction to give NONOates . [ 21 ] However, very few nucleophiles undergo the Traube reaction, either failing to adduce NO or immediately decomposing with nitrous oxide release. [ 17 ]
Nitric oxide reacts with transition metals to give complexes called metal nitrosyls . The most common bonding mode of nitric oxide is the terminal linear type (M−NO). [ 6 ] Alternatively, nitric oxide can serve as a one-electron pseudohalide. In such complexes, the M−N−O group is characterized by an angle between 120° and 140°. The NO group can also bridge between metal centers through the nitrogen atom in a variety of geometries.
In commercial settings, nitric oxide is produced by the oxidation of ammonia at 750–900 °C (normally at 850 °C) with platinum as catalyst in the Ostwald process :
The uncatalyzed endothermic reaction of oxygen (O 2 ) and nitrogen (N 2 ), which is effected at high temperature (>2000 °C) by lightning has not been developed into a practical commercial synthesis (see Birkeland–Eyde process ):
In the laboratory, nitric oxide is conveniently generated by reduction of dilute nitric acid with copper :
An alternative route involves the reduction of nitrous acid in the form of sodium nitrite or potassium nitrite :
The iron(II) sulfate route is simple and has been used in undergraduate laboratory experiments.
So-called NONOate compounds are also used for nitric oxide generation, especially in biological laboratories. However, other Traube adducts may decompose to instead give nitrous oxide . [ 22 ]
Nitric oxide concentration can be determined using a chemiluminescent reaction involving ozone . [ 23 ] A sample containing nitric oxide is mixed with a large quantity of ozone. The nitric oxide reacts with the ozone to produce oxygen and nitrogen dioxide , accompanied with emission of light ( chemiluminescence ):
which can be measured with a photodetector . The amount of light produced is proportional to the amount of nitric oxide in the sample.
Other methods of testing include electroanalysis (amperometric approach), where ·NO reacts with an electrode to induce a current or voltage change. The detection of NO radicals in biological tissues is particularly difficult due to the short lifetime and concentration of these radicals in tissues. One of the few practical methods is spin trapping of nitric oxide with iron- dithiocarbamate complexes and subsequent detection of the mono-nitrosyl-iron complex with electron paramagnetic resonance (EPR). [ 24 ] [ 25 ]
A group of fluorescent dye indicators that are also available in acetylated form for intracellular measurements exist. The most common compound is 4,5-diaminofluorescein (DAF-2). [ 26 ]
Nitric oxide reacts with the hydroperoxyl radical ( HO • 2 ) to form nitrogen dioxide (NO 2 ), which then can react with a hydroxyl radical (HO • ) to produce nitric acid (HNO 3 ):
Nitric acid, along with sulfuric acid , contributes to acid rain deposition.
• NO participates in ozone layer depletion . Nitric oxide reacts with stratospheric ozone to form O 2 and nitrogen dioxide:
This reaction is also utilized to measure concentrations of • NO in control volumes.
As seen in the acid deposition section, nitric oxide can transform into nitrogen dioxide (this can happen with the hydroperoxy radical, HO • 2 , or diatomic oxygen, O 2 ). Symptoms of short-term nitrogen dioxide exposure include nausea, dyspnea and headache. Long-term effects could include impaired immune and respiratory function. [ 27 ]
NO is a gaseous signaling molecule . [ 28 ] It is a key vertebrate biological messenger , playing a role in a variety of biological processes. [ 29 ] It is a bioproduct in almost all types of organisms, including bacteria, plants, fungi, and animal cells. [ 30 ]
Nitric oxide, an endothelium-derived relaxing factor (EDRF), is biosynthesized endogenously from L -arginine , oxygen , and NADPH by various nitric oxide synthase (NOS) enzymes . [ 31 ] Reduction of inorganic nitrate may also make nitric oxide. [ 32 ] One of the main enzymatic targets of nitric oxide is guanylyl cyclase . [ 33 ] The binding of nitric oxide to the heme region of the enzyme leads to activation, in the presence of iron. [ 33 ] Nitric oxide is highly reactive (having a lifetime of a few seconds), yet diffuses freely across membranes. These attributes make nitric oxide ideal for a transient paracrine (between adjacent cells) and autocrine (within a single cell) signaling molecule. [ 32 ] Once nitric oxide is converted to nitrates and nitrites by oxygen and water, cell signaling is deactivated. [ 33 ]
The endothelium (inner lining) of blood vessels uses nitric oxide to signal the surrounding smooth muscle to relax, resulting in vasodilation and increasing blood flow. [ 32 ] Sildenafil (Viagra) is a drug that uses the nitric oxide pathway. Sildenafil does not produce nitric oxide, but enhances the signals that are downstream of the nitric oxide pathway by protecting cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum , allowing for the signal to be enhanced, and thus vasodilation . [ 31 ] Another endogenous gaseous transmitter, hydrogen sulfide (H 2 S) works with NO to induce vasodilation and angiogenesis in a cooperative manner. [ 34 ] [ 35 ]
Nasal breathing produces nitric oxide within the body, while oral breathing does not. [ 36 ] [ 37 ]
In the U.S., the Occupational Safety and Health Administration (OSHA) has set the legal limit ( permissible exposure limit ) for nitric oxide exposure in the workplace as 25 ppm (30 mg/m 3 ) over an 8-hour workday. The National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit (REL) of 25 ppm (30 mg/m 3 ) over an 8-hour workday. At levels of 100 ppm, nitric oxide is immediately dangerous to life and health . [ 38 ]
Liquid nitrogen oxide is very sensitive to detonation even in the absence of fuel, and can be initiated as readily as nitroglycerin. Detonation of the endothermic liquid oxide close to its boiling point (−152 °C or −241.6 °F or 121.1 K) generated a 100 kbar pulse and fragmented the test equipment. It is the simplest molecule that is capable of detonation in all three phases. The liquid oxide is sensitive and may explode during distillation, and this has been the cause of industrial accidents. [ 39 ] Gaseous nitric oxide detonates at about 2,300 metres per second (8,300 km/h; 5,100 mph), but as a solid it can reach a detonation velocity of 6,100 metres per second (22,000 km/h; 13,600 mph). [ 40 ]
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The character ∂ ( Unicode : U+2202) is a stylized cursive d mainly used as a mathematical symbol , usually to denote a partial derivative such as ∂ z / ∂ x {\displaystyle {\partial z}/{\partial x}} (read as "the partial derivative of z with respect to x "). [ 1 ] [ 2 ] It is also used for boundary of a set, the boundary operator in a chain complex , and the conjugate of the Dolbeault operator on smooth differential forms over a complex manifold . It should be distinguished from other similar-looking symbols such as lowercase Greek letter delta (δ) or the lowercase Latin letter eth (ð).
The symbol was introduced originally in 1770 by Nicolas de Condorcet , who used it for a partial differential , and adopted for the partial derivative by Adrien-Marie Legendre in 1786. [ 3 ] It represents a specialized cursive type of the letter d , just as the integral sign originates as a specialized type of a long s (first used in print by Leibniz in 1686).
Use of the symbol was discontinued by Legendre, but it was taken up again by Carl Gustav Jacob Jacobi in 1841, [ 4 ] whose usage became widely adopted. [ 5 ]
The symbol is variously referred to as "partial", "curly d" [ 6 ] or "Jacobi's delta", [ 5 ] or as "del" [ 7 ] (but this name is also used for the "nabla" symbol ∇ ). It may also be pronounced simply "dee", [ 8 ] "partial dee", [ 9 ] [ 10 ] "doh", [ 11 ] [ 12 ] "dow" or "die". [ 13 ]
The Unicode character U+2202 ∂ PARTIAL DIFFERENTIAL is accessed by HTML entities ∂ or ∂ , and the equivalent LaTeX symbol ( Computer Modern glyph: ∂ {\displaystyle \partial } ) is accessed by \partial .
∂ is also used to denote the following:
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In organic chemistry , a nitrile is any organic compound that has a − C ≡ N functional group . The name of the compound is composed of a base, which includes the carbon of the −C≡N , suffixed with "nitrile", so for example CH 3 CH 2 C≡N is called " propionitrile " (or propanenitrile). [ 1 ] The prefix cyano - is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, including methyl cyanoacrylate , used in super glue , and nitrile rubber , a nitrile-containing polymer used in latex-free laboratory and medical gloves . Nitrile rubber is also widely used as automotive and other seals since it is resistant to fuels and oils. Organic compounds containing multiple nitrile groups are known as cyanocarbons .
Inorganic compounds containing the −C≡N group are not called nitriles, but cyanides instead. [ 2 ] Though both nitriles and cyanides can be derived from cyanide salts, most nitriles are not nearly as toxic.
The N−C−C geometry is linear in nitriles, reflecting the sp hybridization of the triply bonded carbon. The C−N distance is short at 1.16 Å , consistent with a triple bond . [ 3 ] Nitriles are polar, as indicated by high dipole moments. As liquids, they have high relative permittivities , often in the 30s.
The first compound of the homolog row of nitriles, the nitrile of formic acid , hydrogen cyanide was first synthesized by C. W. Scheele in 1782. [ 4 ] [ 5 ] In 1811 J. L. Gay-Lussac was able to prepare the very toxic and volatile pure acid. [ 6 ] Around 1832 benzonitrile , the nitrile of benzoic acid , was prepared by Friedrich Wöhler and Justus von Liebig , but due to minimal yield of the synthesis neither physical nor chemical properties were determined nor a structure suggested. In 1834 Théophile-Jules Pelouze synthesized propionitrile , suggesting it to be an ether of propionic alcohol and hydrocyanic acid. [ 7 ] The synthesis of benzonitrile by Hermann Fehling in 1844 by heating ammonium benzoate was the first method yielding enough of the substance for chemical research.
Fehling determined the structure by comparing his results to the already known synthesis of hydrogen cyanide by heating ammonium formate . He coined the name "nitrile" for the newfound substance, which became the name for this group of compounds. [ 8 ]
Industrially, the main methods for producing nitriles are ammoxidation and hydrocyanation . Both routes are green in the sense that they do not generate stoichiometric amounts of salts.
In ammoxidation , a hydrocarbon is partially oxidized in the presence of ammonia . This conversion is practiced on a large scale for acrylonitrile : [ 9 ]
In the production of acrylonitrile, a side product is acetonitrile . On an industrial scale, several derivatives of benzonitrile , phthalonitrile , as well as Isobutyronitrile are prepared by ammoxidation. The process is catalysed by metal oxides and is assumed to proceed via the imine.
Hydrocyanation is an industrial method for producing nitriles from hydrogen cyanide and alkenes. The process requires homogeneous catalysts . An example of hydrocyanation is the production of adiponitrile , a precursor to nylon-6,6 from 1,3-butadiene :
Two salt metathesis reactions are popular for laboratory scale reactions. In the Kolbe nitrile synthesis , alkyl halides undergo nucleophilic aliphatic substitution with alkali metal cyanides . Aryl nitriles are prepared in the Rosenmund-von Braun synthesis .
In general, metal cyanides combine with alkyl halides to give a mixture of the nitrile and the isonitrile , although appropriate choice of counterion and temperature can minimize the latter. An alkyl sulfate obviates the problem entirely, particularly in nonaqueous conditions (the Pelouze synthesis). [ 5 ]
The cyanohydrins are a special class of nitriles. Classically they result from the addition of alkali metal cyanides to aldehydes in the cyanohydrin reaction . Because of the polarity of the organic carbonyl, this reaction requires no catalyst, unlike the hydrocyanation of alkenes. O-Silyl cyanohydrins are generated by the addition trimethylsilyl cyanide in the presence of a catalyst (silylcyanation). Cyanohydrins are also prepared by transcyanohydrin reactions starting, for example, with acetone cyanohydrin as a source of HCN. [ 10 ]
Nitriles can be prepared by the dehydration of primary amides . Common reagents for this include phosphorus pentoxide ( P 2 O 5 ) [ 11 ] and thionyl chloride ( SOCl 2 ). [ 12 ] In a related dehydration, secondary amides give nitriles by the von Braun amide degradation . In this case, one C-N bond is cleaved.
Numerous traditional methods exist for nitrile preparation by amine oxidation. [ 13 ] Common methods include the use of potassium persulfate , [ 14 ] Trichloroisocyanuric acid , [ 15 ] or anodic electrosynthesis . [ 16 ] In addition, several selective methods have been developed in the last decades for electrochemical processes. [ 17 ]
The conversion of aldehydes to nitriles via aldoximes is a popular laboratory route. Aldehydes react readily with hydroxylamine salts, sometimes at temperatures as low as ambient, to give aldoximes. These can be dehydrated to nitriles by simple heating, [ 18 ] although a wide range of reagents may assist with this, including triethylamine / sulfur dioxide , zeolites , or sulfuryl chloride . The related hydroxylamine-O-sulfonic acid reacts similarly. [ 19 ]
In specialised cases the Van Leusen reaction can be used. Biocatalysts such as aliphatic aldoxime dehydratase are also effective.
Aromatic nitriles are often prepared in the laboratory from the aniline via diazonium compounds . This is the Sandmeyer reaction . It requires transition metal cyanides. [ 20 ]
Nitrile groups in organic compounds can undergo a variety of reactions depending on the reactants or conditions. A nitrile group can be hydrolyzed, reduced, or ejected from a molecule as a cyanide ion.
The hydrolysis of nitriles RCN proceeds in the distinct steps under acid or base treatment to first give carboxamides RC(O)NH 2 and then carboxylic acids RC(O)OH . The hydrolysis of nitriles to carboxylic acids is efficient. In acid or base, the balanced equations are as follows:
Strictly speaking, these reactions are mediated (as opposed to catalyzed ) by acid or base, since one equivalent of the acid or base is consumed to form the ammonium or carboxylate salt, respectively.
Kinetic studies show that the second-order rate constant for hydroxide-ion catalyzed hydrolysis of acetonitrile to acetamide is 1.6 × 10 −6 M −1 s −1 , which is slower than the hydrolysis of the amide to the carboxylate (7.4 × 10 −5 M −1 s −1 ). Thus, the base hydrolysis route will afford the carboxylate (or the amide contaminated with the carboxylate). On the other hand, the acid catalyzed reactions requires a careful control of the temperature and of the ratio of reagents in order to avoid the formation of polymers, which is promoted by the exothermic character of the hydrolysis. [ 28 ] The classical procedure to convert a nitrile to the corresponding primary amide calls for adding the nitrile to cold concentrated sulfuric acid . [ 29 ] The further conversion to the carboxylic acid is disfavored by the low temperature and low concentration of water.
Two families of enzymes catalyze the hydrolysis of nitriles. Nitrilases hydrolyze nitriles to carboxylic acids:
Nitrile hydratases are metalloenzymes that hydrolyze nitriles to amides.
These enzymes are used commercially to produce acrylamide .
The "anhydrous hydration" of nitriles to amides has been demonstrated using an oxime as water source: [ 30 ]
Nitriles are susceptible to hydrogenation over diverse metal catalysts. The reaction can afford either the primary amine ( RCH 2 NH 2 ) or the tertiary amine ( (RCH 2 ) 3 N ), depending on conditions. [ 31 ] In conventional organic reductions , nitrile is reduced by treatment with lithium aluminium hydride to the amine. Reduction to the imine followed by hydrolysis to the aldehyde takes place in the Stephen aldehyde synthesis , which uses stannous chloride in acid.
Alkyl nitriles are sufficiently acidic to undergo deprotonation of the C-H bond adjacent to the C≡N group. [ 32 ] [ 33 ] Strong bases are required, such as lithium diisopropylamide and butyl lithium . The product is referred to as a nitrile anion . These carbanions alkylate a wide variety of electrophiles. Key to the exceptional nucleophilicity is the small steric demand of the C≡N unit combined with its inductive stabilization. These features make nitriles ideal for creating new carbon-carbon bonds in sterically demanding environments.
The carbon center of a nitrile is electrophilic , hence it is susceptible to nucleophilic addition reactions:
Nitriles are precursors to transition metal nitrile complexes , which are reagents and catalysts. Examples include tetrakis(acetonitrile)copper(I) hexafluorophosphate ( [Cu(MeCN) 4 ] + ) and bis(benzonitrile)palladium dichloride ( PdCl 2 (PhCN) 2 ). [ 40 ]
Cyanamides are N -cyano compounds with general structure R 1 R 2 N−C≡N and related to the parent cyanamide . [ 41 ]
Nitrile oxides have the chemical formula RCNO . Their general structure is R−C≡N + −O − . The R stands for any group (typically organyl , e.g., acetonitrile oxide CH 3 −C≡N + −O − , hydrogen in the case of fulminic acid H−C≡N + −O − , or halogen (e.g., chlorine fulminate Cl−C≡N + −O − ). [ 42 ] : 1187–1192
Nitrile oxides are quite different from nitriles: they are highly reactive 1,3-dipoles , and cannot be synthesized from the direct oxidation of nitriles. [ 43 ] Instead, they can be synthesised by nitroalkane dehydration, oxime dehydrogenation, [ 44 ] : 934–936 or halooxime elimination in base. [ 45 ] They are used in 1,3-dipolar cycloadditions , [ 42 ] : 1187–1192 such as to isoxazoles . [ 44 ] : 1201–1202 They undergo type 1 dyotropic rearrangement to isocyanates . [ 42 ] : 1700
The heavier nitrile sulfides are extremely reactive and rare, but temporarily form during the thermolysis of oxathiazolones . They react similarly to nitrile oxides. [ 46 ]
Nitriles occur naturally in a diverse set of plant and animal sources. Over 120 naturally occurring nitriles have been isolated from terrestrial and marine sources. Nitriles are commonly encountered in fruit pits, especially almonds, and during cooking of Brassica crops (such as cabbage, Brussels sprouts, and cauliflower), which release nitriles through hydrolysis. Mandelonitrile , a cyanohydrin produced by ingesting almonds or some fruit pits, releases hydrogen cyanide and is responsible for the toxicity of cyanogenic glycosides. [ 47 ]
Over 30 nitrile-containing pharmaceuticals are currently marketed for a diverse variety of medicinal indications with more than 20 additional nitrile-containing leads in clinical development. The types of pharmaceuticals containing nitriles are diverse, from vildagliptin , an antidiabetic drug, to anastrozole , which is the gold standard in treating breast cancer. In many instances the nitrile mimics functionality present in substrates for enzymes, whereas in other cases the nitrile increases water solubility or decreases susceptibility to oxidative metabolism in the liver. [ 48 ] The nitrile functional group is found in several drugs.
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In category theory , a branch of mathematics , an ∞-groupoid is an abstract homotopical model for topological spaces . One model uses Kan complexes which are fibrant objects in the category of simplicial sets (with the standard model structure ). [ 1 ] It is an ∞-category generalization of a groupoid , a category in which every morphism is an isomorphism .
The homotopy hypothesis states that ∞-groupoids are equivalent to spaces up to homotopy. [ 2 ] : 2–3 [ 3 ]
Alexander Grothendieck suggested in Pursuing Stacks [ 2 ] : 3–4, 201 that there should be an extraordinarily simple model of ∞-groupoids using globular sets , originally called hemispherical complexes. These sets are constructed as presheaves on the globular category G {\displaystyle \mathbb {G} } . This is defined as the category whose objects are finite ordinals [ n ] {\displaystyle [n]} and morphisms are given by σ n : [ n ] → [ n + 1 ] τ n : [ n ] → [ n + 1 ] {\displaystyle {\begin{aligned}\sigma _{n}:[n]\to [n+1]\\\tau _{n}:[n]\to [n+1]\end{aligned}}} such that the globular relations hold σ n + 1 ∘ σ n = τ n + 1 ∘ σ n σ n + 1 ∘ τ n = τ n + 1 ∘ τ n {\displaystyle {\begin{aligned}\sigma _{n+1}\circ \sigma _{n}&=\tau _{n+1}\circ \sigma _{n}\\\sigma _{n+1}\circ \tau _{n}&=\tau _{n+1}\circ \tau _{n}\end{aligned}}} These encode the fact that n -morphisms should not be able to see ( n + 1)-morphisms. When writing these down as a globular set X ∙ : G o p → Sets {\displaystyle X_{\bullet }:\mathbb {G} ^{op}\to {\text{Sets}}} , the source and target maps are then written as s n = X ∙ ( σ n ) t n = X ∙ ( τ n ) {\displaystyle {\begin{aligned}s_{n}=X_{\bullet }(\sigma _{n})\\t_{n}=X_{\bullet }(\tau _{n})\end{aligned}}} We can also consider globular objects in a category C {\displaystyle {\mathcal {C}}} as functors X ∙ : G o p → C . {\displaystyle X_{\bullet }\colon \mathbb {G} ^{op}\to {\mathcal {C}}.} There was hope originally that such a strict model would be sufficient for homotopy theory, but there is evidence suggesting otherwise. It turns out for S 2 {\displaystyle S^{2}} its associated homotopy n {\displaystyle n} -type π ≤ n ( S 2 ) {\displaystyle \pi _{\leq n}(S^{2})} can never be modeled as a strict globular groupoid for n ≥ 3 {\displaystyle n\geq 3} . [ 2 ] : 445 [ 4 ] This is because strict ∞-groupoids only model spaces with a trivial Whitehead product . [ 5 ]
Given a topological space X {\displaystyle X} there should be an associated fundamental ∞-groupoid Π ∞ X {\displaystyle \Pi _{\infty }X} where the objects are points x ∈ X {\displaystyle x\in X} , 1-morphisms f : x → y {\displaystyle f:x\to y} are represented as paths , 2-morphisms are homotopies of paths, 3-morphisms are homotopies of homotopies, and so on. From this ∞-groupoid we can find an n {\displaystyle n} -groupoid called the fundamental n {\displaystyle n} -groupoid Π n X {\displaystyle \Pi _{n}X} whose homotopy type is that of π ≤ n X {\displaystyle \pi _{\leq n}X} .
Note that taking the fundamental ∞-groupoid of a space Y {\displaystyle Y} such that π > n Y = 0 {\displaystyle \pi _{>n}Y=0} is equivalent to the fundamental n -groupoid Π n Y {\displaystyle \Pi _{n}Y} . Such a space can be found using the Whitehead tower .
One useful case of globular groupoids comes from a chain complex which is bounded above, hence let's consider a chain complex C ∙ ∈ Ch ≤ 0 ( Ab ) {\displaystyle C_{\bullet }\in {\text{Ch}}_{\leq 0}({\text{Ab}})} . [ 6 ] There is an associated globular groupoid. Intuitively, the objects are the elements in C 0 {\displaystyle C_{0}} , morphisms come from C 0 {\displaystyle C_{0}} through the chain complex map d 1 : C 1 → C 0 {\displaystyle d_{1}:C_{1}\to C_{0}} , and higher n {\displaystyle n} -morphisms can be found from the higher chain complex maps d n : C n → C n − 1 {\displaystyle d_{n}:C_{n}\to C_{n-1}} . We can form a globular set C ∙ {\displaystyle \mathbb {C} _{\bullet }} with C 0 = C 0 C 1 = C 0 ⊕ C 1 ⋯ C n = ⨁ k = 0 n C k {\displaystyle {\begin{matrix}\mathbb {C} _{0}=&C_{0}\\\mathbb {C} _{1}=&C_{0}\oplus C_{1}\\&\cdots \\\mathbb {C} _{n}=&\bigoplus _{k=0}^{n}C_{k}\end{matrix}}} and the source morphism s n : C n → C n − 1 {\displaystyle s_{n}:\mathbb {C} _{n}\to \mathbb {C} _{n-1}} is the projection map p r : ⨁ k = 0 n C k → ⨁ k = 0 n − 1 C k {\displaystyle pr:\bigoplus _{k=0}^{n}C_{k}\to \bigoplus _{k=0}^{n-1}C_{k}} and the target morphism t n : C n → C n − 1 {\displaystyle t_{n}:C_{n}\to C_{n-1}} is the addition of the chain complex map d n : C n → C n − 1 {\displaystyle d_{n}:C_{n}\to C_{n-1}} together with the projection map. This forms a globular groupoid giving a wide class of examples of strict globular groupoids. Moreover, because strict groupoids embed inside weak groupoids, they can act as weak groupoids as well.
One of the basic theorems about local systems is that they can be equivalently described as a functor from the fundamental groupoid Π X = Π ≤ 1 X {\displaystyle \Pi X=\Pi _{\leq 1}X} to the category of abelian groups , the category of R {\displaystyle R} -modules , or some other abelian category . That is, a local system is equivalent to giving a functor L : Π X → Ab {\displaystyle {\mathcal {L}}:\Pi X\to {\text{Ab}}} generalizing such a definition requires us to consider not only an abelian category, but also its derived category . A higher local system is then an ∞-functor L ∙ : Π ∞ X → D ( Ab ) {\displaystyle {\mathcal {L}}_{\bullet }:\Pi _{\infty }X\to D({\text{Ab}})} with values in some derived category. This has the advantage of letting the higher homotopy groups π n X {\displaystyle \pi _{n}X} to act on the higher local system, from a series of truncations. A toy example to study comes from the Eilenberg–MacLane spaces K ( A , n ) {\displaystyle K(A,n)} , or by looking at the terms from the Whitehead tower of a space. Ideally, there should be some way to recover the categories of functors L ∙ : Π ∞ X → D ( Ab ) {\displaystyle {\mathcal {L}}_{\bullet }:\Pi _{\infty }X\to D({\text{Ab}})} from their truncations Π n X {\displaystyle \Pi _{n}X} and the maps τ ≤ n − 1 : Π n X → Π n − 1 X {\displaystyle \tau _{\leq n-1}:\Pi _{n}X\to \Pi _{n-1}X} whose fibers should be the categories of n {\displaystyle n} -functors Π n ( K ( π n X , n ) ) → D ( Ab ) {\displaystyle \Pi _{n}(K(\pi _{n}X,n))\to D({\text{Ab}})} Another advantage of this formalism is it allows for constructing higher forms of ℓ {\displaystyle \ell } -adic representations by using the etale homotopy type π ^ ( X ) {\displaystyle {\hat {\pi }}(X)} of a scheme X {\displaystyle X} and construct higher representations of this space, since they are given by functors L : π ( X ) ^ → D ( Q ¯ ℓ ) {\displaystyle {\mathcal {L}}:{\hat {\pi (X)}}\to D({\overline {\mathbb {Q} }}_{\ell })}
Another application of ∞-groupoids is giving constructions of n -gerbes and ∞-gerbes. Over a space X {\displaystyle X} an n -gerbe should be an object G → X {\displaystyle {\mathcal {G}}\to X} such that when restricted to a small enough subset U ⊂ X {\displaystyle U\subset X} , G | U → U {\displaystyle {\mathcal {G}}|_{U}\to U} is represented by an n -groupoid, and on overlaps there is an agreement up to some weak equivalence. Assuming the homotopy hypothesis is correct, this is equivalent to constructing an object G → X {\displaystyle {\mathcal {G}}\to X} such that over any open subset G | U → U {\displaystyle {\mathcal {G}}|_{U}\to U} is an n -group , or a homotopy n -type . Because the nerve of a category can be used to construct an arbitrary homotopy type, a functor over a site X {\displaystyle {\mathcal {X}}} , e.g. p : C → X {\displaystyle p:{\mathcal {C}}\to {\mathcal {X}}} will give an example of a higher gerbe if the category C U {\displaystyle {\mathcal {C}}_{U}} lying over any point U ∈ Ob X {\displaystyle U\in \operatorname {Ob} {\mathcal {X}}} is a non-empty category. In addition, it would be expected this category would satisfy some sort of descent condition.
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In mathematics , an ∞-topos (infinity- topos ) is, roughly, an ∞-category such that its objects behave like sheaves of spaces with some choice of Grothendieck topology ; in other words, it gives an intrinsic notion of sheaves without reference to an external space. The prototypical example of an ∞-topos is the ∞-category of sheaves of spaces on some topological space . But the notion is more flexible; for example, the ∞-category of étale sheaves on some scheme is not the ∞-category of sheaves on any topological space but it is still an ∞-topos.
Precisely, in Lurie's Higher Topos Theory , an ∞-topos is defined [ 1 ] as an ∞-category X such that there is a small ∞-category C and an ( accessible ) left exact localization functor from the ∞-category of presheaves of spaces on C to X . A theorem of Lurie [ 2 ] states that an ∞-category is an ∞-topos if and only if it satisfies an ∞-categorical version of Giraud's axioms in ordinary topos theory. A " topos " is a category behaving like the category of sheaves of sets on a topological space. In analogy, Lurie's definition and characterization theorem of an ∞-topos says that an ∞-topos is an ∞-category behaving like the category of sheaves of spaces.
It says:
Theorem — Let X {\displaystyle X} be an ∞-category. Then the following are equivalent.
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The #P-completeness of 01-permanent , sometimes known as Valiant's theorem , [ 1 ] is a mathematical proof about the permanent of matrices , considered a seminal result in computational complexity theory . [ 2 ] [ 3 ] In a 1979 scholarly paper , Leslie Valiant proved that the computational problem of computing the permanent of a matrix is #P-hard , even if the matrix is restricted to have entries that are all 0 or 1. [ 4 ] In this restricted case, computing the permanent is even #P-complete , because it corresponds to the #P problem of counting the number of permutation matrices one can get by changing ones into zeroes.
Valiant's 1979 paper also introduced #P as a complexity class . [ 5 ]
Valiant's definition of completeness, and his proof of completeness of 01-permanent, both used polynomial-time Turing reductions . In this kind of reduction, a single hard instance of some other problem in #P is reduced to computing the permanent of a sequence of multiple graphs, each of which could potentially depend on the results of previous permanent computations. A later simplification by Ben-Dor & Halevi (1993) showed that it is possible to use a weaker notion of reduction, a polynomial-time counting reduction , that translates the other problem into a single instance of the permanent problem.
One reason for interest in the computational complexity of the permanent is that it provides an example of a problem where constructing a single solution can be done efficiently but where counting all solutions is hard. [ 6 ] As Papadimitriou writes in his book Computational Complexity :
The most impressive and interesting #P-complete problems are those for which the corresponding search problem can be solved in polynomial time. The PERMANENT problem for 0–1 matrices, which is equivalent to the problem of counting perfect matchings in a bipartite graph [...] is the classic example here. [ 1 ]
Specifically, computing the permanent (shown to be difficult by Valiant's results) is closely connected with finding a perfect matching in a bipartite graph, which is solvable in polynomial time by the Hopcroft–Karp algorithm . [ 7 ] [ 8 ] For a bipartite graph with 2 n vertices partitioned into two parts with n vertices each, the number of perfect matchings equals the permanent of its biadjacency matrix and the square of the number of perfect matchings is equal to the permanent of its adjacency matrix . [ 9 ] Since any 0–1 matrix is the biadjacency matrix of some bipartite graph, Valiant's theorem implies [ 9 ] that the problem of counting the number of perfect matchings in a bipartite graph is #P-complete , and in conjunction with Toda's theorem this implies that it is hard for the entire polynomial hierarchy . [ 10 ] [ 11 ]
The computational complexity of the permanent also has some significance in other aspects of complexity theory: it is not known whether NC equals P (informally, whether every polynomially-solvable problem can be solved by a polylogarithmic-time parallel algorithm ) and Ketan Mulmuley has suggested an approach to resolving this question that relies on writing the permanent as the determinant of a matrix. [ 12 ]
Hartmann [ 13 ] proved a generalization of Valiant's theorem concerning the complexity of computing immanants of matrices that generalize both the determinant and the permanent.
Below, the proof that computing the permanent of a 01-matrix is #P-complete is described. It mainly follows the proof by Ben-Dor & Halevi (1993) . [ 14 ]
Any square matrix A = ( a i j ) {\displaystyle A=(a_{ij})} can be viewed as the adjacency matrix of a directed graph , with a i j {\displaystyle a_{ij}} representing the weight of the edge from vertex i {\displaystyle i} to vertex j {\displaystyle j} . Then, the permanent of A {\displaystyle A} is equal to the sum of the weights of all cycle-covers of the graph; this is a graph-theoretic interpretation of the permanent .
#SAT , a function problem related to the Boolean satisfiability problem , is the problem of counting the number of satisfying assignments of a given Boolean formula. It is a #P-complete problem (by definition), as any NP machine can be encoded into a Boolean formula by a process similar to that in Cook's theorem , such that the number of satisfying assignments of the Boolean formula is equal to the number of accepting paths of the NP machine. Any formula in SAT can be rewritten as a formula in 3- CNF form preserving the number of satisfying assignments, and so #SAT and #3SAT are equivalent and #3SAT is #P-complete as well.
In order to prove that 01-Permanent is #P-hard , it is therefore sufficient to show that the number of satisfying assignments for a 3-CNF formula can be expressed succinctly as a function of the permanent of a matrix that contains only the values 0 and 1. This is usually accomplished in two steps:
Given a 3CNF-formula ϕ {\displaystyle \phi } with m {\displaystyle m} clauses and n {\displaystyle n} variables, one can construct a weighted, directed graph G ϕ {\displaystyle G_{\phi }} such that
Thus if ( # ϕ ) {\displaystyle (\#\phi )} is the number of satisfying assignments for ϕ {\displaystyle \phi } , the permanent of this graph will be 12 m ⋅ ( # ϕ ) {\displaystyle 12^{m}\cdot (\#\phi )} .
(Valiant's original proof constructs a graph with entries in { − 1 , 0 , 1 , 2 , 3 } {\displaystyle \{-1,0,1,2,3\}} whose permanent is 4 t ( ϕ ) ⋅ ( # ϕ ) {\displaystyle 4^{t(\phi )}\cdot (\#\phi )} where t ( ϕ ) {\displaystyle t(\phi )} is "twice the number of occurrences of literals in ϕ {\displaystyle \phi } " – m {\displaystyle m} .)
The graph construction makes use of a component that is treated as a "black box." To keep the explanation simple, the properties of this component are given without actually defining the structure of the component.
To specify G ϕ {\displaystyle G_{\phi }} , one first constructs a variable node in G ϕ {\displaystyle G_{\phi }} for each of the n {\displaystyle n} variables in ϕ {\displaystyle \phi } . Additionally, for each of the m {\displaystyle m} clauses in ϕ {\displaystyle \phi } , one constructs a clause component C j {\displaystyle C_{j}} in G ϕ {\displaystyle G_{\phi }} that functions as a sort of "black box." All that needs to be noted about C j {\displaystyle C_{j}} is that it has three input edges and three output edges. The input edges come either from variable nodes or from previous clause components (e.g., C i {\displaystyle C_{i}} for some i < j {\displaystyle i<j} ) and the output edges go either to variable nodes or to later clause components (e.g., C i {\displaystyle C_{i}} for some o > j {\displaystyle o>j} ). The first input and output edges correspond with the first variable of the clause j {\displaystyle j} , and so on. Thus far, all of the nodes that will appear in the graph G ϕ {\displaystyle G_{\phi }} have been specified.
Next, one would consider the edges. For each variable x i {\displaystyle x_{i}} of ϕ {\displaystyle \phi } , one makes a true cycle (T-cycle) and a false cycle (F-cycle) in G ϕ {\displaystyle G_{\phi }} . To create the T-cycle, one starts at the variable node for x i {\displaystyle x_{i}} and draw an edge to the clause component C j {\displaystyle C_{j}} that corresponds to the first clause in which x i {\displaystyle x_{i}} appears. If x i {\displaystyle x_{i}} is the first variable in the clause of ϕ {\displaystyle \phi } corresponding to C j {\displaystyle C_{j}} , this edge will be the first input edge of C j {\displaystyle C_{j}} , and so on. Thence, draw an edge to the next clause component corresponding to the next clause of ϕ {\displaystyle \phi } in which x i {\displaystyle x_{i}} appears, connecting it from the appropriate output edge of C j {\displaystyle C_{j}} to the appropriate input edge of the next clause component, and so on. After the last clause in which x i {\displaystyle x_{i}} appears, we connect the appropriate output edge of the corresponding clause component back to x i {\displaystyle x_{i}} 's variable node. Of course, this completes the cycle. To create the F-cycle, one would follow the same procedure, but connect x i {\displaystyle x_{i}} 's variable node to those clause components in which ~ x i {\displaystyle x_{i}} appears, and finally back to x i {\displaystyle x_{i}} 's variable node. All of these edges outside the clause components are termed external edges , all of which have weight 1. Inside the clause components, the edges are termed internal edges . Every external edge is part of a T-cycle or an F-cycle (but not both—that would force inconsistency).
Note that the graph G ϕ {\displaystyle G_{\phi }} is of size linear in | ϕ | {\displaystyle |\phi |} , so the construction can be done in polytime (assuming that the clause components do not cause trouble).
A useful property of G ϕ {\displaystyle G_{\phi }} is that its cycle covers correspond to variable assignments for ϕ {\displaystyle \phi } . For a cycle cover Z {\displaystyle Z} of G ϕ {\displaystyle G_{\phi }} , one can say that Z {\displaystyle Z} induces an assignment of values for the variables in ϕ {\displaystyle \phi } just in case Z {\displaystyle Z} contains all of the external edges in x i {\displaystyle x_{i}} 's T-cycle and none of the external edges in x i {\displaystyle x_{i}} 's F-cycle for all variables x i {\displaystyle x_{i}} that the assignment makes true, and vice versa for all variables x i {\displaystyle x_{i}} that the assignment makes false. Although any given cycle cover Z {\displaystyle Z} need not induce an assignment for ϕ {\displaystyle \phi } , any one that does induces exactly one assignment, and the same assignment induced depends only on the external edges of Z {\displaystyle Z} . The term Z {\displaystyle Z} is considered an incomplete cycle cover at this stage, because one talks only about its external edges, M {\displaystyle M} . In the section below, one considers M {\displaystyle M} -completions to show that one has a set of cycle covers corresponding to each M {\displaystyle M} that have the necessary properties.
The sort of covers Z {\displaystyle Z} that do not induce assignments are the ones with cycles that "jump" inside the clause components. That is, if for every C j {\displaystyle C_{j}} , at least one of C j {\displaystyle C_{j}} 's input edges is in Z {\displaystyle Z} , and every output edge of the clause components is in Z {\displaystyle Z} when the corresponding input edge is in Z {\displaystyle Z} , then Z {\displaystyle Z} is proper with respect to each clause component, and Z {\displaystyle Z} will produce a satisfying assignment for ϕ {\displaystyle \phi } . This is because proper covers Z {\displaystyle Z} contain either the complete T-cycle or the complete F-cycle of every variable x i {\displaystyle x_{i}} in ϕ {\displaystyle \phi } as well as each including edges going into and coming out of each clause component. Thus, these covers assign either true or false (but never both) to each x i {\displaystyle x_{i}} and ensure that each clause is satisfied. Further, the sets of cycle covers corresponding to all such Z {\displaystyle Z} have weight 12 m {\displaystyle 12^{m}} , and any other Z {\displaystyle Z} has weight 0 {\displaystyle 0} . The reasons for this depend on the construction of the clause components, and are outlined below.
To understand the relevant properties of the clause components C j {\displaystyle C_{j}} , one needs the notion of an M-completion. A cycle cover Z {\displaystyle Z} induces a satisfying assignment just in case its external edges satisfy certain properties. For any cycle cover of G ϕ {\displaystyle G_{\phi }} , consider only its external edges, the subset M {\displaystyle M} . Let M {\displaystyle M} be a set of external edges. A set of internal edges L {\displaystyle L} is an M {\displaystyle M} -completion just in case M ∪ L {\displaystyle M\cup L} is a cycle cover of G ϕ {\displaystyle G_{\phi }} . Further, denote the set of all M {\displaystyle M} -completions by L M {\displaystyle L^{M}} and the set of all resulting cycle covers of G ϕ {\displaystyle G_{\phi }} by Z M {\displaystyle Z^{M}} .
Recall that construction of G ϕ {\displaystyle G_{\phi }} was such that each external edge had weight 1, so the weight of Z M {\displaystyle Z^{M}} , the cycle covers resulting from any M {\displaystyle M} , depends only on the internal edges involved. We add here the premise that the construction of the clause components is such that the sum over possible M {\displaystyle M} -completions of the weight of the internal edges in each clause component, where M {\displaystyle M} is proper relative to the clause component, is 12. Otherwise the weight of the internal edges is 0. Since there are m {\displaystyle m} clause components, and the selection of sets of internal edges, L {\displaystyle L} , within each clause component is independent of the selection of sets of internal edges in other clause components, so one can multiply everything to get the weight of Z M {\displaystyle Z^{M}} . So, the weight of each Z M {\displaystyle Z^{M}} , where M {\displaystyle M} induces a satisfying assignment, is 12 m {\displaystyle 12^{m}} . Further, where M {\displaystyle M} does not induce a satisfying assignment, M {\displaystyle M} is not proper with respect to some C j {\displaystyle C_{j}} , so the product of the weights of internal edges in Z M {\displaystyle Z^{M}} will be 0 {\displaystyle 0} .
The clause component is a weighted, directed graph with 7 nodes with edges weighted and nodes arranged to yield the properties specified above, and is given in Appendix A of Ben-Dor and Halevi (1993). Note that the internal edges here have weights drawn from the set { − 1 , 0 , 1 , 2 , 3 } {\displaystyle \{-1,0,1,2,3\}} ; not all edges have 0–1 weights.
Finally, since the sum of weights of all the sets of cycle covers inducing any particular satisfying assignment is 12 m {\displaystyle 12^{m}} , and the sum of weights of all other sets of cycle covers is 0, one has Perm ( G ϕ ) = 12 m ⋅ ( # ϕ ) {\displaystyle \operatorname {Perm} (G_{\phi })=12^{m}\cdot (\#\phi )} . The following section reduces computing Perm ( G ϕ ) {\displaystyle \operatorname {Perm} (G_{\phi })} to the permanent of a 01 matrix.
The above section has shown that Permanent is #P-hard. Through a series of reductions, any permanent can be reduced to the permanent of a matrix with entries only 0 or 1. This will prove that 01-Permanent is #P-hard as well.
Using modular arithmetic , convert an integer matrix A {\displaystyle A} into an equivalent non-negative matrix A ′ {\displaystyle A'} so that the permanent of A {\displaystyle A} can be computed easily from the permanent of A ′ {\displaystyle A'} , as follows:
Let A {\displaystyle A} be an n × n {\displaystyle n\times n} integer matrix where no entry has a magnitude larger than μ {\displaystyle \mu } .
The transformation of A {\displaystyle A} into A ′ {\displaystyle A'} is polynomial in n {\displaystyle n} and log ( μ ) {\displaystyle \log(\mu )} , since the number of bits required to represent Q {\displaystyle Q} is polynomial in n {\displaystyle n} and log ( μ ) {\displaystyle \log(\mu )}
An example of the transformation and why it works is given below.
Here, n = 2 {\displaystyle n=2} , μ = 2 {\displaystyle \mu =2} , and μ n = 4 {\displaystyle \mu ^{n}=4} , so Q = 17 {\displaystyle Q=17} . Thus
Note how the elements are non-negative because of the modular arithmetic. It is simple to compute the permanent
so P = 227 mod 1 7 = 6 {\displaystyle P=227{\bmod {1}}7=6} . Then P < Q / 2 {\displaystyle P<Q/2} , so Perm ( A ) = P = 6. {\displaystyle \operatorname {Perm} (A)=P=6.}
Note that any number can be decomposed into a sum of powers of 2 . For example,
This fact is used to convert a non-negative matrix into an equivalent matrix whose entries are all powers of 2. The reduction can be expressed in terms of graphs equivalent to the matrices.
Let G {\displaystyle G} be a n {\displaystyle n} -node weighted directed graph with non-negative weights, where largest weight is W {\displaystyle W} . Every edge e {\displaystyle e} with weight w {\displaystyle w} is converted into an equivalent edge with weights in powers of 2 as follows:
This can be seen graphically in the Figure 1. The subgraph that replaces the existing edge contains r {\displaystyle r} nodes and 3 r {\displaystyle 3r} edges.
To prove that this produces an equivalent graph G ′ {\displaystyle G'} that has the same permanent as the original, one must show the correspondence between the cycle covers of G {\displaystyle G} and G ′ {\displaystyle G'} .
Consider some cycle-cover R {\displaystyle R} in G {\displaystyle G} .
Note that the size of G ′ {\displaystyle G'} is polynomial in n {\displaystyle n} and log W {\displaystyle \log W} .
The objective here is to reduce a matrix whose entries are powers of 2 into an equivalent matrix containing only zeros and ones (i.e. a directed graph where each edge has a weight of 1).
Let G {\displaystyle G} be a n {\displaystyle n} -node directed graph where all the weights on edges are powers of two. Construct a graph, G ′ {\displaystyle G'} , where the weight of each edge is 1 and Perm ( G ) = Perm ( G ′ ) {\displaystyle \operatorname {Perm} (G)=\operatorname {Perm} (G')} . The size of this new graph, ( G ′ ) {\displaystyle (G')} , is polynomial in n {\displaystyle n} and p {\displaystyle p} where the maximal weight of any edge in graph G {\displaystyle G} is 2 p {\displaystyle 2^{p}} .
This reduction is done locally at each edge in G {\displaystyle G} that has a weight larger than 1. Let e = ( u , v ) {\displaystyle e=(u,v)} be an edge in G {\displaystyle G} with a weight w = 2 r > 1 {\displaystyle w=2^{r}>1} . It is replaced by a subgraph J e {\displaystyle J_{e}} that is made up of 2 r {\displaystyle 2r} nodes and 6 r {\displaystyle 6r} edges as seen in Figure 2. Each edge in J e {\displaystyle J_{e}} has a weight of 1. Thus, the resulting graph G ′ {\displaystyle G'} contains only edges with a weight of 1.
Consider some cycle-cover R {\displaystyle R} in G {\displaystyle G} .
In 2011, quantum computer scientist Scott Aaronson proved that the permanent is #P-hard using quantum methods. [ 15 ]
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https://en.wikipedia.org/wiki/♯P-completeness_of_01-permanent
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The baht ( / b ɑː t / ; Thai : บาท , pronounced [bàːt] ; sign : ฿ ; code : THB ) is the official currency of Thailand . It is divided into 100 satang ( สตางค์ , pronounced [sà.tāːŋ] ). Prior to decimalisation , the baht was divided into eight fueang ( เฟื้อง , pronounced [fɯá̯ŋ] ), each of eight at ( อัฐ , pronounced [ʔat̚] ). The issuance of currency is the responsibility of the Bank of Thailand . SWIFT ranked the Thai baht as the 10th-most-frequently used world payment currency as of December 2023. [ 1 ]
The Thai baht, like the pound , originated from a traditional unit of mass . Its currency value was originally expressed as that of silver of corresponding weight (now defined as 15 grams), and was in use probably as early as the Sukhothai period in the form of bullet coins known in Thai as photduang . [ 2 ] These were pieces of solid silver cast to various weights corresponding to a traditional system of units related by simple fractions and multiples, one of which is the baht . These are listed in the following table: [ 3 ] [ 4 ] Though the coins themselves have names like: solot , siao , sik , etc, the formal division of the Thai baht (tical) is 1 baht = 8 fueang = 64 at . This means that one baht is divided into eight fueang , and each one fueang is divided into 8 at . Currently, the Thai baht do not employ the at as a subunit, but the at is the current subunit of the Lao kip .
This predecimal system was in use up until 1897, when the decimal system devised by Prince Jayanta Mongkol , in which one baht = 100 satang, was introduced by his half-brother King Chulalongkorn along with the demonetization of silver bullet coins on 28 October 1904 after the end of silver bullet coin production by the opening of Sitthikarn Royal Mint in 1857. [ 5 ] However, coins denominated in the old units were issued until 1910, and the amount of 25 satang is still commonly referred to as a salueng , as is the 25-satang coin.
Until 27 November 1902, the baht was fixed on a purely silver basis, with 15 grams of silver to the baht. This caused the value of the currency to vary relative to currencies on a gold standard . From 1856 to 1864, the values of certain foreign silver coins were fixed by law, with 5 baht = 3 Spanish dollar = 7 Indian rupees . [ 6 ] Before 1880 the exchange rate was fixed at 8 baht per pound sterling , falling to 10 to the pound during the 1880s.
In 1902, the government began to increase the value of the baht by following all increases in the value of silver against gold but not reducing it when the silver price fell. Beginning at 21.75 baht per pound sterling , the currency rose in value until, in 1908, a fixed peg to the British pound sterling was established of 13 baht per pound. This was revised to 12 baht in 1919 and then, after a period of instability, to 11 baht in 1923. During World War II , the baht was fixed at a value of one Japanese yen on 22 April 1942. [ 7 ] [ 8 ]
From 1956 until 1973, the baht was pegged to the US dollar at an exchange rate of 20.8 baht = one dollar and at 20 baht = 1 dollar until 1978. [ 9 ] [ 10 ] A strengthening US economy caused Thailand to re-peg its currency at 25 to the dollar from 1984 until 2 July 1997, when the country was affected by the 1997 Asian financial crisis . The baht was floated and halved in value, reaching its lowest rate of 56 to the dollar in January 1998. It rose to 30 per dollar in January 2021.
The baht was originally known to foreigners by the term tical , [ 11 ] which was used in English language text on banknotes until the series 2 1925. [ 12 ] [ 13 ]
The currency symbol for the baht is ฿ (a Latin letter B with a vertical stroke). In 1986, this symbol was given a codepoint for computer use in the Thai Industrial Standard 620-2533 (Thailand's extension of ASCII ), at position 0xDF. This national standard was subsequently subsumed into international standards as ISO/IEC 8859-11 ("ISO Latin-Thai"). In turn, the ISO 8859 series were transposed into the Unicode standard, [ 14 ] where the symbol was allocated the codepoint U+0E3F ฿ THAI CURRENCY SYMBOL BAHT . [ 15 ] The symbol is also used for the Panamanian balboa . [ 16 ]
In Thai usage, the baht ( บาท ) is legally abbreviated as บ. according to Section 7 of the Currency Act, B.E. 2501. [ 17 ]
For a time, the baht symbol was appropriated by some as a symbol for Bitcoin , a cryptocurrency . Following representations, [ 18 ] a separate code point ( U+20BF ₿ BITCOIN SIGN , a Latin letter B with two vertical strokes) was allocated in Unicode version 10.0. [ 19 ]
In Unicode 1.0, two codepoints were allocated to the baht, one as the currency symbol in the Thai range and one in the CJK Compatibility block as a square version of the Japanese word for "baht", written in katakana script. [ 20 ] The CJK codepoint, U+332C ㌬ SQUARE PAATU , is documented in subsequent versions of the standard as "a mistaken, unused representation" and users are directed to U+0E3F ฿ THAI CURRENCY SYMBOL BAHT instead. [ 21 ] Consequently, only a few computer fonts have any content for this codepoint and its use is deprecated. [ 20 ]
(The Japanese for "baht" is バ ーツ ( bā tsu ). However, the reference glyph ⟨㌬⟩ and the character name correspond to パ ーツ ( pā tsu , from English "parts"). [ 20 ] )
Before decimalization, the Siamese government employed Chinese , Latin , Jawi ( Malay ), Devanagari , Khmer and Khom , Lanna , and Burmese scripts in banknotes and coins, as seen. The reason is not clear, though it is a common understanding that it is to ease the facilicitation of trade within Siam. It could also be the case that at the time, the capital, Bangkok (Phra Nakhon) was still a multi-cultural city, so as to be more inclusive, the government added various other language onto the currency – though by the second series after the decimalization in the 1900s, the currency was all but monolingual.
圓 ; yuán ( บาท ): This character was use during the times of Rama IV to represent baht, though this was phased out by another character which is in partially and informally used today. The only occurrence of this character was in Rama IV's banknote series.
銖 ; 铢 ; zhū ( บาท ): This character was in use from 1868–1925 officially on banknotes to represent baht. It is still in use today unofficially to refer to the Thai baht in general, as in 泰銖 or 泰铢 .
錢 ; 銭 ; qián ( สลึง ): This character was in use from 1851–1908 officially on banknotes and coins to represent salueng.
方 ; fāng ( เฟื้อง ): This character was in use from 1851–1908 officially on banknotes and coins to represent fueang.
The notation for these Chinese character are written like they are in Thai, though there is a caveat: it is written right to left, as was the convention back then, so one baht is written 圓壹 or 銖壹 , if there are smaller units involved the notation can write like such: 方銭參圓壹 for one baht, three salueng, and one fueang.
80 ticals
(1 Chang)
662 years
4 years
9 years
6 years
13 years
9 years
11 years
Rama V*
29 years
Rama VI*
Rama VII*
9 years
4 years
22 years
5 years
5 years
5 years
(31 years)*
38 years
7 years
*actual year produced vs year in active use
Cowrie shells from the Mekong River had been used as currency for small amounts since the Sukhothai period. Before 1860, Thailand did not produce coins using modern methods. Instead, a so-called "bullet" coinage was used, consisting of bars of metal, thicker in the middle, bent round to form a complete circle on which identifying marks were stamped. [ 23 ] [ 24 ] Denominations issued included 1 ⁄ 128 , 1 ⁄ 64 , 1 ⁄ 32 , 1 ⁄ 16 , 1 ⁄ 8 , 1 ⁄ 2 , 1, 1 + 1 ⁄ 2 , 2, 2 + 1 ⁄ 2 , 4, 4 + 1 ⁄ 2 , 8, 10, 20, 40 and 80 baht in silver and 1 ⁄ 32 , 1 ⁄ 16 , 1 ⁄ 8 , 1 ⁄ 2 , 1, 1 + 1 ⁄ 2 , 2 and 4 baht in gold. One gold baht was generally worth 16 silver baht. Between 1858 and 1860, foreign trade coins were also stamped by the government for use in Thailand.
Photduang , a form of currency used during the Sukhothai period, was characterized by its longer legs, which created a larger and wider hole in the middle. These coins were primarily made of silver and featured a cut across the front of each leg. This cut served a dual purpose: it authenticated the money and allowed for the quality of the silver to be tested. Over time, as the Sukhothai Kingdom declined and became a vassal state of Ayutthaya—which was established as the capital in 1350—the design of photduang evolved. The coins became rounder with shorter legs, and the central hole, while still present, grew smaller. By the end of this era, the hole disappeared completely. The cuts on the legs also reduced in size and were eventually replaced by a small elliptical nick, known as "Met Kao San," on one side of the coin. [ 25 ]
The Thonburi period (1767–1782) and the Rattanakosin period, beginning in 1782, adopted the photduang design from the late Ayutthaya period. The coins from these periods had no central hole, and the legs were even shorter. A key difference was that
Thonburi photduang lacked the elliptical nick, whereas the Rattanakosin coins reintroduced this feature, similar to the Ayutthaya coins. Photduang from these later periods typically featured two stamped marks: the dynasty mark on top and the king's personal mark on the front part. The dynasty mark often symbolized the kingdom's ruling dynasty, while the king's personal mark represented the reigning monarch. [ 25 ]
The markings on photduang coins varied across different periods. During the Sukhothai era, some coins bore no marks, while others had up to 11. This variation was because, at that time, individuals and merchants could produce their own money. However, from the Ayutthaya period onward, the production of photduang was monopolized by the government, making it easier to identify coins from each era. Ayutthaya photduang typically bore two marks: the dynasty mark, which could be a spoked wheel symbolizing the "Wheel of Law" from Buddhist teachings or the Chakra (Vishnu's weapon), represented by a pattern of 8 dots surrounding a central dot. The king's personal mark varied with each ruler and included symbols such as a conch shell, a Garuda bird ( khrut ), an elephant, and an anchor, each symbolizing different aspects of the king's reign or divine associations. [ 25 ]
[ 26 ] *continues in the coin section*
Rama III (1824–1851) was the first king to consider the use of a flat coin. He did so not for the convenience of traders, but because he was disturbed that the creatures living in the cowrie shells were killed. When he learned of the use of flat copper coins in Singapore in 1835, he contacted a Scottish trader, who had two types of experimental coins struck in England. The king rejected both designs. The name of the country put on these first coins was Muang Thai , not Siam . [ 28 ] [ 29 ]
In 1860, modern-style coins were introduced. These were silver 1 sik ; 1 fueang ; 1 and 2 salueng ; 1, 2, and 4 baht; with the baht weighing 15.244 grams and the others weight-related. Tin 1 solot and 1 at followed in 1862, with gold 2 + 1 ⁄ 2 , 4, and 8 baht introduced in 1863 and copper 2 and 4 at in 1865. Copper replaced tin in the 1 solot and 1 at in 1874, with copper 4 at introduced in 1876. The last gold coins were struck in 1895.
During the reign of King Rama III (1824–1851), an initiative was made to introduce Thailand’s first flat coinage, intended to replace the widely used cowrie shells. To aid in this modernization of the monetary system, the king employed Robert Hunter, a Scottish merchant, to produce pattern coins. [ 30 ]
The proposed designs featured an elephant motif, which bore resemblance to the coinage of Lanka (modern-day Sri Lanka). Concerned about the symbolic inappropriateness of the elephant, which could imply foreign influence or association, King Rama III ultimately rejected all of the submitted patterns. As a result, none of the proposed coins were officially adopted or denominated.
These pattern coins, though never circulated, represent an early attempt at modernization of Siamese currency prior to the eventual adoption of machine-struck coinage in the reign of King Rama IV.
๑๑๙๗ (CS. 1197)
เมืองไทย
(Thailand)
๑๑๙๗ (CS. 1197)
เมืองไทย
(Thailand)
๑๑๙๗ (CS. 1197)
ترومن (Trumon)
๑๑๙๗ (CS. 1197)
ترومن (Trumon)
The first issue of coins were commissioned by Rama IV, though it was never brought into circulation. This was one of the first attempt to replace the bullet coins, but few were ever minted without making it into circulation. [ 32 ]
The first circulating issue of the Siamese coins. This marked the start of the move away from using photduang currency. Though in this era, the photduang were still legal tender. In this series, the lower denominations were made of silver, and the higher ones were made of gold. These higher denominations were given nicknames: pot dueng , pit , and tot . Pot dueng means thirty two, as in 1/32 of a chang . The other nickname was the chinkang or one Chinese tamlueng . [ 33 ] The pit means twenty, as in 1/20 of a chang, the other name is ekkang, or one thai tamlueng. [ 34 ] The tot means ten, as in 1/10 of a chang . The coin was also called thukkang , which means two tamlueng . [ 35 ] In the lower denominations materials such as tin , copper and brass are used, since these are quite low value.
According to the Thai Treasury, regarding the gold coins, they were minted during a period when large amounts of gold were entering Thailand. Inspired by the widespread use of gold coins in other countries, such as the gold coins of England, King Mongkut (Rama IV) ordered the production of gold coins for domestic use. These coins, with their higher value, facilitated trade as the silver coins in circulation at the time were of lower value. They were officially issued on October 29, 1863, and were withdrawn from use in 1908. [ 36 ]
This series of coins was produced using manually operated machinery that had been presented as a royal gift by Queen Victoria of England. Due to the limited production capacity of these machines, the coins could not be minted in sufficient quantities to meet the country's demand. Consequently, their use was discontinued. This coincided with the arrival of steam-powered machinery, which allowed for more efficient and larger-scale coin production. [ 37 ] It is worth noting that coins of the half-fuang denomination were not mentioned in official announcements. [ 38 ]
In 1866, These thin copper coins, in sik (half-fuang) and siao (quarter-fuang) denominations, were produced to replace their thicker counterparts, which were heavier and had the same value. The decision to issue lighter, thinner coins was made after an incident where King Mongkut (Rama IV) distributed the thicker coins during a charitable event, and recipients were injured with head wounds and bruises. His Majesty considered that the copper coins already bore stamped marks and inscriptions (indicating that 2 coins equaled 1 fuang and 4 coins equaled 1 fuang), making them trustworthy. Therefore, thinner and lighter coins would still serve their purpose effectively without causing harm. [ 39 ]
+ สิบ หก อัน เป็น เฟื้อง 1/16 F. 方 片 六 十
+ แปด อัน เปน เฟื้อง 1/8 F. 方 片 捌
+ สี่ อัน เปน เฟื้อง 1/4 F. 方 片 四
+ สอง อัน เปน เฟื้อง 1/2 F. 方 片 二
stand in image*
stand in image*
+ สิบ หก อัน เป็น เฟื้อง 1/16 F. 方 片 六 十
The first series to depict king Rama V, the coins of this issue were made of copper, silver, and gold. Though gold was strangely only used for the 1 fueang denomination. [ 40 ] The new shield emblem was introduced in this issue. This shield was separated into three section. Drawing from western influences, symbols within these sections represented territories Siam was controlling. The tree-headed elephant represented Siamese territory , the bottom-left elephant represented Lan Xang , and the warangka represented Siamese Malaya.
Due to a malfunction in the minting machinery at the government mint, which prevented the production of circulating coinage, King Chulalongkorn ordered the design of this coin series and commissioned its production by a mint in Birmingham, England. This marked the first time that coins were minted abroad for circulation in Siam. [ 41 ] The copper coins in this issue were made in the same size as the coins of the United Kingdom, with the Solot being the same size as the Farthing , the Att being the same size as the Half-Penny , and the Siao being the same size as the Penny . The silver coins differ in size to the British counterpart due to the baht being pegged to a different unit of silver. The copper coin in this case were base metal and were not pegged to any standard metal, hence their size tend to differ more throughout history. These copper coins only represent a certain amount of silver.
These silver coins were minted when the Sathit Kuang machinery was put into use in 1889 at the Sathit Kuang Coin Mint, marking the beginning of a new coinage system. The year markings started to appear on the coins from R.S. 120 (1898) onwards. [ 42 ]
+
โสลด (Solot) ๑๖ (16) อันเฟื้อง (makes a fuang)
๑๒๓๖ (CS 1236)
+
อัฐ (At) ๘ (8) อันเฟื้อง (makes a fuang)
๑๒๓๖ (CS 1236)
+
เสี้ยว (Siao) ๔ (4) อันเฟื้อง (makes a fuang)
๑๒๓๖ (CS 1236)
+
สิ้ก (Sik) ๒ (2) อันเฟื้อง (makes a fuang)
๑๒๓๘ (CS 1238)
+
สมเด็จพระปรมินทรมหาจุฬาลงกรณ์ (His Majesty King Chulalongkorn) พระจุลจอมเกล้าเจ้าอยู่หัว (King Chula Chomklao)
+
กรุงสยาม (Siam) รัชกาลที่๕ (5th Reign) เฟื้องหนึ่ง (1 fueang)
(RS. 120)
+
กรุงสยาม (Siam) รัชกาลที่๕ (5th Reign) เฟื้องหนึ่ง (1 fueang)
(dated)
(RS. 120)
+
สมเด็จพระปรมินทรมหาจุฬาลงกรณ์ (His Majesty King Chulalongkorn) พระจุลจอมเกล้าเจ้าอยู่หัว (King Chulalongkorn)
+
กรุงสยาม (Siam) รัชกาลที่๕ (5th Reign) สลึงหนึ่ง (1 salueng)
(dated)
(RS. 120)
+
สมเด็จพระปรมินทรมหาจุฬาลงกรณ์ (His Majesty King Chulalongkorn) พระจุลจอมเกล้าเจ้าอยู่หัว (King Chulalongkorn)
+
กรุงสยาม (Siam) รัชกาลที่๕ (5th Reign) บาทหนึ่ง (1 baht)
(dated)
(RS. 120)
This was a minor issue, in which the lesser denominations' designs were updated to incorporate the three-parted [ clarification needed ] shield into the design. This copper coin was produced to replace previous versions and was minted in England, with additional production by the Royal Mint of Thailand. [ 43 ] In this issue, depending on where the coin was minted, the minting alignment was different. This means that in this specific series, the alignment will show at which mint the coin was minted. [ 44 ] For example, in this series there were four mints which contributed to the minting: Royal Mint of Belgium, Bangkok Mint, Heaton and Sons (Burmingham Mint), and Hamburgische Münze. For the 1 Solot coin, the coin minted in the year R.S. 109 [ clarification needed ] was medal aligned and was minted in the Birmingham Mint, but R.S. 118 coins were minted in Hamburg had coin alignement. [ 45 ]
+
จุฬาลงกรณ์ ป.ร. (Chulalongkorn Rex) พระจุลจอมเกล้าเจ้ากรุงสยาม (King Chula Chomklao of Siam)
+
หนึ่งโสฬศ (1 solot) ๑๑๘ (RS 118)
+
จุฬาลงกรณ์ ป.ร. (Chulalongkorn Rex) พระจุลจอมเกล้าเจ้ากรุงสยาม (King Chula Chomklao of Siam)
+
หนึ่งอัฐ (1 at) ๑๒๒ (RS 122)
+
จุฬาลงกรณ์ ป.ร. (Chulalongkorn Rex) พระจุลจอมเกล้าเจ้ากรุงสยาม (King Chula Chomklao of Siam)
+
หนึ่งเซียว (1 siao) ๑๒๒ (RS 122)
The decimalization of the Thai baht came about at the end of the 19th century. The minister of treasury, Jayanta Mongkol, the Prince Mahisara Rajaharudaya , suggested to King Rama V, that decimalization would make counting easier and further modernize Siam. Initially, there would be one superunit, chang , and one subunit, at . with the baht being in the middle. In summary, 64 at = 1 baht = 1/80 chang . In reality, this was just a simplification of the old system, which was scrapped. [ 46 ] In which, during the period of 1902–1908, Siam went back to the old system. Though in comparison, at is used as the subunit in Laos, compared to the satang in the Thai baht. The second attempt came at the end of Rama V's reign, where it was more widely accepted and put into effective use.
In 1897, the first coins denominated in satang were introduced, cupronickel 2 + 1 ⁄ 2 , 5, 10, and 20 satang. However, 1 solot , 1, and 2 at coins were struck until 1905 and 1 fueang coins were struck until 1910. In 1908, holed 1, 5, and 10 satang coins were introduced, with the 1 satang in bronze and the 5 and 10 satang in nickel. The 1 and 2 salueng were replaced by 25 and 50 satang coins in 1915. In 1937, holed, bronze 1 ⁄ 2 satang were issued.
In 1941, a series of silver coins was introduced in denominations of 5, 10, and 20 satang, due to a shortage of nickel caused by World War II . The next year, tin coins were introduced for 1, 5, and 10 satang, followed by 20 satang in 1945 and 25 and 50 satang in 1946. In 1950, aluminium bronze 5, 10, 25, and 50 satang were introduced whilst, in 1957, bronze 5 and 10 satang were issued, along with 1-baht coins struck in an unusual alloy of copper, nickel, silver and zinc. Several Thai coins were issued for many years without changing the date. These include the tin 1942 1 satang and the 1950 5 and 10 satang, struck until 1973, the tin 1946 25 satang struck until 1964, the tin 50 satang struck until 1957, and the aluminium bronze 1957 5, 10, 25, and 50 satang struck until the 1970s. Cupronickel 1-baht coins were introduced in 1962 and struck without date change until 1982.
In 1972, cupronickel 5-baht coins were introduced, switching to cupronickel-clad copper in 1977. Between 1986 and 1988, a new coinage was introduced, consisting of aluminium 1, 5 and 10 satang, aluminium bronze 25 and 50 satang, cupronickel 1 baht, cupronickel-clad copper 5 baht and bimetallic 10 baht. Cupronickel-clad steel 2 baht were introduced in 2005.
The old monetary system of Siam was based on a binary system that proved challenging for accounting purposes. This system initially consisted of three main units of currency: Chang , Baht , and Att . Under this system, there were 64 Att to 1 Baht and 80
Baht to 1 Chang. Despite its widespread use, the system’s complexity made it difficult to manage and calculate.
Recognizing the inefficiencies, the Minister of Treasury proposed to King Rama V that Siam’s currency system should be decimalized. The proposal aimed to modernize the monetary system and align it with the decimal systems increasingly adopted by other countries at the time. King Rama V approved the transition to a decimal-based currency, which simplified accounting processes.
The transition to a decimal currency system faced numerous challenges even before the new coins were issued. Notably, the word "Anachak" (อาณาจักร) was initially misspelled as "อานาจักร," causing controversy. King Rama V intervened, insisting that the most accurate phrasing should be "Siam Ratcha-Anachak" (สยามราชอาณาจักร; Kingdom of Siam).
Despite the initial enthusiasm for the decimal system, the new coins struggled to gain popularity among the public. Many people were unfamiliar with the decimal system and preferred the traditional currency. Consequently, the new coins quickly faded from circulation, forcing the government to continue producing coins under the old system.
The production of coins from the old system persisted until RS 127 / BE 2451 / AD 1907 . Ultimately, both pre-decimal coins and the early decimal coins were demonetized on May 17, RS 128 / BE 2452 / AD 1909 . Citizens were given a grace period to exchange the demonetized coins for the new decimal currency, with the deadline set for May 16, RS 128 / BE 2452 / AD 1910 .
This gradual shift is shown in the fact that coins after the transition often switched between three calendar systems, the CS (Chulasakarat) system, the RS (Rattanakosin Sok) system, the BE (Buddhist Era / Phutthasakarat) system. [ 47 ]
+
สยามอานาจักร (Kingdom of Siam) ศก๑๑๖ (RS 116)
+
สยามอานาจักร (Kingdom of Siam) ศก๑๑๖ (RS 116)
+
สยามอานาจักร (Kingdom of Siam) ศก๑๑๖ (RS 116)
+
สยามอานาจักร (Kingdom of Siam) ศก๑๑๖ (RS 116)
These coins were all produced abroad, and they feature changes in year formatting and design differences over time. The coins were initially produced with the R.S. year system but transitioned to using the B.E. system from 1913 onwards. [ 48 ] The 1 Baht
coins were replaced with banknotes starting in 1918 due to the high cost of silver. The 2 Salung and 1 Salung coins experienced changes in metal composition due to fluctuating silver prices during World War I, and these coins have slight design variations based on these changes.
During issue, there were also various debasements of the silver content of these coins. Initially, the composition was 80% silver and 20% copper. In 1918, during World War I, silver prices surged, leading to a change in the composition to 65% silver and 35% copper. In 1919, the silver percentage dropped further to 50% silver and 50% copper. After the war, in 1919, the composition returned to 65% silver and 35% copper. [ 49 ] In 1917, the price of silver rose and exceeded the face value of silver coins. The coins were then melted down and sold. The government solved this by changing the pure silver coin to alloy. Vajiravudh eventually forbade exports of Siamese coins. In 1918, the usage of 1-baht coins was nullified and 1-baht banknotes were introduced. Coins were recalled and kept as a national reserve.
Near the end of this issue of coins, the transition into decimal currency was completed. The Rama VII coin was produced in two denominations, 50 Satang and 25 Satang, and marked the transition from the old currency system of "สองสลึง" (two salung) and "หนึ่งสลึง" (one salung) to the new system using Satang as a unit of currency. [ 50 ] Though, people today still refer to these denomination using the old terminology.
+
พ.ศ. ๒๔๗๐ (B.E. 2470)
+
สยามรัฐ ๑ สตางค์ (Siamese State 1 satang)
+
รัฐบารไทย ๑ สตางค์ (Thai Government 1 satang)
+
พ.ศ. ๒๔๗๐ (B.E. 2470)
+
สยามรัฐ ๕ สตางค์ (Siamese State 5 satang)
+
พ.ศ. ๒๔๗๐ (B.E. 2470)
+
สยามรัฐ ๑๐ สตางค์ (Siamese State 10 satang)
+
สมเด็จพระปรมินทรมหาจุฬาลงกรณ์ (His Majesty King Chulalongkorn) พระจุลจอมเกล้าเจ้าอยู่หัว (King Chulalongkorn)
+
กรุงสยาม (Siam) รัชกาลที่๕ (5th Reign) ๕๐ สตางค์ (50 satang)
stand in image*
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จุฬาลงกรณ์ สยามินทร์ (Chulalongkorn, Lord of Siam)
+
สยามรัฐ ร.ศ.๑๒๘ (Siamese State RS 128) หนึ่ง สลึง (1 salueng)
stand in image*
+
จุฬาลงกรณ์ สยามินทร์ (Chulalongkorn, Lord of Siam)
+
สยามรัฐ ร.ศ.๑๒๘ (Siamese State RS 128) สอง สลึง (2 salueng)
+
จุฬาลงกรณ์ สยามินทร์ (Chulalongkorn, Lord of Siam)
+
สยามรัฐ ร.ศ.๑๒๗ (Siamese State RS 127) หนึ่ง บาท (1 baht)
Silver 0.650 1916-1918
Silver 0.500 1919
Silver 0.650 1920-1925
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วชิราวุธ สยามินทร์ (Vajiravud Lord of Siam)
+
สยามรัฐ ๒๔๖๘ (Siamese State BE 2468) หนึ่ง สลึง (1 salueng)
Silver 0.650 1916-1918
Silver 0.500 1919
Silver 0.650 1920-1921
+
วชิราวุธ สยามินทร์ (Vajiravud Lord of Siam)
+
สยามรัฐ ๒๔๕๘ (Siamese State BE 2458) สอง สลึง (2 salueng)
+
วชิราวุธ สยามินทร์ (Vajiravud Lord of Siam)
+
สยามรัฐ ๒๔๖๐ (Siamese State BE 2460) หนึ่ง บาท (1 baht)
+
ประชาธิปก สยามินทร์ (Prajadipok, Lord of Siam)
+
สยามรัฐ ๒๔๗๒ (Siamese State BE 2472) หนึ่ง สลึง (1 salueng)
+
ประชาธิปก สยามินทร์ (Prajadipok, Lord of Siam)
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สยามรัฐ ๒๔๗๒ (Siamese State BE 2472) สอง สลึง (2 salueng)
This series of coins is distinctive as it lacks the royal insignia and the state seal, which were commonly featured in earlier designs. This series also includes a 20 satang denomination; thus at one point the 25-satang and the 20-satang circulated at the same time. [ 51 ] The half-satang was introduced in 1937 to address the issue of low-value currency units in Thailand. The value of 1 Satang was considered too high for certain low-priced items, causing economic hardship for the poor. Previously, 1 Baht could be exchanged for 128 Solot, but after the switch to Satang, 1 Baht was only equivalent to 100 Satang. The introduction of this coin aimed to make it easier for ordinary people to purchase items without the burden of inflated prices. The coin was produced only once and was discontinued soon afterwards. It was minted in Japan and first issued on July 12, 1937. [ 52 ]
In 1942, a group of denominations switched material due to the costs of World War II : the 1-satang coin lost its hole in the middle and was made smaller. [ 53 ]
+
พ.ศ. ๒๔๘๐ (B.E. 2480)
+
สยามรัฐ ๑/๒ สตางค์ (Siamese State 1/2 satang)
+ พ.ศ.๒๔๘๔ (BE 2484)
+
๑ สต. (1 satang) รัฐบาลไทย (Thai Government)
+ พ.ศ.๒๔๘๔ (BE 2484)
+
๕ สต. (5 satang) รัฐบาลไทย (Thai Government)
+ พ.ศ.๒๔๘๔ (BE 2484)
+
๑๐ สต. (10 satang) รัฐบาลไทย (Thai Government)
+ พ.ศ.๒๔๘๕ (BE 2485)
+
๑๐ สต. (20 satang) รัฐบาลไทย (Thai Government)
This was the first series minted in the reign of King Ananda Mahidol (Rama VIII), and it marked the return of national symbols, such as the Garuda emblem, which had been used as the national seal since the Ayutthaya period. This emblem, created during
the reign of King Chulalongkorn (Rama V), became the national seal to be used permanently, avoiding the need for a new one with each reign. There are two versions of this series minted in the same year, the young portrait and the teen portrait. [ 54 ]
(young & teen issue)
+
อานันทมหิดล (Ananda Mahidol) รัชกาลที่ ๘ (8th Reign)
+
รัฐบาลไทย (Thai Government) ๕ สต. (5 satang) พ.ศ.๒๔๘๙ (BE 2489)
+
อานันทมหิดล (Ananda Mahidol) รัชกาลที่ ๘ (8th Reign)
+
รัฐบาลไทย (Thai Government) ๑๐ สต. (10 satang) พ.ศ.๒๔๘๙ (BE 2489)
+
อานันทมหิดล (Ananda Mahidol) รัชกาลที่ ๘ (8th Reign)
+
รัฐบาลไทย (Thai Government) ๒๕ สต. (25 satang) พ.ศ.๒๔๘๙ (BE 2489)
+
อานันทมหิดล (Ananda Mahidol) รัชกาลที่ ๘ (8th Reign)
+
รัฐบาลไทย (Thai Government) ๕๐ สต. (50 satang) พ.ศ.๒๔๘๙ (BE 2489)
(special circ. issues)
The current coin series is the 14th issue.
In 2008, in the 13th issue, the Ministry of Finance and the Royal Thai Mint announced the 2009 coin series, which included changes in materials to reduce production costs as well as an update of the image on the obverse to a more recent portrait of the king. The two-baht coin, confusingly similar in color and size to the one-baht coin, was changed from nickel-clad low-carbon steel to aluminium bronze. New two-baht coin was the first of the new series released on 3 February 2009, followed by the satang coins in April, a five-baht coin in May, a ten-baht coin in June, and a one-baht coin in July 2009.
In 2018, the Royal Thai Mint and the Ministry of Finance issued a new series of general circulation coins, featuring the same standard specifications, but feature a portrait of its current king, Vajiralongkorn .
In February 2010 the Treasury Department of Thailand stated that it has been planning a new circulation 20-baht coin. [ 57 ]
Over the course of Siamese coinage history, various calendar systems were used. The first one to be applied onto the coins was the burmese calendar system or Chula Sakarat (C.S.) , which was subsequently supplanted by the Rattanakosin Sok system (R.S.) which started at the founding of the Rattanakosin Kingdom . The system in use right now is the Phuttha Sakarat system or the Buddhist calendar (B.E.)
1236 CS
118 RS
2472 BE
In 1851, the government issued notes for 1 ⁄ 8 , 1 ⁄ 4 , 3 ⁄ 8 , 1 ⁄ 2 and 1 tical, followed by 3, 4, 6 and 10 tamlueng in 1853. After 1857, notes for 20 and 40 ticals were issued, also bearing their values in Straits dollars and Indian rupees . Undated notes were also issued before 1868 for 5, 7, 8, 12 and 15 tamlueng, and 1 chang. One at notes were issued in 1874.
In 1892, the treasury issued notes for 1, 5, 10, 40, 80, 100, 400 and 800 ticals, called "baht" in the Thai text.
On 10 September 1902, the government introduced notes which were printed by Thomas De La Rue & Company Limited, England , during the reigns of Kings Rama V and Rama VI , denominated 5, 10, 20, 100 and 1000 ticals, still called baht in the Thai text — each denomination having many types, [ 58 ] with 1 and 50 tical notes following in 1918. In 1925, notes were issued in denominations of 1, 5, 10, 20, 100 and 1,000 baht with the denomination in both Arabic and Thai numerals without English text; [ 59 ] English speakers continued to refer to these as "ticals". [ 60 ]
On 27 July 2010, the Bank of Thailand announced that the 16th-series banknotes would enter circulation in December 2010. [ 61 ] [ 62 ] On 9 August 2012, the Bank of Thailand issued a new denomination banknote, 80 baht, to commemorate queen Sirikit's 80th birthday. [ 63 ] It was the first Thai banknote that featured Crane's MOTION security thread.
In 2017, the Bank of Thailand announced a new family of banknotes in remembrance of the late King Bhumibol Adulyadej (Rama IX). The notes are the same size and dimensions as the "Series 16" banknotes, with the front designs as before, but the back designs featuring images of the king's life in infancy, adolescence and maturity. The new family of banknotes were issued on September 20. [ 64 ]
In 2018, the Bank of Thailand announced a new family of banknotes featuring a portrait of the current King Vajiralongkorn (Rama X). The main colors and dimensions of the notes are the same as before, with the back designs featuring images of the Kings of Thailand from past to present. The 20, 50 and 100 baht banknotes were issued on Chakri Memorial Day, April 6, 2018. The final two denominations, 500 and 1,000 baht were issued on the anniversary of the birth of King Maha Vajiralongkorn, July 28, 2018. [ 65 ]
The characteristic of the banknotes of this era was that there were no series issued at the same time, rather they were issued sporadically and had multiple banks producing their own banknotes.
Series 1 was chosen due to the series which precedes this were non-decimal. Series 1 banknotes was the first series to be produced by Thomas De La Rue & Company Limited. In 1900, Charles James Rivett Carnac, a Royal Treasury Ministry advisor proposed that the Siamese baht followed the issuances of banknotes followed the British standard. The banknote department was established quickly thereafter. The main characteristic of this series was that the notes were one-sided and multilingual, containing Chinese , Malay (in Jawi script ), and Latin scripts. [ 66 ] It was also the last series to use the term "tical" to refer to the Thai baht and the largest in term of size of the circulated notes.
Series 2 banknotes were produced by Thomas De La Rue & Company Limited.
Series 3 type 1 banknotes were produced by Thomas De La Rue & Company Limited. This series was actually delayed due to the Siamese revolution to abolish the absolute monarchy and transform it into a constitutional monarchy. The issuance was supposed to happen in the early 1930s.
Series 3 type 2 banknotes were produced by Thomas De La Rue & Company Limited. It was the first series to hold King Rama VIII 's portrait, which replaced King Rama VII 's portrait in the type 1.
Series 4 type 1 banknotes were produced by Thomas De La Rue & Company Limited.
Series 4 type 2 banknotes were produced by Royal Thai Survey Department and the Naval Hydrographic Department. During World War II , Thailand was allied with the Empire of Japan . This meant that the government of Thailand could not order banknotes from Thomas De La Rue & Company Limited.
Series 5 banknotes were produced by Notes Printing Works of Japan.
Series 6 banknotes were produced by Royal Thai Survey Department.
Series 7 banknotes relied on private printing under the supervision of the Bank of Thailand. According to the Bank of Thailand, the quality of this series was barely satisfactory.
The special series were banknotes that were issued during World War II, each at different times.
At the end of World War II, Thomas De La Rue & Company Limited's printing house suffered damage from German bombing, thus the Royal Thai Government turned to the United States government to produce the series 8. The Tudor Press Company produced this series.
These banknotes series are not yet demonetized and hence still legal tender, though they are never seen in circulation anymore.
These banknotes images are allowed under a strict copyright infringement exemption under the Chapter 1: Copyright, Part 6: Exceptions to Infringement of Copyright, Clause 7 of Copyright Act B.E. 2537 (1994) Amended by Copyright Act (NO. 2) B.E. 2558 (2015), and Copyright Act (NO.3) B.E. 2558 (2015) and Copyright Act (NO.4) B.E. 2561 (2018): reproduction, adaptation in part of a work or abridgement or making a summary by a teacher or an educational institution so as to distribute or sell to students in a class or in an educational institution, provided that the act is not for profit. [ 67 ]
So as to serve as an educational material, only one side is shown and any series beyond series 13 is omitted.
Series 9 banknotes were produced by Thomas De La Rue & Company Limited . There are two variations within this series, the young, and new portrait. According to the Bank of Thailand, the color schemes of this series established the denominations' colors for all of the following series due to the series circulating for 20 years. [ 68 ]
Series 10 banknotes were produced by Thomas De La Rue & Company Limited. Due to heavy counterfeiting, series 10 was issued in series 9's stead. [ 69 ] The 100-baht note is the only denomination issued in this series.
In this series, the 500-baht note was introduced for the first time ever. This coincided with the Bank of Thailand fully converting to an in-house production. [ 70 ] As a consequence, the 1-baht note's production was cancelled.
Series 12 and 13 aimed to glorify past Thai monarchs , the Bank of Thailand dubbed this as "The Great Series." The 5-baht note's production was cancelled. The 50-baht and 500-baht notes are part of series 13 and were issued to commemorate the bicentennial celebration of Bangkok in 1982, though their production had to be delayed for the new printing press to be installed. [ 71 ]
Images of banknotes have been removed lest they infringe copyright, [ 72 ] but may be viewed at the Thai-language article linked in the margin.
The series 14 aims to focus on the activities and contributions of the Chakri kings. Officially, only three notes were issued, but the 50-baht notes were also produced alongside this series. The polymer 50-baht is considered to be a part of series 15, even though the production date began in 1994. [ 73 ] [ 74 ]
The series 15 aims to update and expand the previous series 14's design. The 1000-baht note was resized down. There are two variants of this series, with the second and later variant having updated security features. [ 76 ]
Similar to the series 15, the series 16 banknotes update the design to include a more later portrait of King Rama IX . There are two variants of this series, the later one being a circulated commemorative series circulating for a year after King Rama IX's passing. The series 16-2 notes depict the life and achievements of King Rama IX on the reverse.
Ngoen ( เงิน ) is Thai for " silver " as well as the general term for money , reflecting the fact that the baht (or tical) is foremost a unit of weight for precious metals and gemstones . One baht = 15.244 grams . [ 88 ] Since the standard purity of Thai gold is 96.5 percent, the actual gold content of one baht by weight is 15.244 × 0.965 = 14.71046 grams; equivalent to about 0.473 troy ounces . 15.244 grams is used for bullion ; in the case of jewellery , one baht should be more than 15.16 grams.
* the coins mintage date were only in 1863 & 1876 , but they were demonitized by the decimalization.
Decimal coinage
Decimal coinage
Decimal coinage
Decimal coinage
Decimal coinage
The Bank of Thailand adopted a series of exchange controls on 19 December 2006, which resulted in a significant divergence between offshore and onshore exchange rates, with spreads of up to 10 percent between the two markets. Controls were broadly lifted on 3 March 2008 and there is now no significant difference between offshore and onshore exchange rates. [ 90 ]
(Source 1999–2013: usd.fx-exchange.com)
(Source 2014–2020: Bank of Thailand) [3] Archived 2021-01-23 at the Wayback Machine
Due to the fact that during these time periods, often the currencies were non-decimals, hence the non-decimal notations for these currencies.
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https://en.wikipedia.org/wiki/㌬
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(Un)well is an American documentary series about the wellness industry . The series was produced by Left/Right Productions and premiered on August 12, 2020, on Netflix . [ 1 ] Reviewers point out the episodes tend to give more weight to enthusiastic testimonials than to expert advice, painting a positive picture of treatments that are often ineffective or dangerous.
Through interviews with practitioners, consumers and experts, the series questions the efficacy and safety of six treatments offered by the " wellness " industry. Presented without a narrator, the audience is left to make up their own minds about the information presented. [ 2 ] [ 3 ] [ 4 ]
Reviewers give credit to the series for exposing some of the worst abuse of the wellness industry. However, the series suffers from false balance , drowning the advice of experts in lengthy testimonies by sympathetic practitioners of alternative medicine and their clients.
At CNN , Brian Lowry points to the interviews with scientists and journalists sprinkled through the episodes as an explanation of how people can be manipulated by those who seek to sell treatments "more rooted in faith than science". It's also a commentary on the poor state of the healthcare system, with people looking for quick fixes elsewhere. Lowry quotes Steven Novella 's warning that the promises of the wellness industry are often nothing more than false hopes. [ 6 ]
Writing for Science-Based Medicine , Harriet Hall gives the series "two thumbs down". She believes it fails in its attempt to present a balanced view of the issues discussed: "The people who made (Un)well seem to believe testimonials and hearsay are good evidence and are just as credible as scientific studies, perhaps even more so." Hall worries that viewers, seduced by slickly-produced testimonials, will be motivated to try the treatment presented, even though it is likely ineffective and possibly dangerous. [ 7 ]
Jonathan Jarry of the Office for Science and Society says the series "observes but never judges, and this impartial approach causes it to commit the sin of false balance." The advice of experts presented throughout the episodes tends to be drowned out by anecdotes of enthusiastic patients. The show does present people who were severely harmed by pseudoscientific treatments, but always goes back to a practitioner who appears to adopt a more benign approach. In the end, for Jarry, (Un)Well "warns against extremes in the search for health but allows so many pseudoscientific claims to stand unchecked, it practically endorses many of the practices it aims to denounce." [ 8 ]
Writing for The Daily Beast , Laura Bradley worried that despite using interviews with genuine experts, the series risks promoting the conspiracy theorists and health gurus it also presents: "As much as (Un)Well clearly wants to serve as an even-handed guide into the strange world of wellness, the show's insistence on letting each side speak for itself without tipping its hand means all it's really doing is providing a platform for quackery and false hope." While the show clearly identifies problems with some companies ( Young Living gets the harsh treatment), others are let off easy. She also thought the material presented would fit better into a 30-minute format rather than the 50 minutes per episode used. [ 9 ]
Writing for Culture Whisper, Sarah Joan Ross gave the series three stars out of five. The series "does effectively expose a few of the darker sides of the wellness industry", but the scientific analysis does not go very deep. The testimonies of clients who tried the various treatments gives energy to the episodes, but they don't have the humor and production value of a series like The Goop Lab . [ 10 ]
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https://en.wikipedia.org/wiki/(Un)well
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17α-Hydroxyprogesterone ( 17α-OHP ), also known as 17-OH progesterone ( 17-OHP ), [ 1 ] or hydroxyprogesterone ( OHP ), is an endogenous progestogen steroid hormone related to progesterone . [ 2 ] [ 3 ] [ 4 ] It is also a chemical intermediate in the biosynthesis of many other endogenous steroids, including androgens , estrogens , glucocorticoids , and mineralocorticoids , as well as neurosteroids .
17α-OHP is an agonist of the progesterone receptor (PR) similarly to progesterone, albeit weakly in comparison. [ 5 ] In addition, it is an antagonist of the mineralocorticoid receptor (MR) [ 6 ] as well as a partial agonist of the glucocorticoid receptor (GR), albeit with very low potency ( EC 50 >100-fold less relative to cortisol ) at the latter site, also similarly to progesterone. [ 5 ] [ 7 ] [ 8 ]
17α-OHP is derived from progesterone via 17α-hydroxylase (encoded by CYP17A1 ). [ 9 ]
17α-OHP increases in the third trimester of pregnancy primarily due to fetal adrenal production. [ 10 ]
This steroid is primarily produced in the adrenal glands and to some degree in the gonads , specifically the corpus luteum of the ovary . Normal levels are 3-90 ng/dl in children, and in women, 20-100 ng/dl prior to ovulation , and 100-500 ng/dl during the luteal phase . [ 11 ] [ 12 ]
Measurements of levels of 17α-OHP are useful in the evaluation of patients with suspected congenital adrenal hyperplasia as the typical enzymes that are defective, namely 21-hydroxylase and 11β-hydroxylase , lead to a build-up of 17α-OHP. [ 13 ] In contrast, the rare patient with 17α-hydroxylase deficiency will have very low or undetectable levels of 17α-OHP. [ 9 ] 17α-OHP levels can also be used to measure contribution of progestational activity of the corpus luteum during pregnancy as progesterone but note, 17α-OHP is also contributed by the placenta . [ 14 ]
Immunoassays like RIA ( radioimmunoassay ) or IRMA (immunoradiometric
assay) used to clinically determine 17α-OHP are prone to cross-reactivity with the 17α-OHP steroid precursors and their sulphated conjugates. Gas or liquid chromatography and mass spectrometry (e.g. LC-MS/MS) achieves greater specificity than immunoassays. [ 15 ] [ 16 ]
Measurement of 17α-OHP by LC-MS/MS improves newborn screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency , because 17α-OHP steroid precursors and their sulphated conjugates which are present in the first two days after birth and longer in pre-term neonates, cross-react in immunoassays with 17α-OHP, giving falsely high 17α-OHP levels. [ 15 ] [ 16 ]
Although 17α-OHP has not been used as a medication, its pharmacokinetics have been studied and reviewed. [ 17 ]
Esters of 17α-OHP, such as hydroxyprogesterone caproate and, to a far lesser extent, hydroxyprogesterone acetate and hydroxyprogesterone heptanoate , have been used in medicine as progestins . [ 2 ] [ 3 ] [ 4 ]
17α-OHP is the parent compound of a class of progestins referred to as the 17α-hydroxyprogesterone derivatives . [ 18 ] [ 19 ] [ 20 ] Among others, this class of drugs includes chlormadinone acetate , cyproterone acetate , hydroxyprogesterone caproate , medroxyprogesterone acetate , and megestrol acetate . [ 18 ] [ 19 ] [ 20 ]
Hydroxyprogesterone is the generic name of 17α-OHP and its INN Tooltip International Nonproprietary Name and BAN Tooltip British Approved Name . [ 2 ] [ 3 ] [ 4 ]
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https://en.wikipedia.org/wiki/17α-Hydroxyprogesterone
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After the 1991 West Bengal Legislative Assembly election , a mob belonging to the Communist Party of India (CPM) attacked Gopal Patra, a leader of the Indian National Congress . The CPM members chopped off his hands and legs and ripped off the breasts of two women. [ 1 ] The mob chopped off the hands of seven villagers who voted for Congress. The case was filed at Amta police station and the arrested CPM men were released on bail. [ 2 ]
The victims allege that their hands were chopped off for supporting Congress, but they were neglected by the Congress party. [ 3 ] Anandabazar Patrika reports that the attacks were made with swords, rods and spear. 119 people were named in FIR. The accused killed Gopal Patra with swords and chopped off the breasts of one woman. Then they burned 100 huts in the village. [ 4 ]
In 2016, CPM leader Surjya Kanta Mishra mentioned that hand chopping was wrong, after CPM and Congress formed a political alliance against Trinamool Congress during the 2016 West Bengal Legislative Assembly election . [ 5 ]
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https://en.wikipedia.org/wiki/1991_Kandua_hand-chopping
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2,4,5-Trihydroxyamphetamine ( THA ) is a neurotoxin and a metabolite of MDMA . It comes from the ring-hydroxylation of 3,4-methylenedioxyamphetamine (MDA).
In one paper, it was shown to reduce hippocampal tryptophan hydroxylase activity by 54% after short-term treatment. [ 1 ] In another study, it was shown to significantly reduce striatal tyrosine hydroxylase activity. [ 2 ]
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https://en.wikipedia.org/wiki/2,4,5-Trihydroxyamphetamine
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2,4,5-Trihydroxymethamphetamine ( THMA or THM ) is a neurotoxin and a metabolite of MDMA . It has structural similarity to the dopamine neurotoxin 6-hydroxydopamine , and produces lasting serotonin deficits when administered centrally. [ 1 ] [ 2 ]
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https://en.wikipedia.org/wiki/2,4,5-Trihydroxymethamphetamine
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The Kousseri vaccination campaign took place between February 13 and 17 2008. During the campaign over 35,000 infants and children were vaccinated against measles , poliomyelitis or both in Cameroon 's north-eastern district of Kousséri , in an operation led by the Cameroon Ministry of Health, the United Nations , and non-governmental organizations (NGOs) , such as Médecins Sans Frontières – Switzerland (MSF-CH) .
The UN Resident Coordinator , Sophie de Caen, stated that this was in response to the influx of Chadian refugees into the northeast Cameroon earlier in February 2008, in the aftermath of the Battle of N'Djamena , as the potential for epidemics substantially increases whenever there are population movements.
Following fighting in the Chadian capital N'Djamena , which erupted on February 2, at least 30,000 Chadians crossed into Cameroon , reaching Kousséri in northeast Cameroon. Most found refuge in two temporary sites, while many others were hosted in schools, churches, and private homes, according to the United Nations.
The vaccination campaign targeted all children of applicable ages in Kousséri, ensuring protection for Cameroonian and refugee children alike. All children aged six months to 15 years were vaccinated against measles, and all children under 5, including newborns, were vaccinated against poliomyelitis.
Figures released on 21 February 2008 show that a total of 35,615 children were vaccinated against poliomyelitis, while 32,624 were vaccinated against measles. Vitamin A supplement tablets were also provided to approximately 34,000 children along with the vaccinations.
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https://en.wikipedia.org/wiki/2008_Kousseri_vaccination_campaign
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Events:
Topics:
The 2012 Veracruz murder of journalists is about the disappearance, murder and dismemberment of three journalists and a woman who worked in public relations whose bodies were discovered in Boca del Río , Veracruz , Mexico . [ 1 ] [ 2 ] Their bodies were recovered from a canal on World Press Freedom Day , or 3 May 2012, and showed signs of torture and mutilation, which prompted calls for investigations into links with organized crime. The gruesome murder followed other murders of members of the press in the Veracruz area and during the Mexican drug war , and highlighted the danger for working journalists. [ 3 ]
El Programa de Agravios a Periodistas y Defensores Civiles reported 580 incidents affecting the media from 2005 to May 2012, including 79 homicides, 14 missing journalists, and 26 recorded threats. [ 4 ] The number of reported incidents in Mexico has steadily increased over past years, reaching number eight in the Committee to Protect Journalists' (CPJ) impunity index. [ 5 ] Veracruz is well known for the Sinaloa and Zetas drug cartels. These two cartels fight for control of Boca del Río, Veracruz, making it one of the most dangerous Mexican states for the press. In a year and a half, six journalists were reported dead from this area. [ 6 ] The murders of Luna, Huge, Rodríguez, and Becerra brought the total to ten reported deaths.
On World Press Freedom Day, the bodies of Guillermo Luna Varela, Gabriel Huge Córdova, and Esteban Rodríguez, three photojournalists, were recovered from La Zamorana canal in Boca del Río. After not returning from covering a road incident, the families of Guillermo Luna and Gabriel Huge reported them missing. [ 7 ] Police found the dismembered bodies of Luna and Huge in a black plastic bag. They also recovered the bodies of Rodríguez and Irasema Becerra. Becerra and Luna were in a relationship, and she worked for a local newspaper firm.
Luna was a photographer who worked for Notiver and covered police-related stories. Six months prior to his death, he worked for the website Veracruznews , Voz del Sureste, and El Díario de Cardel. His police beat was in Xalapa and Boca del Río in Veracruz. His body was found in Boca del Río alongside his uncle, Huge, and also showed signs of torture. Luna was reported missing a day earlier by his family after not returning from covering a road accident. [ 8 ]
Huge's body displayed signs of torture and was found in a black bag with Luna, his nephew. He worked at Notiver as a photographer and he also worked for a radio station in Poza Rica. After three journalists of The Notiver were murdered the previous year, Huge fled from the city. When he returned, he worked as a freelancer. He disappeared on a Wednesday with Luna while covering a traffic incident. [ 9 ]
Rodríguez was a retired photojournalist and reporter who worked for the Diario AZ . He became a welder after his retirement. After the murder of fellow journalists at The Notiver , Rodríguez temporarily fled the state and retired, returning to Veracruz to work as a welder. [ 4 ]
A fourth body was later identified as Becerra, Luna's companion. While she was not a journalist, she worked for a local paper in public relations.
On Monday, 13 August, the Mexican Navy began to crack the case. "The Mexican Navy announced Monday that a man suspected of being a member of a drug gang had been captured while carrying the identification cards of a recently slain newspaper employee in the state of Veracruz. The authorities link the suspect, Juan Carlos Hernández Pulido, whom they captured Friday, to the killing of the newspaper employee, Irasema Becerra. Her dismembered remains were found in May along with those of three photojournalists." [ 10 ] [ 11 ]
Authorities searched the vehicle of Hernández, also known as "Bertha", when a suspicious individual was reported in a parking lot. In his vehicle, they found more than 150 bags of cocaine and marijuana, which he sold alongside illegal firearms. They also found documents and an ID belonging to Becerra, linking him to the Boca Del Rio homicide. He is accused of working for the Jalisco drug cartel as a hired murderer. [ 10 ] Hernández was not working alone.
Veracruz authorities closed the case 15 August and claimed members of a drug gang confessed to the murders. Some uncertainty about the finality of the case was presented. "But as soon as the arrests were announced on Wednesday, questions began to surface, beginning with the most obvious one. Why would the seven suspects, picked up on drug and weapons charges, spontaneously admit to far more serious crimes, in this case four brutal killings?" [ 12 ] [ 13 ] Nine journalists in the last 18 months have focused attention on the investigations in Veracruz.
Further investigation, along with coincidence, linked several other cases of homicide among journalists and their families. These linked cases are not linked to the Veracruz murder by perpetrator, but by similarities in the brutality of the homicides. The following are related homicide cases:
The murders of Luna, Huge, Rodríguez and Becerra heightened awareness of the dangers for journalists in the Veracruz area. Officials and organizations recognize the need to combat the violence of growing drug cartels. Efforts are made to further increase awareness, especially with outrage from UNESCO, Article 19, and other groups focused on the rights and safety of journalists .
Irina Bokova , director-general of UNESCO , expressed her concerned about the deaths of journalists in the Veracruz area. "News of the murders of Gabriel Huge and Guillermo Luna Varela – tortured and killed less than one week after the assassination of Regina Martínez Pérez – is deeply disturbing, and reflects an alarming state of affairs in the state of Veracruz," she said. [ 6 ]
The bodies of the Boca Del Rio journalists were found nearing World Press Freedom Day. Bokova said, “That these gruesome crimes have been committed on the eve of World Press Freedom Day – a day on which we honour the vital role played by journalists in upholding democratic values, protecting citizens’ rights to be informed and calling those in power to account – makes the situation all the more intolerable." [ 6 ]
Bokova continued in the statement to say, “I condemn these three murders in the strongest possible terms and urge the Mexican authorities to act quickly and decisively to find those responsible. Impunity is not an option."
Article 19 , a group focused on the freedom of expression and information, expressed their outrage of the Boca del Rio incident, "--the Mexican authorities have consistently failed to fulfill their international obligations to guarantee the free exercise of freedom of expression and the mechanisms currently in place do not address the central problem, which is the impunity that follows these crimes." [ 7 ] They also said the authorities of Veracruz did not take the necessary steps in resolving the case.
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https://en.wikipedia.org/wiki/2012_Boca_del_Río_murder_of_journalists
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The 2022 Timika killings or the Timika massacre, was the killing of four Nduga Papuans near the city of Timika , by members of the Indonesian Army and local civilians in August 2022. [ 1 ]
On 22 August 2022, Indonesian soldiers arrested Irian Nirigi, Arnold Lokbere, Atis Tini and Kelemanus Nirigi, for attempting to buy weapons from them in Timika. They shot them dead, dismembered their bodies and stuffed them in sacks which they then threw in the Pigapu river. [ 1 ] [ 2 ] [ 3 ] [ 4 ]
On August 26, the bodies were discovered in the Pigapu river not far from Timika. [ 2 ] Later Kelemanus Nirigi or Leman was identified as a weapons supplier for Egianus Kogoya TPNPB faction in Nduga, he was tasked with collecting munitions in Mimika. [ 5 ]
In August 2022, Mimika military police identified 10 anonymous suspects. From 29 August to 17 September 2022, 9 of the 10 suspects were arrested, four of them (Andre Pudjianto Lee, Dul Uman, Rafles Laksana, and Roy Marten Howay) being civilians, with Howay, an Ayamaru Papuan, having evaded capture and the other six being active soldiers, the soldiers being a captain (Dominggus Kainama), a major (Helmanto Fransiskus Dakhi), and four privates (Rahmat Amin Sese, Robertus Putra Clinsman, Pargo Rumbouw, and Rizky Oktaf Muliawan). [ 4 ] [ 6 ]
On 24 January 2023 a military court sentenced Dakhi to life imprisonment. [ 7 ] On 15 February 2023 another military court sentenced the other four of the six soldiers, two of them were sentenced to life and the other two were sentenced to 15 and 20 years respectively. [ 3 ] Dominggus Kainama died during incarceration on 24 December 2022 before being sentenced. [ 8 ]
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https://en.wikipedia.org/wiki/2022_Timika_killings
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The 21st Century Cancer Access to Life-Saving Early detection, Research and Treatment (ALERT) Act is a bill in the United States Congress to provide funding for cancer research. The bill, intended to modernize the National Cancer Act of 1971 , was introduced by Senators Edward M. Kennedy (sponsor of the original bill) and Kay Bailey Hutchison on March 26, 2009. [ 1 ] The bill has not yet been enacted into law. [ 2 ]
This United States Congress –related article is a stub . You can help Wikipedia by expanding it .
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https://en.wikipedia.org/wiki/21st_Century_Cancer_Access_to_Life-Saving_Early_detection,_Research_and_Treatment_Act
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2Blades is an agricultural phytopathology non-profit [ 1 ] [ 2 ] which performs research to improve durable genetic resistance in crops, [ 3 ] [ 4 ] [ 5 ] and funds other researchers to do the same. 2Blades was co-founded by Dr. Roger Freedman and Dr. Diana Horvath [ 6 ] in 2004. [ 7 ]
2Blades is partly funded by the Gatsby Charitable Foundation [ 3 ] [ 8 ] does its research at The Sainsbury Laboratory , [ 9 ] [ 10 ] among other locations [ which? ] . [ 10 ] One co-founder, Chairman Roger Freedman also works for Gatsby, which was founded by Lord David Sainsbury . [ 11 ] Freedman had pitched an idea to Sainsbury's venture capital company to begin investing in plant genetic engineering technologies, and although the board did so, they found someone else to lead it. [ 12 ] Freedman had wanted to run it, but was told that was not for him by Sainsbury. [ 12 ] Indeed, soon thereafter Sainsbury set up another early investment company specifically for Freedman and a colleague, and a separate non-profit for Freedman to grant money , both for plant science. [ 12 ] The non-profit was 2Blades. [ 12 ]
2Blades routinely works in partnership with other crop disease organizations like CIMMYT [ 4 ] and BGRI . [ 13 ] The foundation also conducts research in partnerships with the industry, including with Bayer CropScience [ 14 ] [ 15 ] [ 16 ] and Monsanto . [ 17 ] The organisation's End the Blight campaign has been joined by CIP (the International Potato Center ) [ 18 ] and Chairman of Joseph P. Kennedy Enterprises Christopher Kennedy . This campaign is advancing research and delivering cultivars specifically for Phytophthora infestans in Africa. Mr Kennedy is chairman of 2Blades African Potato Initiative which is funding the delivery of a Victoria -based cultivar to East African markets. [ 19 ]
Crops and pathogens of research interest to the foundation include P. infestans on potato , [ 20 ] rye , [ 21 ] Phakopsora pachyrhizi on soybean , [ 14 ] [ 17 ] Puccinia graminis f. sp. tritici on wheat , [ 22 ] and Fusarium oxysporum f.sp. cubense on Musa spp. [ 23 ]
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https://en.wikipedia.org/wiki/2Blades
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3,4-Dihydroxymethamphetamine ( HHMA , 3,4-DHMA ), or 3,4-dihydroxy- N -methylamphetamine , also known as α-methylepinine or α, N -dimethyldopamine , is the major metabolite of 3,4-methylenedioxy- N -methylamphetamine (MDMA). [ 1 ] [ 2 ] [ 3 ] It is formed from MDMA by O - demethylation via cytochrome P450 enzymes including CYP2D6 as well as CYP1A2 and CYP3A4 . [ 1 ] [ 3 ] Like MDMA, HHMA is a monoamine releasing agent . [ 4 ]
Along with 3,4-dihydroxyamphetamine (HHA; α-methyldopamine), HHMA may be involved in the serotonergic neurotoxicity of MDMA. [ 1 ] [ 5 ] [ 6 ] [ 3 ] However, findings in this regard are conflicting, and the neurotoxicity of MDMA and related agents may instead be based on their mechanism of action without involvement of metabolites. [ 3 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ]
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https://en.wikipedia.org/wiki/3,4-Dihydroxymethamphetamine
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3,4-Dihydroxyphenylglycolaldehyde ( DOPEGAL ), also known as 3,4-dihydroxymandelaldehyde ( DHMAL ) as well as norepinephrine aldehyde or epinephrine aldehyde , is a metabolite of the monoamine neurotransmitters norepinephrine and epinephrine . DOPEGAL is a noradrenergic neurotoxin . [ 1 ]
DOPEGAL is formed by monoamine oxidase (MAO) via oxidative deamination . [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ] Following its formation, DOPEGAL is metabolized . Through the metabolism process, it is converted into 3,4-dihydroxymandelic acid (DHMA) via aldehyde dehydrogenase (ALDH), or into 3,4-dihydroxyphenylglycol (DHPG) via aldehyde reductase (ALR). [ 2 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ]
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https://en.wikipedia.org/wiki/3,4-Dihydroxyphenylglycolaldehyde
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3,4-Methylenedioxyamphetamine ( MDA ) is an entactogen , stimulant , and psychedelic drug of the amphetamine and MDxx families that is encountered mainly as a recreational drug . [ 3 ] In its pharmacology , MDA is a serotonin–norepinephrine–dopamine releasing agent (SNDRA). In most countries, the drug is a controlled substance and its possession and sale are illegal.
MDA is rarely sought as a recreational drug compared to other amphetamines ; however, it remains widely used due to it being a primary metabolite, [ 4 ] the product of hepatic N -dealkylation, [ 5 ] of MDMA . It is also a common adulterant of illicitly produced MDMA. [ 6 ] [ 7 ]
MDA is bought, sold, and used as a recreational drug due to its enhancement of mood and empathy . [ 8 ] A recreational dose of MDA is sometimes cited as being between 100 and 160 mg. [ 9 ] It produces MDMA -like effects, including entactogen and psychedelic effects. [ 2 ] [ 9 ] [ 10 ]
MDA currently has no accepted medical use.
Side effects of MDA include sympathomimetic effects like increased heart rate and blood pressure as well as increased cortisol and prolactin levels. [ 2 ] [ 10 ]
Symptoms of acute toxicity may include agitation , sweating, increased blood pressure and heart rate , dramatic increase in body temperature , convulsions , and death. Death is usually caused by cardiac effects and subsequent hemorrhaging in the brain ( stroke ). [ 11 ] [ medical citation needed ]
MDA is a substrate of the serotonin , norepinephrine , dopamine , and vesicular monoamine transporters , and in relation to this, acts as a reuptake inhibitor and releasing agent of serotonin , norepinephrine , and dopamine (that is, it is an SNDRA Tooltip serotonin–norepinephrine–dopamine releasing agent ). [ 23 ] It is also an agonist of the serotonin 5-HT 2A , [ 24 ] 5-HT 2B , [ 25 ] and 5-HT 2C receptors [ 26 ] and shows affinity for the α 2A - , α 2B - , and α 2C -adrenergic receptors and serotonin 5-HT 1A and 5-HT 7 receptors . [ 27 ]
In addition to its actions as a monoamine releasing agent, MDA is a potent high- efficacy partial agonist or full agonist of the rodent TAAR1. [ 21 ] [ 22 ] Conversely, MDA is much weaker in terms of potency as an agonist of the human TAAR1. [ 21 ] [ 22 ] [ 28 ] Moreover, MDA acts as a very weak partial agonist or antagonist of the human TAAR1 rather than as an efficacious agonist. [ 21 ] [ 22 ] TAAR1 activation is thought to auto-inhibit and constrain the effects of amphetamines that act as TAAR1 agonists, for instance MDMA in rodents. [ 29 ] [ 30 ] [ 31 ] [ 32 ]
The ( S )- optical isomer of MDA is more potent than the ( R )- optical isomer as a psychostimulant, possessing greater affinity for the three monoamine transporters . [ citation needed ] MDA and its enantiomer ( R )-MDA substitute for the psychedelics LSD and DOM in rodent drug discrimination tests. [ 33 ] MDA and ( R )-MDA produce the head-twitch response , a behavioral proxy of psychedelic -like effects, in rodents. [ 33 ] However, the head–twitch response they produce is very weak in magnitude compared to other related psychedelics such as the DOx drugs. [ 33 ] On the other hand, the response is more similar in magnitude to that of Ariadne . [ 33 ]
In terms of the subjective and behavioral effects of MDA, it is thought that serotonin release is required for its empathogenic effects, dopamine release is required for its euphoriant ( rewarding and addictive ) effects, dopamine and norepinephrine release is required for its psychostimulant effects, and direct agonism of the serotonin 5-HT 2A receptor is required for its mild psychedelic effects. [ medical citation needed ]
MDA can produce serotonergic neurotoxic effects in rodents, [ 34 ] [ 35 ] which might in part be due to transformation into MDA followed by subsequent metabolism . [ 5 ] In addition, MDA activates a response of the neuroglia , though this subsides after use. [ 34 ]
The pharmacokinetics of MDA have been studied. [ 2 ] [ 42 ] Its duration of action has been reported to be about 6 to 8 hours. [ 9 ] The duration of MDA is longer than that of MDMA, about 8 hours for MDA versus 6 hours for MDMA. [ 2 ] [ 42 ] The elimination half-life of MDA is 10.9 hours. [ 2 ] Differences in the duration of MDA versus MDMA may be due pharmacodynamics rather than pharmacokinetics. [ 2 ] [ 42 ]
MDA is a substituted methylenedioxylated phenethylamine and amphetamine derivative . In relation to other phenethylamines and amphetamines, it is the 3,4-methylenedioxy, α-methyl derivative of β-phenylethylamine , the 3,4-methylenedioxy derivative of amphetamine , and the N - desmethyl derivative of MDMA.
In addition to 3,4-methylenedioxyamphetamine , MDA is also known by other chemical synonyms such as the following:
MDA is typically synthesized from essential oils such as safrole or piperonal . Common approaches from these precursors include:
MDA may be quantitated in blood, plasma or urine to monitor for use, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Some drug abuse screening programs rely on hair, saliva, or sweat as specimens. Most commercial amphetamine immunoassay screening tests cross-react significantly with MDA and major metabolites of MDMA, but chromatographic techniques can easily distinguish and separately measure each of these substances. The concentrations of MDA in the blood or urine of a person who has taken only MDMA are, in general, less than 10% those of the parent drug. [ 52 ] [ 53 ] [ 54 ]
MDA constitutes part of the core structure of the β-adrenergic receptor agonist protokylol .
MDA was first synthesized by Carl Mannich and W. Jacobsohn in 1910. [ 46 ] It was first taken in July 1930 by Gordon Alles at a total dose of 126 mg, who experienced hallucinogenic effects, well-being and euphoria , and peripheral effects. [ 55 ] [ 56 ] [ 57 ] However, he did not subsequently describe these effects until 1959. [ 58 ] [ 55 ] [ 56 ] Alles later licensed the drug to Smith, Kline & French . [ 57 ] MDA was first used in animal tests in 1939, and human trials began in 1941 in the exploration of possible therapies for Parkinson's disease . From 1949 to 1957, more than five hundred human subjects were given MDA in an investigation of its potential use as an antidepressant and/or anorectic by Smith, Kline & French . The United States Army also experimented with the drug, code named EA-1298, while working to develop a truth drug or incapacitating agent. Harold Blauer died in January 1953 after being intravenously injected, without his knowledge or consent, with 450 mg of the drug as part of Project MKUltra . MDA was patented as an ataractic by Smith, Kline & French in 1960, and as an anorectic under the trade name "Amphedoxamine" in 1961. MDA began to appear on the recreational drug scene around 1963 to 1964. It was then inexpensive and readily available as a research chemical from several scientific supply houses. Several researchers, including Claudio Naranjo and Richard Yensen, have explored MDA in the field of psychotherapy . [ 59 ] [ 60 ]
The International Nonproprietary Name (INN) tenamfetamine was recommended by the World Health Organization (WHO) in 1986. [ 61 ] It was recommended in the same published list in which the INN of 2,5-dimethoxy-4-bromoamphetamine (DOB), brolamfetamine, was recommended. [ 61 ] These events suggest that MDA and DOB were under development as potential pharmaceutical drugs at the time. [ 61 ] The Multidisciplinary Association for Psychedelic Studies (MAPS) was also founded in 1986. [ 62 ]
Matthew J. Baggott and colleagues conducted some of the first modern clinical studies of MDA in humans and published their findings in the 2010s. [ 2 ] [ 9 ] [ 10 ]
When MDA was under development as a potential pharmaceutical drug, it was given the International Nonproprietary Name (INN) of tenamfetamine . [ 63 ]
MDA is schedule 9 prohibited substance under the Poisons Standards . [ 64 ] A schedule 9 substance is listed as a "Substances which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities." [ 64 ]
MDA is a Schedule I controlled substance in the US.
In 2010, the ability of MDA to invoke mystical experiences and alter vision in healthy volunteers was studied. The study concluded that MDA is a "potential tool to investigate mystical experiences and visual perception". [ 9 ]
A 2019 double-blind study administered both MDA and MDMA to healthy volunteers. The study found that MDA shared many properties with MDMA including entactogenic and stimulant effects, but generally lasted longer and produced greater increases in psychedelic-like effects like complex imagery, synesthesia , and spiritual experiences . [ 2 ]
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https://en.wikipedia.org/wiki/3,4-Methylenedioxyamphetamine
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3-Methylmethcathinone (3-MMC) , also known as metaphedrone , [ 4 ] is a designer drug from the substituted cathinone family. 3-MMC is a monoamine transporter substrate (a substance acted upon by monoamine transporters in the brain) that potently releases and inhibits the reuptake of dopamine and norepinephrine , as well as displaying moderate serotonin releasing activity. [ 5 ] [ 6 ]
3-Methylmethcathinone is a structural isomer of mephedrone (4-methylmethcathinone), and as such is illegal via blanket bans in many countries that have banned mephedrone. However, 3-MMC has still appeared on the recreational drug market as an alternative to mephedrone, and was first identified being sold in Sweden in 2012. [ 7 ] Unlike some other synthetic cathinones, 3-MMC has been evaluated in at least one large mammal study. [ 2 ]
3-MMC was first encountered in Sweden in 2012; [ 8 ] it was created as a designer drug following the control in many countries of the related compound mephedrone . It was sold as a research chemical, usually in powdered form. There is no known or reported medical use of 3-MMC; it is primarily used recreationally.
Side effects of 3-MMC include increased heart rate , increased blood pressure , and decreased appetite . [ 9 ]
A total of 27 fatalities with at least some exposure to 3-MMC have been confirmed as of March 2022. 18 of the 27 reported fatalities involved multiple drugs of abuse, usually opioids and uppers ( "speedballs" ). [ 10 ] Of the 13 cases that specified gender, 12 deaths were male and 1 death was female. Of the 7 males whose age was reported, the median age was 27. The fatalities see a wide range of blood concentrations, from 249 to 1600 ng/mL. [ 11 ] The route of administration in any of these fatalities is not clear.
Of the presumably nine monointoxication deaths involving only 3-MMC that have occurred, two monointoxication cases were reported in the Netherlands and one was reported in France . The death in France was determined to be an accidental overdose . In addition, there has been 291 reported cases of non-fatal 3-MMC intoxications. 213 of these cases (75%) were reported in Poland alone, and 50 cases (17%) were reported in Sweden.
The toxicokinetics of 3-MMC are thought to be similar to those for mephedrone. The first human study conducted in 14 healthy human volunteers concluded that "...low to moderate doses of 3-MMC were well tolerated and safe and that potential health risks might only occur at high or excessive doses of 3-MMC." [ 12 ]
3-MMC potently inhibits the reuptake of monoamines in the human norepinephrine (NET) and dopamine ( DAT ) transporters. It also acts as a triple releasing agent of dopamine, serotonin, and norepinephrine, similar to many other cathinones . As a releasing agent, it is more selective for dopamine and especially norepinephrine , suggesting that it has stronger amphetamine-like stimulant properties compared to mephedrone or MDMA . [ 5 ]
3-MMC also binds to serotonin 5-HT1A , 5-HT2A , 5-HT2C receptors and adrenergic α1A and α2A receptors. [ 13 ] It binds much more strongly to the adrenergic receptors than the serotonergic 5-HT receptors, although it still retains significant serotonin-releasing activity (292 nM in one study). Other receptor interaction data have also been reported. [ 14 ] In contrast to mephedrone, 3-MMC is inactive as a serotonin 5-HT 2A receptor agonist. [ 14 ]
3-MMC is inactive as an agonist of the rat and human TAAR1 ( EC 50 Tooltip half-maximal effective concentration = >10,000 nM). [ 15 ] Conversely, it is a low-potency weak partial agonist of the mouse TAAR1 ( EC 50 = 3,800 nM, E max Tooltip maximal efficacy = 25%). [ 15 ]
The oral bioavailability of 3-methylmethcathinone was determined at 7% [ 2 ] in one pig study, with peak blood concentrations (T max ) attained within 5 to 10 minutes, and a relatively short half-life of 50 minutes. Concentration in blood plasma dropped below detectability 24 hours after oral ingestion. Decreased feeding behavior resulted in weight loss for some.
The metabolism of 3-MMC is not well-described. Known metabolites include 3-methylephedrine and 3-methylnorephedrine. A possible metabolic pathway is β-keto-reduction followed by N - demethylation . [ 17 ]
3-Methylmethcathinone's IUPAC name is 2-(methylamino)-1-(3-methylphenyl)propan-1-one). It is
one of many synthetic cathinones, designer drugs related to amphetamines . It is a structural isomer of mephedrone , and controlled as such. It can also be seen as the β-keto analog of 3-methylmethamphetamine
3-MMC contains a chiral center at the C-2 carbon. Therefore, two enantiomers exist, the R and S enantiomer. It is assumed that the S form is more potent due to its similarity to cathinone, but further research is needed to confirm this. [ 18 ]
There are several ways to synthesize 3-MMC. One route adapted from Power et al. [ 19 ] is to add ethylmagnesium bromide to 3-methylbenzaldehyde (I) to form the product 1-(3-methylphenyl)-1-propanol (II). This product is then oxidized by pyridinium chlorochromate (PCC) on silica gel to the ketone (III) and brominated with hydrobromic acid to yield the bromoketone (IV). This bromoketone is reacted with ethanolic methylamine to produce the 3-MMC free base (V), which can be converted to the hydrochloride salt (VI) by addition of ethereal hydrogen chloride (VI). [ 19 ]
As with mephedrone , users of 3-MMC typically report effects such as an elevated mood , pleasant body sensations, feelings of love and empathy , euphoria , greater appreciation of music, heightened libido , and increased confidence and sociability. [ 20 ]
Adverse effects range from aggression, dry mouth , and jaw clenching , to more serious effects such as hyponatremia , seizures , hyperthermia and rhabdomyolysis . [ 20 ] [ 8 ]
Due to its fleeting duration and dopaminergic effects, 3-MMC is highly addictive and commonly abused. Repeated dosing within a sitting is typical, sometimes using different routes, primarily oral and intranasal . Common self-reported doses range from 50 to 150 mg, up to single 500 mg doses. Intranasal administration, or snorting, is the most common route of administration , followed by oral administration, followed by other routes, such as rectal administration and injection into the bloodstream.
Users may dose repeatedly in order to extend the drugs duration, leading to 0.5—2 gram "sessions" that can span an evening. Single-dose effects last from 30 to 60 minutes, typically peaking around 10-minutes post-dose. In a questionnaire-based study of self-reported 3-MMC users in Slovenia , it was found that 88% of users insufflated the drug while 42% took it orally. The study did not find any instances of users injecting 3-MMC. Moreover, 26% of the users reported taking more than 1.5 grams of 3-MMC in a single sitting and over 50% reported having consumed more than 0.5 grams in a single sitting. [ 21 ]
3-Methylmethcathinone is commonly encountered as a white/off-white crystalline or pasty solid. It can be found sold in capsules. It is assumed to be a racemic mixture like mephedrone.
In the United States, 3-MMC is illegal as a positional isomer of the controlled substance mephedrone [ 22 ] It was explicitly designated as a controlled substance on 13 December 2023. [ 23 ]
Since October 2015, 3-MMC is a controlled substance in China . [ 24 ]
3-MMC is banned in the Czech Republic . [ 25 ]
3-MMC was not banned in 2016 by the United Nations Office on Drugs and Crime (UNODC) after a critical review. [ 26 ] However, following its subsequent abuse beginning in 2019, this decision was overturned and it was placed into schedule II of the 1971 convention in March 2023. [ 1 ]
Effective 28 October 2021, 3-MMC has been scheduled under the Dutch Opium Law and is therefore illegal in the Netherlands . [ 27 ]
3-MMC was given narcotic status in India on 8 February 2024.
3-MMC is under development for use as a pharmaceutical drug in the potential treatment of dyskinesias . [ 28 ] As of August 2023, it is in preclinical research for this indication. [ 28 ] The drug is being developed by Clearmind Medicine. [ 28 ]
3-MMC is currently being developed as a medicine by the American biotech company MindMed . They have filed for a patent to use 3-MMC for problems such as social anxiety disorder , post-traumatic stress disorder (PTSD), and as an adjunct in couples therapy . [ 29 ]
3-MMC is also undergoing clinical trials for its use in treating menstrual symptoms. [ 30 ] A successful trial has been completed in the University of Maastricht . These efforts are led by the small Dutch company Period Pill. [ 31 ] The company has filed for patent coverage in Canada , Mexico , Croatia , the United States , Morocco , Japan , Brazil , Poland , Hungary , and Korea .
The first in-human clinical study of 3-MMC was published in December 2024. [ 9 ]
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https://en.wikipedia.org/wiki/3-Methylmethcathinone
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3Shape is a developer and manufacturer of 3D scanners and CAD/CAM software for the dental and audio industries based in Copenhagen , Denmark . [ 1 ] The company has production facilities and offices in China , Europe , Latin America and the USA .
The underlying technology was developed by Tais Clausen in connection with his master thesis at Technical University of Denmark . He teamed up with Copenhagen Business School graduate student Nikolaj Deichmann, founding the company in 2000. [ 2 ] The company has been named “Entrepreneur of the Year” by Ernst & Young three times. [ 3 ] Flemming Thorup was CEO of the company from 2002 to 2017.
3Shape has been the recipient of the Cellerant Best in Class award for 2015, [ 4 ] 2016, [ 5 ] and 2017. [ 6 ]
This Danish corporation or company article is a stub . You can help Wikipedia by expanding it .
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https://en.wikipedia.org/wiki/3Shape
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4-Fluoroephedrine ( 4-FEP ) is a "novel psychoactive substance" and substituted β-hydroxyamphetamine derivative related to ephedrine . [ 1 ] [ 2 ] [ 3 ]
Similarly to other amphetamines , 4-fluoroephedrine acts as a monoamine reuptake inhibitor and monoamine releasing agent . [ 3 ] [ 4 ] It specifically acts as a selective norepinephrine releasing agent . [ 3 ] [ 4 ] In contrast to many other amphetamines, but similarly to most cathinones , 4-fluoroephedrine lacks affinity for the human trace amine-associated receptor 1 (hTAAR1). [ 3 ] [ 4 ] [ 5 ]
4-Fluoroephedrine, also known as 4-fluoro-β-hydroxy- N -methylamphetamine, is a substituted phenethylamine , amphetamine , and β-hydroxyamphetamine derivative . [ 6 ] [ 1 ] It is the 4- fluoro analogue of ephedrine . [ 6 ] [ 1 ]
The synthesis of 4-fluoroephedrine has been described. [ 7 ]
It can serve as a precursor in the synthesis of 4-fluoromethamphetamine (4-FMA). [ 3 ]
The predicted log P ( XLogP3 ) of 4-fluoroephedrine is 1.0. [ 6 ] For comparison, the predicted log P of ephedrine is 0.9. [ 8 ]
4-Fluoroephedrine was first described in the scientific literature by 1991. [ 7 ] The next mention of it in the literature was in 2013, when it was identified as a "novel psychoactive substance". [ 9 ] The pharmacology of 4-fluoroephedrine was characterized in 2015. [ 3 ] [ 4 ]
4-Fluoroephedrine is known to be a metabolite of 4-fluoromethcathinone (4-FMC; flephedrone). [ 10 ] [ 11 ]
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https://en.wikipedia.org/wiki/4-Fluoroephedrine
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5-Hydroxyindoleacetaldehyde ( 5-HIAL ), also known as 5-hydroxytryptaldehyde or as serotonin aldehyde , is an inactive metabolite and metabolic intermediate of the monoamine neurotransmitter serotonin (5-hydroxytryptamine; 5-HT). [ 2 ] [ 3 ] [ 1 ]
5-HIAL is formed from serotonin by oxidative deamination via monoamine oxidase (MAO). [ 2 ] [ 3 ] MAO-mediated deamination is the primary metabolic pathway of serotonin inactivation. [ 2 ] Monoamine oxidase A (MAO-A) has about 120-fold higher affinity for serotonin than monoamine oxidase B (MAO-B). [ 2 ] In relation to this, MAO-A is the main isozyme of MAO involved in serotonin degradation. [ 2 ]
Following its formation, 5-HIAL is metabolized by aldehyde dehydrogenase (ALDH) to form 5-hydroxyindoleacetic acid (5-HIAA). [ 2 ] [ 3 ] 5-HIAL can also be converted into small amounts of 5-hydroxytryptophol (5-HTOL; also known as 5-hydroxyindolethanol or 5-HIET) by either aldehyde reductase (ALR/ALDR) or alcohol dehydrogenase (ADH). [ 2 ] [ 4 ] However, brain concentrations of 5-HTOL are only 1 to 5% of those of 5-HIAA. [ 2 ] [ 4 ]
Use of ethanol (alcohol) can dramatically increase 5-HTOL formation by inhibiting ALDH and enhancing ADH activity. [ 2 ] [ 5 ] As a result, the ratio of 5-HTOL to 5-HIAA is a sensitive and reliable marker of recent ethanol ingestion and has been suggested for use in clinical and forensic contexts. [ 2 ] [ 5 ]
Besides oxidative deamination by MAO into 5-HIAL, serotonin can also be conjugated by glucuronidation via glucuronyltransferases , conjugated by sulfation via sulfotransferases , acetylated and then methylated into melatonin ( N -acetyl-5-methoxytryptamine) (which occurs mainly in the pineal gland ), and converted into certain other metabolites like 5-hydroxyindole thiazoladine carboxylic acid (5-HITCA). [ 2 ] However, these secondary metabolic pathways appear to play only a minor role in serotonin metabolism. [ 2 ]
5-HIAL has been implicated in producing neurotoxicity and in the development and progression of neurodegenerative diseases . [ 6 ] [ 7 ] [ 8 ]
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https://en.wikipedia.org/wiki/5-Hydroxyindoleacetaldehyde
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The Bauer 5GBioShield , usually shortened to 5GBioShield , is a fraudulent device which was claimed to protect against radiation from 5G mobile networks. The device was invented by clinical pharmacist Jacques Bauer and former scientist Ilija Lakicevic and marketed by alternative medicine activist Sacha Stone . The product, which was sold for approximately £330 through an affiliate marketing scheme, was found to be composed of a normal USB thumb drive and a sticker. As of April 26, 2022, The official website is no longer online. British Trading Standards officials determined that the device was a scam. [ 1 ]
The manufacturers claim that:
"Through a process of quantum oscillation the 5G BioShield USB Key balances and reharmonizes the disturbing frequencies arising from the electric fog induced by devices, such as laptops, cordless phones, wifi, tablets, etc." [ 2 ]
The device is simply a common USB thumb drive containing marketing documents and usage instructions. The USB device is housed in a clear perspex block imprinted with a stylized version of St George slaying a dragon, as based on a medal originally made by William Wyon for Albert, Prince Consort . [ 3 ]
Lakicevic, the co-inventor of the product, describes the device as containing a "new energy" embedded in a sticker, and that the USB stick is merely a carrier and need not be powered on to work. Lakicevic's claims regarding this product were published in an issue of the International Journal of Science and Research (ITNJ), a pay-to-publish science journal with no peer review processes in place. [ 4 ]
The device was recommended in a report published by Glastonbury Town Council. [ 5 ] Town councillor Toby R. Hall stated that the device could be "helpful" and "provide protection" due to a "wearable holographic nano-layer catalyser". [ 6 ]
An analysis by Pen Test Partners, however, concluded that this device was nothing more than a 128 megabyte capacity generic USB thumb drive. [ 7 ] The security firm concluded that the device "should [not] be promoted by publicly-funded bodies". [ 3 ]
Following this report, the device was investigated by Trading Standards and found to be a scam and the matter had been referred to City of London Police Fraud Squad. [ 1 ]
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https://en.wikipedia.org/wiki/5GBioShield
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5β-Pregnane , also known as 17β-ethyletiocholane or as 10β,13β-dimethyl-17β-ethyl-5β-gonane , is a steroid and a parent compound of a variety of steroid derivatives . [ 1 ] It is one of the epimers of pregnane , the other being 5α-pregnane . Derivatives of 5β-pregnane include the naturally occurring steroids 5β-dihydroprogesterone , pregnanolone , epipregnanolone , pregnanediol , and pregnanetriol , and the synthetic steroids hydroxydione , renanolone , ORG-20599 , and SAGE-217 . These derivatives include metabolites of progesterone and endogenous and synthetic neurosteroids . [ citation needed ]
This article about a steroid is a stub . You can help Wikipedia by expanding it .
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https://en.wikipedia.org/wiki/5β-Pregnane
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340273
77706
ENSG00000004846
ENSMUSG00000072791
Q2M3G0
B5X0E4
NM_001163941 NM_001163942 NM_001163993 NM_178559
NM_029961
NP_001157413 NP_001157414 NP_001157465 NP_848654
NP_084237
ATP-binding cassette sub-family B member 5 also known as P-glycoprotein ABCB5 is a plasma membrane-spanning protein that in humans is encoded by the ABCB5 gene . [ 5 ] [ 6 ] ABCB5 is an ABC transporter and P-glycoprotein family member principally expressed in physiological skin and human malignant melanoma . [ 7 ] [ 8 ] [ 9 ]
ABCB5 has been suggested to regulate skin progenitor cell fusion and mediate chemotherapeutic drug resistance in stem-like tumor cell subpopulations in human malignant melanoma, colorectal cancer, and malignant pleural mesothelioma. It is commonly over-expressed on circulating melanoma tumour cells. [ 10 ] [ 11 ] Furthermore, the ABCB5+ melanoma- initiating cells were demonstrated to express FLT1 ( VEGFR1 ) receptor tyrosine kinase which was functionally required for efficient xenograft tumor formation, as demonstrated by shRNA knockdown experiments. [ 12 ]
In colorectal cancer, ABCB5 was shown to act as a mediator of 5-FU patient chemoresistance, and had a further direct role in tumorigenesis shown by shRNA-mediated colorectal cancer cell-line ABCB5 knockdowns that impeded tumorigenesis in human-to-mouse xenografts. [ 13 ] It has been shown that in some highly aggressive tumors, such as mesothelioma and melanoma, ABCB5 contributes to multi-drug chemotherapy resistance, and tumor growth, controlling a proinflammatory signaling circuit utilizing TLR4 , IL-1β , IL8 and CXCR1 signaling involving reciprocal paracrine interactions between the cancer stem cells and tumor bulk population (in a rheostat manner termed "cancer stem cell rheostasis "). [ 14 ] [ 15 ] ABCB5 was shown to maintain the slow-cycling melanoma stem cells using this cytokine signaling loop, which became more differentiated upon ABCB5 interference (e.g. WFDC1 melanocyte differentiation marker increased, cancer cells were faster growing in vitro , tumors were more pigmented), or CXCR1 blockade (slow-cycling ABCB5+ cells entered the cell-cycle). [ 15 ]
In normal physiology, ABCB5 is a functional marker for adult limbal stem cells of the cornea . ABCB5+ cells could regrow a human cornea on a mouse with limbal stem cell deficiency (LSCD - a blindness disease of the corneal limbus ) while ABCB5- cells could not, indicating a therapeutic potential for treating some types of blindness. ABCB5 was further shown to be anti-apoptotic in these adult stem cells. [ 16 ]
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https://en.wikipedia.org/wiki/ABCB5
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ABCD rating , also called the Jewett staging system or the Whitmore-Jewett staging system , is a staging system for prostate cancer that uses the letters A , B , C , and D .
This oncology article is a stub . You can help Wikipedia by expanding it .
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https://en.wikipedia.org/wiki/ABCD_rating
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ABM Abdullah (born 1954) is a Bangladeshi physician, academic and was the personal physician of the former Prime Minister of Bangladesh , Sheikh Hasina . [ 1 ] He was a professor in the Department of Internal Medicine and dean of the Faculty of Medicine at Bangabandhu Sheikh Mujib Medical University . [ 2 ] He currently works as a Medicine Specialist at Central Hospital Limited, Dhanmondi. [ 3 ] He was awarded the Ekushey Padak in 2016 by the Government of Bangladesh . [ 4 ]
This medical article is a stub . You can help Wikipedia by expanding it .
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https://en.wikipedia.org/wiki/ABM_Abdullah
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ABO-incompatible (ABOi) transplantation is a method of allocation in organ transplantation that permits more efficient use of available organs regardless of ABO blood type , which would otherwise be unavailable due to hyperacute rejection . [ 1 ] [ 2 ] Primarily in use in infants and young toddlers, research is ongoing to allow for increased use of this capability in adult transplants. Normal ABO-compatibility rules may be observed for all recipients. [ 2 ] This means that anyone may receive a transplant of a type-O organ, and consequently, type-O recipients are one of the biggest beneficiaries of ABO-incompatible transplants. [ 2 ] While focus has been on infant heart transplants, the principles generally apply to other forms of solid organ transplantation. [ 3 ]
Because very young children (generally under 12 months, but often as old as 24 months [ 3 ] ) do not have a well-developed immune system , [ 4 ] it is possible for them to receive organs from otherwise incompatible donors. This is known as ABO-incompatible (ABOi) transplantation. During the initial study period of 1996–2001, allowing for ABOi heart transplantation reduced infant mortality from 58% to 7%. [ 4 ] Graft survival and patient mortality is approximately the same between ABOi and ABOc recipients. [ 1 ] [ 5 ] [ 6 ] This was found to not only allow for better allocation of organs among donors, but improved graft ischemia by reducing the time required to transport organs to prospective patients. [ 1 ] Children are more likely to be listed for ABOi transplantation if they are UNOS status 1A (i.e. the most critical category.) [ 7 ]
The most important factors are that the recipient not have produced isohemagglutinins , and that they have low levels of T cell-independent antigens . [ 4 ] [ 8 ] Studies have shown that the period under which a recipient may undergo ABOi transplantation may be prolonged by exposure to nonself A and B antigens. [ 9 ] Furthermore, should the recipient (for example, type B-positive with a type AB-positive graft) require eventual retransplantation, the recipient may be medically capable of receiving a new organ of either blood type. [ 3 ] [ 10 ]
In the United States, UNOS policies allow for ABOi transplantation in children under two years of age if isohemagglutinin titers are 1:4 or below, [ 10 ] [ 11 ] and if there is no matching ABO-compatible (ABOc) recipient, [ 7 ] [ 10 ] [ 11 ] UNOS is considering relaxation of the infant heart transplantation policy such that ABO matching is not a consideration for children under 1 year of age, and if titers are 1:16 or below for children up to age 2. [ 12 ] Canadian centers have a heart transplantation policy matching the proposed policy in the United States. [ 3 ]
Intentional ABOi heart transplantation in infants was conceived in the 1960s by Adrian Kantrowitz , [ 13 ] with clinical evidence first being shown by Leonard L. Bailey 's team in the mid-1980s, which he termed " immunologic privilege ." [ 14 ] It was first conducted in practice in 1996 by a team led by Dr. Lori J. West [ 15 ] at the Hospital for Sick Children in Toronto , and published in a seminal 2001 study. [ 16 ] In the United Kingdom, policy since 2000 is that ABOi heart transplantation is de rigueur for infants, and is considered for children under age 4, though proactive measures are often taken to lower titer levels. [ 17 ]
Limited success has been achieved in ABOi heart transplantation in adults, [ 18 ] though this requires that the adult recipients have low levels of anti-A or anti-B antibodies. [ 18 ] Some organs are more conducive to adult ABOi transplant than others, such as the liver [ 6 ] and kidneys . [ 2 ] [ 19 ] Adults are significantly likely to suffer from hyperacute rejection, [ 1 ] thrombosis , or death , but could be considered to be an acceptable risk if the alternative is death. [ 6 ] In the case of ABOi renal transplantation, aggressive antibody removal is required, along with supplemental medication, with the resulting condition being termed "accommodation." [ 10 ] While such recipients are more likely to require re-transplantation early on, long-term graft survival is similar to recipients who receive ABOc kidneys. [ 19 ]
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https://en.wikipedia.org/wiki/ABO-incompatible_transplantation
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ACE mixture is an historical anaesthetic agent for general anaesthesia . It was first suggested by George Harley [ 1 ] and first used in England around 1860. In 1864 it was recommended for use by the Royal Medical and Surgical Society's Chloroform Committee . It was rarely used after the 19th century, except in Germany, where it was used for slightly longer. [ 2 ]
It was a mixture of alcohol , chloroform and ether [ 1 ] [ 3 ] which gives the mixture its name. Its effects were said to be between that of chloroform and ether and it was used when ether alone was contraindicated. [ 1 ] Its boiling point was given as 48 °C (118 °F). [ 4 ] Its actual safety margin over its components alone was marginal. [ 5 ] [ 6 ]
ACE mixture was most commonly made up in the ratio: 1 part alcohol, 2 parts chloroform, and 3 parts ether [ 2 ] although other ratios existed. See ' other preparations ' below.
Chloroform (which was first used in 1847) used on its own produces myocardial depression, however the excitatory properties of the alcohol and ether contained with the chloroform in the ACE mixture was believed to reduce this. [ 2 ] However, some did question this experimentally at the time. [ 7 ]
Many anesthetists favored ACE mixture and one author in 1887 in the British Medical Journal considers the ACE mixture, at the time, the best anesthesia for general use and use in childbirth . He states one downside; the " excited " state of patients on regaining consciousness after the anesthetic, due to the alcohol in the mixture. [ 8 ] Another downside of the mixture, as with most anesthetics at the time, was its high flammability . [ 9 ]
Deaths have been known to occur from the mixture. [ 5 ] [ 10 ] However, fewer deaths from ACE mixture were reported than deaths from chloroform or ether. [ 6 ] [ 11 ]
After widespread use of ACE mixture, anaesthetists would try different mixtures for different patients and different procedures. CE mixture omitted the alcohol and AC mixture omitted the ether. [ 1 ] One doctor described using equal parts alcohol and chloroform in minor operations, but chloroform with Eau de Cologne (which has a high alcohol content) in dental procedures for a more pleasant experience. [ 12 ]
Despite the similar names, the anaesthetic mixture named "bichloride of methylene" did not contain the actual compound that would be called bichloride of methylene (Dichloromethane CH 2 Cl 2 ). Instead, it was later discovered as a mixture of chloroform and alcohol marketed as the bichloride of methylene and even given the formula CH 2 Cl 2 . [ 13 ]
Other mixtures were: [ 1 ]
Not included in table as they include petroleum ether in addition to diethyl (sulphuric) ether:
ACE mixture was also used to anaesthetise animals, including in preparation for vivisection . [ 14 ]
ACE mixture could be given through drops (from a drop bottle [ 5 ] ) on a piece of lint (a towel ), in a Rendle's mask, a cone, or through an inhaler.
Inhalers included: Allis' inhaler, Junker's inhaler (with a funnel mask) for children, Clover's inhaler with bag removed (this inhaler has to be constantly lifted from the face to allow 'free air' to be admitted). Ellis proposed an inhaler to blend vapours in exact proportions, however it was impractical, but Gwathmey modified his idea and created a practical apparatus. Tyrrell created a similar idea called the 'Tyrrell's double-bottle method'. [ 1 ]
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https://en.wikipedia.org/wiki/ACE_mixture
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The ACTH test (also called the cosyntropin , tetracosactide , or Synacthen test ) is a medical test usually requested and interpreted by endocrinologists to assess the functioning of the adrenal glands ' stress response by measuring the adrenal response to adrenocorticotropic hormone (ACTH; corticotropin) or another corticotropic agent such as tetracosactide (cosyntropin, tetracosactrin; Synacthen) or alsactide (Synchrodyn). [ 1 ] [ 2 ] ACTH is a hormone produced in the anterior pituitary gland that stimulates the adrenal glands to release cortisol , dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and aldosterone . [ 3 ]
During the test, a small amount of synthetic ACTH is injected, and the amount of cortisol (and sometimes aldosterone) that the adrenals produce in response is measured. [ 4 ] This test may cause mild side effects in some individuals. [ 5 ] [ 6 ]
This test is used to diagnose or exclude primary and secondary adrenal insufficiency , Addison's disease , and related conditions. [ 2 ] In addition to quantifying adrenal insufficiency, the test can distinguish whether the cause is adrenal (low cortisol and aldosterone production) or pituitary (low ACTH production). [ 1 ] The insulin tolerance test is recognized as the gold standard assay of adrenal insufficiency, but due to the cumbersome requirement for a two-hour test and the risks of seizures or myocardial infarction, the ACTH stimulation test is commonly used as an easier, safer, though not as accurate, alternative. [ 7 ] The test is extremely sensitive (97% at 95% specificity) to primary adrenal insufficiency, but less so to secondary adrenal insufficiency (57–61% at 95% specificity); while secondary adrenal insufficiency may thus be dismissed by some interpreters on the basis of the test, additional testing may be called for if the probability of secondary adrenal insufficiency is particularly high. [ 1 ]
Adrenal insufficiency is a potentially life-threatening condition. Treatment should be initiated as soon as the diagnosis is confirmed, or sooner if the patient presents in apparent adrenal crisis. [ 8 ]
This test can be given as a low-dose short test , a conventional-dose short test , or as a prolonged-stimulation test . [ citation needed ]
In the low-dose short test, 1 μg of an ACTH drug is injected into the patient. In the conventional-dose short test, 250 μg of drug are injected. Both of these short tests last for about an hour and provide the same information. Studies have shown the cortisol response of the adrenals is the same for the low-dose and conventional-dose tests. [ 9 ] [ 10 ]
The prolonged-stimulation test, which is also called a long conventional-dose test , can last up to 48 hours. This form of the test can differentiate between primary, secondary, and tertiary adrenal insufficiency. This form of the test is rarely performed because earlier testing of cortisol and ACTH levels in association with the short test may provide all the necessary information. [ 8 ]
The test should not be given if on glucocorticoids or adrenal extract supplement, as these will affect test results. Stress and recently administered radioisotope scans [ citation needed ] can artificially increase levels and may invalidate test results. Spironolactone , contraceptives , licorice , estrogen , androgen (including DHEA) and progesterone therapy may also affect both aldosterone and cortisol stimulation test results. To stimulate aldosterone, consumption of salt should be reduced to a minimum, and foods high in sodium avoided for 24 hours prior to testing. Women should ideally undergo testing during the first week of their menstrual cycle as aldosterone (and occasionally cortisol) may be falsely elevated in the luteal cycle secondary to progesterone inhibition, leading to a compensatory rise in aldosterone levels. [ 11 ]
Traditionally, cortisol and ACTH levels (separate lavender top tube) are drawn at baseline (time = 0). Next, synthetic ACTH or another corticotropic agent is injected IM or IV, depending on the agent. [ 12 ] Approximately 20 mL of heparinized venous blood is collected at 30 and 60 minutes after the synthetic ACTH injection to measure cortisol levels. [ 13 ] [ 14 ]
ACTH samples are kept on ice and sent immediately to the laboratory, whereas cortisol does not need to be kept on ice. [ 15 ]
Commonly reported reactions are nausea, anxious sweating, dizziness, itchy skin, redness and or swelling of injection site, palpitations (a fast or fluttering heart beat), and facial flushing (may also include arms and torso), but should disappear within a few hours. [ 5 ] [ 6 ] Rarely seen, but serious side effects include rash, fainting, headache, blurred vision, severe swelling, severe dizziness, trouble breathing, irregular heartbeat. [ 6 ]
In healthy individuals, the cortisol level should increase above 18–20 μg/dl within 60 minutes on a 250 mcg cosyntropin stimulation test. [ 16 ]
In Addison's disease, both the cortisol and aldosterone levels are low, and the cortisol will not rise during the cosyntropin stimulation test [ citation needed ]
In secondary adrenal insufficiency, due to exogenous steroid administration suppressing pituitary production of ACTH or due to primary pituitary disorder causing insufficient ACTH production, the adrenal glands will atrophy over time and cortisol production will fall and patients will fail stimulation testing. Early in the development of secondary adrenal insufficiency, the adrenals may not have atrophied and can still stimulate, resulting in a normal cosyntropin stimulation test. [ 17 ]
If secondary adrenal insufficiency is diagnosed, the insulin tolerance test (ITT) or the CRH ( corticotropin-releasing hormone ) stimulation test can be used to distinguish between a hypothalamic (tertiary) and pituitary (secondary) cause but is rarely used in clinical practice. [ 17 ]
Measuring a morning, fasting ACTH level helps assess for the etiology of adrenal insufficiency. [ citation needed ]
ACTH will be high [ 13 ] – usually well above upper limits of reference range.
ACTH will be low [ 13 ] – usually below 35, but most people with secondary fall within the range limit. This is inappropriately normal for the low cortisol level.
In some cases, the actual cause of low ACTH is from low CRH in the hypothalamus. It is possible to have separate ACTH and CRH impairment such as can happen in a head injury. [ 18 ]
The ACTH stimulation test is occasionally used to test adrenal production of aldosterone at the same time as cortisol to also help in determining if primary (hyperreninemic) or secondary (hyporeninemic) hypoaldosteronism is present. [ 4 ] Human ACTH has a slight stimulatory effect on aldosterone, [ 19 ] but the amount of synthetic ACTH given in the stimulation is equivalent to more than a whole days production of natural ACTH, so the aldosterone response can be easily measured in blood serum. [ 20 ] Same as cortisol, aldosterone should double from a respectable base value (around 20 ng/dl, must fast salt 24 hours and sit upright for blood draw) in a healthy individual. [ citation needed ]
The aldosterone response in the ACTH stimulation test is blunted or absent in patients with primary adrenal insufficiency including Addison's disease. [ 4 ] The base value is usually in the mid-teens or less and rise to less than double the base value thus indicating primary hypoaldosteronism ( sodium low, potassium and renin enzyme will be high) and is an indicator of primary adrenal insufficiency or Addison's disease. [ citation needed ]
Aldosterone response of several factors from a low base value. This factoring indicates secondary hypoaldosteronism (sodium low, potassium and renin enzyme will be low). Usually doubling to quadrupling from a low base aldosterone value is what is seen in secondary adrenal insufficiency. Decoupling of aldosterone in the ACTH stimulation test is possible (i.e. 2 ng/dl stimming to 20). [ 21 ] A result of doubling or more of aldosterone may help in tandem with a cortisol stimulation that doubled or more confirm a diagnosis of secondary adrenal insufficiency. In rare cases, an aldosterone stimulation which did not double, but with the presence of low potassium, low renin and low ACTH indicates atrophy of aldosterone production from the prolonged lack of renin.
Similar to the cortisol stimulation in ACTH deficiency, the test interpreter may lack knowledge of how to properly interpret for secondary hypoaldosteronism and think a result of aldosterone doubling or more from a low base value is good.
Recent data showed that Synacthen test results can be used to predict future recovery of HPA axis function in patients with reversible causes of Adrenal Insufficiency. [ 22 ]
The test is also used to diagnose hypoadrenocorticism in dogs and sometimes cats. [ 27 ] [ 28 ] [ 29 ]
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https://en.wikipedia.org/wiki/ACTH_stimulation_test
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In oncology , AFP-L3 is an isoform of alpha-fetoprotein (AFP), a substance typically used in the triple test during pregnancy and for screening chronic liver disease patients for hepatocellular carcinoma (HCC). AFP can be fractionated by affinity electrophoresis into three glycoforms: L1, L2, and L3 based on the reactivity with the lectin Lens culinaris agglutinin (LCA). AFP-L3 binds strongly to LCA via an additional α 1-6 fucose residue attached at the reducing terminus of N-acetylglucosamine; this is in contrast to the L1 isoform. It is the L1 isoform which is typically associated with non-HCC inflammation of liver disease condition. The L3 isoform is specific to malignant tumors and its detected presence can serve to identify patients whom need increased monitoring for the development of HCC in high risk populations (i.e. chronic hepatitis B and C and/or liver cirrhosis ). AFP-L3% is now being considered as a tumor marker for the North American demographic.
AFP-L3 is isolated via an immunoassay and quantified using chemiluminesence on an automated platform. Results for AFP-L3 are represented as a ratio of LCA-reactive AFP to total AFP (AFP-L3%). The AFP-L3% assay, a liquid-phase binding assay, will help to identify at-risk subjects earlier, allowing for more intense evaluation for evidence of HCC according to existing practice guidelines in oncology. AFP-L3% is the standard for quantifying the L3 isoform of AFP in serum of high risk chronic liver disease (CLD) patients. Studies have shown that AFP-L3% test results of more than 10% can be indicative of early HCC [ citation needed ] or early nonseminomatous germ cell tumor . [ 1 ]
Early testimonials from hepatologists indicate that there is a target patient population for the AFP-L3% assay. This target population are those CLD patients who have AFP concentrations in the indeterminate range of 20-200+ ng/mL and a small or indeterminate mass on imaging. It is in this range that doctors experience trouble differentiating non-HCC fluctuations in AFP vs indication of HCC. In such patients these hepatologists recommend utilizing AFP-L3% to clarify the disease state. Some hepatologists also use a positive result to urge insurance companies to pay for more frequent and intensive imaging.
Ultimately AFP-L3% may be used as a rule-in or rule-out assay for transplantation consideration and/or an intermediate step in surveillance precluding costly imaging on patients with fluctuating AFP results but negative for HCC.
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https://en.wikipedia.org/wiki/AFP-L3
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Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes (also known as AIM-HIGH ) was a randomized control trial designed to assess the efficacy of niacin (extended-release) added to statin therapy in reducing cardiovascular events in patients with established atherosclerotic cardiovascular disease (ASCVD). These patients had well-controlled low-density lipoprotein (LDL) cholesterol but persistently low high-density lipoprotein (HDL) cholesterol and elevated triglycerides . 3,414 patients with established ASCVD were enrolled. The mean follow-up period was three years. The trial was stopped early due to a lack of efficacy and a trend towards an increase in the incidence of ischemic stroke. [ 1 ]
Low HDL cholesterol and high triglycerides are recognized risk factors for cardiovascular disease, even in individuals with well-controlled LDL cholesterol. Niacin has been shown to increase HDL cholesterol and lower triglycerides, prompting an investigation into whether adding niacin to statin therapy could further reduce cardiovascular risk in this patient population. [ 1 ]
AIM-HIGH was a multicenter, randomized, double-blind, placebo-controlled trial sponsored by the National Heart, Lung, and Blood Institute (NHLBI). Additional funding and support was provided by Abbott Laboratories and Merck . The study enrolled 3,414 patients with established ASCVD and dyslipidemia, characterized by low HDL cholesterol (<40 mg/dL for men and <50 mg/dL for women) and elevated triglycerides (150–400 mg/dL). All participants were already on statin therapy to maintain LDL cholesterol levels between 40 and 80 mg/dL. Participants were randomly assigned to receive either extended-release niacin (1500–2000 mg daily) or a matching placebo. The primary endpoint was the time to first major cardiovascular event, including nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or death from coronary heart disease. Secondary endpoints were death from coronary heart disease (CHD), nonfatal myocardial infarction, ischemic stroke, or hospitalization for acute coronary syndrome (ACS). [ 1 ]
The results of the AIM-HIGH trial, published in 2011, showed that adding niacin to statin therapy did not significantly reduce the risk of cardiovascular events compared to statin therapy alone: [ 1 ]
The findings of the AIM-HIGH trial had significant implications for the treatment of dyslipidemia in patients with established ASCVD: [ 1 ]
AIM-HIGH contributed to a shift in clinical practice guidelines, emphasizing the limited additional benefit of niacin in patients with low HDL cholesterol and high triglycerides already receiving effective statin therapy. Subsequent guidelines have focused on intensifying statin therapy or considering other agents for specific lipid abnormalities rather than adding niacin. [ 2 ]
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https://en.wikipedia.org/wiki/AIM-HIGH_(trial)
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AKTIP – Konzultační a terapeutický institut Praha ( lit. ' Consultation and Therapeutic Institute Prague ' ) was a private institute in Prague run by the public business company Progressive consulting, offering services in the field of psychosomatic care. [ 1 ] The head of the institute was Czech psychiatrist Jarmila Klímová [ cs ] . [ 2 ]
Controversy about the methods of the institute emerged [ 3 ] when the documentary Infiltrace: Obchod se zdravím ( Infiltration: Health Business ) was broadcast by Czech television on May 21, 2018.
The documentary revealed that the company uses unethical techniques to the detriment of its patients for its financial gain, including pseudoscience , manipulation, and incitement of fear of cancer and anxiety. AKTIP offers examinations and healing by instrumentation [ 4 ] and homeopathic preparations of doubtful effectiveness for various somatic diseases, including thyroid disease . [ 5 ] Although it has physicians on staff, this institution is not a legitimate provider of health services. It is not a medical facility. [ 6 ]
AKTIP is the holder of the Silver Erratic Boulder award in the category of teams for 2016.
"An eventual client meets here imaginary care in a wide range of disciplines. His complex problems will be treated by a graphologist , an expert in oriental diagnostics and bioresonance therapy will also supply its part of information. If it fails, a miraculous ANESA device, known as the non-invasive AMP blood analyzer (Golden Erratic Boulder award for 2011), will come to the scene", said Sisyfos . [ 7 ]
In the awards report its representatives also cite the statement of the head of AKTIP Jarmila Klímová that the human body is set for 400 years of life. "If we really lived only by biological hours, we could be at rest between 380 and 460 years, because this age is set up for our body ... And why do we live only 60 or 80 years? No, because the most important influence outside of ourselves, which fundamentally affects the length and quality of life, we do not accept." [ 8 ]
The practices of AKTIP was already criticized by the Czech Oncological Society in 2014. [ 9 ] Procedures used by AKTIP employees have been critically evaluated by doctors [ 5 ] (f.ex. by cardiologist Věra Adámková) The psychologist Petr Weiss described AKTIP's practices as charlatan fabrications, fraud, and money-pulling activities. [ 10 ]
According to the President of the Czech Medical Chamber Milan Kubka, AKTIP's position in the future could be solved by a law on healers that would force "all such charlatan institutions" to mandatory registration. "This institution only looks like a medical facility, and that's a scam from my point of view." [ 11 ]
Sisyfos, in response to the AKTIP case, has published an article analyzing the principles of some devices used by individual "consultants" of AKTIP. This article also expresses concern that AKTIP is not an exceptional case, but that it is a fairly common phenomenon among institutions that provide services of alternative medicine. [ 12 ]
On May 8, 2019, AKTIP announced end of their activities. [ 13 ]
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https://en.wikipedia.org/wiki/AKTIP_(therapeutic_institute)
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ALMANAC is a major breast cancer trial. The acronym stands for "Axillary Lymphatic Mapping Against Nodal Axillary Clearance." This major randomized trial performed in several centres in the UK produced clear evidence that sentinel node biopsy (SNB), used to stage axillary spread of disease, can be used with low failed localization and false negative rates, provided both radioisotope and blue dye are used to locate the sentinel nodes . [ 1 ]
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https://en.wikipedia.org/wiki/ALMANAC
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The ALS Association is an American nonprofit organization that funds global amyotrophic lateral sclerosis (ALS) research, provides care services and programs to people affected by ALS through its nationwide network of clinical care centers, and works with ALS advocates around the country for state and federal policies that serve people living with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig 's disease. [ 2 ]
The ALS Association has partnerships with Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital , [ 3 ] ALS Finding a Cure, and the Muscular Dystrophy Association . [ 4 ] Additionally, the organization is a research partner for Answer ALS (started by Steve Gleason ), Target ALS (founded by Dan Doctoroff ), [ 5 ] and ALS ONE. The organization also provides funding for the ALS Research Forum, a project of Prize4Life , which has since merged with the ALS Association. [ citation needed ]
Because of the awareness and funding from the Ice Bucket Challenge , the Association committed nearly $90 million in research funding between 2014 and 2018, a 187% increase in its annual research funding. [ 6 ] [ 7 ] This included $81.2 million across 275 research grants in the U.S. and $8.5 million internationally. [ 7 ] The research led to the discovery of five new genes connected to ALS: [ 6 ] [ 8 ] [ 7 ]
According to Hemali Phatnani, director of the Center for Genomics of Neurodegenerative Disease at the New York Genome Center , funds raised from the Challenge led to the creation of one of the largest resources of ALS whole genome-sequencing data, which has been shared with partners around the world. [ 15 ]
In September 2020, the New England Journal of Medicine reported that a new drug combination, AMX0035 , was safe and effective at slowing the progression of ALS in a clinically meaningful way. [ 16 ] The ALS Association had provided early financial support for research into AMX0035 with Ice Bucket Challenge donations. [ 17 ] After the clinical trial outcomes were published, The ALS Association launched a petition asking Amylyx Pharmaceuticals and the Food and Drug Administration to work together to make the drug available to people with ALS as quickly as possible. [ 18 ]
After four years of efforts by thousands of people affected by ALS [ 19 ] to cultivate significant bipartisan support, the ALS Disability Access Act of 2019 was signed into law in December 2020. This bill eliminates the arbitrary five-month waiting period formerly required before people living with ALS could draw on their Social Security Disability Insurance benefits. [ 20 ]
In the summer of 2014, the Ice Bucket Challenge raised $220 million after going viral on social media. [ 6 ] [ 8 ] [ 15 ] The ALS Association received $115 million of that amount. To participate, individuals were challenged to pour a bucket of ice water over themselves and/or donate money to ALS research and care. Individuals such as former president George W. Bush , Bill Gates , Taylor Swift , Benedict Cumberbatch , LeBron James , and Martha Stewart dumped ice water on their heads to raise money to fight ALS. [ 6 ] [ 7 ] [ 8 ] In total, about 17 million people uploaded videos of themselves doing the challenge, and the videos were viewed more than 10 billion times. [ 6 ]
From the challenge, $115 million was raised, and the Association increased the number of patients served by 28%. [ 8 ] Most of the donations were used for research, but there were other uses. For example, local chapters purchased equipment (power wheelchairs, walkers, shower benches, etc.) for ALS patients and were able to provide for everyone on their respective wait-lists. [ 21 ] [ 22 ]
The Association's clinical network also expanded by 50% as a result of the funding from the Challenge. [ 7 ] A study by RTI International reported 29 new ALS Certified Treatment Centers of Excellence, 20 new Recognized Treatment Centers, and 7 new affiliated clinics. [ 23 ] Also according to RTI, the National Institutes of Health (NIH) has invested nearly $416 million in ALS Association-funded researchers since the Challenge. [ 15 ]
Following the 2014 Ice Bucket Challenge, the ALS Association attempted to trademark the term "ice bucket challenge". Following backlash, the association withdrew the trademark application. [ 24 ] In early 2018, a patient group called the "Terminally Persistent" coalition criticized the ALS Association for not spending the $115 million earned from the Ice Bucket Challenge more readily on research. Additionally, the group complained that the organization was not providing funding to BrainStorm Cell Therapeutics, a pharmaceutical company researching treatments for ALS and running Phase III clinical trials; the ALS Association does not fund Phase III clinical trials. [ 25 ]
The association's signature fundraising event each year is the "Walk to Defeat ALS". This event is held each fall through spring in cities across the United States. Since its inception in 2000, this event has raised more than $265 million. [ 26 ]
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https://en.wikipedia.org/wiki/ALS_Association
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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that typically affects adults around 54–67 [ 1 ] years of age, although anyone can be diagnosed with the disease. People diagnosed with ALS live on average 2–4 years after diagnosis due to the quick progression of the disease. [ 2 ] [ 3 ] The progression and severity of ALS is rated by doctors on the ALS Functional Rating Scale , which has been revised and is referred to as ALSFRS-R .
ALSFRS-R includes 12 questions that can have a score of 0 to 4. A score of 0 on a question would indicate no function while a score of 4 would indicate full function. [ 4 ] [ 5 ] This scale has been useful for doctors in diagnosing patients, measuring disease progression and also for researchers when selecting patients for a study and measuring the potential effects of a clinical trial . [ 4 ] [ 6 ]
The ALSFRS-R scale has some limitations though since it is not useful to compare scores of people who present with different onset. In ALS the main type of onset is bulbar followed by limb-onset ALS which describes the region of motor neurons first affected. [ 3 ] Individuals may also present with respiratory-onset ALS , [ 7 ] but this occurs very rarely. Since there are three different types of ALS, ALSFRS-R scores are often grouped in categories depending on type of onset. [ 7 ]
Since there are three main pathways of progression, the questions are also divided in relation to the types of onset. Questions 1 to 3 are related to bulbar onset, questions 4 to 9 are related to limb onset and questions 10 to 12 are related to respiratory onset. [ 7 ] Further developments of the ALSFRS-R include an extended version (ALSFRS-EX) [ 8 ] to mitigate the floor effect and a version with explanatory notes, which is particularly suitable for self-assessment (ALSFRS-R-SE, self-explanatory). [ 9 ]
ALSFRS-R scores calculated at diagnosis can be compared to scores throughout time to determine the speed of progression. The rate of change, called the ALSFRS-R slope can be used as a prognostic indicator. [ 7 ] [ 10 ] [ 11 ]
Although the ALSFRS-R score is a recognized prognostic indicator, [ 5 ] it is more useful to compare various indicators including vital capacity (FVC%) and the Sickness Impact Profile (SIP) [ 5 ] [ 12 ] to increase the accuracy of a given prognosis.
Relating the ALSFRS-R score to staging criteria is also useful in determining prognosis. King's system relies on the clinical spread of disease as a measure of progression [ 5 ] [ 13 ] while Milano-Torino Staging (MiToS) utilizes the subscores produced by the ALSFRS-R to define stages. [ 5 ] [ 14 ]
The questions used to determine an individual's ALSFRS-R score are listed below. [ 5 ]
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https://en.wikipedia.org/wiki/ALS_Functional_Rating_Scale_-_Revised
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The ALS Society of Canada is a Canadian voluntary health organization dedicated to the fight against amyotrophic lateral sclerosis (ALS) and to providing support for those living with ALS.
ALS Canada was founded in 1977 and is a registered not-for-profit organization. The organisation is committed to supporting research towards a cure for ALS, also known as Lou Gehrig 's disease, supporting the provincial ALS societies in their provision of quality care for persons living with ALS, and building public awareness of ALS and its impact.
The mission of the ALS Society of Canada is to fund research for a cure for ALS. [ citation needed ]
Since 2000, ALS Canada has been one of the partners of the Neuromuscular Research Partnership (NRP), which is a collaboration between the Canadian Institutes of Health Research (CIHR), Muscular Dystrophy Canada (MDC) and ALS Canada. The NRP makes grants available for research into the causes, treatments, and ultimately the cure for neuromuscular disorders . [ citation needed ]
ALS Canada is currently funding a national clinical trial, which aims to confirm the effectiveness of lithium in slowing the progression of ALS in patients in the early stages of the disease. At nearly $1,000,000, the lithium trial is ALS Canada's largest research investment to date. The lithium trial is being conducted by a consortium of ALS clinicians in Canada called the Canadian ALS Clinical Trials and Research Network (CALS). The trial is the first joint effort between CALS and the Northeastern ALS Consortium (NEALS) in the United States . [ citation needed ]
The ALS Society of Canada works with the provincial ALS Societies, which develop local chapters and support groups and provide direct support to people with ALS, their families and caregivers. The provincial societies also offer information and referrals, and support for those affected by ALS. They manage equipment programs and engage in advocacy for people with ALS, their families, physicians and health-care providers. [ citation needed ]
The ALS Society of Ontario is a non-profit organization in the Canadian province of Ontario that provides support and assistance to people diagnosed with ALS, their friends and families. [ 1 ] It was founded in 1988 by an affiliation of ALS Society of Canada chapters in Toronto , Hamilton , London , Ottawa , and Windsor . The Toronto chapter seceded after a year to form the ALS Society of Toronto and Area; in 2004, it rejoined the Ontario society as a regional organization. [ 2 ]
Raising awareness of ALS is a key program of the ALS Society of Canada and its provincial partners. [ citation needed ]
June is ALS awareness month in Canada. Throughout the provinces, public awareness and fundraising campaigns are carried out, such as golf tournaments and the WALK for ALS, which takes place in more than 78 communities across the nation. Canadians also show their support by planting blue cornflowers , the ALS Canada emblem flower, in their gardens. [ citation needed ]
In 2008, ALS Canada launched a Public Service Announcement (PSA) campaign to educate the public and increase awareness of ALS in the general population. The campaign consists of two 30- and 60-second television spots, in English and French, called "Head and Shoulders", and a series of three English and French print advertisements, called "No Signal". [ citation needed ]
In 2006, ALS Canada launched an initiative called als411 to help children and teens cope with ALS in their family. This was followed in 2008 by the creation of the als411 website, which has separate sub-sites for younger children and teens in both English and French. Each sub-site offers interactive components that provide age-appropriate education about ALS, personal stories, and additional resources for information and coping as well as a social networking link on the teen sites. [ citation needed ]
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https://en.wikipedia.org/wiki/ALS_Society_of_Canada
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ALVAC-CEA vaccine is a cancer vaccine containing a canary pox virus (ALVAC) combined with the carcinoembryonic antigen (CEA) human gene . [ 1 ]
A phase I trial in 118 patients showed safety in humans. [ 2 ]
This article incorporates public domain material from Dictionary of Cancer Terms . U.S. National Cancer Institute .
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https://en.wikipedia.org/wiki/ALVAC-CEA_vaccine
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The AMA Scientific Achievement Award is awarded by American Medical Association . It may be given to either physicians or non-physician scientists who have contributed significantly to the field of medical science. The award itself consists of a gold medallion. [ 1 ]
The recipients are chosen by the AMA's Board of Trustees, and Physician candidates must be AMA members.
Source: AMA Awards Archived 2016-04-27 at the Wayback Machine
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https://en.wikipedia.org/wiki/AMA_Scientific_Achievement_Award
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The AO Foundation is a nonprofit organization dedicated to improving the care of patients with musculoskeletal injuries or pathologies and their sequelae through research, development, and education of surgeons and operating room personnel. The AO Foundation is credited with revolutionizing operative fracture treatment and pioneering the development of bone implants and instruments. [ 1 ] [ 2 ]
The foundation has its origins in a Swiss study group named Arbeitsgemeinschaft für Osteosynthesefragen (Association of the Study of Internal Fixation), commonly referred to as the AO , that was founded in Switzerland in 1958 [ 3 ] [ 4 ] as a society. The AO became a foundation in December 1984. [ 3 ]
On March 1, 1950 Maurice Müller , one of the founding members of the AO, visited a 70-year old Belgian surgeon named Robert Danis in Brussels, who had been experimenting and treating fracture patients surgically for 25 years. At the time Dr. Müller was 32 years old, and had been practicing medicine for 6 years. [ 5 ] The standard of treatment for fractures at the time was the method usually called "conservative treatment," as originally documented and popularized by Lorenz Böhler . This approach focused on reducing fractures and stabilizing them with splints and plaster, followed by traction. [ 6 ] By the time of Müller's visit, Danis had already published 2 books on osteosynthesis, Technique de l'Ostéosynthèse (1932, Paris), and Theorie et pratique de l’osteosynthese (1949, Paris). [ 7 ]
The one day that Maurice Müller spent in Brussels with Dr. Danis was a significant moment for Müller's subsequent work, who said that Danis' 1949 book was one of the most important works that he had ever read; he also took samples of Danis' own instruments, including one plate and screws, along with the contact information of the manufacturer in Belgium. He quickly developed his own ideas on how to improve the techniques he had seen from Danis. [ 8 ] Between 1951 and 1957, Müller performed numerous surgeries in which he applied what he had learnt from surgical treatment of fractures as well as techniques he developed by himself, first at the General Hospital of the Canton of Fribourg, where he worked as Chief Resident, later at the Balgrist Orthopedic Clinic, and later at the private Hirslanden Clinic. [ 9 ]
Maurice Müller had an agreement with the Balgrist Orthopedic Clinic, through which he enjoyed a day off every week that he used to travel around the region visiting hospitals and other like-minded surgeons. This helped Müller develop a network, which, paired with his reputation of a very talented surgeon, got him recommended and requested to operate on difficult cases in hospitals around the country. In December 1957, Maurice Müller delivered a lecture at the University of Zürich , upon receiving his PD (private lecturer) degree. During his lecture he presented a set of orthopedic surgery principles that he developed, which would soon evolve to become the AO Principles of Fracture Management . In 1958, Müller and some of his close colleagues met and agreed to create a school of thought for surgical orthopedic techniques. It was agreed to call the group the Arbeitsgemeinschaft für Osteosynthesefragen , shortened to the AO.
In the frame of the Swiss Surgical Society meeting in Bern in November 1958, Müller organized the first meeting of the AO, which 12 other surgeons would attend. The meeting took place at the Hotel Elite in Biel/Bienne , and the agenda for the day included a presentation of Müller's Instrumentarium, a set of implants, screws, and tools he developed and fine-tuned first with Zulauf, a woodworking tools manufacturer, and later in collaboration with Robert Mathys, a mechanical engineer from the city of Bettlach , in Switzerland, who owned a small shop specialized in designing and producing stainless steel screws. [ 10 ] The agenda also included a discussion on who would manufacture the implants and tools. Successive meetings covered the AO's legal statutes and by-laws. [ 11 ]
The various instruments that Müller and other AO founders had been using until 1958 was an assortment of existing tools and parts which didn't always match or work well together. The first AO efforts consisted of developing a standardized toolset that was easy to use and had a full tool-implant compatibility. The first version of the AO Instrumentarium consisted of a set of six color-coded aluminium cases, containing pre-sterilized screws, plates, and tools. The AO team ordered 20 of these sets from Mathys, which would be first tested by the AO surgeons, and later used for the first AO course to be held in Davos in December 1960. The AO had decided that surgeons who wanted to purchase the AO Instrumentarium would first have to be trained in its proper use, as well as the latest surgical fracture techniques that the AO founding surgeons decided to teach. [ 12 ]
The AO developed a business model that would provide funding for all AO research activities, the funding of an AO Documentation Center, and the AO educational activities, via licensing fees that the instrument producers would pay. To manage the administration of this industrial area of the AO, Müller recommended to create a company, which would be called Synthes AG Chur.
From 1963 to the early 1980s, the AO developed new implants, tools, and devices; appointed new manufacturers for the AO-developed solutions; and assigned distributors throughout most of the world. The AO Instrumentarium grew from around 200 items in 1961 to over 1,200 items in the early 1980s, and licensing fees in 1982 amounted to over 10 million Swiss Francs, by 1985 it was 13 million Swiss Francs. [ 13 ]
Toward the end of the 1980s, the AO Instrumentarium was being manufactured and marketed by 3 companies: Mathys (privately owned by the Mathys family), Stratec (privately owned by the Straumann family), and Synthes US (privately held and majority owned by Hansjörg Wyss [ 14 ] ). Synthes US acquired the business from the Straumann family in 1999, and the newly formed Synthes-Stratec company acquired the Mathys business 4 years later, in 2003. [ 15 ]
The AO changed its legal status from an association to a foundation in 1984. The significant sales growth of the AO Instrumentarium enjoyed from the 1980s through the 2000s had resulted in royalties payments growing from 14 million Swiss francs in 1986 to 84.1 million Swiss francs in 2004. Some surgeons—leaders in the AO organization—were concerned about the over-marketing of AO products, while others were concerned that they shouldn't profit from the sales of the implants and the devices they used in surgeries for their patients. These concerns, coupled with an increasingly competitive global business landscape in the implant business and a consolidated, single manufacturer and distributor of the AO-approved products, pushed the AO and Synthes to devise a new operating model.
In 2006, the AO sold and transferred the Synthes brand, all its patents to the AO Instrumentarium, and all rights to the products usages to the producer Synthes, for a one-off payment of 1 billion Swiss Francs. Additionally the manufacturer would pay a fixed yearly fee of 50.7 million Swiss Francs, and the AO would in exchange organize a number of educational courses, during which only AO Instrumentarium products would be used. With successive adjustments and negotiations, this has been the operating model under which the AO has continued to cooperate, first with Synthes, and later with Depuy Synthes (renamed after the 2011 acquisition by Johnson & Johnson) [ 16 ] [ 17 ]
The AO Foundation has several pillars of activity:
ARI focuses on pre-clinical research. Scientists working in the AO research facilities located in the Swiss city of Davos conduct fundamental and applied research in the fields of biomechanics and biology of bone, disc and cartilage (including tissue engineering and musculoskeletal infections), and biomaterials science (such as degradable polymers and polymer-based transport systems). The institute also conducts research in the field of new surgical techniques, tools, and devices, such as "smart" implants, and intracorporeal navigation and tools for surgical teams and surgeons. [ 18 ]
The institute, led by Geoff Richards since 1991, employs over 100 scientist and PhD students from all over the world, and is considered the largest institute of its kind. [ 19 ] It is partially funded by the AO Foundation as well as external grants.
The AO Education Institute is responsible for the development of each educational product curriculum as well as creating educational tools and media. It is also in charge of AO faculty development, evaluating and assessing educational outcomes, [ 20 ] and designing and performing medical education research. [ 21 ] [ 22 ]
This division includes the AO Technical Commission, which develops and tests new devices, which will eventually find their way to the market. Other key areas within the Innovation Translation Center include Technology Transfer , which offers seed funding for innovation in the field of surgeon education or other areas of a muskuloeskeletal disorder patient's treatment journey, a development incubator department, and the Clinical Operations and the Clinical Science departments, which focus on clinical research, from management and research execution through outcomes publication. [ 23 ]
The different anatomical and pathology areas are covered by different working groups, task forces, and commissions, split into the following 5 clinical specialties
The main operation of daily activities at the AO Foundation lies in the organization and delivery of educational events, comprising symposia, webinars, seminars, and courses aimed at orthopaedic surgeons, neurosurgeons, craniomaxillofacial surgeons, operating room personnel, and other health professionals. These include hands on experience of using the latest implants, as well as lectures from expert surgeons and discussions. [ 24 ] [ 25 ]
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https://en.wikipedia.org/wiki/AO_Foundation
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APMIS Journal , formerly known as Acta Pathologica, Microbiologica, et Immunologica Scandinavica , is a monthly peer-reviewed medical journal published by Wiley ".
The journal was formed in 1988 by a merger of the three sections of Acta Pathologica, Microbiologica, et Immunologica Scandinavica : Section A, Pathology , Section B, Microbiology , and Section C, Immunology . The original journals dated from 1924, originally published as Acta Pathologica et Microbiologica Scandinavica . Since 2012 it has been an electronic-only publication. [ 1 ]
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https://en.wikipedia.org/wiki/APMIS
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The Alliance for the Prudent Use of Antibiotics ( APUA ) is a non-profit organization founded in 1981 by Stuart B. Levy (1938–2019), Professor of Medicine at Tufts University and headquartered in Boston, Massachusetts . [ 1 ] APUA's mission is to strengthen society's defenses against infectious disease by promoting appropriate access and use to antimicrobial agents ( antibiotics , antivirals , antimalarials etc.) and controlling antimicrobial resistance on a worldwide basis. APUA has a network of affiliated chapters in over 50 countries, and conducts applied antimicrobial resistance research, education, capacity building and advocacy at the global and grassroots levels.
Wide-scale misuse of antibiotics and other antimicrobials and related resistance to these drugs is challenging infectious disease treatment and health care budgets worldwide. Antimicrobials are uniquely societal drugs because each individual patient use can propagate resistant organisms. APUA provides information to individuals, doctors and policy makers aimed at preserving the power of these agents by preventing infection, reducing drug resistance and increasing the effectiveness of treatment for infectious diseases, including acute bacterial diseases, tuberculosis , AIDS and malaria .
Following Stuart Levy's retirement in 2018, APUA merged with the International Society of Antimicrobial Chemotherapy (ISAC), effective from February 2019. ISAC was founded as a charity in 1961 and, in response to the dynamic nature of the subject matter, has focused most recently on antimicrobial stewardship and antimicrobial resistance.
Each year, APUA presents its Leadership Award in recognition of outstanding global contributions and commitment to preserve the power of antibiotics. [ 2 ]
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https://en.wikipedia.org/wiki/APUA_Leadership_Award
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The ASA physical status classification system is a system for assessing the fitness of patients before surgery . In 1963 the American Society of Anesthesiologists (ASA) adopted the five-category physical status classification system; a sixth category was later added. These are:
If the surgery is an emergency, the physical status classification is followed by "E" (for emergency ) for example "3E". Class 5 is usually an emergency and is therefore usually "5E". The class "6E" does not exist and is simply recorded as class "6", as all organ retrieval in brain-dead patients is done urgently. The original definition of emergency in 1940, when ASA classification was first designed, was "a surgical procedure which, in the surgeon's opinion, should be performed without delay," [ 1 ] but is now defined as "when [a] delay in treatment would significantly increase the threat to the patient's life or body part." [ 2 ]
These definitions appear in each annual edition of the ASA Relative Value Guide. There is no additional information that can be helpful to further define these categories. [ 3 ]
An example of an ASA status classification system is that used by dental professionals. [ 4 ] Many include the 'functional limitation' or 'anxiety' to determine classification which is not mentioned in the actual definition but may prove to be beneficial when dealing with certain complex cases. Often different anesthesia providers assign different grades to the same case. [ 5 ] [ 6 ] [ 7 ] [ 8 ]
Some anesthesiologists now propose that like an 'E' modifier for emergency, a 'P' modifier for pregnancy should be added to the ASA score. [ 9 ]
While anesthesia providers use this scale to indicate a person's overall preoperative health, it may be misinterpreted by hospitals, law firms, accrediting boards and other healthcare organizations as a scale to predict risk, [ 10 ] and thus decide if a patient should have – or should have had – an operation. [ 11 ] For predicting operative risk, other factors – such as age, presence of comorbidities , the nature and extent of the operative procedure, selection of anesthetic techniques, competency of the surgical team (surgeon, anesthesia providers and assisting staff), duration of surgery or anesthesia, availability of equipment, medications, blood, implants and appropriate postoperative care – are often far more important than the ASA physical status. [ citation needed ]
In 1940–41, ASA asked a committee of three physicians (Meyer Saklad, Emery Rovenstine , and Ivan Taylor) to study, examine, experiment and devise a system for the collection and tabulation of statistical data in anesthesia which could be applicable under any circumstances. [ 1 ] This effort was the first by any medical specialty to stratify risk. [ 12 ] While their mission was to determine predictors for operative risk, they quickly dismissed this task as being impossible to devise. [ citation needed ] They state:
"In attempting to standardize and define what has heretofore been considered 'Operative Risk', it was found that the term ... could not be used. It was felt that for the purposes of the anesthesia record and for any future evaluation of anesthetic agents or surgical procedures, it would be best to classify and grade the person in relation to his physical status only." [ 11 ]
The scale they proposed addressed the patient's preoperative state only, not the surgical procedure or other factors that could influence surgical outcome. They hoped anesthesiologists from all parts of the country would adopt their "common terminology," making statistical comparisons of morbidity and mortality possible by comparing outcomes to "the operative procedure and the patient's preoperative condition". [ 13 ]
They described a six-point scale, ranging from a healthy person (class 1) to one with an extreme systemic disorder that is an imminent threat to life (class 4). The first four points of their scale roughly correspond to today's ASA classes 1–4, which were first published in 1963. [ 1 ] [ 5 ] The original authors included two classes that encompassed emergencies which otherwise would have been coded in either the first two classes (class 5) or the second two (class 6). By the time of the 1963 publication of the present classification, two modifications were made. First, previous classes 5 and 6 were removed and a new class 5 was added for moribund persons not expected to survive 24 hours, with or without surgery. Second, separate classes for emergencies were eliminated in lieu of the "E" modifier of the other classes. [ 13 ] [ 14 ] The sixth class is now used for declared brain-dead organ donors. Saklad gave examples of each class of patient in an attempt to encourage uniformity. Unfortunately, the ASA did not later describe each category with examples of patients and thus actually increased confusion.
Examples:
This includes patients suffering with fractures unless shock, blood loss, emboli or systemic signs of injury are present in an individual who would otherwise fall in Class 1. It includes congenital deformities unless they are causing systemic disturbance. Infections that are localized and do not cause fever, many osseous deformities, and uncomplicated hernias are included. Any type of operation may fall in this class since only the patient's physical condition is considered.
Examples: Mild diabetes.
Functional capacity I or IIa.
Psychotic patients unable to care for themselves.
Mild acidosis.
Anemia moderate.
Septic or acute pharyngitis.
Chronic sinusitis with postnasal discharge.
Acute sinusitis.
Minor or superficial infections that cause a systemic reaction. (If there is no systemic reaction, fever, malaise, leukocytosis, etc., aid in classifying.)
Nontoxic adenoma of thyroid that causes partial respiratory obstruction.
Mild thyrotoxicosis.
Acute osteomyelitis (early).
Chronic osteomyelitis.
Pulmonary tuberculosis with involvement of pulmonary tissue insufficient to embarrass activity and without other symptoms.
Examples:
Complicated or severe diabetes. Functional capacity IIb. Combinations of heart disease and respiratory disease or others that impair normal functions severely. Complete intestinal obstruction that has existed long enough to cause serious physiological disturbance. Pulmonary tuberculosis that, because of the extent of the lesion or treatment, has induced vital capacity sufficiently to cause tachycardia or dyspnea. Patients debilitated by prolonged illness with weakness of all or several systems. Severe trauma from accident resulting in shock, which may be improved by treatment. Pulmonary abscess.
Examples: Functional capacity III -(Cardiac Decompensation). Severe trauma with irreparable damage. Complete intestinal obstruction of long duration in a patient who is already debilitated. A combination of cardiovascular-renal disease with marked renal impairment. Patients who must have anesthesia to arrest a secondary hemorrhage where the patient is in poor condition associated with marked loss of blood. Emergency Surgery: An emergency operation is arbitrarily defined as a surgical procedure which, in the surgeon's opinion, should be performed without delay.
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https://en.wikipedia.org/wiki/ASA_physical_status_classification_system
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AZD1305 is an experimental drug candidate that is under investigation for the management and reversal of cardiac arrhythmias , specifically atrial fibrillation and flutter . In vitro studies have shown that this combined-ion channel blocker inhibits rapidly the activating delayed-rectifier potassium current (IKr), L-type calcium current, and inward sodium current (INa). [ 1 ]
Atrial fibrillation (AF) is a form of cardiac arrhythmia that arises with disorganized and rapid action upotentials conducted through the atria, resulting in irregular atrial contraction. [ 2 ] Causes of AF include hypertension, cardiomyopathies, alcohol consumption, viral infections, and sleep apnea, which can cause AF by increasing the occurrence of early after depolarizations (EADs). [ 3 ] EAD is an abnormal depolarization and increase in action potential frequency that occurs in cardiac myocytes before normal repolarization is complete. [ 4 ] [ 5 ]
AZD1305 possesses class III anti-arrhythmic activity by blocking the human ether-a-go-go-related gene (hERG) potassium channel. [ 4 ] hERG contributes to the formation of potassium ion channel proteins that are responsible for the conduction of the rapid delayed rectifying potassium current. [ 6 ] Blocking this current prolongs action potential duration (APD), increases refractory period, and delays repolarization of cardiac myocytes in the ventricles and atria. [ 4 ] Delayed repolarizations increase susceptibility to EAD.
AZD 1305 also acts on voltage gated sodium channels (Nav1.5) by attenuating the peak (INapeak) and late sodium current (INalate), though the latter current is more potently inhibited. [ 5 ] Attenuation of INalate by AZD1305 is concentration-dependent and decreases the slope of depolarization and delays repolarization. INalate blockade by AZD1305 depressed the threshold of sodium channel excitation and prolongs APD. [ 7 ] Blockade of IKr may lead to excessive prolongation of APD and repolarization instability, which may promote arrhythmic conditions in the heart, including EAD and Torsade de Pointes (TdP). [ 5 ] Under IKr blockade a pronounced INalate can contribute to the development of arrhythmias by increasing repolarization variability. AZD1305 blockade of the INalate modulates IKr-blockade induced APD instability, repolarization vulnerability, and variability in beat-to-beat APD. [ 4 ] [ 5 ]
In vivo , as well as in vitro studies discovered that inhibition of INa and IKr by AZD1305 is much greater in atrial versus ventricular myocytes. [ 1 ] [ 7 ] This atrial-selective activity of AZD1305 prolongs effective refractory period (ERF) and induces post-repolarization refractoriness (PRR) in atrial myocytes, which aids in suppressing atrial fibrillation. [ 7 ]
AF and TdP may be induced with L-type calcium channel hyperactivity and increased calcium release from the sarcoplasmic reticulum. The L-type calcium current is also blocked by AZD 1305 which suppresses the intracellular rises in calcium levels and calcium oscillations that produce EADs. [ 1 ] [ 4 ] The combined block of INa, IKr, and L-type calcium current is key to the anti-arrhythmic potential of AZD1305 compared IKr blockade alone. [ 1 ]
Available anti-arrhythmic agents (AAD) used for the maintenance of AF are often accompanied with the risk of developing ventricular pro-arrhythmias, as they are often limited to targeting a single ion channel (i.e., Dofeiltide) and have homogenous activity throughout the heart. [ 4 ] AZD1305 offers the advantage of being an atrial-selective AAD and combined ion channel blocker that provides protection against EAD, repolarization dispersion, and ventricular pro-arrhythmias. [ 1 ] [ 4 ] [ 7 ] Simultaneously, AZD1305 suppresses AF in a safe and efficacious manner, which could potentially be an ideal first-line treatment option in the future. [ 1 ]
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https://en.wikipedia.org/wiki/AZD1305
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A History of Medicine is a book by Scottish surgeon Douglas Guthrie that was published in 1945 by Thomas Nelson and Sons . It came to wide attention after it was reviewed by the playwright George Bernard Shaw and marked the beginning for Guthrie of a new career in teaching the history of medicine. [ 1 ]
Guthrie's objective was to bring to a wide audience and in chronological order, the past achievements in the history of medicine, [ 2 ] from Imhotep to William Osler . [ 3 ]
The first edition of the book consisted of 20 chapters, 448 pages and 72 plates, beginning with "The Genesis of Medicine" and ending with a chapter focussed on medical journalism. [ 4 ]
In the preface, Guthrie paid tribute to his mentor, the Scottish physician John Comrie , who had introduced him to the subject of medical history, Alexander Miles who "read the original manuscript and supplied much helpful criticism in the early stages of the work", the librarian of the Royal Society of Medicine G. F. Home and to J. C. Corson from Edinburgh University Library who prepared the index. [ 5 ]
After 10 years' research, the book was published in 1945, the same year that Guthrie retired from clinical work. [ 6 ] It was published in Britain by Thomas Nelson and Sons, [ 3 ] and later in an American edition. [ 2 ] [ 5 ] Translations followed in Spanish (1947), German (1952) and Italian (1966). [ 6 ]
The book received at least 53 English-language reviews [ 6 ] which Guthrie kept in a scrapbook which was passed to his friend Haldane Philp Tait and is now (2019) in the collections of the Lothian Health Service Archive. [ 5 ] [ 7 ]
Nearly all of the reviews were positive and the book was favourably compared with the few contemporary general histories of medicine then available, particularly Charles Singer 's A Short History of Medicine and Garrison 's An introduction to the History of Medicine . [ 5 ]
The British Medical Journal and The Lancet gave favourable reviews and the Journal of the American Medical Association recommended it to all physicians, [ 2 ] but the Bulletin of the History of Medicine responded more critically, identifying a number of inaccurate names and dates. [ 2 ] This intense criticism came from George Rosen , who was of the opinion that Guthrie should have included social context. Guthrie's response, as documented in his scrapbook, described it as "the only really adverse criticism, obviously by a disgruntled reviewer who thinks he could have done better himself". [ 5 ]
The book came to wider attention following a 3,000-word review by George Bernard Shaw in The Observer . [ 6 ] Shaw wrote, "I am floored by the extraordinary discrepancy between his [Guthrie's] knowledge and my knowledge ... Dr Guthrie's job of packing it [the history of medicine] into 400 pages is learnedly and readably done". [ 8 ] Shaw did criticise Guthrie for his omission of practitioners of alternative medicine including osteopaths, herbalists and homoeopaths, which Shaw believed was because "Dr Guthrie either does not know about them or considers them beneath the dignity of a history of medicine". Guthrie's response was that Shaw had provided an unconventional yet entertaining book review. [ 6 ] Aware that Shaw's review had greatly increased the profile and popularity of the book he modestly wrote that "many who had no particular interest in the topic or the author, bought the book just because GBS [Shaw] had reviewed it; they had no special interest in the subject and none needless to say, in the author". [ 6 ] [ 5 ]
Shaw's review was then published in the New York Journal-American , an American daily newspaper which brought the book to the attention of a large readership in the United States. [ 6 ]
In 1956, Guthrie wrote an article "On Writing a History of Medicine", which was then included in his book, Janus in the Doorway (1963). [ 9 ] This book also included chapters on "The Value of Reviews" and "Hints for Historiographers". [ 5 ]
Following reprints in 1945, 1946 and 1947, and American, Spanish and German versions, a new and revised British edition was published in 1958. Most of the revisions were made by amendments to the text but some of the more lengthy notes were collected at the end of the book as a ten-page supplement. This revised book was reprinted in 1960. [ 6 ]
This critical acclaim made Guthrie's name well known in history of medicine circles around the world. He made lecture tours, based on the book, to Central America (1949), Africa (1951–1952), Australasia (1953) and the United States in 1954, 1957 and 1961. [ 6 ]
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A Manual of Diseases of the Nervous System , also known as the ‘Bible of Neurology’, is a medical textbook by William Gowers . It was first published in 1886 by P. Blackiston & Son. A second volume appeared in 1888. [ 1 ] [ 2 ] [ 3 ] [ 4 ]
This article about a medical book is a stub . You can help Wikipedia by expanding it .
This history of medicine article is a stub . You can help Wikipedia by expanding it .
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https://en.wikipedia.org/wiki/A_Manual_of_Diseases_of_the_Nervous_System
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A Short History of Medicine is a book by Charles Singer , published in 1928 by Oxford University Press . [ 1 ] [ 2 ] [ 3 ]
This article about a non-fiction book on history of science is a stub . You can help Wikipedia by expanding it .
This history of medicine article is a stub . You can help Wikipedia by expanding it .
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Aapadbandhavudu ( transl. Protector against danger ) is a 1992 Indian Telugu -language drama film written and directed by K. Viswanath . [ 1 ] Produced by Edida Nageswara Rao 's Poornodaya Movie Creations , the film stars Chiranjeevi and Meenakshi Seshadri while Jandhyala , Sarath Babu , and Geetha play supporting roles. [ 2 ] It was the third collaboration between Chiranjeevi and Viswanath following Subhalekha (1982) and Swayam Krushi (1987).The second half hospital scenes are copied from 1975 hollywood movie One Flew Over the Cuckoo's Nest .
Aapadbandhavudu was an average grosser at the box office. [ 3 ] But, the film won critical acclaim with five state Nandi Awards , including the Nandi Award for Best Actor for Chiranjeevi, and the Filmfare Award for Best Actor – Telugu for Chiranjeevi. The film was screened at the International Film Festival of India , the Asia Pacific Film Festival , and the AISFM Film Festival . [ 4 ] [ 5 ] The film was later dubbed and released into Tamil as Veera Marudhu . [ 6 ]
Madhava is a loyal friend, servant, and cowherd to Hema and her father. He also performs in the local dramas, in which he portrays Shiva . Hema's father is a teacher and talented poet. However, since his classical poetry is no longer popular, he cannot find a publisher to print his poems. Even though Hema and Madhava love each other, neither realize this due to the societal divisions of caste and economic class present in their village. Hema is the first to realize her love for him, during a drama where she portrays Parvati , but suppresses her feelings owing to the social stigma.
One day, in order to pay for the wedding of Hema's elder sister Lalitha, Madhava sells his cows and gives the money to Hema's father through a family friend, as a loan. When Hema's father hears what he has done, he gives Madhava his manuscripts to have them printed. Madhava goes to town to have them printed; however, when he returns, he sees Hema being taken away to an asylum. He learns about the incident which led Hema's current mental state (i.e., Hema's brother-in-law's attempted rape and Lalitha's death).
Madhava pretends to be mentally unstable and is admitted to the same asylum, where he goes through many hardships in order to save Hema. After stopping a guard from attacking her, he is falsely accused of attempted rape and is given shock therapy. He tries many times to help her regain her memory. When she finally does and realizes what he did for her, she wants to marry him after she is safely rescued. However, Madhava objects to her proposal as he is from the lower strata of society. Hema's fiancé Sripathi convinces him to change his mind. Hema and Madhava finally unite.
All songs are composed by M. M. Keeravani and audio is owned by Lahari Music. [ 7 ] [ 8 ]
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The term abdominal surgery broadly covers surgical procedures that involve opening the abdomen ( laparotomy ). Surgery of each abdominal organ is dealt with separately in connection with the description of that organ (see stomach , kidney , liver , etc.) Diseases affecting the abdominal cavity are dealt with generally under their own names.
The most common abdominal surgeries are described below.
Complications of abdominal surgery include, but are not limited to:
Sterile technique, aseptic post-operative care, antibiotics , use of the WHO Surgical Safety Checklist , and vigilant post-operative monitoring greatly reduce the risk of these complications. Planned surgery performed under sterile conditions is much less risky than that performed under emergency or unsterile conditions. The contents of the bowel are unsterile, and thus leakage of bowel contents, as from trauma, substantially increases the risk of infection.
Globally, there are few studies comparing perioperative mortality following abdominal surgery across different health systems. One major prospective study of 10,745 adult patients undergoing emergency laparotomy from 357 centres in 58 high-, middle-, and low-income countries found that mortality is three times higher in low- compared with high-HDI countries even when adjusted for prognostic factors. [ 2 ] In this study the overall global mortality rate was 1.6 percent at 24 hours (high 1.1 percent, middle 1.9 percent, low 3.4 percent), increasing to 5.4 percent by 30 days (high 4.5 percent, middle 6.0 percent, low 8.6 percent). Of the 578 patients who died, 404 (69.9 percent) did so between 24 hours and 30 days following surgery (high 74.2 percent, middle 68.8 percent, low 60.5 percent). Patient safety factors were suggested to play an important role, with use of the WHO Surgical Safety Checklist associated with reduced mortality at 30 days.
Taking a similar approach, a unique global study of 1,409 children undergoing emergency laparotomy from 253 centres in 43 countries showed that adjusted mortality in children following surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries, translating to 40 excess deaths per 1,000 procedures performed in these settings. Internationally, the most common operations performed were appendectomy , small bowel resection , pyloromyotomy and correction of intussusception . After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23)) and middle-HDI (4.42 (1.44 to 13.56)) countries compared with high-HDI countries. [ 3 ]
Absorption of drugs administered orally was shown to be significantly affected following abdominal surgery. [ 4 ]
There is low-certainty evidence that there is no difference between using scalpel and electrosurgery in infection rates during major abdominal surgeries. [ 5 ]
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https://en.wikipedia.org/wiki/Abdominal_surgery
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The abdominojugular test , also known as abdominojugular reflux ( AJR ), is a physical examination test useful in diagnosing right ventricle dysfunction, particularly right ventricular failure . [ 1 ]
AJR is a test for measuring jugular venous pressure (JVP) through the distention of the internal jugular vein . A positive AJR test correlates with the pulmonary artery pressure and thus is a marker for right heart dysfunction, [ 2 ] specifically right ventricular failure . [ 1 ]
Reflux in this context means backup of the circulatory system and is not to be confused with reflex . [ 3 ]
The clinician presses firmly over either the right upper quadrant of the abdomen (i.e., over the liver ) or over the center of the abdomen [ 2 ] for 10 seconds with a pressure of 20 to 35 mm Hg while observing the swelling of the internal jugular vein in the neck and also observing to be sure the patient does not perform a Valsalva maneuver . [ 4 ]
On an otherwise healthy individual, the jugular venous pressure remains constant or temporarily rises for a heartbeat or two, before returning to normal. This negative result would be indicated by a lack of swelling of the jugular vein. Negative abdominojugular reflux is seen in Budd-Chiari syndrome .
A positive result is variously defined as either a sustained rise in the JVP of at least 3 cm or more [ 4 ] or a fall of 4 cm or more [ 2 ] after the examiner releases pressure. The AJR has a reported sensitivity of 24% [ 5 ] to 72% [ 2 ] and a specificity of 93% to 96%. The large discrepancy in sensitivity may be explained by the higher value being reported during performance in optimal conditions of a cardiac lab while the lower value was from a study in an emergency department.
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The abducens nerve or abducent nerve , also known as the sixth cranial nerve , cranial nerve VI , or simply CN VI , is a cranial nerve in humans and various other animals that controls the movement of the lateral rectus muscle , one of the extraocular muscles responsible for outward gaze . It is a somatic efferent nerve .
The abducens nucleus is located in the pons, on the floor of the fourth ventricle , at the level of the facial colliculus . Axons from the facial nerve loop around the abducens nucleus, creating a slight bulge (the facial colliculus) that is visible on the dorsal surface of the floor of the fourth ventricle. The abducens nucleus is close to the midline, like the other motor nuclei that control eye movements (the oculomotor and trochlear nuclei ). [ citation needed ]
Motor axons leaving the abducens nucleus run ventrally and caudally through the pons. They pass lateral to the corticospinal tract (which runs longitudinally through the pons at this level) before exiting the brainstem at the pontomedullary junction. [ citation needed ]
The abducens nerve emerges from the brainstem at the junction of the pons and the medulla , [ 1 ] superior to the medullary pyramid , [ 2 ] and medial to the facial nerve . It runs upwards and forwards from this position to reach the eye.
The nerve enters the subarachnoid space (more precisely, the pontine cistern [ 2 ] ) when it emerges from the brainstem. It runs upward between the pons and the clivus , and then pierces the dura mater to run between the dura and the skull through Dorello's canal . [ 3 ] [ 4 ] At the apex of the petrous part of the temporal bone , it makes a sharp turn forward to enter the cavernous sinus . [ 1 ] In the cavernous sinus, it runs anterior-ward alongside (inferolateral to) the internal carotid artery . It enters the orbit through (medial end of) the superior orbital fissure , passing through the common tendinous ring to reach and innervate the lateral rectus muscle of the eye. [ 2 ]
The human abducens nerve is derived from the basal plate of the embryonic pons .
The abducens nerve supplies the lateral rectus muscle of the human eye . This muscle is responsible for outward gaze. [ 1 ] The abducens nerve carries axons of type GSE, general somatic efferent .
Damage to the peripheral part of the abducens nerve will cause double vision ( diplopia ), due to the unopposed muscle tone of the medial rectus muscle . The affected eye is pulled to look towards the midline. In order to see without double vision, patients will rotate their heads so that both eyes are toward the temple. [ citation needed ] Partial damage to the abducens nerve causes weak or incomplete abduction of the affected eye. The diplopia is worse on attempts at looking laterally.
The long course of the abducens nerve between the brainstem and the eye makes it vulnerable to injury at many levels. For example, fractures of the petrous temporal bone can selectively damage the nerve, as can aneurysms of the intracavernous carotid artery. Mass lesions that push the brainstem downward can damage the nerve by stretching it between the point where it emerges from the pons and the point where it hooks over the petrous temporal bone.
The central anatomy of the sixth nerve predicts (correctly) that infarcts affecting the dorsal pons at the level of the abducens nucleus can also affect the facial nerve, producing an ipsilateral facial palsy together with a lateral rectus palsy. The anatomy also predicts (correctly) that infarcts involving the ventral pons can affect the sixth nerve and the corticospinal tract simultaneously, producing a lateral rectus palsy associated with a contralateral hemiparesis. These rare syndromes are of interest primarily as useful summaries of the anatomy of the brainstem.
Complete interruption of the peripheral sixth nerve causes diplopia (double vision), due to the unopposed action of the medial rectus muscle . The affected eye is pulled medially. In order to see without double vision, patients will turn their heads sideways so that both eyes are looking sideways. On formal testing, the affected eye cannot abduct past the midline – it cannot look sideways, toward the temple. Partial damage to the sixth nerve causes weak or incomplete abduction of the affected eye. The diplopia is worse on attempted lateral gaze, as would be expected (since the lateral gaze muscle is impaired).
Peripheral sixth nerve damage can be caused by tumors, aneurysms, or fractures – anything that directly compresses or stretches the nerve. Other processes that can damage the sixth nerve include strokes (infarctions), demyelination, infections (e.g. meningitis ), cavernous sinus diseases and various neuropathies. Perhaps the most common overall cause of sixth nerve impairment is diabetic neuropathy . Iatrogenic injury is also known to occur, with the abducens nerve being the most commonly injured cranial nerve in halo orthosis placement. [ 5 ] The resultant palsy is identified through loss of lateral gaze after application of the orthosis.
Rare causes of isolated sixth nerve damage include Wernicke–Korsakoff syndrome and Tolosa–Hunt syndrome . Wernicke–Korsakoff syndrome is caused by thiamine deficiency, classically due to alcoholism. The characteristic ocular abnormalities are nystagmus and lateral rectus weakness. Tolosa-Hunt syndrome is an idiopathic granulomatous disease that causes painful oculomotor (especially sixth nerve) palsies.
Indirect damage to the sixth nerve can be caused by any process ( brain tumor , hydrocephalus , pseudotumor cerebri , hemorrhage, edema) that exerts downward pressure on the brainstem, causing the nerve to stretch along the clivus. This type of traction injury can affect either side first. A right-sided brain tumor can produce either a right-sided or a left-sided sixth nerve palsy as an initial sign. Thus a right-sided sixth nerve palsy does not necessarily imply a right-sided cause. Sixth nerve palsies are infamous as "false localizing signs." Neurological signs are described as "false localizing" if they reflect dysfunction distant or remote from the expected anatomical location of pathology. Isolated sixth nerve palsies in children are assumed to be due to brain tumors until proven otherwise.
Damage to the abducens nucleus does not produce an isolated sixth nerve palsy , but rather a horizontal gaze palsy that affects both eyes simultaneously. The abducens nucleus contains two types of cells: motor neurons that control the lateral rectus muscle on the same side, and interneurons that cross the midline and connect to the contralateral oculomotor nucleus (which controls the medial rectus muscle of the opposite eye). In normal vision, lateral movement of one eye (lateral rectus muscle) is precisely coupled to medial movement of the other eye (medial rectus muscle), so that both eyes remain fixed on the same object.
The control of conjugate gaze is mediated in the brainstem by the medial longitudinal fasciculus (MLF), a nerve tract that connects the three extraocular motor nuclei (abducens, trochlear and oculomotor) into a single functional unit. Lesions of the abducens nucleus and the MLF produce observable sixth nerve problems, most notably internuclear ophthalmoplegia (INO).
The sixth nerve is one of the final common pathways for numerous cortical systems that control eye movement in general. Cortical control of eye movement ( saccades , smooth pursuit, accommodation ) involves conjugate gaze , not unilateral eye movement.
15–40% of people with tuberculosis have some resulting cranial nerve deficit. The sixth nerve is the most commonly affected cranial nerve in immunocompetent people with tuberculosis. [ 6 ]
The Latin name for the sixth cranial nerve is "nervus abducens". The Terminologia Anatomica officially recognizes two different English translations: "abducent nerve" and "abducens nerve". [ 7 ]
"Abducens" is more common in recent literature, while "abducent" predominates in the older literature. The United States National Library of Medicine uses "abducens nerve" in its Medical Subject Heading ( MeSH ) vocabulary to index the vast MEDLINE and PubMed biomedical databases. The 39th edition of Gray's Anatomy (2005) also prefers "abducens nerve." [ 1 ]
The abducens nerve controls the movement of a single muscle, the lateral rectus muscle of the eye. In most other mammals it also innervates the musculus retractor bulbi , which can retract the eye for protection. Homologous abducens nerves are found in all vertebrates except lampreys and hagfishes .
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Abductin is a naturally occurring elastomeric protein found in the hinge ligament of bivalve mollusks . It is unique as it is the only natural elastomer with compressible elasticity, as compared to resilin, spider silk, and elastin. [ 1 ] Its name was proposed from the fact that it functions as the abductor of the valves of bivalve mollusks.
The properties of abductin vary across species of bivalves due to the specific use case of the species or the environment the species is found in. In spite of these differences, the same general function of acting opposite of the abductor muscles, where the resilin forces the shells into an open configuration.
Though patents for a specific protein sequences of abductin were approved by the United States Patent and Trademark Offices, there are no large scale commercial uses for abductin as of April 2022.
The amino acid composition of protein within the inner hinge ligament of bivalve mollusks was first discovered by Robert E. Kelly and Robert V. Rice in 1967, who subsequently proposed the protein’s name as abductin. [ 3 ] This was derived from its function as the abductor of the shells of bivalve mollusks. Kelly and Rice discovered that the protein lacked the presence of hydroxyproline and hydroxylysine, which are amino acids indicative of the common protein, collagen. Further analysis showed that abductin is made of three prominent amino acids: glycine, methionine, and phenylalanine, which are arranged in multiple repeating sequences throughout the molecule. [ 4 ] This was found in Placopecten magellanicus. Abductin is similar to elastin and resilin, but has a main difference having high concentrations of glycine and methionine. [ 3 ] The glycine and methionine, and other amino acid residues, vary in concentration with different species. In Argopecten irradians, for example, glycine and methionine make up 57.3% and 14.3% of the protein, respectively. [ 4 ] The high concentration of methionine found in abductin makes it unique because it is not a common occurrence in natural elastomeric proteins.
Peptide sequences such as MGGG, FGGMG, FGGMGGG, GGFGGMGGG, and FGGMGGGNAG are repeated throughout the peptide chain. [ 3 ] It is to note that these peptide sequences all contain glycine. Additionally, in Argopecten irradians, the pentapeptide FGGMG is repeated throughout the molecule. [ 5 ] The main peptide sequence feature of abductin is the presence of many repeating sequences, all of which contain glycine residues. This is similar to that of the structure of elastin.
Abductin is lightly cross-linked, which gives it its high elasticity. The source of cross-linking has been researched, but no concrete explanation has been devised. The lack of tyrosine in the peptide chain suggests that cross-links are not formed through dityrosine links, like it is in resilin. [ 5 ] Hypotheses of the mechanism of cross-linking have been proposed by various researchers. One potential source of cross-linking is due to the presence of a methionine dimer, ½ cystine in some species, or other similar amino acids that contains a disulfide bridge, which creates the cross-link between peptide chains. [ 2 ] [ 3 ] Another study discovered that 3,3'-methylene-bistyrosine could be responsible for the cross-linkage in abductin, similar to how tyrosine and lysine residues are responsible for the cross-linking in resilin and elastin. [ 6 ]
Abductin is acellular and amorphous in structure, as discovered through microscopy and x-ray diffraction, respectively. [ 2 ] Since abductin is insoluble and its isolation from the hinge ligament is difficult, there is a lack of research concerning its structure at the protein level, such as secondary and hierarchical structures. [ 2 ] More recent research on synthetic peptides derived from abductin were found to have polyproline II helix structure in aqueous solutions and type II β-turn structure in hydrophobic solvents. [ 1 ] Combinations of both structures can also be observed for longer abductin-like peptide chains. [ 1 ]
The use of abductin varies among the different species of mollusks in the world. Some, like scallops and file shells, are able to swim using a repetitive motion of opening and closing its shell, the motion of which rapidly intakes and expels water. [ 7 ] In other species of mollusks, the presence of abductin is usually located where the two shells come together to form a hinge. [ 8 ] Unlike the needs of scallops for efficient energy return for the purpose of movement, species like the Apylsia find it necessary to reduce energy return in favor of stability in opening and closing of the shells. [ 8 ] Abductin can be found within the resilium structure, which is used to store mechanical energy for this purpose. [ 7 ] The effectiveness of abductin is highly influenced by the morphological aspects of the mollusk's shell, such as its size and shape. [ 7 ] Other influences on the performance of abductin in mollusks is temperature, where there is a decrease in performance as the temperature of the surrounding environment decreases, and the presence of octopine - which acts as an analogous to lactic acid in mammals. [ 7 ] The implementation of the resilium structure of the clam can be modeled as an oscillatory system, where it works against the abductor muscle to open the shell of the organism; the resilium forces the shell open while the abductor muscle control the shell’s closure. [ 7 ]
Little data exist on the structure and function of compressible elastomeric proteins such as abductin. An understanding of the underlying structural features of these proteins may lead to the development of a new class of highly tailored ‘‘compressible’’ hydrogels. Gaining knowledge of the underlying structural and functional features of compressible natural elastomers, such as abductin, can lead to novel compressible bioelastomers with tailored material properties. [ 9 ]
By interpreting Hurst exponents as Flory, water results to be a poor solvent for the abductin peptides. [ 10 ] Predicting the functional solvent environment for insoluble proteins like abductin is particularly difficult because the protein’s hydrophobicity and the probable cross-linked nature suggest a less polar internal environment than the surrounding solvent. [ 9 ]
The presence of both extended conformations (PPII) and folded conformations (β-turns) in equilibrium to describe abductin has been previously suggested. [ 9 ] Circular Dichroism (CD) spectra revealed that AMP1 (a 25 amino acid abductin sequence) adopts a dominant unordered conformation at 258 °C and a polyproline II (PPII) conformation at 0 °C and 458 °C with a possible minor amount of type II β-turn conformers. [ 9 ] This observation indicates that AMP1 undergoes an inverse temperature transition in that it goes from a dominant unordered conformation to a periodic, extended PPII conformation with increasing temperature. [ 9 ] The secondary structure of abductin was also investigated by Nuclear Magnetic Resonance (NMR) and CD studies of several synthetic peptides. Most synthetic abductin-based peptides adopted polyproline II (PPII) structures, which are left-handed helices, in aqueous solution, whereas they had type II β-turns in trifluoroethanol (TFE), which is a more hydrophobic (less polar) solvent. The coexistence of PPII and type II β-turns and temperature-induced multiconformational transitions were observed with longer synthetic abductin-like peptides such as (FGGMGGGNAG)4 in hexafluoroisopropanol (HFIP). [ 11 ] The secondary structure of AB12 was qualitatively analyzed by comparing the CD spectra to other peptides with known secondary structures. The CD spectra of aqueous solutions of AB12 shows a strong negative peak at 200 nm and a tendency toward positive values at ~218 nm, which are characteristics of PPII helices. An isodichroic point at ~208 nm suggests an equilibrium exists between the PPII structure and other conformations. In addition, because the peak at 218 nm never exceeds zero, the spectra suggest the coexistence of unordered structures and PPII helices. A small negative band can be observed at ~225 nm, which likely results from the aromatic residue, phenylalanine, in the sequence. [ 11 ]
The effect of temperature on the secondary structure was studied. With increasing temperature, the magnitude of both peaks in the CD spectra at 200 and 218 nm decreased, which is typical for PPII helix conformations. In addition, the change in structure because of temperature was fully reversible and did not display any hysteresis. The PPII conformation, which is widely present in elastomeric proteins such as elastin and titin, is believed to play an important role in determining the elasticity of these proteins. [ 11 ] The abductin-based protein possessed reversible Upper Critical Solution Temperature (UCST) behavior and formed a gel-like structure. At high temperatures, it displayed irreversible aggregation behavior. Thermal responsiveness is a useful property for engineering drug delivery systems because the encapsulation and release of drugs can easily be controlled via temperature change. [ 11 ]
The abductin-based protein was cytocompatible, and cells spread slowly when first seeded on the abductin-based protein. [ 11 ] A LIVE/DEAD assay revealed that human umbilical vein endothelial cells had a viability of 98 ± 4% after being cultured for two days on the abductin-based protein. Initial cell spreading on the abductin-based protein was similar to that on bovine serum albumin. These studies thus demonstrate the potential of abductin-based proteins in tissue engineering and drug delivery applications due to the cytocompatibility and its response to temperature. [ 11 ]
Natural abductin has a tensile modulus of 1.25 MPa, which is higher than elastin (0.3−0.6 MPa) but on the same order of magnitude as resilin (0.6−2 MPa). [ 11 ] It has a compressive modulus of 4 MPa, which is higher than resilin (0.6−0.7 MPa). The superior mechanical properties of natural abductin offer the potential for designing protein-based biomaterials that can be utilized in a broader number of applications. [ 11 ]
A solution of AB12 (10 mg/mL in Milli-Q water) was visually observed to turn from transparent to opaque when cooled from room temperature to lower temperatures (incubated on ice). Dynamic Light Scattering (DLS) was used to further investigate the temperature responsiveness of AB12. An abrupt decrease in the hydrodynamic diameter (DH) of AB12 was observed when the protein solution was heated from 2 to 5 °C. This phenomenon is indicative of Upper Critical Solution Temperature (UCST) behavior. The change in DH at low temperatures was reversible and displayed some hysteresis. A moderate increase in DH was observed from 35 °C, and a sharper increase in DH occurred starting at 57 °C (aggregation temperature). Compared to the reversible UCST behavior, the transition that occurred at the aggregation temperature was irreversible. [ 11 ]
In the case of abductin, on compression, the equilibrium extended ⇄ folded should be shifted to the folded structures, decreasing the entropy. The uncompressed, multi-conformational state is recovered by a simple increase in entropy after the removal of the compression force. This is opposite to elastin’s behavior. [ 12 ]
The first patent that is dedicated to the usage and implementation of abductin was accepted by the United States Patent and Trademark Office on October 3, 2000 (Patent No. 6,127,166). [ 13 ] The patent in question details the specific protein sequence of abductin to be manufactured through biological means and the possible applications of the polymer, suggesting possible uses as a copolymer for other naturally occurring polymers, a fabric material, or a material that binds with antibodies. [ 13 ] As of April 2022, there hasn’t been large-scale production, nor application, of polymers derived from the abductin or related polymeric sequences.
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Aberrant subclavian artery , or aberrant subclavian artery syndrome , is a rare anatomical variant of the origin of the right or left subclavian artery . This abnormality is the most common congenital vascular anomaly of the aortic arch , [ 1 ] occurring in approximately 1% of individuals. [ 1 ] [ 2 ] [ 3 ]
This condition is usually asymptomatic. [ 1 ] The aberrant artery usually arises just distal to the left subclavian artery and crosses in the posterior part of the mediastinum on its way to the right upper extremity . [ 2 ] In 80% of individuals it crosses behind the esophagus . [ 2 ] Such course of this aberrant vessel may cause a vascular ring around the trachea and esophagus. Dysphagia due to an aberrant right subclavian artery is termed dysphagia lusoria , although this is a rare complication. [ 2 ] [ 3 ] In addition to dysphagia, aberrant right subclavian artery may cause stridor , dyspnoea , chest pain , or fever . [ 1 ] An aberrant right subclavian artery may compress the recurrent laryngeal nerve causing a palsy of that nerve, which is termed Ortner's syndrome . [ 4 ]
The aberrant right subclavian artery frequently arises from a dilated segment of the proximal descending aorta, the so-called Diverticulum of Kommerell (which was named for the German radiologist Burkhard Friedrich Kommerell (1901–1990), who discovered it in 1936). [ 5 ] [ 6 ] It is alternatively known as a lusorian artery . [ 1 ] [ 3 ]
In the normal embryological development of the aortic arches , the right dorsal aorta regresses caudal to the origin of the 7th intersegmental artery which gives rise to the right subclavian artery . In formation of an aberrant right subclavian artery, the regression occurs instead between the 7th intersegmental artery and the right common carotid so that the right subclavian artery is then connected to the left dorsal aorta via the part of the right dorsal aorta which normally regresses. During growth, the origin of the right subclavian artery migrates until it is just distal to that of the left subclavian. [ 3 ]
An aberrant subclavian artery (ASA) is commonly diagnosed through imaging studies that visualize the structure and origin of blood vessels. Is it often diagnosed incidentally. Here are the primary diagnostic tools used:
Echocardiography: Especially in infants, an echocardiogram may initially detect abnormal vessel placement. Though this method can provide clues, it may not always offer detailed images of the aorta and subclavian arteries.
Computed Tomography (CT) Angiography: CT scans with contrast provide high-resolution, 3D images of blood vessels, allowing clear visualization of the ASA’s location and course relative to the trachea and esophagus.
Magnetic Resonance Imaging (MRI): MRI or MR angiography can similarly detail the vascular anatomy and is often used in children to reduce radiation exposure.
Barium Swallow Study: If there are symptoms like dysphagia, this test can reveal if the esophagus is compressed by the aberrant artery, suggesting the presence of a vascular ring.
Each of these techniques provides unique insights into the vascular structure, helping determine the presence, orientation, and potential impact of an aberrant subclavian artery.
Surgery is occasionally used to treat the condition. [ 7 ]
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AbioCor was a total artificial heart (TAH) developed by the Massachusetts -based company AbioMed . It was fully implantable within a patient, due to a combination of advances in miniaturization, biosensors, plastics and energy transfer. The AbioCor ran on a rechargeable source of power . The internal battery was charged by a transcutaneous energy transmission (TET) system, meaning that no wires or tubes penetrated the skin, reducing the risk of infection. However, because of its size, this heart was only compatible with men who had a large frame. It had a product life expectancy of 18 months. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]
AbioCor was surgically introduced into 15 total patients, 14 of them during a clinical trial and one after FDA approval. However, due to insufficient evidence of its efficacy, AbioMed abandoned further development of the product. [ 6 ] [ 7 ] [ 8 ]
AbioMed was founded by Param Singh and David Lederman . The company began development of the AbioCor device in the 1990s, beginning animal studies in 1998 in preparation to demonstrate readiness for formal clinical trials in humans. [ 5 ] On January 30, 2001, the FDA granted AbioMed an investigational device exemption (IDE) for implantation into humans via a clinical trial. [ 9 ] This opened the door for the first implantation of the AbioCor into Robert Tools on July 2, 2001. He lived for 151 days before having a fatal cerebrovascular accident . [ 3 ] [ 10 ] [ 11 ] Time magazine awarded the AbioCor its Invention of the Year award in late 2001. [ 11 ]
The second patient, Tom Christerson, who was given less than a 20 percent chance of surviving 30 days at the time of his surgery, lived for 512 days after receiving the AbioCor, dying on February 7, 2003, due to the wearing out of an internal membrane of the AbioCor. [ 12 ] An additional 12 patients had the device implanted into 2004, resulting in an average life span of less than five months among all 14 patients. In some cases the device extended survival by several months, allowing the patients to spend valuable time with family and friends. In two cases, the device extended survival by 10 and 17 months respectively, and one patient was discharged from the hospital to go home. For a patient to be eligible for implantation with the AbioCor, the person must have had severe heart failure (with failure of both ventricles ) and had to be likely to die within two weeks without transplantation . [ 1 ] [ 2 ]
Though the device was initially rejected by FDA Circulatory System Devices Panel in 2005 for Humanitarian Device Exemption (HDE) status, [ 1 ] it was eventually approved by the Food and Drug Administration on September 5, 2006, for HDE status. [ 13 ] However, only one patient received the AbioCor after approval, a "76-year-old man with congestive heart failure, who did not qualify for a heart transplant." [ 14 ]
In August 2012, key AbioCor researcher and developer David Lederman died from pancreatic cancer. [ 15 ]
The company also had plans to improve the AbioCor with a second version based upon the AbioCor ventricles and the Penn State energy converter. It was expected to last for five years, more than triple the life expectancy of AbioCor. The company stated it would be 30 percent smaller than the original model, and it could be implanted in smaller men and women. Additional modifications were planned to reduce the patient's risk of stroke, which was a concern of the FDA. [ 10 ] [ 16 ] As of March 2016 [update] , AbioCor II has not come to fruition, however. Additionally, the AbioCor product has been removed from the AbioMed website, with several news agencies reporting in 2015 that the company had quietly abandoned further development of the device. [ 6 ] [ 7 ]
In 2019, Abiomed was marketing the Impella Ventricular Support Systems, left-side heart pump models "intended to help pump blood in patients who need short-term support (up to 6 days)". [ 17 ]
The AbioCor heart is featured in the 2009 film Crank: High Voltage , when it is transplanted into the main character Chev Chelios 's ( Jason Statham ) chest after he had been abducted by Chinese mobsters in the very beginning of the movie. However, the heart depicted in the film has a much lower battery life but gives Chev superhuman athleticism when fully charged (for dramatic purposes). [ 18 ] The model of the heart in the movie is called AviCor.
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Abiomed, Inc. is a medical device technology company that operates as a stand-alone business within Johnson & Johnson's MedTech Segment. [ 2 ] Abiomed develops and manufactures temporary external and implantable mechanical circulatory support devices. The company is headquartered in Danvers, Massachusetts with additional offices in Woburn , Baltimore , Berlin , Aachen , and Tokyo .
Andrew Greenfield is President of the company, with Dr. Thorsten Siess as Executive Vice President and Chief Technology Officer and Dr. Chuck Simonton as Executive Vice President and Chief Medical Officer. [ 2 ] According to Bloomberg, the company "engages in the research, development, and sale of medical devices to assist or replace the pumping function of the failing heart. It also provides continuum of care to heart failure patients". [ 3 ]
As of 2022, the company had secured five FDA approvals and 1,408 patents with 1,416 pending. [ 4 ] For fiscal year 2022, Abiomed reported $1.032 billion in revenue and reported diluted earnings per share was $2.98 for the year. [ 1 ]
On December 22, 2022, Johnson & Johnson completed the acquisition of Abiomed. [ 5 ]
Abiomed was founded in Danvers, Massachusetts by David M. Lederman in 1981 as Applied Biomedical Corporation. [ 6 ] That year, the company commenced the development of an artificial heart . [ 7 ] Funded by federal research grants, [ 8 ] Lederman partnered with The Texas Heart Institute to develop the AbioCor , a grapefruit -sized electromagnetic device with an internal battery that completely replaces the heart without wires or tubes passing through the skin. [ 6 ] In July 2001, AbioCor became the first artificial heart successfully implanted in a patient, where it pumped more than 20 million times. [ 9 ] Fourteen of the AbioCor devices were implanted, during clinical trials from 2001 to 2004, with the longest-living recipient surviving 512 days. [ 6 ] The AbioCor won FDA approval in 2006 for patients who are near death and do not qualify for a heart transplant . [ 7 ]
In 2004, Michael R. Minogue became president and CEO of Abiomed. [ 10 ] In 2005, Abiomed purchased ventricular assist device company Impella CardioSystems AG of Aachen, Germany , [ 11 ] maker of the Impella heart pump, developed by Thorsten Siess, [ 12 ] who is now the chief technology officer at Abiomed. [ 13 ] [ self-published source ] After Abiomed acquired Impella the company's focus shifted from heart replacement to heart recovery. [ 14 ]
In July 2014, Abiomed acquired German heart pump maker ECP in a deal worth up to $30 million. The deal included a nearly $2.8 million buyout of AIS GmbH Aachen Innovative Solutions, which owns some of the patents licensed to ECP. [ 15 ]
In May 2018, Abiomed was added to the S&P 500 index . [ 16 ] During the S&P's rise from 2000 to 3000, Abiomed was the index's top performing stock. [ 17 ]
In 2018, Abiomed built a $17 million Innovation Center to facilitate research and product development at its headquarters in Danvers. [ 18 ] The 29,800-square-foot facility features laboratories for blood, optical, software, mechanical and electrical research, plus a production line. [ 19 ]
In 2019, Barron's ranked Abiomed the fourth best stock of the 2010s, with total return of 1,983%. [ 20 ] while Fortune ranked Abiomed 19th on the magazine's list of 100 fastest-growing companies. [ 21 ]
In April 2020, Abiomed acquired medical device company Breethe, a startup that spun out of the University Of Maryland. [ 22 ] The startup had developed a portable extracorporeal membrane oxygenation (ECMO) system that acts like an artificial lung, oxygenating and removing carbon dioxide from the blood of a patient in cardiogenic shock or respiratory failure. [ 23 ] The technology, now known as the Abiomed Breethe OXY-1 System, received FDA 510(k) clearance later that year. [ 24 ]
In June 2020, Abiomed appointed Charles A. Simonton, MD, as vice president and Chief Medical Officer. [ 25 ] Also in 2020, the FDA granted Emergency Use Authorization for the Impella heart pump to stabilize COVID-19 patients following the removal of pulmonary blood clots, as well as the use of the Impella in combination with the Breethe extracorporeal membrane oxygenation (ECMO) system, which pumps more oxygen into the bloodstream. [ 26 ]
In February and April 2021, Abiomed appointed neurosurgeon Myron Rolle and cardiologist Paula Johnson to the board of directors. [ 27 ] Drs. Rolle and Johnson serve on the Governance and Nominating Committee and Regulatory and Compliance Committee of the board. [ 28 ] [ 29 ]
In June 2021, Abiomed acquired preCARDIA, a catheter developer whose system allows for a less-invasive option when treating acute decompensated heart failure (ADHF) patients. [ 30 ]
In November 2022, Abiomed announced that it would be acquired by Johnson & Johnson in a $16.6 billion deal. [ 31 ] The deal closed on December 22. [ 32 ] Following the acquisition, Abiomed continues to operate as a standalone business within Johnson & Johnson's MedTech segment. [ 2 ]
Impella is the world's smallest heart pump. [ 16 ] It sits in the heart, spinning up to 50,000 revolutions per minute, sending blood throughout the body, allowing the heart to rest and recover. It is inserted through a minimally invasive procedure and guided through an artery to the heart. [ 14 ] In 2007, the Impella 2.5 heart pump was among 35 healthcare products to receive a 2007 Medical Design Excellence Award. [ 33 ] As of 2022, the Impella heart pump products include the Impella 2.5, Impella 5.0, Impella CP with SmartAssist, Impella 5.5 with SmartAssist, Impella RP with SmartAssist and Impella Connect, which gives providers 24/7 secure access to Impella status data in the cloud for Impella-supported patients. [ 34 ]
The Abiomed Breethe OXY-1 System is an extracorporeal membrane oxygenation (ECMO) system that pumps, oxygenates and removes carbon dioxide from blood of patients suffering from cardiogenic shock or respiratory failure due to ARDS, H1N1, SARS and COVID-19 among other causes. It can be used alone or in conjunction with the Impella heart pump. [ 24 ]
Since 2005 when Abiomed acquired the Impella technology, [ 35 ] the heart devices have received a series of FDA approvals. [ 36 ] Notably, in 2015, Abiomed received FDA approval to use the Impella 2.5 heart pump during elective and urgent high-risk percutaneous coronary intervention procedures. The FDA approval was based on the PROTECT II randomized controlled trial, which found high-risk percutaneous coronary intervention (PCI) patients who underwent PCI with Impella had fewer major adverse events at 90 days (although statistically non-significant), compared to patients who underwent PCI with the intra-aortic balloon pump (IABP). [ 37 ] In 2016, the Impella RP system became the first percutaneous single-access heart pump designed for right-heart support to receive FDA approval. [ 38 ]
There is a lack of data from randomized controlled trials for Impella devices in cardiogenic shock, despite calls from the medical community. [ 39 ] While early studies suggested short term benefits, propensity-matched analyses comparing the Impella device with intra-aortic balloon pump (IABP) showed no benefit for clinically relevant outcomes such as mortality. [ 40 ] This may be partly due to increased risk of bleeding and peripheral vascular complications with the Impella device. [ 41 ] Some studies have even suggested an increased risk of mortality with Impella devices, compared to the intra-aortic balloon pump (IABP), with an additional expense of >$50,000 at 30 days. [ 42 ] There are currently no adequately powered randomized controlled trials of the Impella device for clinically relevant outcomes such as mortality.
In 2021, the FDA granted pre-market approval to the Impella RP with SmartAssist, a first single-access, dual-sensor technology device to provide temporary percutaneous ventricular support for patients with acute right heart failure or decompensation after implanting a left ventricular assist device, myocardial infarction, heart transplant or open-heart surgery. [ 43 ] The FDA also granted breakthrough device designation for its smallest heart pump, the Impella ECP, which measures only 3mm in length. [ 44 ]
In April 2022, Abiomed's Impella Bridge-to-Recovery (BTR) minimally-invasive heart pump was successfully implanted in the first patient treated with the device as part of an early feasibility study. [ 45 ] In August 2022, results from the Restore EF study were published in The Journal of the Society of Cardiovascular Angiography and Interventions . The study demonstrated that Impella-supported high-risk percutaneous coronary intervention (PCI) led to significant improvements in left ventricular ejection fraction (LVEF), angina symptoms, and heart failure symptoms at the 90-day follow-up. [ 46 ] In October 2022, the FDA granted pre-market approval to the Impella RP Flex with SmartAssist for treatment of acute right heart failure for up to 14 days. [ 47 ]
Andrew Greenfield is Abiomed's President since the company was acquired by Johnson & Johnson in December 2022. He succeeded Michael R. Minogue who retired after serving as chairman, President and CEO since 2004 when Abiomed's founder, David Lederman, had stepped down. [ 2 ] [ 7 ]
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Abraham Low Self-Help Systems ( ALSHS ) is a non-profit organization formed from the merger of Recovery International and the Abraham Low Institute. ALSHS facilitates the estimated 600 worldwide Recovery International meetings and all projects formerly run by the Abraham Low Institute including the Power to Change program. The organization is named after Abraham Low , founder of the mental health self-help organization now known as Recovery International.
Recovery, Inc., often referred to simply as Recovery, was officially formed November 7, 1937, by neuropsychiatrist Abraham Low in Chicago, Illinois . [ 5 ] Low created the organization to facilitate peer support self-help groups for former mental patients and later allowed for participation of those who had not been hospitalized, but with a desire to improve their mental health. [ 6 ] During the organization's annual meeting in June 2007 it was announced that Recovery, Inc. would thereafter be known as Recovery International. [ 7 ] As of 2008 there were over 600 weekly Recovery International meetings held throughout North America , Ireland , the United Kingdom , Israel and India . [ 8 ]
The Abraham Low Institute was founded in 1989 to develop programs, in addition to Recovery, based on Low's self-help principles. [ 4 ] [ 9 ] The Institute awarded grants to further scholarly research on Low's work, provided research resources for people interested in Low's methods, and developed the Power to Change program and The Relatives Project. [ 10 ]
On January 1, 2008 Recovery International merged with The Abraham Low Institute and provisionally renamed the new organization Recovery International / The Abraham Low Institute (RI/TALI). [ 8 ] [ 11 ] Celinda Jungheim, a community volunteer from Los Angeles , was elected as president of the Board of Directors. [ 3 ] Abraham Low Self-Help Systems was incorporated on January 1, 2009, completing the merger of Recovery International and The Abraham Low Institute. Abraham Low Self-Help Systems is now the provider of Recovery International community, phone and online meetings and The Power to Change program, which was a program of The Abraham Low Institute. [ 1 ]
The Relatives Project, found in 1993, provides support for family and friends of people who have mental and emotional problems. [ 12 ] The Relatives Project teaches coping skills and stress management through meetings similar to those held in Recovery International groups, but using literature written by Abraham Low specifically for the families of his patients. Relatives are taught to maintain empathy and unconditional positive regard for their ill relative, while reframing their domestic environment to provide an empowering atmosphere for all members. The Relatives Project groups are open to adults and teenagers, and allow professionals to observe but only to participate if it is in support of a family member's mental health. [ 13 ] Mental health becomes a shared goal for a family, and all family members share in responsibility to achieve it. [ 14 ]
Power to Change is a cognitive-behavioral peer-to-peer program based on Low's self-help principles. Power to Change primarily teaches at-risk students and ex- prisoners principles of Low's Self-Help system in peer-to-peer groups. [ 4 ] [ 15 ] Power to Change groups generally consist of 8-12 members, meeting weekly, who learn the principles of the Low Self-Help System by describing their personal experience of disturbing events and commenting on each other's experiences using a highly structured format. [ 4 ] [ 9 ]
Specifically, Power to Change consists of five components:
The four-part example consists of an objective description an event; a report of the feelings, sensations, thoughts, and impulses experienced in the members mind and body; how the member used the Power to Change tools to manage the experience; and a self-endorsement to remind the member of the progress made and to reward their effort. The Power to Change groups use much of the language suggested in the Recovery International program, such as identifying "temper" and avoiding judgment of right and wrong. [ 15 ]
The W. K. Kellogg Foundation has provided grants for Power to Change since 2003. The most recent grant was awarded in November 2008, and will provide funding until November 2010. [ 2 ] [ 10 ] [ 16 ]
In 2007 Urban Networks Associates (UNA) conducted an evaluation of Power to Change as it was implemented in seventeen secondary and middle schools in the Chicago Public School system. In each school 12-24 group sessions were held and facilitated by either staff from the Abraham Low Institute or by a local facilitator trained by the Abraham Low Institute. Participating students showed significant improvement in prosocial behavior as measured by pre-testing and post-testing of emotional intelligence , specifically increasing self-restraint and decreasing violent behaviors . Although statistically significant , the effect sizes of changes were low or medium. [ 17 ]
UNA's SEM evaluation of the Power to Change logic model , the required steps and conditions for the program to be effective, found it fit the data collected well. To improve the effectiveness of the program UNA recommended improving communication with and training of local facilitators, encouraging students to develop plans to apply program tools outside of the group, updating the literature used to make it more age appropriate for the young students, adding activities to encourage confidentiality of what was said in group meetings and developing more interactive activities to teach program concepts. UNA also suggested asking for a commitment from participating schools to guarantee facilities were always available and that students would not be prohibited from attending group sessions. [ 17 ]
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An abrasion collar , also known as an abrasion ring or abrasion rim , is a narrow ring of stretched, abraded skin immediately surrounding projectile wounds, such as gunshot wounds . It is most commonly associated with entrance wounds and is a mechanical defect due to a projectile's penetration through the skin. It is caused by a temporary over-stretching of the skin surrounding the projectile's point of penetration. Like all skin abrasions, the abrasion collar tends to dry out due to scraping away of the skin's outer layers and the collapse and dehydration of the underlying cells; it therefore becomes easier to discern with time. [ 1 ] This defect is most often seen around rifled firearm entrance wounds due to the striations or grooves in the bullet's surface caused by the rifling on the inside of the weapon's barrel ; however, certain other high-velocity projectile wounds can also have the same effect. [ 2 ]
An abrasion collar is usually found in association with a contusion collar of bruising caused by damaged blood vessels in the skin by hydrostatic forces from the bullet's entry. [ 3 ] An abrasion rim defect is also possible in firearm exit wounds under certain circumstances, such as if the skin at the exit was crushed between the outgoing bullet and an unyielding object pressed against the skin over the exit site, or if the projectile exits at an extreme angle. Careful examination of the wound under magnification may show signs of everted (outward-turned) edges characteristic of an exit wound. [ 4 ] Multiple projectiles impacting in close proximity together, such as in a close-range shotgun blast, will usually still produce an abrasion rim or artefact, though the wound will likely be irregular in shape. [ 3 ]
In the case of gunshot wounds from unjacketed lead alloy bullets or dirty bullets, a phenomenon known as bullet wipe may be observed, which forms a ring of greasy residue known as a grease or dirt collar that overlays the abrasion collar and is caused by deposits on the skin's surface. Generally, these deposits contain lead from the unjacketed projectile or oil from inside the weapon's barrel, but they may simply be dirty. Studies using high-speed photography have shown that bullet wipe is caused only by the head of the bullet—instead of the body—because the skin recoils away from the bullet as it penetrates due to the force of entry. [ 1 ]
The bullet's angle of trajectory at the point where it penetrates the skin can influence the shape of the abrasion collar. This can be used by forensic pathologists in discerning an approximate angle of entry and is important in investigations of gunshot wound victims, where evidence of the gunshot's origin is necessary to determine whether the death was homicidal , suicidal , or accidental. Generally, if the bullet impacts at an angle perpendicular to the skin surface, the abrasion collar will be symmetrical, concentric, round, and evenly-shaped. As the angle between the trajectory and the skin surface decreases, the abrasion collar becomes more distorted and often more distinct at the point of entry, having a semi-lunar or "half-moon" shape with the broadest width pointing in the direction of the gunshot's origin. [ 3 ] This is caused by the exterior of the bullet contacting and scraping over the skin's surface for a certain distance before penetrating the skin. [ 1 ]
The bullet shape influences the size of the abrasion collar. [ 5 ] High velocity bullets with pointed, narrow, or spitzer tips, such as rifle rounds, and full metal jacket bullets are less likely to produce abrasion collars compared to lower-velocity, semi-jacketed civilian bullets, such as bullets fired from handguns , which have rounded noses. [ 6 ]
If the wound is caused by a high-velocity rifle bullet, the abrasion collar may be smaller, but it may have minute tears in the surface of the skin surrounding the wound entrance. This is because the skin is not capable of stretching quickly enough if the bullet's velocity is too high. If the wound is made over bone , such as a head wound in the scalp , the abrasion collar may not be round at all; it instead becomes stellate or "star-shaped" with ragged and torn edges caused by the skin over-stretching and tearing. In the case of skull entrance wounds, the skin that includes the abrasion collar may be torn away because the underlying tissue is unable to flex away from the force of the bullet's entry. [ 1 ]
Towards the end of a bullet's effective range, it tends to lose axial stability and will begin to yaw or even tumble end-over-end. This means it may impact the skin while travelling sideways, and the resulting wound may be distorted, irregular in shape, or even slit-like, such that it does not resemble a conventional entrance wound. In this case, an abrasion artefact may be absent. [ 3 ] Similarly misshapen wounds can be caused by the distortion of the bullet if it hits an intermediate object (including another part of the victim's own body, in what is known as a re-entrant wound ) before penetrating the skin surface. However, careful examination of the wound under magnification may show the inverted wound edges and signs of an irregularly-shaped abrasion rim characteristic of entry wounds. [ 1 ]
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Absolute risk (or AR) is the probability or chance of an event . It is usually used for the number of events (such as a disease) that occurred in a group, divided by the number of people in that group. [ 1 ]
Absolute risk is one of the most understandable ways of communicating health risks to the general public. [ 2 ]
In difference to absolute risk, the relative risk (RR) is the ratio of the probability of an outcome (probability) in an exposed group to the probability of an outcome in an unexposed group.
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In dentistry , an abutment is a connecting element. [ 1 ] This is used in the context of a fixed bridge (the "abutment teeth" referring to the teeth supporting the bridge), partial removable dentures (the "abutment teeth" referring to the teeth supporting the partial) and in implants (used to attach a crown , bridge , or removable denture to the dental implant fixture). The implant fixture is the screw-like component that is osseointegrated .
Dental bridge abutments are made such that the path of insertion of the teeth involved is nearly parallel with each other.
Partial denture abutments [ 2 ] are unique in that they may incorporate elements such as rest seats, guide planes, and recontouring.
These are usually called prosthetic implant abutments and are responsible for making the connection between the prosthesis and the implant. [ 3 ] These abutments can be made from a variety of materials, such as titanium , surgical stainless steel , gold and zirconia .
The adjacent images show how a ceramic abutment can enhance a ceramic crown by giving it a more lifelike appearance. Ceramic abutments have to be used with care, since their compressive strength is nowhere near that of titanium, gold or other noble metals. Most clinicians feel more comfortable using a metal prosthetic abutment in the posterior molar areas, due to the increased masticatory forces present in these areas.
An abutment is not necessarily parallel to the long axis of the implant. It is utilized when the implant is at a different inclination in relation to the proposed prosthesis. Most crowns and fixed partial dentures have a cemented or screw-retained fixation on the abutment.
In a three-piece implant the abutment is fixed on the implant with a screw butt joint . [ 4 ] This screw needs to be tightened to a predetermined torque with a dental torque wrench , in order to avoid screw loosening during chewing, which can often create a counter-clockwise torque on the implant–abutment interface, encouraging the abutment screw to come loose. This can largely be prevented with proper screw design and torquing of the abutment.
In a two-piece implant the abutment is morse tapered or [Note: Titanium metal does not cold weld|weldguru.com</ref>] on the implant. Microbial leakage and colonization between the implant and the abutments can result in inflammatory reactions and crestal bone loss. Morse taper conical abutments showed a cumulative implant survival rate of 98.23% [ 5 ] in terms of seal performance, microgap formation, torque maintenance, and abutment stability. [ 6 ]
A one-piece implant incorporates the trans-mucosal abutment as an integral part of the implant. [ 7 ] This type of implant is often used with a flapless procedure and immediate loading (the crown is placed a short time after placing the implant). [ 8 ]
An impression is taken from the implant site using conventional impression materials or digital scanning. [ 9 ] This impression serves as a template for the fabrication of the abutment and the final prosthesis. [ 10 ] [ 11 ] [ 12 ] Based on the treatment plan, the implantologist selects the appropriate type and design of the abutment, taking into consideration factors such as aesthetics, functional requirements, and the patient's anatomical features. The chosen abutment is carefully installed onto the implant and secured in place. Depending on the abutment system, a fastening screw or a special attachment mechanism may be used to connect to the implant. [ 13 ] [ 14 ] [ 15 ] The abutment screw is tightened, ensuring a reliable and stable connection between the abutment and the implant. To ensure proper alignment and load distribution within the restoration, occlusal adjustment may be performed. Immediately after screwing in the metal components, a healing abutment is embedded. The healing abutments are the primary mounted component, after which the patient transitions to one of the types of abutments. In some cases, after the implant is initially placed, a healing abutment is installed. It helps shape the soft tissues during the healing phase and is later replaced with the final abutment once the desired gum contours are achieved.
Titanium metal is not suitable to be cold welded weldguru.com<weldguru.com/ weldminds.com>
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Academic detailing is " university or non-commercial -based educational outreach." [ 1 ] The process involves face-to-face education of prescribers by trained health care professionals, typically pharmacists , physicians , or nurses . The goal of academic detailing is to improve prescribing of targeted drugs to be consistent with medical evidence from randomized controlled trials , which ultimately improves patient care and can reduce health care costs . A key component of non-commercial or university-based academic detailing programs is that they (academic detailers/clinical educators, management, staff, program developers, etc.) do not have any financial links to the pharmaceutical industry .
Academic detailing has been studied for over 25 years [ 2 ] and has been shown to be effective at improving prescribing of targeted medications about 5% from baseline. [ 3 ] Though it is primarily used to affect prescribing, it is also used to educate providers regarding other non-drug interventions , such as screening guidelines .
Many academic detailing programs exist around the world. In the United States , university-based state programs exist in Illinois, [ 4 ] Vermont , [ 5 ] Oregon [ 6 ] and South Carolina . [ 7 ] The nonprofit organization Alosa Health [ 8 ] runs an academic detailing program in Pennsylvania, Massachusetts and Washington, DC called the Independent Drug Information Service (IDIS). The National Resource Center for Academic Detailing (NaRCAD), funded by the Agency for Healthcare Research and Quality (AHRQ) in 2010, was created to help organizations with limited resources to establish and improve their own programs and to create a network of academic detailing programs. The U.S. Department of Veterans Affairs Pharmacy Benefits Management pilot tested the National Academic Detailing Service in 2010 to enhance veterans' outcomes by empowering clinicians and promoting the use of evidence-based treatments using delivered by clinical pharmacy specialists. [ 9 ] After the pilot, in March 2015, the Interim Under Secretary for Health issued a memorandum requiring implementation of AD programs throughout the Veterans Health Administration . [ 10 ]
Programs also exist in Canada through the Canadian Academic Detailing Collaboration (CADC) , [ 11 ] including the Centre for Effective Practice's (CEP) academic detailing service [ 12 ] in Ontario, [ 13 ] and Australia through the Drug and Therapeutics Information Service (DATIS) and the National Prescribing Service (NPS). In Belgium academic detailing is provided by Project Farmaka.
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The Academy of Clinical Laboratory Physicians and Scientists is a learned society for scientists in the fields of clinical pathology and laboratory medicine . It was founded on November 12, 1966, in Bethesda , Maryland by a group of fifty-one individuals, led by David Seligson, Jon
Straumfjord, George Z. Williams, Ernest Cotlove, and Ellis Benson. The society's founding mission was to represent scientists in the fields of clinical pathology and laboratory medicine in both the United States and Canada . [ 1 ] As of 2015, it had 295 active members, as well as an additional 127 associate members, 195 emeritus members, and 5 honorary members. [ 2 ] Along with the American Society for Clinical Pathology , it co-sponsors the American Journal of Clinical Pathology . [ 3 ]
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Accelerated idioventricular rhythm is a ventricular rhythm with a rate of between 40 and 120 beats per minute. Idioventricular means “relating to or affecting the cardiac ventricle alone” and refers to any ectopic ventricular arrhythmia. [ 1 ] Accelerated idioventricular arrhythmias are distinguished from ventricular rhythms with rates less than 40 ( ventricular escape ) and those faster than 120 ( ventricular tachycardia ). [ 2 ] Though some other references limit to between 60 and 100 beats per minute. [ 3 ] It is also referred to as AIVR and "slow ventricular tachycardia."
It can be present at birth, [ 4 ] however, it is more commonly associated with reperfusion after myocardial injury . [ 2 ] AIVR is generally considered to be a benign abnormal heart rhythm. It is typically temporary and does not require treatment.
The accelerated idioventricular rhythm occurs when depolarization rate of a normally suppressed focus increases to above that of the "higher order" focuses (the sinoatrial node and the atrioventricular node ). This most commonly occurs in the setting of a sinus bradycardia . [ 5 ]
Accelerated idioventricular rhythm is the most common reperfusion arrhythmia in humans. However, ventricular tachycardia and ventricular fibrillation remain the most important causes of sudden death following spontaneous restoration of antegrade flow. [ 6 ] Prior to the modern practice of percutaneous coronary intervention for acute coronary syndrome , pharmacologic thrombolysis was more common and accelerated idioventricular rhythms were used as a sign of successful reperfusion. [ 7 ] It is considered a benign arrhythmia especially in the setting of STEMI(where it is conventionally thought to be an indicator of reperfusion) that does not require intervention, though atrioventricular dyssynchrony can cause hemodynamic instability, which can be treated through overdrive pacing or atropine . [ 2 ]
AIVR appears similar to ventricular tachycardia with wide QRS complexes (QRS >0.12s) and a regular rhythm. It can most easily be distinguished from VT in that the rate is less than 120 and usually less than 100 bpm. There may or may not be AV dissociation depending on whether it is due to ventricular escape or AV block. [ 8 ]
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Accelerated phase chronic myelogenous leukemia is a phase of chronic myelogenous leukemia in which the disease is progressing. [ 1 ]
Common symptoms include fever , bone pain , and swollen spleen . [ 2 ]
Patients treated with imatinib , dasatinib , and nilotinib have shown meaningful rates of hematologic and cytogenetic response. [ 3 ]
Prognosis is very poor once chronic myelogenous leukemia reaches the accelerated phase; it behaves similarly to acute myeloid leukemia .
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An acceleromyograph is a piezoelectric myograph , used to measure the force produced by a muscle after it has undergone nerve stimulation. Acceleromyographs may be used, during anaesthesia when muscle relaxants are administered, to measure the depth of neuromuscular blockade and to assess adequacy of recovery from these agents at the end of surgery. Acceleromyography is classified as quantitative neuromuscular monitoring . [ citation needed ]
Patients who undergo anesthesia may receive a drug that paralyzes muscles, facilitating endotracheal intubation and improving operating conditions for the surgeon. Longer-acting drugs have higher prevalence of residual blockade in the PACU or ICU than shorter acting drugs. Different clinical tests to measure or exclude evidence of residual muscle weakness have been described but cannot exclude postoperative residual curarization . [ 1 ] Small degrees of muscle blockade can only accurately be measured by the use of quantitative neuromuscular monitoring. Specifically, the observer cannot reliably measure muscular fade when train-of-four ratios are between 0.4 and 0.9. [ 2 ]
Acceleromyographs measure muscle activity using a miniature piezoelectric transducer that is attached to the stimulated muscle. A voltage is created when the muscle accelerates and that acceleration is proportion to force of contraction. The mass of the piezoelectric transducer is known and the acceleration is measured therefore the force can be calculated, ( Force = mass × acceleration ). Acceleromyographs are more costly than the more common twitch monitors, but have been shown to better alleviate residual blockade and associated symptoms of muscle weakness, and to improve overall quality of recovery. [ citation needed ]
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The Accreditation Commission on Colleges of Medicine ( ACCM ) is an international medical review and accreditation agency service for medical schools . [ 1 ]
The National Committee on Foreign Medical Education and Accreditation (NCFMEA), part of the United States Department of Education , has listed ACCM as "found to use standards to accredit their medical schools that are comparable to the standards used to accredit medical schools in the United States." [ 1 ]
In 2017 ACCM was granted a 10-year recognition by the World Federation on Medical Education (WFME) [ 2 ]
The ACCM works on behalf of the governments in relation to medical school standards in the following Caribbean countries and one middle Eastern country and according to its site there is only one ACCM accredited medical school in each of the countries:. [ 3 ]
As of 2020, various schools ( Aureus University School of Medicine in Aruba , Arabian Gulf University (AGU) in Bahrain and Jordan University of Science & Technology in Jordan ) were pending onsite full accreditation inspection which would be scheduled after travel restrictions associated with the COVID-19 global pandemic were removed. [ 4 ]
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Achiria , also referred to as "Simple Allochiria ", is a neurological disorder in which a patient is unable to recognise or perceive one side of their body. [ 1 ] It is oftentimes associated with dyschiria , also known as a form of unilateral neglect or hemispatial neglect . The term achiria is seldom used in modern scientific literature.
Psychologists in the past defined dyschiria as the inability of patients to distinguish the side of which a given stimulus is generated from. There are three forms of dyschiria: achiria, allochiria and synchiria, of which achiria is considered to be the primary stage. [ 2 ]
Patients with achiria would have deficits in sensory, motor and introspective areas of consciousness. The symptoms are associated with hysteria , spinal lesions and unilateral neglect syndrome . In Greek terminology, "chiria" or "χεiρ" means hand, while the "a-" prefix means "without" or "not". [ 3 ] [ 4 ] However, in actual clinical practice, achiria is also referred to the inability to localize stimuli from other parts of the body.
Sensory achiria describes the situation when the patient is not able to feel the sidedness of a stimulus when it is applied to a body part. According to Welsh psychiatrist Ernest Jones , patients with sensory achiria are certain that they do not know which side of the body the stimulus comes from, instead of being uncertain and struggling between picking a side. [ 1 ]
Despite the spatial disorder , the patient's sensory acuity is not necessarily affected. He/she might be able to effectively tell the position, intensity and nature of the stimulus applied, with the exception of the side of the body of which it is applied. Allochiria is the modern term that covers this phenomenon. [ 5 ]
Motor achiria describes the situation when the patient is not able to move the limb or body part in question without assistance due to the inability to distinguish left and right limbs. Voluntary movement is possible when cues other than left or right are given to the patient, but the movement is of a disproportionate strength. [ 1 ]
However, it is also reported that involuntary movements or habitual movements do occur in the limb in question. Similar to other disorders related to hysteria , the movement of limbs is more impaired as the movement itself is more under conscious control . [ 2 ] The modern term with approximately the same meaning is motor neglect , where the patients rarely use their contralateral limbs.
Introspective achiria describes the situation when the patient is not able to feel or retain sensory memory of the body part in question. Even when the patient knows that that body part exists on their body, they still could not feel it. [ 1 ]
The first reported case of achiria was discovered in 1899 by Pierre Janet , a pioneering French psychologist. Janet noticed that a patient had an unusual symptom, of which he was not able to localize physical touch on his body. Janet named the phenomenon "simple allochiria". [ 6 ]
The term "achiria" was first coined by Welsh psychiatrist Ernest Jones in 1907. [ 7 ] After reviewing the past literature on allochiria from Janet , Austrian neurologist Heinrich Obersteiner and other psychologists, Jones redefined the term allochiria into two separate terms: "True allochiria" and "False allochiria" (also known as alloesthesia). False allochiria is the mislocalization of stimuli in all directions, while true allochiria is the mislocalization of stimuli only in the horizontal direction to the exact same location of the contralateral side of the body. When being touched at the inner ankle, patients with false allochiria could feel the sensation at the outer ankle, the knee, or the opposite ankle; while patients with true allochiria could only feel it at the exact same location of the inner ankle of the opposite limb. Furthermore, Jones proposed that true allochiria would be one of the three stages of a mental syndrome called dyschiria, alongside achiria and synchiria, hence the term "achiria" is coined. [ 7 ]
Achiria often refers to the complete absence of chirognostic sense, or the sense of "sidedness" on the body. Therefore, a patient with achiria would be able to accurately tell the position and intensity of stimuli, but was unable to identify which side of the body the stimuli originated from. [ 2 ]
There are a number of different approaches that explain the origin and symptoms of achiria.
The first theory was proposed by William A. Hammond in 1883. This theory posits that achiria (the term was not officially coined at the time) is caused by an obstruction in the efferent path , which results in impulses being passed to the contralateral side of the body, hence reaching the cerebral hemisphere opposite to where the impulses originated from. [ 8 ]
In 1891, Albert Paul Weiss tried to validate this theory by blocking the posterior columns of the spinal cord. [ 9 ] Bosc also did a similar demonstration in 1892, but he blocked one side of the cerebral hemisphere instead of the spinal cord, such that the signals trying to get to that hemisphere have to pass through the corpus callosum to the opposite hemisphere instead of other pathways. [ 10 ]
The second theory was proposed by Ernest Jones in 1909. [ 2 ] Jones argued that Hammond's theory was merely a speculation because it ignored observable facts about achiria and allochiria, such as their associations with Brown-Sequard hemisection syndrome . Brown-Sequard hemisection syndrome features a unilateral block in the spinal cord, but allochiria has been recorded in patients with this syndrome. This contradicted what Hammond's theory suggests. [ 2 ]
Jones posits that achiria is a dissociation disorder resulting from the loss of the chirognostic sense, or the sensation of "sidedness". Chirognostic sense is a type of autosomastognostic sense, or "memory senses", which we acquire through our memories of the past; as opposed to the aesthesic senses, which are senses we acquire at any given moment and through our immediate interaction with the outside world, such as heat, touch and pain, etc. [ 2 ]
He further elaborated that functional diseases could cause damage to both types of senses. During the recovery of the functional disease, aesthesic senses may recover faster than the autosomatognostic senses, resulting in a gap between the recovery pace of different senses. This gap is called "paradoxical cleavage". Thus, a patient could accurately detect touch and pain, but is not able to recall the sidedness of this sensation. The larger the paradoxical cleavage, the more severe the symptoms would be. [ 2 ]
Jones regarded achiria as the primary stage of dyschiria, of which the patients have a complete loss of their chirognostic senses. When they slowly regain back their chirognostic senses, the symptoms of achiria would transit to those of allochiria . [ 2 ] The theory behind this change is as follows:
When a patient transits from achiria to allochiria, there is a gain in both motor function (the patient would be able to move their limbs in both sides of the body, instead of just one) as well as a gain in chirognostic memories, albeit them being distorted and the memory of one side is recalled as those of the opposite side. [ 2 ]
The improvement of motor function and the redemption of memory senses, which were absent or incomplete in achiria patients, enhances their general well-being and their feelings of strength, power and completeness. Therefore, allochiria should be seen as a more stable and improved status than achiria, while achiria should be seen as a transitional stage. This theory was supported by the comparative prevalence of achiria and allochiria. Out of the thirty cases that Jones had collected from past literature, allochiria was present in all cases, while achiria was only present in one. [ 2 ]
The previous experiments related to dyschiria were not enough to make a theoretical influence. [ 11 ] The term dyschiria was replaced by the term unilateral neglect in 1970 when Austrian neurologist Marcel Kinsbourne published a study called "A Model for the Mechanism of Unilateral Neglect of Space". [ 12 ] In the study, Kinsbourne briefly mentioned the lack of awareness to the contralateral side to the brain lesion . Since there had already been previous studies related to unilateral neglect , this term was used instead of dyschiria. In fact, studies about unilateral neglect had started in the late 19th century, but not until a century later that it became a major topic in neurology. [ 13 ] However, previous studies mainly focused on other aspects of unilateral neglect, like the visual aspect. For visual neglect, patients would ignore one side of their visual field. [ 14 ]
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Acholia or hypocholia [ 1 ] is pallor of the feces , which lack their normal brown colour, as a result of impaired bile secretion into the bowel . [ 2 ] Acholia is a sign pointing to reduced or lacking flow of conjugated bilirubin into the bowel, as a result of a problem in the liver itself or in the biliary tree . [ 3 ]
Ancient Greek : a + chole (without bile).
A condition in which little or no bile is secreted or the flow of bile into the digestive tract is obstructed. The acholia is a sign of many diseases, such as hepatitis .
Acholia causes the color of feces to fade. [ 3 ]
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Acland's Video Atlas of Human Anatomy is a series of anatomy lessons on video presented by Robert D. Acland . [ 1 ] Dr. Acland was a professor of surgery in the division of plastic and reconstructive surgery at the University of Louisville School of Medicine . The Atlas was originally released as a series of VHS tapes, published individually between 1995 and 2003. [ 2 ] The series was re-released in 2003 on DVD as Acland's DVD Atlas of Human Anatomy .
The series uses unembalmed human specimens to illustrate anatomical structures. [ 3 ] Intended for use by medical, dental and medical science students, the video teaching aid uses simple language and high quality images.
The authors claim: "Each minute of the finished product took twelve hours to produce: five in creating the script, five in making the shots, and two in post-production." [ 2 ]
The British Medical Journal wrote that "Robert Acland’s video atlas series represents a powerful force against .. perceived dumbing down and has set about reinvigorating the subject through its crystal clear presentation of human anatomy." [ 4 ]
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The acoustic reflex (also known as the stapedius reflex , [ 1 ] stapedial reflex , [ 2 ] auditory reflex , [ 3 ] middle-ear-muscle reflex ( MEM reflex , MEMR ), [ 4 ] attenuation reflex , [ 5 ] cochleostapedial reflex [ 6 ] or intra-aural reflex [ 6 ] ) is an involuntary muscle contraction that occurs in the middle ear in response to loud sound stimuli or when the person starts to vocalize.
When presented with an intense sound stimulus, the stapedius and tensor tympani muscles of the ossicles contract. [ 7 ] The stapedius stiffens the ossicular chain by pulling the stapes (stirrup) of the middle ear away from the oval window of the cochlea and the tensor tympani muscle stiffens the ossicular chain by loading the tympanic membrane when it pulls the malleus (hammer) in toward the middle ear. The reflex decreases the transmission of vibrational energy to the cochlea , where it is converted into electrical impulses to be processed by the brain .
The acoustic reflex threshold (ART) is the sound pressure level (SPL) from which a sound stimulus with a given frequency will trigger the acoustic reflex. The ART is a function of sound pressure level and frequency.
People with normal hearing have an acoustic reflex threshold (ART) around 70–100 dB SPL. People with conductive hearing loss (i.e., bad transmission in the middle ear ) may have a greater or absent acoustic reflex threshold. [ 8 ]
The acoustic reflex threshold is usually 10–20 dB below the discomfort threshold. However the discomfort threshold is not a relevant indicator of the harmfulness of a sound: industry workers tend to have a higher discomfort threshold, but the sound is just as harmful to their ears. [ 9 ]
The acoustic reflex threshold can be decreased by the simultaneous presentation of a second tone (facilitator). The facilitator tone can be presented to either ear. This facilitation effect tends to be greater when the facilitator tone has a frequency lower than the frequency of the elicitor (i.e. the sound used to trigger the acoustic reflex). [ 10 ]
The main hypothesized function of the acoustic reflex is the protection of the organ of Corti against excessive stimulation (especially that of the lower frequencies). This protection has been demonstrated both in humans and animals, but with limited effects. [ 13 ]
According to the article Significance of the stapedius reflex for the understanding of speech , the latency of contraction is only about 10ms, but maximum tension may not be reached for 100 ms or more. [ 13 ] According to the article Le traumatisme acoustique , the latency of contraction is 150 ms with noise stimulus which SPL is at the threshold (ATR), and 25–35 ms at high sound pressure levels. Indeed, the amplitude of the contraction grows with the sound pressure level stimulus. [ 17 ]
Because of this latency, the acoustic reflex cannot protect against sudden intense noises. [ 17 ] [ 13 ] However, when several sudden intense noises are presented at a pace higher than 2–3 seconds of interval, the acoustic reflex is able to play a role against auditory fatigue. [ 17 ] [ 18 ]
Moreover, the full tension of the stapedius muscle cannot be maintained in response to continued stimulation. Indeed, the tension drops to about 50% of its maximum value after a few seconds. [ 13 ]
In damage risk criteria for exposure to impulse noise, the acoustic reflex is integral to the Auditory Hazard Assessment Algorithm for Humans model and the Integrated Cochlear Energy models. These two models estimate the response of the basilar membrane in response to an input stimulus and summate the vibration of the segments of the basilar membrane to predict the potential risk for hearing loss. The acoustic reflex can be activated before an impulse reaches the ear through an assumed conditioned response or it can be activated after the stimulus exceeds a specific level (e.g. 134 dB).
Recent measurements of the acoustic reflex with a group of 50 subjects found that only 2 of the subjects exhibited any pre-activation of the reflex in the warned (countdown) or volitional control of the eliciting stimulus. [ 19 ]
An alternative hypothesis for the role of the acoustic reflex is the prevention of auditory masking of high-frequencies by low-frequencies, which are predominant in natural sounds. [ 20 ]
Most of the time, the stapedius reflex is tested with tympanometry . The contraction of the stapedius muscle stiffens the middle-ear, thus decreasing middle-ear admittance; this can be measured thanks to tympanometry. [ 8 ] The acoustic stapedius reflex can also be recorded by means of extratympanic manometry (ETM). [ 14 ]
The stapedial reflex can be measured with laser Doppler velocimetry . Jones et al. [ 19 ] focused a laser on the light reflex of the manubrium in awake human subjects. The amplitude of a 500 Hz probe tone was used to monitor the vibrations of the tympanic membrane. Various elicitors were presented to the subjects: 1000 Hz tone-burst for 0.5 s at 100 dB SPL, recorded .22 caliber gunshot noise with a peak level of 110 dB SPL. The amplitude of the 500 Hz probe tone was reduced in response to the eliciting stimuli. Time constants for the rate of onset and recovery were measured to be about 113 ms for the tone and 60-69 ms for the gunshot recordings.
As the stapedius muscle is innervated by the facial nerve , [ 21 ] a measurement of the reflex can be used to locate the injury on the nerve. If the injury is distal to the stapedius muscle, the reflex is still functional.
A measurement of the reflex can also be used to suggest a retrocochlear lesion (e.g., vestibular schwannoma). [ 8 ]
The acoustic reflex normally occurs only at relatively high intensities; contraction of middle ear muscles for quieter sounds can indicate ear dysfunction (e.g. tonic tensor tympani syndrome -TTTS).
The pathway involved in the acoustic reflex is complex and can involve the ossicular chain (malleus, incus and stapes), the cochlea (organ of hearing), the auditory nerve, brain stem, facial nerve, superior olivary complex, and cochlear nucleus. Consequently, the absence of an acoustic reflex, by itself, may not be conclusive in identifying the source of the problem. [ 21 ] [ 19 ]
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Acoustic trauma is the sustainment of an injury to the eardrum as a result of a very loud noise. Its scope usually covers loud noises with a short duration, such as an explosion , gunshot or a burst of loud shouting. Quieter sounds that are concentrated in a narrow frequency may also cause damage to specific frequency receptors. [ 1 ] The range of severity can vary from pain to hearing loss. [ 2 ]
Acute acoustic trauma can be treated by combining hyperbaric oxygen therapy (HBO) with corticosteroids . Acute noise exposure causes inflammation and lower oxygen supply in the inner ear. Corticosteroids hinder the inflammatory reaction and HBO provides an adequate oxygen supply. This therapy has been shown to be effective when initiated within three days after acoustic trauma. Therefore, this condition is considered an ENT emergency. [ 3 ]
Hazardous noise causes injury to the hearing mechanisms in the inner ear. Acoustic trauma may result in sensorineural HL (SNHL) that is either temporary (temporary threshold shift, TTS) or permanent (permanent threshold shift, PTS). A TTS will resolve with time, while the time frame for hearing recovery is unique in every case, any SNHL that persists beyond eight weeks after injury is most likely permanent and should be considered PTS. [ 4 ]
Acoustic trauma is an injury to the inner ear that's often caused by exposure to a high- decibel noise. This injury can occur after exposure to a single, loud noise or from exposure to noises at significant decibels over a longer period of time. [ medical citation needed ] Many cases have included a period of reduced hearing after exposure to loud sounds. Examples include after a concert or a visit to a discotheque or having worked with noisy equipment. This kind of hearing impairment is often temporary. After some recovery time, the acoustic trauma often will stop. [ 5 ]
Acoustic trauma occurs when a continuous transient sounds transfers enough energy to a cochlea to result in necrosis of the outer hair cells (OHC), inner hair cells (IHC), and cause glutamate excitotoxicity of first-order afferent neurons of the spiral ganglion ( cochlear synaptopathy ). This can occur when an impact or impulse sound like an explosion occurs abruptly. When excessive, this force can lead to cellular metabolic overload, cell damage and cell death. [ 7 ] The force of that transient sound exceeds the elastic limit of the tissues. The organ of Corti can be sheared off the basilar membrane when the sound coming through the ear canal, middle ear and cochlea exceeds 132 dB. If the sound is more intense than 184 dB, the eardrum is ruptured. 184 dB and above usually comes from military sound exposures, such as with the explosion of an IED ( improvised explosive device ). When a person has a shock wave, not only is the eardrum ruptured, but also has ossicular discontinuities. The explosion or blast if powerful can cause traumatic brain injury. As a result, a person could have an auditory processing disability. Lung injures can develop as well as some injuries to the viscera. [ 8 ] Once exposure to damaging noise levels is discontinued, further significant progression of hearing loss stops. Individual susceptibility to noise-induced hearing loss varies greatly, but the reason that some people are more resistant to it while others are susceptible is not well understood. [ 7 ]
The diagnosis is based on what environmental factors of that loud noise that was exposed. Audiometry will be used to detect signs of acoustic trauma. In this test, there are different sounds of varying loudness and of different tones that are exposed to more carefully assess what can be heard and what can't be heard. [ 5 ]
There are various treatment methods available depending on how severe the acoustic trauma is. Acoustic trauma cannot be reversed as of today. The goal of treatment is to protect the ear from further damage. [ 9 ] Below are possible preventive measures and treatment methods that could help in cases of acoustic trauma
Each episode of acoustic trauma results in permanent damage within the inner ear, even though the majority of patients, the symptoms will disappear and an audiogram will show normal hearing within a few hours to a few days. In some cases, the changes seen in the audiogram will only partially improve or remain permanent. One of the signs and symptoms of acoustic trauma is tinnitus and this may persist for a long time. In some cases, tinnitus may become a permanent condition. [ 10 ] There is no specific study done on Life Expectancy or statistical information for the prognosis of acoustic trauma. Overall, depending on how powerful the noise was and how and what degree of the severity, the prognosis is quite difficult to predict. [ 11 ]
The prevalence depends on the environmental factors. Acoustic trauma is quite common during military service and during hunting activities, where it is mainly associated with gun sports and particularly accidental shots. [ 12 ] Of teenagers, 20-50 percent experience exposure to noise levels high enough to cause acute acoustic trauma. [ 10 ] Hearing loss due to noise is the second most common sensorineural hearing loss, after age-related hearing loss ( presbycusis ). Of more than 28 million Americans with some degree of hearing impairment, as many as 10 million have hearing loss caused by in part by excessive noise exposure in the workplace or during recreational activities. [ 13 ]
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Acquired cystic kidney disease-associated renal cell carcinoma is rare subtype of renal cell carcinoma . [ 1 ] It is most commonly seen in people with end-stage kidney disease who have a much higher risk of developing acquired cystic kidney disease (ACKD). Affected individuals have small kidneys with several cysts and their risk of renal cell carcinoma is 30 times higher than people without ACKD.
Bloody urine and flank pain in a person with end-stage kidney disease raise suspicion for ACKD-associated renal cell carcinoma. Although people with ACKD have a substantially higher risk of renal cell carcinoma, routine screening is not recommended. ACKD-associated renal cell carcinoma is an uncommon cause of death for people with end-stage kidney disease.
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Acromegaly is a disorder that results in excess growth of certain parts of the human body. It is caused by excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. [ 3 ] There may also be an enlargement of the forehead, jaw, and nose. Other symptoms may include joint pain , thicker skin, deepening of the voice, headaches , and problems with vision . [ 3 ] Complications of the disease may include type 2 diabetes , sleep apnea , and high blood pressure . [ 3 ]
Features that may result from a high level of GH or expanding tumor include: [ citation needed ]
About 98% of cases of acromegaly are due to the overproduction of growth hormone by a benign tumor of the pituitary gland called an adenoma . [ 14 ] These tumors produce excessive growth hormone and compress surrounding brain tissues as they grow larger. In some cases, they may compress the optic nerves . Expansion of the tumor may cause headaches and visual disturbances. In addition, compression of the surrounding normal pituitary tissue can alter the production of other hormones , leading to changes in menstruation and breast discharge in women and impotence in men because of reduced testosterone production. [ 15 ]
A marked variation in rates of GH production and the aggressiveness of the tumor occurs. Some adenomas grow slowly and symptoms of GH excess are often not noticed for many years. Other adenomas grow rapidly and invade surrounding brain areas or the sinuses , which are located near the pituitary. In general, younger people tend to have more aggressive tumors. [ 16 ]
Most pituitary tumors arise spontaneously and are not genetically inherited. Many pituitary tumors arise from a genetic alteration in a single pituitary cell that leads to increased cell division and tumor formation. This genetic change, or mutation , is not present at birth but is acquired during life. The mutation occurs in a gene that regulates the transmission of chemical signals within pituitary cells; it permanently switches on the signal that tells the cell to divide and secrete growth hormones. The events within the cell that cause disordered pituitary cell growth and GH oversecretion currently are the subject of intensive research. [ 16 ]
Pituitary adenomas and diffuse somatomammotroph hyperplasia may result from somatic mutations activating GNAS , which may be acquired or associated with McCune–Albright syndrome . [ 17 ] [ 18 ]
In a few people, acromegaly is caused by tumors of the pancreas , lungs , and adrenal glands . These tumors also lead to an excess of GH, either because they produce GH themselves or, more frequently, because they produce GHRH (growth hormone-releasing hormone), the hormone that stimulates the pituitary to make GH. When these nonpituitary tumors are surgically removed, GH levels fall and the symptoms of acromegaly improve. [ citation needed ]
Diagnosis is by measuring growth hormone after a person has consumed a glucose solution, or by measuring insulin-like growth factor I in the blood. After diagnosis, medical imaging of the pituitary is carried out to determine if an adenoma is present. If excess growth hormone is produced during childhood, the result is the condition gigantism rather than acromegaly, and it is characterized by excessive height. [ 3 ]
An MRI of the brain focusing on the sella turcica after gadolinium administration allows for clear delineation of the pituitary and the hypothalamus and the location of the tumor. [ citation needed ]
Pseudoacromegaly is a condition with the usual acromegaloid features but without an increase in growth hormone and IGF-1. It is frequently associated with insulin resistance. [ 19 ] Cases have been reported due to minoxidil at an unusually high dose. [ 20 ] It can also be caused by a selective post-receptor defect of insulin signalling, leading to the impairment of metabolic, but preservation of mitogenic, signaling. [ 21 ]
Treatment options include surgery to remove the tumor, medications, and radiation therapy . Surgery is usually the preferred treatment; the smaller the tumor, the more likely surgery will be curative. If surgery is contraindicated or not curative, somatostatin analogues or GH receptor antagonists may be used. Radiation therapy may be used if neither surgery nor medications are completely effective. [ 3 ] Without treatment, life expectancy is reduced by 10 years; with treatment, life expectancy is not reduced. [ 6 ]
The primary current medical treatment of acromegaly is to use somatostatin analogues – octreotide (Sandostatin) or lanreotide (Somatuline).
These somatostatin analogues are synthetic forms of a brain hormone, somatostatin , which stops GH production. The long-acting forms of these drugs must be injected every 2 to 4 weeks for effective treatment. Most people with acromegaly respond to this medication. In many people with acromegaly, GH levels fall within one hour and headaches improve within minutes after the injection. Octreotide and lanreotide are effective for long-term treatment. Octreotide and lanreotide have also been used successfully to treat people with acromegaly caused by non-pituitary tumors. [ citation needed ]
Somatostatin analogues are also sometimes used to shrink large tumors before surgery. [ 22 ]
Because octreotide inhibits gastrointestinal and pancreatic function, long-term use causes digestive problems such as loose stools, nausea, and gas in one-third of people. In addition, approximately 25 percent of people with acromegaly develop gallstones , which are usually asymptomatic. [ 23 ] In some cases, octreotide treatment can cause diabetes because somatostatin and its analogues can inhibit the release of insulin . [ citation needed ] With an aggressive adenoma that is not able to be operated on, there may be a resistance to octreotide in which case a second-generation SSA, pasireotide, may be used for tumor control. However, insulin and glucose levels should be carefully monitored as pasireotide has been associated with hyperglycemia by reducing insulin secretion. [ 24 ]
For those who are unresponsive to somatostatin analogues, or for whom they are otherwise contraindicated, it is possible to treat using cabergoline . As tablets rather than injections, they cost considerably less. These drugs can also be used as an adjunct to somatostatin analogue therapy. They are most effective in those whose pituitary tumours also secrete prolactin . Side effects of these dopamine agonists include gastrointestinal upset, nausea, vomiting, light-headedness when standing, and nasal congestion. These side effects can be reduced or eliminated if medication is started at a very low dose at bedtime, taken with food, and gradually increased to the full therapeutic dose. [ citation needed ]
The latest development in the medical treatment of acromegaly is the use of growth hormone receptor antagonists. The only available member of this family is pegvisomant (Somavert). By blocking the action of the endogenous growth hormone molecules, this compound is able to control the disease activity of acromegaly in virtually everyone with acromegaly. Pegvisomant has to be administered subcutaneously by daily injections. Combinations of long-acting somatostatin analogues and weekly injections of pegvisomant seem to be equally effective as daily injections of pegvisomant. [ citation needed ]
Surgical removal of the pituitary tumor is usually effective in lowering growth hormone levels. Two surgical procedures are available for use. The first is endonasal transsphenoidal surgery, which involves the surgeon reaching the pituitary through an incision in the nasal cavity wall. The wall is reached by passing through the nostrils with microsurgical instruments. The second method is transsphenoidal surgery during which an incision is made into the gum beneath the upper lip. Further incisions are made to cut through the septum to reach the nasal cavity, where the pituitary is located. Endonasal transsphenoidal surgery is a less invasive procedure with a shorter recovery time than the older method of transsphenoidal surgery, and the likelihood of removing the entire tumor is greater with reduced side effects. Consequently, endonasal transsphenoidal surgery is the more common surgical choice. [ citation needed ]
These procedures normally relieve the pressure on the surrounding brain regions and lead to a lowering of GH levels. Surgery is most successful in people with blood GH levels below 40 ng/ml before the operation and with pituitary tumors no larger than 10 mm in diameter. Success depends on the skill and experience of the surgeon. The success rate also depends on what level of GH is defined as a cure. The best measure of surgical success is the normalization of GH and IGF-1 levels. Ideally, GH should be less than 2 ng/ml after an oral glucose load. Complications of surgery may include cerebrospinal fluid leaks, meningitis , or damage to the surrounding normal pituitary tissue, requiring lifelong pituitary hormone replacement . [ citation needed ]
Even when surgery is successful and hormone levels return to normal, people must be carefully monitored for years for possible recurrence. More commonly, hormone levels may improve, but not return completely to normal. These people may then require additional treatment, usually with medications. [ citation needed ]
Radiation therapy is usually reserved for people who have tumours remaining after surgery. These people often also receive medication to lower GH levels. Radiation therapy is given in divided doses over four to six weeks. This treatment lowers GH levels by about 50 percent over 2 to 5 years. People monitored for more than 5 years show significant further improvement. Radiation therapy causes a gradual loss of production of other pituitary hormones with time. Loss of vision and brain injury, which have been reported, are very rare complications of radiation treatments. [ citation needed ]
Life expectancy of people with acromegaly is dependent on how early the disease is detected. [ 25 ] Life expectancy after the successful treatment of early disease is equal to that of the general population. [ 26 ] Acromegaly can often go on for years before diagnosis, resulting in poorer outcome, and it is suggested that the better the growth hormone is controlled, the better the outcome. [ 25 ] Upon successful surgical treatment, headaches and visual symptoms tend to resolve. [ 9 ] One exception is sleep apnea, which is present in around 70% of cases but does not tend to resolve with successful treatment of growth hormone level. [ 8 ] While hypertension is a complication of 40% of cases, it typically responds well to regular regimens of blood pressure medication. [ 8 ] Diabetes that occurs with acromegaly is treated with the typical medications, but successful lowering of growth hormone levels often alleviates symptoms of diabetes. [ 8 ] Hypogonadism without gonad destruction is reversible with treatment. [ 8 ] Acromegaly is associated with a slightly elevated risk of cancer. [ 27 ]
Acromegaly affects about 3 per 50,000 people. It is most commonly diagnosed in middle age. [ 3 ] Males and females are affected with equal frequency. [ 28 ] It was first described in the medical literature by Nicolas Saucerotte in 1772. [ 29 ] [ 30 ] The term is from the Greek ἄκρον ( akron ) meaning "extremity", and μέγα ( mega ) meaning "large". [ 3 ]
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https://en.wikipedia.org/wiki/Acromegaly
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Acrotomophilia (from the Greek ἀκρότομος "having the top cut off"; from ἄκρον akron "extremity" and - -τομος -tomos from τέμνω temno "I cut" and φιλία philia "love") is a paraphilia in which an individual expresses strong sexual interest in amputees . It is a counterpart to apotemnophilia , the desire (although not necessarily sexual) to be an amputee.
Acrotomophiles may be attracted to amputees because they like the way they look or they may view the amputee's stump as a phallic object which can be used for sexual pleasure . [ 1 ] Acrotomophiles may enjoy the idea of dominating the amputee during couples play and they may also become aroused with the thought of having to take care of an amputee.
In a survey of acrotomophiles, leg amputations were preferred over arm amputations, amputations of a single limb over double amputations, and amputations that left a stump over amputations that left no stump. [ 2 ] According to Per Solvang (2007), "Devotees adhere to standard conceptions of attractiveness in all other matters outside of amputations." [ 3 ]
Some people [ who? ] question whether amputating one's own body parts or operating on a partner for the sake of sexual pleasure is ethical. For some, [ who? ] modifying the body is a private ritual of self-ownership and freedom of choice. Psychiatrists may make a diagnosis of body integrity identity disorder . [ 4 ] [ 5 ]
The term amelotatism has also been used to describe acrotomophilia. The sexual interest in being an amputee is apotemnophilia . [ 6 ] [ 7 ] John Money (1977) used the terms autoapotemnophilia and alloapotemnophilia to describe the erotic interest of wanting to be or appear as an amputee versus wanting amputees as sexual partners; [ 8 ] neither term has been widely used since. The term teratophilia is used to describe arousal from deformed or monstrous people. [ 9 ]
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https://en.wikipedia.org/wiki/Acrotomophilia
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Acta Neurochirurgica is a monthly peer-reviewed medical journal covering all aspects of neurosurgery . It was established in 1950 and is published by Springer Science+Business Media . The editor-in-chief is T. Mathiesen ( University of Copenhagen ).
The journal is abstracted and indexed in:
According to the Journal Citation Reports , the journal has a 2020 impact factor of 2.216. [ 7 ]
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https://en.wikipedia.org/wiki/Acta_Neurochirurgica
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