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GtR The Gateway to Research: UKRI portal onto publically funded research Consolidated Grant in Solar Physics Lead Research Organisation: University of Glasgow Department Name: School of Physics and Astronomy Abstract The physics of plasmas - particularly plasmas permeated by a magnetic field - dictates the behaviour of much of the visible universe. Close at hand, we need to understand and measure plasmas, fields and particles understand the dynamic Sun and its interaction with the heliosphere. In this proposal we focus on several key unsolved problems in solar physics that are also prototypes for a wider and deeper understanding of cosmic plasmas as a whole. Our top-level questions are: how do high-energy radiating particles behave in solar flares and in interplanetary space? How are they accelerated, are they beamed and do they play a key role in flares and their terrestrial impact? How does the Sun store and release energy in its magnetised atmosphere, and what can we learn about this process by computer simulations and by studying the radiation that is emitted? The magnetic field is key to everything that happens in the Sun's atmosphere. Concentrated magnetic regions emerge through the Sun's surface and into its atmosphere. Here they interact with the pre-existing magnetic field and the result is intense bursts of energy known as flares, which accelerate sub-atomic particles (electrons and ions), cause heating to millions of degrees, and can also lead to expulsion of magnetised plasma into space, which can lead to damaging `space weather'. Flares have distinctive radiation signatures that are closely related to the structure of the magnetic field, and to the way that energy is transmitted along the magnetic field from the corona down to the solar surface and out into the distant heliosphere, and converted into other forms as it goes. By interpreting this radiation we can understand what is happening in a flare. More generally solar magnetic fields create eccentric and dynamic shapes in the solar atmosphere, for example swirling `tornado-like' structures in which the plasma, and perhaps the magnetic field supporting it, is rotating. Our programme combines observational data with theoretical and numerical modelling to address all of these topics, and spans a wide range of astronomical and technical problems, from the modeling of the path of radiation in a plasma to high-energy particle acceleration; from electromagnetic waves to relativistic particle beams; from image processing to statistical analysis of weak signals, and from mathematical `pen-and-paper' calculations to advanced numerical simulations. We will bring all these skills to bear on questions at the heart of current efforts to better understand our nearest star. Some aspects of our work will also help us to assess the potential threat of eruptions on the Sun, which is a key element of space weather forecasting. Planned Impact All Co-Is on the grant are involved in trying to ensure that our STFC-funded research efforts are used to the wider benefit of society, through reaching out to cognate disciplines, engagement with policy-makers and industry, and an extremely active schools and public outreach programme. We are actively involved, and contribute to the agendas of, with several initiatives in space weather and sensors, both internal and external to Glasgow University. This includes an STFC-funded space weather network. We have received University support for joint projects with the Schools of Engineering and Mathematics & Statistics, which has led to significant cross-disciplinary research, supported by a PhD student. Our research, and the involvement that it brings us with high profile projects and missions, will benefit the public. As can be seen from our extensive list of outreach engagements we are extremely active in communicating our work through public events, tens of talk per year to science centres, schools and societies, and science-art projects. We dedicate particular effort to bringing our work to remote sites in Scotland. Plans are in place for several new initiatives, such as the 'Cetus' sky- and whale-watching observatory in Isle of Lewis, as well as continuing the programme of talks, observatory visits and observing nights etc which are co-ordinated by the group secretary and run by group members (note, we have an 'Outreach' website at: http://www.astro.gla.ac.uk/outreach/index.php which acts as a single point of contact for all outreach requests). We strongly encourage the involvement of our RAs and particularly our PhD students in this activity as well, ensuring a lively and continued programme. Keeping at the forefront of our respective research areas ensures that we remain credible speakers for the public, as evidenced by many repeat invitations. We are also closely involved with schools activities, giving many talks, planetarium shows, and running projects school-specific projects. This activity is undertaken by staff and PhD students alike and is co-ordinated as above via our outreach website and group secretary. Funded Value: £713,351 Funded Period: Mar 17 - Mar 21 Funder: STFC Project Status: Closed Project Category: Research Grant Project Reference: ST/P000533/1 Principal Investigator: Lyndsay Fletcher Research Subject: Solar & terrestrial physics (100%) Research Topic: Solar & Solar-Terrestrial Phys (10%) Solar Studies (90%) If populated the following is a graphic depicting where in the UK the given postcode is located. Armstrong J (2019) Fast Solar Image Classification Using Deep Learning and Its Importance for Automation in Solar Physicsin Solar Physics Armstrong J (2021) A machine-learning approach to correcting atmospheric seeing in solar flare observationsin Monthly Notices of the Royal Astronomical Society Aschwanden M (2019) Global Energetics of Solar Flares. VIII. The Low-energy Cutoffin The Astrophysical Journal Barczynski K (2021) Spectro-imagery of an active tornado-like prominence: Formation and evolutionin Astronomy & Astrophysics Battaglia M (2019) Electron Distribution and Energy Release in Magnetic Reconnection Outflow Regions during the Pre-impulsive Phase of a Solar Flarein The Astrophysical Journal Bian N (2018) Heating and Cooling of Coronal Loops with Turbulent Suppression of Parallel Heat Conduction.in The Astrophysical journal Bian N (2019) A Fokker-Planck Framework for Studying the Diffusion of Radio Burst Waves in the Solar Coronain The Astrophysical Journal Birn J (2017) Can Substorm Particle Acceleration Be Applied to Solar Flares?in The Astrophysical Journal Borissov A (2017) Particle acceleration with anomalous pitch angle scattering in 2D magnetohydrodynamic reconnection simulationsin Astronomy & Astrophysics Borissov A (2020) Particle acceleration with anomalous pitch angle scattering in 3D separator reconnectionin Astronomy & Astrophysics
https://gtr.ukri.org/projects?ref=ST%2FP000533%2F1
Sustainability | Free Full-Text | Transforming Communication Channels to the Co-Creation and Diffusion of Intangible Heritage in Smart Tourism Destination: Creation and Testing in Ceutí (Spain) Creating smart tourism destinations requires innovative solutions which cover the main pillars of sustainability as sociocultural, environmental, and economic aspects, in order to spread the cultural heritage of these tourist destinations to their visitors. One of the most demanded approaches by the new hyper-connected visitors is the expectation of plunging and becoming a short-term resident to receive a real experience during their visit. Therefore, the scope of this research covers the objective of designing an innovative communication channel between a visitor and a point of interest (POI), which in turn allows agile experiences to be built and provided and increases the dissemination of cultural heritage through new technologies, considering the real needs of the territories and the new digital visitors. In order to address these topics, this paper proposes an innovative and co-created progressive Web-App for visitors called Be Memories in order to spread the intangible heritage of a tourist destination, where the content is co-created by residents of the destination. The tool has been tested in Ceutí, a Spanish village with a high cultural value, which needs to be disseminated through new innovative tools. The trial was launched during local festivities of the village using an Internet of Things device, called a Smart Spot, to establish a communication channel between the visitor and POI. The results of the test were measured using Google Analytics, the reactions of Be Memories in social networks, and the acceptance of other cities and European committees. The results have concluded that Be Memories is able to enable a local experience via agile, fresh, and crowd-sourced content that people enjoy. This channel presents a complementary level of information with respect to official sources, documentaries, and local guide tours, at the same time enabling a mechanism to promote physical visits, walking tours, and cultural heritage via low-cost and sustainable infrastructure. Transforming Communication Channels to the Co-Creation and Diffusion of Intangible Heritage in Smart Tourism Destination: Creation and Testing in Ceutí (Spain) by Andrea Gomez-Oliva 1,2,* , Joanna Alvarado-Uribe 3 , Maria Concepcion Parra-Meroño 2,* and Antonio J. Jara 4 1 Social Sciences, Law and Business Administration Department, Catholic University of Murcia (UCAM), Campus de Los Jeronimos, Guadalupe, 30107 Murcia, Spain 3 Computer Science Department, School of Engineering and Sciences, Tecnologico de Monterrey, Carretera Lago de Guadalupe Km. 3.5, Col. Margarita Maza de Juarez, Atizapan de Zaragoza 52926, Estado de México, Mexico 4 Institute of Information Systems, University of Applied Sciences Western Switzerland (HES-SO), 3960 Sierre, Switzerland * Authors to whom correspondence should be addressed. Sustainability 2019 , 11 (14), 3848; https://doi.org/10.3390/su11143848 Received: 29 April 2019 / Revised: 1 July 2019 / Accepted: 11 July 2019 / Published: 15 July 2019 (This article belongs to the Special Issue Cultural Heritage and Smart Tourism ) Abstract : Creating smart tourism destinations requires innovative solutions which cover the main pillars of sustainability as sociocultural, environmental, and economic aspects, in order to spread the cultural heritage of these tourist destinations to their visitors. One of the most demanded approaches by the new hyper-connected visitors is the expectation of plunging and becoming a short-term resident to receive a real experience during their visit. Therefore, the scope of this research covers the objective of designing an innovative communication channel between a visitor and a point of interest (POI), which in turn allows agile experiences to be built and provided and increases the dissemination of cultural heritage through new technologies, considering the real needs of the territories and the new digital visitors. In order to address these topics, this paper proposes an innovative and co-created progressive Web-App for visitors called Be Memories in order to spread the intangible heritage of a tourist destination, where the content is co-created by residents of the destination. The tool has been tested in Ceutí, a Spanish village with a high cultural value, which needs to be disseminated through new innovative tools. The trial was launched during local festivities of the village using an Internet of Things device, called a Smart Spot, to establish a communication channel between the visitor and POI. The results of the test were measured using Google Analytics, the reactions of Be Memories in social networks, and the acceptance of other cities and European committees. The results have concluded that Be Memories is able to enable a local experience via agile, fresh, and crowd-sourced content that people enjoy. This channel presents a complementary level of information with respect to official sources, documentaries, and local guide tours, at the same time enabling a mechanism to promote physical visits, walking tours, and cultural heritage via low-cost and sustainable infrastructure. Keywords: smart tourism destination ; point of interest ; co-creation ; tourist guides ; hyper-connected users ; prosumers ; residents ; Internet of Things (IoT) ; 1. Introduction The sustainability of tourism destinations is one of the main current pillars of the territories building smart tourism destinations and smart cities. This approach to the sustainable development of cities and towns, in addition to considering the environment as a fundamental aspect, also involves cultural and economic aspects as important roles in the creation of sustainable territories. Therefore, sustainable tourism is based on three main aspects when building a smart environment: the environment, socio-culture, and economy [ 1 ]. Organizations such as United Nations World Tourism (UNWTO) [ 2 ] have highlighted the relevance of the sustainability of tourism destinations to be considered smart when using its resources with powerful strategies. This aspect is not only affecting the tourism domain as it is also related to the growing concept of the smart city, which was born to apply sustainability in city management. Therefore, the purpose of smart cities is to design strategies based on the real needs and resources of the city in order to transform the territory based on improvement of its different processes and networks [ 3 ]. It is here where the role of information and communication technologies (ICTs) stands out because they are able to improve these strategies and changes by taking advantage of the benefits that these technologies provide, such as Big Data collection, the automation of processes, sensors, wearables, etc. The evolution of new technologies in cities and towns, coupled with the advantage of smart and sustainable cities, have defined the main pillars of the smart tourism destination concept, representing a new way to build destinations that gives rise to the opportunity of living personalized experiences between cultural heritage and visitor’s due to technological tools [ 1 ]. In addition, these new types of territories deploy a smart infrastructure to obtain knowledge on the needs of tourism/visitors and improve the offer with different strategies. Therefore, smart tourism destinations must meet the main pillars of sustainability: the environment, economy, and socio-culture, establishing a perfect combination of the three parties by leveraging ICTs and data analysis [ 4 , 5 ]. In the field of smart tourism destinations, Spain is one of the pioneer countries in promoting them. SEGITTUR, the Spanish State Society for the Tourist Innovation and Technologies Management, has the Smart Tourism Destination Project ( Destino Turístico Inteligente ) [ 6 ], which helps with and manages the tourism sector with the aim that its tools, strategies, and solutions will evolve towards a smart approach, making them more sustainable. As a result of the new paradigm that mixes sustainability, smart tourism destinations, and new technologies, this research presents a solution for smart tourism destinations called Be Memories to valorize the culture of smart territories based on previous experiences like the TreSight project [ 7 ] as a real deployment in a Spanish town called Ceutí. This solution is based on the digital natives (users) providing cultural stories of their regions and designing a new guide, being co-created by the residents and visitors, and at the same time, reducing the work of the tourist managers. The scope covers the objectives of designing an innovative communication channel that builds agile experiences, increases cultural dissemination, and validates the feasibility of creating a sustainable cycle of content through the cooperation of digital visitors and prosumers, equipping the tourist destination with a sustainable tool for cultural heritage, at the same time as improving the role of the town on a regional and national level, being respectful of their environment. Be Memories is a new concept in the form of a visitor’s guide that uses new technologies and local knowledge of the residents of a territory. This tool disseminates cultural content between visitors and residents of smart tourism destinations, which is based on two lines of innovation: A new channel of easy and agile interaction: through devices called Smart Spots, which enable an open Wi-Fi network and can be located in different cultural points of interest (POIs) of the city, Be Memories creates delimited smart areas named Smart POIs (smart points of interaction). Thereby, any user with a smartphone can interact with Be Memories and access the tool’s content when connecting to the Wi-Fi network generated by the available Smart POIs. This network automatically opens a website stored in the device with all the information about the cultural POI. A new way to know the city through the voice of its residents: Be Memories bases its content on the intangible heritage that resides in the popular knowledge of residents, integrating visitors into the city’s network. These stories are presented in a short-time video-interviews format that visitors and residents can watch and listen to while visiting the different POIs in the cities where Smart POIs are enabled. The tool has been validated in Ceutí, with a highly cultural value, which requires new tools to spread their culture. To carry out the test of Be Memories, 15 Internet of Things (IoT) devices were deployed throughout the village. These devices are called Smart Spots. A Smart Spot generates an area called a smart point of interaction (Smart POI), which sends a notification (non-intrusive) with a URL through Bluetooth (nearby Google technology) and Wi-Fi (captive portal). This communication channel functions without the need to download a native application, facilitating the interaction by proximity [ 8 ]. The content of the pilot is composed of a progressive Web-App that offers a seed content (short video-interviews where the residents tell popular stories). The trial was launched during local festivities (6–19 August 2018). The structure of this article begins with the state-of-the-art, where the value of the pillars of sustainable tourism is presented. In addition, the concepts of a smart city and smart tourism destination are explained as the basis of the research. For this, the role and needs of the new digital visitor are also analyzed. In the second section, the methodology used to design the pilot, according to the research and analysis of the main characteristics of the city living lab (Ceutí), is described. The results section encompasses all the processes realized to improve the first draft, based on the Smart POI concept [ 9 ] presented in previous studies, to adapt it to Ceutí needs through research on the target and meetings with the city council managers. In the discussion, the outcomes and repercussions of the city pilot are given and compared with other solutions and studies. Finally, the conclusions show a global research and result vision and the following steps. 2. State-of-the-Art This study explores the use of technological innovative channels, tested in a real-world environment, to offer agile visitors experiences according to new visitors and the city profile focused on economic, environmental, and socially sustainable tourist destination areas. Therefore, the concepts of sustainable solutions for smart cities, smart tourism destinations, and the new visitor profile, among others, are introduced and analysed in the following. 2.1. Sustainable Tourism In 1987, the sustainable concept was defined in the Brudtland report as “ development that satisfies the requirements of the current generation without compromising the capacity of further generations to satisfy their own necessities ” [ 10 ]. After the publication of this report, safeguarding of the environment and cultural heritage has been a constant matter for international organizations, governments, and society in general. Regarding tourism areas, in 1989, the World Tourism Organization (UNWTO) declared, in The Hague Declaration on tourism, that not only were natural, cultural, and human environments essential for tourism development, but also, that suitable tourism management could contribute to the physical environment and cultural heritage protection, enhancing the residents’ quality of life [ 11 ]. Therefore, the UNWTO has defined sustainable tourism as “ Tourism that takes full account of its current and future economic, social and environmental impacts, addressing the needs of visitors, the industry, the environment, and host communities ” [ 4 ]. Moreover, it has declared that the development of sustainable tourism satisfies the current necessities of both visitors and host regions, protecting and enhancing opportunities for the future. By concentrating on the integral management of resources, the fulfillment of economic, social, and aesthetic requirements is achieved while respecting the cultural integrity, essential ecological processes, biological diversity, and life-support systems. On the other hand, the Members of the World Committee on Tourism Ethics, when reuniting in Madeira in 2007, insisted that the application of the Global Code of Ethics for Tourism is vital for the successful development of the tourist industry, in this way contributing to the growth of sustainable societies [ 12 ]. Further, the United Nations (UN) General Assembly resolution 66/288 of 27 July 2012, endorses the document of the UN Conference on Sustainable Development entitled “ The Future We Want ”. In this document, it is remarked upon that well-designed and guided tourism can make a great contribution to the three dimensions of sustainable development (economic, environmental, and sociocultural), as well as generate commercial opportunities and decent jobs [ 13 ]. An emphasis is placed, in the Charter for Sustainable Tourism [ 2 ], on the following eight relevant aspects about how sustainable tourism must be developed: Tourism development must be based on sustainability that is ecologically bearable in the long-term, economically viable, ethical, and socially equitable for the local community; Tourism must contribute to sustainable development and integrate itself within the natural, cultural, and human environment; Tourism must consider its effects on the cultural heritage and traditions of each local community; Tourism contributes to sustainable development in an active manner through solidarity, mutual respect, and the participation of all tourism actors; Tourism must preserve, protect, and appreciate the value of the natural and cultural heritage, as well as propitiate cooperation between those responsible by assuming the cultural, technological, and professional innovation challenge; Quality criteria must be determined in conjunction with the local community and must be present in the main objectives of the formulation of tourism strategies to both satisfy the visitors and preserve the tourist destination; If tourism wants to participate in sustainable development, it must be based on different opportunities that contribute to the local economy; Any tourism development option must enhance the quality of life and influence the sociocultural enrichment of the tourist destination. Furthermore, the tourist sector has an extraordinary capacity to link the economic, social, and environmental aspects of sustainability. This is possible since tourism as an economic activity is based on intact environments, rich cultures, and welcoming communities. Therefore, technological tools, such as the one described in this research work, allow the generation of jobs and incomes from cultural experiences [ 14 ]; in this study case, from the intangible cultural heritage of the community that held the tourist destination. 2.2. Smart Cities Before introducing the smart city concept, it is crucial to understand the city as an environment where people and communities evolve and live. Landret describes cities as a sensorial and emotional place where people live, grow, and have experiences [ 15 ]. The smart city concept is heterogeneous since it describes many actions and areas of city networks; for that reason, the literature shows different points of view about this concept. The term has been evolving since 1994, with the first definition emerging in 2011, when the European Union echoed its importance [ 16 ] due to different events, such as the Kyoto Protocol (1997). This event placed smart cities in the international spotlight, being of great interest for big organizations such as the Organization for Economics Co-operations and Development (OECD). Through the analysis of papers and research published about smart cities, crossed with important world events, A. Cocchia [ 17 ] analyzed and found five outstanding dates when the smart city concept witnessed an expansion: 1997: As previously mentioned, in this year, the Kyoto Protocol was defined and the United Nations established environmental protection as one of the main issues to solve, as well as the intentions to join forces to reduce the six main greenhouse gases (CO 2 , CH 4 , N 2 O, HFC S , PFC S , and SF 6 ) [ 18 ]. The cities of the participant countries started to work on environmental strategies due to this commitment; 2000: The Internet started to be part of the personal, academic, and business sectors. Moreover, Information and Communication Technologies enabled the processes of cities and people routines [ 19 ]; 2005: The Kyoto Protocol started the development of the previously defined environmental protection strategies; 2008: International Business Machines (IBM ® ) corporation defined the smart planet concept in the middle of an economic crisis, a field that proposed Big Data potential exploitation by councils, governments, and businesses to improve their strategies [ 20 ]. In addition, the Covenant of Mayor was defined, a European cities initiative to work on climatic change through different cities’ synergies [ 21 ]; 2010: The Europe 2020 framework was presented by the European Union as a program with funding of €80 billion, for the period 2014–2020, to improve the competitiveness of Europe in global growth [ 22 ]. The smart city is a new approach for cities that is based on the need for urban strategies in the care and improvement of inhabitants’ life and environment [ 3 ]. For that reason, smart cities have to work across several research domains to provide multidisciplinary solutions and strategies that address the needs and issues of a city network. Furthermore, these new solutions and strategies must respect the cultural (religion, ethnic, immaterial heritage, folklore, etc.) and environmental value (waste generation, pollution, use of natural resources, etc.) of communities and regions. For example, in diverse smart city approaches, experts analyze the implication of these solutions in the fields of the economy, people, environment, governance, mobility, and human-wellbeing [ 23 ]. Other authors support this vision of the concept in terms of three big trends of urban development: green, digital, and knowledge cities [ 24 ]. In addition to the smart strategies related to urbanization, ICTs are one of the growing trends employed to improve and protect environmental factors, day-to-day life, and communication channels between people, communities, and territories. ICT in smart cities is indisputable; it has a big role in the new cities as an enabler, making these new environments more agile and sustainable for people and managers in all the different areas. Authors such as Nam and Pardo [ 25 ] have highlighted three main pillars in these type of territories ( Figure 1 ): technology, human, and institutional dimensions. Smart cities adaptation is a complex process; Europe is on top, and the Spanish role is very important, as one of the first countries working on this new concept. The IDC Consultant ( https://idcspain.com/ ) analysed 44 Spanish smart cities by considering the dimensions and human initiatives, as well as the economic and technological resources used [ 26 ], and cities such as Málaga, Barcelona, Santander, Madrid, and Donostia were highlighted for different institutions as a domain referent [ 27 ]. 2.3. Smart Tourism and Smart Tourism Destination According to the UNWTO description, tourism is a movement of people outside of their usual area for professional and personal reasons that spend money in such new areas. Visitors are users that visit these areas and they can be residents and non-residents of the destination, while tourists are the visitors who stay overnight in the area and are non-residents [ 28 ]. The destination is one of the main pillars in tourism analysis; experts have defined it as the place where culture, geography, and marketing are combined by producers, consumers, people, and authorities to build a final product that works within the economy, culture, global network, and local communities’ fields [ 29 ]. The high impact of tourism as an economic activity in destinations requires the development of strategies based on sustainable and adaptable models that can be easily adapted to new trends. For that reason, the smart adjective in tourism and destination domains, a phenomenon that began to be used in tourism research five years ago, is an extrapolation of smart city strategies to the tourism domain. Yigitcanlar [ 30 , 31 ] found eight pillars in the smart city concept that were acquired from destinations and smart tourism concepts: governance, planning productivity, innovation, liveability, wellbeing, sustainability, and accessibility. Smart tourism is highly related to technologies, and Buhalis and Amaranggana [ 32 , 33 ] have explained how ICTs and IoT can improve the experience and increment the competitiveness of the destinations by providing personalized products andservices during the travel. It is noteworthy that different researchers make a distinction between smart tourism and e-tourism [ 34 ]: E-tourism: Uses the benefits of ICTs to create channels in order to exchange information through digital chains and the virtualization of tourism and smart tourism destination services. This concept is used in the three levels of the visit (previous, during, and post visit). An example is platforms to book hotels in which visitors can interact before their visit to book it, during the visit for any questions and contact during their accommodation, and after the visit to value the hotel commodities. Smart tourism: Adopts the benefits of virtual processes and tools, combining it with the physical world to build a strong destination and government for it. Smart tourism only works in the experience field as opposed to e-tourism. An example is an interactive visitor’s tool through Quick Response Barcodes (QR), Beacons, Near Field Communication (NFC), and others smart tags for the visitor’s interaction with the physical territory during their visits. Through the comprehension of smart tourism, e-tourism, and the smart city concept, the smart tourism destination is defined as a territory of interest for visitors that is effectively managed due to the opportunities that the use of data and ICTs provide [ 35 ]. These destinations need to be innovative and they are built on technological infrastructure for the sustainability and accessibility of the territory, working on the visitor’s integration and quality of experiences [ 6 ]. Because of that new vision of the destinations, the visitors’ smartphone is placed in the spotlight of the cities and destination marketing organizations as the device is capable of allowing a new type of communication among territories and visitors/residents, as well as representing a new method for understanding the needs and requirements of users [ 36 ]. This trend has resulted in the emergence of the mobile tourism concept [ 37 ], which transforms the city services in apps, Web-Apps, platforms, and social network profiles to allow the user to interact via smartphones and tablets to, for example, buy tickets [ 38 ]. The high relevance of the development of smart tourism destinations has led the UNWTO to recently promote the Annual World Congress on Smart Tourism Destinations. This congress aims to discuss the challenges and opportunities in the tourism sector that arise from the development of innovative tourist products based on new technological solutions. This has the objective of leading to new development tourist models based on the five principles previously mentioned: innovation, technology, sustainability, governance, and accessibility. These congresses constitute the largest world forum of experts in the tourism and academy sector, public administrations, technological centers, local agents, and civil society to analyze and build the tourist model of the twentieth century [ 39 ]. Destinations such as Spain, China, and South Korea are at the forefront of the smart destination research and development [ 40 ]. SEGITTUR has a project named Smart Tourism Destination ( Destino Turístico Inteligente —DTI), an innovative proposal in the international domain developed to help destinations in this evolution. Their recommendations are based on a first integral diagnosis to design an action plan working on five pillars: governance, technology, innovation, accessibility, and sustainability [ 24 ]. This project is being pursued to improve the positioning of Spain as a world tourist destination. To achieve this, innovation and ICTs are promoted, and differentiation of the offered services is researched. Consequently, this project has allowed a homogeneous framework to be built that establishes the minimum requirements for classifying a tourist destination as a smart tourism destination based on smart cities [ 41 ]. With this purpose, AENOR ( Asociación Española de Normalización y Certificación ) approved the UNE ( acronym of Una Norma Española ) Policy 178501:2018 that regulates the smart tourist destinations management system, an international pioneer policy for a new tourist destinations management model in the XXI century [ 42 ]. This policy specifies the requirements that a smart tourist destinations management system must accomplish based on the four pillars on which smart tourism destinations are founded: innovation, technology, accessibility, and sustainability. Several examples, such as the following, can be highlighted: “ Palma de Mallorca (Balearic islands) built the largest free Wi-Fi zone of Europe and developed its tourist monitoring platform. Las Palmas de Gran Canaria started its first model to boost shopping tourism in the city through multiple language mobile technologies, and had the first tourist information office to be completely digitalized. On the other hand, Badajoz implemented the first tourism information integral system, which gathers and manages millions of structured and unstructured data in real time. And last but not least, the island “El Hierro” (Canary islands) is considered the first smart island in the world ” [ 43 ]. In order to foment a smart tourist destinations network, the website “ www.destinosinteligentes.es ” created in Spain incorporates a special section within the tourism destinations that is part of the DTI Project. These destinations include El Hierro, Villajoyosa, Castelldefels, Palma de Mallorca, Las Palmas de Gran Canaria, Marbella, Murcia, Almería, Badajoz, Loret de Mar, Jaca, and Valle de Arán, as well as Cozumel and Tequila, which are both in Mexico. Furthermore, in April of 2019, Spain received the WTTC Global Champion Award granted by the World Travel & Tourism Council (WTTC) in the category of innovation and technology for the DTI project [ 44 ]. 2.4. New Target and Tools for Smart Tourism Destinations The emergence of smart tourism destinations has been influenced by technology and smartphone strengths in labor and personal daily life. Due to the emergence of this domain, the visitor has become a smart visitor; that is, a visitor that is more informed than before and that seeks assistance from technology during the three phases of the trip (before, during, and after) [ 45 , 46 ]. Throughout these changes is where the digital visitor appears. Digital visitors are mainly composed of people who are between 20 years old and 35 years old, commonly called “Millennials” (born between 1981 and 1996), that identify tourism as one of their main needs. Furthermore, digital visitors also comprehend those individuals that are characterized by new demands (Z Generation—people born between 1996 and 2010) and from those that acquired ICTs as their main information tools (Hashtag Generation) [ 47 ]. These generations can be perceived as travelers who want to learn and put aside the routine, seeking personalized adventures to feel integrated as residents while experiencing personal development. These new visitors’ profile rejects tinned experiences and participates in activities related to social trends. For this reason, the digital tourist/visitor will share their personal data if it permits living a personalized tourist experience [ 48 ]. Inside of the new social tourism paradigm, it is important to consider the prosumer profile. This profile refers to a producer and consumer of content who generates and shares opinions, experiences, and information through their digital contact network [ 49 ]. Currently, tourist services and tools’ content do not depend on the business; prosumers seek their participation in the co-creation of content based on their experiences [ 7 ]. The digital tourists/visitors are more influenced by comments/recommendations shared on social networks by other users than by information provided by a tourist agent. For that reason, new tourists/visitors grant the main role to experienced visitors as generators of useful content to plan and enjoy a trip. The new tourism concept opens a digital and online tourist market which allows interaction among the visitors/tourists and the territory via a smartphone. These solutions should be social, interactive, and customizable to leave behind the traditional holiday package scheme and they must promote a trend towards the client-to-client approach (C2C) [ 50 ]. It is important to combine the smart part of the technology with the hospitality and social aspects of human interaction [ 51 ]. Intangible heritage is gaining relevance as a personalized territorial offer, which needs to be lived in person. Researchers such as Greg Richards have highlighted the relevance of studying intangible tourism for destinations for two big reasons: tangible heritage is increasingly hard to conserve over time and new visitors want to enjoy new experiences. In his research, Richards [ 52 ] defines cultural tourism as “ A type of tourism activity in which the visitor’s essential motivation is to learn, discover, experience, and consume the tangible and intangible cultural attractions/productions in a tourism destination ”. Moreover, the author declares that cultural tourism improves the smart tourism destination sector by helping to preserve heritage areas and that the use of technologies and social networks could help to establish contact with visitors after their trip. This trend has resulted in the emergence of the mobile tourism concept [ 53 ], which involves special attention to the design, user experience, and content of apps and websites [ 54 ], as well as their dissemination and communication. In addition, it is important to define the purpose of these tools in the tourism domain to build a successful solution. Visitors search for help and information on their app marketplace and browser during their visit, transforming their smartphone into the new tourist office of the cities. An example of these tools is TAIS (Tourist Assistant Infomobility System) [ 55 ], an infomobility tool system, which combines information and recommendations about a region based on a user´s preferences and location, behaving as a personalized tourist guide. Beyond the apps and websites for smartphones that are used during the visits, it is now possible to find solutions that interact with the territory to offer content based on location. As part of the content offer, tourists can find smart points of interaction; that is, smart areas that cover from 1 m to 80 m of radio, where they can interact with their smart device (smartphone or tablet). This interaction is achieved due to the use of devices called Smart Spots. These devices disseminate content through Wi-Fi (captive portal) as an open Wi-Fi network. Furthermore, they allow access though Physical Web technology developed by Google (Bluetooth and GPS) [ 8 ]. In addition, according to the environmental pillar of tourism sustainability, these devices are the basis of Internet of Things deployments, including sensors that allow the counting of people, air quality measurement (gases and particles), and noise monitoring. One previous project was the TreSight in Trento, which used IoT to create an immersive tourism experience [ 56 ]. The TreSight project’s objective was to combine innovation and traditions with a tool that offered information and recommended local businesses to visitors by using the Open Data of Trento; where points of interest, restaurants, and environmental data are stored. At the tourism office, visitors receive both a wearable device (bracelet) that collects data about the user’s environment and location, as well as a website link to download the app that gives suggestions based on the crossed data. According to this new tourism domain, focused on the use of new technologies to develop tools and services for the visitants, territories and ICT companies are seeking solutions based on their needs. Among the big mobile marketplace of tourist solutions, specific objective tools and other solutions that intend to gather the required information during the tourist experience can be found. Spanish regions have deployed interactive tourist solutions, such as the case of Smart Wine Route Ribera del Duero. The project designed the first smart Spanish wine route, creating digital panels based on the Physical Web technology (Bluetooth connection with smartphones nearby). In total, 103 beacons have been used to deploy the Physical Web connection that is detected by the Inventrip app ( https://inventrip.com/ ), a platform oriented to travel management. In this way, it increases the number of tourist information offices to 103. This project uses devices based on the Physical Web in conjunction with information from physical signals to create a geolocated experience [ 57 ]. The results of this research work highlight the solution to the Ribera del Duero signage problem through the use of beacons, and the aperture of a new research line focused on updating the cultural heritage communication channels. 3. Research Methodology 3.1. Purpose and Research Assumptions Due to the current need to evolve tourist destinations to a smart version, this section defines the purpose and assumptions of the research and development proposed in this article to support this evolution. Subsequently, the methodology proposed to achieve the objectives defined in this section is described. The proposed research work aims to design and validate an interactive and agile tool to disseminate the cultural content of a territory between visitors, based on the real needs of a territory and with the main pillars of sustainable smart tourism destinations. According to the needs of the Ceutí visitors and the needs of the city council, the solution proposed should be a tourist guide that transforms visitors into short-time residents. On the other hand, the research intends to design a scalable solution, which can be installed in different types of territories according to their size and cultural offer. For that purpose, this solution will use ICT tools since they allow the benefits of the new implicated resident and the target digital visitor to be increased in order to create a sustainable information cycle, which involves a low level of participation of the destination managers. Therefore, according to all the information, this research work proposes a smart tourism destination tool designed in two phases: A first artefact based on the state-of-the-art/ICT analysis and its adaptation to Ceutí, which will be evaluated and validated (prototype). The prototype development is composed of two main pillars of innovation: A communication channel based on smart point of interactions (Smart POIs), created with the Smart Spot devices, which send non-intrusive push notifications to users’ smartphones with online geolocated content through Bluetooth (nearby technology) and Wi-Fi (captive portal), without the need to download an application for the users [ 8 ]; Content disseminated by Smart POIs about the Point of Interest (POI) of Ceutí, created by different resident communities, and focused on the culture and heritage of the territory, addressing stories, experiences, and traditions in short-time video-interviews. To achieve these objectives, the following methodology is proposed. 3.2. Research Method Qualitative: Study the state-of-the-art. The research methodology begins with a study of the state-of-the-art about the sustainability concept, which is the major principle of smart cities and smart tourism destinations. In addition, these research lines have been analyzed to obtain knowledge on the global situation and the role of them in Spain as one of the leading countries in the field. In the same way, a study of different ICT tools and deployments used for tourist destinations at a global level is carried out; Detect the needs of the tourism destination from interviews. This study will explore the needs and problems of tourism innovation that the tourism destination requires to boost its visitor activity in a smart manner; that is, to spread its culture and tourist information and to determine how it can capture the interest of its visitors. This study will be carried out through different meetings and interviews with the tourism and City Council managers; Quantitative: Define the profile of the visitor from a survey. Once the needs of the tourist destination are defined, the research analyzes the target profile of the user of the solution to generate a solution based on their preferences. This process is carried out through a non-probabilistic cluster survey aimed at a representative sample of the population to gain knowledge on how they use digital tourist resources; Description of the trial: Define the first draw of the solution. After analyzing the state-of-the-art, a first artefact of the tourist guide is defined to disseminate tourist content between visitors. This solution must provide an innovative communication channel (the first pillar of innovation) based on the possibilities of ICT technologies, using IoT devices called Smart Spots [ 8 ] to create interactive areas for users; Research the Territory. To test the artefact of the solution, research about the tourist destination is carried out in information sources related to tourism and through meetings with the tourism managers of that territory; Develop and deploy the prototype. According to the context obtained from the previous investigations, the POIs are established by the people in charge of tourism in the territory. This solution provides an innovative communication channel, as well as content co-created by the residents of the tourist destination, the second pillar of innovation of the prototype, highlighting the intangible cultural heritage. Subsequently, deployment of the solution in the tourist destination is carried out. For this, the type of content of the solution is defined to motivate the participation of residents who may be involved with said content. Therefore, it is proposed that a dissemination campaign should be designed. The objective of this campaign is to disseminate the proposed solution between residents and visitors of the tourist destination to spread the prototype of the territory, as well as to motivate the co-creation of content among the inhabitants of the place; Know the impact of the prototype. To know the impact of the proposed solution, this research will analyze the acceptance of the proposed tool in the territory through quantitative information provided by tools, such as Google Analytics and social networks, as well as through meetings with the city council about the impact on the tourism office. 3.3. Sampling In order to know the profile of the visitor of Ceutí, a representative sample of the population will be established to provide the designed survey. To establish a representative sample of Ceutí visitors, the available tourism statistics were consulted. However, the official data are not divided by municipality, but by larger geographical areas and with similar characteristics, in terms of the environment and proximity. Therefore, the tourism received by the central area of the Region of Murcia is taken as a reference because Ceutí belongs to this area, composed of a set of localities with similar characteristics, such as a rural environment. This area receives, according to official data, mostly visitors that are resident in Spain (between 80% and 90% of the total), whilst the rest are foreigners with an average stay of 1.53 nights [ 58 ]. These data were confirmed by the city council technicians, responsible for tourism in the town, who reported that approximately 85% of their visitors were residents in the Region of Murcia. Thereby, the representative sample is established based on 200 people: 173 surveys to residents in Spain (86.5%), mainly from the Region of Murcia, and 27 surveys to non-residents in Spain. In addition, three clusters of age groups for residents of Spain are established to distribute the surveys; however, for non-resident visitors in Spain, age clusters are not defined since there is no data related to age. As good average representation of the period of time (taking into account the months with a high and low number of visits) of the monthly visits of Ceutí during the year, the survey uses the data of February 2017, when the center of Vega Media of Murcia had an influx of 3979 Spanish travelers, where 3437 (86.4%) were residents of Murcia and 542 (13.6%) were non-residents [ 58 ]. The original data do not specify the locations of travelers residing in Spain, so with regards to qualitative research based on official statistics of visitors from the area under study and with a consultation with municipal technicians, it was established that visitors in Ceutí were residents from the Region of Murcia and nearby zones. Due to the number of foreseen visitors being too low, the locations for the respondents were not specified. Hence, a clusters survey (Survey: https://docs.google.com/forms/d/e/1FAIpQLSfItF0WtZOVJ7sOuzw14SGEqnXxKmtPEAEwk_vHAZvxZMlY2w/viewform ) was designed for conglomerates. The target respondent of this survey was members of the population over 18 years old that resided in the Region of Murcia in 2016, as the last data obtained by the census ( Table 1 ). The survey was designed to research the user’s habits during their tourism experience and to support the development of a recommendation algorithm called “HyRa: Hybrid Recommendation Algorithm focused on Smart POIs” [ 59 ], which could be adapted in the final solution. The survey was structured as three sections: Personal information; Use of digital tools during their tourism experiences; Respondents who go sightseeing within the Region of Murcia. 4. Results 4.1. First Artefact Using ICTs to Build Smart Tourism Destinations As a first result of the research, based on the analysis of available ICTs and the state-of-the-art, a tourism tool composed of an IoT device called a Smart Spot and a Web-App was produced. This design of a new tourism tool is based on the Design Thinking methodology. This device determines the artefact to be tested in the application scope in order to know the issues that could arise during the actual deployment to discover these aspects during the product/service definition process [ 60 ]. This draft is based on previous research called Smart Tourism Destination & Cultural Heritage: A New Unexplored Sector in Smart Cities Development [ 9 ], which analysed the tourism domain and Internet of Thing (IoT) technologies. Therefore, this paper establishes the use of IoT devices called Smart Spots ( Figure 2 ) [ 8 ], which allow the cultural point of interest (POI) to be transformed into a smart point of interaction denominated as Smart POI [ 9 ]. These smart areas create a new communication channel between the cultural offer and the residents/visitors as the first pillar of innovation of the prototype. The Smart POIs spread over an area of one to 80 m, where the user can interact with their smartphone in two ways ( Figure 3 ): Wi-Fi: The device creates an open Wi-Fi network using the city Internet network or a SIM card. When the user connects their smartphone to the Wi-Fi network indicated in a cartouche, a webpage with content about the POI is opened automatically; Physical Web: Additionally, the device disseminates the same content through the Bluetooth signal, sending a push notification (push notification: A simple way to interact with the smartphones of users through a non-intrusive mobile notification) to the nearby smartphones, which have the Bluetooth and GPS options turned on. Smart Spots can be installed in facades, streetlights, and masts, etc., in either rural or urban areas. These devices can obtain the electricity they need to operate from a battery or from solar panels, avoiding the need to wait for electrical wiring infrastructure and an Internet-wired connection. Thanks to their versatility, the Smart Spots allow the Smart POIs to be created in all types of areas, disseminating their content through the visitors´ smartphones, without the need to download an app. Similarly, their capability to provide the Internet makes it possible to enjoy multimedia content, podcasts, and other types of content without the need to use the user’s Internet connection. 4.2. Research on the Territory to Test the Artefact The final tool was adapted to face the needs of the city lab, Ceutí, with the aim of knowing the issues, benefits, and real-world impact of this device in the town’s daily life. The town is an agricultural village and its cultural heritage is interesting, being based on irrigation agriculture culture, ancient detachable canning factories, and avant-garde contemporary art represented in the streets [ 61 ]. This culture shock makes this territory the perfect place to carry out the proposed experiment since the use of new technologies can be the most useful tool to transform all this cultural content into an attractive offer. 4.2.1. Ceutí as a Destination According to research on the territory carried out to execute the trial, based on interviews with city managers and the revision of other projects and documents, the research defined the main characteristics of Ceuti as a tourism destination. Ceutí has a broad cultural and artistic heritage in its streets. This village has an outdoor museum with a collection composed of big murals, sculptures, churches, and different international museums. The municipality, which has less than 20,000 habitants [ 61 ], is visited because of its gastronomy and artistic offer by habitants of the same region (Region of Murcia), who spend the weekend there. A secondary visitor source is composed of motorhome tourists, who park in Ceutí´s large esplanade, and French people, who emigrated years ago and are visiting their families. This research on Ceutí´s target audience was accomplished through meetings with the city council managers, who supported the project during the entire process. The first findings have been documented in the article called “Towards the Development of a Smart Tourism Application based on Smart POI and Recommendation Algorithms: Ceutí as a Study Case” [ 62 ]. The city council described the majority of people that visit Ceutí as visitors, not tourists. The reason for this is the limited number of hotels offered, with only one hotel outside of the town. Many visitors of Ceutí go sightseeing and eat in typical restaurants, visit the museums, and go to sleep to the Archena hotel, a famous natural spa ( https://balneariodearchena.com/ ), near the municipality. In addition, the tourists that go to the Region of Murcia for its rural culture and orchard visit different towns of the Vega del Segura in the same trip and Ceutí is one of the typical planned visits for one day from places such as Mula, Cehegín, Fortuna, Archena, etc. In addition, the residents in the Region of Murcia and nearby territories such as Almeria usually go to visit other territories on Sundays for one day by car, which is a very typical activity for Spanish families and groups of friends. According to the research, the tourism is based on two small fonts: caravan parking and emigrants who visit families. It has a big caravan park where families and couples (mainly French people) park and spend some days in the center zone of the region. The park is cheap, big, and comfortable, providing water and a power supply, with a big supermarket nearby. According to the emigrants, a few years ago, the majority of Ceutí residents who worked in the orchard had to go to France and Holland to work, collecting fruits and vegetables in the high seasons. Many of those emigrants established their residence in other countries for job opportunities and created new families there. For that reason, they visit their families in Ceutí in holiday periods, and stay overnight in the families’ houses. As a rural territory, its main visitor season is during the winter and autumn, according to the weather in the Southeast of Spain, when the climate is better to visit such territories than in the summer. However, it is important to take into account that during August, a lot of visitors go to Ceutí to enjoy the local festivities of the territory as a high attraction event in the regional area; mainly the residents that cannot go to the coast during the summer. Previously, Ceutí was not a big destination at a tourism level. It did not have big buildings and historical places and the city council has changed that through a new strategy based on creating an outdoor museum with different cultural attractions related to its canning, rural, and orchard culture, mixed with new points of interest that are more focused on the contemporary art. In this way, it has much to offer for many types of visitor, which has improved the economic sector and built a more friendly/cultural environment for the residents. Since 2000, it has deployed many cultural points as sculptures, murals, and museums [ 63 ]. Its outdoor museum is formed of [ 63 ]: Bronze nudes (José Planes); Violinist (Paco Barón); Flying low (Paco Barón); Torso (Eduardo Lastre); Michelina (Fernando Bellver); Customs murals (Marisa Peagudo); Canning woman sculpture (Salvador Susarte); Live Alegory (Torregar); Child in the ditch (Manolo Belzunce); Emigrant sculpture; My metaphysic Garden (Ouka Leele); Contemporary Art Center La Conservera; Antonio Campillo Museum; 7 Chimneys Ethnographic Museum. 4.2.2. Detect the Needs with the City Council through Qualitative Interviews As one of the initial activities during the research and in accordance with the main pillars of smart cities, the interviews with the city council managers and technicians represented the first contact with the real needs of the territory. Through these interviews, the researchers involved in this article obtained a list of qualitative results that will help in the development of the final tool, in search of a result based on the real economic, socio-cultural, and environmental needs of the territory. During these interviews, the following relevant aspects were detected for the research: Revalorize the intangible culture: Thanks to the previous project called iBrave [ 64 ], it was concluded that Ceutí has to work on branding itself through valorization of its intangible heritage by popular knowledge; Engaged residents: The residents of Ceutí are proud of its homeland heritage. Therefore, Ceutí is full of communities involved in the preservation of their culture and environment [ 65 ]. These communities cooperate with the city council managers to improve their territory through different meetings called Cross-Sectorial Tables, which are regularly organised. Through these collaboration workshops, the residents contribute to the development of their town in different ways, such as through cultural activities. This strong cooperation between residents and the city council has been analyzed and used in several territories as a source of support in the successful preservation and dissemination of heritage, as in the case of Bogda World Natural Heritage in Xinjiang [ 66 ]; Necessity of new attractive tools: This municipality wants to have more tools to spread POI information; Digitize intangible heritage: As with other territories like Brandenburg, where an interest in digitizing the cultural heritage of different European initiatives exists [ 67 ]. Ceutí seeks to preserve its popular stories to save the essence of the village as the main pillar of its tourist brand. 4.2.3. Ceutí Visitor’s Profile With regard to the results on the tourism relation with the Region of Murcia, 76% go sightseeing in the region and 70.5% visit the municipality. The main reason for visiting this municipality is to go sightseeing, visit relatives, work, and experience the gastronomy. However, age is a key factor when it comes to sightseeing in the region. Older people make more trips through the region, a behavior that can also be observed among visitors of Ceutí. Furthermore, the users included in older age groups have sightseeing as their main reason for visiting Ceutí, while the gastronomy of this municipality does not interest the youngest. Most of respondents consult one or two sources during their experience (83%). According to the collected data, the favorite source is the browser (37.7%), followed by the traditional visitor guide (28%), Facebook (16.4%) and, a downloaded app (14.6%). There is no relationship between gender and consulted sources when traveling. The respondents who are 31–50 years old are those who consult their browsers (41%), as well as those who consult the traditional visitors guide (38.8%). The same thing happens when consulting the traditional visitors guide: the middle-aged individuals are those who consult it the most, with a value of 38.8%. However, those who most consult Facebook are the youngest (45%). Age is a decisive factor when posting on social networks: the youngest are those who publish on different social networks, with Facebook being the first option (77.5%) and Instagram being the second option (49%). 4.3. Prototype of the Project in Ceutí: Be Memories The acquired knowledge has allowed the first prototype to be improved by creating a smart visitors guide with content co-created by residents, according to the needs of Ceutí. The final solution, called Be Memories, is based on two pillars of innovation: A new communication channel to disseminate tourist content through the use of IoT devices (Smart Spots) that create interactive areas (Smart POIs); Personalized context-aware content created by the residents in a multimedia format, which intends to be as interesting as it is entertaining. The installation of the Smart Spots devices ( Figure 4 ) allowed the city council of Ceutí to deploy 15 Smart POIs in the facades of the main POIs of the outdoor museum ( Figure 5 ). Thereby, the communication channel, people, and these POIs were established through a Wi-Fi network, without the need to download an app, as explained in Section 4.1 . Thereby, Be Memories content can be accessed by interacting with the Smart POIs through a progressive Web-App, through only having the Bluetooth and GPS options turned on or the Wi-Fi option. The progressive Web-App is a webpage adapted and designed as a native app for enhancing the user experience. This new concept avoids the download of an application to any smart device since access to this type of application is gained through a link (URL) from the browser and the users can directly access it on their smartphones (simulating a native application) if they want. The use and design of Be Memories are based on the knowledge acquired by analyzing the tourism apps, the stakeholder surveys, and the current trends ( Figure 6 ). Regarding the second pillar of innovation, the content offered is based on the stories, experiences, and traditions of Ceutí, which were provided by the residents involved in the local culture. The content is in a multimedia format in the form of short-time video-interviews (see a trailer of the video-interviews here: https://bememories.hopu.eu/#/login ). To generate this content, with the support of the city council, the people involved in this project contacted different communities of the territory, such as students, associations, and museum guides, among others, as well as the artists who participated in the tangible cultural heritage of Ceutí. Once the contact was established, the researchers involved and the city managers carried out different meetings with residents interested in telling their stories to later select and record the best stories. Thereby, seed content was created to test the solution and, in turn, to encourage the participation of new narrators. The short-time video-interviews were recorded without a plot, with the narrators telling their story as they lived it. Therefore, through this methodology, the videos can show the essence of the native culture. In the same way, the selection of participants was carried out in such a way that the profiles were inclusive, considering children, art lovers, elderly people, and workers, among others. International artists were also involved. For example, among the people interviewed, there were international artists like Jose Antonio Torregrosa “Torregar”, a neo-realistic painter who created a big mural for Ceutí. In addition, the records contain a group of town students who know the different stories of museums, as well as two workers from the old canning factories of Ceutí who describe how they lived in Ceutí 30 years ago as the economic pillar of their family, among others. The Smart POIs deployed in Ceutí are for the visitors, residents, and non-residents of the town, without the need of overnight visitors in the municipality, as the main stakeholders of the cultural content of the territory. For that reason, Be Memories is designed to provide information for the user that walk through the town as an agile experience to discover the local culture in a short time period. All of the Smart POIs are signaled with an outside cartouche near of the POI for the visitor’s knowledge ( Figure 7 ). 4.4. Project Dissemination Campaign During the test of the prototype in Ceutí, a Be Memories dissemination campaign was carried out to make it known to visitors and residents of Ceutí. For that purpose, a Facebook page dedicated to Be Memories was opened called @BeMemoriesCeutí ( https://www.facebook.com/BememoriesCeutí/?eid=ARDUXoN5jIfowHXwFIyJhFVhj7dmZumqh3wGNoOg_C_Ce1cHGYcMNkBHe1-e0RiGP3brlmhWoX-ftYpr ) and, at the same time, flyers and posters were designed to distribute them around the region’s streets ( Figure 8 ). The content of this campaign was used to extol the local identity and the recorded material during the video-interviews. According to this, the flyers, posters, and Facebook provided curious facts about the town, gathered from the information of the videos, and introduced the narrators through a header that described their participation in Be Memories. During the campaign, on the one hand, on the Facebook page, the residents involved were tagged, with the aim of encouraging post sharing to reach their Facebook regional followers. Furthermore, the regional media helped in the dissemination within the Region of Murcia, such as the case of ROM Murcia (Radio Online Murcia) ( http://www.romradio.es/2017/06/06/queremos-que-sean-los-Ceutíenses-quienes-den-a-conocer-su-tierra-andrea-gomez/ ). On the other hand, the flyer and poster indications about how to use Be Memories were distributed in local businesses, restaurants, street walls, and tourist offices for new visitors. The launch of the trial occurred during the local festivities of Ceutí, from 6 August to 19 August. During the first 15 days of the campaign, the Facebook page of Be Memories Ceutí had 161 followers and the posts reached 300 users ( Figure 9 ). 4.5. Data Obtained during the Trial Since the test deployment was based on 15 Outdoor Museum POIs, which were selected to install the Smart Spots, the content of the 15 Smart POIs was generated in collaboration with the residents. This co-creation of content was successfully achieved thanks to the project page created on Facebook and the help of the city managers. From this, a trial of the solution was launched during the local festivities of Ceutí (6–19 August), which was also supported by a campaign to disseminate the project through the Facebook page, flyers, and posters. Therefore, as a pilot study, the analysis of the results was performed with the data obtained from the local festivities based on the data collected from the main Smart POI deployed in the city council square, where outdoor activities take place, such as the San Roque Proclamation and local games. This Smart POI showed a trailer of all the recorded video-interviews ( https://bememories.hopu.eu/#/login ) that make up Be Memories. During the analysis time, the proposed Web-App accessed through Smart POIs was evaluated using Google Analytics to know how many people watched the short-time videos, as explained below. Google Analytics was installed in the progressive Web-App to know how many users visited the Smart POIs because the video is only available through the Be Memories communication channel. The report confirmed that during the first 15 days (the trial period), more than 400 users connected with the main Smart POI and saw the video-interviews, achieving 30 visualizations per day. This number evolved to 5051 visualizations in May 2019, with week peaks higher than 240 users connected ( Figure 10 and Figure 11 ). During the trial period, the Be Memories progressive Web-App obtained more than 26 good comments and no bad comments. The video received 160 likes and five users contacted the project through the Facebook page to participate in the video-interviews. Furthermore, 90% of the users connected during the 15 first days were Spanish people, including Region of Murcia residents, such as those from Molina de Segura and Cartagena, and residents from other Spanish cities, such as Madrid, Barcelona, Valencia, and Sevilla ( Figure 12 ). 5. Discussion Due to the last results about the two weeks of the trial, the research has provided lessons learned based on the advantage and problems of Be Memories in Ceutí. As another indicator of success, different national territories have shown interest in replicating Be Memories with their residents. A Spanish town called Mula ( http://mula.es/web/ ) showed interest in deploying Be Memories in its territory, and Cartagena Puerto de Culturas (Cartagena Puerto de Culturas: https://www.cartagenapuertodeculturas.com/ ), as a cultural organization of the maritime city of Cartagena, wants to adapt the solution from its museum offer. These indicators are promising because one of the main research objectives was to build a scalable solution to solve the problems of different territories to disseminate their culture among the new digital visitor. In addition, the impact of the tool at the European level was highlighted. On the one hand, Be Memories won the open call to participate in the ICT Flame project to deploy the same solution in the Millennium Square in the City of Bristol, using the technological advantages of the project platform to improve the video reproduction during the user experience (ICT Flame web https://www.ict-flame.eu/news/winners-1st-flame-open-call-announced/ ). This opportunity will allow Be Memories to be tested with other user profiles in a territory with more inhabitants. On the other hand, the tool is the basis of the ERASMUS+KA2 project, called Walk a Story (Walk a Story web: http://www.walkastory.com/site_dnm/ ), which is constituted of partners from Poland, Denmark, Turkey, Croatia, and Romania. The ERASMUS+KA2 project aims to find a methodology to discover and record the local stories of old people among intergenerational walks in order to build tourist content to disseminate through Smart POIs based on the cooperation of local communities. In addition, Be Memories won the label of the European Commission for the European Year of Cultural Heritage (EYCH). In accordance with the needs involved in the creation of a tourism tool that fits the pillars of sustainable tourism, smart cities, and smart tourism destinations, the results obtained with the Be Memories trial satisfactorily cover the main factors presented in the state-of-the-art: Tool for sustainable tourism. According to the pillars exposed by UNWTO [ 2 ], Be Memories is a tool that does not exert an ecological impact in the environment where it has been installed, not making use of natural resources in the short and long term. Regarding the economic aspect, Be Memories is ethical and egalitarian in terms of the diversity of local communities, transforming them into essential active agents for the operation of the tool (creation of content), thereby reducing the economic investment that local managers and technicians have to make in the creation and publication of contents, which is one of the main problems of small and medium municipalities in Spain. Therefore, Be Memories supports integration of the environment, including the natural (rural areas) and urban environment, with the culture (intangible heritage) and the human factors (local communities with different ideologies and cultures), creating a triangle that is supported to generate a representative and sustainable tourist tool of the municipality. Thanks to the integration of local communities, who contribute their knowledge on and traditions of the locality, Be Memories has a positive impact on the intangible cultural heritage of this territory and in turn diffuses and transmits these traditions and intangible cultural heritage to other local communities of different ages, social classes, and ideologies, as well as to visitors who are not resident in the municipality, revaluing these traditions and cultures as a strong cultural attraction. At the same time, the diffusion of these traditions and local culture through the use of new technologies, from different points of view, has supported the feeling of solidarity and mutual respect in the municipality and this vision has been transmitted abroad, creating tourism content for the visitor who supports all these values. Thereby, the tourist actors, artists, and local businesses have been involved with the communities to create an ecosystem of solidarity and respect, working together to create all this content. In summary, Be Memories enhances the local potential through the involvement of the territory’s ecosystem: commerce, the city council, and communities, enriching the municipality with the use of new technologies to transform it into a sustainable and smart tourism destination; Tool for smart cities and smart tourism destinations. As detailed in the state-of-the-art, smart cities have their origins in the idea of sustainability and in turn, a smart tourism destination must be based on the pillars of these cities, making use of the opportunities of ICTs. Nam and Pardo [ 25 ] indicate that everything proposed for a smart territory must work on three main pillars: technological, institutional, and human. Therefore, Be Memories is the result of the search for a system that uses the currently existing technologies to create a tool for the visitor (use of Smart POIs) that takes into account the institutional needs, while the social infrastructure of the territory participates and nurtures itself (communities that create content). The concept of a smart tourism destination requires new strategies to improve its tourist offer for both visitors and residents. To achieve this goal, the state-of-the-art shows that the use of technological tools helps destinations to transform their processes and systems into a new sustainable, smart, practical, and attractive approach. Therefore, Be Memories is a possible way for small and medium tourism destinations to transform their processes in accordance with current innovation trends by using technological tools and local resources to build a sustainable dissemination channel for their culture. Be Memories can contribute to the sustainable tourism development of smart tourism destinations as presented in the three main aspects of the UNWTO Guidebook for sustainable tourism [ 13 ]: economic, environmental, and socio-cultural: Economic sustainability: The contribution of technological tools, such as Be Memories, can attract new digital tourist’s eager for online content, which will result in higher revenues for the local tourism industry and, therefore, in more jobs for the local community; Environmental sustainability: Firstly, Be Memories has no impact on the local environment, thus being a sustainable environmental tool in the short and long term, as described in the point of sustainable tourism. In addition, the Smart Spot devices contribute to automatic data collection to build indicators of the environmental impact of the tourist activity in the smart destination, alerting local authorities of the load capacity of tourism in terms of impact on the territory. This includes factors such as air quality, light pollution, noise pollution, deterioration of the natural environment, among others. Similarly, with this type of application, environmental education content about the smart tourism destination itself can be generated. Thereby, future generations can be actively involved in the conservation and sustainability of the destination; Sociocultural sustainability: Be Memories respects and enhances the existing cultures in the tourism destination, as well as the promotion of relationships between people with different socioeconomic statuses and cultures that are not always similar. In this article, the cultural factor is the one that has more relation with the presented research. For the cultural sustainability of a tourism destination to take place, its history, customs, celebrations, beliefs, and traditions, among other aspects that shape its own and differential identity, must be taken into account in the tourist development of the territory, and they also must acquire special relevance; that is, to preserve the intangible cultural heritage of the host community integrated into the tourism destination. In this research, a progressive Web-App has been developed, accessed through Smart POIs, which promotes the cultural sustainability of the tourism destination and which focuses on the protection and conservation of intangible cultural heritage through the creation of videos that contain experiences, memories, and curiosities of the residents about tourist POIs of the destination. The POIs chosen are different from those found in traditional tourist guides and in guided tours by professionals in the sector. Thereby, the intangible cultural heritage is transmitted to visitors and remain in the collective memory for a longer period of time, taking advantage of the opportunities generated by the new ICTs. Regarding the main needs detected through interviews with local managers and technicians, as well as in previous studies analyzed, Be Memories has covered these objectives as follows: Build a sustainable and smart tourism destination: Based on the definition provided in the state-of-the-art section, a sustainable smart tourism destination is a territory of interest for visitors, effectively managed due to the opportunities of ICTs [ 35 ]. Be Memories is a tool that has helped Ceutí to position itself as an innovative territory, where intangible heritage and ICTs are combined to offer new tourist communication and dissemination channels to new visitors, promoting and protecting its main attraction: cultural heritage. After the installation of Be Memories in Ceutí, the town has been present in different national media and events, placing it on the visitors´ maps ( https://www.laopiniondemurcia.es/especiales/fitur-region-murcia/2019/01/Ceutí-vista-europa-n1571_16_46437.html ). This is reflected in the number of visitors that have come to the tourism office of the city council, as it has increased in the last year, according to the information obtained from the interviews conducted with the city’s stakeholders. The success of Be Memories in Ceutí is also due to the fact that it helps the tourism managers to offer a new more agile approach to tell stories related to the tourism destination (Smart POI channel) that are more attractive (local stories) and involve less time (co-creation of content) for visitors when they require information about POIs; Revalorize the intangible culture: According to previous projects developed by the City Council of Ceutí, such as iBrave [ 64 ], an essential goal of this project (Be Memories) is to enhance the intangible cultural heritage of Ceutí abroad to make it the main tourist attraction and in turn, promote the entire outdoor museum. In addition, research on the UNWTO Chapter for Sustainable Tourism has been considered [ 2 ]. Be Memories took this into account from the start as the main goal of the project. Thanks to the profile of the communities of this territory, which are very involved with the actions of Ceutí and its cultural heritage, this content could be generated and used in the tool. The participation of the city council managers and technicians was very important for carrying out the interviews and locating those people who had something to say that could be of interest and respectful to the visitors, such as popular stories and anecdotes that occurred in the territory, which could not be located in the books and were transmitted, until now, from mouth to mouth. Fifteen interviews were recorded, where residents were interviewed and the camera recorded the entire interview. In this way, in post-production, the content of greatest interest could be segmented, making final videos of approximately 1 min that could be easily consumed by the visitors. Among those stories, old workers of the factories of preserves of Ceutí, who narrate what it was like to be the economic pillar in their houses more than 40 years ago; an artist who painted a mural of Ceutí at the beginning of his career, exposing the reasons for this mural; or the town’s chronicler, who opened the ethnographic museum, telling the listeners how that process was, can be seen. In turn, distributing these stories in video format through the Smart POI has improved the “from mouth to mouth” process, used so far to disseminate this intangible heritage, revaluing it within its own territory and making it visible to non-resident visitors; Engaged residents: Another relevant aspect of the Be Memories deployment is that the participation of residents has been promoted and supported, since different communities have worked together to create the content of Be Memories under the idea of showing their local culture [ 65 ]. Based on the UNWTO chapter to build sustainable tourism destinations, the integration and acceptation of the local network is one of the more important aspects when building sustainable tourism activities [ 2 ]. So far, more than five residents have recorded new videos for the next update of the content of Be Memories, which shows the positive impact that Be Memories has had on the population. Similarly, it should be noted that some disruptive contemporary pieces of art like “Allegory of Life” ( http://www.Ceutíturistico.es/al/es/plazanueva.html ) have been explained by the artists themselves through Be Memories, improving the local acceptance of the most innovative pieces of art. The aspect of co-creating content for Be Memories is one of the main pillars of the resulting solution. This content creation approach, in conjunction with resident participation through videos introducing local stories, is a strategy based on the smart cities and smart tourism guidelines. In this case, Ceutí has great potential, by having a strong local culture and pride in its local environment, which works as an attraction for visitors; therefore, the city council’s managers seek to improve and renew their POIs with a low investment. This purpose has been achieved when deploying Be Memories in Ceutí. In addition, the co-created content improves the resident’s collaboration by joining different types of communities to record interviews. As one of the main lessons learned during the project, the cooperation with local residents must be impartial, that is, without any political and ideological involvement, showing all aspects of the town and including all the communities interested in these activities. In this way, open collaboration with all of them will allow the content of Be Memories to be attractive, inclusive, and representative of the local culture. Considering city managers, this content update approach allows them to reduce the time spent on this type of activity, which makes it more sustainable for small- and medium-sized cities with fewer resources. That is, the city council only needs to verify the content uploaded by the resident and promote activities for the creation of content, involving three objectives with the same activity: improving the resident network, generating the visitor’s information, and developing good advertisement of the local communities; Innovation based on the visitors profile (necessity of new attractive tools): Similarly, according to the results of the surveys conducted in this research, it is detected that both the resident and the target visitor of Ceutí do not use native applications for going sightseeing since they prefer to search for information on a web browser. In addition, research on the new visitor’s profile, composed of Millennials, the Z generation, and the Hashtag generation, describes the role of the new technologies and mobile tourism concept as the main channel for offering the tourism content to visitors [ 47 , 53 ]. Therefore, Be Memories is designed according to this finding by being a tool that can be accessed from the web browser without the need to download a native application, offering an experience similar to websites. Another advantage of Be Memories is that it does not use the Internet connection of the visitor’s smartphone since the Smart Spots provide a Wi-Fi network from where the content of the application can be consumed. Another perspective, the integration of ICTs into small- and medium-sized cities and territories, leads to two major problems: there is a small population group with little capacity for technological tools and limited knowledge of technological concepts, and a sector of users has vintage smartphones that can pose problems. However, changing the focus of the content for visitors is necessary because their new profile requires new experiences and tools to revalue the territories. Therefore, Ceutí’s strategy of using local knowledge to create a new attraction for visitors is a good practice for places where the local culture is strong in empowered local communities that have lived and grown in the territory. This approach supposes an advance in the cultural POIs of Ceutí when showing them in the media with its new contents. In addition, this type of content is very useful for cities and towns where the main visitors are people from the same region and country. On the one hand, anecdotes and local stories that include areas of the town and local, regional, or national knowledge are more attractive for users linked to the area because they have prior knowledge to enjoy the content and feel more interested in this type of information. On the other hand, the stories of artists and information provided by the residents about the process of creating pieces of art that the visitor can simultaneously observe are better for people who do not reside in Ceutí, such as the case of Torregar, a Mural painter who participated in introducing his mural and art studio; Digitalize the intangible heritage: According to other European projects such as Brandenburg [ 67 ], Ceutí needs to digitalize its intangible heritage, so Be Memories has built a digital documentation of local folklore to use it as a tourism content to explain the outdoor museum at the same time as digitalizing the intangible heritage so that it survives over time. Regarding the generation of Smart POIs, it is necessary to emphasize that the Be Memories design principles are focused on promoting the physical visit to the POIs; for that reason, specific content for a POI is delivered and available only when people are near the POI; that is, Smart POIs build a local network around 20 m from the POI to create this geo-target. Thereby, POIs are promoted in their location since Smart POIs allow an augmented version of the POI based on media content and additional meta-information to be provided. This content is unique since the videos are not available on social networks or public channels, such as YouTube, so it is not feasible to consume them before attending the POI and consequently, it does not replace the POI’s visit. As mentioned, to access the content of Be Memories, it is necessary to be in front of a POI. According to a previous project called TreSight (TreSight video presentation: https://vimeo.com/131875612TreSight video presentation: https://vimeo.com/131875612 ) [ 56 ], the comparison indicates that the use of smartphones, as the only device required to enjoy a tourist experience, has better results when motivating participation. Moreover, the Open Data trends, which are addressed by Trento’s project, will be the next step to be incorporated into Be Memories, as a system to recommend and personalize the user experience. At the same way, the research of Smart Wine Route Ribera del Duero presents a strong idea of smart routes, but the need to download an application to experience the route could be a problem for users, as the analysis of surveys shows. For that reason, the use of progressive Web-Apps could be a good solution for this problem, such as that which Be Memories proposes. 6. Conclusions and Next Steps The pillars of sustainability (economic, environmental, and sociocultural) are the focus of the new strategies of cities. The importance of the term influences the development of smart cities and smart tourism destinations because both are based on the idea of building strategies with sustainable and smart approaches to improve the city, using the available resources and opportunities. During the research on the main fields, it can be observed that there is a growing need for new ICT solutions for smart tourism destinations because the new digital visitors use the new technologies to plan and enjoy travels and visits. According to a previous project and research on technological tools for tourism, several findings have been highlighted to develop the first artifact of the project: The use of wearables and audio-guides supposes a problem for the visitors as external devices. It is advisable to develop tools to use with the user’s smartphone, as the main device for visitor interaction; Big Data allows the user experience to be personalized, such as the case of TreSight [ 7 ]; The creation of smart routes is a good way to offer cultural POIs, such as the case of the Smart Wine Route [ 57 ]; The smartphone-oriented solutions should be of interest to the tourism business, tourist agents, and local managers because the smartphone is the best channel through which to engage visitors. For that reason, this research presents an artifact that uses the opportunities of ICTs to provide a sustainable and smart solution for smart tourism destinations. The tool is composed of a device called a Smart Spot [ 8 ], which transforms the POIs of a city into Smart POIs. These smart areas allow the user’s to connect through the smartphone, receiving information about the POI without the need to download a native application. The Smart POIs interact with the users through Wi-Fi (captive portal) and Bluetooth and GPS (Physical Web). To test the artifact in a real environment, the research has adapted the solution to Ceutí, analyzing the product value. To build the final prototype, the needs and interests of Ceutí have been studied. The results of the research are: They need to promote the municipality between the region and country to be interesting for the new digital tourism/visitors through new approaches, tools, and activities; The residents have an important role in the town, so the project worked with the different communities of the town to enhance the image of the local culture for the residents and external visitors. For that reason, the Ceutí culture has to be digitized, adapting it to the new younger visitors as part of the final prototype; The main profile of the Ceutí culture and tourist offer is the visitor who spends a day (Sunday), goes sightseeing, and enjoys the local gastronomy. As one-day visitors, they usually live near Ceutí (in the Region of Murcia and adjacent cities/towns); The foreigners who visit Ceutí represent a small group and they usually go to the caravan park of the municipality. In addition, the second foreign source of visitors are emigrants who went to other countries years ago and return to visit their family on holidays; The strong tourism seasons in Ceutí are the winter and autumn, but in the summer, the number of visitors increases due to the local festivities being one of the main attractive events for regional people in the interior regional area (without coasts). Furthermore, after the study carried out the design and validated the first artifact of Be Memories, the research also emphasized the opportunities of intangible heritage and communities’ potential, as mentioned in previous town projects, such as SPAHCO [ 65 ] and iBrave [ 64 ]. Moreover, through meetings with the city council and an analysis of the target public, the research defined the following conclusions: Original content, created by the communities of residents, is more attractive for the new digital visitor (Millennials, Z Generation, and #Generation); Intangible heritage has a high value as a cultural offer for cities and towns to build a local brand; Communities of residents have a high interest in participating in and collaborating with their municipality; Most visitors to Ceutí are inhabitants from the Region of Murcia; The main reason for adults visiting Ceutí is sightseeing; The younger visitors are not interested in the local gastronomy; The main tool used by respondents during their visits is the browser on their smartphones (Google Chrome and Safari). Most of them do not download tourism apps. Therefore, according to these results, the first artifact was evolved into a final prototype to test in Ceutí and was named Be Memories. The prototype has been tested in Ceutí with 15 Smart POIs deployed, connected to the local Wi-Fi and lighting of Ceutí’s outdoor museum. They were configured to send, through Wi-Fi, and complementarily by Bluetooth and GPS, a URL of a progressive Web-App that contains short video-interviews, where the residents tell stories about the cultural POIs of the town. These videos were seed content to test Be Memories and to motivate new participation. At the same time, a dissemination campaign of Be Memories was conducted through a Facebook page and posters/flyers distributed between local commerce and walls. The analysis of the trial results was based on the data obtained of the main Smart POI located in the city council square during the local festivities (from 6 to 19 August). The results showed that the solution has great potential because user participation was high. More than 400 users accessed the Be Memories Web-App and they saw the video-interviews, achieving 30 users per day. In addition to this, other national cities, such as Mula and Cartagena, and at the international level, such as Bristol, have shown interest in deploying Be Memories. At the same time, the tool received the European Cultural Heritage Year label by the European Commission as a solution that enhances the intangible heritage of cities. Thereby, Be Memories achieved the objective proposed in this work: to build a scalable innovative communication channel that provides agile experiences and disseminates the culture of a city through the communities’ participation (sustainable cycle of content). Through Be Memories, Ceutí is growing as a smart tourism destination and its tourist offer is appearing in different regional and national media and events, promoting the town from the power of intangible heritage and new technologies. The number of visitants who ask for information in the tourism office has augmented due to the Be Memories deployment. This tool has helped the local guides (residents as “museum friends” and professionals) to show the different POIs among the visitants, providing a new innovative method which empowers the value of the town. The co-creation aspect of the tool has improved the communication between the different ideological communities. In addition, the Be Memories project supposes a development based on the sustainability of tourism. For that reason, it has increased the sociocultural value of the town through the community’s cooperation and dissemination of the cultural value between visitors and residents. Furthermore, the project also covers the other two pillars of sustainability. The economic sector, as a more complex line of study, is difficult to improve in a short period, but Be Memories has augmented the number of visitors who search for activities and POIs in Ceutí. Lastly, according to the environmental aspect of sustainable smart tourism destinations, the deployment of digital tools reduces the use of natural resources with the help of ICTs. In addition, the infrastructure of Smart Spots, as IoT devices, presents infrastructure to measure and control environmental parameters, such as the air quality, particle matter, and noise, reducing the cost and time required to control them [ 8 ]. The next steps of Be Memories are promising. As a technological tool, the HyRA algorithm [ 59 , 60 ] will be included in the tool to personalize new routes for the users. In addition, Open Data about the city and environment will improve the recommendations through artificial intelligence. Regarding the user experience, Be Memories will be tested with the Bristol residents and visitors through the ICT Flame. The project will analyze the user experience to understand the strengths and weaknesses of Be Memories in new areas. Lastly, with the partners of the Walk a Story project, Be Memories will develop a sustainable methodology to obtain new resident stories through healthy local activities. Acknowledgments A.G.-O. is grateful to UCAM, the institution where she is studying for her doctoral degree, within the industrial doctorate programme. J.A.-U. was supported by a CONACYT studentship during the development of this research. All authors also thank HOP Ubiquitous, SmartSDK project, Ceutí City Council, Synchronicity Large Scale Pilot Project (732240), and Tecnologico de Monterrey for the support in carrying out this research project (the SmartSDK project is co-funded by the EU’s Horizon2020 programme under agreement number 723174-c 2016 EC and by CONACYT agreement 737373), Geo-Trust: Geo-aware security protocol for enabling cross-border trustable operations and data exchange in a global digital economy of the HASLER Foundation ( https://haslerstiftung.ch/en/ ) and Isabel Serna and Antonio Campillo for the support offered to conduct the research on Ceutí, as well as Yair Barrera for the support of the revision of the language in some parts of the manuscript. We really appreciate the participation, collaboration, and review of the people involved in this research and development work. Conflicts of Interest The authors declare no conflicts of interest. 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Available online: https://www.ibraveproject.eu/files/manual-final.pdf (accessed on 2 January 2019). SPAHCO Project. “#Project,” 2016. Available online: http://www.spahco.eu/#project (accessed on 25 November 2018). Han, F.; Yang, Z.; Shi, H.; Liu, Q.; Wall, G. How to promote sustainable relationships between heritage 616 conservation and community, based on a survey. Sustainability 2016 , 8 , 886. [ Google Scholar ] [ CrossRef ] Preuss, U. Sustainable Digitalization of Cultural Heritage—Report on Initiatives and Projects in 618 Brandenburg, Germany. Sustainability 2016 , 8 , 891. [ Google Scholar ] [ CrossRef ] Figure 1. The main pillars of a smart city [ 25 ]. Figure 1. The main pillars of a smart city [ 25 ]. Figure 2. Smart Spot. Figure 2. Smart Spot. Figure 3. Smart Spot functions. Figure 3. Smart Spot functions. Figure 4. Smart point of interactions (POIs) for Be Memories. Figure 4. Smart point of interactions (POIs) for Be Memories. Figure 5. Smart Point of Interaction (Smart POI) deployed in Ceutí. Figure 5. Smart Point of Interaction (Smart POI) deployed in Ceutí. Figure 6. Progressive Web-App design. Figure 6. Progressive Web-App design. Figure 7. Example of a smart point of interactions (POIs) cartouche in Ceutí. Figure 7. Example of a smart point of interactions (POIs) cartouche in Ceutí. Figure 8. Banners for Social Networks about the project Figure 8. Banners for Social Networks about the project Figure 9. Facebook post with impact. Figure 9. Facebook post with impact. Figure 10. Visits of the progressive Web-App during the test (own elaboration based on the results of Google Analytics). Figure 10. Visits of the progressive Web-App during the test (own elaboration based on the results of Google Analytics). Figure 11. Visits of the progressive Web-App after the test (own elaboration based on the results of Google Analytics). Figure 11. Visits of the progressive Web-App after the test (own elaboration based on the results of Google Analytics). Figure 12. Residence of the users during the trial (own elaboration based on the Google Analytics data). Figure 12. Residence of the users during the trial (own elaboration based on the Google Analytics data). Table 1. Clusters of age groups for residents of Spain. Table 1. Clusters of age groups for residents of Spain. Age Range Percentage Number of Users 18–30 24.5% 41 31–50 40% 71 >50 35.5% 61 Total 100% 173 Gomez-Oliva A, Alvarado-Uribe J, Parra-Meroño MC, Jara AJ. Transforming Communication Channels to the Co-Creation and Diffusion of Intangible Heritage in Smart Tourism Destination: Creation and Testing in Ceutí (Spain). Sustainability. 2019; 11(14):3848. https://doi.org/10.3390/su11143848 Chicago/Turabian Style Gomez-Oliva, Andrea, Joanna Alvarado-Uribe, Maria Concepcion Parra-Meroño, and Antonio J. Jara. 2019. "Transforming Communication Channels to the Co-Creation and Diffusion of Intangible Heritage in Smart Tourism Destination: Creation and Testing in Ceutí (Spain)" Sustainability11, no. 14: 3848. https://doi.org/10.3390/su11143848 Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here . Gomez-Oliva A, Alvarado-Uribe J, Parra-Meroño MC, Jara AJ. Transforming Communication Channels to the Co-Creation and Diffusion of Intangible Heritage in Smart Tourism Destination: Creation and Testing in Ceutí (Spain). Sustainability. 2019; 11(14):3848. https://doi.org/10.3390/su11143848
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Infectious Diseases Associated with Hydrometeorological Hazards in Europe | Encyclopedia MDPI Encyclopedia is a user-generated content hub aiming to provide a comprehensive record for scientific developments. All content free to post, read, share and reuse. Infectious Diseases Associated with Hydrometeorological Hazards in Europe History Subjects: Public, Environmental & Occupational Health Contributor: Maria Mavrouli , Spyridon Mavroulis , Efthymios Lekkas , Athanassios Tsakris Hydrometeorological hazards comprise a wide range of events, mainly floods, storms, droughts, and temperature extremes. Floods account for the majority of the related disasters in both developed and developing countries. Flooding alters the natural balance of the environment and frequently establishes a favorable habitat for pathogens and vectors to thrive. Diseases caused by pathogens that require vehicle transmission from host to host (waterborne) or a host/vector as part of their life cycle (vector-borne) are those most likely to be affected by flooding. infectious disease floods waterborne disease rodent-borne disease vector-borne disease outbreak 1. Introduction Hydrometeorological hazards comprise a wide range of events, mainly floods, storms, droughts, and temperature extremes along with their cascading effects. Despite their atmospheric, hydrological, or oceanographic origin, they can have considerable impact to hazards belonging to other categories, such as biological health hazards (e.g., infectious disease outbreaks and epidemics). Hydrometeorological hazards are characterized by high potential to adversely affect the structural environment including buildings and infrastructures, but also the public health in several ways. Based on the International Disaster Database EM-DAT compiled by the Center for research on the Epidemiology of Disasters (CRED), one of the foremost international databases of such events, floods, and storms holds the highest number of occurrences during the last 30 years (1990–2020) [ 1 ]. As regards 2020, floods accounted for 51.67% of all incidents (ranking first), 40.92% of all fatalities (ranking second after extreme temperatures), 33.71% of the population affected (ranking second after storms), and 29.95% of economic losses in billion USD (ranking second after storms) by all disasters caused by natural hazards worldwide [ 2 ]. Taking into consideration the aforementioned numbers and percentages, it is obvious that floods account for the majority of the related disasters in both developed and developing countries. Various definitions of floods have been provided from several sources [3,4,5,6]. However, their common point is the temporary partial or complete water inundation of normally dry land resulting from various processes and leading to loss of human life, dramatic effects on the natural environment, and considerable damage to the built environment. Regardless of classifications, floods have a wide range of health consequences that can be characterized in terms of time [7]. The immediate health effects of floods include drowning, injury, gastroenteritis outbreaks, and skin and respiratory infections, while the medium-term ones comprise of infected wounds, injury complications, poisoning, starvation and communicable diseases [8]. In the long-term, chronic disease, disability, poor mental health, and poverty-related diseases including malnutrition are usually recorded [8]. Infectious disease spread in populations is a consequence of the interaction and connection between the three components of the Epidemiologic Triangle: an external agent, a susceptible host, and an environment in which the agent and the host are brought together [9]. A vector that transfers the pathogen from one host to another without causing the disease itself could be involved in the infectious disease [10]. However, the effects of each triad component may vary substantially for different settings. Flooding alters the natural balance of the environment and frequently establishes a favorable habitat (breeding ground) for pathogens and vectors to thrive. Diseases caused by pathogens that require vehicle transmission from host to host (waterborne) or a host/vector as part of their life cycle (vector-borne) are those most likely to be affected by flooding [7,11,12]. Since early 2020, amid the evolving COVID-19 pandemic and the ongoing climate crisis, which increase the frequency and magnitude of extreme weather events, floods of various magnitudes have been generated in many countries worldwide (e.g., [1,13,14,15,16,17]) including Europe. Among the most notable recent destructive events are the July 2021 floods that occurred in and affected several Central Europe countries. Excessive rainfall along with saturated soils caused rivers to overflow their banks, resulting in extreme floods and devastation. Several urban and rural residential areas were inundated. Flooding led to significant damage to buildings and business property or equipment as well as destruction of crops and farms. Large parts of the road and railway network were submerged and bridges collapsed resulting in traffic and communication disruption. The water supply network was also compromised, thus negatively affecting the safety of drinking water and causing supply interruption and water shortage in the affected residential areas. The electric power supply network suffered damage to its structural elements, leaving hundreds of thousands households without electricity, telephone, and internet, and making the 112 Emergency Communications Service inaccessible. During intense flooding, the capacity of sewerage was exceeded, thus the sewer systems overflowed and inundated streets and buildings with raw sewage. More than 243 fatalities were reported (196 in Germany, 43 in Belgium, 2 in Romania, 1 in Italy, and 1 in Austria) and attributed to the aforementioned adverse effects of inundation and flooding. About 1000 residents were stranded in inaccessible areas for days, while hundreds of thousands had to evacuate flood-affected areas. 2. Waterborne Diseases Waterborne diseases are mainly caused by drinking water contaminated with pathogenic microorganisms (bacteria, viruses and parasites) originating from human or animal feces. Flood-related waterborne diseases have been reported in the United Kingdom, the Republic of Ireland, Norway, Sweden, Finland, Denmark, the Netherlands, Austria, Hungary, France, Spain, Germany, Italy, and Greece. A case-crossover study analyzed rainfall-induced drinking water-related outbreaks reported in England and Wales for the period extending from 1910 to 1999 following both low and excessive rainfall [ 19 ]. Various parasites and bacteria such as Giardia , Cryptosporidium , Escherichia coli , Salmonella typhi , Salmonella paratyphi , Campylobacter , and Streptobacillus moniliformis were among the pathogens implicated in 89 outbreaks studied [ 19 ]. Street flooding and/or flooding of combined sewerage systems contribute to the mixing of rainwater with sewage, significantly contaminating flood waters with fecal matter. As a result, pathogens such as noroviruses, enteroviruses, and Campylobacter , which are all known causative agents of gastrointestinal and respiratory diseases, may be detected in floodwater [ 20 , 21 ]. Diarrhea and vomiting are the most commonly reported symptoms of waterborne disease; however, other infections of skin, ear, respiratory tract, or eye are also identified [ 22 ]. Flooding of households in Lewes, Southern England was strongly associated with earache in patients of all ages, while weaker associations were observed for skin rash, respiratory illness, and all categories of injury [ 23 ]. However, an increase in the risk of gastroenteritis occurrence was significantly associated with depth of flooding [ 23 ]. Stomach upsets and recurring flu-like symptoms such as sore throat, cough and general sickness were attributed to the floods and were reported by people whose homes had been affected in Cumbria, northwest England [ 24 ]. Direct hand contact with floodwater was found to be significantly associated with increased incidence of gastrointestinal, respiratory, and/or dermatological complaints in the Netherlands and Germany [21,25,26,27]. In parallel, participation in post-flooding cleanup tasks was associated with the development of influenza-like symptoms [27] or both acute gastroenteritis (AGE) and acute respiratory infection (ARI) emergence [21]. Having walked or cycled through floodwater was also related to the development of influenza-like symptoms [27] or AGE occurrence [21]. Waterborne diseases can also be spread while bathing, washing, or eating food exposed to contaminated water. Harder-Lauridsen et al. [ 28 ] demonstrated that after an extreme rainfall, physical contact with and unintentional intake of sewage-polluted recreational water can increase the risk of severe gastrointestinal illness. A triathlon sports competition took place in Copenhagen, Denmark shortly after an extreme rainfall in August 2010. The athletes who participated in this event swam in water with high post-flooding bacterial contamination and were found to develop gastrointestinal illness five times more often than athletes who had swum the same distance in unpolluted water [ 28 ]. Intense precipitation can transfer pathogenic microorganisms of human or animal fecal origin to the aquatic environment through discharge of raw and treated sewage and run-off from the soil, increasing the microbial load on surface water. A gastroenteritis outbreak occurred in Elassona city, central Greece in March 2012 and was characterized as waterborne because the region had suffered heavy rainfall the week before the gastroenteritis episodes began [ 29 ]. Heavy rainfall at the beginning of the month could have contributed to water runoff from fields into rivers, contaminating the water supply with human or animal waste from neighboring dwellings and breeding farms and resulting in increased water turbidity [ 29 ]. Tornevi et al. [ 30 ] analyzed the relationship between daily fluctuations in gastrointestinal symptoms in Gothenburg population and the amount of rainfall upstream of the drinking water utility exposed to upstream run-offs from agricultural areas and occasionally from overflowing combined sewer systems. It was found that heavy rainfall was associated with an increase in nurse advice calls for gastrointestinal illness on the same day and around 5–6 days later [ 30 ]. A matched case-control study in four Nordic countries (Denmark, Finland, Norway, and Sweden) over a 21-year period (1992–2012) was conducted to investigate the association between heavy precipitation events and waterborne outbreaks [ 31 ]. Heavy precipitation was found to be positively associated with the occurrence of waterborne outbreaks, especially in spring and summer seasons. It was also noted that groundwater sources as well as single household supplies were particularly vulnerable to extreme weather events [ 31 ]. Flooding favored the emergence and incidence increase of waterborne diseases in European countries, as shown inTable S1. Increased incidence or outbreaks of waterborne diseases caused by parasites ( Cryptosporidiumand Giardia), viruses (norovirus and hepatitis A virus), and bacteria ( Campylobacter, Escherichia coli, Salmonella, Shigella) were detected (Table S1) and are thoroughly described below. 2.1. Parasites: Cryptosporidium Heavy rainfall and flooding contributed to an increased risk of Cryptosporidiuminfection in European countries. Confirmed cryptosporidiosis cases were mainly reported in the United Kingdom (UK) [32,33,34,35,36,37] and the Republic of Ireland [38,39,40,41], while only one large cryptosporidiosis outbreak was detected in Germany [42]. Cryptosporidium infection may be asymptomatic or develop into diarrhea that spontaneously resolves over a couple of weeks in healthy individuals. On the contrary, immunocompromised patients may experience frequent, life-threatening watery diarrhea that is difficult to treat with currently available medications. Oocysts ingestion, direct contact with infected people or animals, and contaminated water and food are all methods of Cryptosporidium fecal-oral transmission. Oocysts of this intestinal parasite can survive in moist soil, water or even harsh environmental conditions for long periods of time. Cryptosporidium can also resist conventional disinfection treatments such as chlorination, which increases the risk of water distribution systems contamination [ 43 ]. Cryptosporidiosis outbreaks were usually attributed to consumption of unboiled tap water from a specific source [33,36]. Heavy rainfall in the reservoir catchment area supplying raw water to the treatment works contributed to the introduction of Cryptosporidiumoocysts from the environment into the raw water supply [34,44,45]. The origin of the outbreak was confirmed by the detection of Cryptosporidiumoocysts in samples from water treatment plants and domestic taps [36]. The spatial distribution of the affected residences in Ayrshire (UK) revealed that most of them shared the same public drinking water supply [32]. A strong statistical correlation has been demonstrated between the reported cryptosporidiosis cases and the residence in an area supplied from two groundwater sources, one of which was found to drain surface water directly from a field carrying cattle feces [35]. In the Republic of Ireland, two cryptosporidiosis outbreaks were reported in April–May 2002 and February–March 2007, and all of the cases were found in regions that used lakes surrounded by farmland as the water source [38,39]. The entry of animal waste into the lake could have been facilitated by heavy rainfall [38,39]. Cryptosporidiumoocysts were found in the lake’s raw and treated water, as well as in the surrounding environment [38]. A Cryptosporidiumparvum outbreak was recorded among 35 people (27 pupils and 8 teachers), who took part in a school trip to an outdoor adventure farm in South West England, from May 22 to 26 May 2006. The two most plausible routes of transmission were drinking water from a private well or coming into contact with feces-contaminated surface water following heavy rainfall [37]. Boudou et al. [ 41 ] found that the increase in cryptosporidiosis cases across the Republic of Ireland from November 2015 to January 2016 was associated with hydrometeorological variables such as cumulative antecedent rainfall, surface water run-off, and groundwater level [ 41 ]. Apart from heavy local rainfall, other environmental factors such as river overflow, shutdown of treatment plants due to mechanical problems, increase in water turbidity, and damage to sewage systems could all contribute to an increased risk of cryptosporidiosis [ 33 , 42 ]. 2.2. Viruses: Norovirus, Hepatitis A Virus Human noroviruses (NoVs) represent the leading cause of gastroenteritis outbreaks worldwide, affecting all age groups and being mainly transmitted via an oral-fecal route [46]. NoV is highly contagious due to its low infectious dose and persistence of virus in fecal excretion even weeks after patient recovery [47,48]. NoVs were identified as the main causative agents of the waterborne gastroenteritis epidemics reported in Finland [49,50], France [51,52], Italy [47,51], Greece [53,54], Austria [55], Sweden [56], the Netherlands [57], and Hungary [58]. Acute gastrointestinal disease was detected and related to the microbiological contamination of water supplies following heavy rainfall and flooding events [58]. Floods and surface runoff due to snow melting in spring contributed to groundwater contamination with fecal microbes in Finland and Sweden [49,50,56]. Outbreaks were attributed to drinking non-disinfected ground water [49,50]. According to data from epidemiological and molecular studies, residents living in households connected to the public water network were at a higher risk of developing NoV gastroenteritis [47,56]. In Sicily (Italy), sewage overflowing from septic tanks and latrines as a result of the rainfall caused the contamination with human feces of the wells and springs supplying the public water network [47]. The majority of individuals with symptoms of acute gastroenteritis were drinking water from a single well in Xanthi town, North Eastern Greece [53]. Another large outbreak of non-bacterial gastroenteritis caused by NoVs was reported after heavy rainfall in the same Greek region almost 2 years after the gastroenteritis outbreak described by Papadopoulos et al. [54]. Direct exposure to floodwater contaminated with raw sewage caused the occurrence of a NoV outbreak among American tourists and firefighters who helped pump floodwater out of a hotel inundated due to an extremely heavy rainfall in Salzburg, Austria [55]. Overflow of sewage treatment plants due to heavy rainfall led to the fecal contamination of lakes and rivers in France [ 51 , 52 ]. Consumption of oysters harvested from the Etang de Thau, the second largest lagoon in France, was responsible for NoV gastroenteritis outbreaks not only in France but also in Italy [ 51 ]. Oyster consumption following floods near a lagoon with shellfish farming activity was the most important contributing factor in the occurrence of another foodborne viral gastroenteritis outbreak in France [ 59 ]. Water contamination by several NoV strains caused an acute gastroenteritis outbreak among swimmers following participation in the Amsterdam City Swim event. Two days before this event, an unusually heavy rainfall caused severe flooding and overflow of the sewage system into the city canals [57]. Hepatitis A virus (HAV) is transmitted through contaminated food and water and thrives in poor sanitary conditions. Increased incidence of HAV infection after flooding was observed in Spain and Italy [60,61]. Apart from extreme rainfall, other climate factors such as weekly day of rainfall and snow were also associated with a rise in the number of Hepatitis A cases in Spain [60]. 2.3. Bacteria: Escherichia coli, Campylobacter jejuni, Shigella sonnei Escherichia coliwere the most commonly isolated bacteria followed by Campylobacter jejuniand Shigella sonnei[19,62,63,64,65,66,67,68]. Shiga toxin or verotoxin-producing Escherichia coli (STEC/VTEC) have been related to foodborne and waterborne outbreaks. STEC/VTEC causes a wide range of human gastrointestinal disorders, from watery and bloody diarrhea to hemorrhagic colitis. Infection can also result in the life-threatening hemolytic uremic syndrome (HUS), which is considered to be caused by Shiga toxins (Stx) [ 69 , 70 ]. It is demonstrated that heavy rainfall and high temperature are statistically significantly associated with the occurrence of waterborne VTEC outbreaks [ 71 ]. Although cattle are considered to be the primary reservoir of STEC/VTEC strains, sheep are also important carriers of these pathogens [72]. In eastern Scotland, heavy rainfall caused localized flooding on an agricultural showground that was generally used for sheep grazing and hosted a scout camp [62]. E. coliO157 infection was detected in 20 campers, and E. coliO157 was transmitted from the environment to cases via contaminated hands [62]. In August 2004, seven cases of E. coliO157 infection were identified in children on holiday in Cornwall, southwest England [63]. The source of infection was a contaminated freshwater stream flowing across a seaside beach. Because of heavy rainfall in the days preceding the outbreak, feces from cattle found grazing upstream and potentially contaminated by E. coliO157 infiltrated the stream, thereby causing the outbreak [63]. Extremely heavy summer rainfall in the Republic of Ireland resulted in high water table levels, intense run-off, and widespread flooding that significantly increased the potential for microbiological contamination of drinking water [64]. During periods of heavy rainfall, areas of stagnogley soils with mixed animal grazing may be more susceptible to Campylobacterexposure and spread, increasing the likelihood of human cases of the disease [73]. In Finland, two outbreaks of Campylobacter jejunienteritis were recorded in 2000 and 2001 and were associated to fecal contamination of drinking water sources by surface water runoff after rain [65]. Following an exceptionally heavy rainfall in June 2009, an outbreak of Campylobactergastroenteritis (163 cases) occurred in the Danish town of Tune [66]. Drinking tap water was the only exposure identified as being related with gastroenteritis, with a clear dose–response association between the amount of tap water drunk and the risk of gastroenteritis. Drinking-water contamination was caused by congestion of the combined rainwater drainage and sewage system [66]. Residents of an economically deprived housing estate built on a steep hill and surrounded by agricultural pastures developed C. jejunigastroenteritis after severe rainfall on the surrounding hills in the South Wales Valleys (UK) [67]. An outbreak of acute Shigella sonneigastroenteritis occurred in the town of Santa Maria de Palautordera (Spain), following heavy rainfall that resulted in mud and organic material entering the treatment plants, which were not designed to treat highly turbid water [68]. 3. Rodent-Borne Diseases Flood-related rodent-borne diseases have been reported in Finland, Denmark, France, Belgium, Germany, the Czech Republic, Italy, Austria, Croatia, Bosnia and Herzegovina, Montenegro, Serbia, Republic of North Macedonia, and Bulgaria. 3.1. Leptospira Rodent-borne diseases may also increase during heavy rainfall and flooding due to altered patterns of contact among humans, pathogens, and rodents [74]. Numerous outbreaks of leptospirosis, a spirochetal zoonosis, have been associated with extreme weather events and flooding in a wide-range of countries around the world [75,76,77,78,79,80]. Humans can acquire infection through direct contact with infected animal hosts such as rodents, domestic pets, and livestock, or through exposure to surface water or soil contaminated by infected animal urine [81,82]. During floods, the increase in leptospirosis transmission is mainly attributed to closer contact between animal hosts and humans, direct contamination of floodwaters, and damage to water and sanitation networks [83]. There have been reports of flood events associated with sporadic and outbreak cases of Leptospirosis from a wide range of countries in Europe such as Bulgaria [84], the Czech Republic [85], Italy [86,87], Germany [88,89], Austria [90], France [91], and Denmark [92,93,94] (Table S2). Water-based outdoor sports and recreational activities are becoming increasingly popular. Triathletes, canoers and kayakers, rowers, and wild swimmers have all been known to have acquired leptospirosis infection when participating in outdoor sports and activities [95]. Higher recreational activity, ideal temperature, and rainfall favor Leptospirasurvival in the environment and could plausibly explain the peaks in leptospirosis incidence during the summer months in Bulgaria [84]. Recreational exposure to water, particularly in relation to water sports, is thought to be a key risk factor for leptospirosis occurrence among triathlon athletes in Germany and Austria [89,90]. Heavy rainfall preceding these endurance multisport races is likely to have contributed to the contamination of the man-made lake or the river with Leptospira[89,90]. Leptospirosis has traditionally been thought of as an occupational disease, with humans getting infected predominantly through work exposure. Sewage maintenance, animal husbandry, agriculture, mining, and military exercises are activities that increase the risk of contracting leptospirosis [96]. A leptospirosis outbreak was also detected among seasonal harvesters from Eastern Europe, working in the largest field of a strawberry-producing farm in North Rhine-Westphalia, Germany in July 2007 [88]. The warm winter of 2006–2007 enhanced rodent population growth and expansion. The disease risk increased with each day spent working in the rain and the most likely source of the outbreak was direct contact of hand lesions with contaminated water or soil and infected rodents [88]. Work-related cases accounted for nearly half of all leptospirosis cases reported over a 32-year period (1980–2012) in Denmark [92]. Fish farmers, farmers, and sewage workers were the most frequently notified professions [92]. Improper and poor waste management and garbage accumulation attract rat infestation that is related to leptospirosis infection among urban dwellers [96,97]. The emergence of sporadic laboratory-confirmed human cases of leptospirosis in the city of Marseille, France was associated with heavy rainfall periods accompanied by flooding and garbage collection strikes [91]. Garbage left uncollected contributed to expansion of the urban rat population. Residents of Marseille may have been exposed to Leptospirathrough contact with contaminated surface water or rat urine near garbage deposits [91]. High prevalence of pathogenic Leptospiraspp. in rodents, street flooding, and garbage accumulation could also explain the occurrence of two human leptospirosis cases in the city of Palermo, Italy [87]. Flooding was found to have a significant association with increased incidence of human leptospirosis. When compared to non-flooded areas, widespread flooding may contribute to an increased risk of leptospirosis or create conditions conducive to a leptospirosis outbreak [82]. According to Zitek and Benes [85], the rates of serologically confirmed leptospirosis cases in the Czech Republic were three times higher than usual after the massive floods of 1997 and 2002. Two thirds of these cases came from flooded areas, while half of them were directly exposed to residual water and flood mud in cellars [85]. In August 2002, an excessive rainfall produced a devastating flooding in a suburban area of Vicenza in the northeastern part of Italy. Since only a small percentage of people were wearing personal protective equipment (e.g., gloves and boots) during post-flooding cleanup activities, inundation appeared to be the only demonstrable risk factor for the occurrence of serologically confirmed Leptospirainfection [86]. Following the 2011 flash floods that left large areas of Copenhagen inundated, a cluster of five leptospirosis cases was detected in Copenhagen [93,94]. 3.2. Hantavirus Hantaviruses are carried by different types of rodents, and humans get infected by inhaling aerosolized urine, saliva, or droppings of infected rodent hosts [98]. In Asia and Europe, Old World hantaviruses including Puumala virus, Seoul virus, Dobrava Belgrade virus, and hantaan virus infect the highly differentiated endothelial cells of the kidney, causing acute renal failure with tubular and glomerular involvement, also known as hemorrhagic fever with renal syndrome (HFRS) [98,99]. Globally, 150,000–200,000 cases of hantavirus infection are reported annually, whereas more than 10,000 HFRS cases are diagnosed each year in Europe and their number is growing [98,99]. Heavy rainfall brought on by a cyclone contributed to increases in severe flooding events in the Balkans in mid-May 2014 [ 100 ]. HFRS incidence was significantly increased in 2014 in five flood-affected Western Balkan (WB) countries including Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia, and Serbia [ 101 ]. A significantly strong negative correlation was found between the monthly incidence of HFRS and the number of months after the May floods for the entire WB area [ 101 ]. Higher mean annual precipitations are assumed to reflect higher air humidity and should increase the probability of HFRS occurrence. Zeimes et al. [ 102 ] showed a positive association between the risk of HFRS and the annual precipitation in France, Belgium, and Finland, which could be attributed to the good survival of the virus not only within the host but also in a wet environment or to the migration of the rodent population into the human environment in search of food supplies, especially when climatic conditions deteriorate [ 102 ]. 4. Vector-Borne Diseases Vector-borne diseases are infections transmitted by the bite of infected arthropod species, such as mosquitoes, ticks, triatomine bugs, sandflies, and blackflies. Arthropod vectors are especially susceptible to climatic factors, thus weather influences their survival and reproduction rates. The geographical distribution of vector-borne diseases is determined by the geographical distribution of both vertebrate host and vector [ 83 ]. Consequently, the risk of vector-borne diseases could increase if vector-borne pathogens are present along with their competent vectors in the flooded areas. Precipitation changes are known to affect the reproduction; development; and behavior of arthropod vectors, their pathogens, and non-human vertebrate reservoirs [ 55 ]. Floods may indirectly increase the incidence of vector-borne diseases through the expansion in the number and range of vector habitats. Flood waters initially overwhelm breeding habitats and temporarily wash out mosquito populations. However, receding water could provide ideal mosquito breeding grounds and, therefore, enhance the potential for exposure of the flood-affected population and emergency responders to mosquito-borne pathogens causing diseases such as West Nile fever, malaria, and dengue fever [ 103 ]. In a 6-year investigation (2011–2016), three zoonotic arboviruses comprising of Usutu, Sindbis, and Batai viruses were found circulating in the German mosquito fauna. According to Scheuch et al., the Elbe flood could explain the relatively high number of pathogen findings in 2013, as flood events favor the mass development of high numbers of mosquitoes, which in turn facilitate enhanced virus circulation [104]. Outbreaks of mosquito-borne diseases associated with heavy rainfall or floods have mainly been observed in tropical areas [103,105]. In Europe, flooding events following extreme rainfall have been mainly linked to the emergence and incidence increase of West Nile virus (WNV), Chikungunya virus (CHIKV), and Tahyna virus (TAHV) infections in Romania, the Czech Republic, Greece, Italy, and France [106,107,108,109,110,111,112]. In the summer of 1996, an unprecedented epidemic of WNV meningoencephalitis (393 hospitalized cases and 17 deaths) occurred in southeastern Romania. Han et al. [ 106 ] found WNV infection to be associated with specific residence characteristics, such as presence of mosquitoes indoors and flooded basements of apartment buildings. It is worth mentioning that the basements were inundated with sewage-contaminated water from poorly maintained plumbing, resulting in a high-organic environment conducive to mosquito breeding [ 106 ]. After heavy rainfall in Moravia (Czech Republic), the devastating flooding of the Morava River occurred in July 1997. In the flood-affected area, the abrupt increase of mosquitoes infected with arboviruses such as WNV and TAHV contributed to the detection of confirmed and probable cases of WNV infection in that area [107]. Climatic parameters such as high temperature and increased precipitation might have a lagged direct effect on the incidence of WNV infection in Northern Italy [112]. In August 2002, a massive flood struck Prague, the capital of the Czech Republic, as well as extensive rural areas along the Vltava and Labe Rivers. An elevated incidence of “Valtice fever” caused by TAHV was found among inhabitants of the flood-affected areas in Central Bohemia, while WNV, Sindbis virus, and Batai virus infections were not reported. The prevalence of antibodies against TAHV increased with decreasing distance from areas with high mosquito abundance and floodplain forests, the primary mosquito breeding habitats [ 108 , 109 ]. Roiz et al. carried out surveillance of the Asian tiger mosquito Aedes albopictus, a well-known CHIKV vector in Montpellier (France) and found that extreme rainfall that inundated the city in 2014 clearly contributed to an increase of mosquito population growth and abundance, as well as to the prolongation of the autochthonous CHIKV transmission period [111]. An outbreak of WNV infection occurred in the Central Macedonia, (northern Greece) in the summer of 2010. A total of 197 patients with neuroinvasive disease were reported, of whom 33 (17%) died [110]. Danis et al. (2011) noticed that the 2010 WNV outbreak was preceded by unusual precipitation. According to meteorological data for the area, 2010 was warmer than previous years and unusually wet [113]. This entry is adapted from10.3390/ijerph191610206
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PRIME PubMed | scleredema journal articles from PubMed PubMed Journal articles for scleredema were found in PRIME PubMed. Download Prime PubMed App to iPhone, iPad, or Android (scleredema) 544 results Post-streptococcal scleredema an unusual rare mimicker of scleroderma: a case report. [Case Reports] Reumatismo . 2023 May 08; 75(1) Gorial FI, Awadh NI, … Hasan HJ R cleredema of Buschke is a rare pathological disorder of connective tissue, which is characterized by a woody, diffuse induration of the skin, most often in the upper extremities. We report an extremely rare complication of post-streptococcal infection in a six-year-old male complaining of gradually progressing, painless skin thickening and tightness which was preceded by a one-month history of fe… cleredema of Buschke is a rare pathological disorder of connective tissue, which is characterized by a woody, diffuse induration of the skin, most often in the upper extremities. We report an extremely rare complication of post-streptococcal infection in a six-year-old male complaining of gradually progressing, painless skin thickening and tightness which was preceded by a one-month history of fever, cough, and tonsillitis. By reporting this case, we hope to contribute to the creation of a database for future research aimed at better understanding the incidence, pathophysiology, and management of this extremely rare complication. Efficacy and Satisfaction of Low Doses UVA1 Phototherapy: A Spanish Experience from a Single Centre. [Journal Article] Life (Basel) . 2023 Feb 28; 13(3) Velasco-Amador JP, Linares-Gonzalez L, De la Torre-Gomar FJ ↑48 CONCLUSIONS: We present a review of treatment with UVA1 phototherapy at low doses with good response in a wide variety of dermatological pathologies. Atypical Case of Combined Types I and II Scleredema Mimicking Morphea on Histopathology. [Case Reports] Cureus . 2023 Jan; 15(1):e34077. Alhunaif SA, Alsarheed A, … Almutairi G Scleredema is a rare sclerotic skin disorder that typically develops in conjunction with diabetes, monoclonal gammopathy, or infection and commonly involves the neck, back, trunk, and arms. Scleredema can be categorized into three types according to its cause. The local examination of the lesion is characterized by non-pitting induration that follows a symmetrical spread with sparing of the hands… Scleredema is a rare sclerotic skin disorder that typically develops in conjunction with diabetes, monoclonal gammopathy, or infection and commonly involves the neck, back, trunk, and arms. Scleredema can be categorized into three types according to its cause. The local examination of the lesion is characterized by non-pitting induration that follows a symmetrical spread with sparing of the hands and feet. We present a case of a 19-year-old female patient that presented to the outpatient clinic complaining of facial skin lesions that have been progressive for four years. The skin lesions were found to involve the neck, back, trunk and both arms sparing the hands and there was no systemic involvement of the disease. The patient is non-diabetic but reported frequent attacks of tonsillitis over the past months. Initially, punch biopsy showed no signs of scleredema; however, repeated biopsy at follow-up confirmed the presence of mucin deposits which are suggestive features of scleredema. Due to the similarities with various other diseases, the diagnosis requires clinical and histopathological exclusion which makes the diagnosis quite challenging. It almost always starts in the neck but can present initially in rare cases from the face spreading symmetrically. Close follow-up and continuous monitoring are necessary for systemic organ involvement. Identifying the potential origin of mucin in primary cutaneous mucinoses-A retrospective study and analysis using histopathology and multiplex fluorescence staining. [Journal Article] J Eur Acad Dermatol Venereol . 2023 Feb 21 [Online ahead of print] Steinmann S, Guillet C, … Maul JT JE CONCLUSIONS: Various cell types seem to contribute to mucin production in PCM. Using MFS, we showed that CD8+ T cells seem to be more involved in the production of mucin in FM than in dermal mucinoses, which could indicate that mucin in dermal and follicular epithelial mucinoses have different origins. Publisher Full Text (DOI) Löfgren syndrome associated with scleroedema adultorum of Buschke. [Journal Article] Clin Exp Dermatol . 2023 Jan 20; 48(1):39-40. Gambichler T, Susok L, … Chatzipantazi M CE Novel cutaneous eruptions in the setting of programmed cell death protein 1 inhibitor therapy. [Case Reports] JAAD Case Rep . 2023 Jan; 31:124-127. Mital R, Cartron AM, … Chung CG ↓1 ↑15 Scleredema diabeticorum. [Journal Article] Dermatol Reports . 2022 Nov 21; 14(4):9477. Pereira M, Pinheiro RR, … Bártolo E DR Scleredema of Buschke is a rare connective tissue disease with a poorly understood pathogenesis. Three types of scleredema have been distinguished according to its association with preceding or underlying conditions. Type 1 is usually secondary to a febrile infection, type 2 is mostly associated with paraproteinemia and type 3, usually named scleredema diabeticorum, has a strict association with … Scleredema of Buschke is a rare connective tissue disease with a poorly understood pathogenesis. Three types of scleredema have been distinguished according to its association with preceding or underlying conditions. Type 1 is usually secondary to a febrile infection, type 2 is mostly associated with paraproteinemia and type 3, usually named scleredema diabeticorum, has a strict association with Diabetes mellitus. A diffuse, non-pitting swelling and induration of the skin define this disease. The skin histology is characterized by a normal or slightly thinned epidermis, and the dermis containing a decreased number of elastic fibers and thick large swollen collagen bundles separated by mucopolysaccharide deposits in the deep reticular dermis. In this report we present a 58-year-old man with scleredema diabeticorum controlled with a topical steroid cream and an optimization of glycemic control. We reviewed clinical, histopathological characteristics and the various possible treatments. Recurrent Generalized Scleredema in an Adolescent Girl With Uncontrolled Type 1 Diabetes Mellitus. [Journal Article] Indian Pediatr . 2022 11 15; 59(11):886-887. Verma P, Varshney GA, … Agrawal S ↑5 IP PMC Free PDF StatPearls: Scleredema [BOOK] StatPearls . StatPearls Publishing: Treasure Island (FL) RaboudiAsmaAFaculty of Medicine of TunisLitaiemNoureddineNUniversity of Tunis El Manar BOOK Scleredema of Buschke is a rare pathological condition of connective tissue. Its pathogenesis is poorly understood. First described by Curizo in 1752, the disease was well defined afterward by Buschke in 1902. It belongs to the spectrum of scleroderma-like disorders. Clinically, it is responsible for a fibro-mucinous progressive induration of the skin, involving the neck, shoulders and proximal u… Scleredema of Buschke is a rare pathological condition of connective tissue. Its pathogenesis is poorly understood. First described by Curizo in 1752, the disease was well defined afterward by Buschke in 1902. It belongs to the spectrum of scleroderma-like disorders. Clinically, it is responsible for a fibro-mucinous progressive induration of the skin, involving the neck, shoulders and proximal upper members and eventually the face.[1] It occurs most commonly following an infectious episode. It has also been linked to diabetes mellitus and more rarely to hematological disorders. Histological features include dermal fibrosis with thickened collagen bundles and variable amounts of mucin deposits.[2] Scleredema developing after SARS-CoV-2 infection: a possible novel skin manifestation of coronavirus disease. [Journal Article] Eur J Dermatol . 2022 02 01; 32(1):124-145. Sánchez-Díaz M, Lobato-Cano R, … Arias-Santiago S Scleredema with biopsy-confirmed cardiomyopathy: A case report. [Case Reports] J Scleroderma Relat Disord . 2021 Oct; 6(3):311-315. Nakatsuji M, Ishimaru N, … Kinami S Scleredema is a rare cutaneous mucinosis characterized by diffuse swelling and non-pitting induration. A 63-year-old man reported a 5-year history of skin thickening of the trunk and a 3-week history of dyspnea. Echocardiography revealed diffuse hypokinesis. Skin biopsies obtained from the waist showed thickened dermis with mucin. Myocardial biopsies showed alcian blue-stained tissue between the … Scleredema is a rare cutaneous mucinosis characterized by diffuse swelling and non-pitting induration. A 63-year-old man reported a 5-year history of skin thickening of the trunk and a 3-week history of dyspnea. Echocardiography revealed diffuse hypokinesis. Skin biopsies obtained from the waist showed thickened dermis with mucin. Myocardial biopsies showed alcian blue-stained tissue between the muscle fibers. The patient was referred to a dermatologist for phototherapy. Cardiomyopathy should be considered in patients with scleredema. Scleredema usually has a good prognosis; however, the mortality risk could be high when accompanied by cardiomyopathy. New and emerging conditions of acquired cutaneous mucinoses in adults. [Review] J Eur Acad Dermatol Venereol . 2022 Jul; 36(7):1016-1024. Rongioletti F JE Cutaneous mucinoses are a heterogenous group of conditions, characterized by the deposition of glycosaminoglycans (mucin) in the dermis, follicles, or in the epidermis. Major cutaneous mucinoses include lichen myxedematosus, scleredema, mucinoses associated with thyroid disease, reticular erythematous mucinosis, papulonodular mucinosis associated with connective tissue diseases, and cutaneous foc… Cutaneous mucinoses are a heterogenous group of conditions, characterized by the deposition of glycosaminoglycans (mucin) in the dermis, follicles, or in the epidermis. Major cutaneous mucinoses include lichen myxedematosus, scleredema, mucinoses associated with thyroid disease, reticular erythematous mucinosis, papulonodular mucinosis associated with connective tissue diseases, and cutaneous focal mucinosis. The aim of this review is to provide an update of what has currently been reported in the last 30-year literature about several new or emerging conditions of acquired cutaneous mucinoses in adults. Two new clinico-pathologic entities have been described: (i) Obesity-associated lymphedematous mucinosis and pretibial stasis mucinosis; (OACM) (ii) Nodular mucinosis of the breast (NMB). Two relatively new disease categories encompassing cutaneous mucinoses with a common pathogenetic mechanism have been identified: (i) Cutaneous mucinoses associated with drug exposure including biologic therapy, anti-colony-stimulating factor 1 receptor (CSF1R) and subcutaneous intralesional interferons (toxic dermal mucinoses); (ii) Cutaneous mucinosis following physical agents including mechanical traumas and after knee replacement. Monoclonal Gammopathy-Associated Scleredema Adultorum of Buschke in a Patient with Diabetes Mellitus Successfully Treated with Intravenous Immunoglobulin and Narrow-Band Ultraviolet B Phototherapy: A Case Report. [Journal Article] Ann Dermatol . 2021 Dec; 33(6):586-588. Hong KR, Hong JY, … Kim JE Clinical and Histopathological Features of Scleroderma-like Disorders: An Update. [Review] Medicina (Kaunas) . 2021 Nov 20; 57(11) Foti R, De Pasquale R, … Ramondetta A Scleroderma-like disorders include a set of entities involving cutis, subcutis and, sometimes, even muscular tissue, caused by several pathogenetic mechanisms responsible for different clinical-pathological pictures. The absence of antinuclear antibodies (ANA), Raynaud's phenomenon and capillaroscopic anomalies constitutes an important element of differential diagnosis with systemic sclerosis. Wh… Scleroderma-like disorders include a set of entities involving cutis, subcutis and, sometimes, even muscular tissue, caused by several pathogenetic mechanisms responsible for different clinical-pathological pictures. The absence of antinuclear antibodies (ANA), Raynaud's phenomenon and capillaroscopic anomalies constitutes an important element of differential diagnosis with systemic sclerosis. When scleroderma can be excluded, on the basis of the main body sites, clinical evolution, any associated pathological conditions and specific histological features, it is possible to make a correct diagnosis. Early Physical Linear Growth of Small-for-Gestational-Age Infants Based on Computer Analysis Method. [Journal Article] J Healthc Eng . 2021; 2021:7227928. Ruixiang L, Mingrong Y, … Rongxiu Z This article proposes that machine learning can break through the technical limitations of the linear growth test for the early physique of infants smaller than gestational age and can accurately calculate and predict the consequences of the disease. For testing the linear growth of the early physique of infants smaller than gestational age, the data collection and judgment are carried out accord… This article proposes that machine learning can break through the technical limitations of the linear growth test for the early physique of infants smaller than gestational age and can accurately calculate and predict the consequences of the disease. For testing the linear growth of the early physique of infants smaller than gestational age, the data collection and judgment are carried out according to the computer analysis method. Experimental results show that 47.3% of infants younger than gestational age may have suffocation. The experimental subjects designed in this study are small-for-gestational-age infants who were hospitalized in the neonatal intensive care unit from January 2020 to January 2021. According to the relationship between gestational age and birth weight, the survey subjects were divided into two groups: early group and late group. Male and female small-for-gestational-age infants accounted for 68% and 32%, respectively. Among them, the proportion of early gestational age was the most, with more boys than girls, and sick singleton was more than twins. In the early group, the incidence was 52.1% for neonatal asphyxia, 22.5% for feeding intolerance, 14.8% for intracranial hemorrhage, 6.3% for scleredema, 24.7% for neonatal hyperbilirubinemia, 24.6% for hypoglycemia, 1.1% for apnea, and 3.2% for respiratory distress syndrome. Infants develop differently at different stages of corrected gestational age. The incidence of low body weight (6%) after correction for 3 months was significantly reduced compared with correction for gestational age, and the difference was statistically significant (P < 0.05). The nutrient absorption of infants younger than gestational age can promote physical catch-up growth, physical development, and neurodevelopment. Therefore, the physical growth of infants younger than gestational age requires supplementation that focuses on nutrition. Indurated plaques on the back: distinguishing stiff skin syndrome from scleredema and morphea. [Letter] Int J Dermatol . 2022 10; 61(10):e393-e394. Raef HS, Nassim JS, Fedeles F IJ Scleredema adultorum of Buschke associated with hypothyroidism and liver cirrhosis. [Case Reports] J Postgrad Med . 2021 Jul-Sep; 67(3):174-176. Muralidharan S, Arun K, … Devi B Scleredema adultorum of Buschke is a rare disorder of the connective tissue, involving the skin. Here, we present a 61-year-old male, who is a known case of compensated liver cirrhosis with a past history of being treated for autoimmune thyrotoxicosis, who presented with complaints of alopecia, skin tightening, dry skin, pruritus, and woody indurated plaques on the skin of the upper back, shoulde… Scleredema adultorum of Buschke is a rare disorder of the connective tissue, involving the skin. Here, we present a 61-year-old male, who is a known case of compensated liver cirrhosis with a past history of being treated for autoimmune thyrotoxicosis, who presented with complaints of alopecia, skin tightening, dry skin, pruritus, and woody indurated plaques on the skin of the upper back, shoulder, and arms. Skin biopsy of the arm revealed the characteristic features of scleredema. He was extensively evaluated for known literature-cited causes of scleredema, and the work up revealed a negative result. He was also found to be hypothyroid on presentation. Hence, we present a case of scleredema occurring in a patient with hypothyroidism and chronic liver disease, which to our knowledge is being described for the first time in literature. [Scleredema: Beyond the hardening of the skin]. [Journal Article] Semergen . 2021 10; 47(7):501-503. Hernaiz Calvo LM, Abadías Granado I, … Gilaberte Calzada Y S Publisher Full Text (DOI) Cutaneous Manifestations of Diabetes. [Review] Med Clin North Am . 2021 Jul; 105(4):681-697. Hines A, Alavi A, Davis MDP Diabetes mellitus is a significant worldwide health concern and cutaneous manifestations are common. This review describes characteristic skin findings of diabetes, general skin findings related to diabetes, and findings related to diabetes treatment with a focus on clinical presentation, diagnosis, pathophysiology, epidemiology, and treatment. As the prevalence of diabetes continues to rise, cut… Diabetes mellitus is a significant worldwide health concern and cutaneous manifestations are common. This review describes characteristic skin findings of diabetes, general skin findings related to diabetes, and findings related to diabetes treatment with a focus on clinical presentation, diagnosis, pathophysiology, epidemiology, and treatment. As the prevalence of diabetes continues to rise, cutaneous manifestations of diabetes mellitus likely will be encountered more frequently by physicians in all disciplines including dermatologists and primary care physicians. Accordingly, knowledge regarding the prevention, diagnosis, and management of cutaneous manifestations is an important aspect in the care of patients with diabetes. Scleredema diabeticorum - A case report. [Case Reports] J Family Med Prim Care . 2021 Feb; 10(2):1037-1039. Kyriakou A, Zagalioti SC, … Patsatsi A Scleredema diabeticorum is an uncommon skin disorder which is characterized by stiffness and hardening of the subcutaneous tissues located on the upper back and posterior neck. Patients with this skin disease typically experience pain and stiffness on the neck. Scleredema associated with diabetes mellitus may often go unrecognized. We report a case of a 55-year-old female patient with diabetes me… Scleredema diabeticorum is an uncommon skin disorder which is characterized by stiffness and hardening of the subcutaneous tissues located on the upper back and posterior neck. Patients with this skin disease typically experience pain and stiffness on the neck. Scleredema associated with diabetes mellitus may often go unrecognized. We report a case of a 55-year-old female patient with diabetes mellitus type 1, who presented with skin tightness on her upper back and decreased range of motion. Scleredema diabeticorum is rare and its treatment is difficult and tricky, as no specific regimen has been instituted to treat this skin disease. Screening for the presence of scleroedema adultorum of Buschke in patients with diabetes mellitus: newly diagnosed patients had a high prevalence of dyslipidaemia. [Journal Article] Lipids Health Dis . 2021 May 05; 20(1):47. Csonka V, Bódis B, … Varjú C ↑40 CONCLUSIONS: Diabetes patients with scleroedema had more severe dyslipidaemia and higher occurrence of vascular complications compared to those without scleroedema. In addition to poorly controlled type 2 diabetes mellitus requiring insulin treatment, high non-HDL-C levels may be another contributing factor to the development of scleroedema. Cutaneous Manifestations of Nutritional Excess: Pathophysiologic Effects of Hyperglycemia and Hyperinsulinemia on the Skin. [Review] Cutis . 2021 Feb; 107(2):74-78. Svoboda SA, Shields BE Hyperglycemia is defined by excess blood glucose and, when persistent, may lead to prediabetic and diabetic states. Insulin is a hormone produced by the beta cells of the pancreas in response to elevated blood glucose. Dysregulated insulin secretion or clearance results in hyperinsulinemia, which also is closely associated with type 2 diabetes mellitus (T2DM) and metabolic disturbances. Hyperglyc… Hyperglycemia is defined by excess blood glucose and, when persistent, may lead to prediabetic and diabetic states. Insulin is a hormone produced by the beta cells of the pancreas in response to elevated blood glucose. Dysregulated insulin secretion or clearance results in hyperinsulinemia, which also is closely associated with type 2 diabetes mellitus (T2DM) and metabolic disturbances. Hyperglycemia and hyperinsulinemia are endemic within the United States and impart considerable morbidity and mortality. Cutaneous manifestations of chronic hyperglycemia and hyperinsulinemia include acanthosis nigricans (AN), diabetic dermopathy (DD), scleredema diabeticorum (SD), ichthyosiform skin changes, acrochordons, and keratosis pilaris (KP). Necrobiosis lipoidica (NL), bullosis diabeticorum (BD), and generalized granuloma annulare (GA) are more rarely reported in association with hyperglycemia and hyperinsulinemia; however, the strength of these associations remains unclear. It is crucial for dermatologists to recognize these cutaneous manifestations, as they may be the first signs of metabolic syndrome and insulin resistance. Early identification and management of these conditions is key to improving patient health outcomes and reducing health care costs. Herein, we review the clinical presentations of these conditions and their underlying pathophysiologic mechanisms. Scleredema diabeticorum in a patient: un uncommon etiology of restrictive lung pattern Escleredema diabeticorum en un paciente: una etiología infrecuente de patrón restrictivo pulmonar. [Case Reports] Dermatol Online J . 2021 Mar 15; 27(3) García-Arpal M, Bujalance-Cabrera C, … Villasanti-Rivas N DO Scleredema adultorum of Buschke is a rare skin disease characterized by skin thickening and tightening typically at the neck and the upper part of the body. This thickening results from increased mucin deposition in the reticular dermis. Three variants are recognized. Scleredema diabeticorum is one subtype associated with diabetes mellitus. We report a man with a history of poorly controlled diab… Scleredema adultorum of Buschke is a rare skin disease characterized by skin thickening and tightening typically at the neck and the upper part of the body. This thickening results from increased mucin deposition in the reticular dermis. Three variants are recognized. Scleredema diabeticorum is one subtype associated with diabetes mellitus. We report a man with a history of poorly controlled diabetes presenting with extensive scleredema adultorum of the trunk in a "cuirasse" pattern associated with restrictive lung disease. Cutaneous ultrasonography revealed a marked thickening of the dermis as well as various echogenic spots in the dermis. Cutaneous hardness secondary to scleredema may cause limited mobility. Therefore, respiratory manifestations may be associated and assessed, mainly in cases of extensive scleredema involving trunk and shoulders. Moreover, cutaneous ultrasonography may be useful to monitor the evolution of scleredema and confirm the diagnosis. Diabetes-associated dermatological manifestations in primary care and their association with vascular complications. [Journal Article] J Diabetes Metab Disord . 2020 Dec; 19(2):989-996. Trihan JE, Lanéelle D, … Frances P ↓1 ↑37 JD CONCLUSIONS: In primary care, DM-associated dermatological manifestations present similar prevalence rates to a tertiary care setting, based on litterature. Complete dermatological examination of diabetic patients is essential and could lead to a better overall management of the pathology, as diabetic cutaneous manifestations appear as a sign of vascular involvement. Usefulness of high-frequency Doppler ultrasound skin thickness measurement for disease staging and assessing treatment response in patients with scleredema: A case-control study. [Letter] J Am Acad Dermatol . 2022 01; 86(1):189-191. Giavedoni P, Pousa-Martínez M, … Mascaró JM Concurrent Scleredema and Pyoderma Gangrenosum: Case Report and Review of Comorbid Conditions. [Case Reports] Cureus . 2020 Dec 20; 12(12):e12188. Jacob JS, Cohen PR Scleredema is a connective tissue disorder that presents as diffuse induration of skin, most often involving the upper body. Scleredema can be associated with prior infection, monoclonal gammopathy, and diabetes mellitus. Pyoderma gangrenosum is a neutrophilic dermatosis that presents as an ulcer with violaceous borders. Pyoderma gangrenosum can be idiopathic or associated with various conditions… Scleredema is a connective tissue disorder that presents as diffuse induration of skin, most often involving the upper body. Scleredema can be associated with prior infection, monoclonal gammopathy, and diabetes mellitus. Pyoderma gangrenosum is a neutrophilic dermatosis that presents as an ulcer with violaceous borders. Pyoderma gangrenosum can be idiopathic or associated with various conditions. A 66-year-old man with a 20-year history of scleredema diabeticorum presented with idiopathic pyoderma gangrenosum in the affected area of scleredema on his neck. His pyoderma gangrenosum resolved after treatment with topical and intralesional corticosteroids. Diseases associated with scleredema, pyoderma gangrenosum or both are reviewed. Unilateral Linear Induration of the Skin: A Case Report of an Unusual Presentation of Scleredema. [Case Reports] J Clin Aesthet Dermatol . 2020 Dec; 13(12):E53-E55. Muhaidat J, Al-Qarqaz F, Alshiyab D ↑17 Scleredema is an idiopathic condition with specific clincopathological findings, including symmetrical and diffuse nonpitting induration of the upper body and thickened dermis due to deposition of acid mucopolysaccharides. Here, we report a case of linear scleredema in a healthy female patient, who presented with firm induration of the skin over her right shoulder and arm in a Blaschkolinear dist… Scleredema is an idiopathic condition with specific clincopathological findings, including symmetrical and diffuse nonpitting induration of the upper body and thickened dermis due to deposition of acid mucopolysaccharides. Here, we report a case of linear scleredema in a healthy female patient, who presented with firm induration of the skin over her right shoulder and arm in a Blaschkolinear distribution. The onset was insidious in childhood and stable over several years. While the clinical picture has closely mimicked linear morphea, the diagnosis of scleredema was confirmed by the typical histopathological findings. To the best of our knowledge, linear scleredema is a unique presentation that has not been previously reported. Hyaluronidase in Dermatology: Uses Beyond Hyaluronic Acid Fillers. [Journal Article] J Drugs Dermatol . 2020 Oct 01; 19(10):993-998. Searle T, Ali FR, Al-Niaimi F Hyaluronidase is mostly widely recognized for its off-label use in correction of complications of hyaluronic acid fillers. However, its utility in other aspects of dermatology is less widely acknowledged. We describe the varied uses of hyaluronidase in dermatology and the underlying evidence base for its dermatological indications. This includes its uses in enhancing drug delivery (for local anes… Hyaluronidase is mostly widely recognized for its off-label use in correction of complications of hyaluronic acid fillers. However, its utility in other aspects of dermatology is less widely acknowledged. We describe the varied uses of hyaluronidase in dermatology and the underlying evidence base for its dermatological indications. This includes its uses in enhancing drug delivery (for local anesthesia, keloid and hypertrophic scars, and for Kaposi&rsquo;s sarcoma), in the treatment of disorders associated with mucin deposition (myxedema, scleroderma, scleredema, and cutis verticis gyrata) and its potential uses in surgery (as a pre-operative adjuvant in dermatofibrosarcoma protuberans, for periorbital edema, and for hematomas). In select circumstances, hyaluronidase might be more efficacious than more established treatments with fewer adverse effects. We propose hyaluronidase as the latest addition to our global dermatological armamentarium and implore dermatologists to consider its use to enhance their practice. J Drugs Dermatol. 2020;19(10):993-998. doi:10.36849/JDD.2020.5416. A case of paraproteinemia-associated scleredema successfully treated with thalidomide. [Case Reports] JAAD Case Rep . 2020 Oct; 6(10):1039-1041. Barnes M, Kumar V, … Barnes H Woody Erythematous Induration on the Posterior Neck. [Case Reports] Cutis . 2020 07; 106(1):14, 21-22. Faraj Y, Gray T, … Miller R C
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Gross Hours and Earnings of Production Workers on Manufacturing Payrolls, by State and Selected Areas - Page 105 | Toc | FRASER | St. Louis Fed Gross Hours and Earnings of Production Workers on Manufacturing Payrolls, by State and Selected Areas from Employment and Earnings, March 1982 Title: Gross Hours and Earnings of Production Workers on Manufacturing Payrolls, by State and Selected Areas Gross Hours and Earnings of Production Workers on Manufacturing Payrolls, by State and Selected Areas DATE: March 1982 PART OF: Employment and Earnings : March 1982 AUTHOR: United States. Bureau of Labor Statistics Table of Contents Employment and Unemployment Developments Employment Status of the Noninstitutional Population 16 Years and Over Employment Status of the Noninstitutional Population 16 Years and Over by Sex Employment Status of the Noninstitutional Population by Sex, Age, and Race Labor Force, by Sex, Age, and Race Employment Status of Black Workers by Sex and Age Employment Status of Noninstitutional Population by Race, Sex, and Age Employment Status of the Noninstitutional Population 16-21 Years of Age by Major Activity, Sex, and Race Full and Part-Time Status of the Civilian Labor Force by Sex, Age, and Race Employment Status of the Noninstitutional Population in Family Relationship Unemployed Persons, by Marital Status, Sex, Age, and Race Unemployed Persons by Occupation and Sex Unemployed Persons by Industry and Sex Unemployed Persons, by Reason for Unemployment, Sex, Age, and Race Unemployed Persons by Reason for Unemployment, Sex, and Age, Duration of 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Biology | Free Full-Text | Quantitative Proteomics and Network Analysis of Differentially Expressed Proteins in Proteomes of Icefish Muscle Mitochondria Compared with Closely Related Red-Blooded Species Antarctic icefish are extraordinary in their ability to thrive without haemoglobin. We wanted to understand how the mitochondrial proteome has adapted to the loss of this protein. Metabolic pathways that utilise oxygen are most likely to be rearranged in these species. Here, we have defined the mitochondrial proteomes of both the red and white muscle of two different icefish species (Champsocephalus gunnari and Chionodraco rastrospinosus) and compared these with two related red-blooded Notothenioids (Notothenia rossii, Trematomus bernacchii). Liquid Chromatography-Mass spectrometry (LC-MS/MS) was used to generate and examine the proteomic profiles of the two groups. We recorded a total of 91 differentially expressed proteins in the icefish red muscle mitochondria and 89 in the white muscle mitochondria when compared with the red-blooded related species. The icefish have a relatively higher abundance of proteins involved with Complex V of oxidative phosphorylation, RNA metabolism, and homeostasis, and fewer proteins for striated muscle contraction, haem, iron, creatine, and carbohydrate metabolism. Enrichment analyses showed that many important pathways were different in both red muscle and white muscle, including the citric acid cycle, ribosome machinery and fatty acid degradation. Life in the Antarctic waters poses extra challenges to the organisms that reside within them. Icefish have successfully inhabited this environment and we surmise that species without haemoglobin uniquely maintain their physiology. Our study highlights the mitochondrial protein pathway differences between similar fish species according to their specific tissue oxygenation idiosyncrasies. Quantitative Proteomics and Network Analysis of Differentially Expressed Proteins in Proteomes of Icefish Muscle Mitochondria Compared with Closely Related Red-Blooded Species Adam Dowle 2 , 1 School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington LE12 5RD, UK 2 Department of Biology, Bioscience Technology Facility, University of York, York YO10 5DD, UK 3 Biology Department, University of Padova, Via U. Bassi, 58/b, 35121 Padova, Italy 4 Alfred Wegener Institute, 27570 Bremerhaven, Germany 5 MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, Liverpool L7 8TX, UK Author to whom correspondence should be addressed. Biology 2022 , 11 (8), 1118; https://doi.org/10.3390/biology11081118 Abstract : Simple Summary Antarctic icefish are unusual in that they are the only vertebrates that survive without the protein haemoglobin. One way to try and understand the biological processes that support this anomaly is to record how proteins are regulated in these animals and to compare what we find to closely related Antarctic fish that do still retain haemoglobin. The part of the cell that most clearly utilises oxygen, which is normally transported by haemoglobin, is the mitochondrion. Therefore, we chose to catalogue all the proteins and their relative quantities in the mitochondria (pl.) from two different muscle types in two species of icefish and two species of red-blooded notothenioids. We used an approach called mass spectrometry to reveal relative amounts of the proteins from the muscles of each fish. We present analysis that shows how the connections and relative quantities of proteins differ between these species. Abstract Antarctic icefish are extraordinary in their ability to thrive without haemoglobin. We wanted to understand how the mitochondrial proteome has adapted to the loss of this protein. Metabolic pathways that utilise oxygen are most likely to be rearranged in these species. Here, we have defined the mitochondrial proteomes of both the red and white muscle of two different icefish species ( Champsocephalus gunnari and Chionodraco rastrospinosus) and compared these with two related red-blooded Notothenioids ( Notothenia rossii , Trematomus bernacchii ). Liquid Chromatography-Mass spectrometry (LC-MS/MS) was used to generate and examine the proteomic profiles of the two groups. We recorded a total of 91 differentially expressed proteins in the icefish red muscle mitochondria and 89 in the white muscle mitochondria when compared with the red-blooded related species. The icefish have a relatively higher abundance of proteins involved with Complex V of oxidative phosphorylation, RNA metabolism, and homeostasis, and fewer proteins for striated muscle contraction, haem, iron, creatine, and carbohydrate metabolism. Enrichment analyses showed that many important pathways were different in both red muscle and white muscle, including the citric acid cycle, ribosome machinery and fatty acid degradation. Life in the Antarctic waters poses extra challenges to the organisms that reside within them. Icefish have successfully inhabited this environment and we surmise that species without haemoglobin uniquely maintain their physiology. Our study highlights the mitochondrial protein pathway differences between similar fish species according to their specific tissue oxygenation idiosyncrasies. Keywords: icefish ; proteomics ; mitochondria ; muscle ; network analysis ; notothenioid 1. Introduction Mitochondria are crucial organelles that produce ATP via oxidative phosphorylation, a process that involves the transfer of electrons between multi-subunit complexes (I to IV) of the electron transport chain (ETC), resulting in the reduction of molecular oxygen. These organelles are also known for their involvement in many vital cellular activities such as apoptosis, calcium homeostasis, and regulation of cell homeostasis. Due to this, there has been an increasing interest in the structure and function of mitochondrial proteins [ 1 , 2 , 3 , 4 ]. Efforts have been made to decipher the structure, assembly process, coupling mechanism, and associated pathologies of respiratory chain complexes [ 5 , 6 ]. Haemoglobin (Hb) synthesis requires a coordinated production of both haem and globin. Hb is a multi-subunit globular molecule made up of four polypeptide subunits, two alpha and two beta subunits. Each of the four subunits has a haem moiety that contains iron [ 7 ]. The prosthetic group haem is synthesised in a series of steps shuttling between the mitochondrion and the cytosol of immature erythrocytes [ 8 ]. To understand the role of haemoglobin, it can be useful to examine eukaryotic systems that express this important protein at different levels. There is a wide range of evidence that suggests Hb has dynamic locations in cell, neurons, endothelial cells, mitochondria, and vascular expression [ 9 , 10 , 11 , 12 , 13 ]. Previously, we have shown that haemoglobin proteins are located in the mitochondrion and both direct and indirect links have been established between mitochondria function and Hb expression [ 10 , 14 , 15 ]. Interestingly, a group of vertebrates known as Antarctic icefish are “null-mutants” for haemoglobin that have some likely relevant cellular modifications, including a high mitochondrial density [ 16 ]. Antarctic icefish/white-blooded fish, (subfamily Channichthyidae, family Nototheniidae, suborder Notothenioidei [ 17 ]) are the only known vertebrates that do not possess functional haemoglobin genes and red blood cells (RBCs), in stark contrast to all the others that depend upon Hb to get oxygen to tissues and cells, via RBCs [ 18 , 19 , 20 ]. The loss of Hb in the Antarctic icefish is postulated to be a mutational process, resulting in the loss of the β-globin (hbb) gene and partial omission of the α-globin (hba) gene from α-/β-globin, causing the locus to become functionally inactive. Fifteen out of the sixteen icefish species are known to retain only a 3′ fragment of an α-globin gene [ 21 ]. The sixteenth species, Neopagetopsis ionah , retains an intact but unexpressed hba gene fused to two β-globin pseudogenes [ 22 ]. As might be expected, some proteins have been shown to be altered in icefish and reasons have been suggested for these differences. Previously, studies have shown changes in the iron transporting proteins such as transferrin, ceruloplasmin, and ferritin [ 23 ]. Not all notothenioid species express myoglobin (Mb), an intracellular oxygen-binding protein in the muscle. In total, six of the sixteen icefish species do not express Mb in their heart ventricles, a loss that occurred through four different mutational events [ 24 ]. Icefish have large hearts [ 25 ], which do not contain the mitochondrial creatine kinase [ 26 ]. They also have high mitochondrial densities, which is postulated to counter the effects of cold temperature [ 27 ]. The high density of mitochondria rich in lipids serves as a pathway that enhances oxygen storage and diffusion, which compensates for the lack of Hb and Mb [ 28 ]. An observed increase in mitochondrial phospholipids may be due to an upregulation in the glycerol-lipid synthesis pathway. There is still a lot to be learned about protein networks and pathways in icefish [ 29 ]. Proteomics can be used to identify protein-protein interactions, which in turn influence protein expression or regulation [ 30 ]. In silico methods and web servers have been developed to predict the function and structure of proteins [ 31 ]. Although large-scale mitochondrial comparative proteomic data have been accumulated, mitochondrial proteomics still faces the challenge of how to investigate the functions of the identified mitochondrial proteins and how to build mitochondria specific signalling networks. An integrative network analysis approach can accommodate information from PPIs and proteomics and bridge the gap between the two. Hence, using an interactive network approach could lay the foundation for a better understanding of mitochondrial changes in icefish [ 32 ]. Here, we establish for the first time the proteomes of red muscle mitochondria (RMM) and white muscle mitochondria (WMM) from four species of the suborder Notothenioidei: two icefish, Champsocephalus gunnari ( C. gunnari ) devoid of Hb and Mb (the loss of Hb and Mb completely) and Chionodraco rastrospinosus ( C. rastrospinosus ), devoid of Hb but with tissue specific expression of Mb that is only expressed in the hearts of these species, are compared to their closely related red-blooded species Notothenia rossii ( N. rossii ) and Trematomus bernacchii ( T. bernacchii ), both the species belonging to the Nototheniidae, expressing Hb, and having tissue specific expression of Mb only in heart ventricles. Mammalian skeleton muscles are mainly composed of two kinds of fibres, white-fast twitch type that makes the white muscle and red-slow twitch type that makes the red muscle [ 33 ]. White muscle requires a greater capacity for anaerobic energy production to meet the demands of the fast-twitch fibres [ 34 ]. In contrast to mammalian white muscle tissue, the central regions of icefish red muscle contain numerous mitochondria [ 16 ]. In establishing these proteomes, we can understand how the mitochondrial proteome has adapted to the loss of this protein and potentially understand the role and interaction pathways of haemoglobin in the context of mitochondrial biology. 2. Methodology Antarctic Fish Muscle tissue: SVMS Clinical Ethical Review, University of Nottingham, (ref # 2744 190509). White and red muscle samples of Antarctic notothenioid fish, N. rossii , T. bernacchii (red-blooded species—Cruise PS112, Weddell Sea in 2013–2014), C. gunnari and C. rastrospinosus [icefish species—Cruise ANTXXVIII (PS79), Antarctic Peninsula in 2012]. N. rossii and T. bernacchii have 30–45% of haematocrit and 18–28% haematocrit respectively. Ethics Statement: The proposal for the Antarctic Fish project was approved by Veterinary School′s Clinical Ethical Review panel, University of Nottingham, with responses from at least four members of the panel. No ethical issues were raised by the panel. The Ethical project Number issued: 2744 190509. Subcellular fractionation: The white and red muscle tissues were stored at −80 °C and while obtaining the fractions were put on ice throughout. The tissues were cut with a sterile blade and then homogenised using Dounce homogeniser, in 2 mL mitochondria extraction buffer (50 mM Tris-Cl pH 7.4, 100 mM KCl, 1.5 mM MgCl2, 1 mM EGTA, 50 mM HEPES and 100 mM sucrose). The homogenized mixture was centrifuged at 800 rpm for 10 min at 4 °C to remove the insoluble fraction, and the first supernatant was centrifuged at 1000 rpm to pellet nuclear fraction. The supernatant obtained from the second centrifuge, was centrifuged at 10,500 rpm at 4 °C for 30 min to obtain the mitochondrial fraction. The supernatant which contained the cytosolic fraction was transferred into a separate tube and the pellet contained the mitochondrial fraction. The quality of the crude fractions was confirmed using standard western blotting techniques with nuclear, mitochondrial and cytoplasmic markers (Histone H3, ab1791 (Abcam) Rb pAB; COX IV ab16056 (Abcam) Rb Ab; and GAPDH, Sigma G9545 Rb respectively) as described previously specific blots or this study can be found [ 15 ]. A majority of the proteins identified are associated with mitochondrial processes, confirming the successful fractionation. Liquid Chromatography-Mass spectroscopy proteomic analysis ( LC-MS/MS ) : Complete mass spectrometry data sets and proteomic identifications are available to download from MassIVE (MSV000089644), [doi:10.25345/C5PZ51Q9F] and ProteomeXchange (PXD034498). Red Muscle: The extracted mitochondrial fractions of three specimens per species ( C. gunnari: samples 639, 673, 690; C. rastrospinosus : sample 1005, 1020, 1355; N. rossii : 4–10, 4–27, 5–14; T. bernacchii : samples 7–23, 7–56, 8–24) were captured in gel and sent to the Metabolomics and Proteomics Lab (University of York, York, UK) for Liquid Chromatography-Mass spectroscopy (D-100) proteomic analysis. A label-free, intensity-based quantification for comparing relative protein amounts between samples approach was used. Mass spectrometry data were analysed using PEAKSX software. The mapped ion areas were used as metric for significance testing for changes in the abundances between groups by using the PEAKSQ interpretation of the significance of the B model. These were converted into relative percent of the total ion area for analysis. The PEAKSQ significance values have been multiply-test-corrected using the Hochberg and Benjamin FDR approach ( q < 0.01). Protein identification: The spectra from PEAKSX studio were searched against the combined NCBI deposited proteins from Notothenia coriiceps (32,361 sequences; 15,554,893 residues) , Chaenocephalus aceratus (223 sequences; 59,314 residues) , Dissostichus mawsoni (210 sequences; 61,335 residues) and Eleginops maclovinus (193 sequences; 53,595 residues), in addition to 115 common proteomic contaminant proteins. Protein identifications were filtered to achieve <1% false discovery rate (FDR) as assessed against a reverse database. Identifications were further filtered to require a minimum of two unique peptide identifications per protein group. White Muscle: The extracted mitochondrial fractions of three specimens per species ( C. gunnari: 675, 708, 641 samples; C. rastrospinosus : 1006, 1021, 1386 samples; T. bernacchii : 7–37, 7–54, 8–22 samples; N. rossii : 4–25, 4–42, 4–59 samples) were captured in gel and sent to the Metabolomics and Proteomics Lab (University of York, UK) for Liquid Chromatography-Mass spectroscopy (D-270) proteomic analysis. The same approach was applied for analysing the mass spectrometry data for the white muscle mitochondria samples and was matched against the previously mentioned NCBI deposited proteins. From the proteomic data, we used ‘number of spectral matches’ as it shows the best metric for the presence and absence of a predicted protein. For the quantitative analysis of the changes in protein proportions, we used the relative percent of total ion map area for comparison of the proteins. Proteins that were individually low in abundance or higher in abundance for each species were characterised using the number of spectral matches and Ion Map Area ( Supplementary Tables S1–S12 ). The proteins from those lists present in species-specific quantities were grouped and used for comparing the abundance of proteins in red-blooded species ( N. rossii & T. bernacchii ) samples and with icefish species ( C. gunnari & C. rastrospinosus ) samples. This also took in account the proteins that followed a similar trend in their amounts, i.e., more in abundance in icefish in comparison to red-blooded species and vice versa. There is no proteomic or genomic data available for these samples so searching against other species was the only option. To help ameliorate issues such as the case of divergent sequences of proteins or/and quantification data of identified peptides, three rounds of searches were performed—initially against Notothenia coriiceps, Chaenocephalus aceratus, Dissostichus mawsoni, and Eleginops maclovinus, which were publicly available using conventional parameters; subsequently, searching was expanded to include 313 common PTMs and single point amino acid substitutions. The inclusion of single point substitution can allow for better coverage between non-identical species. The similarity in mitochondrial proteins between these species and this coupled strategy helps elevate that issue. The similarity in mitochondrial proteins between these species, coupled with the search strategy applied, means that this divergence in species does not appear to be too dramatic in these samples STRING Network analysis and Clustering : The list of proteins that were found to follow a definite pattern in the proteome of the icefish in comparison to the red-blooded fish were checked as separate groups in the STRING database ( http://string-db.org ; accessed on 20 February 2021). The protein IDs of the selected protein was extracted from the proteomics data and the respective FASTA sequences were extracted. The multiple FASTA sequence of the proteins was searched against the closest available species on the STRING db, Danio rerio (zebrafish) using the multiple sequence. The STRING networks were generated with a medium confidence (0.400) and 5% FDR. Network analyses were visualised in Cytoscape_v3.8.0 [ 35 ] and to obtain the top hub proteins, a molecular complex detection plug-in (MCODE) was used to obtain the modules. The criteria used were Degree cut-off = 2, node score cut-off = 0.2, k-core = 2 and max Depth = 100 [ 36 ]. The top modules (score > 4) were selected for graphical representation. The hub nodes (proteins) in the PPI were also analysed by their topological relevance using the Cytoscape plugin CentiScaPe [ 37 ] ( Supplementary Figures S2, S3, S5 and S6 ) with default options. The plots were generated using the plot by node option and supports the importance of those highlighted hubs, specifically pointing out the shortest path betweenness and centroid values. Cytoscape with the GeneMANIA plugin was used to identify the genes most related to the groups of gene sets to form a network of functional genes based on their interaction, such as co-expression, physical-interaction, and shared protein domains. GeneMANIA, a plug-in for Cytoscape, predicts the function of the identified gene sets by using a ‘guilt-by-association’ approach informed by functional networks from multiple organisms [ 38 ]. The gene symbols for the proteins were inputted with default parameters using in-built D. rerio gene information, which have been collected from GEO, BioGRID and organism-specific functional genomic data sets. The pathway enrichment was analysed for GO terms ‘biological significance’ and ‘associated metabolic pathways in KEGG’. The enrichment database fishENRICHR was run using gene symbols ( Table 1 , Table 2 , Table 3 and Table 4 ); these were sorted according to the p values ( p < 0.05, probability of any gene belonging to any set) [ 39 , 40 ]. Graphical representation: R package ggplot2 v.3.5.1. was used for generating heatmaps and volcano plots. 3. Results 3.1. LC/LC-MS Data for RMM and WMM The purpose of the study was to identify mitochondrial and mitochondrial-associated proteins in icefish and to understand how the loss of haemoglobin affects the proteome. LC-MS/MS data were analysed using PEAKSX for reliable matching to the available sequence database and the data were filtered to a 1% false discovery rate by at least two unique peptides for each protein group ( Figure 1 (A1,B1)). For red muscle mitochondria (RMM), 1148 proteins were identified belonging to unique protein groups; this contrasts with white muscle mitochondria (WMM), where 429 proteins were identified. Haemoglobin α, β and γ were only identified in the red-blooded fish confirming sample specificity. The two types of muscle are faced with very different energetic demands; however, previously it has been shown that there are no large differences in mitochondrial protein expression when surveying different porcine muscle tissues [ 41 ]. Group 1 consisted of the proteins that were significantly more abundant, and group 2 consisted of less abundant proteins in the two icefish species when compared with the red-blooded species ( Table 1 , Table 2 , Table 3 and Table 4 ). The reported significance value is the –log10 p value, with the null hypothesis being that the protein is of equal abundance in all samples. The higher the significance value the greater the probability that the protein is not equal in abundance in all groups. The volcano plot distinctively shows the significant differentially expressed proteins (DEPs) ( q < 0.05) that were downregulated (green) and upregulated (red). The WMM had fewer proteins that were not significant when compared to the RMM. A heat map that includes the differentially expressed proteins (DEPs) in red muscle ( Figure 1 (A2)) and white muscle ( Figure 1 (B2)) mitochondria illustrates that protein expression profiles are characteristic for the haemoglobin-less species when compared with red-blooded groups. The mapped ion areas were converted to relative percent values by weighting each protein equally to point out differences between groups. There was a common increase in abundance in the complex V proteins and a group of ribosomal proteins (more evidently in the white muscle) in the icefish in both the muscle mitochondria tissues. A few mitochondrial import proteins were also seen to be increased such as ADP/ATP translocases, voltage-dependent anion channels, and heat shock proteins. A common decrease in abundance in the proteins for the icefish were seen in Hb and haem/Hb-associated proteins such as cytochrome c, transferrin, haem oxygenase 2 and hemopexin. Apart from those, a decrease in the abundance was seen in muscle proteins such as creatine kinase, troponin, titin, and myosin heavy chain. The two groups of proteins from both the tissues RMM and WMM were mapped into protein-protein interaction (PPI) networks constructed using STRINGdb. The enrichment p -value for each of the three PPI networks is lesser than10 −16 , indicating that proteins share more interactions than would be expected for a random set of proteins of similar size drawn from the proteome and suggesting at least partial biological connection as a group [ 42 ]. The network was retrieved and analysed using Cytoscape software, which allowed us to visualize and analyse molecular interaction networks [ 43 ] (Figures 2 and 4) [ 38 ]. 3.2. Analysis of Proteins More in Abundance in Icefish Forty-three proteins were differentially expressed with higher abundance in the RMM of the two icefishes compared to the red-blooded nonfamilial species. Fifty-seven proteins were significantly higher expressed in the WMM ( Table 1 and Table 2 ). Most proteins that were seen upregulated in both RMM and WMM were found to be part of the complex V, ribosomal and proteosome machineries in addition to a common upregulated expression of malate dehydrogenase and Fragile X mental retardation isoform 2 protein. In RMM, components of complex V of the electron transport chain and proteins involved in transportation across mitochondria were observed. The upregulated proteins of WMM were involved in the citrate cycle and carbon metabolism. GeneMANIA (based on zebrafish) analysis for interactions of the proteins with increased abundance in icefish produced one network per each muscle tissue ( Figure 2 A,B). In RMM, co-expression occupied 98.66% of the interactions seen in the network; shared protein domains occupied 1.13%; physical interaction, 0.21%. The network showed shared domains among proteins slc25a5, slc25a6, slc25a20, vdac3 and slc25a12, and, between atp5a1 and atp5b. The network showed physical interactions between atp5a1, atp5o, predicted cyc1 and coq9. In WMM, co-expression occupied 98.46% of the interactions seen in the network; physical interactions occupied 1.431%; and shared protein domains occupied 0.11%. The network showed physical interactions between ribosomal proteins and separately also between proteasome proteins. Figure 3 A shows the PPI network generated using the FASTA sequences (corresponding NCBI IDs) for the proteins using STRING. The 43 identified DEPs that were more abundant in RMM were analysed and connected with a PPI enrichment p -value < 1.0 × 10 −16 , with 42 nodes (proteins RPL27 was not identified for organism D. rerio ), 143 edges, and an average node-degree of 6.8. Four of forty-two DEPs (RTN4IP1, PFKMA, FRX2 and HAPLN1b) did not connect to any type of network (STRING interaction score = 0.4). Thirty-eight of the remaining DEPs were connected to networks by complex relationships. RPL23, MDH1AA, ATP5B, and VDAC3 showed network hubs highly associated with other nodes in PPI. ( Supplementary Figure S2 ). A single network was formed between DEPs ITIH4, A2ML, KNG1, F2 and APOBB. The highly connected proteins are majorly involved in energy metabolism and protein metabolism. Three distinctive clusters were seen for RMM upregulated proteins. Cluster 1 had proteins involved in ETC and oxidative phosphorylation, Cluster 2, proteins involved in cell signalling, and Cluster 3, proteins involved in fatty acid biosynthesis ( Supplementary Figure S1 ). Functional enrichment analysis (FDR < 1.9 × 10 −2 ) showed proteins involved in the TCA cycle, oxidative phosphorylation, degradation of RNA, cristae formation, mitochondrial protein import, and carbon metabolism (See Figure 3 A), using the STRINGdb information provided under KEGG and Reactome pathways. Using FishENRICHR [ 39 , 40 ], the most used GO Terms for different biological processes were: GO:0019674, NAD metabolic process; GO:0070306 lens fibre cell differentiation; GO:0006754 ATP biosynthesis; GO:0006839 mitochondrial transport; GO:0045898 regulation of RNA polymerase II transcriptional pre-initiation complex assembly. (See Figure 3 (C1,C2)). Using the same steps as for RMM, a PPI network was generated for WMM DEPs ( Figure 3 B). As for the WMM, the intra network connections were strongest (PPI enrichment p -value < 1.0 × 10 −16 , with fifty-six nodes, 382 edges, and an average node-degree of 13.6). Nine of the fifty-six DEPs did not connect to any network (RTNA1, MYOZ1B, HSPB1, KLH41B, TUBA8L2, VTG2, ZGC:110377, PALLD, and FXR2- Table 2 ). The remaining forty-seven of the differentially expressed proteins were connected to networks where differentially expressed proteins ATP5B, GNB2L1, RPL11, RPL13, RPSA, and PKMA are the major protein-hubs (See Supplementary Figure S3 ). A single network was formed between DEPs MYLPFB, AMPD, ACTN2, and VCLA. Three distinctive clusters were seen for WMM upregulated proteins similar to RMM. Cluster 1 had proteins of ribosome machinery, Cluster 2 proteins involved in ETC and TCA, and Cluster 3 proteins involved in fatty acid biosynthesis ( Supplementary Figure S1 ). Functional enrichment analysis (FDR < 1.4 × 10 −2 ) showed proteins involved in TCA, ribosomal proteins, downstream signalling events of B cell receptors, and L13a-mediated translational silencing of ceruloplasmin. The fishENRICHR identified, GO:0000463: “maturation of LSU-rRNA”, GO:0045727 and GO:0000470: “positive regulation of translation”, GO:0000027 and GO:0042273: “ribosomal large subunit assembly” as most common GO terms. Enriched KEGG pathways included ribosome, glycolysis, and gluconeogenesis, and the pentose pathway (pathways sorted according to p -values) ( Figure 3 (C3,C4)). The proteins involved in gluconeogenesis have previously been reported altered in their expression in rainbow trout. The study goes on to show an increase in the enzyme FB2, a key enzyme of gluconeogenesis to be increased in red muscle of the fish. On contrary we see FB2 to be increased fourfold in the white muscle tissue for icefish rather than the red muscle [ 44 ]. The protein networks between RMM and WMM differ. In RMM, there is one quite dense cluster with some weak “satellites” and another cluster with similar connectivity as seen in WMM. In WMM there are three separate clusters with good and quite similar connections. 3.3. Proteins with Lower Abundance in Icefish Forty-eight proteins were found in lower quantities in RMM (ENSDARG00000030638, ca1, casq, gdh, mdh, pygm, rdh13, wu:fd55e03 were not recognised by GENEmania) and thirty-two proteins were differentially expressed in WMM in icefish compared to their red-blooded relatives ( Table 3 and Table 4 ). As before, GeneMANIA was used to analyse the interactions and produced one network per tissue ( Figure 4 A,B). In RMM, co-expression accounted for 96.14% of the total interactions seen in the network; and shared protein domains occupied 3.86%. In WMM, co-expression occupied 94.76%; physical interactions occupied 5.02%; and shared protein domains occupied 0.21%. The network showed physical interactions between ribosomal proteins and nebulin and this was predicted for the neighbouring protein tropomodulin. In RMM, PPI networks include forty-eight protein nodes ( Figure 5 A), nine proteins (MUT, RPN1, CKMT2A, PDPR, DHRS7CB, ALDH7A1, WU:FD55e03, USP5, PLIN3) did not connect to any type of network (STRING interaction score = 0.4). The PPI enrichment ( p -value < 1.0 × 10 −16 ) had thirty-nine nodes, fifty-three edges, and an average node degree of 2.52. The rest of the DEPs were connected to networks by complex relationships, where proteins ACTN3B, TTNA, CKMB, MYBPC1, TTNT3B, and CYCSB showed network hubs highly associated with many proteins ( Supplementary Figure S5 ). Single networks were observed between FBN2A and TFA, SLC4A1A and HBAE1. Two distinctive clusters were seen for RMM. Cluster 1 had proteins involved in striated muscle contraction, and Cluster 2 proteins involved in oxidative stress ( Supplementary Figure S4 ). In WMM, six (ZGC:153629, HBZ, HBAA1, MYOM1A, EVA1BA and, MDH1AA) out of the thirty-two protein nodes in the network did not connect to any type of network ( Figure 5 B). Proteins FGA, TFA, and TTNA represent network hubs, highly associated with other proteins ( Supplementary Figure S6 ). The PPI enrichment ( p -value < 3.49 × 10 −12 ) gave thirty-two nodes with forty-five edges and an average node-degree of 2.58. Three distinctive clusters were seen for WMM downregulated proteins. Cluster 1 had proteins of actin filament regulation, Cluster 2, proteins involved in muscle contraction, and Cluster 3, proteins involved with collagen ( Supplementary Figure S4 ). The functional enrichment analysis (FDR < 3.8 × 10 −3 ) for RMM reduced proteins in icefish were involved in striated muscle contraction, erythrocytes absorbing oxygen, fibrin clot formation hemostasias, and haem-associated proteins ( Figure 5 A). The following GO terms for biological processes were found overrepresented: GO:0006941 and GO:0006936: “striated muscle contraction” and GO:0045214: “sarcomere organisation”. The following KEGG pathways were affected: amino acid metabolism, fatty acid degradation, and peroxisome, glyoxylate, and dicarboxylate metabolism ( Figure 5 (C1,C2)). The functional enrichment analysis (FDR < 2.5 × 10 −4 ) for white muscle downregulated proteins in icefish identified multiple pathways, including translational silencing proteins and signal-recognition particle SRP-dependent co-translational protein targeting, the latter being involved in binding to the endoplasmic reticulum (ER) ( Figure 5 B). Based on fishENRICHR analysis, the most used GO Terms for different biological processes were: GO:0019674 NAD metabolic process, GO:0060956 endocardial cell differentiation, GO:0020027 haemoglobin metabolic process, and GO:1903512 endoplasmic reticulum to cytosol transport ( Figure 5 (C4)). AGE-RAGE signalling pathway metabolism, glyoxylate and dicarboxylate metabolism, amino acid metabolism, ECM-receptor interaction, and focal adhesion were identified by KEGG pathway analysis (See Figure 5 (C3)). 4. Discussion The paper presents the comparative analysis of the mitochondrial proteomes of white (WMM) and red muscle (RMM) of icefish that do not express haemoglobin protein and closely related red-blooded species. We wanted to understand how the mitochondrial proteome has adapted to the loss of this protein. The differentially expressed proteins are identified using the LC/LC-MS technique. The network built using the STRING database provided unbiased identification of network hubs as it builds all the networks entirely on external information. Network enrichment analysis provided several KEGG pathways that were linked to protein machinery, amino acid metabolism, energy production, and fatty acid metabolism. 4.1. Proteins Involved in Energy Metabolism The RMM and WMM tissues had a few proteins following a similar trend in their protein abundance in the icefish. The proteins involved in the ribosomal machinery and cellular hypoxia were found to be commonly increased in the icefish (RMM: ATP5O, ATP5D ATP5B1, ATP5G; WMM: PSMD12, PSMA8). In cluster 1 of the red muscle tissue, apart from involvement in hypoxia, some were also involved in ETC, oxidative phosphorylation, and the TCA cycle ( Figure 3 A; increased abundance in icefish). ATP synthase subunit O (ATP5O), stress 70 protein (HSPA9), and malate dehydrogenase (MDH1AA) were found to be highly connected to the other nodes, and changes in any highly connected network proteins are likely to be lethal for an organism [ 45 , 46 , 47 ]. ATP5O is a component of the multi-subunit enzyme ATP synthase (complex V of the electron transport chain), which is located in the stalk that connects the catalytic core (F 1 ) to the membrane proton channel (F O ) [ 48 ]. The protein is known to influence the proton conductance by conformational changes [ 48 ]. ATP5O has also been found to interact directly with sirtuin 3 (SIRT3), which is significantly involved in energy production and stress responses [ 49 ]. ATP5O may contribute to the age-associated decline in association with SIRT3, mitochondria dysfunction, and diseases linked to mitochondrial homeostasis under hypoxia [ 49 , 50 ]. Another component of complex V, ATP synthase subunit gamma (ATPγ), which is also a part of the central stalk, was comparably high in the icefish cohort. ATPγ helps in the binding change mechanism by helping in the rotation of the β subunit. Icefish have been previously reported to show an increased coupling of proton transport and ATP synthase compared with red-blooded notothenioids [ 51 ] and this could be correlated to the increase in the specific subunits of complex V that are directly involved in proton translocation. Previously, we have shown the ATP synthase subunit 6 of complex V to be sequentially and structurally different in the icefish C. gunnari when compared to its red-blooded related species [ 52 ]. One of the proteins densely connected in RMM (a hub node) in cluster 1 also involved in the TCA was the dihydrolipoyllysine-residue acetyltransferase component (DLAT). The increase in the abundance of this protein subunit, a component of the pyruvate dehydrogenase complex (PDH), involved in the breakdown of pyruvate to acetyl-CoA that requires converting NAD + to NADH, in icefish could be a response to moderate pyruvate levels. This could be to prevent pyruvate being converted into acetyl-CoA for TCA and instead be used to meet muscle energetic demands via anaerobic respiration [ 53 , 54 ]. The skeletal muscle is known to have metabolic flexibility in meeting the energy demands of the tissue and responding and adapting to environmental changes [ 53 , 55 ]. The hearts and skeletal muscle of icefish have been suggested to have a dual oxidative-anaerobic metabolism to maintain ATP levels [ 56 , 57 , 58 , 59 ]. An increase in the metabolites of fatty acid metabolism in icefish have also been suggested previously [ 59 ]. This could further suggest that the increase in DLAT is to maintain pyruvate levels, which could be converted to oxaloacetate for fatty acid cholesterol biosynthesis via the glycolytic pathway [ 53 ]. PDH has been seen to be involved in metabolic rate depression in vertebrates, which is a common element of anaerobiosis [ 60 ]. The regeneration of NAD + either happens aerobically via OxPhos or anaerobically by fermentation wherein lactate dehydrogenase (LDH) converts pyruvate to lactate. The LDH enzyme has previously been reported to be highly increased in the icefish myocardium, which indicates involvement of anaerobic energetics in the icefish heart muscle [ 57 ] LDH is regulated by the relative concentrations of its substrates, and an increase in pyruvate could inhibit the enzyme [ 61 , 62 , 63 ]. 4.2. Muscle-Contraction Proteins A common decrease in the expression in icefish of the proteins associated with biological processes of striated muscle contraction (RMM: MYBPC1, MYBPHA, NEB, TNA3, TTN3A, TNNT3A; WMM: MYBPC1, MYHB, MYBPC2A, MYBPC2B, MYBPC3, TTNA), creatine metabolism (RMM: CKMT2A, CKMB; WMM: CKMT2A), and amino acid/protein metabolism (RMM: GCDH, OGDHA, BCKDHA, PSME2, CKMT2A; WMM: CCT8, VCP, TFA, RPS11, RPS3A) was observed in both RMM and WMM. Creatine kinase (CK), which has previously been shown by Western blot to be absent in the hearts of icefish, did not appear in our protein lists from skeletal muscle mitochondria [ 26 ]. The mitochondria are enlarged in the oxidative muscle of icefish, which decreases the distance for the diffusion of oxygen and for ATP between mitochondria and myofibrils, which might reduce the demand for CK [ 29 ]. Mitochondrial CK helps maintain flux through the respiratory chain by maintaining low ATP levels [ 64 ]. This is coherent with our observation of an increase in the abundance of proteins of complex V. Notothenioids lacking mtCK may compensate by increasing levels of ADP/ATP nucleotide translocases and voltage dependent anion-selective channel proteins (VDACs), as observed in our proteomics study as well, where VDAC3 is selectively seen higher. The lower levels or absence of this enzyme has previously also been reported to be an example of a ‘paedomorphic trait’, a juvenile trait that persists into adulthood. This trait observed as a result of delayed development has been seen as a common feature in icefish; whether this is energetically efficient or not is still debatable [ 26 , 65 ]. A common muscle protein that was found to be downregulated both in RMM and WMM tissues is myosin binding protein C isoforms (MYBPC), which encodes myosin binding protein C. MYBPC is a thick filament associated protein that has both structural and regulatory roles in sarcomere assembly [ 66 ]. The protein was seen to decrease four- fold in the icefish C. gunnari when compared to the red-blooded species, but the amount was comparable in the icefish C. rastrospinosus . MYBPC mutations have been shown to increase the energetic cost of contraction in the muscle, and usually are found to act by reducing the protein content [ 67 , 68 , 69 ]. The downregulation of this protein in icefish is in contrast to a study that has shown significant upregulation of MYBPC in colder temperatures, which is consistent with the observation of the amount of this protein seen in their closely related red-blooded species [ 70 ]. Previously, mutations in MYBPC were seen to be involved in increased cardiac oxidative stress in the mouse model [ 71 ]. The other sarcomere protein that was seen significantly less in abundance in icefish was myosin heavy chain b (MYBPH); the activity of this protein has been used as a model to explain the mechanism underlying alterations in skeletal muscle contraction [ 72 ]. The ATPase reaction of a muscle fibre is determined by its myosin heavy chain composition, which might be altered with ageing, as seen previously in human skeletal muscle [ 73 ]. An impaired sarcomere energetics such as mutations in muscle contractions protein can cause mitochondrial dysfunction due to a Ca 2+ imbalance or ROS accumulation impairing oxidative phosphorylation capacity [ 74 ]. The other proteins that were connected to MYBPH were titin, nebulin, and CK. Titin, nebulin, and CK proteins have previously been seen to be downregulated under long term exposure to hypoxia in the zebrafish model [ 75 ]. Chaperonin proteins, T-complex protein 1 encoded by CCT8 are known for their role in the folding of cytoskeleton proteins upon ATP hydrolysis and changes in the protein can cause defects in the functioning of the cytoskeleton and mitosis arrest. A study with C. elegans showed CCT8 as a candidate to sustain proteostasis during organismal ageing [ 76 ]. The decrease in the level of the protein is observed in human brain ageing and neurodegenerative diseases [ 77 ]. 4.3. Redox The proteins GCDH- glutaryl-CoA dehydrogenase and Aldh7a1- Alpha aminoadipic semialdehyde dehydrogenase were remarkedly seen lower in the icefish C. gunnari , specifically in WMM tissue. GCDH is a mitochondrial enzyme necessary for the metabolism of lysine/tryptophan and hydroxylysine. The absence of this enzyme is known to result in mitochondrial dysfunction. ALDH7A1 is an enzyme that metabolises betaine aldehyde to betaine, which is an important cellular osmolyte and methyl donor that helps in protecting the cell from oxidative stress. The enzyme is seen to be involved in lysine catabolism and helps in maintaining the cellular nitrogen pool [ 78 ]. The changes in expression of these proteins might indicate the red-muscle tissue of N. rossii and T. bernacchii and even C. rastrospinosus (that has the expression mb) has enhanced defences against oxidative stress, which is consistent with the previous observation made in the cardiac mitochondrial protein expression data [ 79 ]. In WMM, we see that transmembrane protease serine 2-like is very reduced and perhaps missing in icefish. This protein has not been investigated very much to date and has not been reported as absent in these fish previously; the higher levels of it in the red-blooded fish suggest this difference may be of biological relevance. 4.4. Haem-Associated Proteins Consistent with all the studies of icefish, haemoglobin alpha and beta were solely identified in red-blooded species. We also show that hemopexin (Hx) protein is reduced in the WMM of icefish. It was previously shown that Hx transcription occurs at levels comparable to those in the red-blooded notothenioids; however, it seems possible that there is a discrepancy between transcript and protein levels of Hx [ 80 ]. Cytochrome c oxidase (CO) is an important haem-containing protein just like haemoglobin and in our study was also found to be much reduced in icefish RMM. As this protein performs a multitude of functions, including cell apoptosis and energy metabolism, it remains to be seen what this reduced level means for the physiology of this tissue [ 81 , 82 ]. The oxygen-carrying capacity of their blood is only 10% compared to that of red-blooded species. Cytochrome c oxidase is at first the terminal electron carrier of the respiratory chain, so lower protein expression may indicate a modification in redox metabolism in icefish. Previously, it has also been shown that maximal capacities of CO and activities of another mitochondrial enzyme, citrate synthase, to be higher in red-blooded fish species in comparison to icefish [ 83 ]. Transferrin was another protein that was found to be significantly reduced (five-fold) in the WMM of the icefish C. gunnari . 4.5. Ribosome Machinery in WMM Overall, a striking finding in the samples we interrogated is the numbers of 26S, 40S and 60S ribosome proteins that are differentially (mostly) upregulated in icefish. There have been extensive studies on close interaction between mitochondria and the endoplasmic reticulum [ 84 ]. FXR2P, a ribosomal binding protein, was also measured at much higher levels in icefish muscle; it would be interesting to probe the connections between ribosome and mitochondrial biology in these organisms. FXR2P protein has not been found to be present in mammalian muscle and therefore its role in icefish muscle remains to be elucidated [ 85 ]. With this study, we have established biological pathways and proteins that can be used to understand the unique ‘haemoglobin-free’ biology of icefish. We analysed samples directly taken from the field in the late summer season, ensuring that the pressures of a captive environment are not a factor. We show that muscle mitochondrial proteomes are distinct between fish with different quantities of haemoglobin. We expect our contribution will direct researchers in this field to focus on the identified proteins and pathways that allow these remarkable and unique fish to survive and thrive in Antarctic waters. Supplementary Materials The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/biology11081118/s1 , Figure S1: Top modules obtained from the PPI network using Cytoscape’s plugin MCODE for Red muscle tissue network (C) and white muscle tissue network (D) for upregulated proteins in the icefish, Figure S2: Highly connected protein nodes for RMM PPI using CentiScaPe, Cytoscape plugin, Figure S3: Highly connected protein nodes for WMM PPI, Figure S4: Top modules obtained from the PPI network using Cytoscape’s plugin MCODE for Red muscle tissue network (C) and white muscle tissue network (D) for upregulated proteins in the icefish, Figure S5: Highly connected protein nodes for RMM PPI, Figure S6: Highly connected protein nodes for WMM PPI; Table S1: Proteins higher in abundance in N. rossii (RMM), Table S2: Proteins lower in abundance in N. rossii (RMM), Table S3: Proteins higher in abundance in C. rastrospinosus (RMM), Table S4: Proteins lower in abundance in C. rastrospinosus (RMM), Table S5: Proteins more in abundance in C. gunnari (RMM), Table S6: Proteins less in abundance in C. gunnari (RMM), Table S7: Proteins higher in abundance in N. rossii (WMM), Table S8: Proteins lower in abundance in N. rossii (WMM), Table S9: Proteins higher in abundance in C. rastrospinosus (WMM), Table S10: Proteins lower in abundance in C. rastrospinosus (WMM), Table S11: Proteins more in abundance in C. gunnari (WMM), Table S12: Proteins less in abundance in C. gunnari (WMM). Author Contributions Conceptualization: L.C., C.P. and M.L.; Methodology: A.D., L.C. and G.K.; Software: A.D. and G.K.; Validation: A.D., G.K., B.E. and L.C.; Formal analysis: G.K., B.E., A.D. and L.C.; Investigation: G.K., B.E., A.D., C.P., M.L., L.C. and F.S.; Resources: C.P., M.L. and C.P.; Data Curation: G.K., B.E., A.D. and L.C.; Writing- original draft preparation: G.K., B.E. and L.C.; Writing review and editing: G.K., B.E., A.D. and L.C.; Visualization: G.K., B.E. and A.D.; Supervision: L.C.; Project administration: L.C.; Funding acquisition: L.C. All authors have read and agreed to the published version of the manuscript. Funding Gunjan Katyal was supported by Vice Chancellor’s International Scholarship for Research Excellence, University of Nottingham (2018–2021). Brad Ebanks was supported by the Biotechnology and Biological Sciences Research Council [grant number BB/J014508/1]. This collaboration was made possible by a University of Nottingham International Research Collaboration Fund award. Institutional Review Board Statement The animal study protocol was approved by the Institutional Review Board (or Ethics Committee) of University of Nottingham SVMS (ref # 2744 190509). Data Availability Statement Complete mass spectrometry data sets and proteomic identifications are available to download from MassIVE (MSV000089644), [doi:10.25345/C5PZ51Q9F] and ProteomeXchange (PXD034498). Acknowledgments The York Centre of Excellence in Mass Spectrometry was created thanks to a major capital investment through Science City York, supported by Yorkshire Forward with funds from the Northern Way Initiative, and subsequent support from EPSRC (EP/K039660/1; EP/M028127/1). 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Genes that are upregulated are on the right side of the graph and those that down regulate are on the left side of the graph (FDR > 0.01). DEPs in red muscle mitochondria ( A2 ) and white muscle mitochondria ( B2 ) for the four species (Red is significantly more highly expressed). The heat maps are produced using the relative percent of total ion area that is used for comparing the change in abundance for the same protein from different samples. A clear distinction in the expression of the protein abundance among different species can be seen, red being more abundant and yellow being less (List of proteins Table 1 , Table 2 , Table 3 and Table 4 ). Figure 1. Volcano Plot and Heat Map of DEPs for the two tissue types. Volcano plot for differentially expressed proteins ( A1 , B1 ). The x axis depicts log fold change and y axis depicts FDR; the lower genes are low p values, less significant. Genes that are upregulated are on the right side of the graph and those that down regulate are on the left side of the graph (FDR > 0.01). DEPs in red muscle mitochondria ( A2 ) and white muscle mitochondria ( B2 ) for the four species (Red is significantly more highly expressed). The heat maps are produced using the relative percent of total ion area that is used for comparing the change in abundance for the same protein from different samples. A clear distinction in the expression of the protein abundance among different species can be seen, red being more abundant and yellow being less (List of proteins Table 1 , Table 2 , Table 3 and Table 4 ). Figure 2. Gene interaction networks for DEPs with increased abudance in icefish. ( A ) RMM Analysis and ( B ) WMM Analysis. A GeneMANIA gene–gene interaction network for protein abundance following the pattern N. rossii (+/+), T. bernacchii (+/+), C. rastrospinosus (−/+) and C. gunnari (−/−) in increasing order of their protein abundance, laid out and visualised with Cytoscape, showing interaction strength (edge thickness), interaction type (colour-bottom right), multiple edges between nodes, and protein score (node size). Black nodes indicate query proteins, and grey nodes are neighboring proteins with interactions as co-expressed, physical, or shared protein domains. Figure 2. Gene interaction networks for DEPs with increased abudance in icefish. ( A ) RMM Analysis and ( B ) WMM Analysis. A GeneMANIA gene–gene interaction network for protein abundance following the pattern N. rossii (+/+), T. bernacchii (+/+), C. rastrospinosus (−/+) and C. gunnari (−/−) in increasing order of their protein abundance, laid out and visualised with Cytoscape, showing interaction strength (edge thickness), interaction type (colour-bottom right), multiple edges between nodes, and protein score (node size). Black nodes indicate query proteins, and grey nodes are neighboring proteins with interactions as co-expressed, physical, or shared protein domains. Figure 3. Network analysis of more highly abundant proteins in icefish mitochondria compared with closely related red-blooded species. ( A ) RMM DEPs, number of nodes 42 with 143 edges, the average node degree is 6.8 and ( B ) WMM, number of nodes 56 with 382 edges with an average node degree of 13.6. Network analysed using STRINGdb. The network highlights proteins involved in different pathways curated by STRINGdb from KEGG and Reactome databases. Nodes are coloured according to pathways. The edge shows type of interactions, experimentally determined interactions derived from databases, predicted interactions such as gene neighbourhood, gene co-occurrence, and gene fusions, respectively, co-expression interactions, text-mining interactions, and homology; the thicker the edge, the higher the confidence obtained by the mentioned sources. ( C ) Using FishEnrichr [ 39 , 40 ] analyser KEGG Pathways and GO terms for Biological process showed proteins in different pathways. The length of the bar represents the significance of that specific gene-set or term. Brighter colours are highly significant. Figure 3. Network analysis of more highly abundant proteins in icefish mitochondria compared with closely related red-blooded species. ( A ) RMM DEPs, number of nodes 42 with 143 edges, the average node degree is 6.8 and ( B ) WMM, number of nodes 56 with 382 edges with an average node degree of 13.6. Network analysed using STRINGdb. The network highlights proteins involved in different pathways curated by STRINGdb from KEGG and Reactome databases. Nodes are coloured according to pathways. The edge shows type of interactions, experimentally determined interactions derived from databases, predicted interactions such as gene neighbourhood, gene co-occurrence, and gene fusions, respectively, co-expression interactions, text-mining interactions, and homology; the thicker the edge, the higher the confidence obtained by the mentioned sources. ( C ) Using FishEnrichr [ 39 , 40 ] analyser KEGG Pathways and GO terms for Biological process showed proteins in different pathways. The length of the bar represents the significance of that specific gene-set or term. Brighter colours are highly significant. Figure 4. Gene interaction network for proteins with lower abundance in icefish ( A ) RMM and ( B ) WMM. ( A ) GeneMANIA gene–gene interaction network for protein abundance following the pattern N. rossii (+/+), T. bernacchii (+/+), C. rastrospinosus (−/+) and C. gunnari (−/−) in decreasing order of their protein abundance, laid out and visualised with Cytoscape, showing interaction strength (edge thickness), interaction type (colour-bottom right), multiple edges between nodes, protein score (node size) Black dots indicate query proteins, and grey dots depict neighbouring proteins. Figure 4. Gene interaction network for proteins with lower abundance in icefish ( A ) RMM and ( B ) WMM. ( A ) GeneMANIA gene–gene interaction network for protein abundance following the pattern N. rossii (+/+), T. bernacchii (+/+), C. rastrospinosus (−/+) and C. gunnari (−/−) in decreasing order of their protein abundance, laid out and visualised with Cytoscape, showing interaction strength (edge thickness), interaction type (colour-bottom right), multiple edges between nodes, protein score (node size) Black dots indicate query proteins, and grey dots depict neighbouring proteins. Figure 5. Network analysis of proteins lower expressed in icefish in comparison to closely related red-blooded species. ( A ) RMM DEPs, number of nodes 48 with 53 edges, the average node degree is 2.52 and ( B ) WMM, number of nodes 32 with 45 edges, the average node degree is 2.5. Network analysed using STRINGdb. The network highlights proteins involved in different pathways curated by string from Reactome database. The nodes are coloured according to the pathways determined with Reactome Pathway Database. The edge shows type of interactions, experimentally determined interactions derived from databases, predicted interactions such as gene neighbourhood, gene co-occurrence, and gene fusions, respectively, co-expression interactions, text-mining interactions and homology, thicker the edge higher the confidence obtained the mentioned sources. (C) Using FishEnrichr analyser KEGG Pathway and GO terms for biological process showed proteins involved in different pathways. Figure 5. Network analysis of proteins lower expressed in icefish in comparison to closely related red-blooded species. ( A ) RMM DEPs, number of nodes 48 with 53 edges, the average node degree is 2.52 and ( B ) WMM, number of nodes 32 with 45 edges, the average node degree is 2.5. Network analysed using STRINGdb. The network highlights proteins involved in different pathways curated by string from Reactome database. The nodes are coloured according to the pathways determined with Reactome Pathway Database. The edge shows type of interactions, experimentally determined interactions derived from databases, predicted interactions such as gene neighbourhood, gene co-occurrence, and gene fusions, respectively, co-expression interactions, text-mining interactions and homology, thicker the edge higher the confidence obtained the mentioned sources. (C) Using FishEnrichr analyser KEGG Pathway and GO terms for biological process showed proteins involved in different pathways. Table 1. Differentially expressed proteins (DEPs) among the four species in RMM—higher abundance in icefish. Table 1. Differentially expressed proteins (DEPs) among the four species in RMM—higher abundance in icefish. S. No. Protein Abundance—Higher in Icefish (Red Muscle Mitochondria) Relative Percent of Total Ion Area (Mapped)—Converted from Total Sum of Ion Area to Relative Percent of Total Ion Area Protein Name Gene Name Quant Significance H&B Multiple Test Corrected q -Value N. rossii T. bernacchii C. rastrospinosus C. gunnari Accession Number 1 26S protease regulatory subunit 4 isoform X1 & X2 psmc1a 1.25 × 10 −6 4.9 6.6 7 81.4 XP_010780333.1 2 Apolipoprotein B-100-like partial apobb 3.76 × 10 −19 3.2 3.3 27.9 65.6 XP_010781933.1 3 NAD(P) transhydrogenase mitochondrial-like nnt 2.95 × 10 −19 5.5 5.8 29.6 59.2 XP_010786020.1 4 Hyaluronan and proteoglycan link protein 1 hapln1 7.26 × 10 −20 9.1 5.2 30 55.7 XP_010767902.1 5 Sarcolemmal membrane-associated protein-like isoform X1 & X2 slmapa 9.73 × 10 −3 15.2 15.7 24 45.1 XP_010782086.1 6 ADP/ATP translocase 2-like slc25a5 1.03 × 10 −18 13 6.2 36.5 44.3 XP_010765274.1 7 Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex dlat 9.09 × 10 −12 15.9 16.3 27.3 40.5 XP_010773292.1 8 Alpha-2-macroglobulin-like partial a2ml 1.23 × 10 −4 14.7 22.1 23.1 40.1 XP_010771939.1 9 Inter-alpha-trypsin inhibitor heavy chain H4-like itih3a.2 1.37 × 10 −11 12.1 12.7 35.9 39.3 XP_010793736.1 10 Stress-70 protein mitochondrial-like hspa9 1.58 × 10 −5 20 18.3 33.7 28.1 XP_010766277.1 11 Epoxide hydrolase 1 ephx1l 3.79 × 10 −20 10.2 21.6 31.1 37.1 XP_010790338.1 12 Sorting and assembly machinery component 50 homolog samm50 1.65 × 10 −19 17.4 8.9 37.3 36.4 XP_010773400.1 13 Calcium-binding mitochondrial carrier protein Aralar1 slc25a12 1.21 × 10 −19 23 7.8 32.8 36.4 XP_010768357.1 14 Long chain fatty acyl CoA synthetase acsl1a 5.88 × 10 −7 2.6 19.1 42.1 36.1 AAK07470.1 15 Malonyl-CoA decarboxylase mitochondrial mlycd 3.73 × 10 −20 10.9 18.7 34.7 35.6 XP_010792494.1 16 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8 mitochondrial ndufb8 6.625 × 10 −7 13.1 19.5 31.9 35.6 XP_010779169.1 17 60S ribosomal protein L27a isoform X1 & X2 rpl27a 5.17 × 10 −20 10.7 14.8 38.9 35.6 XP_010790259.1 18 Fatty acid binding protein H8-isoform fabp3 2.43 × 10 −19 2.4 25.6 37.2 34.8 AAC60356.1 19 ATP-dependent 6-phosphofructokinase muscle type-like pfkm 2.02 × 10 −10 22.3 12.5 31 34.2 XP_010794434.1 20 Carnitine/acylcarnitine carrier protein slc25a20 1.2 × 10 −19 20 9.9 36.2 33.9 XP_010773584.1 21 ATP synthase subunit O atp5o 4.06 × 10 −8 24.6 13.4 29.1 32.9 XP_010772138.1 22 Proliferation-associated protein 2G4-like pa2g4b 4.31 × 10 −3 19 21.8 27.3 32 XP_010782747.1 23 ATP synthase subunit g mitochondrial atp5l 2.26 × 10 −7 23.1 10.6 34.4 31.9 XP_010779232.1 24 Voltage-dependent anion-selective channel protein 3 vdac3 4.6 × 10 −19 13.2 12.1 43.2 31.6 XP_010782516.1 25 ATP synthase subunit alpha mitochondrial atp5fa1 7.02 × 10 −9 22.2 14.9 31.7 31.2 XP_010779868.1 26 ATP synthase subunit beta mitochondrial zgc:163069 1.07 × 10 −8 24.7 13.4 31.1 30.8 XP_010765728.1 27 ATP synthase subunit gamma mitochondrial isoform X1 atp5g 2.53 × 10 −14 18.3 10 41.5 30.1 XP_010778067.1 28 60S ribosomal protein L35 rpl35 2.93 × 10 −15 14.9 15.2 40.2 29.6 XP_010790499.1 29 ATP synthase F(0) complex subunit B1 mitochondrial atp5pb 1.54 × 10 −15 23 11.6 36 29.5 XP_010786327.1 30 ATP synthase subunit delta mitochondrial atp5d 6.63 × 10 −3 18.8 23.4 28.4 29.4 XP_010775450.1 31 Prothrombin partial f2 7.41 × 10 −20 14.3 23.2 33.2 29.3 XP_010786167.1 32 ADP/ATP translocase 3 slc25a6 5.06 × 10 −12 23.5 13.6 33.9 29 XP_010784438.1 33 60S ribosomal protein L18a-like rpl18a 3.97 × 10 −8 18.2 18.8 34.1 28.9 XP_010774792.1 34 ATP synthase subunit d mitochondrial atp5pd 8.44 × 10 −20 25.2 8.6 37.5 28.7 XP_010766730.1 35 Malate dehydrogenase cytoplasmic-like partial mdh1aa 7.88 × 10 −16 13.2 16.9 42.1 27.8 XP_010766317.1 36 Cytochrome c oxidase subunit 5A mitochondrial isoform X2 cox5a 5.67 × 10 −20 16.5 9.2 46.4 27.8 XP_010766309.1 37 60S ribosomal protein L23 rpl23 1.13 × 10 −12 15.9 20.4 37 26.7 XP_010783746.1 38 Prohibitin phb 2.72 × 10 −6 18.1 18.4 39.1 24.5 XP_010773724.1 39 Ubiquinone biosynthesis protein COQ9 coq9 8.44 × 10 −11 17.2 17.6 42.1 23 XP_010793356.1 40 26S proteasome non-ATPase regulatory subunit 6 psmd6 3.76 × 10 −2 8.5 15 28.3 48.1 XP_010773228.1 41 Fragile X mental retardation syndrome-related protein 2 fxr2 7.06 × 10 −2 9.6 10.5 16.4 63.5 XP_010770797.1 42 Reticulon-4-interacting protein 1 homolog mitochondrial-like rtn4ip1 1.04 × 10 −1 19.8 20.5 28.7 31 XP_010790805.1 43 Kininogen-1 kng1 1.28 × 10 −1 13.7 16.6 25.8 43.8 XP_010787469.1 Table 2. DEPs between WMM with increased abundance in icefish specifically seen upregulated in icefish Champsocephalus gunnari . Table 2. DEPs between WMM with increased abundance in icefish specifically seen upregulated in icefish Champsocephalus gunnari . Protein Abundance—Higher in Icefish (White Muscle) Relative Percent of Total Ion Area (Mapped)—Converted from Total Sum of Ion Area to Relative Percent of Total Ion Area S. No. Protein Name Gene Name Quant Significance H&B Multiple Test Corrected q -Value N. rossii T. bernacchii C. rastrospinosus C. gunnari Accession Number 1 Myosin regulatory light chain 2 skeletal muscle isoform-like mylpfb 3.42 × 10 −19 1 2.2 2.3 94.4 XP_010770965.1 2 Myozenin-1 isoform X1 & X2 myoz1b 1.54 × 10 −7 0 7.8 13.3 78.9 XP_010791910.1 3 Heat shock protein beta 1 hspb1 9.48 × 10 −5 9.9 4.1 11.5 74.6 XP_010788098.1 4 60S ribosomal protein L35 rpl35 4.58 × 10 −20 3.4 7.9 32.7 56 XP_010790499.1 5 40S ribosomal protein S16 isoform X1 rps16 9.29 × 10 −3 12.3 16.9 17.9 52.8 XP_010773777.1 6 60S ribosomal protein L7 rpl7 1.08 × 10 −6 6.9 7.8 33.1 52.3 XP_010770361.1 7 Fragile X mental retardation syndrome-related protein 2 fxr2 6.55 × 10 −4 4.6 11.6 32.2 51.6 XP_010770797.1 8 40S ribosomal protein S12 rps12 1.13 × 10 −4 8.4 13.8 27 50.8 XP_010783785.1 9 60S ribosomal protein L30 rpl30 8.33 × 10 −5 3.1 22.6 24 50.3 XP_010765856.1 10 60S ribosomal protein L12 isoform X2 rpl12 5.13 × 10 −20 9.9 11.7 28.5 49.8 XP_010779104.1 11 Reticulon rtn1a 5.51 × 10 −20 14.9 13 22.7 49.4 XP_010790870.1 12 Palladin-like palld 1.07 × 10 −14 2.7 15.9 32.1 49.2 XP_010785200.1 13 60S ribosomal protein L9 rpl9 4.70 × 10 −20 4.2 3.4 43.7 48.7 XP_010776310.1 14 AMP deaminase 1 isoform X1 & X2 ampd1 1.65 × 10 −19 18.6 10.9 22.8 48.4 XP_010793467.1 15 ADP/ATP translocase 3 slc25a5 3.22 × 10 −10 7.8 10.6 33.7 47.8 XP_010784438.1 16 40S ribosomal protein S13 rps13 9.87 × 10 −4 13.1 10.6 29.1 47.3 XP_010794693.1 17 40S ribosomal protein S8-like partial rps8 2.91 × 10 −10 9.1 11.8 33 46 XP_010787537.1 18 Alpha-actinin-2 actn2 1.42 × 10 −8 12.1 18.2 23.6 46 XP_010791686.1 19 Kelch-like protein 41b klhl41b 5.57 × 10 −20 4.2 11.6 38.5 45.7 XP_010791686.1 20 60S ribosomal protein L6 rpl6 4.536 × 10 −20 7 11.3 36.3 45.4 XP_010774286.1 21 40S ribosomal protein S5 rps5 7.75 × 10 −4 17 12.2 25.5 45.3 XP_010782543.1 22 Cytochrome c oxidase subunit II mt-co2 5.91 × 10 −13 2.6 26.8 25.9 44.7 XP_010783741.1 23 40S ribosomal protein S25 rps25 6.64 × 10 −3 13 14.5 28.4 44.2 YP_004581500.1 24 60S ribosomal protein L11 rpl11 4.98 × 10 −20 15.6 11.7 29.1 43.7 XP_010776714.1 25 Voltage-dependent anion-selective channel protein 2 vdac2 8.76 × 10 −7 15.6 10.6 30.4 43.5 XP_010779161.1 26 40S ribosomal protein S4 rps4x 6.41 × 10 −20 7.5 16 33.6 43 XP_010767141.1 27 40S ribosomal protein S2 rps2 5.4 × 10 −20 6.8 11.4 39 42.8 XP_010792965.1 28 60S ribosomal protein L10a rp10a 2.26 × 10 −14 14.8 15.1 29.7 40.4 XP_010783756.1 29 40S ribosomal protein S9 rps9 4.40 × 10 −8 12.5 17.9 29.3 40.3 XP_010791484.1 30 ATP synthase subunit g atp5l 4.66 × 10 −20 18.7 11.6 32.7 37 XP_010786813.1 31 Vinculin vcla 1.15 × 10 −7 18.7 11.6 32.7 37 XP_010794136.1 32 60S ribosomal protein L13 rpl13 5.51 × 10 −11 8.2 16 39.4 36.5 XP_010787927.1 33 Fructose-1 6-bisphosphatase isozyme 2-like fbp2 5.63 × 10 −20 9.8 26 28.1 36.1 XP_010789836.1 34 40S ribosomal protein SA isoform X2 rpsa 6.10 × 10 −20 10 17.7 37.1 35.3 XP_010781656.1 35 Succinyl-CoA ligase suclg1 6.66 × 10 −11 5.5 10.2 49.4 35 XP_010768032.1 36 Tubulin alpha chain-like isoform X1 & X2 tuba8l2 4.49 × 10 −4 11.3 23.9 29.9 34.9 XP_010778226.1 37 60S ribosomal protein L23a rpl23a 5.29 × 10 −8 3.5 9.8 56.9 34.8 XP_010766070.1 38 NADH-ubiquinone oxidoreductase mt-nd1 8.21 × 10 −7 3.5 9.8 51.9 34.7 XP_010791811.1 39 Alpha-enolase-like eno1a 4.27 × 10 −4 13 22.3 30.3 34.5 XP_010777506.1 40 Isocitrate dehydrogenase idh1 1.22 × 10 −19 20.6 11 35.7 32.6 XP_010765339.1 41 26S proteasome non-ATPase regulatory subunit 12 psmd12 1.19 × 10 −3 10 11.8 47.6 30.6 XP_010791048.1 42 ATP synthase F(0) complex subunit B1 atp5pb 2.06 × 10 −10 19 6.4 44.2 30.2 XP_010777584.1 43 Peptidyl-prolyl cis-trans isomerase-like pplb 1.02 × 10 −3 8 27.2 35.3 29.5 XP_010786327.1 44 Malate dehydrogenase mdh1aa 1.71 × 10 −19 15.1 9 46.6 29.4 XP_010790691.1 45 ATP synthase subunit O atp5o 5.16 × 10 −4 16.1 9.4 45.9 28.6 XP_010780749.1 46 NAD(P) transhydrogenase nnt 5.81 × 10 −8 15.9 16.7 39 28.3 XP_010772138.1 47 Glycogen phosphorylase muscle form-like pygma 8.47 × 10 −6 17.7 25.3 30 26.9 XP_010776087.1 48 Ubiquitin carboxyl-terminal hydrolase 5 isoform X1 usp5 4.8 × 10 −4 9.3 19.1 44.8 26.7 XP_010788355.1 49 Cytochrome b-c1 complex subunit 2 uqcrfs1 4.32 × 10 −4 11.7 10.4 52.9 25 XP_010769500.1 50 ATP synthase subunit gamma atp5g 1.41 × 10 −12 13.4 12.3 49.6 24.7 XP_010784571.1 51 ATP synthase subunit beta zgc:163069 9.98 × 10 −16 17.5 12.4 46.2 23.8 XP_010778067.1 52 Pyruvate kinase PKM pkma 5.13 × 10 −19 11 10.3 56 22.7 XP_010765728.1 53 Vitellogenin-1-like vtg2 1.38 × 10 −2 0 2 93.6 4.4 XP_010766216.1 54 Proteasome subunit alpha type-7-like psma8 1.96 × 10 −2 9.6 11.7 55.1 23.6 XP_010779640.1 55 Guanine nucleotide-binding protein subunit beta-2-like 1 gnb2l1 1.57 × 10 −2 13.2 21 29.6 36.2 XP_010783619.1 56 ATP-dependent 6-phosphofructokinase muscle type-like pfkmb 1.84 × 10 −2 16.7 17.3 26.1 39.9 XP_010780163.1 57 Inter-alpha-trypsin inhibitor heavy chain H3-like zgc:110377 1.92 × 10 −2 0 14.4 46.5 39.1 XP_010782695.1 Table 3. DEPs in RMM with decreased abundance in icefish specifically seen downregulated in icefish Champsocephalus gunnari . Table 3. DEPs in RMM with decreased abundance in icefish specifically seen downregulated in icefish Champsocephalus gunnari . Protein Abundance—Lower in Icefish (Red Muscle) Relative Percent of Total Ion Area (Mapped)—Converted from Total Sum of Ion Area to Relative Percent of Total Ion Area S. No. Protein Name Gene Name Quant Significance H&B Multiple Test Corrected q -Value N. rossii T. bernacchii C. rastrospinosus C. gunnari Accession Number 1 Hemoglobin subunit alpha-1 hbae1 1.88 × 10 −19 60 38.7 0.8 0.5 NP_001290227.1 2 Calsequestrin-1 casq1 6.08 × 10 −20 33.3 44.4 18.6 3.7 XP_010782377.1 3 Perilipin-3 plin3 1.53 × 10 −19 48.8 35.6 11.1 4.5 XP_010778108.1 4 creatine kinase S-type mitochondrial-like ckmt2a 4.35 × 10 −19 71.4 22.4 1.4 4.8 XP_010772488.1 5 Transferrin tfa 8.36 × 10 −20 34 54.2 17.3 5.5 CAL92189.1 6 Dehydrogenase/reductase SDR family member 7C dhrs7cb 3.01 × 10 −9 68.9 18.2 7.1 5.7 XP_010784042.1 7 Myosin-binding protein H-like mybpha 9.09 × 10- 20 66.6 20.7 5.9 6.8 XP_010764981.1 8 Band 3 anion transport protein slc4a1 1.91 × 10 −8 39 52 2.1 6.9 XP_010785995.1 9 Cytochrome c oxidase subunit 4 isoform 2 mitochondrial-like cox4i2 5.79 × 10 −20 60.1 22.5 9.6 7.7 XP_010770791.1 10 Titin-like ttna 2.47 × 10 −11 50.9 21.6 19.4 8.1 XP_010787367.1 11 Glutaryl-CoA dehydrogenase mitochondrial-like gcdh 4.92 × 10 −20 34 28.8 28.2 9 XP_010795730.1 12 Fibrillin-1-like isoform X1 fbn2a 5.14 × 10 −20 67.5 17.5 6 9 XP_010767938.1 13 heme oxygenase 2 hmox1 1.18 × 10 −4 48.5 20.6 21.3 9.7 XP_010786435.1 14 NADP-dependent malic enzyme me1 1.29 × 10 −19 33.9 40.3 16 9.8 XP_010776993.1 15 Pyruvate dehydrogenase phosphatase regulatory subunit pdpr 8.30 × 10 −9 24.9 48.6 15.4 11.1 XP_010773093.1 16 Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 1 rpn1 7.17 × 10 −12 38.5 30.1 20.2 11.2 XP_010777725.1 17 CDGSH iron-sulfur domain-containing protein 1 zgc:110843 4.54 × 10 −20 41 36 11.6 11.5 XP_010767760.1 18 Glutamate dehydrogenase gdh 3.06 × 10 −19 29.9 48.6 11.1 11.9 P82264.1 19 Thioredoxin-dependent peroxide reductase mitochondrial prdx3 6.46 × 10 −20 31.2 29.5 27.2 12.1 XP_010779546.1 20 malate dehydrogenase mdh 1.178 × 10 −12 32.5 37 18.4 12.1 XP_010765488.1 21 Cytochrome c cycsb 5.55 × 10 −20 42.8 28.7 16.1 12.5 XP_010792793.1 22 Troponin T fast skeletal muscle isoforms-like isoform X1 to X3 tnnt3a 4.89 × 10 −20 37.2 29.6 20.5 12.7 XP_010784864.1 23 Superoxide dismutase [Mn] mitochondrial sod2 1.01 × 10 −10 42 33.4 11.5 13.1 XP_010771234.1 24 Carnitine O-acetyltransferase crat 6.46 × 10 −13 29.1 38.8 19 13.1 XP_010795330.1 25 PDZ and LIM domain protein 7 ENSDARG00000030638 1.44 × 10 −8 45.5 21 20.3 13.3 XP_010765699.1 26 Protein FAM162B-like fam162a 4.13 × 10 −4 41.5 32 13 13.6 XP_010783349.1 27 Aconitate hydratase mitochondrial aco1 4.14 × 10 −19 45.3 26.8 14 14 XP_010781940.1 28 Retinol dehydrogenase 13-like isoform X1 & X2 wu:fd55e03 2.59 × 10 −13 42.1 26.2 17.6 14.1 XP_010791045.1 29 Myosin-binding protein C slow-type isoform X1 to X17 mybpc 2.39 × 10 −3 39.8 27.3 18.8 14.1 XP_010774860.1 30 Lumican lum 2.21 × 10 −7 47.8 26.9 11.3 14.1 XP_010795529.1 31 Retinol dehydrogenase 13-like isoform X1 rdh13 2.59 × 10 −13 26.2 42.1 17.6 14.1 XP_010791045.1 32 PDZ and LIM domain protein 7-like isoform X2 ENSDARG00000030638 4.70 × 10 −20 40.6 26.1 18.9 14.4 XP_010785930.1 33 Glycogen phosphorylase pygm 7.81 × 10 −20 30.6 44.1 10.9 14.4 XP_010788472.1 34 Alpha-aminoadipic semialdehyde dehydrogenase aldh7a1 1.25 × 10 −19 36.3 28.9 20 14.7 XP_010772035.1 35 Myozenin-1-like myoz1a 7.07 × 10 −20 46.5 26.8 12 14.7 XP_010764663.1 36 Collagen alpha-1(I) chain-like col1a1a 9.40 × 10 −20 52.6 27.3 5.3 14.8 XP_010768975.1 37 Peroxiredoxin-5 mitochondrial prdx5 8.32 × 10 −7 30.5 28.9 25.2 15.4 XP_010783999.1 38 Short-chain specific acyl-CoA dehydrogenase mitochondrial acads 4.54 × 10 −8 32.5 26.7 25.1 15.8 XP_010779541.1 39 Troponin alpha-3 chain-like tnnt3b 1.56 × 10 −19 36.9 35.9 11 16.1 XP_010771394.1 40 Creatine kinase M-type ckmb 4.11 × 10 −5 34.8 25.6 23.3 16.3 XP_010791917.1 41 Glycerol-3-phosphate dehydrogenase mitochondrial gpd2 1.13 × 10 −10 42.6 23.5 17 16.9 XP_010791177.1 42 electron transfer flavoprotein subunit beta etfb 2.38 × 10 −5 33.9 24.8 24.2 17.1 XP_010791064.1 43 1 4-alpha-glucan-branching enzyme gbe1b 2.20 × 10 −10 28.1 44.4 10.4 17.1 XP_010775191.1 44 Ubiquitin carboxyl-terminal hydrolase 5 isoform X1 & X2 usp5 8.40 × 10 −5 34.9 25.9 21.1 18 XP_010769508.1 45 Methylmalonyl-CoA mutase mitochondrial mut 2.48 × 10 −4 33.7 26.7 21.5 18 XP_010784587.1 46 probable acyl-CoA dehydrogenase 6 zgc:85777 1.82 × 10 −3 31.3 26.9 23.2 18.6 XP_010772948.1 47 Alpha-actinin-3 actn3b 5.52 × 10 −19 39.5 28.5 13.3 18.7 XP_010784415.1 48 Carbonic anhydrase 1 ca1 7.88 × 10 −20 49.4 20 10.9 19.6 XP_010765900.1 Table 4. DEPs between WMM with decreased abundance in the icefish. Table 4. DEPs between WMM with decreased abundance in the icefish. Protein Abundance—Lower in Icefish (White Muscle) Relative Percent of Total Ion Area (Mapped)—Converted from Total Sum of Ion Area to Relative Percent of Total Ion Area S. No. Protein Name Gene Name Quant Significance H&B Multiple Test Corrected q -Value N. rossii T. bernacchii C. rastrospinosus C. gunnari Accession Number 1 Calreticulin calr 5.72 × 10 −3 75.4 4.7 19.8 0 XP_010773398.1 2 Creatine kinase S-type mitochondrial-like ckmt2a 1.19 × 10 −19 78.2 14.8 6.4 0.7 XP_010772488.1 3 Myosin heavy chain fast skeletal 13 zgc:66156 3.68 × 10 −3 37.8 34.7 26.6 0.9 XP_010791001.1 4 Prothrombin partial f2 7.77 × 10 −4 37.3 30.3 31.2 1.1 XP_010786167.1 5 Fibronectin fn1a 1.33 × 10 −5 33.1 30.2 34.9 1.8 XP_010794764.1 6 Transmembrane protease serine 2-like LOC571565 6.81 × 10 −3 81.2 16.8 0 2 XP_010778161.1 7 Hemoglobin subunit zeta hbz 2.98 × 10 −4 80.5 16.4 0.3 2.5 XP_010778322.1 8 Fibrinogen alpha chain-like fga 2.67 × 10 −5 51.4 39.8 5.2 2.8 XP_010771898.1 9 Alpha globin hbaa1 7.77 × 10 −20 79.6 16.5 0.4 3.3 AAC25100.1 10 Beta-globin ba-1 7.45 × 10 −9 87.5 9.1 0 3.4 AAC60372.1 11 Haemoglobin hb 7.33 × 10 −9 87.5 9.1 0 3.4 NP_001290226.1 12 Ryanodine receptor 1- ryr1a 3.16 × 10 −4 54.5 19.7 21.1 4.5 XP_010787188.1 13 Keratin type I cytoskeletal 19-like zgc:153629 8.84 × 10 −20 54.7 31.8 8.9 4.6 XP_010787448.1 14 Myosin heavy chain fast skeletal muscle-like myhb 4.58 × 10 −12 46.7 27.6 19.2 6.5 NP_001290213.1 15 Malate dehydrogenase cytoplasmic mdh1aa 5.56 × 10 −7 54.8 24.1 13.3 7.8 XP_010765488.1 16 Apolipoprotein A apoa1 1.282 × 10 −19 54.4 20 16.1 9.3 XP_010792180.1 17 Myomesin-1-like myom1 1.31 × 10 −19 31.1 29.8 21.8 17.3 XP_010789743.1 18 Betaine-homocysteine S-methyltransferase 1-like bhmt 7.32 × 10 −20 53.1 20.8 14.4 11.6 XP_010794476.1 19 Collagen alpha-1(I) chain-like col1a1b 6.56 × 10 −4 37.2 34.6 15.8 12.4 XP_010768975.1 20 Hemopexin zgc:152945 3.14 × 10 −6 40.7 26.6 19.7 13 XP_010788340.1 21 T-complex protein 1 subunit theta cct8 3.34 × 10 −6 60.6 18.2 7.4 13.9 NP_001290219.1 22 Transitional endoplasmic reticulum ATPase-like vcp 3.10 × 10 −3 51.4 20.5 12.7 15.4 XP_010770092.1 23 40S ribosomal protein S11 rps11 8.261 × 10 −4 43.2 32.7 8.7 15.5 XP_010791578.1 24 Titin-like partial ttna 1.66 × 10 −3 32.9 28.7 21.1 17.2 XP_010790363.1 25 Calmodulin calm1a 1.197 × 10 −10 36.2 30.9 14 18.9 XP_010768524.1 26 40S ribosomal protein S3a rps3a 9.93 × 10 −12 35.1 30.1 15.3 19.5 XP_010773841.1 27 Obscurin isoform X2 obscnb 2.1 × 10 −2 36.8 30.2 14.9 18.1 XP_010790854.1 28 Transferrin tfa 3.14 × 10 −2 36.3 33.5 22.7 7.6 CAL92189.1 29 Collagen alpha 1(XII) chain isoform X1, X2, X3, X4 & X5 col12a1a 8.53 × 10 −2 68.8 18.2 8.5 4.5 XP_010777236.1 30 Nebulin-like isoform X4 neb 2.23 × 10 −1 54.2 23.8 9.2 12.7 XP_010772593.1 31 Myosin-binding protein C slow-type isoform X1 to X17 mybpc3 1.31 × 10 −1 45.6 26.9 12.6 14.9 XP_010774870.1 32 Collagen alpha-2(I) chain isoform X1 col1a2 2.91 × 10 −1 54.6 20.8 9.6 14.9 XP_010772950.1
https://www.mdpi.com/2079-7737/11/8/1118/xml
4 Undervalued Retailers - Miscellaneous Specialty Stocks for Thursday, March 23 | AAII Discover the top 4 undervalued Retailers - Miscellaneous Specialty stocks for Thursday, March 23 based on AAII’s Stock Grades. 4 Undervalued Retailers - Miscellaneous Specialty Stocks for Thursday, March 23 Featured Tickers: BBW BBWI SPWH WOOF Based on key financial metrics such as theprice-to-salesratio, shareholder yield and the price-earnings ratio, the following 4 stocks made the list for top value stocks in the Retailers - Miscellaneous Specialty industry. Those looking for value stocks to add to their portfolio may want to use this list as a starting point for further investment research. Latest Retailers - Miscellaneous Specialty Stock News Before choosing which top Retailers - Miscellaneous Specialty stock to buy, be sure to conduct proper due diligence: analyze various financial metrics and look at historical data, public statements and news coverage. Our fundamental outlook for the specialty stores sub-industry is neutral, as the constituents of S&P Composite 1500 Specialty Stores Index are a mixed bag. Store openings will continue to be the rocket fuel of their multifaceted growth narratives. On the other hand, Amazon has wreaked havoc on many small-cap names like Office Depot and Michaels. Taking a deeper look at FIVE, we think it is wellpositioned to capitalize on the widening wealth gap. Even with the passage of three rounds of stimulus checks, the U.S. poverty rate continues to climb almost every month, jumping from 9.3% in June 2020 to 11.3% in January 2021, and marking the single largest year-over-year increase since the government began tracking the rate in 1960. As lower-income households are seeing fewer and fewer opportunities to build wealth, they are leaning more and more on off-price retailers to fulfill discretionary and non-discretionary needs. Looking at TSCO, we believe the market underappreciates structural and sustainable tailwinds, namely the significant potential for market gains as 2020 trends like all-time high pet ownership (livestock pet products 47% of sales in 2019), rural revitalization, and self-reliant lifestyle movement persist through 2021. We see robust omni-solutions (nation’s first major general merchandiser to expand same-day delivery to all stores; Q4 2020 marked third consecutive quarter of “triple-digit” e-commerce growth) and financial flexibility supporting its market share seize (90 new store openings we see in 2021). In the case of ULTA, we believe it is uniquely positioning as a Covid-19 winner (capturing market share) and reopening play (easier year over year comparisons). While Covid-19 survivors have been forced to drastically cut expenses, ultimately poorly positioning them to capitalize on secular changes in consumer behavior, ULTA has had luxury of playing offense, creating sustainable competitive advantages, including investments to bolster artificial intelligence (GLAMlab), partnerships (Target, which should allow ULTA to capitalize on TGT’s strong comps, mitigate competitive pressures and broaden target market), and omni-solutions (doubled digital sales in FY 21; rolled out curbside within a month of lockdown). Why Focus on Undervalued Retailers - Miscellaneous Specialty Stocks? Value investors seek to buy stocks at a discount to their intrinsic value. Long-term returns show that such strategies are advantageous. Value stocks, as a group, tend to outperform growth stocks over extended periods of time. Typically, value investors perform financial analysis of numerous metrics, don’t follow the herd and are long-term investors.AAII’sA+ InvestorValue Grade is derived from a stock’s Value Score. The Value Score is the percentile rank of the average of the percentile ranks of the price-to-sales ratio, price-earnings ratio, enterprise-value-to-EBITDA (EV/EBITDA) ratio, shareholder yield, price-to-book-value ratio and price-to-free-cash-flow ratio. The score is variable, meaning it can consider all six ratios or, should any of the six ratios not be valid, the remaining ratios that are valid. To be assigned a Value Score, stocks must have a valid (non-null) ratio and corresponding ranking for at least two of the six valuation ratios. What Goes Into AAII’s Value Grade? Stock evaluation requires access to huge amounts of data as well as the knowledge and time to sift through it all, make sense of financial ratios, read income statements and analyze recent stock movement. AAII createdA+ Investor, a robust data suite that condenses data research in an actionable and customizable way suitable for investors of all knowledge levels, to help investors with that task.AAII’s proprietary stock grades come withA+ Investor. These offer intuitive A–F grades for more than just value. It is possible for a stock to appear cheap based on one valuation metric but appear expensive on another. It is also possible for one valuation ratio to be associated with outperforming stocks during certain periods of time but not others. Some stocks may even have null values for certain metrics like the price-earnings ratio or theprice-to-bookratio but not others. An example of this would be a company with losses instead of profits or a negative book value because of heavy borrowing. Negative earnings or book value result in non-meaningful ratios that are left blank or null.Click the button below to learn more about A+ Investor and subscribe today. 4 Undervalued Retailers - Miscellaneous Specialty Stocks Of course, there are countless value stocks that are worth mentioning, but this is a concise list of the top 4 undervalued stocks in the Retailers - Miscellaneous Specialty industry for Thursday, March 23, 2023. Let’s take a closer look at their individual scores to see how they measure up against each other and the Retailers - Miscellaneous Specialty industry median. The Value Grade is assigned based on how each stock’s composite valuation compares to all other stocks.The process for assigning grades starts with each variable for a given stock. The percentile rankings for all valid ratios that a stock has are calculated. So, for instance, a stock could have a price-to-book ranking in the 43rd percentile, a price-earnings ranking in the 67th percentile, a price-to-sales ranking in the 23rd percentile, etc. Then, those rankings are averaged for each stock. (A minimum of two valid variables are required, though all six will be used if available.)Once the average of the individual variables is calculated, that average is ranked against all stocks. Put another way, each stock’s composite valuation is compared to all other stocks. These ranks are then sorted into quintiles from the cheapest 20% (a grade of A) to the most expensive 20% (a grade of F).As always, we recommend that you conduct proper due diligence and research before investing in any security. We also suggest that investors utilize numerous grades, not just value, when it comes to deciding whether a company is a good fit for theirallocationneeds. Build-A-Bear Workshop, Inc’s Value Grade Value Grade: Metric Score BBW Industry Median Price/Sales 28 0.74 0.57 Price/Earnings 22 7.5 17.9 EV/EBITDA 11 3.3 8.9 Shareholder Yield 13 6.6% 0.9% Price/Book Value 79 3.55 1.54 Price/Free Cash Flow 87 71.1 42.9 Build-A-Bear Workshop, Inc. is a multi-channel retailer of plush animals and related products. The Company operates through three segments, namely direct-to-consumer (DTC), commercial, and international franchising. Direct-to-consumer segment includes the operations of corporately managed locations and other retail delivery operations in the United States, Canada, Puerto Rico, Ireland, and the United Kingdom, including its e-commerce sites. Commercial segment includes the Company's transactions with other businesses, mainly consisting of licensing the Company's intellectual properties for third-party use and wholesale activities. International franchising segment includes the licensing activities of the Company's franchise agreements with store locations in Asia, Australia, the Middle East, Africa, and South America. The Company operates approximately 347 corporately managed locations and has 66 franchised stores operating internationally.Stocks with a Value Score from 81 to 100 are considered deep value, those with a score between 61 and 80 are value and so on.Build-A-Bear Workshop, Inc has a Value Score of 66, which is considered to be undervalued.When you look at Build-A-Bear Workshop, Inc’s price-to-sales ratio at 0.74 compared to the industry median at 0.57, this company has a higher price relative to revenue compared to its peers. This could make Build-A-Bear Workshop, Inc’s stock less attractive for value investors.Build-A-Bear Workshop, Inc’s price-earnings ratio is 7.50 compared to the industry median at 17.90. This means it has a lower share price relative to earnings compared to its peers. This could make Build-A-Bear Workshop, Inc more attractive for value investors.Now, let’s assess Build-A-Bear Workshop, Inc’s EV/EBITDA ratio, also known as enterprise multiple. At 3.3, when compared to the industry median of 8.9, the company may be considered undervalued in relation to its peers. Value investors could use the enterprise multiple to identify stocks that are considered overvalued or undervalued relative to their industry.Shareholder yield is the sum of a stock’s dividend yield (paid over previous 12 months minus special dividends) and the percentage of net share buybacks over the previous 12 months. Build-A-Bear Workshop, Inc’s shareholder yield is higher than its industry median ratio of 0.90%. Value investors may look for an attractive shareholder yield because it can be a powerful tool for identifying if the company has a good management team.As one of the most common value metrics, the price-to-book ratio evaluates a company’s current market price relative to its book value. Build-A-Bear Workshop, Inc’s price-to-book ratio is higher than its industry median ratio of 1.54. This could make Build-A-Bear Workshop, Inc less attractive to investors looking for a new addition to their portfolio.Lastly, let’s take a look at Build-A-Bear Workshop, Inc’s price-to-free-cash-flow ratio (P/FCF), which can indicate a company’s market value relative to its operating cash flow. Build-A-Bear Workshop, Inc’s price-to-free-cash-flow ratio is higher than its industry median ratio of 42.90. This could make Build-A-Bear Workshop, Inc less attractive because the higher P/FCF ratio indicates that Build-A-Bear Workshop, Inc is undervalued. The P/FCF ratio metric can also be viewed over a long-term time frame to see if the company's cash flow to share price value is generally improving or worsening. Bath & Body Works Inc’s Value Grade Value Grade: Metric Score BBWI Industry Median Price/Sales 36 1.06 0.57 Price/Earnings 34 10.2 17.9 EV/EBITDA 45 8.9 8.9 Shareholder Yield 4 14.2% 0.9% Price/Book Value na na 1.54 Price/Free Cash Flow 43 12.6 42.9 Bath & Body Works, Inc. is an omnichannel retailer. The Company sells merchandise through its Company-operated retail stores in the United States and Canada, and through its Websites and other channels, under the Bath & Body Works, White Barn and other brand names. The Company's international business is primarily conducted through franchise, license, and wholesale partners. It offers a range of fragrances for the body and home, including collections for fine fragrance mist, body lotion and body cream, 3-wick candles, home fragrance diffusers and liquid hand soap. Its products are differentiated through a combination of fragrance and packaging. It also sells products under its sub brands, including White Barn and Aromatherapy. Its merchandise is sold through about 1,802 Company-operated stores and e-commerce sites in the United States and Canada, and in 427 stores and 31 e-commerce sites in more than 45 other countries operating under franchise, license, and wholesale arrangements.Stocks with a Value Score from 81 to 100 are considered deep value, those with a score between 61 and 80 are value and so on.Bath & Body Works Inc has a Value Score of 79, which is considered to be undervalued.Bath & Body Works Inc’s price-earnings ratio is 10.2 compared to the industry median at 17.9. This means that it has a lower price relative to its earnings compared to its peers. This makes Bath & Body Works Inc more attractive for value investors.You can read more about Bath & Body Works Inc’s key financial metrics like shareholder yield, price-to-free-cash-flow and EV/EBITDA ratio, or learn more about its Momentum and Growth Grades, by subscribing toA+ Investor. Sportsmans Warehouse Holdings Inc’s Value Grade Value Grade: Metric Score SPWH Industry Median Price/Sales 8 0.21 0.57 Price/Earnings 7 3.9 17.9 EV/EBITDA 14 3.7 8.9 Shareholder Yield 5 12.5% 0.9% Price/Book Value 34 1.07 1.54 Price/Free Cash Flow 58 21.0 42.9 Sportsman's Warehouse Holdings, Inc. is an outdoor sporting goods retailer. The Company has an outdoor specialty store base in the Western United States and Alaska. It operates approximately 127 stores in 29 states, which are located in power, neighborhood and lifestyle centers. Its stores are organized into six departments, the Camping department offers backpacks, camp essentials, canoes and kayaks, outdoor cooking equipment, sleeping bags, tents and tools. The Apparel department offers jackets, outerwear, sportswear, technical gear and workwear. The Fishing department provides bait, fishing rods, flotation items, fly fishing, lures, and small boats. The Footwear department offers boots, socks, and casual shoes. The Hunting and Shooting department offers ammunition, archery items, firearms, firearms safety and storage, reloading equipment, and shooting gear. The Optics, Electronics, Accessories, and Other department offers gift items, lighting, binoculars, two-way radios and more.Stocks with a Value Score from 81 to 100 are considered deep value, those with a score between 61 and 80 are value and so on.Sportsmans Warehouse Holdings Inc has a Value Score of 94, which is considered to be undervalued.Sportsmans Warehouse Holdings Inc’s price-earnings ratio is 3.9 compared to the industry median at 17.9. This means that it has a lower price relative to its earnings compared to its peers. This makes Sportsmans Warehouse Holdings Inc more attractive for value investors.Sportsmans Warehouse Holdings Inc’s price-to-book ratio is higher than its peers. This could make Sportsmans Warehouse Holdings Inc less attractive for value investors when compared to the industry median at 1.54.You can read more about Sportsmans Warehouse Holdings Inc’s key financial metrics like shareholder yield, price-to-free-cash-flow and EV/EBITDA ratio, or learn more about its Momentum and Growth Grades, by subscribing toA+ Investor. Petco Health and Wellness Company Inc’s Value Grade Value Grade: Metric Score WOOF Industry Median Price/Sales 15 0.37 0.57 Price/Earnings 70 25.6 17.9 EV/EBITDA 45 8.8 8.9 Shareholder Yield 54 (0.6%) 0.9% Price/Book Value 29 0.96 1.54 Price/Free Cash Flow na na 42.9 Petco Health and Wellness Company, Inc. is a pet health and wellness company. The Company is focused on improving the lives of pets, pet parents and its Petco partners. The Company offers various services, including in-store events, grooming, positive dog training, veterinary services, Petco insurance, pet adoption and a resource center. The Company also offers a veterinary service platform, which includes full-service veterinary hospitals, Vetco clinics, and tele-veterinarian services. The Company operates approximately 1,500 pet care centers across the United States (U.S), Mexico and Puerto Rico, which also includes a network of more than 150 in-store veterinary hospitals, and offers a complete resource for pet health and wellness through the Petco.com Website and the Petco app. The Company also operates an independent nonprofit organization, Petco Foundation.Stocks with a Value Score from 81 to 100 are considered deep value, those with a score between 61 and 80 are value and so on.Petco Health and Wellness Company Inc has a Value Score of 61, which is considered to be undervalued.Petco Health and Wellness Company Inc’s price-earnings ratio is 25.6 compared to the industry median at 17.9. This means that it has a higher price relative to its earnings compared to its peers. This makes Petco Health and Wellness Company Inc less attractive for value investors.Petco Health and Wellness Company Inc’s price-to-book ratio is higher than its peers. This could make Petco Health and Wellness Company Inc less attractive for value investors when compared to the industry median at 1.54.You can read more about Petco Health and Wellness Company Inc’s key financial metrics like shareholder yield, price-to-free-cash-flow and EV/EBITDA ratio, or learn more about its Momentum and Growth Grades, by subscribing toA+ Investor. Other Retailers - Miscellaneous Specialty Stock Grades Value is just one of the five Stock Grades included in ourA+ Investorservice. AAII members can see the top-graded stocks—those with grades of A or B for value, growth, momentum, earnings estimate revisions and quality—on the A+ Stock Grades Screener.Also, if you want full access to all of AAII’s premium services, you can subscribe to one convenient bundled plan called AAII Platinum where you can try outA+ Investor, AAII Dividend Investing, the Stock Superstars Report, Growth Investing and VMQ Stocks. With the other premium services, you can dive deep into additional metrics, portfolios, commentary and information about Retailers - Miscellaneous Specialty stocks as well as other industrys. Choosing Which of the 4 Best Retailers - Miscellaneous Specialty Stocks Is Right for You Choosing which value stocks to invest in will ultimately depend on your individual goals and allocation; however, comparing similar value stocks in the same industry can help you analyze which might be better investments for you in the long run. So, let’s take a look at the Value Grade for all of our stocks. Build-A-Bear Workshop, Inc stock has a Value Grade of B. Bath & Body Works Inc stock has a Value Grade of B. Sportsmans Warehouse Holdings Inc stock has a Value Grade of A. Petco Health and Wellness Company Inc stock has a Value Grade of B. Now that you have a bit more background about each of the 4 undervalued stocks in the Retailers - Miscellaneous Specialty industry as well as their overall grades, it’s time for you to conduct additional research to see if these could fit your portfolio needs based on your goals and risk tolerance. AAII can help you figure out both and identify which investments align with what works best for you.We do so through a program of education that teaches you to invest for yourself and become an effective manager of your own wealth—no more relying on others for your financial independence. You can rely on AAII for timeless articles on financial planning and stock-picking, unbiased research and actionable analysis that makes you a better investor.A+ Investoradds to that qualitative teaching by giving you a powerful data suite that helps you whittle down investment decisions to find stocks,exchange-traded funds(ETFs) or mutual funds that meet your needs.
https://www.aaii.com/investingideas/article/47801-4-undervalued-retailers---miscellaneous-specialty-stocks-for-thursday-march-23
Difference between revisions of "Aminoguanidine" - Sciencemadness Wiki Difference between revisions of "Aminoguanidine" Revision as of 10:17, 10 November 2019 ( view source ) Diachrynic ( Talk | contribs ) ← Older edit Latest revision as of 20:00, 12 March 2021 ( view source ) Mabus ( Talk | contribs ) ( → ‎ Preparation ) (4 intermediate revisions by 2 users not shown) Line 121: Line 121: ==Preparation== ==Preparation== − Aminoguanidine can be prepared from [[calcium cyanamide]] and [[hydrazine sulfate]]. Reaction produces aminoguanidine carbonate . To obtain the free base, a strong base, like [[sodium methoxide]] is added.<ref>https://www.youtube.com/watch?v=mvh_cV8eaG4</ref> + Aminoguanidine can be prepared from [[calcium cyanamide]] and [[hydrazine sulfate]]. Reaction produces impure aminoguanidine , which is then converted to [[aminoguanidinium bicarbonate|aminoguanidine bicarbonate]], for easier purification . To obtain the free base, a strong base, like [[sodium methoxide]] is added and the freebase aminoguanidine is extracted .<ref>https://www.youtube.com/watch?v=mvh_cV8eaG4</ref> − Aminoguanidine canso al be prepared by reducing [[nitroguanidine]] with [[zinc]] powder in [[acetic acid]].<ref>http://www.orgsyn.org/demo.aspx?prep=CV3P0073</ref> Reaction produces aminoguanidine acetate, which can be converted into pure base by dissolving the solid in another solvent, then adding a strong base, like [[sodium methoxide]]. + Aminoguanidine can also be prepared by reducing [[nitroguanidine]] with [[zinc]] powder in [[acetic acid]].<ref>http://www.orgsyn.org/demo.aspx?prep=CV3P0073</ref> Reaction produces aminoguanidine acetate, which can be converted into pure base by dissolving the solid in another solvent, then adding a strong base, like [[sodium methoxide]]. + + A better reduction of nitroguanidine can be performed by adding zinc powder to a stirred suspension of nitroguanidine in [[ammonium sulfate]] solution. The zinc oxide sludge is filtered off and remaining zinc is kept dissolved by adding [[ammonia]] solution, the aminoguanidine is precipitated as the bicarbonate.<ref>https://patents.google.com/patent/US2537328A/en</ref><ref>https://www.lambdasyn.org/synfiles/aminoguanidinhydrogencarbonat.htm</ref> ==Projects== ==Projects== *Make aminoguanidinium nitrate *Make aminoguanidinium nitrate *Make tetrazoles *Make tetrazoles + *Make nickel complexes<ref>https://www.youtube.com/watch?v=Lfnx0wjltyA</ref> ==Handling== ==Handling== Line 141: Line 144: ==Gallery== ==Gallery== <gallery widths="200" position="center" columns="4" orientation="none"> <gallery widths="200" position="center" columns="4" orientation="none"> − Aminoguanidine_bicarbonate.jpg|Aminoguanidine bicarbonate + Aminoguanidine_bicarbonate.jpg|Aminoguanidine bicarbonate made from calcium cyanamide + Aminoguanidine_bicarbonate_2.jpg|Aminoguanidine bicarbonate made from nitroguanidine + Aminoguanidine_bicarbonate_micro.jpg|Aminoguanidine bicarbonate under the microscope, image width is about 3 mm + Nickel_aminoguanidine_sulfate_and_nitrate.jpg|Bis(aminoguanidine)nickel(II) sulfate (left) and nitrate (right) + Nickel_aminoguanidine_perchlorate.jpg|Bis(aminoguanidine)nickel(II) perchlorate + Nickel_aminoguanidine_perchlorate_micro.jpg|Bis(aminoguanidine)nickel(II) perchlorate under the microscope, image width is about 3 mm </gallery> </gallery> Line 148: Line 156: ===Relevant Sciencemadness threads=== ===Relevant Sciencemadness threads=== *[http://www.sciencemadness.org/talk/viewthread.php?tid=29341 Aminoguanidine from Nitroguanidine?] *[http://www.sciencemadness.org/talk/viewthread.php?tid=29341 Aminoguanidine from Nitroguanidine?] + *[https://www.sciencemadness.org/whisper/viewthread.php?tid=155675 An improved synthesis of aminoguanidine bicarbonate] [[Category:Chemical compounds]] [[Category:Chemical compounds]] Latest revision as of 20:00, 12 March 2021 Aminoguanidine Names IUPAC name 2-Aminoguanidine Other names Guanyl hydrazine Hydrazinecarboximidamide Imino semicarbazide Monoaminoguanidine Pimagedine Properties Chemical formula CH 6 N 4 Molar mass 74.085 g/mol Odor Odorless Density 1.72 g/cm 3 Boiling point 261 °C (502 °F; 534 K) Solubility Reacts with acids Hazards Safety data sheet None Related compounds Related compounds Guanidine Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references Aminoguanidine , also known as pimagedine , is an organic base, a derivate of guanidine . Contents 1 Properties 1.1 Chemical 1.2 Physical 2 Availability 3 Preparation 4 Projects 5 Handling 5.1 Safety 5.2 Storage 5.3 Disposal 6 Gallery 7 References 7.1 Relevant Sciencemadness threads Properties Chemical Aminoguanidine is highly basic, and will readily absorb carbon dioxide forming aminoguanidine carbonate/bicarbonate. Physical Aminoguanidine is a white solid. Availability Pure aminoguanidine is difficult to find, but its salts are more readily available. Preparation Aminoguanidine can be prepared from calcium cyanamide and hydrazine sulfate . Reaction produces impure aminoguanidine, which is then converted to aminoguanidine bicarbonate , for easier purification. To obtain the free base, a strong base, like sodium methoxide is added and the freebase aminoguanidine is extracted. [1] Aminoguanidine can also be prepared by reducing nitroguanidine with zinc powder in acetic acid . [2] Reaction produces aminoguanidine acetate, which can be converted into pure base by dissolving the solid in another solvent, then adding a strong base, like sodium methoxide . A better reduction of nitroguanidine can be performed by adding zinc powder to a stirred suspension of nitroguanidine in ammonium sulfate solution. The zinc oxide sludge is filtered off and remaining zinc is kept dissolved by adding ammonia solution, the aminoguanidine is precipitated as the bicarbonate. [3] [4] Projects Make aminoguanidinium nitrate Make tetrazoles Make nickel complexes [5] Handling Safety There is little information about the toxicity of this compound and its salts. Pimagedine, like other guanidine derivates, has been investigated in the treatment of diabetes, more specifically diabetic kidney disease. Storage In closed bottles. Disposal No special disposal is required. Can be poured down the drain. Gallery Aminoguanidine bicarbonate made from calcium cyanamide Aminoguanidine bicarbonate made from nitroguanidine Aminoguanidine bicarbonate under the microscope, image width is about 3 mm Bis(aminoguanidine)nickel(II) sulfate (left) and nitrate (right) Bis(aminoguanidine)nickel(II) perchlorate Bis(aminoguanidine)nickel(II) perchlorate under the microscope, image width is about 3 mm References ↑ https://www.youtube.com/watch?v=mvh_cV8eaG4 ↑ http://www.orgsyn.org/demo.aspx?prep=CV3P0073 ↑ https://patents.google.com/patent/US2537328A/en ↑ https://www.lambdasyn.org/synfiles/aminoguanidinhydrogencarbonat.htm ↑ https://www.youtube.com/watch?v=Lfnx0wjltyA
https://www.sciencemadness.org/smwiki/index.php?diff=13883&oldid=12141&title=Aminoguanidine
Sustainability | Free Full-Text | ESG: Research Progress and Future Prospects The sustainable development of the global economy and society calls for the practice of the environmental, social and governance (ESG) principle. The ESG principle has been developed for 17 years following its formal proposal in 2004. Countries around the world continue to promote the coordinated development of the environment, society, and governance in accordance with the ESG principle. In order to review and summarize ESG research, this study takes the literature related to ESG research as the research object and presents the cooperation status, hot spots, and trends of ESG research with the help of the literature analysis tool CiteSpace. On the basis of quantitative analysis results, this study presents an examination and comprehensive summary of progress in the research into ESG combined with a systematic literature review. This includes the theoretical basis of ESG research, the interaction between the dimensions of ESG, the impact of ESG on the economic consequences, the risk prevention role of ESG, and ESG measurement. Based on the systematic summary of research progress, this paper further refines the characteristics of ESG research, reveals the shortcomings of ESG research, and propose a focus for ESG research in the future in order to provide a reference for academic research and the practice of ESG. ESG: Research Progress and Future Prospects by Ting-Ting Li 1,* , Kai Wang 1 , Toshiyuki Sueyoshi 2,3 and Derek D. Wang 1 1 College of Business Administration, Capital University of Economics and Business, Beijing 100070, China 2 Department of Management, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USA 3 School of Environment and Society, Tokyo Tech World Research Hub Initiative, Tokyo Institute of Technology, Tokyo 108-0023, Japan * Author to whom correspondence should be addressed. Sustainability 2021 , 13 (21), 11663; https://doi.org/10.3390/su132111663 Received: 30 June 2021 / Revised: 2 September 2021 / Accepted: 11 October 2021 / Published: 21 October 2021 (This article belongs to the Special Issue ESG and Sustainability: A Global Perspective ) Abstract The sustainable development of the global economy and society calls for the practice of the environmental, social and governance (ESG) principle. The ESG principle has been developed for 17 years following its formal proposal in 2004. Countries around the world continue to promote the coordinated development of the environment, society, and governance in accordance with the ESG principle. In order to review and summarize ESG research, this study takes the literature related to ESG research as the research object and presents the cooperation status, hot spots, and trends of ESG research with the help of the literature analysis tool CiteSpace. On the basis of quantitative analysis results, this study presents an examination and comprehensive summary of progress in the research into ESG combined with a systematic literature review. This includes the theoretical basis of ESG research, the interaction between the dimensions of ESG, the impact of ESG on the economic consequences, the risk prevention role of ESG, and ESG measurement. Based on the systematic summary of research progress, this paper further refines the characteristics of ESG research, reveals the shortcomings of ESG research, and propose a focus for ESG research in the future in order to provide a reference for academic research and the practice of ESG. Keywords: ESG ; bibliometric ; literature review ; future research navigation 1. Introduction Human society never ceases in its pursuit of progress. Today, with the development of the economy and society, the world is faced with not only many opportunities, but also challenges. In 2020, “Black Swan” events occurred frequently. With the global spread of COVID-19, four meltdowns in the US stock market in a fortnight, the plague of locusts in Africa, Luckin Coffee being delisted following fraud, etc., environmental (E), social (S), and governance (G) issues have aroused global concern. The theme of sustainable and comprehensive development has, once again, become a hot topic of discussion worldwide. In response to the increasingly severe sustainable development problems in the environment, society, and the financial market, international organizations and countries worldwide have put forward sustainable development action plans such as ESG to build a sustainable and comprehensive development framework of human society. The ESG principle is a framework system including environmental (E), social (S), and governance (G) factors (see Table 1 ) [ 1 ]. ESG stems from responsible investment. The principles for responsible investment (PRI) define responsible investment as “a strategy and practice to incorporate environmental, social and governance (ESG) factors in investment decisions and active ownership” [ 2 ]. Therefore, ESG is usually a standard and strategy used by investors to evaluate corporate behavior and future financial performance. As an investment concept for evaluating the sustainable development of enterprises, the three basic factors of ESG are the key points to be considered in the process of investment analysis and decision making. Moreover, environmental, social, and governance (ESG) factors help to measure the sustainability and social impact of business activities [ 3 ]. As the EBA (European Banking Authority) states, ESG factors are “environmental, social or governance matters that may have a positive or negative impact on the financial performance or solvency of an entity, sovereign or individual” [ 1 ]. Therefore, as a value of sustainable and coordinated development that takes into account economic, environmental, social, and governance benefits, ESG is an investment philosophy that pursues long-term value growth, and it is a comprehensive, concrete, and down-to-earth governance method. Table 1. ESG framework (international frameworks). Since the ESG principle was formally proposed in 2004, it has been actively practiced in Europe, America, and other developed countries. A series of achievements promote the development and maturity of the environmental, social, and governance factors, as well as ESG as a whole, such as the establishment of the ESG evaluation system, the ESG disclosure standards, and the ESG index system. These factors are constantly building a new pattern of sustainable development. With the concept of ESG gradually becoming mainstream, ESG has been widely examined, practiced, and popularized in the practical field, and it has aroused the interest of scholars from all over the world. At present, there are few literature reviews on ESG research. Moreover, they mainly focus on ESG investment (Daugaard, 2020) [ 4 ], the importance of ESG metrics in SRI (socially responsible investment) (Widyawati, 2020) [ 5 ], the influence of the ESG score on measuring corporate sustainability performance (Drempetic et al., 2020) [ 6 ], the origin and significance of the name of ESG in investment (Eccles and Viviers, 2011) [ 7 ], and the importance and role of ESG factors in the financial decision-making process (Ziolo et al., 2019) [ 8 ]. In addition, there are literature reviews on the role and performance of corporate governance (G) in ESG (Yoshikawa et al., 2021) [ 9 ] and discussions of the relationship between corporate governance and corporate social responsibility (Aluchna and Roszkowska-Menkes, 2019) [ 10 ]. At present, it can be observed that ESG reviews mainly focus on one aspect of ESG factors, and there is a scarcity of literature on the environmental (E) and social (S) factors. However, after combing the relevant literature of ESG research, this paper finds that ESG, as an integrated framework and concept of environmental, social, and governance factors, displays an interactive relationship between its dimensions, and many studies focusing on the interaction between the environmental (E), social (S), and governance (G) factors have emerged. In addition, the environmental, social, and governance factors play an important role in measuring the future financial performance and social influence of enterprises. Therefore, as an investment principle integrating the environmental, social, and governance factors, ESG is an important driving force to trigger the sustainable development of enterprises, and the interactive relationship between its dimensions is also a key point that deserves attention. In order to promote the global economy and society to improve in quality, this paper systematically reviews the research on ESG and looks forward to the future development direction of ESG research. The paper is structured as follows. Section 1 , introduction including definition of ESG and research background. Section 2 , the literature related to the research of ESG is analyzed including the theoretical basis of ESG, the interaction between the three dimensions of ESG, the impact of ESG on economic consequences, the risk prevention role of ESG, and ESG measurement. Section 3 is conclusions and future research. This paper is expected to arouse the interest of stakeholders who care about and explore the essence and significance of ESG, such as enterprises, government regulators, financial institutions, and academic institutions. At the same time, this paper also provides a useful reference and guidance for the promotion of further development and practice of ESG. 2. Analysis of ESG Literature in Top International Journals 2.1. Method ESG emerged from developed countries such as Europe and the US. The practice and development of ESG in companies are relatively mature. As a result, there is a wealth of literature on ESG research. In order to systematically and objectively review the research achievements of ESG in the last 17 years, this paper presented the research progress of ESG by combining bibliometric analysis with a literature review. Firstly, this paper used CiteSpace to objectively quantify ESG-related research on “UTD24”, and showed the maturity, hot spots, and trends of ESG research with objective data. As bibliometric analysis software with relatively complete functions, CiteSpace has advantages that other bibliometrics software cannot match. In this paper, the use of CiteSpace could directly and objectively show the situation of ESG in academic community cooperation and the hot spots and trends of ESG research. Secondly, on the basis of the quantitative analysis results, by combing the ESG-related literature in the “UTD24” journal, the interactions between the environmental (E), social (S), and governance (G) factors and ESG’s related influencing factors were further summarized, and the results quantified by CiteSpace were verified to clarify the research progress and research trend of ESG since 2004. Therefore, the bibliometric analysis results and the systematic literature review are mutually connected and verified. This paper presents ESG research in a comprehensive and objective form. 2.2. Data Collection The literature searched in this paper was obtained from the Web of Science (WOS) database of the top journals published in “UTD24” from January 1985 to December 2020, focusing on business, economics, finance, information, marketing, and management science. This was because we believe that the above areas are closely related to the ESG practice of a company. In selecting the “topic,” we found that although ESG has been proposed, there is no clear definition. Practitioners in various industries and scholars have given different explanations. In order to comprehensively retrieve the literature needed in this paper, after consulting the relevant literature, we found that ESG, corporate responsibility, sustainability, and socio-environmental governance are used as synonyms (Garcia et al., 2017) [ 11 ]. In addition, since ESG is derived from CSR, ESG and CSR are two terms that can be used interchangeably (Garcia et al., 2017) [ 11 ]. Therefore, the “topic” includes environmental, social, and governance (ESG), corporate social responsibility (CSR), corporate responsibility, sustainability, and socio-environmental governance, which were used in the final search of a total of 793 pieces of literature. The search showed that the related research on the topic of ESG began in 2004. Then, CiteSpace was used to eliminate duplicates, and 593 pieces of literature were selected for bibliometric analysis. 2.3. Bibliometric Analysis 2.3.1. Analysis of Academic Community Collaboration on ESG The dynamic, complex nature of professional research fields requires the development of subject areas through research collaboration and the integration of resources at the individual and institutional levels. ESG is an emerging field of research, and in 2004, Kofi Annan and 18 financial institutions drafted the report “Who Cares Wins: Connecting Financial Markets to a Changing World.” This report called for the integration of ESG factors into financial analysis, asset management, and security brokerage. The concept of ESG has gradually emerged in Europe and the US. The study of environmental (E), social (S), and governance (G) factors, as well as ESG as a whole, has gradually become an important issue after CSR. The cooperative co-occurrence analysis in CiteSpace can intuitively reflect the degree and level of cooperation in a professional research field. Therefore, first, this paper shows the progress and maturity of ESG research through the level of academic community cooperation. Academic institutions represented by European and American countries have a high level of cooperation. This paper uses “Country” and “Institution” as network nodes and CiteSpace to map out the cooperation network map of countries and academic institutions. The visualization in Figure 1 shows the maturity and diffusion of the ESG sustainability concept in foreign countries. In the field of ESG research, the cooperation between Europe and the US seems to be close. Taking the top three countries as an example, the US has a frequency of 386 collaborations in ESG and a centrality of 0.91, and it has been in a partnership since 2004. The frequency of cooperation in Canada is 85, with a centrality of 0.21. The frequency of cooperation in the UK is 75, with a centrality of 0.33. As observed, cooperation in developed countries, such as the United States, Canada, and the United Kingdom, shows a highly centralized and high level of practice. In terms of collaborating institutions, academic institutions represented by Harvard University, the University of Pennsylvania, the University of Minnesota, and Boston University have strong collaborative links in ESG research, with a frequency of 16, 16, 15, and 14 collaborations, respectively, and centrality of 0.02, 0.04, 0.01, and 0.03, respectively. Compared to developed countries, such as those in Europe and the US, the level of research cooperation in ESG in developing countries, represented by China, is relatively low. Figure 1. Collaboration network among countries and academic institutions. Source: mapped by CiteSpace. 2. The cooperation network among scholars is decentralized, and the degree of cooperation is low. CiteSpace is used in this study for author cooperation co-occurrence to demonstrate the network and profile of author collaborations in the field. The timeline set here is from 2004 to 2020, and the time slice is set to 5 years. The resulting graph of the author cooperation network is shown in Figure 2 . After clustering, it can be observed that modularity = 0.8834, which is greater than 0.3, and silhouette = 0.9672, which is greater than 0.7, indicating a significant and plausible clustering structure. As seen from the authors’ collaboration map, ESG research has formed a collaborative network centered on the works of Christopher Marquis, Caroline Flammer, Rodolphe Durand, Donal Crilly, George Serafeim, Michael D. Pfarrer, Heli Wang, and other scholars. However, there is a lack of close and extensive collaborative links between each team. In general, the network structure of collaboration among scholars on ESG research is too fragmented, and the level of collaboration among scholars is low. Figure 2. Author collaboration network. Source: mapped by CiteSpace. Through the analysis of the academic community, it can be seen that the current research on ESG is mainly concentrated in developed countries, such as those in Europe and the United States. However, the closeness of cooperation among scholars is not high and is relatively scattered. Therefore, ESG research is still in the development stage. 2.3.2. Statistics of Research Hotspots on ESG Keywords abstract the core points of research in the field. This paper used CiteSpace software for keyword co-occurrence analysis, which can reveal the research hotspots of ESG in different periods and show the context and progress of ESG research. In this paper, we used CiteSpace to analyze the co-occurrence of keywords, selected “Keyword” as the node type, and clustered the keywords to obtain the keyword co-occurrence map in Figure 3 . As the result shows, modularity = 0.431, which is greater than 0.3, and therefore, the clustering structure is significant, while silhouette = 0.7421, which is greater than 0.7, indicating that the results are plausible. Firstly, through the cluster analysis of co-keywords, it can be observed that the topics focus on happiness, transparency, shareholder value, organizational performance, corporate philanthropy, organization, and institutional theory. Secondly, from the analysis of word frequency, the top 10 most frequent keywords are corporate social responsibility (234 times), performance (140 times), sustainability (125 times), management (113 times), financial performance (83 times), firm (80 times), impact (80 times), social responsibility (80 times), governance (74 times), and strategy (71 times). All of these were concentrated between 2004 and 2007 (see Table 2 ). Lastly, ranking by centrality shows the importance of keywords in the co-occurrence network. In terms of keyword centrality, the research hotspots with high importance are concentrated on firm (0.16), behavior (0.13), impact (0.12), strategy (0.1), competitive advantage (0.09), corporate social responsibility (0.08), management (0.08), sustainability (0.07), governance (0.07), and organization (0.07) (see Table 3 ). Figure 3. Keyword co-occurrence graph. Source: mapped by CiteSpace. Table 2. Statistic information of keywords (by frequency 1–50). Table 3. Statistic information of keywords (by centrality 1–50). 2.3.3. Statistics of Research Trend on ESG The burst terms indicate that the frequency of a keyword sharply increases within a certain period of time. When the frequency of a keyword becomes higher, its importance also increases. That is, burst terms can reveal the research hotspot and navigate the research direction in a field in a designated timeframe. In this paper, CiteSpace is used for the analysis of burst terms, and 19 burst terms were obtained. As can be observed, in terms of the intensity of keywords, the focus of research is financial performance, philanthropy, company, self-regulation, framework, technology, firm value, competition, perspective, and organization. By contrast, over the past five years, the focus was on financial performance, philanthropy, self-regulation, firm value, and director. In terms of trends, ESG research tends to focus on the interaction between the organizational level and social responsibility of companies and related research (see Table 4 ). Table 4. Statistic information of burst terms. From the statistical results of CiteSpace, some characteristics and regularities of ESG research can be observed. Firstly, ESG research mainly focuses on the topics of happiness, shareholder value, organizational performance, corporate philanthropy, transparency, organization, and institutional theory (see Figure 3 ). Secondly, it can be observed from the statistical results of keywords and burst terms that ESG research focuses on detailed exploration of the three dimensions of environmental, social, and governance, while the research taking ESG as a whole does not show an obvious trend. 2.4. Analysis of Research Progress in ESG This subsection presents the analysis of the research progress of ESG according to the importance, frequency, and attention of research hotspots based on the statistical results of ESG research hotspots and research trends combined with a systematic literature review. 2.4.1. The Theoretical Basis of ESG The theoretical basis is the cornerstone of academic research. From the results of the keyword co-occurrence map (see Figure 3 ), keyword statistics (see Table 2 and Table 3 ), and burst terms statistics (see Table 4 ), it can be observed that the theoretical basis of ESG research mainly focuses on institutional theory and stakeholder theory. In terms of institutional theory, Chatterji and Toffel (2010) explained the impact of ESG rating on improving environmental performance [ 12 ], Jayachandran et al. (2013) demonstrated the impact of social performance on corporate performance [ 13 ], Koh et al. (2014) studied the risk prevention role played by ESG [ 14 ], and Flammer et al. (2019) studied the binding effect of social responsibility contracts on executives [ 15 ]. In general, ESG research discusses the role of the legitimacy behavior of corporate in the sustainable development of a company based on institutional theory. In terms of stakeholder theory, Kölbel et al. (2017) studied the relationship between corporate social irresponsibility and financial risk [ 16 ], Surroca et al. (2010) studied the relationship between corporate responsibility and financial performance [ 17 ], Muller and Kräussl (2011) studied the relationship between corporate charitable donations and return on investment [ 18 ], and Flammer and Kacperczyk (2019) explored the impact of ESG practice on employee management [ 19 ]. In general, based on stakeholder theory, ESG research suggested that enterprises that respond better to the ESG requirements of stakeholders will perform better than irresponsible enterprises. 2.4.2. The Interaction between the Environmental (E), Social (S), and Governance (G) Dimensions The three factors of ESG are of great significance for the operation and sustainable development of enterprises. It can be observed from the results of quantitative analysis in this paper that the current research on ESG is mainly based on the environmental (E), social (S), and governance (G) dimensions. At the same time, through our systematic literature review, it can be observed that there are a considerable number of studies on the interaction between E, S, and G. Therefore, this paper systematically summarizes the research on the interaction between the environmental (E), social (S), and governance (G) dimensions. Interaction Research of Environmental (E) Dimension The environment has always been a central problem occupying academia’s concerns. The environmental (E) dimension in ESG research mainly regards the interaction between the environmental (E) and governance (G) dimensions. In the research on the interaction between the environmental (E) and governance (G) dimensions, the related keywords are management, governance, green, environment, and environmental performance. The frequencies of the keywords are, respectively, 113, 74, 22, 16, and 14, and they all rank in the top 48 (see Table 2 ). The centrality of the first four keywords is, respectively, 0.08, 0.07, 0.04, and 0.04, and they all rank in the top 27 (see Table 3 ). Therefore, the interaction between the environmental (E) and governance (G) dimensions is a hot spot of ESG research. First, from the perspective of executive factors, Flammer et al. (2019) found that the CSR contract drives the attention of executives to stakeholders, which can improve the corporate governance and its impact on society and the environment in the long run. Thus, integrating the environment and social performance into senior executive compensation is of great importance [ 15 ]. Davidson et al. (2019) found that enterprises led by non-materialistic CEOs have good performance in social responsibility, such as their treatment of the environment, and this is positively correlated with stock price performance [ 20 ]. Second, from the perspective of stakeholder factors, Cheng et al. (2014) pointed out that the excellent performance of corporate social responsibility strategies will bring better financing channels. Specifically, the improvement in the participation of stakeholders reduces the agent cost, and the increased transparency reduces the information asymmetry, so the performance of social responsibility is negatively correlated with capital constraint, leading to better financing channels. The environmental dimension is one of the factors that promotes this relationship [ 21 ]. Among the studies mentioned in this paper, there is little research on the interaction between the environmental (E) and social (S) dimensions, because the environmental (E) dimension is usually attributed to the social (S) dimension in measurements and research. 2. Interaction between the Social (S) and Governance (G) Dimensions From the ranking of word frequency and centrality of keywords, it can be seen that the research hotspots of ESG focus on the social (S) and governance (G) levels. In the interactive relationship between the social (S) and governance (G) dimensions, the related keywords include corporate social responsibility, management, social responsibility, governance, organization, behavior, responsibility, shareholder value, identity, capability, stakeholder theory, corporate governance, and ownership. The frequencies are, respectively, 234, 113, 80, 74, 61, 38, 33, 29, 27, 19, 19, 18, and 16, and they all rank in the top 41 (see Table 2 ). In addition, their centrality degrees are, respectively, 0.08, 0.08, 0.06, 0.07, 0.07, 0.13, 0.02, 0.03, 0.04, 0.06, 0.02, and 0.02, and they all rank in the top 50 (see Table 3 ). Therefore, in terms of either word frequency or importance, research on the interaction between the social (S) and governance (G) dimensions is a hot topic. A large number of studies on the interaction between them are also presented in the literature review. Combing the bibliometrics analysis results and the systematical literature review, this study suggests that the interaction between the social (S) and governance (G) dimensions mainly focuses on the interaction between the social (S) dimension and executives and the interaction between the social (S) dimension and stakeholders. (1) The Social (S) Dimension and Executive Factors From the statistical results of the burst terms, it can be observed that the keyword represented by “director” has been the focus of attention at the governance (G) level in recent years (see Table 4 ). Secondly, among the above high-frequency words, management, governance, behavior, identity, capability, corporate governance, and ownership are closely related to executive factors. Therefore, this paper first addresses the interaction between the social (S) dimension and executive factors. ① The Impact of the Social (S) Dimension on Executive Factors The role of social responsibility in corporate governance is first reflected in the impact of the social (S) dimension on executive factors. Kim et al. (2012) found that senior executives practicing CSR are unlikely to be investigated by the SEC regarding violations of GAAP, because social responsibility can play an important role in constraining earning management, making enterprises more conservative in accounting and business decision making; provide more transparent financial information; and encourage executives to produce high-quality financial reports [ 22 ]. Gao et al. (2014) found a significant negative correlation between social good and insider trading of senior executives, because the social responsibility image can be used as a governance mechanism to restrict self-interest behaviors, such as insider trading [ 23 ]. Hubbard et al. (2017) studied social responsibility investment and the possibility of CEOs being dismissed. The results show that when financial performance is poor, more investment in corporate social responsibility will increase the possibility of CEOs being dismissed. Moreover, when financial performance is good, the possibility of CEOs being dismissed will be reduced. Hence, social responsibility activities have an essential effect on CEOs [ 24 ]. ② The Impact of Executive Factors on the Social (S) Dimension It cannot be overemphasized how important the role of senior management is in determining the future and operation of a company. This explains why they are able to affect the realization of social responsibility. For instance, studies by Fu et al. (2020) concluded that the chief sustainability officer (CSO) has an impact on the social performance of a company and that the creation of a CSO position can increase the socially responsible activities of a company while reducing the chances of irresponsible behavior occurring. Moreover, the presence of a CSO position has a greater impact on reducing irresponsible corporate behavior. This especially occurs when the company is part of a controversial or condemned industry [ 25 ]. Notably, the personal traits, behaviors, and characteristics of the CEO, who possesses the lifeblood of the company, will greatly impact what a company will do and how far it will go in taking social responsibility. Regarding the traits of CEOs, Tang et al. (2015) found that a CEO’s arrogance is negatively correlated with corporate social responsibility behavior but positively correlated with corporate social irresponsibility behavior. However, the relationship between a CEO’s arrogance and corporate social irresponsibility diminishes when companies rely more on stakeholders for resources and external markets become more uncertain or competitive in the marketplace [ 26 ]. Petrenko et al. (2016) found that a leader’s concern for personal image and the need to enhance it are associated with social responsibility. CEOs being narcissistic has a positive impact on the level and image of corporate social responsibility [ 27 ]. Tang et al. (2018) examined the different roles and effects of narcissistic and arrogant CEOs on corporate social responsibility. The research shows that narcissistic and arrogant CEOs hold different attitudes about how many social responsibility activities their companies should undertake. Narcissistic CEOs show more concern about social responsibility than arrogant CEOs do. Further research carried out on this topic showed that the positive relationship between CEOs with narcissistic traits and social responsibility activities is reinforced when peer firms invest less in social responsibility activities than in the firms that they run. Under the same conditions, the negative relationship between the arrogant CEO and social responsibility activities has been strengthened [ 28 ]. In addition, Davidson et al. (2019) studied the impact of CEO materialism on corporate social responsibility performance. The research used data from the KLD database to calculate corporate social responsibility scores and found that companies led by materialistic CEOs had more “weaknesses” than “strengths,” which rendered a lower score on social responsibility. In contrast, the social responsibility performance of companies led by non-materialistic CEOs in terms of environment, diversity, and product safety can positively influence the stock price of the company and the positive relationship between the “strengths” of corporate social responsibility and profitability. Thus, CEOs who seek material benefits are more likely to invest in social responsibility activities with a desire to increase their interests, while CEOs who are non-materialistic have the goal of increasing their shareholder value [ 20 ]. In terms of CEOs’ values and political ideologies, it is suggested that the fair market ideology, as a psychological antecedent influencing the beliefs and moral feelings of senior executives, influences the moral values and feelings of individuals. Specifically, senior executives with business, economics, and legal educational backgrounds show a higher degree of participation in social responsibility. This is because their educational backgrounds lead to their belief in the relationship between corporate social performance and corporate financial performance, which is derived from the fair market ideology (Hafenbrädl and Waeger, 2017) [ 29 ]. In addition, in terms of the research on the relationship between political ideology and social responsibility, Chin et al. (2013) found that liberal CEOs pay more attention to social responsibility compared to those who believe in conservatism. When CEOs have more power, their political liberalism regarding social responsibility will be amplified. Meanwhile, the recent financial performance of the enterprise will have less of an impact on the action of liberal CEOs in the aspect of social responsibility [ 30 ]. Furthermore, Gupta et al. (2019) pointed out that liberal CEOs are more likely to carry out social responsibility activities. Moreover, they suggested that the extroversion and narcissism characteristics of CEOs will amplify the relationship between liberal ideology and social responsibility [ 31 ]. After research on the influence mechanism of CEOs’ liberal ideology on social responsibility commitment, Gupta et al. (2021) studied how CEOs’ ideology affects their peers’ appointment of senior positions in relation to social responsibility. It was observed that, compared with liberal CEOs, when conservative CEOs set up senior executive positions related to CSR, other companies were more likely to follow suit [ 32 ]. Moreover, such senior executive positions will have a positive impact on corporate social responsibility (Fu et al., 2020) [ 25 ]. In terms of CEO demographic variables, the age of the CEO is also an important factor affecting corporate social responsibility activities because of the characteristics of large investment and the slow effect of social responsibility investment. Kang’s (2016) research showed that CEOs due for retirement have a negative effect on social responsibility commitment. However, this negative effect will weaken when they retire at a relatively old age or they retain their positions in the BOD [ 33 ]. Furthermore, where CEOs come from is a notable factor influencing their strategic decision-making styles. Notably, local CEOs appear to make decisions that will benefit long-term growth by paying more state taxes and being more socially responsible when compared with non-local CEOs. Hence, choosing local CEOs is more likely to control the phenomenon of short-termism in management (Lai et al., 2020) [ 34 ]. Similarly, from the perspective of social identity theory, Bertrand et al. (2021) observed that when a local firm hires a non-local CEO, the firm needs to demonstrate better performance in social responsibility practices and social performance levels to increase its legitimacy and credibility in response to bias and pressure from the outside, as a non-local CEO is perceived as an external leader by local stakeholders [ 35 ]. In addition to the direct effect of the above-mentioned senior executive factors on social responsibility, the influence of senior executive governance on social responsibility will also occur via other factors. Church et al. (2019) studied how the measurement basis (financial or non-financial) affects the decision-making behavior of middle and senior managers in social responsibility projects. The research found that when executives favor corporate social responsibility, the level of social responsibility investment based on the non-financial measurement is higher than that based on financial measurement. Moreover, executives who support corporate social responsibility investment invest more based on financial and non-financial measurement than based on financial measurement only. Thus, non-financial measures increase the social attention of executives who support corporate social responsibility, while social attention regulates their investment decisions in turn [ 36 ]. In addition, Han et al. (2019) researched whether studying or training abroad will affect the corporate social responsibility practice of private enterprises. It was found that enterprises operated by executives with backgrounds of studying abroad show a higher social responsibility performance level than that of enterprises led by local executives [ 37 ]. Luo et al. (2021) studied how executives with backgrounds of studying or working abroad in the BOD influence social responsibility according to the data of listed companies in China from 2000 to 2012. It can be observed that the existence of these returners has largely improved these enterprises’ participation in social responsibility, especially in the form of corporate donations [ 38 ]. In addition, Li and Lu (2020) developed a dual mechanism model containing public agents (government officials) and private agents (CEOs) based on “China’s 12th Five Year Plan” to study under what circumstances enterprises will respond to the government initiative by increasing social responsibility. The research showed that it is more likely for enterprises to take more CSR actions to respond to government initiatives when the CEO has a greater interest in legitimacy. Specifically, CEOs are more likely to take social responsibility actions when their tenure as a CEO is relatively short, and they need legitimacy by building credibility. Thus, corporate social responsibility is an action taken by CEOs to respond to external stress [ 39 ]. (2) The Social (S) Dimension and Stakeholder Factors From the statistical results of the burst terms, it can be seen that the keywords represented by “stakeholder theory” and “incentive” are the focus of attention at the governance (G) level (see Table 4 ). Secondly, the high-frequency words related to governance (G) include management, governance, organization, behavior, shareholder value, identity, capability, stakeholder theory, and ownership, which are closely related to stakeholder factors (see Table 2 ). The participation of stakeholders is the key to ESG practice. Whether these stakeholders can bring benefits to the enterprises through social responsibility activities depends on whether these social responsibility activities can attract the attention of stakeholders; namely, whether these social responsibility activities are valued by the stakeholders (Madsen and Rodgers, 2015) [ 40 ]. Research on the relationship between social responsibility practice and stakeholders is mainly concentrated on the interaction between the social (S) dimension and employees and the interaction between the social (S) dimension and investors. ① The Impact of the Social (S) Dimension on Stakeholder Factors Regarding the incentive effects for employees, Flammer and Luo (2015) found that social responsibility can contribute to motivating employees and improving their workplace behavior as an employee governance tool [ 41 ]. Moreover, Balakrishnan et al. (2011) pointed out that employees’ contributions to enterprises will significantly increase with the improvement in the enterprise donation level. Thus, social responsibility activities serve as effective leverage to motivate employees to contribute for themselves and the organization [ 42 ]. In addition, Carnahan et al. (2017) researched the relationship between social responsibility investment and employee retention. They found that due to the value preference of employees for meaningful work, the social responsibility practice of enterprises may provide employees with more retention willingness [ 43 ]. Moreover, in regard to the impact of social responsibility activities on human resource management, Farooq et al. (2017) studied the relationship between social responsibility and employee attitude and behavior. Their research showed that social responsibility activities focusing on employee welfare may enhance perceived respect and further affect the organizational identification of employees [ 44 ]. Regarding investors, Elliott et al. (2014) studied the relationship between corporate social responsibility performance and investors’ assessment. It was observed that there is an unexpected causality between corporate social responsibility performance and investors’ assessment of basic value, and investors’ explicit assessment of the corporate social responsibility performance will weaken this relationship. The impact of investors without a clear assessment of corporate social responsibility performance is unintentional, because they inadvertently use their emotional response to corporate social responsibility performance to estimate the basic value [ 45 ]. Hence, it is important to assess corporate social responsibility (with an index or evaluation system), since it can affect the investment decision of investors. ② The Impact of Stakeholder Factors on the Social (S) Dimension Regarding employees and the practice of social responsibility, employees exert a significant influence on social responsibility as an important component of enterprises. Muller et al. (2014) found that employees serve as a vital driving force for the charitable efforts of enterprises, whose motivation may function through psychological factors such as compassion [ 46 ]. Gupta et al. (2017) explained how the political beliefs of organizational members shape the performance of social responsibility from a more detailed entry point, from the perspective of organizational politics. The employee donations to the two major political parties in the United States are considered a new measure of organizational political ideology. The results show that enterprises with liberal employees are more engaged in social responsibility activities than those with conservative employees. Therefore, social responsibility activities may be shaped by the values of employees in the organization [ 47 ]. Investors also play an important role in the practice of social responsibility. Mun and Jung (2018) pointed out that overseas institutional investors and local corporate social responsibility experts impact the practice of social responsibility, mainly reflected in the increase in the number of women in the BOD and management positions [ 48 ]. Naughton et al. (2019) found that investors’ sentiments toward social responsibility activities change with time, and their sentiments can exert some influence on the corporate social responsibility commitment [ 49 ]. 2.4.3. The Impact of ESG on Economic Consequences In general, the ESG performance index is likely to clarify the relationship between sustainable investment and financial performance (Khan et al., 2016) [ 50 ]. According to CiteSpace’s statistics on keywords, from the perspective of word frequency (see Table 2 ) and centrality (see Table 3 ), related keywords include corporate social responsibility, performance, sustainability, financial performance, social responsibility, responsibility, firm performance, shareholder value, and firm value, and their frequency of occurrence is 234, 140, 125, 83, 80, 33, 30, 29, and 14, respectively. In terms of centrality, except for firm value, the centrality of the other eight keywords is 0.08, 0.06, 0.07, 0.06, 0.06, 0.02, 0.02, and 0.03, respectively. It can be observed that the related keywords rank top in terms of word frequency and centrality. In terms of time, “financial performance” was a research hotspot in 2006 and 2016. Moreover, “firm performance” and “firm value” became hot topics in 2010 and 2017, respectively. In addition, from the statistical results of the burst terms, the keywords represented by “financial performance” and “firm value” attracted much attention between 2016 and 2020 (see Table 4 ). Therefore, the research on the relationship between ESG and economic consequences is a hot topic. For example, Awaysheh et al. (2020) used the KLD database to measure the overall situation of ESG. They studied the benchmarking of enterprises in the fixed effect of time and industry, identifying the best (top 10%) and worst enterprises (last 10%). It was found that the best enterprises have a higher level of operating performance and a higher relative market valuation than those of their peers. When the governance (G) dimension is removed, the result remains unchanged [ 51 ]. Research on the relationship between corporate social irresponsibility and financial risks showed that the negative media coverage on the environmental, social, and governance (ESG) issues will increase the credit risks of enterprises and lead to an increase in enterprise financial risks (Kölbel et al., 2017) [ 16 ]. Moreover, different scholars measure the sustainable development behavior of enterprises from different perspectives, which can be divided into four types, namely, positive correlation, negative correlation, non-linear relationship, and indirect relationship. Positive Correlation First, most of the existing studies on this topic measure ESG activities from the perspective of the combination of the environmental (E) and social (S) dimensions and empirically test the relationship between ESG activities and corporate financial performance and corporate value. Mackey et al. (2007) used the KLD database and concentrated on the environmental (E) and social (S) dimensions, believing that there is a positive correlation between ESG activities and corporate values [ 52 ]. Jayachandran et al. (2013) studied the impact of corporate social performance (CSP) on corporate performance. The results of the study using the classification measures of the social dimension (product social performance) and environmental dimension (environmental and social performance) show that compared with the environmental (E) dimension, the social (S) dimension has a stronger, positive impact on corporate performance [ 13 ]. In addition, Flammer et al. (2019) studied the effectiveness and implications of integrating environmental and social performance standards into executive compensation. It was found that the contract not only alleviated the myopia of enterprises but also improved corporate performance and corporate value significantly, which indicates the increase in long-term operating profit. Moreover, enterprises using the contracts improve their environmental and social performance, especially in the environment and local communities [ 15 ]. Secondly, we reviewed the studies that only focus on the environmental (E) dimension. Environmental social performance has a positive impact on corporate performance (Jayachandran et al., 2013) [ 13 ], but environmental screening conditions reduce corporate financial performance (Barnett and Salomon, 2006) [ 53 ]. Matsumura et al. (2014) studied the impact of carbon emissions and voluntary disclosure of carbon emissions on corporate value by collecting environmental performance data. It was found that carbon emissions are inversely proportional to corporate value and that the decision and level of managers’ disclosure of carbon emissions are directly proportional to corporate value [ 54 ]. Finally, we also reviewed the studies that only focus on the social (S) dimension. Godfrey (2005) studied the relationship between philanthropic activities and shareholder wealth and concluded that corporate philanthropy could generate positive moral capital between communities and stakeholders. This kind of moral capital could provide shareholders with an insurance-like mechanism of intangible values based on corporate relationships. This protective mechanism could also help to increase shareholders’ wealth [ 55 ]. Wang and Qian (2011) researched the relationship between corporate philanthropy and corporate financial performance. Corporate philanthropy is expected to have a positive impact on corporate financial performance because it helps companies to gain socio-political legitimacy, thereby enabling companies to receive positive stakeholder responses and gain political opportunities. For companies with a higher public profile and companies with better past performance, the relationship between positive philanthropy and performance is stronger because of a more positive response from stakeholders to the philanthropy of these companies. However, private companies or companies with no political connections can benefit more from philanthropy because obtaining access to political resources is critical. Therefore, researchers believe that corporate philanthropy could improve corporate financial performance by stimulating a positive response from key stakeholders, such as employees, customers, and investors, and by obtaining political resources from the government [ 56 ]. Furthermore, Kaul and Luo (2018) studied the conditions for corporate social responsibility to provide positive benefits to the company, and found that if social responsibility is related to a company’s core business or does not overlap with non-profit activities, it can provide financial benefits to the company [ 57 ]. 2. Negative Correlation There is a negative relationship between ESG activities and economic consequences. The research conducted by Manchiraju and Rajgopal (2017) showed a significant negative correlation between corporate social responsibility and shareholder value [ 58 ]. Similarly, the research conducted by Chen et al. (2018) found that the mandatory disclosure of corporate social responsibility not only reduces performance but also increases social responsibility costs, which generate positive externalities at the expense of shareholders’ interests [ 59 ]. 3. Non-Linear Relationship There are studies that show that the relationship between corporate sustainable development behavior and financial performance is not linear. For example, the study conducted by Barnett and Salomon (2006), which analyzed the relationship between social performance and financial performance based on environmental (E) and social (S) dimensions, found that financial returns began to decline as the number of social (S) dimensional screening projects used by socially responsible investment increased. However, the financial returns rebounded again as the number of screenings continued to increase. In other words, the study found a curve relationship [ 53 ]. Furthermore, Barnett and Salomon (2012) found a U-shaped relationship between corporate social performance and corporate financial performance. Specifically, companies with low CSP have higher financial performance than those with medium CSP, but companies with high CSP have the highest financial performance. That is, the companies with the highest CSP usually have the highest financial performance [ 60 ]. Moreover, Zhao and Murrell (2016) pointed out that corporate social performance may not have a positive impact on corporate financial performance. On the contrary, there is a complex relationship between corporate social performance and corporate financial performance, so it cannot be simply said that doing good will do well [ 61 ]. 4. Indirect Relationship Surroca et al. (2010) found that there is no direct relationship between corporate social responsibility and financial performance. Instead, mediating factors, such as innovation, human capital, reputation, and culture, are required to form an indirect relationship [ 17 ]. The research conducted by Hull and Rothenberg (2008) found that supporting innovation and the level of industry differences are factors that could regulate the positive relationship between corporate social performance and financial performance [ 62 ]. Ramchander et al. (2012) discovered the role of information asymmetry in explaining the relationship between corporate social responsibility and financial performance [ 63 ]. Similarly, the research conducted by Lys et al. (2015) found that the positive correlation between corporate performance and corporate social responsibility expenditure is more likely to be due to the signal of corporate social responsibility expenditure [ 64 ]. Later, Hawn and Ioannou (2016), on the basis of the neo-institutional theory, suggested that corporate social responsibility is related to better market value by distinguishing between external and internal corporate social responsibility actions [ 65 ]. Furthermore, Surroca et al. (2020) found that companies are facing tremendous pressure to achieve short-term goals in a free market economy, especially when companies participate in internally oriented corporate social responsibility projects and the combination of managerial entrenchment provisions (MEPs) and corporate social responsibility creates shareholder value. However, the combination of managerial entrenchment provisions (MEPs) and corporate social responsibility will destroy shareholder value when corporate social responsibility is externally oriented [ 66 ]. Among the studies reviewed in this paper, few use governance (G) as a measurement dimension to study the impact of ESG on corporate financial performance or corporate value. The reason for this is that the influencing factors of the economic consequences of a company should be a comprehensive manifestation of multiple dimensions. Although the corporate governance structure could have an impact on it, a separate corporate governance structure has little significance for the economic consequences of a company. 2.4.4. The Risk Prevention Role of ESG As a kind of non-financial investment of enterprises, ESG is a mechanism and means of risk prevention for enterprises. According to the analysis results of CiteSpace regarding keywords, from the word frequency results (see Table 2 ), the frequency of sustainability, strategy, legitimacy, risk, institutional theory, reputation, and competitive advantage is 125, 71, 27, 24, 23, 21, and 20, respectively, ranking in the top 29. From the results of centrality (see Table 3 ), the centrality of strategy, competitive advantage, sustainability, legitimacy, and institutional theory is 0.1, 0.09, 0.07, 0.03, and 0.02, respectively, ranking in the top 47. It can be seen that ESG practice can meet the legitimate needs of stakeholders in the process of the sustainable development of enterprises. It can not only improve the social reputation of enterprises, but also play a role in resisting risks as a means of competition. Therefore, the risk prevention role of ESG in business activities is a research hotspot. With regard to the ESG as a whole. Koh et al. (2014) took ESG as a whole as their research object and put forward the viewpoint of risk management. The authors used the KLD database to standardize multiple dimensions of community relations, diversity, employee relations, environment, and products and constructed an overall measurement index of corporate social performance. It is believed that social performance can be used as an insurance mechanism that is more valuable to companies with higher litigation risks [ 14 ]. Mithani (2017) found that philanthropy can alleviate the liability of foreignness (LOF) of companies after disasters in a specific country and can strengthen the position of multinational companies. Therefore, philanthropy has important strategic significance for multinational companies after disasters [ 67 ]. Zhou and Wang (2020) found that the fulfillment of corporate social responsibilities by subsidiaries can be used as a means to buffer the negative spillover effects caused by the parent company’s reputation risk. Specifically, the social responsibility activities of subsidiaries could help them to obtain social legitimacy and form an insurance-like mechanism [ 68 ]. With regard to the environmental (E) dimension. Flammer (2013) researched the response of the stock market to environmental social responsibility and found that the active participation of enterprises in environmental aspects can create new competitive resources for companies and play an insurance-like role. On the one hand, shareholders will respond positively to companies that announce eco-friendly initiatives. Conversely, a company’s environmental social responsibility will play an insurance-like role when an eco-harmful event occurs, thereby allowing the enterprise to suffer fewer losses [ 69 ]. With regard to the social (S) dimension. Shiu and Yang (2017) measured the social dimension through the KLD database and found that corporate social responsibility can play an insurance-like role in the negative events of stock and bond prices. This role can have a great impact on the first negative event [ 70 ]. Similarly, Jia et al. (2020) studied whether corporate social responsibility investment could be used as an insurance mechanism for corporate risk prevention. Specifically, when companies face higher external risks brought about by Reg SHO, pilot companies will pursue corporate social responsibility to obtain an insurance-like protective effect to reduce their short positions. Secondly, companies facing the threat of short-selling can increase their corporate social performance by addressing the “concerns” item of corporate social responsibility to deal with the short-selling threat. Finally, the increased corporate social responsibility will reduce the short equity of the pilot company’s stocks. This decrease is attributed to the insurance effect of corporate social responsibility [ 71 ]. With regard to the governance (G) dimension. Gao et al. (2014) used the KLD database to exclude the governance (G) dimension to construct a corporate social responsibility net score and found the significant negative relationship between social good and inside-trading of executives [ 23 ]. Flammer and Kacperczyk (2019) found that using corporate social responsibility as a strategic tool to address the threat of knowledge encroachment from competitors can not only reduce the tendency of employees to join competing companies, but also decrease the possibility of valuable information leakage, even if employees join competing companies [ 19 ]. In a recent study, Bertrand et al. (2021) focused on the social pillar scores in the ESG scores of the Thomson Reuters ASSET4 database. It was observed that CEOs can improve corporate social responsibility practices and corporate social performance to respond to biases from outside when local companies have a foreign CEO [ 35 ]. 2.4.5. ESG Measurement ESG measurement is the basis for testing the effectiveness of enterprise ESG practice and the standard for enterprise ESG disclosure. The analysis results of CiteSpace showed that the centrality of the keyword “framework” in 2005 was 0.04 (see Table 3 ). Moreover, from the statistical results of the burst terms (see Table 4 ), the intensity of “framework” was 4.31. It was a keyword that received widespread attention in ESG research from 2005 to 2014, which is consistent with the rise of ESG research. A reasonable ESG framework is the basis for its measurement. Secondly, according to the term frequency of keywords (see Table 2 ), the word “disclosure” appeared most frequently in 2016, at 15 times. From the perspective of ESG development, the establishment of the ESG evaluation system promotes the rise of research issues related to ESG disclosure. Based on this, we summarized the measurement methods of ESG. In the selected literature in this paper, the data for measuring ESG overall or each dimension index score mainly originated from the KLD database and Thomson Reuters ASSET4 database. This study organized the advantages and disadvantages, measurement methods, and score construction based on the two databases in the literature (see Table 5 ). Table 5. Organization of data sources for ESG score construction. Measurement based on KLD Database In terms of ESG measurement, Kim et al. (2021) proposed a practical technique to evaluate corporate social responsibility policies [ 72 ], that is, to quantify corporate social responsibility insurance mechanisms. However, managers, investors, and researchers know little about whether these ratings measure corporate social responsibility accurately (Chatterji et al., 2016) [ 73 ]. The most widely used database in the literature is the KLD database, which can provide data relating to sustainable development. It is the most widely used database in previous studies on ESG (Shiu and Yang, 2017) [ 70 ], corporate social responsibility (Deckop et al., 2006) [ 74 ], corporate commitment to social good, the measurement of CSR performance (Gao et al., 2014) [ 23 ], and the relationship between social responsibility and financial performance (Ioannou and Serafeim, 2015) [ 75 ]. KLD is widely used because it has the following advantages. First, the KLD database covers a wide range of industries and a long-time frame. The database was built in 1991, and the total number of companies it has tracked since 2003 has reached 3100. Other databases with sustainability data, such as Thomson Reuters ASSET4, have shorter time series and cover fewer US companies. Second, the KLD database provides relevant information in a standardized form. It rates important attributes of corporate social performance and uses a set of objective evaluation standards to ensure the consistency of evaluation. Third, the KLD database is used by professional investment personnel to construct investment portfolios and is a comprehensive data source for tracking corporate social performance. The research and ratings of ESG include the environmental, social, and governance (ESG) factors, using a proprietary research method to evaluate the ESG performance of companies. Before 2001, there were 33 projects in the KLD database, and this number had increased to 40 projects by 2007 (Shiu and Yang, 2017) [ 70 ]. The KLD database contains a wide range of corporate social responsibility ratings, including seven key stakeholder attributes: community, employee relations, diversity, environment, human rights, product quality, and corporate governance. At the same time, there are multiple sub-dimensions within each dimension. For example, environmental issues include waste management, environment, climate change, and water pressure. Social issues include the performance of issues such as community participation, human rights, union relations, labor diversity, and funding access. Governance issues include the implementation of issues such as report quality, corruption, and political instability, financial system instability, governance structure, and business ethics (Khan et al., 2016) [ 50 ]. In addition, the KLD database also includes six exclusive screening categories, namely, alcohol, gambling, military contracting, nuclear energy, and tobacco. In terms of measurement, KLD is a binary system that includes “strengths” and “concerns” (weaknesses). “Strengths” are policies, procedures, and results that can help companies to produce a positive impact on key issues—that is, socially responsible behavior. However, “concerns” are the opposite. In the KLD database, “1” is used to indicate the existence of screening (standard), and “0” is used to indicate its absence. In other words, if a company meets the description of the evaluation item, the company’s score is “1”. Otherwise, it is “0”. Therefore, the overall evaluation project score reflects the overall level of the company’s corporate social responsibility participation. Specifically, two methods are used to measure ESG as a whole or in various dimensions. First, the KLD index can be constructed by accumulating all of the “strengths” items related to research variables. In addition, it can also be measured by constructing a “net” KLD index. The usual practice is constructing the KLD index by calculating the difference between the total “strengths” and the total “concerns” after accumulating the two indexes separately. However, studies have shown that this method has certain shortcomings. Due to the lack of convergence effectiveness of KLD’s “strengths” and “concerns,” it is difficult to provide an effective corporate social responsibility measurement standard (Kacperczyk, 2009) [ 76 ]. Therefore, the empirical analysis of ESG research focuses more on the cumulative method, and the “net” KLD index can be used as a robustness test. In addition, there are studies performing further processing based on the ESG score measurement method. The standardized scores of each category in the selected categories are averaged to calculate the annual composite score of each company. This kind of corporate social responsibility index can not only conduct a simple assessment of corporate social responsibility actions, but is also usually used by professionals to assess the degree of corporate social responsibility effort as a comprehensive index (Chatterji et al., 2016) [ 73 ]. 2. Measurement based on Thomson Reuters ASSET4 Database Thomson Reuters ASSET4 specializes in providing objective, relevant, and systematic non-financial ESG information and investment analysis tools for professional investors. The database has been providing comprehensive corporate social responsibility data for companies in the Russell 1000 since 2002. Its data sources generally include stock exchange literature, annual financial, and sustainability reports, as well as the websites of non-governmental organizations and various news sources. Its dedicated research analysts collected 900 evaluation points for each company, and all data used must be objective and public. After collecting the annual ESG data, analysts unified the units for quantitative analysis of these qualitative data. The database mainly focuses on the finance, corporate governance, environmental, and social aspects. In the environmental dimension, the data include energy use, water recycling, carbon dioxide emissions, waste recycling, and spill and pollution disputes. In the social dimension, the data include employee turnover, injury rates, training hours, female employees, donations, and health and security disputes. In the governance dimension, the data include executive compensation, board experience, board diversity, anti-takeover devices, and pay-cheque disputes. The data are divided into two categories: “drivers” and “outcomes.” “Drivers” refer to policies on issues such as emission reduction, human rights, and shareholder rights. “Outcomes” refer to quantitative results of greenhouse gas emissions, personnel turnover, and maximum salary packages. In terms of measurement, studies that measure ESG overall usually select annual environmental scores, social scores, and governance scores to construct a corporate social responsibility index by assigning equal weight to each pillar in the three dimensions. The corporate social responsibility index is the average of the three ESG indexes (Kim et al., 2021) [ 72 ] or the equally weighted average of the company’s environmental, social, and governance scores (Cheng et al., 2014; Surroca et al., 2020) [ 21 , 66 ]. In addition, some studies only select the environmental (E) and social (S) dimensions (Lys et al., 2015) [ 64 ] or only the social (S) dimension (Kim et al., 2021) [ 72 ]. In summary, this paper systematically examined and summarized the research of ESG through the combination of a bibliometric analysis and a literature review. It was found that the research related to ESG is mainly divided into five modules: the theoretical basis of ESG, the interaction between the three dimensions of ESG, the impact of ESG on economic consequences, the risk prevention role of ESG, and ESG measurement. These studies are mainly based on three dimensions, namely environmental, social, and governance. They not only focus on the interaction between these three dimensions, but also emphasize the role and significance of each individual dimension in ESG. Therefore, based on the analysis of ESG research progress, this paper further refines the specific characteristics of ESG research and proposes the future research direction of ESG (see Figure 4 ). Figure 4. Research progress and future prospects. 3. Conclusions and Future Research 3.1. Conclusions This paper systematically examined and analyzed the research progress of ESG, and the conclusions presented below were drawn. 3.1.1. The Theoretical Basis Is Centralized and Diverse The theoretical basis of ESG research is mainly based on “institutional theory” and “stakeholder theory.” From the keyword co-occurrence map (see Figure 3 ), “institutional theory” is an important topic of ESG research. In terms of word frequency statistics (see Table 2 and Table 3 ), “institutional theory” became the focus of ESG research in 2011, with a frequency of 23 and a centrality of 0.02, and “stakeholder theory” became the focus of ESG research in 2007, with a frequency of 19 and a centrality of 0.02. In addition, from the statistics of the burst terms (see Table 4 ), “stakeholder theory” became a hot topic from 2012 to 2013, with an intensity of 2.97. The decision making and sustainable development of enterprises are interdependent with their stakeholders. Moreover, the production and development of enterprises depend on their legitimate activities in the internal and external environments. This is the reason for the current research’s focus on these two theories. However, through a literature review, we found that there are also studies on natural-resource-based theory, resource dependence theory, affect-as-information theory, place attachment theory, upper echelons theory, signaling theory, agency theory, attribution theory, transaction cost theory, system justification theory, and social identity theory. Different studies start from different angles and objects to study the performance and effect of ESG in various aspects. Therefore, ESG research appeared to be centralized and possess diverse characteristics in terms of theoretical basis. 3.1.2. ESG Research Is Specific Focus on the interaction between the dimensions of the environmental (E), social (S), and governance (G). From the perspective of word frequency (see Table 2 2. ESG research tends to be from the perspective of internal governance. Firstly, from the statistics of the burst terms (see Table 4 ), the keywords developed from “company” to “incentive” and “director” from 2004 to 2020. The theme of the research shows the trend and characteristics from macro to micro. Secondly, from the statistics of the keywords (see Table 2 and Table 3 ), the keywords related to internal governance include governance, organization, behavior, shareholder value, identity, capability, determinant, stakeholder theory, choice, corporate governance, ownership, consumer, disclosure, work, self-regulation, and commitment. Accounting for nearly one-third of the top 50 keywords, internal governance is the research focus of ESG. It is embodied in the interaction between executive factors and the social (S) dimension, the interaction between executive factors and the environmental (E) dimension, the interaction between stakeholder factors and the social (S) dimension, the interaction between stakeholder factors and the environmental (E) dimension, and the role of governance (G) in risk prevention. Therefore, in terms of the research hot topic and contents, ESG research is more inclined to the perspective of internal governance. 3.1.3. Economic Consequences Are an Important Topic in ESG Research The keyword co-occurrence map demonstrated that “organizational performance” is one of the issues of ESG research (see Figure 3 ). In terms of the importance of research, the research on the impact of ESG on economic consequences has always been a hot topic. Firstly, “financial performance” was a hot research topic in 2006 and 2016, with word frequency of 83 and 16 and centrality of 0.06 and 0.02, respectively (see Table 2 and Table 3 ). Moreover, “firm performance” became a hot research topic in 2010, with a word frequency of 30 and a centrality of 0.02. In addition, “firm value” became a hot research topic in 2017, with a word frequency of 14 and a centrality of 0.01. Therefore, it can be seen from the distribution of time that economic consequences have always been a hot topic in ESG research. Secondly, from the statistics of the burst terms (see Table 4 ), “financial performance” was a hot research topic in 2016–2017, with an intensity of 4.75, ranking first. Moreover, “firm value” was a hot topic from 2017 to 2020, with an intensity of 3.67. These topics all show high outbreak intensity, which can sufficiently explain the important position of economic consequences in ESG research. Moreover, in terms of research content, it is mainly divided into four parts: positive correlation, negative correlation, non-linear relationship, indirect relationship. Regarding the dimensions, it mainly focuses on the combination of the environmental (E) and social (S) dimensions, a separate environmental (E) dimension, and a separate social (S) dimension to measure the impact of ESG on the economic consequences of enterprises. However, from the statistical results of the word frequency and centrality of keywords and the analysis results of the burst terms, “firm value” is a topic that has only emerged in recent years in ESG research. Firm value can reflect a company’s future value-adding capabilities, risk control, and other capabilities of sustainable development, which are vital to its future growth. Similarly, ESG, as a value that considers the sustainable and coordinated development of economic, environmental, social, and governance benefits, and an investment philosophy that pursues long-term value growth, coincides with the importance of firm value. Hence, future research focusing on exploring the relationship between ESG and firm value is of vital importance to further verify companies’ sustainable development capabilities. 3.1.4. ESG Measurement Has Limitations Through a systematic literature review, we found that the commonly used ESG data have the following two characteristics: on the one hand, because ESG research is an emerging topic, the data mainly come from the KLD database and Thomson Reuters ASSET4 database. However, there are certain differences in the measured dimensions and criteria for selection. Therefore, the lack of a unified standard for measurement may lead to deviations in the results of various studies. On the other hand, although existing research institutions have formed ESG measurement and evaluation systems, they are relatively limited in terms of the diversity and breadth. In the current research, although the KLD database and Thomson Reuters ASSET 4 database maintain their mainstream status, ESG, as a comprehensive measure to solve the global sustainable development problem, should be embedded in different institutional backgrounds and industry characteristics. The validity and reliability of the KLD database and Thomson Reuters ASSET4 database in ESG measurement in emerging countries remain to be considered. Therefore, we should not only unify the standards globally to improve their credibility and persuasiveness, but also consider the special institutional background of each country and the characteristics of different industries; therefore, we should analyze some specific problems and establish a comprehensive and mature ESG measurement system. We look forward to the further improvement of the ESG measurement system to facilitate academic research on ESG. 3.2. Future Research Based on the above review of the contents and limitations of ESG research, we look forward to furthering the advancement of ESG research in the following aspects. Clarification of the unified definition of ESG concepts. ESG, as a non-financial index of enterprises, represents the practice and performance of an enterprise in terms of environmental, social, and governance. Before the concept of ESG was widely known, it was usually called “responsible investment” and was also defined as “CSR.” Therefore, the concept of ESG has not yet been unified and clarified. In addition, there are differences in the selection of ESG index types in various dimensions, which results in the inconsistency of the definition of ESG and its dimensions. This, in turn, affects the authority and credibility of the definition of ESG. In the future, academic institutions and scholars in various countries should strengthen cooperation and continue to endeavor to define the ESG concept and the deepening of ESG research. 2. Strengthening the theoretical basis of ESG research. The theoretical basis of ESG research is centralized and diverse, mainly based on “institutional theory” and “stakeholder theory.” Meanwhile, there is also research based on natural-resource-based theory, resource dependence theory, affect-as-information theory, place attachment theory, upper echelons theory, signaling theory, agency theory, attribution theory, transaction cost theory, system justification theory, and social identity theory. However, to date, there has not been a unified and appropriate theoretical basis that can systematically explain the internal mechanism of corporate ESG practice. Therefore, with the development and maturity of ESG research, further exploration and improvement are needed in the theoretical basis in the future. 3. The content of ESG research continues to deepen. Through the analysis of the second part, we found that ESG research gradually showed a more detailed feature. In terms of content, it focuses on the interaction between various dimensions and on internal governance. However, there is still room for further improvement. On the one hand, there is a lack of research on the interaction between the environmental (E) and social (S) dimensions. The reason for this is that the existing studies usually classify the environmental (E) dimension as a social (S) dimension. They rarely study it as a separate dimension, which is specifically reflected in the selection of ESG indexes. From the perspective of sustainable development, the environmental (E) issue is one of the important issues, since it is the basis for the sustainable development of the economy and society. In the future, the environmental (E) dimension should be separated from the social (S) dimension. Furthermore, future studies should aim to explore the relationship between the environmental (E) and social (S) dimensions, enrich the interactive research between the environmental (E) and governance (G) dimensions, and highlight the significance and importance of the environmental (E) dimension under the theme of ESG. On the other hand, the governance (G) dimension is the focus of ESG research, but there are few studies on the relationship between governance (G) and economic consequences. Although the influencing factors of economic consequences are a multi-dimensional comprehensive embodiment, governance (G), as the core of management, is an important factor affecting firm performance. With the development of the economy and society, governance (G) is an important factor in further promoting high-quality development. In the future, we should further explore the research of governance (G) regarding the impact of ESG on economic consequences. Therefore, ESG, as an important factor affecting the investment and return of enterprises, continues to deepen the research content of ESG, forms a complete closed loop, and explores the importance of ESG in the process of sustainable development from a more specific and detailed perspective, which is of great significance for future research. 4. Promotion of the improvement in the ESG evaluation system. An effective and consistent evaluation system is a standard for measuring the sustainable development activities of various enterprises in the industry. In the literature, the evaluation system used for ESG measurement is mainly based on the relevant data in the KLD database and Thomson Reuters ASSET4 database. However, the overall ESG and the standards of various dimensions measured by various databases lack uniformity. Most of the evaluation systems are established using expert scoring, and so there is a certain degree of subjectivity. At the same time, the database lacks applicability and feasibility based on different national systems and industry backgrounds. Therefore, a unified and mature ESG evaluation system is the foundation for the study of corporate sustainable development, the key to the credibility of corporate social responsibility information disclosure, and a quantitative standard for promoting the effectiveness of ESG practices. Simple, accurate, and efficient quantitative methods guarantee the implementation of ESG concepts and are also important modules that need to be further clarified in future research. 5. Promotion of the ESG practice of various organizations. ESG is the core framework for enterprises to pursue sustainable development. Integrating it into business management and investment decision making has become an international passport for enterprises to practice sustainable development. Through the analysis and summary of ESG research progress, we expect to provide substantive enlightenment and suggestions to enterprises, government regulators, financial institutions, and academic institutions. Firstly, in terms of enterprises, companies should re-examine internal governance to consider how to give full play to the positive impact of ESG on the economic consequences with regard to the aspects of senior management appointment and organizational structure design and employee training in order to actively build effective risk prevention and a “protection” mechanism. Secondly, in terms of government regulators, based on fully understanding the importance of ESG practice in sustainable development, reasonable policies, regulations, and information disclosure systems should be formulated to standardize enterprise behavior. At the same time, the construction and unification of the ESG evaluation system should be actively promoted to provide a basis for the investment decision making of financial institutions. In addition, in terms of financial institutions, through the systematic analysis of governance (G), we could provide more detailed and comprehensive non-data investment decision-making information for financial institutions. Moreover, we assume that financial institutions will be able to provide substantive suggestions for improving the ESG evaluation system from the perspective of practice. Finally, in terms of academic institutions, through the review of ESG research, we clarified the context of ESG research, summarized the characteristics of the past research in terms of trends and content, and highlighted the shortcomings in order to propose several future research directions and a vision for the future research of ESG. Author Contributions Writing: T.-T.L.; providing ideas and data: T.-T.L. and K.W.; providing revised advice: T.S. and D.D.W. All authors have read and agreed to the published version of the manuscript. Funding This research was funded by Beijing Social Science Fund Project (grant number: 18GLC076). Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement Not applicable. Conflicts of Interest The authors declare no conflict of interest. References EBA. EBA Report on Management and Supervision of ESG Risks for Credit Institutions and Investment Firms. 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Dimension Factors Definition Environmental (E) GHG emissions Energy consumption and efficiency Air pollutants Water usage and recycling Waste production and management (water, solid, hazardous) Impact and dependence on biodiversity Impact and dependence on ecosystems Innovation in environmentally friendly products and services Environmental matters that may have a positive or negative impact on the financial performance or solvency of an entity, sovereign, or individual. Social (S) Workforce freedom of association Child labor Forced and compulsory labor Workplace health and safety Customer health and safety Discrimination, diversity, and equal Opportunity Poverty and community impact Supply chain management Training and education Customer privacy Community impacts Social matters that may have a positive or negative impact on the financial performance or solvency of an entity, sovereign, or individual. Governance (G) Codes of conduct and business principles Accountability Transparency and disclosure Executive pay Board diversity and structure Bribery and corruption Stakeholder engagement Shareholder rights Governance matters that may have a positive or negative impact on the financial performance or solvency of an entity, sovereign, or individual. Source: own elaboration base on the EBA report on ESG risk management and supervision. Available online: https://www.eba.europa.eu/sites/default/documents/files/document_library/Publications/Reports/2021/1015656/EBA%20Report%20on%20ESG%20risks%20management%20and%20supervision.pdf (accessed on 31 July 2021). Table 2. Statistic information of keywords (by frequency 1–50). No. Freq Centrality Year Keywords No. Freq Centrality Year Keywords 1 234 0.08 2004 corporate social responsibility 26 22 0.04 2005 green 2 140 0.06 2004 performance 27 22 0.03 2004 company 3 125 0.07 2007 sustainability 28 21 0.01 2009 reputation 4 113 0.08 2004 management 29 20 0.09 2004 competitive advantage 5 83 0.06 2006 financial performance 30 20 0.06 2009 construction 6 80 0.16 2004 firm 31 19 0.06 2008 capability 7 80 0.12 2004 impact 32 19 0.04 2012 determinant 8 80 0.06 2007 social responsibility 33 19 0.02 2016 CSR 9 74 0.07 2006 governance 34 19 0.02 2007 stakeholder theory 10 71 0.1 2007 strategy 35 18 0.03 2011 resource based view 11 61 0.07 2005 organization 36 18 0.03 2009 choice 12 61 0.06 2004 model 37 18 0.02 2012 corporate governance 13 44 0.07 2006 perspective 38 17 0.06 2005 industry 14 38 0.13 2004 behavior 39 17 0.03 2010 competition 15 37 0.04 2007 business 40 16 0.04 2006 environment 16 33 0.04 2005 market 41 16 0.03 2012 ownership 17 33 0.02 2006 responsibility 42 16 0.02 2016 financial performance 18 30 0.02 2010 firm performance 43 15 0.06 2006 consumer 19 29 0.03 2011 shareholder value 44 15 0.02 2009 information 20 29 0.03 2007 innovation 45 15 0.01 2015 philanthropy 21 27 0.06 2008 cost 46 15 0 2016 disclosure 22 27 0.04 2011 identity 47 14 0.02 2012 work 23 27 0.03 2005 legitimacy 48 14 0.02 2010 environmental performance 24 24 0.01 2013 risk 49 14 0.01 2017 firm value 25 23 0.02 2011 institutional theory 50 14 0 2015 self-regulation Source: own elaboration based on CiteSpace. Table 3. Statistic information of keywords (by centrality 1–50). No. Freq Centrality Year Keywords No. Freq Centrality Year Keywords 1 80 0.16 2004 firm 26 19 0.04 2012 determinant 2 38 0.13 2004 behavior 27 16 0.04 2006 environment 3 80 0.12 2004 impact 28 13 0.04 2005 framework 4 71 0.1 2007 strategy 29 9 0.04 2004 consequence 5 20 0.09 2004 competitive advantage 30 29 0.03 2011 shareholder value 6 234 0.08 2004 corporate social responsibility 31 29 0.03 2007 innovation 7 113 0.08 2004 management 32 27 0.03 2005 legitimacy 8 125 0.07 2007 sustainability 33 22 0.03 2004 company 9 74 0.07 2006 governance 34 18 0.03 2011 resource based view 10 61 0.07 2005 organization 35 18 0.03 2009 choice 11 44 0.07 2006 perspective 36 17 0.03 2010 competition 12 140 0.06 2004 performance 37 16 0.03 2012 ownership 13 83 0.06 2006 financial performance 38 12 0.03 2005 quality 14 80 0.06 2007 social responsibility 39 12 0.03 2008 knowledge 15 61 0.06 2004 model 40 11 0.03 2009 response 16 27 0.06 2008 cost 41 10 0.03 2015 social movement 17 20 0.06 2009 construction 42 9 0.03 2006 product 18 19 0.06 2008 capability 43 7 0.03 2006 alliance 19 17 0.06 2005 industry 44 6 0.03 2005 commitment 20 15 0.06 2006 consumer 45 33 0.02 2006 responsibility 21 7 0.06 2006 altruism 46 30 0.02 2010 firm performance 22 37 0.04 2007 business 47 23 0.02 2011 institutional theory 23 33 0.04 2005 market 48 19 0.02 2016 CSR 24 27 0.04 2011 identity 49 19 0.02 2007 stakeholder theory 25 22 0.04 2005 green 50 18 0.02 2012 Corporate governance Source: own elaboration based on CiteSpace. Table 4. Statistic information of burst terms. Keywords Strength Begin End Duration 2004–2020 company 4.36 2004 2009 5 framework 4.31 2005 2014 9 technology 3.98 2006 2010 4 perspective 3.37 2006 2009 3 altruism 3.14 2006 2012 6 capability 2.99 2008 2011 3 competition 3.66 2010 2013 3 consumption 3.17 2012 2013 1 choice 3.07 2012 2013 1 stakeholder theory 2.97 2012 2013 1 organization 3.28 2013 2014 1 philanthropy 4.63 2015 2018 3 self-regulation 4.32 2015 2018 3 standard 3 2015 2016 1 financial performance 4.75 2016 2017 1 firm value 3.67 2017 2020 3 moderating role 3.2 2018 2020 2 incentive 3.18 2018 2020 2 director 2.91 2018 2020 2 Source: own elaboration base on CiteSpace. Note: In the last column, the bold part means the duration. Table 5. Organization of data sources for ESG score construction. Source: own elaboration, based on literature review. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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PEOPLE v. VS. OMAR MEDINA Y LUMBERIO GR No. 126575, (1998-12-11) EN BANC [ GR No. 126575, Dec 11, 1998 ] PEOPLE v.  VS. OMAR MEDINA Y LUMBERIO + DECISION 360 Phil. 281 EN BANC [ G.R. No. 126575, December 11, 1998 ] THE PEOPLE OF THE PHILIPPINES,  PLAINTIFF-APPELLEE, VS. OMAR MEDINA Y LUMBERIO,  ACCUSED-APPELLANT. D E C I S I O N MARTINEZ, J.: Accused-appellant Omar L. Medina was convicted of having raped the 13-year old daughter of his common-law spouse four (4) times in 1995, and was sentenced to suffer the death penalty for each of the four (4) counts of rape, with all its accessory penalties. Omar Medina was likewise ordered to pay the victim, Lodalyn Flores, for each count the sum of P50,000.00 as indemnity, P50,000.00 as moral damages and another P50,000.00 as exemplary damages. The judgment of conviction was rendered by the Regional Trial Court of Parañaque, Metro Manila, Branch 259, in a consolidated Decision [1] dated September 23, 1996, in Criminal Cases No. 95-710 to 713. The judgment of the trial court is now before us for automatic review pursuant to Article 47 of the Revised Penal Code, as amended by Section 22 of Republic Act No. 7659, [2] and Sections 3 (e) and 10, Rule 122 of the Revised Rules of Court. These four (4) cases of rape were commenced on the basis of four (4) separate complaints signed by complainant Lodalyn Flores and, upon prior authority by the Provincial Prosecutor, the same were filed with the trial court on November 24, 1995, docketed as Criminal Cases No. 95-710, 95-711, 95-712, and 95-713. The crime was allegedly perpetrated by Omar Medina on four (4) occasions as set forth in each of the four (4) complaints which are similarly worded (except with reference to the dates the crime was allegedly committed), thus: "The undersigned complainant accuses Omar Lumberio Medina of the crime of Rape, committed as follows: "That on or about (July 25, 1995, [3] August of 1995, [4] September of 1995 [5] and October of 1995 [6] ), in the Municipality of Parañaque, Metro Manila, Philippines and within the jurisdiction of this Honorable Court, the above-named accused, by means of force and intimidation, did then and there willfully, unlawfully and feloniously have carnal knowledge of the complainant LODALYN FLORES, a minor, 13 years old, against her will. "CONTRARY TO LAW." [7] (dates in parenthesis supplied) Upon arraignment on the four (4) complaints, Omar Medina entered a plea of not guilty. Based on the testimonies of complainant Lodalyn Flores and Dr. Floresto Arizala, Jr., the evidence for the prosecution runs as follows: Lodalyn Flores is the stepdaughter of Omar Medina, he being the common-law husband of her mother, Lolita Flores. Having been born on March 26, 1982, Lodalyn was thirteen (13) years of age and a grade four student at the time she was raped by Omar. She has a younger brother, Rizaldy, nine years of age, and a four-year old half-sister, Aileen, who is Omar's daughter with Lolita. [8] On July 25, 1995, at about 1:00 o' clock in the afternoon, Lodalyn was awakened from her nap at their bedroom in Champaca St., UPS IV, Parañaque, when Omar covered her mouth and tied her hands. Omar threatened Lodalyn with a knife which he placed at her side and forcibly removed Lodalyn's T-shirt and shorts, including her undershirt and panty. He then removed his shorts and brief and placed himself on top of Lodalyn. He boxed her thighs and succeeded in sexually penetrating her. Afterwards, Lodalyn noticed some blood and slimy discharge in her vagina. At the time Lodalyn was sexually abused by Omar, there was no one else inside the house as her brother and sister were playing outside. [9] Lodalyn kept mum about the unfortunate incident as she was afraid of Omar's threat to kill her and her mother. Sometime in August of 1995, Omar again raped Lodalyn when her mother was away from their house and while her younger brother and sister were asleep as it was already 7:00 o' clock in the evening. This happened after Omar asked Lodalyn to prepare her mother's food and to get his T-shirt from the cabinet in the bedroom. While already inside the bedroom, Lodalyn noticed that Omar was at her back. He then gagged her mouth with a piece of cloth he was holding. Lodalyn struggled to free herself, but Omar boxed her stomach to submission and succeeded in sexually ravishing her. Again, Omar threatened to kill her and her mother if she would tell anyone about the incident. [10] The third time Lodalyn was raped by Omar occurred in September of 1995 while her mother was not home yet and her brother and sister were at school. Omar asked Lodalyn to get the P20.00 under the pillow. She complied but as she turned around, Omar was already in front of her. Lodalyn boxed Omar in the chest but he slapped her and placed her on the bed. Omar raised her skirt, removed her panty, then his clothes and sexually assaulted Lodalyn. [11] The fourth and last time Omar ravished Lodalyn took place in October of 1995. This time it was more violent. Omar repeatedly boxed Lodalyn in different parts of her body until she lost consciousness. When she regained consciousness, she felt pain in her vagina and noticed something sticky on the bedsheet where she was lying. [12] On November 17, 1995, after Lodalyn and her mother quarreled when she confronted her mother about Omar's having hurt her brother by hitting the latter at the nape, Lodalyn confided to Consuelo Bofete, a neighbor, what she had suffered in the hands of Omar. In turn, Consuelo relayed to Fely Bofete what Lodalyn told her. Fely then informed Lolita Flores what Omar did to Lodalyn. Lolita was enraged over the report that he ordered Lodalyn, her brother and sister to leave the house. [13] Lodalyn and Fely Bofete sought the assistance of Kagawad Fernando Beltran and the three then went to the National Bureau of Investigation (NBI). Dr. Floresto Arizala, Jr., a medico-legal officer of the NBI, conducted a medical examination on Lodalyn on November 23, 1995. In his medical report, the doctor found, among others, that Lodalyn's hymen has an "old healed deep laceration at 6:00 o'clock position" and "admits a tube 2.5 cm. in diameter." [14] Thereafter, Lodalyn lodged a complaint at the police station which eventually led to the filing of the four (4) charges of rape against Omar. In his defense, Omar Medina admits that Lodalyn Flores, who is about 13 to 14 years of age, is his stepdaughter, he being a common-law husband of Lolita Flores (Lodalyn's mother). He testified that he has never been charged of any crime, except the present four (4) cases of rape. He denied, however, that he sexually abused or raped Lodalyn whom he treats as his very own daughter. During those dates of the alleged rape incidents, he was busy tending his household chores and was then cleaning their pigpens, fetching water and washing their clothes. He believes that the reason why he was charged by Lodalyn is that he used to scold her for entertaining her suitors. [15] Lodalyn's brother, Rizaldy Flores, nine (9) years of age, also testified that Lodalyn seems to dislike Omar since the latter has been telling her not to be too friendly with boys. Lodalyn has a boyfriend by the name of Singcol. Omar washes clothes, cleans the house, takes care of the pigs, fetches water everyday and also cooks for them. He never saw Omar kiss Lodalyn nor did he see them in any intimate situation. It is not true that Omar raped Lodalyn because before he leaves for school and when he comes home, his mother is at their house. [16] After trial, the court a quo rendered judgment finding Omar Medina guilty beyond reasonable doubt of four (4) counts of rape based on the testimony of the victim, Lodalyn, whose version was considered "highly credible." [17] He was sentenced to the maximum penalty of death for each count pursuant to Section 11 of Republic Act No. 7659 on account of his relationship with the victim. In his brief, Omar claims that "it is unlikely" for him to rape Lodalyn since he treats her as his very own daughter. [18] We do not think so. The bestiality in man whose conscience has been seared by his insatiable greed for lust shows no respect for blood or close kinship with his victim. The blood relationship between a father and a daughter does not by itself discount the probability of the father committing rape against his own daughter. More so in this case, considering that Omar is merely the common-law spouse of the victim's mother. In fact, this Court, in the recent case of People v. Gallo, [19] has made the following factual observation: "It is disturbing enough to see that there has been a noticeable increase in the incidents of rape but one is left completely appalled that this still growing number includes cases of the bestial act being perpetrated on the young and innocent and, no longer too infrequently it seems, compounded by the close kinship of the offender and the victim. "In People vs. Malgar (238 SCRA 512), the Court has had occasion to state that - `A father is looked up to as the protector and as the guardian of his family, remaining ever wary of even the slightest harm that might befall it. It is difficult to thus imagine that any such man could instead stand as the predator of his own flesh and blood. Yet, we occasionally would find ourselves so regrettably contending with it as a fact.' [20] (at p. 513)"[underscoring supplied] In rape cases, the accused may be convicted solely on the testimony of the victim, provided that such testimony is credible, natural, convincing and consistent with human nature and the normal course of things. [21] This is so because by its very nature, rape is committed with the least possibility of being seen by the public. [22] In fact, the presence of eyewitnesses could even raise serious doubts of its commission. [23] The court a quo gave credence to the testimony of Lodalyn. And rightly so. Lodalyn was thirteen (13) years old at the time she was raped by Omar four times in 1995. As correctly observed by the trial court, no young and decent Filipina would publicly admit that she was ravished and her honor tainted unless such was true, for it is instinctive of her to protect her honor. [24] It is highly inconceivable for a lass of tender age to concoct a tale of defloration, allow the examination of her private parts, and undergo the expense, trouble, inconvenience, not to mention the trauma of a public trial, unless she was in fact raped. [25] Lodalyn's failure to immediately report the rape after its initial occurrence does not cast grave doubts on her credibility. Such delay is understandable. It is not uncommon for a young innocent girl to conceal for some time the assaults on her virtue because of the rapist's threat on her life, more so when the rapist is living with her. [26] Omar is Lodalyn's stepfather and he lived with her. She was in constant fear of Omar who threatened to kill her and her mother. Being the stepfather, Omar also exercised moral ascendancy and influence over her, who is thus expected to yield to his threats and intimidation. In People v. Casil, [27] we held: ". . . in rape committed by a father against his own daughter, the father's moral ascendancy and influence over the latter substitutes for violence and intimidation. The foregoing principle applies in the case of a sexual assault of a stepdaughter by her stepfather and of a goddaughter by a godfather in the sacrament of confirmation. "In the present recourse, appellant being in fact, if not in law, the stepfather of the victim, who was at the tender age of thirteen years when the first defilement was perpetrated, definitely enjoyed moral and physical ascendancy over complainant. The latter could thus be expected to yield to the threats and intimidation of appellant with less resistance by reason of his dominance over her." Lodalyn's story was full of details that it could not be a product of fabrication. At her age, she could not have narrated in such a straight-forward and convincing manner her defloration, if it were not true. Note her pertinent testimony: "Q - At around 1:00 p.m. of July 25, 1995, where were you? "A - I was at home, in the bedroom. "Q - What were you doing then? "A - I was playing with my brother and sister. "Q - After playing with your brother and sister, what did you do next? "A - After playing, I was able to sleep at about 1:00 p.m. "Q - After you woke up, what did you see or what did you notice, if any? "A - My mouth was gagged and my hands were tied. x x x "Q - When you woke up and saw yourself gagged by the mouth and your hands were tied, where was accused Omar Medina? "A - He was on top of my thigh. x x x "Q - So, while Omar Medina was on top of you, did you notice if Omar Medina was armed or not at that time? "A - He was armed, sir. "Q - What kind of arm did he have? "A - A big knife. "Q - And what was he doing with that knife? "A - He place the knife on my side. "Q - While Omar Medina was on top of you, what was he doing to you? "A - He forcibly removed my panty and shorts and then my t-shirt and sando. x x x "Q - After Omar Medina removed your panty as well as your shorts and tore off your t-shirt, what did he do next, if any? "A - He removed his shorts and brief up to his knees. "Q - After that, what did he do next? "A - Pinatungan niya ang dalawa kong hita.' "Q - 'What was his purpose in laying on top of your legs? "A - To rape me. "Q - Madam witness, how did Omar Medina manage to separate your legs? "A - He boxed my thighs. "Q - After you were boxed, you already spread your legs, is that correct? "A - Yes, sir. "Q - What did you feel when you were boxed by Omar Medina on both thigh? "A - 'Nanlambot po ako.' "Q - After you have already spread your legs, what did Omar Medina do after that? "A - He was forcing to insert his penis inside my private organ. "Q - Going back in the stage wherein the accused Omar Medina was already inserting his penis inside your private organ, did he succeed in inserting his penis inside your vagina? "A - Yes, sir. x x x FISCAL RAMOLET: While Omar Medina, the accused in this case, was inserting his penis inside your vagina, what did you do, if any? "A - I was trying to struggle. "Q - While you were struggling, what did Omar Medina do, if any, on you? "A - 'Dinaganan niya ang dalawa kong hita' so that I cannot move. "Q - You claimed that Omar Medina, the accused in this case, succeeded in inserting his penis to your private part, why did you say that he succeeded in inserting his penis to your private organ? "A - I felt his penis getting in and out of my private organ. x x x "Q - Madam witness, in August 1995, were you raped again by accused Omar Medina? "A - Yes, sir. x x x "Q - So, you were gagged by accused Omar Medina? "A - Yes, sir. "Q - After you were gagged, what happened next? "A - I tried to run away. "Q - And what happened? "A - I was not able to go out. "Q - Why? "A - Because he pulled me and then when he pulled me, I tried to struggle but he boxed me. "Q - What part of your body did the accused box you? "A - In my stomach. "Q - What did you feel when you were boxed by the accused in your abdomen? "A - It was painful, sir. "Q - After that, what did he do? "A - After that he carried me and brought me to bed. "Q - After you were brought to bed, what did he do, if any? "A - He kneeled on my palms. "Q - So, he knelt on your palms when you were already lying down on the bed? "A - Yes, sir. "Q - And after the accused knelt on your palms, what did you do next, if any? "A - None, because I could not struggle. I could not do anything. "Q - After that, what happened next, if any? "A - He removed my shorts and panty. "Q - Which hand did he use in removing your panty and shorts? "A - His right hand. "Q - What about the left hand, what was he doing with his left hand when he was removing your shorts and panty with his right hand? "A - 'Nakatukod po uli.' "Q - Where was that left hand pointed to? "A - On the side of my body. "Q - Up to what extent was the accused managed to remove your underwear and shorts? "A - Below my knees. x x x "Q - And after the accused lowered your shorts and panty, what did he do, if any? "A - He removed his shorts and brief up to his legs. x x x "Q - After the accused lowered already his shorts and brief, what happened next, if any? "A - After that, he held his penis and inserted it on my private organ. x x x "Q - Was he able to make a penetration in your private part? "A - Yes, sir. x x x "Q - Did he succeed in inserting his penis on your private part? "A - Yes, sir. "Q - Where did the accused rape you in September 1995? "A - Also in their bedroom. x x x "Q - And will you tell this Honorable Court how were you raped by the accused Omar Medina in September 1995 inside their bedroom? "A - He asked me to get the P20.00 under the pillow as my additional baon. "Q - Did you get it? "A - There was no money under the table. "Q - When you found out that there was no money, what happened next? "A - 'Pagharap ko,' he was already in front of me. "Q - When he was already in front of you, what did he do, if any, at you? "A - He gagged my mouth with the piece of cloth he was holding. x x x "Q - And after you were gagged by the accused, what did you do, if any? "A - After he gagged my mouth, I was able to run but he caught me by holding my t-shirt. x x x "Q - Madam witness, when you were caught by the accused, what did you do? "A - When he pulled me, I boxed him on the chest. "Q - While you were boxing him, what happened next? "A - He slapped me. "Q - When you were slapped by him, what happened next? "A - I cried. "Q - After that, what did the accused do, if any? "A - He pushed me on the bed. "Q - Then after that, what happened, if any? "A - When I was already on the bed, he placed himself on top of me. "Q - While he was on top of you, what was he then doing? "A - He raised my skirt and removed my panty. "Q - What about his clothes, what did the accused do with his clothes? "A - He also removed his clothes. x x x "Q - When the accused already removed his clothes, what happened next, if any? "A - He spread my legs. "Q - And how did he spread your legs? "A - 'Pinatungan ng dalawang paa niya' and he spread my legs with his feet. "Q - After your legs were already spread by the accused, what happened next, if any? "A - I saw him held his penis. "Q - And then? "A - He forcibly inserted his penis inside my private organ. x x x "Q - In October 1995, did the accused rape you again? "A - Yes, sir. x x x "Q - How did the accused manage to rape you again for the fourth time? "A - He kept on boxing me. x x x "Q - After you were boxed by Omar Medina, what happened to you? "A - I lost consciousness. x x x "Q - You said you became unconscious because you were repeatedly boxed by accused Omar Medina, when you regained consciousness, what did you see or notice, if any, about yourself? "A - My shirts was up and my t-shirt also. "Q - What about your underwear, where was your panty when you regained consciousness? "A - I was still wearing it. "Q - Did you happen to see your private part after you regained consciousness? "A - No, sir. "Q - Did you notice anything when you woke up of bed? "A - Yes, sir. "Q - What was that? "A - When I woke up, I noticed something wet on the bedsheet and I touched it and found it to be a sticky substance. x x x "Q - But immediately after regaining consciousness, did you feel any body pain? "A - Yes, sir. "Q - What about your vagina, did you feel anything at all? "A - It was painful." [28] In contrast, the denials interposed by Omar are shallow and incredible. Obviously, the trial court rejected them. Omar claims that at the time the incidents of rape took place, he was busy doing the household chores and the cleaning of the pigpen. But this assertion is puerile, especially so in the absence of any showing that the pigpen was located at a far distance from their house that it was impossible for him to be at home at those times that the rape occurred. Omar also ascribes to Lodalyn ill-motive for filing the rape charges against him. He maintains that his having scolded her many times for entertaining her suitors has impelled her to get even with him. The motive ascribed is too trivial as to cause Lodalyn to charge appellant with such a serious crime that she had to expose herself to shame and scandal of a public trial. Moreover, the physical evidence of her defloration was corroborated by the medico-legal findings which showed that her hymen has an "old healed deep laceration at 6:00 o'clock position." [29] While we agree with the trial court that the charge of rape against Omar was proven beyond reasonable doubt, we however cannot subscribe to the penalty of death imposed against him as this is contrary to the law and jurisprudence. Although the matter of the proper imposition of the penalty is not assigned as an error by the appellant, nevertheless, it is a well-established rule in criminal procedure that an appeal in a criminal proceeding throws the whole case open for review and it becomes the duty of the appellate court to correct an error as may be found in the appealed judgment, whether it is made the subject of assignment of errors or not. [30] The four (4) separate complaints for rape filed against Omar merely charged him with the simple crime of rape under Article 335 of the Revised Penal Code which warrants the imposition of the penalty of reclusion perpetua. The basis for the imposition of the death penalty by the trial court was the existence of the attendant circumstance of relationship between the offender and the victim pursuant to Republic Act No. 7659 which amended Article 335 of the Revised Penal Code. Section 11 of R.A. 7659 reads: " ART. 335. When and how rape is committed. - Rape is committed by having carnal knowledge of a woman under any of the following circumstances. "1. By using force or intimidation; "2. When the woman is deprived of reason or otherwise unconscious; and "3. When the woman is under twelve years of age or is demented. "The crime of rape shall be punished by reclusion perpetua. "Whenever the crime of rape is committed with the use of deadly weapon or by two or more persons, the penalty shall be reclusion perpetua to death. "When by reason or on the occasion of the rape, the victim has become insane, the penalty shall be death. "When the rape is attempted or frustrated and a homicide is committed by reason or on the occasion thereof, the penalty shall be reclusion perpetua to death. "When by reason or on the occasion of the rape, a homicide is committed, the penalty shall be death. "The death penalty shall also be imposed if the crime of rape is committed with any of the following attendant circumstances: "1. When the victim is under eighteen (18) years of age and the offender is a parent, ascendant, step-parent, guardian, relative by consanguinity or affinity within the third civil degree, or the common-law spouse of the parent of the victim. "2. When the victim is under the custody of the police or military authorities. "3. When the rape is committed in full view of the husband, parent, any of the children or other relatives within the third degree of consanguinity. "4. When the victim is a religious or a child below seven (7) years old. "5. When the offender know that he is afflicted with Acquired Immune Deficiency Syndrome (AIDS) disease. "6. When committed by any member of the Armed Forces of the Philippines or the Philippine National Police or any law enforcement agency. "7. When by reason or on the occasion of the rape, the victim has suffered permanent physical mutilation." [underscoring supplied] In the recent cases of People v. Garcia [31] and People v. Ramos, [32] this Court en banc, speaking through the learned Justice Florenz D. Regalado,[33] declared that these seven new attendant circumstances introduced in Section 11 of R.A. No. 7659 "partake of the nature of qualifying circumstances and not merely aggravating circumstances," since the said qualifying circumstances are punishable by the single indivisible penalty of death and not by reclusion perpetua to death. A qualifying circumstance increases the penalty by degree, while an aggravating circumstance affects only the period of the penalty but does not increase it to a higher degree. [34] In the aforecited case of People v. Ramos, we further explained that: "While Republic Act No. 7659 did not give a legal designation to the crime of rape attended by any of the seven new circumstances introduced in Article 335 on December 31, 1993, this Court has referred to such crime as qualified rape in a number of its decisions. However, with or without a name for this kind of rape, the concurrence of the minority of the victim and her relationship with the offender give a different character to the rape defined in the first part of Article 335. They raise the imposable penalty upon a person accused of rape from reclusion perpetua to the higher and supreme penalty of death. Such an effect conjointly puts relationship and minority of the offended party into the nature of a special qualifying circumstance." In the present case, we note that the qualifying circumstance of relationship was not alleged in the four (4) complaints of rape and, therefore, the said charges are not in its qualified form to fall under the circumstances stated in Section 11 of R.A. 7659. Thus, the penalty of death prescribed in R.A. 7659 should not have been imposed against appellant Omar. In the aforecited case of People v. Garcia, we ruled: "x x x, it has long been the rule that qualifying circumstances must be properly pleaded in the indictment. If the same are not pleaded but proved, they shall be considered only as aggravating circumstances (People v. Collado, 60 Phil. [1934]; People v. Jovellano, et al., 56 SCRA 156 [1974]; People v. Fuertes, 229 SCRA 289 [1994]; People v. Rodico, et al., 249 SCRA 309 [1995] ), since the later admit of proof even if not pleaded (U.S. v. Campo, 23 Phil. 368 [1912]; People v. Domondon, 60 Phil. 729 [1934]; People v. de Guzman, 164 SCRA 215 [1988]). Indeed, it would be a denial of the right of the accused to be informed of the charges against him and, consequently, a denial of due process, if he is charged with simple rape and be convicted of its qualified form punishable with death, although the attendant circumstance qualifying the offense and resulting in the capital punishment was not alleged in the indictment on which he was arraigned. "Recapitulating, the information filed against the appellant charged only the felony of simple rape and no attendant qualifying circumstance, specifically that of his being supposedly a guardian of the victim, was alleged. On this additional consideration, he cannot, therefore, be punished with the penalty of death even assuming arguendo that he is such a guardian. Neither can that fact be considered to aggravate his liability as the penalty for simple rape is the single indivisible penalty of reclusion perpetua (Article 63, Revised Penal Code). "x x x. He must, x x x, be further held liable for the corresponding indemnity to the victim, as well as exemplary damages for each count of rape (People v. Villanueva, 254 SCRA 202 [1996] )." (underscoring supplied) Since the qualifying circumstance of relationship was not alleged in the subject complaints for rape against Omar, he cannot be convicted of qualified rape as he was not properly informed that he is being accused of qualified rape. [35] Omar's conviction of qualified rape violates his constitutional right to be properly informed of the nature and cause of accusation against him. [36] In a criminal prosecution, it is the fundamental rule that every element of the crime charged must be alleged in the complaint or information. The main purpose of this requirement is to enable the accused to properly prepare his defense. He is presumed to have no independent knowledge of the facts that constitute the offense. [37] The non-allegation of the relationship between the appellant and the victim in the complaints for rape is a bar to the imposition of death penalty. Having been informed only of the elements of simple rape, the appellant can only be convicted of such crime and accordingly be punished with reclusion perpetua. [38] As regards the indemnity, moral and exemplary damages awarded by the trial court, we find the same to be proper. In the recent case of People v. Prades, [39] it was ruled that the award of moral damages to the victim is proper even if there was no proof presented during the trial as basis therefor. The circumstance of relationship between the offender and the victim as an aggravating circumstance becomes necessary in the matter of awarding civil damages. [40] The award of exemplary damages by the trial court is correct since the complainant has been correctly granted compensatory damages. Exemplary damages may be awarded in criminal cases when the crime was committed with one or more aggravating circumstances after proof that the offended party is entitled to moral, temperate or compensatory damages. [41] WHEREFORE, the judgment of conviction against accused-appellant Omar L. Medina rendered by the Regional Trial Court of Parañaque, Metro Manila, Branch 259, in Criminal Cases Nos. 95-710 to 713, is hereby MODIFIED only relative to the death penalty for each of the four (4) counts of rape and is hereby REDUCED to RECLUSION PERPETUA. SO ORDERED. Davide, Jr., C.J., Romero, Bellosillo, Melo, Puno, Vitug, Kapunan, Mendoza, Panganiban, Quisumbing, Purisima, and Pardo JJ., concur. [1] Penned by Judge Zosimo V. Escano, Rollo, pp. 18-28. [2] This amendatory law, entitled "AN ACT TO IMPOSE THE DEATH PENALTY ON CERTAIN HEINOUS CRIMES, AMENDING FOR THAT PURPOSE THE REVISED PENAL CODE, AS AMENDED, OTHER SPECIAL PENAL LAWS, AND FOR OTHER PURPOSES," took effect on December 31, 1993 (see People vs. Simon, 234 SCRA 555, 569 [1994]). [3] Criminal Case No. 95-713. [4] Criminal Case No. 95-712. [5] Criminal Case No. 95-711. [6] Criminal Case No. 95-710. [7] Rollo, pp. 4-7. [8] TSN, July 11, 1996, pp. 4-5; August 20, 1996, pp. 3-6. [9] Ibid., pp. 7-15. [10] TSN, July 11, 1996, pp. 16-27. [11] TSN, July 20, 1996, pp. 31-34. [12] TSN, July 20, 1996, pp.35-38. [13] TSN, July 20, 1996, pp. 38-49. [14] TSN, August 12, 1996, p. 5; Exhibits "F" and "G". [15] TSN, August 20, 1996, pp. 2-15. [16] TSN, August 19, 1996, pp. 2-28. [17] Decision of RTC, p. 9; Rollo, p. 26. [18] Appellant's Brief, p. 6. [19] 284 SCRA 590 [January 22, 1998]. [20] Ibid., at pp. 592-593. [21] People v. Pasayan, 261 SCRA 558, 572 [1996]. [22] People v. Magana, 259 SCRA 380, 397 [1996], citing People v. Masongsong, 174 SCRA 39, 47 [1989]. [23] Ibid. [24] People v. Cagto, 253 SCRA 455, 468 [1996]. [25] Ibid. [26] People v. Vitor, 245 SCRA 392, 403 [1995]. [27] 241 SCRA 285, 292 [1995]. [28] TSN, July 11, 1996, pp. 39-46, 50, 57-62, 64-73. [29] Exhs. "F" and "G". [30] See Section 11, Rule 124; People vs. Correa, et al., G.R. No. 119246 [Jan. 30, 1998], citing People vs. Olfindo, et al., 47 Phil. 1; People vs. Borbano, 76 Phil. 702, 708; People v. Garcia, 281 SCRA 463, 484 [1997]. [31] 281 SCRA 463, 489 [Nov. 6, 1997]. [32] G.R. No. 129439 [En Banc], Sept. 25, 1998. [33] Retired as of October 12, 1998. [34] People v. Ramos, G.R. No. 129439, September 25, 1998. [35] People v. Ramos, supra. [36] Section 14(2), Article III, Constitution. [37] People v. Ramos, supra, citing Balitaan v. CFI Batangas, Branch II, et al., 115 SCRA 729 [1982]. [38] People v. Ramos, supra. [39] G.R. No. 127569, July 30, 1998. [40] People v. Ramos, supra. [41] People v. Ramos, supra, citing Articles 2230 and 2234, Civil Code. tags
https://lawyerly.ph/juris/view/c8f09
Jeremiah 9 BSB ISV Parallel BSB Parallel ISV [BSB CSB ESV HCS KJV ISV NAS NET NIV NLT HEB] <table><tbody><tr><td> Berean Study Bible</td><td> International Standard Version</td></tr></tbody></table> <table><tbody><tr><td> 1 Oh, that my head were a spring of water, and my eyes a fountain of tears! I would weep day and night over the slain daughter of my people.</td><td> 1 "Oh, that my head were a spring of water, and my eyes a fountain of tears, for then I would cry day and night for those of my people who have been killed.</td></tr></tbody></table> <table><tbody><tr><td> 2 If only I had a traveler’s lodge in the wilderness, I would abandon my people and depart from them, for they are all adulterers, a crowd of faithless people.</td><td> 2 Oh, that I had a lodging place for travelers in the desert, so that I could leave my people and go away from them. For all of them are adulterers, a band of traitors.</td></tr></tbody></table> <table><tbody><tr><td> 3 “They bend their tongues like bows; lies prevail over truth in the land. For they proceed from evil to evil, and they do not take Me into account,” declares the LORD.</td><td> 3 They use their tongues like a bow. Lies rather than truth fly throughout the land. They progress from one evil to another, and they don't know me," declares the LORD.</td></tr></tbody></table> <table><tbody><tr><td> 4 “Let everyone guard against his neighbor; do not trust any brother, for every brother deals craftily, and every friend spreads slander.</td><td> 4 "Beware of your neighbors, and don't trust any of your relatives. For all of your relatives act deceitfully, and every friend goes around as a slanderer.</td></tr></tbody></table> <table><tbody><tr><td> 5 Each one betrays his friend; no one tells the truth. They have taught their tongues to lie; they wear themselves out committing iniquity.</td><td> 5 People deceive their friends, and they don't tell the truth. They have taught their tongues to tell lies. They exhaust themselves practicing evil.</td></tr></tbody></table> <table><tbody><tr><td> 6 You dwell in the midst of deception; in their deceit they refuse to know Me,” declares the LORD.</td><td> 6 You yourself live in the midst of deception, and because they are deceived they do not know me," declares the LORD.</td></tr></tbody></table> <table><tbody><tr><td> 7 Therefore this is what the LORD of Hosts says: “Behold, I will refine them and test them, for what else can I do because of the daughter of My people?</td><td> 7 Therefore, this is what the LORD of the Heavenly Armies says: "Look, I'm about to refine and test them. Because they're my people, what else can I do?</td></tr></tbody></table> <table><tbody><tr><td> 8 Their tongues are deadly arrows; they speak deception. With his mouth a man speaks peace to his neighbor, but in his heart he sets a trap for him.</td><td> 8 Their tongue is a deadly arrow that speaks deceit. With his mouth a person says, 'Peace,' to his friend, but inwardly he sets a trap for him.</td></tr></tbody></table> <table><tbody><tr><td> 9 Should I not punish them for these things? declares the LORD. Should I not avenge Myself on such a nation as this?”</td><td> 9 Should I not punish them for these things?" asks the LORD, "and should I not avenge myself on a nation like this?"</td></tr></tbody></table> <table><tbody><tr><td> 10 I will take up a weeping and wailing for the mountains, a dirge over the wilderness pasture, for they have been scorched so no one passes through, and the lowing of cattle is not heard. Both the birds of the air and the beasts have fled; they have gone away.</td><td> 10 I'll weep and mourn for the mountains, and lament for the desert pastures, because they are desolate and no one passes through them. They don't hear the lowing of the cattle. Both the birds of the sky and the animals have fled. They're gone!</td></tr></tbody></table> <table><tbody><tr><td> 11 “And I will make Jerusalem a heap of rubble, a haunt for jackals; and I will make the cities of Judah a desolation, without inhabitant.”</td><td> 11 "I'll make Jerusalem a heap of ruins, a refuge for jackals. I'll make the towns of Judah desolate, without inhabitants."</td></tr></tbody></table> <table><tbody><tr><td> 12 Who is the man wise enough to understand this? To whom has the mouth of the LORD spoken, that he may explain it? Why is the land destroyed and scorched like a desert, so no one can pass through it?</td><td> 12 Who is the wise person who understands this, and to whom has the LORD spoken so that he may declare it? Why is the land destroyed, ruined like the desert, without anyone passing through it?</td></tr></tbody></table> <table><tbody><tr><td> 13 And the LORD answered, “It is because they have forsaken My law, which I set before them; they have not walked in it or obeyed My voice.</td><td> 13 The LORD said, "It is because they have forsaken my Law that I gave them. They didn't obey me and didn't live according to it.</td></tr></tbody></table> <table><tbody><tr><td> 14 Instead, they have followed the stubbornness of their hearts and gone after the Baals, as their fathers taught them.”</td><td> 14 Instead, they followed their rebellious hearts and the Baals, as their ancestors taught them."</td></tr></tbody></table> <table><tbody><tr><td> 15 Therefore this is what the LORD of Hosts, the God of Israel, says: “Behold, I will feed this people wormwood and give them poisoned water to drink.</td><td> 15 Therefore, this is what the LORD of the Heavenly Armies, the God of Israel, says: "Look, I'll make these people eat wormwood and drink poisoned water.</td></tr></tbody></table> <table><tbody><tr><td> 16 I will scatter them among the nations that neither they nor their fathers have known, and I will send a sword after them until I have finished them off.”</td><td> 16 I'll scatter them among nations that neither they nor their ancestors have known, and I'll pursue them with the sword until I've finished them off."</td></tr></tbody></table> <table><tbody><tr><td> 17 This is what the LORD of Hosts says: “Take note, and summon the wailing women; send for the most skillful among them.</td><td> 17 This is what the LORD of the Heavenly Armies says: "Think about what I'm saying! Indeed, call out the professional mourners! Send for the best of them to come.</td></tr></tbody></table> <table><tbody><tr><td> 18 Let them come quickly and take up a lament over us, that our eyes may overflow with tears, and our eyelids may gush with water.</td><td> 18 Let them hurry and lament for us. Let tears run down from our eyes, and let our eyelids flow with water.</td></tr></tbody></table> <table><tbody><tr><td> 19 For the sound of wailing is heard from Zion: ‘How devastated we are! How great is our shame! For we have abandoned the land because our dwellings have been torn down.’ ”</td><td> 19 For a sound of mourning is heard from Zion: 'How we're ruined! Our shame is very great, because we have left the land, because our houses are torn down.'"</td></tr></tbody></table> <table><tbody><tr><td> 20 Now, O women, hear the word of the LORD. Open your ears to the word of His mouth. Teach your daughters to wail, and one another to lament.</td><td> 20 "Now, you women, hear the message from the LORD; listen to what he has to say! Teach your daughters how to mourn, let every woman teach her friend how to lament.</td></tr></tbody></table> <table><tbody><tr><td> 21 For death has climbed in through our windows; it has entered our fortresses to cut off the children from the streets, the young men from the town squares.</td><td> 21 For death comes up through our windows; it has come into our palaces to eliminate children from the streets and young men from the town squares.</td></tr></tbody></table> <table><tbody><tr><td> 22 Declare that this is what the LORD says: “The corpses of men will fall like dung upon the open field, like newly cut grain behind the reaper, with no one to gather it.”</td><td> 22 Speak! 'This is what the LORD says: "The corpses of people will fall like dung on the surface of the field, and like a row of cut grain behind the harvester when there is no one to gather it."'"</td></tr></tbody></table> <table><tbody><tr><td> 23 This is what the LORD says: “Let not the wise man boast in his wisdom, nor the strong man in his strength, nor the wealthy man in his riches.</td><td> 23 This is what the LORD says: "The wise man is not to boast in his wisdom; the strong man is not to boast in his strength; and the rich man is not to boast in his riches.</td></tr></tbody></table> <table><tbody><tr><td> 24 But let him who boasts boast in this, that he understands and knows Me, that I am the LORD, who exercises loving devotion, justice and righteousness on the earth—for I delight in these things,” declares the LORD.</td><td> 24 Rather, let the one who boasts, boast in this: that he understands and knows me, for I am the LORD who acts with gracious love, justice, and righteousness in the land. I delight in these things," declares the LORD.</td></tr></tbody></table> <table><tbody><tr><td> 25 “Behold, the days are coming,” declares the LORD, “when I will punish all who are circumcised yet uncircumcised:</td><td> 25 "Look, days are coming," declares the LORD, "when I'll punish all who are circumcised only in the flesh:</td></tr></tbody></table> <table><tbody><tr><td> 26 Egypt, Judah, Edom, Ammon, Moab, and all the inhabitants of the desert who clip the hair of their temples. For all these nations are uncircumcised, and the whole house of Israel is uncircumcised in heart.”</td><td> 26 Egypt, Judah, Edom, the people of Ammon, Moab, all those who live in the desert and shave the corners of their beard; indeed all the other nations that are uncircumcised, and all the house of Israel that is uncircumcised of heart."</td></tr></tbody></table> <table><tbody><tr><td> The Berean Bible (Berean Study Bible (BSB)© 2016, 2018 byBible HubandBerean.Bible. Used by Permission. All rights Reserved.</td><td> The Holy Bible: International Standard Version® Release 2.1 Copyright © 1996-2012 The ISV FoundationALL RIGHTS RESERVED INTERNATIONALLY.</td></tr></tbody></table>
https://www.biblehub.com/p/bsb/isv/jeremiah/9.shtml
Study evaluates dosage adjustments of Agenerase | EurekAlert! Science News A study that evaluated dosage adjustments of the protease inhibitor (PI) Agenerase® (amprenavir) capsules in HIV patients treated with efavirenz or nevirapine, antiretroviral (ART) agents known to affect the plasma levels of amprenavir, was presented here today at the 40th annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Study evaluates dosage adjustments of Agenerase A study that evaluated dosage adjustments of the protease inhibitor (PI) Agenerase® (amprenavir) capsules in HIV patients treated with efavirenz or nevirapine, antiretroviral (ART) agents known to affect the plasma levels of amprenavir, was presented here today at the 40th annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). A total of 86 PI-experienced patients received Agenerase in combination with efavirenz or nevirapine with treatment based on phenotypic or genotypic resistance testing. Efavirenz and nevirapine are non-nucleoside reverse transcriptase inhibitors (NNRTIs) that have been shown to affect plasma levels of amprenavir. "When low doses of ritonavir were added to the treatment regimen of PI-experienced patients taking efavirenz or nevirapine, preliminary data from this study showed that therapeutic plasma concentrations of amprenavir were maintained at 6 or 12 weeks," said G. Peytavin, X. Bichat-Cl. Bernard Hospital, Paris, France, principal author of the study. Plasma concentrations (Cmin) of the treatment compounds were determined at two weeks after initiation of treatment and at week 6 or 12. When Cmin of amprenavir fell below therapeutic levels (100 ng/ml), patients' physicians were offered a choice of two dosage regimens: Agenerase 600 mg twice a day plus 100 mg of ritonavir twice-a-day, or 1200 mg of Agenerase three times a day. At week two, 70 percent (60/86) of patients -- 87 percent (52/60) of whom were in the group treated with efavirenz -- had Cmin of amprenavir below 100 ng/ml. Dosage adjustments of Agenerase were proposed for all 60 patients. The recommendations were carried out by the physician in 50 percent (30/60) of patients at week 6 or 12. Of patients that received a dose adjustment, 93 percent (28/30) received the Agenerase plus ritonavir combination. The Cmin of amprenavir rose above 100 ng/ml in all cases, despite the presence of efavirenz or nevirapine. Plasma concentration was 2.7 ±; 2.0 mg/l (186) for efavirenz and 5.9 ±; 4.4 mg/l (46) for nevirapine. "These preliminary data provide new information about the potential for maintaining therapeutic plasma levels of amprenavir in the presence of other antiretrovirals known to induce metabolism of amprenavir," said Lynn Smiley, M.D., vice president, HIV and Opportunistic Infections Clinical Development at Glaxo Wellcome. Agenerase in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection. This indication is based on analyses of plasma HIV RNA levels and CD4 cell counts in controlled studies up to 24 weeks in duration. At present, no results from controlled trials evaluating long-term suppression of HIV RNA or disease progression with Agenerase have been submitted to the FDA for evaluation. The safety of Agenerase was studied in 736 adult patients. In patients receiving protease inhibitors, diabetes mellitus, hyperglycemia, acute hemolytic anemia and redistribution/ accumulation of fat have been reported. Severe and life-threatening drug interactions could be associated with therapy with Agenerase (see full prescribing information for specific drug interactions). Severe and life-threatening skin reactions, including Stevens-Johnson syndrome, have been associated with Agenerase. There have been reports of spontaneous bleeding in patients with hemophilia A and B treated with protease inhibitors. The majority of adverse events were of mild to moderate intensity (grade 1-2), early to onset and transient. Treatment-limiting (grade 3-4) adverse events occurred in 5 percent or less of patients. The most frequently reported adverse events in grades 2-4 (grades 1-4 included parenthetically) were up to 31 percent nausea (73 percent), 22 percent diarrhea (56 percent), 11 percent vomiting (29 percent), 20 percent rash (25 percent) and 2 percent perioral paresthesia (30 percent). Because of the potential risk of toxicity from the large amount of the excipient propylene glycol contained in Agenerase Oral Solution, that formulation is contraindicated in certain patient populations and should be used with caution in others. ### Agenerase was discovered by scientists at Vertex Pharmaceuticals of Cambridge, MA. Glaxo Wellcome has been responsible for product formulation and manufacture of Agenerase, design and implementation of clinical trials, and regulatory submissions to the FDA. Glaxo Wellcome also leads the marketing efforts for Agenerase with co-promotion assistance from Vertex Pharmaceuticals. Glaxo Wellcome is a pharmaceutical industry leader in HIV research and therapies. In addition to Agenerase, Glaxo Wellcome also manufactures and markets the anti-HIV drugs Combivir® (lamivudine/zidovudine), Epivir® (lamivudine), Retrovir® (zidovudine) and Ziagen® (abacavir sulfate). The company is engaged in basic research programs designed to investigate new targets to treat HIV. Complete prescribing information for Agenerase is available athttp://www.agenerase.com. For additional information, please go tohttp://www.combivir.com,http://www.epivir.com,http://www.agenerase.com. Keywords
https://archive.eurekalert.org/pub_releases/2000-09/PCI-Seda-1809100.php
Risk factors for cisplatin‑induced acute kidney injury: A pilot study on the usefulness of genetic variants for predicting nephrotoxicity in clinical practice Risk factors for cisplatin‑induced acute kidney injury: A pilot study on the usefulness of genetic variants for predicting nephrotoxicity in clinical practice Authors: Hiroyasu Oda Toshiro Mizuno Makoto Ikejiri Maki Nakamura Akira Tsunoda Mikiya Ishihara Kanako Saito Satoshi Tamaru Yoshiki Yamashita Yuhei Nishimura Kaname Nakatani Naoyuki Katayama Published online on: September 1, 2020 https://doi.org/10.3892/mco.2020.2127 Article Number: 58 Abstract Several studies have reported risk factors for predicting cisplatin‑induced acute kidney injury (AKI), including old age, female sex, smoking, hypoalbuminemia, hypokalemia, hypomagnesemia, a high body surface area, advanced cancer and the total dose of cisplatin administered. Recently, some studies have focused on the associations between genetic alterations in the genes coding for renal drug transporters, such as organic cation transporter 2 (OCT2), and the nephrotoxicity of cisplatin. However, genetic variants have not been fully elucidated for clinical use. Patients who had received cisplatin (≥50 mg/m 2 )‑containing chemotherapy as a first‑line treatment were considered as eligible for the present study. The occurrence of AKI and its associations with baseline characteristics, conventional biomarkers and single‑nucleotide variants (SNV) were assessed. AKI was defined as an increase in the serum creatinine level of >0.3 mg/dl or to 1.5‑2 times the baseline level. Genotyping was conducted using the DMET platform (DMET Plus), which characterizes 1,936 genetic variants (1,931 SNV and 5 copy number variations) in 231 genes. Between April 2014 and June 2016, a total of 28 patients (22 men and 6 women) were enrolled. AKI occurred in 8 of the 28 enrolled patients (28.6%). Univariate analyses demonstrated that the urinary β2‑microglobulin level and body surface area were significantly higher in the AKI group (P<0.05). As regards the associations between AKI and SNV, none of the examined SNV were found to be associated with cisplatin‑induced AKI. The findings of the present study suggested that certain clinical factors were associated with the onset of AKI, but no associations were identified with genetic factors, including OCT2. Although this was a small pilot study, the findings indicated that genetic factors may not be of value for predicting AKI in clinical practice. Introduction Cisplatin is a cytotoxic agent, which is used to treat a variety of neoplasms. While the toxicities of cisplatin include emesis, loss of appetite, ototoxicity and peripheral neuropathy, the main dose-limiting side effect of cisplatin is nephrotoxicity. Several studies have reported risk factors for predicting cisplatin-induced acute kidney injury (AKI), such as old age, female sex, smoking, hypoalbuminemia, hypokalemia, hypomagnesemia, a high body surface area, the frequency of cisplatin treatment, the combined use of cisplatin and paclitaxel, advanced cancer, the total dose of cisplatin administered, cardiovascular disease and diabetes mellitus ( 1-6 ). Recently, some studies have focused on the associations between genetic alterations in the genes coding for renal drug transporters, such as organic cation transporter 2 (OCT2), and the nephrotoxicity of cisplatin ( 7-10 ). One of the problems with these studies on genetic variants is that their analyses are based on several different definitions of renal injury. In clinical practice, the measurement of serum creatinine concentration is widely used for the detection of AKI. Therefore, the usefulness of genetic information must also be verified using a widely accepted definition of renal damage, such as that included in the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE). The aim of the present pilot study was to elucidate the usefulness of genetic variants in predicting AKI using serum creatinine measurements. Materials and methods Study design and participants This was a single-center pilot study. Patients were selected for this study according to the following criteria: i) Administration of cisplatin (≥50 mg/m 2 )-containing chemotherapy as first-line treatment; ii) creatinine clearance rate (CCR) of ≥50 ml/min and a normal serum creatinine level; iii) Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; iv) adequate organ function, and v) age ≥20 years. The exclusion criteria were as follows: Uncontrolled hypertension, diabetes mellitus, hyperuricemia, pleural effusion and/or ascites that required drainage to reduce the associated symptoms, and a history of previous treatment with cisplatin-containing chemotherapy. The present study was conducted in accordance with the principles outlined in the Declaration of Helsinki and the International Conference on Harmonization and Good Clinical Practice guidelines. The study protocol was approved by the Institutional Ethics Committee of Mie University Hospital (approval no. 2721). All the patients provided written informed consent. Procedures All the cisplatin-containing regimens were administered in the inpatient setting. Cisplatin was administered in 500 ml of 0.9% normal saline over 2 h. All patients were pre- and posthydrated with infusions of ≥1,000 ml of saline. For antiemetic prophylaxis, 5-HT 3 serotonin receptor antagonists and dexamethasone were administered 15-30 min before the start of the cisplatin treatment, and a neurokinin 1 receptor antagonist was administered 60 min before the start of cisplatin treatment in all cases. Laboratory testing (hematological, serological and urological tests) were conducted at baseline (days -5-0) and on days 2-4, 7-9, 12-18 and 19-25 after chemotherapy. For the genetic analysis, genomic DNA samples were isolated from blood samples using the Qiagen DNA isolation kit (Qiagen GmbH) and quantified using a NanoDrop spectrophotometer at 260 nm (Thermo Fisher Scientific, Inc.). The samples were genotyped using the DMET platform (DMET™ Plus, Affymetrix; Thermo Fisher Scientific, Inc.) according to the standard protocol described by the manufacturer. The DMET Plus GeneChip enables the genotyping of 1,936 functionally significant genetic variants [1,931 single-nucleotide variants (SNV) and 5 copy number variations] in 231 genes, including phase I and II drug-metabolizing enzyme-coding genes and drug transporter-coding genes. The DMET Plus platform examines various types of genetic variations, including biallelic and triallelic SNV, copy number variations and insertions/deletions, and includes efficient and comprehensive molecular inversion probe technology. Then, a genotype profile for the 1,931 SNV was generated using the DMET™ console, v1.3 (Affymetrix; Thermo Fisher Scientific, Inc.). Outcomes In accordance with previous studies ( 1-14 ), cisplatin-induced nephrotoxicity was evaluated based on two definitions. AKI as defined by CTCAE v4.0 In terms of the clinical-practical aspects, AKI is defined as an increase in the serum creatinine level of >0.3 mg/dl or to 1.5-2 times the baseline level with reference to the NCI-CTCAE v4.0. Changes in estimated glomerular filtration rate (eGFR) Several previous studies on genetic factors have adopted changes in the eGFR as outcomes ( 7 , 11 , 12 ). Therefore, regarding genetic variants that are considered to be associated with renal impairment, we evaluated not only their associations with AKI (CTCAE v4.0), but also their effect on the mean changes from baseline eGFR after the first cycle of chemotherapy. Statistical analysis The patients' baseline characteristics, including information on age, sex, ECOG performance status, height, weight, body mass index, body surface area, complications, smoking history, site of the primary tumor, tumor histology, clinical stage, combination chemotherapy, concurrent radiotherapy, laboratory data and SNV, were recorded. Two-sided Student's t-test, Mann-Whitney U test, or Fisher's exact test were used to compare the baseline characteristics of the groups with and without cisplatin-induced AKI. All statistical analyses were performed with IBM SPSS statistics v23.0 (IBM Corp.). All P-values were two-sided, and P<0.05 was considered to indicate statistically significant differences. To identify genetic variants that were associated with the changes in eGFR, each genotype of every genetic variant was first converted to numerical values as follows: A/A to 1, A/C to 2, A/G to 3, A/T to 4, C/C to 5, C/G to 6, C/T to 7, G/G to 8, G/T to 9 and T/T to 10. We then converted the quantitative values to Z scores, based on the mean and standard deviation values for patients with each SNV. The changes in eGFR (difference between the minimum value and the baseline value) were also converted to Z scores based on the mean and standard deviation values for each endpoint. The SNVs associated with the changes in eGFR were identified using Pavlidis Template Matching in the TM4 MeV package ( 15 , 16 ) using P<0.05 as a threshold. Results Baseline characteristics A total of 28 patients (22 men and 6 women) were enrolled in this trial between April 2014 and June 2016. The baseline characteristics of the patients are listed in Table I . Their median age was 65 years (range, 55-77 years). All the patients had a good performance status (0 or 1) according to the ECOG scale. A total of 13 patients (46.4%) had hypertension and 8 (28.6%) patients had diabetes mellitus. A total of 23 (82.1%) patients had a history of smoking. The predominant primary tumor site was the esophagus (75%). The other primary tumor sites included the stomach in 4 cases (14.3%), the lungs in 2 cases (7.1%) and the pancreas in 1 case (3.6%). The predominant histological type was squamous cell carcinoma (60.7%). There were 7 cases (25%) of adenocarcinoma, and 4 cases (14.3%) of neuroendocrine carcinoma. A total of 11 patients (39.3%) received cisplatin as neoadjuvant or adjuvant chemotherapy, 15 (53.6%) received cisplatin as palliative chemotherapy and 2 (7.1%) received cisplatin as concurrent chemoradiotherapy. The median serum creatinine level was 0.73 mg/dl, the median eGFR was 82.3 ml/min/1.73 m 2 , and the median CCR was 88.1 ml/min. Table I Baseline characteristics of the patients. Table I Baseline characteristics of the patients. Characteristics No. (%) Age (years), median (range) 65 (55-77) Sex Male 22 (78.6) Female 6 (21.4) ECOG performance status score 0 9 (32.1) 1 19 (67.9) Predominant primary tumor site Esophagus 21 (75.0) Stomach 4 (14.3) Pancreas 1 (3.6) Lung 2 (7.1) Predominant histological type Squamous cell carcinoma 17 (60.7) Adenocarcinoma 7 (39.3) Neuroendocrine carcinoma 4 (14.3) Setting Neoadjuvant/adjuvant 11 (39.3) Metastatic 15 (53.6) Concurrent chemoradiotherapy 2 (2.7) Co-administered drugs Fluorouracil 20 (71.4) Etoposide 4 (14.3) S-1 3 (10.7) Pemetrexed 1 (3.6) Cisplatin dose (mg/m 2 ), median (range) 70 (60-80) Creatinine (mg/dl), median (range) 0.73 (0.40-0.99) eGFR (ml/min/1.73 m 2 ), median (range) 82.3 (61.2-142.5) Creatinine clearance (ml/min), 88.1 (50.0-206) median (range) Comorbidities Hypertension 13 (46.4) Diabetes 8 (28.6) History of smoking Yes 23 (82.1) No 5 (17.9) [i]eGFR, estimated glomerular filtration rate; ECOG, Eastern Cooperative Oncology Group. Incidence of AKI AKI, as defined by CTCAE v4.0, occurred in 10/28 patients (35.7%). Of these 10 patients with AKI, 2 suffered ileus or vomiting during chemotherapy. As such adverse events can cause pre-renal injuries, these 2 patients were excluded from our analysis. In total, 8 patients (28.6%) developed cisplatin-induced AKI, whereas 18 patients (64.2%) had no indications of cisplatin-induced AKI. A comparison of various parameters in terms of the presence or absence of AKI is presented in Table II . The patients' median age and the median dosage of cisplatin were similar between the two groups. The pretreatment CCR of the patients with AKI was similar to that of patients without AKI. In the present study, the majority of the patients developed AKI on days 7-9. Among the 8 patients with AKI, the serum creatinine levels of 6 patients subsequently returned to normal, whereas 2 patients developed irreversible renal failure. Table II Comparison of the baseline characteristics of the patients with and without AKI. Table II Comparison of the baseline characteristics of the patients with and without AKI. Characteristics AKI + (n=8) AKI - (n=18) Age (years), median (range) 66 (57-76) 63 (55-77) Sex, n (%) Male 7 (87.5) 13 (72.2) Female 1 (12.5) 5 (27.8) ECOG performance status score, n (%) 0 4 (50.0) 4 (22.2) 1 4 (50.0) 14 (77.8) Tumor location, n (%) Esophagus 5 (62.5) 15 (83.3) Stomach 2 (25.0) 1 (5.6) Pancreas 1 (12.5) 0 (0) Lung 0 (0.0) 2 (11.1) Co-administered drugs, n (%) Fluorouracil 4 (50.0) 15 (83.3) Etoposide 2 (25.0) 2 (11.1) S-1 2 (25.0) 0 (0.0) Pemetrexed 0 (0.0) 1 (5.6) Cisplatin dose (mg/m 2 ), median (range) 80 (60-80) 80 (75-80) Creatinine (mg/dl), median (range) 0.79 (0.40-0.93) 0.68 (0.40-0.99) CCR (ml/min), median (range) 81.7 (61.2-116.9) 89.2 (50-206.2) [i]AKI, acute kidney injury; CCR, creatinine clearance rate; ECOG, Eastern Cooperative Oncology Group. Risk factors Clinical factors Univariate analyses were used to identify clinical risk factors for cisplatin-induced AKI. The results of the univariate analyses demonstrated that the baseline urinary β2-microglobulin level and body surface area were significantly higher in the AKI group (P<0.05; Table III ). In addition, the baseline serum cystatin C level and the baseline urinary levels of N-acetyl-β-D-glucosaminidase and chloride were slightly higher in patients with AKI compared with those in patients without AKI. Other clinical factors, such as the serum levels of albumin, potassium and magnesium, as well as age, which have previously been reported as risk factors for cisplatin-induced AKI, were not found to be significantly associated with cisplatin-induced AKI in the present study. Table III Clinical risk factors for AKI. Table III Clinical risk factors for AKI. Factors AKI + (mean ± SD) AKI - (mean ± SD) P-value Urinary β2-microglobulin, µg/l 730.0±888.0 150.7±189.5 0.016 Body surface area, m 2 1.6±0.11 1.5±0.12 0.022 Cystatin C, mg/l 1.1±0.26 0.93±0.12 0.075 Urinary chloride, mEq/l 134.5±54.0 101.0±41.6 0.097 Urinary NAG, U/gCrea 15.2±12.2 12.5±15.1 0.107 Uric acid, mg/dl 5.5±1.3 4.5±1.3 0.114 Urinary sodium, mEq/l 132.6±34.5 105.5±38.8 0.134 Creatinine, mg/dl 0.76±0.16 0.67±0.16 0.203 Sodium, mEq/l 141.1±1.1 139.2±3.8 0.208 eGFR, ml/min 78.6±16.04 88.5±19.7 0.226 Urinary α1-microglobulin, mg/l 7.8±6.7 5.2±5.0 0.289 Chloride, mEq/l 104.5±2.5 102.7±3.6 0.300 Age, years 66.2±5.4 64.0±5.5 0.347 Urinary albumin, mg/gCrea 175.2±469.5 17.1±39.6 0.373 Creatinine clearance, ml/min 84.8±22.3 95.2±33.8 0.487 Phosphorus, mg/dl 3.3±0.47 3.1±0.49 0.546 Urinary potassium, mEq/l 38.8±29.0 33.7±19.8 0.602 Potassium, mEq/l 4.0±0.34 4.1±0.42 0.628 Magnesium, mg/dl 2.0±0.21 2.0±0.17 0.64 Urinary creatinine, mg/dl 106.1±54.8 122.8±121.6 0.717 Blood urea nitrogen, mg/dl 12.1±4.3 12.6±5.2 0.804 Calcium, mg/dl 9.4±0.85 9.3±0.98 0.865 Albumin, g/dl 3.6±0.50 3.5±0.35 0.975 Urinary calcium, mg/dl 13.6±6.7 15.4±13.3 1.000 [i]AKI, acute kidney injury; SD, standard deviation; NAG, N-acetyl-β-D-glucosaminidase; eGFR, estimated glomerular filtration rate. Genetic factors In genetic analysis of the associations between AKI and genetic variants, none of the examined genetic variants were found to be associated with cisplatin-induced AK. OCT2 rs316019, which was considered to be representative of renal injury-related genetic factors, was not associated with cisplatin-induced AKI (P=0.667, Fisher's exact test). Similarly, none of the other examined OCT2 gene variants were found to be associated with AKI. By contrast, as regards the associations between the mean changes in eGFR and SNV, 5 SNVs (ABCC4 rs3742106, CYP7A1 rs13251066, CYP39A1 rs7761731, MAT1A rs17102596 and UGT1A3 * 4 rs45625338) were found to be associated with the mean changes in eGFR ( Fig. 1 ). Figure 1Associations between SNV and mean changes in the eGFR. (A) The mean change in the eGFR was significantly associated with rs3742106; ABCC4 c.*38T>G (TT vs. GG, P=0.048), (B) rs13251066; CYP7A1 c.-5096T>C (TT vs. CC, P=0.002), (C) rs7761731; CYP39A1 c.972T>A (TT vs. TA, P=0.034), (D) rs17102596; MAT1A c.769-218A>G (AA vs. AG, P<0.001), and (E) rs45625338; UGT1A3*4 c.133C>T (CC vs. TT, P<0.001). Asterisks indicate extreme outliers (greater than three times the height of the boxes). SNV, single-nucleotide variant; eGFR, estimated glomerular filtration rate. Discussion Cisplatin has been widely used as a cytotoxic agent to treat several solid tumors, such as esophageal, gastric, ovarian and lung cancer. However, other platinum-based drugs, such as carboplatin and oxaliplatin, have recently become standard treatments for these diseases; therefore, cisplatin is used less frequently than before. The main reason for avoiding to use cisplatin is its adverse effects, particularly because it is highly emetic and nephrotoxic. Nausea and vomiting are serious adverse events that affect the quality of life of patients during treatment with cisplatin-containing regimens ( 17 ). However, recent advances in antiemetic therapies, such as 5-HT 3 antagonists, aprepitant and olanzapine, appear to have resolved these problems ( 17 ). With regards to carboplatin and oxaliplatin, there appear to be three main limitations to their use: Hypersensitivity reactions, thrombocytopenia and peripheral neuropathy ( 18 ). Thus, determining the risk factors for cisplatin nephrotoxicity would assist clinicians in selecting patients for cisplatin-based chemotherapy among those who are not medically fit to receive carboplatin or oxaliplatin, which would be clinically significant. In the present study, univariate analyses revealed significant differences in body surface area and pretreatment urinary β2-microglobulin levels between the patients who did and did not develop AKI. By contrast, none of the SNVs that were previously described as risk factors for renal injuries, including OCT2, were found to be associated with AKI (CTCAE 4.0). Although this is a small pilot study, the results indicate that genetic factors may not be useful for predicting AKI as defined by CTCAE in clinical practice. Previous studies investigating the associations between genetic variants and renal injuries, defined changes in eGFR ( 7 , 11 , 12 ), cystatin C ( 8 ) and KIM-1( 13 ) as kidney injury. In the present study, we found that some gene variants, including ABCC4, which is involved in drug transport in kidney tubular cells, were significantly associated with mean changes in eGFR. Cystatin C and KIM-1 may be useful for early and accurate detection of kidney injury; however, these novel biomarkers require further investigation. To apply nephrotoxicity-related genetic information to clinical decision-making, a study with an appropriate definition of nephrotoxicity, such as that defined by the CTCAE, is required. Another approach is to construct a risk prediction model that combines genetic variants with clinical factors. Several studies on genetic factors associated with adverse drug reactions to various antitumor drugs have been reported ( 19-21 ). Unfortunately, the prediction of adverse events based on genetic variants has not been sufficiently incorporated into daily clinical practice; however, there are some exceptions, such as the association between variants in the UGT1A1 gene and the effects of irinotecan. Considering the current situation, a risk prediction model that integrates clinical and genetic factors may be a practical approach to using genetic information in daily clinical practice. In summary, we herein performed a pilot study to elucidate the clinical usefulness of genetic factors for predicting renal damage, with the intend of examining the associations between cisplatin-induced AKI and genetic factors in a large-scale study with an appropriate definition of nephrotoxicity. Acknowledgements The authors would like to thank Professor Masahiro Okuda (Department of Pharmacy, Mie University Hospital), Mr. Kenji Ikemura (Department of Pharmacy, Mie University Hospital) and Dr Eiji Ishikawa (Department of Nephrology, Mie University Hospital), whose comments/suggestions helped improve this study. Funding Funding was received from Mie University Hospital, Tsu, Japan (The Director Research Grant in 2017). Availability of data and materials The datasets used during the present study are available from the corresponding author upon reasonable request. Authors' contributions HO designed the study and wrote the initial draft of the manuscript. TM contributed to interpretation of data, and assisted in the preparation of the manuscript. MaI, MN, YN and KN contributed to analysis and interpretation of data. HO, AT, MiI, KS, ST and YY contributed to clinical treatment. NK supervised the patient treatment. All authors critically reviewed the manuscript and approved the final version of the manuscript. Ethic approval and consent to participate This article does not contain any studies with animals performed by any of the authors. The study was conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization and Good Clinical Practice guidelines. The study protocol was approved by the Institutional Review Board of Mie University Hospital. Informed consent was obtained from all subjects. Patient consent for publication Not applicable. Competing interests All the authors declare that they have no competing interests. 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E-Library - Information At Your Fingertips: Printer Friendly FIRST DIVISION [ G.R. No. 232769. November 03, 2020 ] MAREY BETH D. MARZAN, PETITIONER, VS. CITY GOVERNMENT OF OLONGAPO, HON. ROLEN C. PAULINO, ANGIE SOCORRO S. BARROGA, AND ARCHITECT TONY KAR BALDE III, RESPONDENTS. DECISION CAGUIOA, J: The Case This is a Petition for Review on Certiorari [1] (Petition) filed under Rule 45 of the Rules of Court against the Decision [2] dated October 26, 2016 (assailed Decision) and Resolution [3] dated July 4, 2017 (assailed Resolution) in CA G.R. SP No. 139549 rendered by the Court of Appeals [4] (CA). The assailed Decision and Resolution affirmed the following issuances of the Regional Trial Court (RTC) of Olongapo City, Branch 72 in Civil Case No. 113-0-2013: Decision dated October 2, 2014 which dismissed the "Petition for Mandamuswith Prayer for Writ of Preliminary Mandatory Injunction, Damages, and Attorney's Fees" (Petition for Mandamusor RTC Petition) filed by petitioner Marey Beth D. Marzan (Marzan); and Order dated January 15, 2015 denying Marzan's motion for reconsideration. The Facts The facts, as narrated by the CA, are as follows: On January 16, 2008, [Marzan] was appointed as City Government Department Head II [of] the City Planning and Development Office of Olongapo City [(CPDO)]. The appointment was issued by then City Mayor James Gordon, Jr. [(Mayor Gordon)] and approved by the Civil Service Commission [(CSC)] on June 7, 2011. On December 1, 2011, Mayor Gordon issued a Memorandum appointing [Marzan] as City Budget Officer (City Government Department Head II) of the City Budget Office [(CBO)]. [Marzan] was to discharge said functions concurrently with her functions as Zoning Administrator/Zoning Officer. According to [Marzan], Mayor Gordon directed [respondent Angie Socorro S. Barroga (Barroga), as Acting Chief Administrative Officer of the Human Resource Management Office of Olongapo City, [5] ] to facilitate [Marzan's] lateral transfer to her concurrent position as Budget Officer. [On May 6, 2013, Rolen C. Paulino (Mayor Paulino) was elected as mayor of Olongapo City. [6] Upon assumption into office, Mayor Paulino appointed respondent Tony Kar Balde, III (Balde) to Marzan's former position as Department Head II of the CPDO.] [7] On August 16, 2013, however, the [CSC], through Director Carlos P. Rabang [(Director Rabang)], wrote [Mayor Paulino] informing the latter of the disapproval of [Marzan's] appointment as City Government Department Head II of the [CBO]. The ground for the disapproval of [Marzan's] appointment was the discrepancy between the date the appointment was signed by Mayor Gordon [(November 16, 2012) [8] ] and [its] approval by the Sangguniang Panglungsod [(December 21, 2011) [9] ]. On August 29, 2013, [Barroga] wrote a letter [(City Termination Letter)] to [Marzan] informing [her] that the City Government of Olongapo would be terminating her services effective September 14, 2013 on the basis of the August 16, 2013 letter of [Director Rabang] [(August 2013 CSC Letter)]. The [City Termination Letter] was noted by Mayor Paulino. On even date, [Marzan] wrote a letter to the [CSCJ Regional Office III inquiring as to the effect of the disapproval of her appointment as City Government Department Head II of the [CBO]. [Marzan] sought clarification on the following matters: Who is the accountable officer responsible in ensuring compliance [with] the CSC [r]ules on [a]ppointment relative to the documentary requirements of my appointment? x x x x x x x Does the [d]isapproval of a [t]ransfer [a]ppointment of a permanent employee result [in] termination of services? What is my status following such disapproval? Am I deemed separated from service as alleged or shall I revert x x x to my [previous] CSC-approved position as per CSC [r]ules? x x x x x x x On September 4, 2013, [Marzan] wrote back to [Barroga stating that] nowhere in the [August 2013 CSC Letter] was it mentioned that her services were being terminated. [Marzan] further explained that [said letter] merely stated that while [Marzan] met the minimum qualifications for the position of City Government Department Head II for the [CBO], the reason for the disapproval of her appointment was the accountable officer's failure to perform the latter's ministerial duty of facilitating [her] appointment. [Marzan] thus inquired as to [which] specific [term of] service was being referred to in [the City Termination Letter] considering that prior to [the disapproval of her] appointment as City Government Head II for the [CBO], she was holding the permanent position of City Government Department Head II of the [CPDO]. [Marzan] further cited the provision in the Civil Service Law which allegedly provides that a disapproved permanent appointment results in automatic reversion [to] the previously approved appointment x x x. On September 6, 2013, [Barroga replied to [Marzan's letter, reiterating that her] service to the [C]ity [G]overnment of Olongapo would only be until September 14, 2013. [Marzan], in the meantime, continued to report for work. On September 13, 2013, [Marzan] wrote a letter addressed to Mayor Paulino and [Barroga] informing them of her letter to the [CSC] Regional Office x x x. [Marzan] also informed [them] that [CSC] Provincial Director Cristina Gonzales advised [her] to await the Regional Office's reply x x x. [Marzan] likewise informed [Mayor Paulino and Barroga] that status quo will have to be observed in the meantime while the [CSC] Regional Office resolves [her query]. Consequently, [Marzan] informed [Mayor Paulino and Barroga] that x x x she cannot heed [the latter's] directive for her to cease working for the [C]ity [G]overnment. x x x The records show that [Marzan's] letter was received by the Office of the City Mayor of Olongapo at 4:00 o'clock in the afternoon. x x x [T]he records likewise show that [Barroga] received a copy of said letter on the same date. At about 5:00 o'clock in the afternoon of the same date, [Marzan] was shocked and surprised when upon opening the door of her office, she saw six (6) men from the Civil Security Service Unit and [Balde] in her office. x x x [Balde] x x x insisted that [Marzan] remove her things immediately [and] further instructed his men to forthwith evict [Marzan from her office]. x x x On September 16, 2013, [Marzan] wanted to report for work. However, she received a text message x x x informing her that men were manning her work area with instruction[s] to prevent her from coming to work. x x x To avoid embarrassment, [Marzan] decided not to work on that day. x x x On September 24, 2013, [Marzan] received a letter dated September 18,2013 [(September 2013 CSC Letter)] from Director Rabang [informing her] that as a matter of policy, his office does not render opinions or give categorical answers to queries which may later be brought before it on appeal. However, Director Rabang answered [Marzan's] queries in accordance with the Civil Service laws, rules and regulations x x x[.] [10] On September 30, 2013, [Marzan], accompanied by her sister, met with Mayor Paulino to inquire if the latter was aware of the cessation order issued to [Marzan]. Mayor Paulino allegedly admitted that while the order was his own decision, [it] was based on [Barroga's recommendation]. [11] (Emphasis and underscoring supplied) RTC Proceedings Aggrieved, Marzan filed with the RTC a Petition for Mandamus against the City Government of Olongapo, Mayor Paulino, Barroga and Balde (collectively, respondents). [12] The RTC Petition prayed for the following reliefs: The issuance of a writ of preliminary mandatory injunction directing respondents to immediately reinstate Marzan as Department Head of the CPDO; The issuance of a writ of mandamuscommanding respondents to respect Marzan's rights and allow her to perform her functions as Department Head of the CPDO; Payment of: (i) moral damages amounting to P250,000.00; (ii) exemplary damages amounting to P100,000.00; (iii) attorney's fees and expenses of litigation amounting to P100,000.00; and (iv) costs of suit. [13] Respondents filed their Joint Answer to the RTC Petition. First, respondents alleged that when Marzan was appointed as Department Head of the CBO, she vacated her position as Department Head of the CPDO. Thus, Mayor Paulino acted within his authority as local chief executive when he appointed Balde to fill the vacant position. According to respondents, Marzan's reinstatement would effectively impair Mayor Paulino's power to appoint. [14] In addition, respondents argued that Marzan's reliance on Section 13 of the Omnibus Rules Implementing Book V of Executive Order No. 292 and Other Pertinent Civil Service Laws (Omnibus Rules) is misplaced. Respondents averred that in order for Section 13 to apply, there must be a series of promotions which are simultaneously submitted to the CSC for approval. Respondents stressed that these circumstances do not obtain in this case. [15] Finally, respondents asserted that Marzan's resort to mandamus is premature. According to respondents, Marzan should have exhausted available administrative remedies by seeking reconsideration of her termination before the Office of the City Mayor, and subsequently, by filing an appeal with the CSC Regional Office. [16] On January 6, 2014, the RTC denied Marzan's prayer for injunctive relief. Marzan's subsequent motion for reconsideration was also denied. [17] Thereafter, the RTC directed the parties to file their respective memoranda on the substantive issues. [18] On October 2, 2014, the RTC issued a Decision dismissing the Petition for Mandamus . [19] On the procedural aspect, the RTC held that Marzan failed to exhaust available administrative remedies. [20] On the substantive issues, the RTC agreed with respondents' assertion that Marzan vacated her position as Department Head of the CPDO upon acceptance of her appointment as Department Head of the CBO. As basis, the RTC cited the Appropriations Act of Olongapo City [21] which tagged Marzan's old position as vacant. The RTC noted that Marzan must have been aware of such fact, as she was a member of the finance committee that was tasked to prepare the city's budget. [22] Finally, the RTC ruled that mandamus cannot issue to compel Marzan's reinstatement, such act being discretionary on the part of Mayor Paulino as appointing authority. [23] Marzan filed a motion for reconsideration which the RIC also denied in its Order dated January 15, 2015. [24] CA Proceedings Unsatisfied, Marzan filed an appeal with the CA via Rule 42 of the Rules of Court. Therein, Marzan questioned the dismissal of the Petition for Mandamus without having undergone a full-blown trial. As well, she maintained that her immediate resort to mandamus was proper. On October 26, 2016, the CA issued the assailed Decision, the dispositive portion of which reads: WHEREFORE , in view of the foregoing, the appeal is DENIED . The October 2, 2014 Decision and the January 15, 2015 Order of [the RTC] are AFFIRMED . SO ORDERED. [25] Foremost, the CA held that under Rule 65, a full-blown hearing is not required prior to the resolution of a petition for mandamus . [26] Further, the CA echoed the RTC's findings with respect to Marzan's failure to exhaust all available administrative remedies. However, the nature of the issues raised by Marzan precludes outright dismissal on procedural grounds, inasmuch as these issues relate to her right to security of tenure. [27] Nonetheless, the CA held that Marzan's action fails on the merits. Citing Divinagracia, Jr. v. Sto. Tomas [28] ( Divinagracia ), the CA held that Section 13 of the Omnibus Rules does not apply, as Marzan's movement from the CPDO to the CBO was a lateral transfer, and not a promotion contemplated under the Omnibus Rules. [29] Thus, contrary to Marzan's claims, her reinstatement as Department Head of the CPDO is not automatic, but rather discretionary on the part of the appointing authority. For this reason, Marzan's prayer for issuance of a writ of mandamus cannot prosper. [30] The CA also denied Marzan's subsequent motion for reconsideration through the assailed Resolution. [31] Marzan, through counsel, received a copy of the assailed Resolution on July 18, 2017. [32] On August 1, 2017, Marzan filed a Motion for Extension of Time to File Petition for Review [33] praying for an additional period of thirty (30) days from August 1, 2017, or until August 31, 2017 to file her petition for review. On August 31, 2017, Marzan filed this Petition. In compliance with the Court's Resolution dated June 6, 2018, respondents filed their Joint Comment on the Petition, [34] to which Marzan filed her Reply. [35] In this Petition, Marzan insists that she was unlawfully removed from a permanent government position in violation of "pertinent Civil Service Laws". [36] Hence, Marzan prays that she be reinstated to her former position as Department Head of the CPDO. As well, Marzan reiterates her claim for moral and exemplary damages, attorney's fees, litigation expenses, and costs of suit. [37] The Issues The issues presented for the Court's resolution are: Whether Marzan's immediate resort to judicial remedies was proper; and Whether mandamuswill lie to compel respondents to reinstate Marzan as Department Head of the CPDO. The Court's Ruling The Court rules in favor of respondents. <table><tbody><tr><td> As an exception to the rule on exhaustion of administrative remedies, immediate resort to judicial remedies may be allowed if the issue involved presents a pure question of law.</td><td></td></tr></tbody></table> The Administrative Code of 1987 [38] (Administrative Code) constitutes the CSC as the central personnel agency of the government. [39] As such, the CSC is authorized to "[p]rescribe, amend and enforce rules and regulations [to carry] into effect the provisions of the Civil Service Law and other pertinent laws." [40] The CSC is also empowered to "[h]ear and decide administrative cases instituted by or brought before it directly or on appeal x x x." [41] Prevailing at the time of the disapproval of Marzan's appointment as Department Head of the CBO and her consequent termination from service was CSC Memorandum Circular No. 40-98 [42] (CSC MC No. 40-98) or the Revised Omnibus Rules on Appointments and Other Personnel Actions. Rule VI of CSC MC No. 40-98 governs the submission, approval and disapproval of civil service appointments. Its relevant provisions state: SEC. 1. An appointment shall be submitted to the [CSC] within thirty (30) calendar days from the date of issuance, which shall be the date indicated below the signature of the appointing authority. Otherwise it shall be made effective thirty (30) days prior to date of submission to CSC. In case of appointments issued by accredited agencies, the Report of Personnel Actions (ROPA) together with photocopies of appointments issued during the month shall be submitted within [fifteen (15)] days of the succeeding month. Appointments not submitted within the prescribed period shall be made effective [thirty (30)] days prior to date of submission If the appointee does not assume office within thirty (30) calendar days from receipt of the approved appointment, the same may be cancelled by the appointing authority and reported to the [CSC] for record purposes. The position is automatically deemed vacant without the need for an approval or declaration by the [CSC]. If the appointee is not allowed to assume office by the appointing authority despite of the [CSC's] approval of the appointment, said official shall be held administratively liable therefor. SEC. 2. Request for reconsideration of, or appeal from, the disapproval of an appointment may be made by the appointing authority and submitted to the Commission within fifteen (15) calendar days from receipt of the disapproved appointment. SEC. 3. When an appointment is disapproved, the services of the appointee shall be immediately terminated, unless a motion for reconsideration or appeal is seasonably filed. Services rendered by a person for the duration of his disapproved appointment shall not be credited as government service for whatever purpose. If the appointment was disapproved on grounds which do not constitute a violation of civil service law, such as failure of the appointee to meet the Qualification Standards (QS) prescribed for the position, the same is considered effective until disapproved by the [CSC] or any of its regional or field offices. The appointee is meanwhile entitled to payment of salaries from the government. If a motion for reconsideration or an appeal from the disapproval is seasonably filed with the proper office, the appointment is still considered to be effective. The disapproval becomes final only after the same is affirmed by the [CSC]. (Emphasis and underscoring supplied) In turn, the procedure on appeals involving personnel actions, including disapproval of appointments and termination of services, is set forth under Rule 23 of the Revised Rules on Administrative Cases in the Civil Service (RRACCS), the set of rules prevailing during the relevant period. Sections 110 to 114 thereof state: Section 110. Appeal from Decisions on Other Personnel Actions. - Other personnel actions, such as, but not limited to, separation from the service due to unsatisfactory conduct or want of capacity during probationary period, dropping from the rolls due to Absence Without Official Leave (AWOL), physical and mental unfitness, and unsatisfactory poor performance, protest, action on appointments , reassignment, transfer, reappointment, detail, secondment, demotion, or termination of services, may be brought to the [CSC Regional Office], by way of an appeal . Section 111. When and Where to File. - A decision or ruling of an agency head may be appealed within fifteen (15) days from receipt thereof by the party adversely affected to the [CSC Regional Office] and finally, to the [CSC] within the same period. However, if the decision is made by the Department Secretary, the same shall be appealable to the [CSC] within fifteen (15) days from receipt thereof. A motion for reconsideration may be filed with the same office which rendered the decision or ruling within fifteen (15) days from receipt thereof. Section 112. When deemed filed. - An appeal sent by registered mail shall be deemed filed on the date shown by the postmark on the envelope which shall be attached to the records of the case. In case of personal delivery, it is deemed filed on the date stamped thereon by the proper office. Section 113. Appeal Fee. - The appellant shall pay an appeal fee and a copy of the official receipt thereof shall be attached to the appeal. Section 114. Perfection of an Appeal . - To perfect an appeal, the appellant shall submit three (3) copies of the following documents: Appeal memorandum containing the grounds relied upon for the appeal, together with the certified true copy of the decision, resolution or order appealed from, and certified copies of the documents or evidence. The appeal memorandum shall be filed with the appellate authority, copy furnished the appointing authority. The latter shall submit the records of the case, which shall be systematically and chronologically arranged, paged and securely bound to prevent loss, with its comment, within fifteen (15) days from receipt, to the appellate authority. Proof of service of a copy of the appeal memorandum to the appointing authority; Proof of payment of the appeal fee; and A statement or certificate of non-forum shopping. When an appellant fails to comply with any of the above requirements within the reglementary period, the [CSC] shall direct compliance within a period of ten (10) days from receipt thereof, with a warning that failure to comply shall be construed as failure to perfect an appeal and shall cause the dismissal of the appeal with prejudice to its refiling. (Emphasis and underscoring supplied) Accordingly, Marzan should have questioned her termination by filing an appeal before the CSC Regional Office. However, instead of doing so, Marzan wrote a letter to Regional Director Rabang seeking an advisory opinion on matters relating to the disapproval of her appointment as Department Head of the CBO, and her consequent termination from service. Thus, in the September 2013 CSC Letter, the CSC Regional Office refrained from categorically responding to Marzan's queries, and advised Marzan to file an appeal in accordance with Section 110 of the RRACCS. The relevant portion of said letter reads: On the last issue, your allegation that you were not allowed by your Office to be restored to your former position as City Government Department Head [(CPDO)] after the disapproval of your transfer appointment is a legal matter that may be brought to the [CSC] in the form of an appeal pursuant to Section 110, Rule 23 of the [RRACCS]. [43] By failing to perfect an appeal with the CSC Regional Office and observing the procedure set forth under the RRACCS, Marzan violated the well-established rule on exhaustion of administrative remedies: x x x Where the enabling statute indicates a procedure for administrative review and provides a system of administrative appeal or reconsideration, the courts - for reasons of law, comity, and convenience - will not entertain a case unless the available administrative remedies have been resorted to and the appropriate authorities have been given an opportunity to act and correct the errors committed in the administrative forum. [44] Nonetheless, the rule on exhaustion of administrative remedies admits of exceptions: x x x A party may directly resort to judicial remedies if any of the following is present: when there is a violation of due process; when the issue involved is purely a legal question; when the administrative action is patently illegal amounting to lack or excess of jurisdiction; when there is estoppel on the part of the administrative agency concerned; when there is irreparable injury; when the respondent is a department secretary whose acts as an alter ego of the President bear the implied and assumed approval of the latter; when to require exhaustion of administrative remedies would be unreasonable; when it would amount to a nullification of a claim; when the subject matter is a private land in land case proceedings; when the rule does not provide a plain, speedy and adequate remedy; and when there are circumstances indicating the urgency of judicial intervention. [45](Emphasis supplied) Here, Marzan does not assail the disapproval of her appointment as Department Head of the CBO. What Marzan questions is respondents' refusal to reinstate her to her former position as Department Head of the CPDO, claiming that such reinstatement is mandated by Section 13, Rule VI of the Omnibus Rules. Clearly, Marzan seeks judicial intervention in order to determine whether Section 13, Rule VI of the Omnibus Rules applies. This question is one that is purely legal, and thus constitutes an exception to the rule on exhaustion of administrative remedies. In this light, the Court finds that Marzan's direct resort to the courts may be permitted. Be that as it may, the Petition fails on the merits. Section 13, Rule VI of the OmnibusRules does not apply. Foremost, Marzan insists that her reinstatement as Department Head of the CPDO is mandatory under Section 13, Rule VI of the Omnibus Rules. The provision states: SECTION 13. All appointments involved in a chain of promotions must be submitted simultaneously for approval by the Commission. The disapproval of the appointment of a person proposed to a higher position invalidates the promotion of those in lower positions and automatically restores them to their former positions. However, the affected persons are entitled to the payment of salaries for services actually rendered at a rate fixed in their promotional appointments. In Divinagracia , the Court summarized the requirements for the application of Section 13, Rule VI, thus: x x x [B]efore a public official or employee can be automatically restored to her former position, there must first be a series of promotions ; second, all appointments are simultaneously submitted to the CSC for approval ; and third, the CSC disapproves the appointment of a person proposed to a higher position . [46] (Emphasis supplied) It is thus clear that Section 13, Rule VI presupposes that the appointment of the official or employee concerned constitutes a promotion. CSC MC No. 40-98 defines promotion as "the advancement of an employee from one position to another with an increase in duties and responsibilities as authorized by law, and usually accompanied by an increase in salary." [47] In contrast, a transfer contemplates "the movement of [an] employee from one position to another which is of equivalent rank, level or salary without break in the service involving the issuance of an appointment." [48] Keeping these distinctions in mind, the Court echoes the findings of the CA: x x x A comparison between the two (2) appointments issued to [Marzan] for the two (2) positions shows that these are of the same rank and salary grade level. Both positions even have the same appellation - City Government Department Head II - only that each belongs to different offices albeit under the same local government unit. x x x [49] Marzan does not dispute these findings. Moreover, as respondents correctly point out, Marzan herself conceded in her Judicial Affidavit that her appointment to the CBO was not a promotion, but rather a "lateral transfer". [50] Assuming arguendo that Marzan's appointment qualifies as a promotion, all three requisites for the application of Section 13, Rule VI are still lacking, considering that said appointment was not part of a series of promotions simultaneously submitted to the GSC for approval. Evidently, Section 13, Rule VI of the Omnibus Rules does not apply. <table><tbody><tr><td> The circumstances which impelled the Court to reinstate respondent in Divinagracia are not present in this case.</td><td></td></tr></tbody></table> Further, Marzan claims that the Court's ruling in Divinagracia should be adopted in this case. Marzan stresses that in Divinagracia , the Court correctly directed the reinstatement of respondent therein on the basis of the latter's right to security of tenure. However, a scrutiny of said ruling reveals that Divinagracia is not on all fours. In Divinagracia , Filomena Mancita (Mancita) was appointed as Municipal Development Coordinator (MDC) of the Municipality of Pili (Pili) on August 1, 1980. Mancita was terminated on July 1, 1985 due to the reorganization of the municipal government of Pili. Following said reorganization, private respondent Prescila Nacario (Nacario), who was then the Municipal Budget Officer (MBO) of Pili, was appointed to the position of Municipal Planning and Development Coordinator (MPDC) on June 10, 1985. In 1988, the Local Government Officers Services was nationalized and placed under the supervision of the Department of Budget and Management (DBM). Under this nationalized regime, the power to appoint local budget officers was transferred to the DBM Secretary. Accordingly, petitioner Alexis San Luis (San Luis) was temporarily appointed by the DBM Secretary as MBO of Pili, the position previously held by Nacario before she was appointed as MPDC. When control over the Local Government Officers Services was returned to the local government units by virtue of the Local Government Code of 1991, San Luis was reappointed to the same position by Mayor Delfin N. Divinagracia (Mayor Divinagracia) on June 22, 1992, this time, in a permanent capacity. Meanwhile, Mancita assailed her termination before the Merit Systems and Protection Board (Merit Board). The Merit Board declared Mancita's termination illegal, inasmuch as she was qualified to hold the newly created position of MPDC, as it was equivalent to the position she held prior to the re-organization of the municipal government of Pili. Accordingly, the Merit Board directed Mayor Divinagracia to reinstate Mancita to the position of MPDC. On appeal, the CSC affirmed the Merit Board's findings through CSC Resolution No. 90-657. Hence, on October 15, 1990, Mayor Divinagracia informed Nacario that she was being relieved of her position as MPDC effective November 16, 1990 in compliance with the Merit Board's directives. Nacario eventually sent a query to the CSC, asking about her status as a permanent employee after she had accepted the position of MPDC. In a letter dated December 8, 1992 (December 1992 Opinion), the CSC opined that the reinstatement of Mancita to the position of MPDC was not a valid cause for Nacario's termination, and that Nacario had the right to return to the position of MBO, the position already occupied by San Luis. Mayor Divinagracia sought reconsideration of the December 1992 Opinion. However, such reconsideration was denied through CSC Resolution No. 93-1996. This prompted Mayor Divinagracia and San Luis to file a Petition for Certiorari before the Court, claiming that CSC Resolution No. 93-1996 had been issued with grave abuse of discretion. Mayor Divinagracia and San Luis raised, among others, that Nacario could no longer be reinstated to her former position as MBO as she was deemed to have vacated said position when she accepted her new appointment as MPDC. The Court denied the Petition for Certiorari, and ordered the reinstatement of Nacario to her former position as MBO. What impelled the Court to rule as it did was its finding that Nacario's movement from the position of MBO to MPDC constituted an "unconsented lateral transfer" which was tantamount to removal without cause. Hence, the Court held: Let us now examine whether the lateral transfer of private respondent was validly made in accordance with Sec. 5, par. 3, Rule VII, Omnibus Rules Implementing Book V of E.O. 292. If not, then private respondent is entitled to be protected in her security of tenure. Sec. 5, par. 3, of Rule VII provides that - Transfer shall not be considered disciplinary when made in the interest of public service, in which case, the employee concerned shall be informed of the reasons therefor . If the employee believes that there is no justification for the transfer, he may appeal his case to the [CSC]. x x x According to Nacario[,] she never applied or sought appointment by transfer to the position of MPDC since she even had no prior knowledge of her appointment. She assumed the new position only in order to comply with the move of Mayor Prila to supposedly "reorganize" the municipal government of Pili. Nacario did not question her transfer because she revered the mayor and did not in any way intend to displease him. The submissive attitude displayed by private respondent towards her transfer is understandable. Although Nacario was not informed of the reasons therefor she did not complain to the mayor or appeal her case to the CSC if in fact the same was not made in the interest of public service. For it is not common among local officials, even those permanent appointees who are more secured and protected in their tenurial right, to oppose or question the incumbent local executive on his policies and decisions no matter how improper they may seem. x x x x Private respondent was the Budget Officer of Pili for almost eight (8) years from August 1980 until her transfer in Jnly, 1988. Nacario appeared to be satisfied with her work and felt fulfilled as Budget Officer until Mayor Prila appointed her MPDC to fill up the position, which was not even vacant at that time. It was only seven (7) days after Nacario's appointment when Mayor Prila informed Mancita that her services were being terminated. Simply put, Mayor Prila was so determined in terminating Mancita that he conveniently pre-arranged her replacement by Nacario. Although Nacario continued to discharge her duties, this did not discourage her from trying to regain her former position. Undaunted, she applied with the Office of the Budget Secretary for the position of Budget Officer upon learning that it was placed under the Department of Budget and Management. She was not however successful. In Sta. Maria v. Lopez we distinguished between a transfer and a promotion and laid down the prerequisites of a valid transfer thus - A transfer is a 'movement from one position to another which is of equivalent rank, level and salary, without break in service.' Promotion is the 'advancement from one position to another with an increase in duties and responsibilities as authorized by law, and is usually accompanied by an increase in salary' x x x A transfer that results in promotion or demotion, advancement or reduction or a transfer that aims to 'lure the employee away from his permanent position,' cannot be done without the employees' consent. For that would constitute removal from office. Indeed, no permanent transfer can take place unless the officer or employee is first removed from the position held, and then appointed to another position x x x The rule that unconsented transfers amount to removal is not however without exception. As we further said in Sta. Maria , Concededly there are transfers which do not amount to removal. Some such transfers can be effected without the need for charges being proffered, without trial or hearing, and even without the consent of the employee x x x The clue to such transfers may be found in the 'nature of the appointment' Where the appointment does not indicate a specific station, an employee may be transferred or assigned provided the transfer affects no substantial change in title, rank and salary x x x. Such a rule does not proscribe a transfer carried out under a specific statute that empowers the head of an agency to periodically reassign the employees and officers in order to improve the service of the agency x x x. Neither does illegality attach to the transfer or reassignment of an officer pending the determination of an administrative charge against him; or to the transfer of an employee from his assigned alleged station to the main office, effected in good faith and in the interest of the service pursuant to Sec. 32 of the Civil Service Act. Clearly then, the unconsented lateral transferof Nacario from the Budget Office to the Office of MPDC was arbitrary for it amounted to removal without cause, hence, invalid as it is anathema to security of tenure. When Nacario was extended a permanent appointment on [August 1, 1980] and she assumed the position, she acquired a legal, not merely an equitable, right to the position. Such right to security of tenure is protected not only by statute, but also by the Constitution, and cannot be taken away from her either by removal, transfer or by revocation of appointment, except for cause, and after prior notice. The guarantee of security of tenure is an important object of the civil service system because it affords a faithful employee permanence of employment, at least for the period prescribed by law, and frees the employee from the fear of political and personal prejudicial reprisal. Consequently, it could not be said that Nacario vacated her former position as Budget Officer or abdicated her right to hold the office when she accepted the position of MPDC since, in contemplation of law, she could not be deemed to have been separated from her former position or to have terminated her official relations therewith notwithstanding that she was actually discharging the functions and exercising the powers of MPDC. The principle of estoppel, unlike in Manalo v. Gloria , cannot bar her from returning to her former position because of the indubitable fact that private respondent reluctantly and hesitantly accepted the second office. The element of involuntariness tainted her lateral transfer and invalidated her separation from her former position. For another thing, the appointment of San Luis as Budget Officer carried with it a condition. At the back of his appointment is inscribed the notation Sa kondisyon nasa ayos ang pagkakatiwalag sa tungkulin ng dating nanunungkulan which when translated means "Provided that the separation of the former incumbent is in order." Considering that the separation of Nacario who was the former incumbent was not in order, San Luis should relinquish his position in favor of private respondent Nacario. This is, of course, without prejudice to San Luis' right to be reinstated to his former position as Cashier II of the DENR, he being also a permanent appointee equally guaranteed security of tenure. [51] (Emphasis and underscoring supplied; citations omitted) The factual circumstances in this case do not warrant a similar ruling. To recall, Mayor Gordon appointed Marzan as Department Head of the CPDO on January 16, 2008. On June 7, 2011, the CSC approved said appointment and accorded Marzan permanent status. Subsequently, on December 1, 2011, Mayor Gordon appointed Marzan as Department Head of the CBO. Marzan never assailed the validity of her lateral transfer. As well, she never once claimed that such transfer was without her consent. On the contrary, the records show that Marzan had been fully aware that her former position had been declared vacant following acceptance of her new appointment. As correctly observed by the lower courts, in the Appropriations Act of Olongapo City for 2012, which she, as member of the finance committee helped prepare, the position of Department Head of the CPDO was tagged vacant. Moreover, unlike in Divinagracia , there are no circumstances which indicate that Marzan's lateral transfer from the CPDO to the CBO was part of a ploy to ease her out of her permanent position. It bears stressing that: (i) Marzan's appointment to the CBO was effected by Mayor Gordon, not Mayor Paulino; and (ii) Marzan vacated her former position as Department Head of the CPDO before Mayor Paulino assumed office. Thus, when Mayor Paulino assumed office following his victory in the May 2013 local elections, he merely appointed Balde to fill in a position that had become vacant prior to his term. Unlike San Luis' appointment in Divinagracia , Balde's appointment does not appear to be subject to the condition that the separation of the previous holder of the office be in order. Thus, Marzan's reinstatement at Balde's expense would effectively violate the very right which she now invokes. <table><tbody><tr><td> Mandamus will not lie to compel Marzan's reinstatement.</td><td></td></tr></tbody></table> Section 3, Rule 65 of the Rules of Court sets forth the circumstances which warrant the issuance of a writ of mandamus: SEC. 3. Petition for mandamus . - When any tribunal, corporation, board, officer or person unlawfully neglects the performance of an act which the law specifically enjoins as a duty resulting from an office, trust, or station, or unlawfully excludes another from the use and enjoyment of a right or office to which such other is entitled , and there is no other plain, speedy and adequate remedy in the ordinary course of law, the person aggrieved thereby may file a verified petition in the proper court, alleging the facts with certainty and praying that judgment be rendered commanding the respondent, immediately or at some other time to be specified by the court, to do the act required to be done to protect the rights of the petitioner, and to pay the damages sustained by the petitioner by reason of the wrongful acts of the respondent. (Emphasis supplied) The writ of mandamus shall only issue to compel the performance of a ministerial act, or "one in which an officer or tribunal performs in a given state of facts, in a prescribed manner, in obedience to a mandate of legal authority , without regard to or the exercise of his own judgment upon the propriety or impropriety of an act done." [52] Thus, mandamus will not lie to compel the performance of a discretionary act. To stress: Mandamus is never issued in doubtful cases. It cannot be availed against an official or government agency whose duty requires the exercise of discretion or judgment. For a writ to issue, petitioners should have a clear legal right to the thing demanded, and there should be an imperative duty on the part of respondents to perform the act sought to be mandated. In the absence of a clear and unmistakable provision of a law, a mandamus petition does not lie to require anyone to a specific course of conduct or to control or review the exercise of discretion; it will not issue to compel an official to do anything which is not his duty to do or which is his duty not to do or give to the applicant anything to which he is not entitled by law. [53] Considering that Section 13, Rule VI of the Omnibus Rules does not apply, and that Marzan freely and knowingly vacated her former position as Department Head of the CPDO, Marzan's reinstatement thereto constitutes a discretionary act which cannot be compelled through a writ of mandamus . In this light, the Court finds no basis to grant Marzan's prayer for moral and exemplary damages, litigation expenses and costs of suit. In closing, it must be emphasized that Balde's silence with respect to the alleged hostilities which took place on Marzan's last day in office does not escape the Court's attention. Moreover, the fact that the duty to review all requirements and supporting documents relating to personnel appointments of the City Government of Olongapo falls on respondent Barroga as Acting Chief Administrative Officer of the Human Resource Management Office is not lost on the Court. [54] However, the Court necessarily limits the scope of this Decision to the resolution of the sole substantive issue raised therein, that is, whether or not mandamus will lie to compel the reinstatement of Marzan to her former position as Department Head of the CPDO. Nevertheless, the denial of the present Petition and the concomitant dismissal of Marzan's plea for mandamus shall be without prejudice to any administrative liability which may be determined in appropriate proceedings. WHEREFORE , premises considered, the Petition is DENIED . The Decision and Resolution respectively dated October 26, 2016 and July 4, 2017 rendered by the Court of Appeals in CA G.R. SP No. 139549 are AFFIRMED . SO ORDERED. Peralta, C. J., (Chairperson), Carandang, Zalameda , and Gaerlan, JJ. , concur. [1] Rollo , pp. 6-29, excluding Annexes. [2] Id. at 31-53. Penned by Associate Justice Maria Elisa Sempio Diy, with the concurrence of Associate Justices Ramon M. Bato, Jr. and Pedro B. Corales. [3] Id. at 55-56. [4] Special Twelfth Division and Former Special Twelfth Division, respectively. [5] Rollo , p. 8. [6] Id. at 9. [7] See Reply, id. at 109. [8] Petition, id. at 22. [9] Id. [10] Pertinent portions of the September 2013 CSC Letter read: On the 1 st issue, your agency Human Resource Management Office [(HRMO)] shall be responsible that all documentary requirements to support the appointments issued have been complied with and found to be in order as provided for under Section 1, Rule VII of the Omnibus Rules on Appointments and Other Personnel Actions. This is evidenced by the certification of the HRMO at the back of the appointment. x x x On the 2 nd issue, the services of a permanent employee in the government may be terminated only after the final disapproval of his/her appointment and/or upon the order of a competent court/authority that has become final and executory. On the 3 rd issue, Section 13. Rule V of the Omnibus Civil Service Rules and Regulations provides as follows: Section 13. All appointments involved in a chain of promotions must be submitted simultaneously for approval by the [CSC]. The disapproval of the appointment of a person proposed to a higher position invalidates the promotion of those in lower positions and automatically restores them to their former positions. x x x. On the 4 th issue, the appointing authority being the disciplining person is the authorized person to terminate your services in accordance with the Civil Service Law, rules and regulations. x x x x On the last issue, your allegation that you were not allowed by your Office to be restored to your former position as City Government Department Head [CPDO] after the disapproval of your transfer appointment is a legal matter that may be brought to the [CSC] in the form of an appeal pursuant to Section 110, Rule 23 of the Revised Rules on Administrative Cases in the Civil Service. Rollo , pp. 36-37. [11] Rollo , pp. 32-38. [12] Id. at 38. [13] Id. [14] Id. at 38-39. [15] Id. at 39. [16] See id. [17] Id. at 39-40. [18] Id. at 39. [19] Id. at 40. [20] Id. [21] Ordinance No. 27, series of 2012. [22] Rollo , p. 40. [23] Id. at 41. [24] Id. [25] Id. at 52. [26] Id. at 43. [27] See id. at 46-48. [28] 314 Phil. 550 (1995). [29] See rollo , pp. 48-49. [30] Id. at 51-52. [31] Id. at 55-56. [32] Id. at 8. [33] Id. at 3-4. [34] Id. at 75-81. [35] Id. at 107-114. [36] See id. at 23. [37] Id. at 110-111. [38] Executive Order No. 292, INSTITUTING THE "ADMINISTRATIVE CODE OF 1987," July 25, 1987. [39] ADMINISTRATIVE CODE OF 1987, Book V, Title I, Subtitle A, Chapter 1, Sec. 1. [40] Id., Chapter 3, Sec. 12(2). [41] Id., Chapter 3, Sec. 12(11). [42] Issued on December 14, 1998. [43] Rollo , p. 37. [44] Mohammad v. Belgado-Saqueton , 789 Phil. 651, 658-659 (2016). [45] Buena, Jr. v. Benito , 745 Phil. 399, 416-417 (2014). [46] Divinagracia, Jr. v. Sto. Tomas , supra note 28, at 563. [47] CSC MC No. 40-98, Rule III, Sec. 4(c). [48] Id., Sec. 4(d). [49] Rollo , p. 49. [50] Id. at 78. [51] Divinagracia, Jr. v. Sto. Tomas , supra note 28, at 565-570. [52] I-Popefrancis v. Department of Budget and Management , G.R. No. 206689, August 24, 2016 (Unsigned Resolution). Italics supplied. [53] Id. [54] CSC MC No. 40-98, Rule VII, Sec. 1 states: SEC. 1. The Human Resource Management Officer (HRMO), Personnel Officer (PO) or the duly authorized personnel in charge of personnel matters shall: Review thoroughly and check the completeness of all the requirements and supporting papers in connection with all cases of appointments before submission to the Commission. Sign the following certifications at the back of the appointment. Certification as to the completeness of the requirements Certification that the vacant position to be filled has been duly published Ensure that the Chairman of the Personnel Selection Board (PSB) has signed the certification at the back of the appointment, when applicable. The Human Resource Management Officer shall be a regular member of the PSB. Ensure that all questions in the Personal Data Sheet (CS Form 212) of the appointee are answered properly and completely with his recent photograph attached, his right thumbmark affixed and his current Community Tax Certificate indicated therein. Furnish appointee with a photocopy of his appointment for submission to the Commission. Ensure that appointee acknowledges receipt of a photocopy of said appointment by signing on the duplicate and other copies thereof. Submit appointments with the prescribed transmittal form indicating the names of the appointees, their position and the corresponding date of issuance. Officially transmit to the appointee original copy of his appointment acted upon by the Commission. Submit a quarterly report of employee accession and separation to the Commission. x x x x <here is a image 8d65ecaee3044548-b9d0c1b586b3e1c0> <here is a image 28e0c7ef23e90277-3239906ae0120470> Source: Supreme Court E-LibraryThis page was dynamically generatedby the E-Library Content Management System (E-LibCMS)
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LocalGov.co.uk - Your authority on UK local government - Museums and galleries to receive £48m boost Museums and galleries to receive £48m boost Image: elRoce / Shutterstock.com. Cultural venues across the country are set to receive £48m of funding to help improve access to the arts, the Government has announced. More than 60 organisations in England will receive a slice of the funding which is being released as part of the Government’s Cultural Investment Fund, which was first unveiled in 2019. Public venues such as Birmingham Museum & Art Gallery and the museum and former top-secret Second World War code-breaking centre Bletchley Park will receive funding. Support will also go to smaller venues such as True’s Yard Fisherfolk Museum in King’s Lynn which celebrates 900 years of the fishing industry, and heritage sites including Berwick Barracks in Northumberland. ‘Culture is the bedrock of society. It brings people together, entertains and informs us, and helps us to understand our common past and shared future,’ said arts minister Lord Parkinson of Whitley Bay. ‘Today we are announcing a raft of new funding for treasured cultural institutions up and down the country. ‘This will help them to continue their great work, advance our work to level up access to arts and culture so they can be enjoyed by people no matter where they live, and protect these cherished institutions for future generations to enjoy.’ Last month, the Public Campaign for the Arts found spending on public libraries, entertainment venues, museums, galleries and recreation facilities by councils has dropped to £59.90 per person per year, from £118.93 just over a decade ago. Jack Gamble, director of the Public Campaign for the Arts, commented: ‘The arts are not a luxury – they provide vital benefits to our lives and communities. We appreciate the financial pressures that local councils are under, partly due to cuts from national government since 2010, but sacrificing our cultural services is not the answer.’ #Museums #Funding #Cultural Services Analysis Boosting urban biodiversity with new innovations in green infrastructure Cities play a critical role in addressing biodiversity loss. Alexander Ilsink, Mobilane, looks at how to maximise the potential of green infrastructure. Toro leads the way of Stage V compliant out-front rotaries APT Skidata Launches New Touchless Parking Solution SmartCell fire detection system – the smartest investment for HMO properties Eye-catching EcoArc Recycling Station APT SKIDATA launches new smart remote assistance tool to further enhance its digital solutions Case Studies Energy Efficient High Mast Lighting for UK City of Culture Active Light Milton Keynes City Council offsets rising energy prices with Telensa smart street lighting Building vibrant local economies MICHELIN’s Connected Fleet leads to nearly 50% drop in engine idling Evacuation alert system from Advanced helps protect residents in Merseyside social housing UltraCrete prevents dangerous accident in Carmarthen Decarbonising the UK's housing stock – a practical example Tough Patch® saves Ringway Jacobs time and money UltraCrete repairs troublesome chamber on busy London road City of York tackles congestion and pollution with Alchera Technologies Panasonic Heats Renovated Chapel in Devon with Unique Air Source Heat Pump & Fan Coil Solution A DLUHC-funded PropTech win uses 3D images and voice technology to bring local planning into the modern age Protecting Cumbria’s dark skies – a collaborative effort between Thorn Lighting and Cumbria County Council Adur & Worthing Councils verify property discounts and exemptions using Aspire Warwickshire Pub Installs Panasonic nanoe™ X to improve indoor environment Thorn ensures the perfect setting at Queens Quay and Titan Crane Basin Traffic Management Contract secured in Thurrock SWARCO and APT Skidata provide the technology solution for Wembley car parks Thorn’s Urba bollards lead the way at Coed Melyn Park Matrix appoints Roger Clements as first CMO to lead transformational growth Recuriter: Essex County Council Supervising Social Worker £34712 - £46751 per annum Please note interviews for this role will be held on 5th June.Here in Essex, we continue to raise the bar about practice and our investment in our wor England, Essex, Chelmsford Recuriter: Essex County Council Housing Benefit Assessment Officer £29508 The Housing Benefit Team has been at the forefront of the government’s response to the pandemic and cost of living crisis, and this is an exciting time to join us!  One Angel Square, Northampton Recuriter: West Northamptonshire Council Training and Resilience Officer £29508 We’re a new local authority, created in April 2021. We’re at the beginning of our journey of shaping what the Benefits Team looks like at West Northants Council, so there is plenty of opportunity to contribute to developing processes, and shaping our One Angel Square, Northampton Recuriter: West Northamptonshire Council Partner Content Circular highways is a necessity not an aspiration – and it’s within our grasp Shell is helping power the journey towards a circular paving industry with Shell Bitumen LT R, a new product for roads that uses plastics destined for landfill as part of the additives to make the bitumen. Support from Effective Energy Group for Local Authorities to Deliver £430m Sustainable Warmth Funded Energy Efficiency Projects Effective Energy Group is now offering its support to the 40 Local Authorities who have received a share of the £430m to deliver their projects on the ground by surveying properties and installing measures. Pay.UK – the next step in Bacs’ evolution Dougie Belmore explains how one of the main interfaces between you and Bacs is about to change. Need To Know Who is considered a keyworker? Pre-election period (purdah) and local government
https://www.localgov.co.uk/Museums-and-galleries-to-receive-48m-boost/53852
Study: Bariatric surgeries can double peak blood alcohol levels, patients Credit: Photo by L. Brian Stauffer CHAMPAIGN, Ill. -- A new study of 55 women found that two of the most popular forms of bariatric surgery - Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy - may dramatically change patients' sensitivity to and absorption of alcohol. Some women's sensitivity to Study: Bariatric surgeries can double peak blood alcohol levels, patients may be unaware Credit: Photo by L. Brian Stauffer CHAMPAIGN, Ill. — A new study of 55 women found that two of the most popular forms of bariatric surgery – Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy – may dramatically change patients’ sensitivity to and absorption of alcohol. Some women’s sensitivity to alcohol increased so much after bariatric surgery that the amount they could consume before feeling the effects was reduced by half compared with their pre-surgery drinking habits, while others had reduced sensitivity, researchers at the University of Illinois at Urbana-Champaign found. After consuming an alcoholic beverage that was equivalent to having two standard drinks, women who had gastric bypass or sleeve gastrectomy surgery experienced blood alcohol-concentration peaks sooner and about twice as high – 50% above the .08% blood alcohol content that’s the legal threshold for drunk driving in many states – compared with gastric band patients. However, some women in the U. of I. study who reached this heightened peak were less sensitive to the effects of alcohol and reported almost no sedative effects from it, said M. Yanina Pepino, a professor of food science and human nutrition who led the study. “About a third of women in the study felt almost no sedative effects, even when they reached peak blood alcohol concentrations that were comparable to those of women in the general population consuming four standard drinks,” Pepino said. “People who have not had bariatric surgery and are less sensitive to the sedative or impairing effects of alcohol, and those who are more sensitive to its stimulant effects, are generally at greater risks for developing alcohol problems, even decades later.” The findings, which were based on the women’s responses on several surveys about how alcohol affected them and analyses of their blood alcohol concentrations after drinking an alcoholic beverage, help shed light on why postoperative gastric bypass and sleeve gastrectomy patients may be at increased risks of developing alcohol problems after having weight-loss surgery. The women in the study had undergone bariatric surgery at medical centers in Illinois and Missouri within the previous five years. Of them, 16 had received Roux-en-Y gastric bypass surgery, which reduces the stomach to the size of an egg and reroutes the small intestine; 28 had undergone sleeve gastrectomy, which removes a majority of the stomach and reduces the remainder to a slender banana shape; and 11 had an adjustable gastric band placed around the top of the stomach to reduce it to a small pouch. At the beginning of the study, participants filled out the Alcohol Sensitivity Questionnaire, which asked about the number of drinks they needed to consume to experience various effects, such as becoming more talkative or flirtatious, or experiencing hangovers. “These and other effects such as feeling sedated can be signals to stop drinking, and being insensitive to them increases one’s chances of consuming greater amounts of alcohol and the risk for an alcohol-use disorder,” said Maria Belen Acevedo, a postdoctoral research associate at the U. of I. and the study’s first author. Participants completed the questionnaire twice – recalling how alcohol affected them before and after the surgery on separate questionnaires. Of the women who completed the questionnaires, 45 also participated in tests that assessed their individual response to alcohol. The tests consisted of drinking a nonalcoholic juice beverage on one day and drinking the same beverage mixed with alcohol on another day, and having their blood alcohol concentrations measured at numerous points on both days. The smell and flavor of the alcohol was masked so that participants could not tell if the drink contained it on their first sip. Before drinking either beverage and at several time points afterward, the participants completed surveys about any effects they were feeling, while the researchers collected multiple blood samples. Screening post-bariatric surgery patients with the Alcohol Sensitivity Questionnaire could help identify people who might be at increased risk of alcohol problems after the surgery and enable clinicians to deliver more effective prevention programs for these patients, according to the researchers. The study, currently in press with the journal Surgery for Obesity and Related Diseases, was supported by grants from the National Institutes of Health and the U.S. Department of Agriculture National Institute of Food and Agriculture’s Hatch Project. Co-authors of the study were human development and family studies professor Dr. Margarita Teran-Garcia, and kinesiology and community health professors Nicholas A. Burd and Naiman Khan, all of the U. of I.; Dr. Blair Rowitz, the associate dean for clinical affairs of the Carle Illinois College of Medicine; University of Missouri psychology professor Bruce D. Bartholow; and psychiatry professor Kathleen K. Bucholz and Dr. J. Christopher Eagon, both of the Washington University School of Medicine. Original Source https://news.illinois.edu/view/6367/806386 Tags: Addiction Diet/Body Weight Gastroenterology Medicine/Health Metabolism/Metabolic Diseases Nutrition/Nutrients
https://bioengineer.org/study-bariatric-surgeries-can-double-peak-blood-alcohol-levels-patients-may-be-unaware/
HEC-HMS based rainfall-runoff model for Punpun river basin | Water Practice & Technology | IWA Publishing HIGHLIGHTS. A rainfall-runoff model for the Punpun river basin has been developed.Various statistical indices have been computed to check the performance of the HEC-HMS based rainfall-runoff model for Punpun river basin Shashi Ranjan ; 1 Department of Civil Engineering, National Institute of Technology Patna, Patna, Bihar 800005, India Water Practice and Technology (2022) 17 (5): 986–1001. https://doi.org/10.2166/wpt.2022.033 Article history Shashi Ranjan ,Vivekanand Singh; HEC-HMS based rainfall-runoff model for Punpun river basin. Water Practice and Technology1 May 2022; 17 (5): 986–1001. doi:https://doi.org/10.2166/wpt.2022.033 Abstract Various hydrological models were used in different river basins to simulate the runoff on available rainfall, land use and soil property data. The HEC-HMS model is used by several researchers to estimate the water potential of the basin through rainfall-runoff modeling. In this study, a rainfall-runoff model for the Punpun river basin has been developed using HEC-HMS. Daily rainfall and runoff data from the years 2005 to 2017 were used for the development of model. ArcGIS has been used to analyze the hydrological parameters, preparation of LULC, soil and slope maps for the computation of curve number as input into the HEC-HMS model. Daily, monthly and monsoonal rainfall-runoff models have been developed. The performance of all the models has been evaluated using statistical indices–coefficient of determination (R 2), Nash-Sutcliffe efficiency (NSE), percent bias (PBIAS) and RMSE-observations standard deviation ratio (RSR). R 2and NSE values for all the models are greater than 0.75 and PBIAS is less than 10, which shows very good results from all the models except the daily model, in which NSE values are less than 0.75. Based on statistical indices, the monthly model performs better than the daily and monsoonal models. HIGHLIGHTS A rainfall-runoff model for the Punpun river basin has been developed. Various statistical indices have been computed to check the performance of the model. Comparison of daily, monthly and monsoonal models have been made. Graphical Abstract Graphical Abstract Graphical Abstract GIS , HEC-HMS model , Punpun river basin , rainfall-runoff model INTRODUCTION Water is the most important natural resource on the earth. Human life will not survive without water (Abdullah 2013) and thus it is also called the gift of God. Water moves along the natural slope of ground surface through concentrated small rivulets and flows down in defined streams and thus stream flow is generated (Cunha et al.2016;Efthimiou 2018). The estimation of stream flow or runoff from a catchment is necessary for the purposes of assessing the flood peaks, water availability for municipal needs, design of storage facilities for multiple purposes, planning of irrigation operations for agricultural or other industrial purposes, wildlife protection, estimating future dependable water supplies for power generation etc. Further, rainfall is the basic input of the hydrological cycle that can be measured easily and economically, while runoff is a dependent variable that needs to be estimated for the corresponding rainfall. The measurement of rainfall has been practiced for a long time and it is easily available as compared to runoff (Scharffenberg 2013;Tan et al.2017;Tassew et al.2019). Precipitation characteristics, catchment shape and size, soil types, land use and topography are the main factors affecting runoff from a catchment (Jean-Baptiste et al.2011). Land use land cover (LULC) and soil type have been proved to be most sensitive factors in hydrological behavior as compared to catchment shape and size that affect the generation of stream flow (Chinnasamy & Agoramoorthy 2015;Hassan & Jin 2016;Jaiswal et al.2020). It was observed that the hydrological response of a catchment is most sensitive to the percentage of land-use and distribution of soil type (Houborg et al.2012;Ismael et al.2017;Opie et al.2020). Study of the effects of catchment behavior on floods, prediction of catchment response to changes in the input conditions, modeling of river behavior, real-time flood forecasting, adjusting and evaluation of water resource management and effects of river's activity such as erosion and sedimentation can be made with the help of geographic information systems (GIS). GIS can be defined as ‘a computer system capable of capturing, storing, analyzing and displaying geographically referenced information; that is, data identified according to location’ (Nenwiini & Kabanda 2013;USGS 2016;Koltsida & Kallioras 2019). The data for rainfall-runoff (R-R) modeling ranges from a digital elevation model (DEM) to derive physical basin characteristics, soil characteristics (for parameters about infiltration loss and soil moisture holding capability) and land use classes derived from satellite images etc. (Banerjee et al.2020;Kumar & Bhattacharjya 2021). With the advent of GIS, these data can be easily processed and analyzed to estimate hydrological modeling parameters (Prasad & Narayanan 2016;Seekao & Pharino 2016;Kumar & Himanshu 2017). ArcGIS is a more advanced tool and provides a larger user base with better interface (Khatami & Khazaei 2014). ArcGIS developed by Environmental Systems Research Institute (ESRI) is the versatile and comprehensive GIS package used by the water resources group of researchers, academicians and engineers. Several modules of ArcGIS are specially developed for these purposes. Hydrologic Engineering Center (HEC) develops the extension tool viz. hydro arc tool and HEC Geo-HMS to prepare the HEC-HMS (Hydrologic Engineering Center-Hydrologic Modeling System) database. The ArcGIS tool is used to perform terrain analysis using DEM to delineate the basin and river-stream network. HEC Geo-HMS computes the various basin characteristics such as basin area, stream length, slope etc., which are necessary for developing the conceptual rainfall-runoff model in HEC-HMS (Ghani et al.2012;Halwatura & Najim 2013;Khoshtinat et al.2019;Roy & Saha 2019). HEC-HMS is software that simulates the rainfall-runoff processes in river basin systems. It can be used to solve various problems. The HEC-HMS model can be used to conduct studies on water availability, urban drainage, flow forecasting, simulating flood event, future urbanization impact, flood damage reduction, wetland hydrology, reservoir spillway design, flood plain regulation, and system operation (Ashish et al.2012;Gautam et al.2013;Oleyiblo & Li 2010;Shrestha et al.2014;Sok & Oeurng 2016;Pichuka et al.2017;Kazezyilmaz-Alhan et al.2021). The rainfall-runoff model is broadly classified into empirical, conceptual and physical models. The empirical model, also called a data-driven model, requires fewer parameters, which can be calibrated and measured from field properties or fixed through an empirical procedure (Ntoanidis et al.2013;Gebre 2015;Gull & Shah 2020). Conceptual models are mostly applied in small homogeneous areas by spatial lumping and replacement of various components of the hydrological cycle by conceptual storage elements (Song et al.2011;Khaddor et al.2017;Pichuka et al.2017;Winarta et al.2019). The physical model is based on the understanding of hydrological processes and relates to catchment parameters. It is a distributed model and incorporates spatial and temporal variability of all the parameters. It is the most complicated model and requires a large amount of distributed data of topography, LULC, soil distribution etc. The differences in the model's characteristics affect the applicability, accuracy and reliability of the runoff response from extreme rainfall or prediction of runoff in catchments. Catchment morphology is one of the most important natural environmental factors that significantly affect hydrological processes. Researches on HEC-HMS showed its ability to simulate and forecast stream flow based on various datasets and catchment types, especially for the small catchments. Though the HEC-HMS model has been used globally, very few studies have been made in Indian region catchments. STUDY AREA Figure 1presents a map of the study area, the Punpun river basin. It originates in the hills of Palamu district of Jharkhand state at an elevation of 300 meters at a latitude of 24° 11′ N and longitude 84° 9′ E. After flowing 25 km, it joins river Ganga at Fatuha, downstream of Patna. It carries high discharge during monsoons, creates floods and inundate the adjoining area but has no flow during lean periods. Both problems, high discharge and no flow, lead to water management issues in the basin (Panda & Wahr 2016). This river basin receives heavy rainfall during the months August to October. Generally, the climate in and around the basin is humid, with moderate to high wind velocity. The average annual rainfall varies from 99 cm near the confluence of the Ganga (Patna district) to 134 cm in the upper reaches (Palamu district). The Punpun basin receives 80–87% of its annual rainfall during the monsoon. Precipitation is uniform and does not vary frequently in the lower part of the catchment. A Central Water Commission gauging site is located at Sripalpur at a Latitude of 25° 30′ 06″ N and longitude of 85° 06′ 08″ E in the Patna district. The river outlet is considered to be at Sripalpur and accordingly the basin is delineated as shown inFigure 1. The study area of the Punpun river basin is 7055 km 2. The geology of the area is diverse from granite, gneiss and charnokites in the hills to recent alluvium in the plains. Infiltration losses vary with location due to differences in soil and slope characteristics. Figure 1 Map showing study area of Punpun river basin. Figure 1 Map showing study area of Punpun river basin. Data used ADEM of 30-meter pixel size was taken from the website of the United States Geological Survey (https://earthexplorer.usgs.gov/).Figure 2shows the DEM of the study area. Daily rainfall data at four rain gauge stations (Sherghati, Inderpuri, Arwal and Patna) were collected for the period 2005–2017 from the Indian Meteorological Department (IMD) Pune. The monthly average rainfall during monsoon at rain gauge stations Sherghati, Inderpuri, Arwal and Patna were 420, 481, 398 and 480 mm, respectively. The average annual rainfall is 950 mm and the maximum rainfall generally occurs in month of September. Figure 2 Digital Elevation Model (DEM) of the study area. Figure 2 Digital Elevation Model (DEM) of the study area. The mean daily rainfall over the basin has been computed using the Thiessen polygons method from the years 2005 to 2017. The daily discharge data at the Sripalpur gauge site from the years 2005 to 2017 were collected from the Central Water Commission, Patna. The soil map of the Punpun river basin was collected from the World Soil Database, with 1 km resolution (https://www.fao.org/soils-portal/). In the uppermost part of the basin is mostly forest cover, while the lower part is suitable for agriculture purposes. The Landsat image used for classification of study area in different land use cover was collected from the website of United States Geological Survey (https://earthexplorer.usgs.gov/). METHODOLOGY GIS database development Figure 3presents the flow chart of different processes carried out using ArcGIS. Role of elevation is most important in the hydrological studies of any catchment for which a DEM is required. DEM is used to obtain geographical, morphological and topographical properties of the basin (Coulibaly et al.2005;Young & Liu 2015). Basin physical parameters such as slopes, centroid, longest flow paths, information associated with elevation of the basin, river flow direction, stream orders of the river and drainage pattern have been obtained. Based on the data, slope and topographic elevation maps with contours for the basin have been obtained. Figure 3 Flow chart of GIS processing. Figure 3 Flow chart of GIS processing. Basin delineation HEC-HMS is a semi=distributed model, in which data can be heterogeneous within basin but it is homogenous within sub-basins (Beven 2012). The basin has been delineated by generating 3 sub-basins based on physical properties of study area, i.e. LULC and soil distribution using ArcGIS for a particular river portion. These sub-basins (SB1, SB2 and SB3) are shown inFigure 4. Figure 4 Punpun river basin imported to HEC-HMS model showing 3 sub-basins. Figure 4 Punpun river basin imported to HEC-HMS model showing 3 sub-basins. Preparation of LULC and soil map The supervised classification has been performed to prepare the LULC map of the basin. Hydrologic soil groups (HSGs) are commonly classified into 4 groups: A, B, C and D based on rainfall, runoff and infiltration (Rodell et al.2009;Roy et al.2013;Derdour et al.2018;Efthimiou 2018;Frappart & Ramillien 2018). Group A indicates high infiltration rate and low runoff capacity. Group B represents silt loam having moderate infiltration rates and moderately coarse texture. Group C represents clay loam, which has slow infiltration rates and moderately fine textures. Generally, clay loam soil is good for every type of plants' growth. Group C soils have moderate water transmission rate, while Group D soils have low infiltration and high runoff. The soil map of the Punpun river basin was obtained with 1 km of resolution from the World Soil Database. The dominant soil in the Punpun river basin is DOMSOIL and HSG is determined based on FAO. Curve number map of punpun river basin Curve number (CN) depends on soil type, slope and land use of the study area. Its value varies from 30 to 100. A lower value of CN indicates a low runoff coefficient whereas a high value shows a high runoff coefficient. Soil and land use maps are required along with the slope map for the generation of the CN map. A slope map has been prepared by identifying the contour line of the basin in the ArcGIS. The CN in ArcGIS is generated using land use, soil map, slope map and DEM of the basin. The average CN for each sub-basin was computed using the equation given below: (1) where, i is the number of sub-basin, A i is the area of the particular sub-basin and A Total is the total area of the basin. Hydrological modeling using HEC-HMS model The hydrological characteristics of the basin have been computed using the physical properties of all the sub-basins for simulation. The SCS-CN loss method has been used to compute rainfall losses. This method was chosen due to the availability of data for the region and the lack of complexity in nature (Song et al.2011;Hoseini et al.2017;Yu et al.2018;Tassew et al.2019). The CN of each sub-basin is required to estimate infiltration using the CN method. The detailed procedure of CN creation and operation of the HMS model is shown inFigure 5. Figure 5 Flow Chart of HEC-HMS simulation. Figure 5 Flow Chart of HEC-HMS simulation. SCS unit hydrograph transformation SCS-UH method was used to calculate the outflow at the specified outlet. This is an innovative method that needs lag time and percentage impervious area of the basin (Khaddor et al.2017;Barman & Bhattacharjya 2020;Tassew et al.2019). The basin lag time was taken as 0.6 times the concentration time (Subramanya 2013).Table 2presents the percentage impervious layer, potential soil storage, composite CN, initial abstraction, lag time and time of concentration computed for each sub-basin of the Punpun river. The SCS method has been given in many text books, so it is not repeated here. Stream flow routing HEC-HMS uses various methods to compute the stream flow at the basin's outlet, including the Muskingum method, which is simple and does not require multiple inputs (Song et al.2011;Tassew et al.2019). The Muskingum method is used to predict stream flow at the outlet. Kand xare two important input parameters in the Muskingum method. The value of K is computed by dividing the length of reach by the average flow velocity and the value of xlies between 0.0 and 0.5. The channel has minimum attenuation if xis equal to 0.5 and maximum attenuation if xis 0.0. The calibration parameters were set to a value of 0.2 as an initial value, which was then modified during the calibration. Calibration and validation of model Historical data of different periods were used for calibration and validation of HEC-HMS model. Daily rainfall and runoff data from the years 2005 to 2012 were used for calibration and from the years 2013 to 2017 were used for validation. LULC and soil characteristics of the sub-basin were assumed as unchanged during the calibration and validation period. In HEC-HMS, Nelder Mead and univariate gradient are two algorithms to optimize the objective function. In this study, peak weighted RMS error was minimized using the Nelder-Mead algorithm to get the optimized model parameters for the best outcomes of simulated model. Optimized parameters were used to validate the model. Sensitivity analysis was also performed to recognize the expected parameters and for required accuracy. The RMSE and Nash-Sutcliffe Efficiency were used to evaluate the performance of HEC HMS model. Root mean square error (RMSE) The RMSE is generally used to analyze the variation of computed values from the observed values. It is given as (2) where, X obs is observed data and X model is the computed values at time i and n is the number of observations. NSE The NSE is applied to measure the forecasting efficiency of hydrological models ( Moriasi et al. 2007 ). It is given as follows: (3) where, X obs is observed data, X model is the computed values and is the mean of observed discharge values at time/place i . NSEs, E, vary from −∞ to 1. Its value is considered good if it ranges between 0.65 to 0.75 and very good between 0.75 to 1. An efficiency of 1 ( E= 1) shows a perfect match of computed values with the observed data. PBIAS PBIAS assesses the normal drift of the simulated data to be larger or smaller than their observed counterparts. The optimal value of PBIAS is 0.0, with low values showing realistic model simulation. Positive values of PBIAS show underestimation and negative values show overestimation of bias. PBIAS is computed as: (4) where, is observed values and is simulated values at time/place i . RSR RSR, a standard evaluation statistic for model performance, is based on the recommendation by various researchers. RSR normalizes RMSE values using the observation's standard deviation. RSR is computed as the ratio of the RMSE and standard deviation of computed data, and is given as: (5) where, is observed values, is simulated values and is the mean of observed discharge values at time/place i . RESULTS AND DISCUSSION LULC, soil and curve number CN maps The LULC map was prepared from Landsat image using ArcGIS. Supervised classification has been carried out for Agriculture land, Barren land, Built-up area, Forest, Water body and Wetland, which are shown inFigure 6. The prepared LULC map indicates that the most of the study area consist agriculture and forest lands, which means the runoff coefficient is in the range from moderate to high. The urban built-up area is very small compared to agricultural land. An HSG map was prepared from world soil data base and shown inFigure 7. It shows that 74% area has HSG C and 26% area has HSG B. It means a major portion of study area has HSG C with moderate to high runoff potential zone.Table 1presents the percentage area of the soil groups. Table 1 Soil classification of Punpun river basin Name . Hydrological soil group . % Area . Other Luvisols (Clay Loam) C 65 Ferric Luvisols (Silt Loam) B 12 Chromic Cambisols (Silt Loam) B 14 Calcaric Fluvisols (Clay Loam) C 9 Name . Hydrological soil group . % Area . Other Luvisols (Clay Loam) C 65 Ferric Luvisols (Silt Loam) B 12 Chromic Cambisols (Silt Loam) B 14 Calcaric Fluvisols (Clay Loam) C 9 Table 2 T lagand T cof three sub-basin of Punpun river basin Sub-Basin (SB) . % Impervious layer . Potential Max Retention . (I a ) mm . Composite Curve No. . T lag (By Denver method), hr. . Time of concentration, T c , hr. . SB1 24.8 52 10.4 83 24.78 41.2 SB 2 24.4 123 23.9 78 21.33 35 SB 3 16 67 13.13 81 6.24 10.4 Sub-Basin (SB) . % Impervious layer . Potential Max Retention . (I a ) mm . Composite Curve No. . T lag (By Denver method), hr. . Time of concentration, T c , hr. . SB1 24.8 52 10.4 83 24.78 41.2 SB 2 24.4 123 23.9 78 21.33 35 SB 3 16 67 13.13 81 6.24 10.4 Figure 6 Supervised classification of LULC map of Punpun river basin. Figure 6 Supervised classification of LULC map of Punpun river basin. Close modal Figure 7 HSG map of the basin. Figure 7 HSG map of the basin. Based on the LULC and soil maps, the CN map has been generated and presented inFigure 8. It shows that CN values are high in the major portion and thus, the runoff potential of Punpun river basin is moderate to high. The average CN value is computed for each sub-basin and presented inTable 2. Figure 8 Generated CN map of Punpun river basin. Figure 8 Generated CN map of Punpun river basin. Model development Three models have been developed using HEC-HMS software to simulate daily, monthly and monsoonal flow in Punpun river basin. These models have been calibrated using rainfall and observed flow data from the year 2005 to 2012 and validated with the data from 2013 to 2017. The objective function in HEC-HMS is peak-weighted RMSE during calibration.Table 3presents the optimal value of various parameters for HEC-HMS. Table 3 Different optimal parameters and their corresponding values for the Punpun river basin with objective function sensitivity Parameters . Initial value . Optimized . Objective function sensitivity . Initial abstraction (mm) 24.7 24.52 0 Lag time (minutes) 1,042.3 1,095.3 − 0.07 Muskingum parameter K (hr.) 0.6 1.024 0 Muskingum parameter x 0.2 0.18 0 CN 78 75.2 0.06 CN scale factor (for all sub-basins) 1 0.1842 0.06 Initial abstraction scale factor (for all sub-basins) 1 1.12 0 Parameters . Initial value . Optimized . Objective function sensitivity . Initial abstraction (mm) 24.7 24.52 0 Lag time (minutes) 1,042.3 1,095.3 − 0.07 Muskingum parameter K (hr.) 0.6 1.024 0 Muskingum parameter x 0.2 0.18 0 CN 78 75.2 0.06 CN scale factor (for all sub-basins) 1 0.1842 0.06 Initial abstraction scale factor (for all sub-basins) 1 1.12 0 Daily model The daily flow model is developed using daily rainfall and daily observed stream flow data at Sripalpur gauging site on Punpun river.Figures 9and10presents the results of calibration and validation of the daily model, respectively. The simulated stream flow matches well with observed flow data during calibration and validation except for few peaks. During calibration, the simulated stream flow was slightly lower than the observed values during the year 2005–2009, but after that it was slightly higher than the observed values. In validation, the simulated stream flow was slightly lower than the observed in the last two years (2016 and 2017). The differences in the simulated and observed data may be due to LULC map, which was prepared by Landsat data of year 2009 and it was used for the whole study period (2005–2017). In post-monsoon seasons, Peak flows were overestimated by 19% during calibration and underestimated by 23.1% during validation. Overall, the pattern of simulated stream flow was in good agreement with observed. Figure 9 Simulated versus observed daily stream flow during calibration. Figure 9 Simulated versus observed daily stream flow during calibration. Figure 10 Simulated versus observed daily stream flow during validation. Figure 10 Simulated versus observed daily stream flow during validation. To check the accuracy of the daily model, a linear regression was fitted between the simulated and observed stream flows for calibration and validation and shown inFigure 11. The coefficients of determination were 0.88 and 0.79 during calibration and validation, respectively. Figure 11 Linear regression plot of simulated discharge versus observed discharged (a) during calibration (b) during validation. Figure 11 Linear regression plot of simulated discharge versus observed discharged (a) during calibration (b) during validation. Monthly model The monthly model has been developed using the monthly data of rainfall and stream flow.Figures 12and13present the comparison of simulated and observed monthly stream flow during calibration and validation of the monthly model, respectively. The simulated stream flow matches well with the observed data during calibration whereas during validation, simulated stream flows were greater during the 23rd–26th months. Linear regression plots were also drawn to check the accuracy level and the value of coefficient of determination during calibration and validation were 0.85 and 0.82, respectively and presented inFigure 14. Figure 12 Simulated versus observed monthly stream flow during calibration of monthly model. Figure 12 Simulated versus observed monthly stream flow during calibration of monthly model. Figure 13 Simulated versus observed monthly stream flow during validation of monthly model. Figure 13 Simulated versus observed monthly stream flow during validation of monthly model. Figure 14 Linear regression plot between simulated and observed monthly stream flow (a) during calibration (b) during validation. Figure 14 Linear regression plot between simulated and observed monthly stream flow (a) during calibration (b) during validation. Monsoonal model In this model, monsoonal stream flow data from the months June to October for all the years were used for calibration and validation.Figures 15and16present the comparison of simulated and observed monsoonal stream flow during calibration and validation, respectively. The simulated stream flows were in good agreement with the observed data during calibration, whereas during validation, simulated stream flows were slightly higher in some months.Figure 17presents the linear regression plots between simulated and observed monsoonal data. The values of coefficient of determination were 0.78 and 0.82 during calibration and validation, respectively. Figure 15 View large Download slide Simulated versus observed seasonal discharge during calibration of the monsoonal model. Figure 15 Simulated versus observed seasonal discharge during calibration of the monsoonal model. Figure 16 Simulated versus observed seasonal discharge during validation of the monsoonal model. Figure 16 Simulated versus observed seasonal discharge during validation of the monsoonal model. Figure 17 Linear regression plot between observed and simulated monsoonal data (a) during calibration (b) during validation. Figure 17 Linear regression plot between observed and simulated monsoonal data (a) during calibration (b) during validation. Table 4presents the statistical parameters R 2, NSE, PBIAS and RSR for the analysis of the three models (daily, monthly and monsoonal) in HEC-HMS. R 2values for all the models are above 0.75, thus it shows good calibration of the model. NSE values for the daily model lies between 0.65 and 0.75, thus show good result whereas for monthly and monsoonal models, it is greater than 0.75, and thus it shows very good results. PBIAS values are less than 10 in all the models, thus show very good results. RSR values for daily and monsoonal models are less than 0.5, which shows very good results, whereas for the monthly model, it is slightly greater than 0.5 and it shows good results. The performance evaluation of all the models shows that the monthly model performs better than the daily and monsoonal models. Table 4 Details of the statistical efficiencies values for daily, monthly and monsoonal models Parameters . Daily model . Monthly model . Monsoonal model . Calibration . Validation . Calibration . Validation . Calibration . Validation . R 2 0.88 0.78 0.85 0.82 0.78 0.83 NSE 0.69 0.68 0.89 0.86 0.81 0.79 PBIAS 7.23 6.86 8.11 9.42 8.93 8.56 RSR 0.44 0.46 0.52 0.54 0.49 0.47 Parameters . Daily model . Monthly model . Monsoonal model . Calibration . Validation . Calibration . Validation . Calibration . Validation . R 2 0.88 0.78 0.85 0.82 0.78 0.83 NSE 0.69 0.68 0.89 0.86 0.81 0.79 PBIAS 7.23 6.86 8.11 9.42 8.93 8.56 RSR 0.44 0.46 0.52 0.54 0.49 0.47 CONCLUSIONS A HEC-HMS based rainfall runoff model has been developed for the Punpun river basin. Three models have been developed using daily, monthly and monsoonal data. The model has been calibrated and validated using data from the years 2005 to 2012 and 2013 to 2017, respectively. Performance of the model has been evaluated using statistical parameters: R 2, NSE PBIAS and RSR. Based on R 2, NSE and PBIAS values, the monthly model performs better both in calibration and validation as compared to the daily and monsoonal models but RSR values are slightly higher than the other models. Thus it can be concluded that the monthly model is better than the daily and monsoonal models. It can also be concluded that HEC-HMS based rainfall runoff model can be used to forecast the stream flow in Punpun river basin. The assumption of this study is that only one LULC scenario in the mid-time period has been considered in whole study period due to the major agricultural land use area, which did not change much on a yearly basis. DATA AVAILABILITY STATEMENT Application of the HEC-HMS model for runoff simulation of Upper Blue Nile River Basin Journal of Waste Water Treatment & Analysis Sungai Pahang digital flood mapping: 2007 flood Ungauged runoff simulation in Upper Manyame Catchment, Zimbabwe: applications of the HEC-HMS model Physics and Chemistry of the Earth Application of the HEC-HMS model for runoff simulation in a tropical catchment Environmental Modelling and Software
https://iwaponline.com/wpt/article/17/5/986/88163/HEC-HMS-based-rainfall-runoff-model-for-Punpun
Sustainability | Free Full-Text | Investigating Company& rsquo;s Technical Development Directions Based on Internal Knowledge Inheritance and Inventor Capabilities: The Case of Samsung Electronics This paper proposes a new method to analyze technical development directions of a company using knowledge persistence-based main path analysis and co-inventor network analysis. Main path analysis is used for identifying internal technical knowledge flows and inheritances over time within a company, and knowledge persistence-based main path analysis can well identify major knowledge streams of each sub-domain within a relatively small knowledge network generated by one company without omission of significant inventions. A co-inventor network analysis is used for identifying key inventors who can be represented as the major technical capabilities of a company. The method is a meaningful attempt in that it applies knowledge persistence-based main path analysis to analyzing a company& rsquo;s internal technical development and combines the two approaches to provide the information on both base technical capabilities and new technical characteristics. To test the method, this paper conducted an empirical study of Samsung Electronics. The results show that the method generated major knowledge flows and identified key inventors of Samsung Electronics. In particular, the method can identify the base technical knowledge as the & lsquo;backbone& rsquo; and newly injected knowledge as & lsquo;fresh blood& rsquo; for forecasting future technical development. Based on the identified clue information, this paper forecasted the potential future technologies for each sub-domain of Samsung Electronics with technical keywords and descriptions. Investigating Company’s Technical Development Directions Based on Internal Knowledge Inheritance and Inventor Capabilities: The Case of Samsung Electronics by Fang Han 1 , Sejun Yoon 2 , Nagarajan Raghavan 3 and Hyunseok Park 2,* 1 National Science Library, Chinese Academy of Sciences, Beijing 100190, China 2 Department of Information Systems, Hanyang University, Seoul 04763, Korea 3 Engineering Product Development Pillar, Singapore University of Technology and Design, Singapore 487372, Singapore * Author to whom correspondence should be addressed. Sustainability 2022 , 14 (5), 3117; https://doi.org/10.3390/su14053117 Received: 19 February 2022 / Revised: 3 March 2022 / Accepted: 6 March 2022 / Published: 7 March 2022 Abstract This paper proposes a new method to analyze technical development directions of a company using knowledge persistence-based main path analysis and co-inventor network analysis. Main path analysis is used for identifying internal technical knowledge flows and inheritances over time within a company, and knowledge persistence-based main path analysis can well identify major knowledge streams of each sub-domain within a relatively small knowledge network generated by one company without omission of significant inventions. A co-inventor network analysis is used for identifying key inventors who can be represented as the major technical capabilities of a company. The method is a meaningful attempt in that it applies knowledge persistence-based main path analysis to analyzing a company’s internal technical development and combines the two approaches to provide the information on both base technical capabilities and new technical characteristics. To test the method, this paper conducted an empirical study of Samsung Electronics. The results show that the method generated major knowledge flows and identified key inventors of Samsung Electronics. In particular, the method can identify the base technical knowledge as the ‘backbone’ and newly injected knowledge as ‘fresh blood’ for forecasting future technical development. Based on the identified clue information, this paper forecasted the potential future technologies for each sub-domain of Samsung Electronics with technical keywords and descriptions. Keywords: knowledge persistence ; main path analysis ; social network analysis ; corporate technology strategy ; technology forecasting 1. Introduction Technologies have been considered as a key resource for achieving and sustaining a competitive advantage. The internal technical capability as a basis for obtaining new technical knowledge can determine the technical competitiveness and development directions of companies. Since it fundamentally requires much time and effort for technical human resources to develop and improve the internal technical capability, most tech-oriented companies, even service companies, devote much attention to developing it through continual R&D activities. To achieve competitive advantages, companies should provide relatively better customer’s values than competitors, and so it is essential to know competitors’ technical capabilities and understand their developmental directions through technical monitoring. There have been many studies on monitoring the technical landscape of a specific technical field using technical data; patents as the reliable, free-accessible, and structured technical data, have been widely used for technical monitoring. Lee et al. [ 1 ] developed a patent map approach to discovering new technical opportunities in a technical domain. Daim et al. [ 2 ] presented a bibliometric approach for monitoring and forecasting emerging technologies using patent data. Zhang et al. [ 3 ] proposed a term of clumping steps for technical monitoring. Moehrle and Caferoglu [ 4 ] employed a semantic patent analysis to discover the emerging technologies in a camera domain. Park et al. [ 5 ] suggested an analytic framework to evaluate companies’ technical capability within a specific technical field using a patent semantic analysis. Yoon et al. [ 6 ] developed a method to identify technical competition trends for R&D planning using a dynamic patent map approach. Mun et al. [ 7 ] proposed a method to analyze technical trends in a specific technical field from the functional perspective using a function scoring approach. Mun et al. [ 8 ] suggested a method to assess the technical capability of firms for the business diversification purpose using patent metrics. Even though previous methods are useful to identify competitive relationships and evaluate technical capabilities of firms, there have been few researches that focus on the specific development trajectories of internal technical capability and future development directions based on the technical capability. To overcome this, we propose a new method to investigate the technical development directions of a company based on its internal knowledge inheritance and inventor capabilities. Specifically, this paper combined the main path analysis and inventor network analysis to identify a firm’s internal technical trajectories and predict its future development directions. A main path analysis has been widely used for understanding technical changes [ 9 , 10 , 11 , 12 , 13 , 14 ] and trajectories under a technical field [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. This approach identifies the major knowledge flows within a knowledge network by minimizing the network complexity, and so it can show the major knowledge flows within a company. In addition, the last nodes in a main path can be the specific clues to predict future development directions [ 28 ]. Given that the technical capabilities of a company cannot be evolved in short time, but accumulated and inherited over time through continuous R&D activity, we adopted the knowledge persistence (KP)-based main path analysis, which can quantify how much knowledge of a patent was inherited to later inventions [ 23 , 29 ]. A co-inventor network analysis assesses the inventors’ impact or power in a co-inventor network and finds key inventors who make a huge influence on the internal technical development [ 30 , 31 , 32 , 33 ]. Since key inventors play a critical role for the internal knowledge flows and inheritance, the specific technical areas of key inventors are closely aligned with the firm’s R&D directions. Companies develop new inventions based on the combination of internal technical capability as a ‘backbone’ and new technical knowledge from outside as ‘fresh blood’. Therefore, the technical knowledge in the end-nodes on the main paths and major technical capabilities, or technical fields, of key inventors can be the ‘backbone’ for future technologies, and new technical knowledge adopted to the end-nodes or recently emerged technical areas of key inventors can be the unconventional knowledge sources that enable one to achieve novel and breakthrough features as ‘fresh blood’. To test the method, this paper applied it to the case of Samsung Electronics. Since Samsung Electronics has a great number of patents (Top 2 assignee in the world) and complex internal technical structures, this company can be a great case to test the proposed method. The empirical analysis shows/found that KP-based main path analysis can represent the major technical knowledge flows and inheritance, and co-inventor network analysis can objectively identify key inventors in each technical field of the focal company. In particular, new technical knowledge, or technical fields, employed by the inventions through backward citations and added to the key inventors was identified in the later inventions. Therefore, the proposed method is useful for predicting future development directions of a company, and this paper forecasted the potential future technologies for each sub-domain of Samsung Electronics with technical keywords and descriptions. The rest of this paper is structured as follows. The related literature is reviewed in Section 2 . Section 3 explains the proposed method. The empirical case study is conducted in Section 4 . Section 5 presents the discussion and conclusion. 2. Literature Review 2.1. KP-Based Main Path Analysis Main path analysis has been widely exploited for analyzing and understanding the technical changes and innovation under a specific area. The basic concept of main path analysis is to reduce the network complexity of a citation-based big/huge knowledge network. A knowledge network is usually constructed based on citation relationships. So, each citing and cited relationship represents knowledge flow between two inventions. Since early inventions cannot cite later inventions and citations basically have directions, the network is an unweighted and directional acyclic network. This type of network does not work well with common metrics from a social network analysis. Therefore, most main path analysis studies developed or adopted a new network algorithm. The first attempt is a search path-based approach developed by Hummon and Dereian [ 34 ]. This main path analysis generates a single path based on the traversal counts. Most previous studies adopted the basic concept of the Hummon and Dereian [ 34 ]’s main path analysis for investigating scientific and technical knowledge trajectories [ 16 , 35 , 36 , 37 , 38 , 39 , 40 ]. Since a single main path is insufficient to analyze technical domains, Verspagen [ 16 ] suggested an improved main path approach that can generate multiple main paths. Verspagen [ 16 ]’s main path analysis integrates the main path for specific periods. For example, if the whole period is 10 years and the year scale is one year, there are nine main paths from the first year to n -th year ( n = 2~10). Verspagen’s main path analysis was useful to analyze the technical domains having multiple sub-fields. Many studies have adopted it for various purposes [ 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. However, the critical limitations of this approach were the high network complexity and omission of the dominant technologies on the main paths. To overcome the limitations, Park and Magee [ 29 ] developed the knowledge persistence (KP)-based main path analysis. KP-based main path analysis first identifies the dominant knowledge using KP that quantifies how much technical influence an invention has on the latest technical developments and then connects the adjacent nodes having the highest KP scores using backward–forward path analysis [ 29 ]. The clear benefit of KP-based main path analysis is that it can generate multiple main paths by significantly reducing the network complexity without omission of any dominant inventions. Since this research adopts a main path analysis to identify the major knowledge trajectories of a specific company, a main path analysis must show the multiple technical domains of a company, inherited knowledge flows over time and the most significant inventions of the focal company. Considering the mentioned advantages, this paper adopted the KP-based main path analysis. 2.2. Co-Inventor Network Analysis In a scholarly data analysis, inventors or authors are important bibliographic information for various research purposes. Since R&D human resources can represent the scientific and technical capability of organizations, their co-occurrence relations with other bibliographic information, such as a country, organization, or research field, can be used for better understanding the collaboration trends [ 48 , 49 , 50 ], regional characteristics [ 33 , 51 , 52 , 53 , 54 , 55 , 56 ], or technical changes and innovation [ 33 , 54 , 57 , 58 , 59 , 60 , 61 ]. In particular, co-inventor relationships within an organization can show some significant inventors who are strategically allocated to major R&D projects and so usually lead most R&D projects. Therefore, key inventors’ technical capability and major technical fields are aligned with the firm’s R&D directions. A co-inventor network can be constructed based on the co-occurrence relationships among inventors. A co-inventor network is usually a weighted and undirected cyclic network, and so the metrics from social network analysis can provide good performance. There have been many studies that used a social network analysis to analyze patent co-inventor networks. Han and Park [ 62 ] developed a method to calculate inter-industrial knowledge diffusions using patent citation-based network analysis. Cantner and Graf [ 30 ] investigated the local inventor relationships in Jena using co-inventor network analysis. Lei et al. [ 63 ] employed patent-based assignee and co-inventor network analysis to analyze the collaboration relationships in the solar photovoltaic domain. This paper used the degree and betweenness centrality to identify key inventors in a company. 3. Method 3.1. Data Collections This paper collected all granted United States patents of Samsung Electronics from 1 January 1976 to 31 December 2020. We first constructed a patent database using USPTO (United States Patent and Trademark Office) data through PatentsView ( www.patentsview.org ) and collected patents of Samsung Electronics by searching the patents containing the assignee name ‘samsung’ and then filtering out the patents not having ‘electronics’. Total 112,334 patents were collected. For co-inventor network analysis, inventor name disambiguation should be processed. We disambiguated inventor names by considering technical fields and co-inventor relationships. 3.2. Identification of Internal Knowledge Flows To understand the technical development process, it is important to identify the flows of technical knowledge over time, and this paper used the KP-based main path analysis to identify knowledge flows within a company. KP is a quantitative metric that measures the technical influence of a patent on the latest technologies in a knowledge network. KP can be measured as follows. First, the patent citation network is constructed. Second, the layer length of the patent citation network is measured by identifying the longest path from the start-point to the end-point. Third, each patent is rearranged by the defined layer structure. Fourth, the weight of each edge between two patents is calculated based on knowledge in-flows through backward citations. Specifically, the weight of the edge from the cited to the citing patent is calculated by 1/the number of all backward citations of the citing patent. Finally, KP of a patent is calculated by the following formulation [ 29 ]: KP P a t e n t A = ∑ i = 1 n ∑ j = 1 m i ∏ k = 1 l j − 1 1 B a c k w a r d C i t a t i o n P a t e n t i j k (1) where KP P a t e n t A is the knowledge persistence value of the focal patent A , n is the number of directly or indirectly connected end nodes, i is the number of the last layer nodes directly or indirectly connected to P a t e n t A , l j is the number of nodes on the j -th path between P a t e n t i and P a t e n t A , and m i is all paths can be generated between P a t e n t i and P a t e n t A . P a t e n t i j k is the k -th patent on the j -th path between P a t e n t i and P a t e n t A ; B a c k w a r d C i t a t i o n P a t e n t i j k is the number of the cited patents (backward citations) by P a t e n t i j k . To identify the important patents, the KP value of each patent is max normalized from the global point of view (GP: Global Knowledge persistence) and the local point of view (LP: Local Knowledge Persistence). This paper sets the threshold for the important patents as GP ≥ 0.3 or LP ≥ 0.8, based on the previous studies [ 29 , 64 , 65 ]. To identify the main paths, all important patents are connected by the backward and forward searching technique ( Figure 1 ). The backward and forward searching finds the highest KP patents on the backward and forward layers of the focal patent. Therefore, KP-based main path analysis can dramatically reduce a network complexity without missing the important patents. Figure 1. Backward and forward searching for main path identification. 3.3. Identification of Key Inventors To investigate R&D efforts of Samsung Electronics, the co-inventor network was constructed based on all the Samsung patents. Each node in the network represents an inventor, and the edge between two nodes indicates that the two inventors co-invented one patent. The co-inventor network in this research is generated and analyzed using iGraph—a network analysis package for Python. Based on [ 59 ], we determined the key inventors whose research activeness or broadness is dramatically higher than other inventors. The research activeness of inventors can be calculated by the degree centrality and broadness can be calculated by the betweenness centrality. The formulation of the degree centrality is as follows [ 66 ]: DEGREE = d i , (2) where d i means the number of the linked nodes with the focal node i in a network. The inventors, having high degree score, have higher co-inventing experiences from many R&D projects than other inventors and so can be considered as the active inventors in a company [ 59 ]. The research broadness of inventors can be calculated by using betweenness centrality. The betweenness centrality identifies nodes that act as a bridge or brokerage in an inventor network, and so an inventor having high betweenness centrality scores is likely to be an R&D head or leader. The formulation of for the normalized betweenness centrality is as follows [ 66 ]: b i = ∑ j , k ∈ V , i ≠ j ≠ k n g j i k g j k / n − 1 n − 2 2 , (3) where b i is the betweenness centrality of the node i , g jik is the number of the shortest paths between the node j and k that pass through the node i . g jk is the number of shortest paths from the node j to k , n is the number of total nodes in the network. The key inventors in the whole network as well as the main paths are identified based on the above two indicators. The next step is to analyze the key inventors’ technical fields where they are mainly focused, which could be identified by the patent classification, e.g., Cooperative Patent Classification (CPC). Analyzing the major CPCs of the key inventors can indicate the important technologies that are related to the corporate strategy. In addition, the technical knowledge of key inventors in the main paths are helpful to forecast the further R&D directions. The details on the metrics will be described in Section 3.4 . 3.4. Future Direction Analysis From the knowledge-based view, the main paths show the knowledge genetic map of the firm. Each node in the main paths inherits knowledge from the ancestor nodes. Thus, we could predict the future possible technologies based on the nodes in the last layer of the main. The embodied knowledge in the nodes in the last layer could be divided into two types: one is from the internal knowledge flows that are inherited from the ancestor inventions of the company, and the other is the external knowledge from outside the company. Based on the knowledge recombination theory [ 67 , 68 , 69 , 70 , 71 , 72 , 73 ], the injected external knowledge is often regarded as the main source of innovation, and so the external knowledge injected to the last nodes can be the signal or major characteristics of the future technologies. Our empirical study in Section 4.3.1 also supports this point: almost half of new emerging CPCs in the main paths have presented in the external citation to their cited nodes in the last layer. Based on this, the CPCs in the external citations of the nodes in the last layer that have not been presented in each sub-domain are utilized to predict the possible new emerging knowledge in the next layer. As mentioned above, the key inventors’ major technical fields are related to the R&D strategy of a firm, and our experiments also indicate that the key inventors’ recent major technical capability, i.e., CPCs, can be considered as the internal inheritable knowledge ( Section 4.3.2 ). In this study, the key inventors are defined as the inventors with top 1% high degree or top 1% high betweenness indicators among all the inventors in all patents of Samsung Electronics. The key inventors’ recent major technical capability can be analyzed by the top 10 CPCs of all their patents in the recent five years, and their top CPCs that have already appeared in the sub-domain are used to predict the possible future technologies that would appear again in the next layer. In summary, this paper predicts future technologies based on the key inventors’ recent major CPCs and the CPCs within and injected to the last nodes in each sub-domain. The former denotes the base knowledge that has high possibilities to be employed as ‘backbone’ for the future technologies, and the latter denotes ‘fresh blood’ that is unconventional knowledge for innovative or novel characteristics. Figure 1 illustrates the detailed process to predict future technologies. In Figure 1 , a and b are two last nodes on the main paths for the sub-domain A. a 1 , a 2,, and a m (and b 1 , b 2,, and b n ) are the cited nodes by the last node a (and b ) and so they are neither Samsung Electronics’ inventions, nor on the main paths. The aim is to predict the potential CPCs that would be involved in patent x (the next layer). The CPCs in the external citations that have not presented in the main paths of sub-domain A are identified as New CPCs, which are “fresh blood”, as explained above, and they are possibly involved in patent x as the new technical fields. In this study, the recent capabilities of key inventors in sub-domain A are analyzed based on all the key inventors’ patents published in the last 3 years. Top 10 CPCs in these patents are identified as the “recent capabilities” of the key inventors, and the CPCs that have already appeared among the top 10 are supposed to have high possibilities to be present in patent x. 4. Results and Discussion 4.1. Internal Knowledge Flows The initial knowledge network contains 86,429 nodes and 67,729 edges based on the citing–cited relationship. The main paths of Samsung Electronics are generated by KP-based main path analysis, and 54 patents on the main paths were identified ( Figure 2 ). Figure 2. The process of predicting future technologies. Based on the topological structure of the patents on the main paths and their specific information (bibliographic information and technical texts of the patents), we divided the technical structure of Samsung Electronics into two main technical fields: LED (including 11 patents on the main paths) and Memory Device (including 43 patents on the main paths). Then the Memory Device domain was divided into the further two sub-domains: Memory Circuits and Semiconductor Devices ( Figure 2 ). The nodes highlighted with the black dotted circle are the patents on the main paths that were invented by the key inventors (the metrics are described in Section 4.2 ). Table 1 shows the summary table for the results of the main paths and co-inventor network analysis. There are seven key inventors whose inventions are HPPs in the main paths and they are identified. The Semiconductor Devices’ and Memory Circuits’ sub-domains have relatively more key inventors. The LED domain includes only one key inventor in the main paths ( Figure 3 ). Figure 3. Main paths of Samsung Electronics. Table 1. Result summary. 4.2. Key Inventor Identification 4.2.1. Co-Inventor Network Analysis This research analyzes the co-inventor network of Samsung Electronics patents using the iGraph package for Python. The overall results are as follows ( Table 2 ). First, the density of the network is very low (0.0002). This is because Samsung Electronics has many business units, such as memory, mobile phone, and domestic appliances, and inventors in different business units that are not tightly connected to each other. Second, the mean value of the degree is 1.333 and the standard variation is 2.221. Since most inventions are co-invented, co-inventor network analysis can be properly applied. Finally, the average of betweenness centrality is 24,044.413 and the standard variation is 114,686.498. Since the standard variation is greater than the value of the degree centrality, few inventors have dramatically high betweenness centrality. The result shows that the degree (4.199) and betweenness centrality (147,706.880) in the co-inventor network for 171 inventors on the main paths are both much higher than the average level in the overall network. Table 2. Co-inventor network analysis for whole patents and patents on main paths. 4.2.2. Technical Fields of Inventors The top 20 CPCs of all inventors in Samsung Electronics are shown in Table 3 . The result shows that many inventors are involved in semiconductor devices (with six related CPCs), smart phones (five related CPCs), and personal computers (four related CPCs). Table 3. Inventor distribution for top 20 CPCs. The next analysis is about the CPC distribution on the main paths ( Table 4 ). There are 171 inventors on the main paths, and many inventors are involved in CPC G11C/16, which is related to the erasable programmable read-only memories. Among them, 59 inventors are related to G11C16/0483 and some are related to G11C16/10, G11C16/08, G11C16/26 and so on. This shows that Samsung Electronics focuses on the transistor architecture, and memory circuits and memory storage are the core technical areas of Samsung Electronics. Table 4. Inventor distribution for top 10 CPCs on main paths. 4.2.3. Key Inventors on Main Paths This paper analyzed the degree and betweenness centrality of each inventor. The inventors having the top 1% degree or betweenness centrality were identified as the key inventors, and 330 key inventors were identified. Table 5 shows the statistical result for the different sets. The average degree of the 330 key inventors is 15,863, and the average betweenness is 1,068,664.526, which are much higher than the average value of all inventors. Among them, seven key inventors have patents on the main paths. Based on the major CPCs of the seven key inventors’ patents, the major technical capability of them were analyzed and shown in Table 5 . Table 5. Key inventors (top 1% in whole networks) on main paths. 4.3. Future R&D Directions We selected some patents to find the knowledge inheritance phenomenon on the main paths and the relationship between the future technologies and key inventors’ technical capability ( Appendix A ). The results are shown as follows. 4.3.1. Identification of Newly Injected External Knowledge The emergence of new technical knowledge in a sub-domain is highly related to the newly injected or adopted external knowledge represented as knowledge flows through backward citations. Among 111 CPCs in the nine selected nodes, 52 CPCs appeared for the first time in the sub-domains, and 23 out of the 52 CPCs were also included in the backward citations of the end-nodes. This result is consistent with the knowledge recombination theory [ 67 , 68 , 69 , 70 , 71 , 72 ] that stresses the role of unconventional knowledge for creating innovative knowledge. 4.3.2. Identification of Key Inventors’ Capabilities Among 111 CPCs of the nine selected nodes, 54 CPCs are also frequently included in the key inventors’ patents in the recent five years and so these technical fields (54 CPCs) can be considered as the key inventors’ recent technical capabilities. Most of them (39 CPCs out of 43 CPCs) are not new technical fields, and this shows that the key inventors’ recent technical capabilities are highly related to the inheritable knowledge in the sub-domain ( Appendix A ). The results indicate that the key inventors’ latest technical capabilities can be the key clue to predict the technical development directions of firms. In particular, the key inventors’ technical capabilities, unlike the external knowledge, can represent the central knowledge basis for corporate R&Ds. Therefore, the future technologies can be predicted based on combining the new technical fields in backward citations of end nodes and the key inventors’ latest (recent five years) technical fields in a sub-domain. 4.3.3. Forecasting Future Technologies Based on the above results, the external citations of seven patents on the last layer of the main paths, combined with key inventors’ latest major capabilities, are used to extend the last layer of the main paths. Table 6 shows the new CPCs through external citations and the key inventors’ recent CPCs in each of sub-domains, and Table 7 shows keywords and key topics qualitatively extracted from the patents. Table 6. CPCs for forecasting future directions. Table 7. Keywords and key topics extracted from patents of key inventors and external citations. The potential technical fields with technical descriptions of each sub-domain of Samsung Electronics were forecasted. LED : Based on the CPCs H01L33/32 and H01L2924/0002, new CPCs H01L33/38, H01L33/40, or B82Y20/00 can be added in the future. The potential emerging technologies in the LED sub-domain are mainly related to the materials of luminous diodes. For example, CPC B82Y20/00 is related to nano optics (e.g., quantum optics). The quantum dot light emitting diodes (QLED) have both more technical and economic advantages than the organic light-emitting diode (OLED) which is one of the mainstream products now. A GaN (Gallium nitride)-based semiconductor light emitting device is also the potential emerging technology in the future. A GaN-based micro LED developed by Samsung Electronics in recent years will be more efficient and brighter with less power than a liquid crystal display (LCD) or OLED. Besides, technologies related to the LED laser radiation, n-type semiconductor layer, and indium tin oxide (ITO) material could possibly be adopted in the future LED sub-domain. Memory circuits : Based on CPC G11C16/04, G11C16/34, G11C16/10, G11C16/26, and H01L27/115, the new CPC G11C16/0466, G11C16/0475, or G11C11/5628 can be added to the memory circuit technologies of Samsung Electronics. Specifically, NAND memory technologies have high possibilities to dominate the future directions in the memory sub-domain. NAND memory is one of Samsung Electronics’ main products in recent years. Actually, Samsung Electronics will expand the scale of production of V-NAND and V-NAND chips, and they will become the future dominant memory chip market. The memory cell array which is related to the active region, transistors and interconnection, and the error detection or error correction may still be the key technologies in the future. Technologies related to the word line control circuit, input/output (I/O) data management or control circuits, and programming or writing circuits might be the new important technological topics after the current main paths. Semiconductor devices : The new CPCs, G06F11/00, G06F11/076, G06F11/08, and so on, will be supplemented based on major base CPCs, including G11C16/0483, G11C16/10, and G11C16/26. Technologies related to memory block, memory circuits, and read voltage seem to last for the next layer. Besides, the technologies related to electrically programmable read-only memories (EPROM) and NAND flash will be in the next layer again. New dominant technologies in this sub-domain will include the word-lines and read voltage technologies. In addition, the semiconductor sector in Samsung Electronics will focus more on some basic technologies, including correct programming, log-likelihood ratio computation and counting exceeding the word or bit in memory. 5. Conclusions This paper proposes a new method to analyze technical development directions of a company using the KP-based main path analysis and co-inventor network analysis. From the empirical test using the patents of Samsung Electronics, we found the following results and implications. First, the KP-based main path analysis is useful to identify internal knowledge flows of a company and it can properly show the developmental trajectories of each sub-domain, even though the method used only one company’s patents. Second, the combination of KP-based main path analysis and co-inventor network analysis provides the rich information for forecasting a company’s future technical directions. The empirical results show that the new technical capability of key inventors in Samsung Electronics and the newly injected technical knowledge through backward citations were actually identified in the later inventions. This result can support the usefulness of the proposed method. However, some limitations should be resolved in the future works. First, since this paper mainly focused on developing a new method, we conducted only one empirical case to test the method. However, further research should conduct more empirical analyses for finding potential methodological limitations to be revised and then strengthening the performance and quality. Second, since the method only uses the patent classification information for forecasting, it cannot provide specific directions. One potential idea can be the tracing from the patent classification to the relevant keywords and key-concepts. Therefore, the future work will focus on the method to identify more clear clues for forecasting. Third, the KP-based main path analysis requires a huge computing resource and remains as further qualitative work for decomposing the main paths into sub-domains. In the further work, the KP calculation algorithm should be revised to reduce the computing time, and the technique to decompose the main paths into several sub-domains should be focused on. Fourth, although the method and its empirical result seems to be useful for forecasting the future technologies after the last layer of the main paths, further research should concentrate on improving prediction power of the method. One possible attempt is to supplement other technical documents, e.g., papers. By analyzing the main paths and inventor network using papers of the company, some information that cannot be identified from a patent analysis might be identified. Moreover, patents and papers can be linked through their citations, and it can provide rich information for increasing prediction power. Lastly, this paper qualitatively described the details of future technologies to increase the quality of forecasting. Even though a qualitative effort is still important and critical to provide the detailed and complex implications, it is useful or worthwhile to apply a quantitative approach for reducing cost and time and providing more robust information. In fact, we tested some NLP (Natural Language Processing) tools, including RAKE [ 74 ], Topic modeling [ 75 ], and TextRank [ 76 ], for extracting keywords or key phrases in a patent. Some extracted keywords were helpful to understand the details of inventions, but most of the keywords were insufficient to represent the technical knowledge of the inventions. Therefore, the further research will focus on how to extract key information of the clue inventions for better forecasting the technical directions. Author Contributions Conceptualization: F.H. and H.P., Methodology: F.H., S.Y., N.R. and H.P., Validation: F.H., N.R. and H.P., Data curation: F.H. and S.Y., Writing: F.H. and H.P., Review and editing: N.R. and H.P., Visualization: F.H. and S.Y., Funding acquisition: H.P., Supervision: H.P. All authors have read and agreed to the published version of the manuscript. Funding This research was supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (No. 2019S1A5A8036427) and supported by Hanyang University (Grant number: HY-2020). Institutional Review Board Statement Not applicable. Informed Consent Statement Informed consent was obtained from all subjects involved in the study. Data Availability Statement Data are not publicly available, though the data may be made available on request from the corresponding author. Conflicts of Interest The authors declare no conflict of interest. Appendix A Table A1. Summary of CPCs for forecasting technical directions. Table A1. Summary of CPCs for forecasting technical directions. Patent ID CPC New in Sub-Domain In External Citations Recent Major Capabilities of Key Inventor (s) Memory Circuits 86116 G11C11/4074 O G11C5/025 O G11C5/06 O G11C11/409 O G11C11/4085 O G11C16/0483 O O O G11C16/10 O O O G11C16/26 O O O G06F11/141 O G11C11/5621 O O G11C16/08 O O G11C16/3427 O O G11C29/021 O O G11C29/028 O O G11C29/52 O O G11C2029/0411 O O G11C2211/5648 O G06F11/00 O 81009 G11C16/0483 O O H01L27/11582 O O G11C16/10 O O H01L27/11556 O O O G11C16/26 O O G11C16/24 O G11C16/3404 O G11C8/08 O O G11C8/12 O G11C16/08 O O G11C16/3427 O O 84462 G11C16/0483 O O G11C11/5671 O G11C16/08 O O G11C16/10 O O G11C16/12 O G11C16/26 O O H01L27/11582 O O G11C16/30 O O G11C5/04 O G11C11/5628 O O O G11C11/5642 O O O G11C16/3404 Semiconductor Device 44286 G11C16/04 O O G11C16/08 O O G11C16/16 O O G11C16/14 O H01L27/1157 O H01L27/11582 O 51823 H01L29/7889 O H01L29/7926 G11C16/3418 O O G11C16/0483 O O H01L27/11582 H01L27/11556 O G11C16/10 O 79000 G11C16/28 O G11C11/5628 O O O G11C11/5642 O O G11C16/04 O O G11C16/0466 O G11C16/0483 O O G11C16/26 O O G11C16/3495 O O G11C29/021 G11C29/028 O G11C29/50004 O G11C16/10 O O G11C2211/5634 O G11C2029/5004 G11C11/5671 O O G11C2211/563 O 74214 G11C29/50004 O G11C16/0466 O O G11C16/10 O O G11C16/26 O O O G11C16/0483 O O G11C2029/5004 O G11C11/5642 O O O G11C29/021 O G11C29/028 O O LED 75042 H01L33/387 O O H01L33/32 O O H01L33/42 O O H01L33/46 O O H01L33/54 O H01L33/62 O O H01L2933/0016 O O H01L33/06 O O H01L33/10 O H01L2224/48091 O H01L33/405 O O H01L2224/16245 O H01L2924/00014 O H01L33/382 O O H01L33/48 O H01L33/60 O O 85827 H01L33/42 O H01L33/54 H01L33/46 O H01L33/62 O O H01L33/32 O O H01L33/387 O O H01L33/405 O O H01L2224/16245 H01L33/10 H01L33/06 O H01L2224/48091 O H01L2933/0016 O O H01L33/382 O O H01L33/48 H01L33/60 O H01L2924/00014 O References Lee, S.; Yoon, B.; Park, Y. 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Sub-Domain # Patents # Key Inventors Key Inventors Degree Betweenness Major Technical Capabilities LED 11 1 KIM,TAE HYUNG 12 863,637.760 H01L51/502, C09K11/883, H01L33/0093, H01L33/32, H01L51/5072 Memory circuits 27 4 SON,HONGRAK 23 749,000.051 G11C16/26, G11C16/0483, G11C11/5642, G11C16/10, G11C11/5628 KONG,JUNJIN 27 1,893,719.455 G11C11/5628, G11C11/5642, G11C16/10, G11C16/0483, G11C16/26 PARK,KITAE 10 735,754.670 G11C16/0483, G11C16/10, G11C16/26, G11C11/5628, G11C16/08 JANG,JAEHOON 10 819,919.954 H01L27/11582, G11C16/0483, H01L27/11556, H01L27/11551, H01L27/1157 Semiconductor devices 10 5 PARK,KITAE 10 735,754.670 G11C16/0483, G11C16/10, G11C16/26, G11C11/5628, G11C16/08 CHOI,JUNGDAL 17 365,547.398 H01L27/115, G11C16/0483, H01L27/11521, H01L27/11524, H01L27/11568 KONG,JUNJIN 27 1,893,719.455 G11C11/5628, G11C11/5642, G11C16/10, G11C16/0483, G11C16/26 SON,HONGRAK 23 749,000.051 G11C16/26, G11C16/0483, G11C11/5642, G11C16/10, G11C11/5628 BYEON,DAESEOK 15 365,547.398 G11C16/0483, G11C16/10, G11C16/26, G11C16/08, G11C16/30 Total 54 7 Table 2. Co-inventor network analysis for whole patents and patents on main paths. Density Degree (All Inventors) Betweenness (All Inventors) Degree (171 Inventors on Main Paths) Betweenness (171 Inventors on Main Paths) Mean 0.0002 1.333 24,044.413 4.199 147,706.880 Standard Deviation 2.221 114,686.498 5.364 309,291.731 Table 3. Inventor distribution for top 20 CPCs. ID CPC Class Definition Technical Field # Inventor 1 H01L2924/00 Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies, as covered by H01L 24/00 Semiconductor devices 3231 2 H01L2924/0002 Technical content checked by a classifier 2276 3 H01L2924/00014 The subject-matter covered by the group, the symbol of which is combined with the symbol of this group, being disclosed without further technical details 2059 4 G06F3/0488 using a touch-screen or digitizer, e.g., input of commands through traced gestures Smart phone 1813 5 Y02D30/70 Reducing energy consumption in wireless communication networks Wireless network solution 1797 6 G06F3/04883 Inputting data by handwriting, e.g., gesture or text Smart phone 1744 7 Y02D10/00 Energy efficient computing, e.g., low power processors, power management or thermal management Base technology 1725 8 G06F3/0482 Interaction with lists of selectable items, e.g., menus Smart phone 1698 9 H01L2224/48091 Arched loop shape of an individual wire connector Semiconductor devices 1493 10 H01L2924/00012 Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies, as covered by H01L 24/00 1325 11 H04W4/80 Services using short range communication, e.g., near-field communication [NFC], radio-frequency identification [RFID] or low energy communication Smart phone 1313 12 G06F3/04842 Selection of displayed objects or displayed text elements Semiconductor devices 1221 13 H01L2924/181 Encapsulation 1216 14 H04W88/02 Terminal devices specially adapted for wireless communication networks, e.g., terminals, base stations or access point devices Wireless communication 1204 15 G06F3/0481 Based on specific properties of the displayed interaction object or a metaphor-based environment, e.g., interaction with desktop elements like windows or icons, or assisted by a cursor’s changing behavior or appearance Personal computer 1195 16 G06F3/14 Digital output to display device 1169 17 B82Y10/00 Nanotechnology for information processing, storage or transmission, e.g., quantum computing or single electron logic Smart phone 1111 18 G06F3/04817 Interaction techniques based on graphical user interfaces [GUI] using icons Personal computer 1104 19 G06F1/1626 with a single-body enclosure integrating a flat display, e.g., Personal Digital Assistants 1103 20 G06F3/04886 Interaction techniques based on graphical user interfaces [GUI] by partitioning the display area of the touch-screen or the surface of the digitizing tablet into independently controllable areas, e.g., virtual keyboards or menus 1068 Table 4. Inventor distribution for top 10 CPCs on main paths. ID CPC # Inventors CPC Definition 1 G11C16/0483 59 Comprising cells having several storage transistors connected in series 2 G11C16/10 43 Programming or data input circuits 3 G11C16/08 36 Address circuits; decoders; word-line control circuits 4 G11C16/26 31 Sensing or reading circuits; data output circuits 5 G11C16/16 23 For erasing blocks, e.g., arrays, words, groups 6 G11C16/14 21 Circuits for erasing electrically, e.g., erase voltage switching circuits 7 G11C16/12 19 Programming voltage switching circuits 8 G11C16/06 17 Auxiliary circuits, e.g., for writing into memory 9 H01L27/115 17 Electrically programmable read-only memories; multistep manufacturing processes therefor 10 H01L27/11556 17 Channels comprising vertical portions, e.g., U-shaped channels Table 5. Key inventors (top 1% in whole networks) on main paths. Inventor Betweenness Degree Patents on Main Paths Major Capabilities KIM, TAE HYUNG 863,637.760 12 3 LED materials and structures SON, HONG RAK 749,000.051 23 3 Programming; data I/O circuits JANG, JAE HOON 819,919.954 10 2 Channel design; read-only memories PARK, KITAE 735,754.670 10 1 Data I/O circuits; decoders; word-line control BYEON, DAE SEOK 365,547.398 15 3 Decoders; power supply circuits; data I/O circuits CHOI, JUNG DAL 697,039.692 17 1 Transistors; memory core region; read-only memories KONG, JUN JIN 1,893,719.455 27 3 Programming; data I/O circuits Average 874,945.569 16.286 All inventors of Samsung Patents * 24,044.413 1.333 All key inventors of Samsung Patents * 1,068,664.526 15.864 LED * 143,398.244 4.412 Memory circuits * 152,559.905 3.788 Flash memory * 113,652.820 3.538 Semiconductor device * 177,307.210 4.712 *: The average value of inventors in the set. Table 6. CPCs for forecasting future directions. Sub-Domain Patent ID New CPCs in External Citations Recent Major CPCs of Key Inventors LED 75042 H01L33/38 H01L33/40 B82Y20/00 H01L33/36 H01L21/268 H01L2224/45144 H01L2224/48463 H01L2224/85181 H01L33/30 H01L2224/1403 ... H01L33/32 H01L2924/0002 85827 Memory Circuits 84462 G11C16/0466 G11C16/0475 G11C11/5628 G11C16/04 G11C11/4074 G11C11/4085 G11C11/4096 G11C11/5635 G11C11/5642 G11C11/5671 ... G11C16/04 G11C16/34 G11C16/10 G11C16/26 H01L27/115 81009 86116 85950 Semiconductor Devices 83243 G06F11/00 G06F11/076 G06F11/08 G06F11/1068 G06F11/1072 G06F12/0246 G11C16/3404 G11C16/3454 H03M13/3927 G11C16/00 ... G11C16/0483 G11C16/10 G11C16/26 G11C11/5628 G11C11/5642 H01L27/115 G11C16/08 G11C16/3418 H01L27/11521 H01L27/11524 Table 7. Keywords and key topics extracted from patents of key inventors and external citations. LED Memory Circuits Semiconductor Devices Recent major capabilities from key inventors (existing keywords from key inventors’ patents) first electrode layer first light first semiconductor layer insulating layer second electrode layer semiconductor device control logic flag cells nonvolatile memory device plurality of memory cells plurality of word lines upper surface word line driver word line voltages NAND memory bit line controls operation erasing method external device memory block memory cells nonvolatile memory device plurality of word lines plurality of memory cells read command with respect read operation selected memory block voltage generator New or unconventional keywords from external citations distributed bragg reflection n-type semiconductor layer ITO DBR layer ohmic contact layer GaN-based semiconductor layer upper surface dummy string selection horizontal layers memory cells coupled string selection transistors unselected word line word line driver upper word line unselected word lines unselect read voltage sampling read voltage reference pages lower word line level look-up table cell counting operation Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. MDPI and ACS Style Han, F.; Yoon, S.; Raghavan, N.; Park, H. Investigating Company’s Technical Development Directions Based on Internal Knowledge Inheritance and Inventor Capabilities: The Case of Samsung Electronics. Sustainability 2022, 14, 3117. https://doi.org/10.3390/su14053117 AMA Style Han F, Yoon S, Raghavan N, Park H. Investigating Company’s Technical Development Directions Based on Internal Knowledge Inheritance and Inventor Capabilities: The Case of Samsung Electronics. Sustainability. 2022; 14(5):3117. https://doi.org/10.3390/su14053117 Chicago/Turabian Style Han, Fang, Sejun Yoon, Nagarajan Raghavan, and Hyunseok Park. 2022. "Investigating Company’s Technical Development Directions Based on Internal Knowledge Inheritance and Inventor Capabilities: The Case of Samsung Electronics" Sustainability14, no. 5: 3117. https://doi.org/10.3390/su14053117
https://www.mdpi.com/2071-1050/14/5/3117/htm#table_body_display_sustainability-14-03117-t007
Dispatch Working Group A. Allen, Ed. Internet-Draft Research in Motion (RIM) Intended status: Informational January 11, 2011 Expires: July 15, 2011 Using the International Mobile station Equipment Identity(IMEI)URN as an Instance ID draft-allen-dispatch-imei-urn-as-instanceid-02 Abstract This specification defines how the Uniform Resource Name namespace reserved for GSMA (Global Sstandard for Mobiles Association) identities and its sub namespace for the IMEI (International Mobile station Equipment Identity) can be used as an instance-id as specified in RFC 5626 [1] and also as used by RFC 5627 [2]. Status of this Memo This Internet-Draft is submitted in full conformance with the provisions of BCP 78 and BCP 79. Internet-Drafts are working documents of the Internet Engineering Task Force (IETF). Note that other groups may also distribute working documents as Internet-Drafts. The list of current Internet- Drafts is at http://datatracker.ietf.org/drafts/current/. Internet-Drafts are draft documents valid for a maximum of six months and may be updated, replaced, or obsoleted by other documents at any time. It is inappropriate to use Internet-Drafts as reference material or to cite them other than as "work in progress." This Internet-Draft will expire on July 15, 2011. Copyright Notice Copyright (c) 2011 IETF Trust and the persons identified as the document authors. All rights reserved. This document is subject to BCP 78 and the IETF Trust's Legal Provisions Relating to IETF Documents (http://trustee.ietf.org/license-info) in effect on the date of publication of this document. Please review these documents carefully, as they describe your rights and restrictions with respect to this document. Code Components extracted from this document must include Simplified BSD License text as described in Section 4.e of the Trust Legal Provisions and are provided without warranty as Allen Expires July 15, 2011 [Page 1] Internet-Draft Using IMEI URN as an Instance ID January 2011 described in the Simplified BSD License. Table of Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 3 2. Terminology . . . . . . . . . . . . . . . . . . . . . . . . . . 3 3. Background . . . . . . . . . . . . . . . . . . . . . . . . . . 4 4. User Agent Client Procedures . . . . . . . . . . . . . . . . . 5 5. Security considerations . . . . . . . . . . . . . . . . . . . . 5 6. Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . 5 7. References . . . . . . . . . . . . . . . . . . . . . . . . . . 6 7.1. Normative references . . . . . . . . . . . . . . . . . . . 6 7.2. Informative references . . . . . . . . . . . . . . . . . . 6 Author's Address . . . . . . . . . . . . . . . . . . . . . . . . . 7 Allen Expires July 15, 2011 [Page 2] Internet-Draft Using IMEI URN as an Instance ID January 2011 1. Introduction This specification defines how the Uniform Resource Name namespace reserved for GSMA identities and its sub namespace for the IMEI (International Mobile station Equipment Identity) as defined in draft-montemurro-gsma-imei-urn-06 [3] can be used as an instance-id as specified in RFC 5626 [1] and also as used by RFC 5627 [2]. RFC 5626 [1] defines the "+sip.instance" Contact header field parameter which contains a URN as per RFC 2141 [4] defined as an instance-id that uniquely identifies a specific UA instance. This instance-id is used as defined in RFC 5626 [1] so that registrar can recognize that the contacts from multiple registrations correspond to the same UA. The instance-ID is also used as defined by RFC 5627 [2] to create Globally Routable User Agent URIs (GRUUs) that can be used to uniquely address a UA when multiple UAs are registered with the same Address of Record (AoR). RFC 5626 [1] defines that a UA SHOULD create a Universally Unique Identifier (UUID) URN as defined in RFC 4122 [6] as its instance-id but allows for the possibility of other URN schemes to be used. If a URN scheme other than UUID is used, the UA MUST only use URNs for which an RFC (from the IETF stream) defines how the specific URN needs to be constructed and used in the "+sip.instance" Contact header field parameter for outbound behavior. This specification meets this requirement by specifying how the GSMA IEMEI URN is used in the "+sip.instance" Contact header field parameter for outbound behavior and draft-montemurro-gsma-imei-urn-06 [3] defines how the GSMA IMEI URN is constructed The GSMA IMEI is an identifier for a namespace for the IMEI a globally unique identifier that identifies Mobile Equipment used in Global System for Mobile (GSM), Universal Mobile Telecommunications System (UMTS) and 3GPP LTE (Long Term Evolution)networks. The IMEI allocation is managed by the GSMA to ensure that the IMEI values are globally unique. Details of the formatting of the IMEI as a URN are defined in draft-montemurro-gsma-imei-urn-06 [3] and the definition of the IMEI is contained in 3GPP TS 23.003 [7]. Further details about the GSMA role in allocating the IMEI and the IMEI allocation guidelines can be found in GSMA PRD DG.06 [8] 2. Terminology The key words "MUST", "MUST NOT", "REQUIRED", "SHALL", "SHALL NOT", "SHOULD", "SHOULD NOT", "RECOMMENDED", "MAY", and "OPTIONAL" in this document are to be interpreted as described in [5]. Allen Expires July 15, 2011 [Page 3] Internet-Draft Using IMEI URN as an Instance ID January 2011 3. Background GSM and UMTS capable mobile devices represent 90% of the mobile devices in use worldwide. GSM and UMTS mobile devices each have an IMEI allocated which uniquely identifies the mobile device from all other GSM/UMTS mobile devices deployed. Amongst other things in some regulatory jurisdictions the IMEI is used to identify a stolen mobile is being used and help to identify the subscription that is using it and to prevent its use. Whilst GSM was originally a circuit switched system enhancements such as GPRS (General Packet Radio Service) and UMTS have added IP data capabilities which along with the definition of the IP Multimedia Subsystem (IMS) has made SIP based calls and IP multimedia sessions from mobile devices possible. The latest enhancment known as LTE will introduce even higher data rates and dispenses with the circuit switched domain completely meaning that with LTE voice calls will need to be conducted using IP and IMS. However, the transition to all IP, SIP based IMS networks worldwide will take a great many years and mobile devices being mobile will need to operate in both IP/SIP/IMS mode and circuit switched mode. In fact calls and sessions will need to be handed over between IP/ SIP/IMS mode and circuit switched mode during a call. Also as many existing GSM and UMTS radio access networks are unable to support IP/ SIP/IMS based voice services in a commercially acceptable manner some sessions may have some media types delivered via IP/IMS simultaneously with voice media delivered via circuit switched with the same mobile device simultaneously attached via both the IP/SIP/ IMS domain and the circuit switched domain. To meet this need 3GPP has specified how to maintain session continuity between the IP/SIP/ IMS domain and the circuit switched domain in 3GPP TS 24.237 [9] and how to access IMS hosted services via both the IP/SIP/IMS domain and the circuit switched domain in 3GPP TS 24.292 [10]. In order for the the mobile device to access SIP/IMS services via the circuit switched domain 3GPP has defined a MSC (Mobile Switching Center) server enhanced for ICS which controls mobile voice call setup over the circuit switched radio access while establishing the corresponding voice session in the core network using SIP/IMS. To enable this the MSC server enhanced for ICS (IMS centralized services) performs SIP registration on behalf of the mobile device which may simultaneously also be directly registered with the IP/SIP/ IMS domain. The SIP/IMS network needs to be able to identify that both of these SIP registrations are from the same UA instance and also correctly handle sessions establishment requests addressed using GRUUs as defined in RFC 5627 [2] when the mobile device is attached using the circuit switched domain. The only mobile device identifier that is transportable using GSM/UMTS/LTE signaling is the IMEI therefore the instance-id used by the MSC server enhanced for ICS when registering on behalf of the mobile device and the instance-id Allen Expires July 15, 2011 [Page 4] Internet-Draft Using IMEI URN as an Instance ID January 2011 when the mobile device registers directly needs to be based on the IMEI. Additionally in order to meet the regulatory requirements to use the IMEI to identify a stolen mobile is being used and help to identify the subscription that is using it and to prevent its use the same IMEI that is obtained from the circuit switched signaling needs to be obtainable from SIP signaling. 3GPP TS 24.237 [9] and 3GPP TS 24.292 [10] already define the use of the URN namespace for the GSMA and IMEI as defined in draft-montemurro-gsma-imei-urn-06 [3] as the instance-id used by mobile devices and the MSC server enhanced for ICS for SIP/IMS registrations for these reasons. 4. User Agent Client Procedures A UAC that has an IMEI as defined in 3GPP TS 23.003 [7] SHALL include in the "sip.instance" media feature tag the GSMA IMEI URN according to the syntax defined in draft-montemurro-gsma-imei-urn-06 [3] when performing the registration procedures defined in RFC 5626 [1] or RFC 5627 [2] or any other procedure requiring including the "sip.instance" media feature tag. The UAC must provide lexically equivalent URNs in each registration [1]. Hence, any optional or variable components of the URN (e.g., the "vers" and "svn" parameters) must be presented with the same values and in the same order in every registration as in the first registration. 5. Security considerations In order to protect from tampering the REGISTER requests containing the GSMA IMEI URN SHOULD be sent using a security mechanism such as TLS [11] (or other security mechanism that provides equivalent levels of protection). 6. Acknowledgements The author would like to thank Paul Kyzivat and Dale Worley for reviewing this draft and providing their comments. 7. References Allen Expires July 15, 2011 [Page 5] Internet-Draft Using IMEI URN as an Instance ID January 2011 7.1. Normative references [1] Jennings, C., Mahy, R., and F. Audet, "Managing Client- Initiated Connections in the Session Initiation Protocol (SIP)", RFC 5626, October 2009. [2] Rosenberg, J., "Obtaining and Using Globally Routable User Agent URIs (GRUUs) in the Session Initiation Protocol (SIP)", RFC 5627, October 2009. [3] Montemurro, M., "A Uniform Resource Name Namespace For The GSM Association (GSMA) and the International Mobile station Equipment Identity(IMEI), work in progress", Internet Draft draft-montemurro-gsma-imei-urn-06, January 2011. [4] Moats, R., "URN Syntax", RFC 2141, May 1997. [5] Bradner, S., "Key words for use in RFCs to Indicate Requirement Levels", BCP 14, RFC 2119, March 1997. 7.2. Informative references [6] Leach, P., Mealling, M., and R. Salz, "A Universally Unique IDentifier (UUID) URN Namespace", RFC 4122, July 2005. [7] 3GPP, "TS 23.003: Numbering, addressing and identification (Release 8)", 3GPP 23.003, September 2008, <ftp://ftp.3gpp.org/Specs/archive/23_series/23.003/>. [8] GSMA Association, "IMEI Allocation and Approval Guidelines", PRD DG.06 version 3.6, February 2008, <http://gsmworld.com/newsroom/document%2Dlibrary/>. [9] 3GPP, "TS 24.237: Mobile radio interface Layer 3 specification; Core network protocols; Stage 3 (Release 8)", 3GPP 24.237, March 2009, <ftp://ftp.3gpp.org/Specs/archive/24_series/24.237/>. [10] 3GPP, "TS 24.292: IP Multimedia (IM) Core Network (CN) subsystem Centralized Services (ICS); Stage 3 (Release 8)", 3GPP 24.292, March 2009, <ftp://ftp.3gpp.org/Specs/archive/24_series/24.292/>. [11] Dierks, T. and C. Allen, "The TLS Protocol Version 1.0", RFC 2246, January 1999. Allen Expires July 15, 2011 [Page 6] Internet-Draft Using IMEI URN as an Instance ID January 2011 Author's Address Andrew Allen (editor) Research in Motion (RIM) 2550 West Golf Road Rolling Meadows, Illinois 60008 USA Phone: unlisted Fax: unlisted Email: aallen@rim.com Allen Expires July 15, 2011 [Page 7]
https://www.potaroo.net/ietf/all-ids/draft-allen-dispatch-imei-urn-as-instanceid-02.txt
Agronomy | Free Full-Text | Intra- and Inter-Population Genetic Diversity of & ldquo;Russello& rdquo; and & ldquo;Timilia& rdquo; Landraces from Sicily: A Proxy towards the Identification of Favorable Alleles in Durum Wheat Climate change and global population growth call for urgent recovery of genetic variation from underexploited or unexplored durum wheat (Triticum turgidum ssp. durum) landraces. Indeed, these untapped genetic resources can be a valuable source of favorable alleles for environmental adaptation and tolerance or resistance to (a)biotic stress. In southern Italy, in addition to the widespread modern and highly productive durum wheat cultivars, various landraces have been rediscovered and reused for their adaptation to sustainable and low-input cropping systems and for their peculiar qualitative characteristics. Sicily is a semiarid area rich in landraces, some of which are independently reproduced by many farmers. Among these, “Timilia” and “Russello” have been independently grown in various areas and are now cultivated, mostly under organic systems, for their hypothetical greater benefits and height, which give them a high level of competitiveness against weeds despite their low yield potential. So far, there is little information on the genetic variations of “Timilia” and “Russello” despite their putative origin from a common funder. This work aims to dissect the genetic variation patterns of two large germplasm collections of “Timilia” and “Russello” using SNP genotyping. The analysis of intra- and inter-population genetic variation and the identification of divergent loci between genetic groups showed that (i) there are two “Russello” genetic groups associated with different Sicilian geographical areas, which differ in important traits related to gluten quality and adaptation, and (ii) the individuals of “Timilia”, although presenting wide genetic variation, have undergone a conservative selection, likely associated with their distinctive traits. This work paves the way for a deeper exploration of the wide genetic diversity in Sicilian landraces, which could be conveniently exploited in future breeding programs, and points out that intra-population genetic diversity should be taken into account when ‘conservation varieties’ are to be registered in national registers of crops. Francesca Taranto 1,* , Ermanno Di Serio 2 , Monica Marilena Miazzi 3 , Stefano Pavan 3 , Sergio Saia 4 , Pasquale De Vita 5,* and Nunzio D’Agostino 2 1 Institute of Biosciences and Bioresources (CNR-IBBR), 70126 Bari, Italy 2 Department of Agricultural Sciences, University of Naples Federico II, Via Università 100, 80055 Portici, Italy 3 Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Via Amendola 165/A, 70126 Bari, Italy 4 Department of Veterinary Sciences, University of Pisa, 56129 Pisa, Italy 5 Council for Agricultural Research and Economics (CREA), Research Centre for Cereal and Industrial Crops (CREA-CI), S.S. 673, Km 25,200, 71122 Foggia, Italy * Authors to whom correspondence should be addressed. Agronomy 2022 , 12 (6), 1326; https://doi.org/10.3390/agronomy12061326 Received: 11 May 2022 / Revised: 27 May 2022 / Accepted: 28 May 2022 / Published: 30 May 2022 Abstract : Climate change and global population growth call for urgent recovery of genetic variation from underexploited or unexplored durum wheat ( Triticum turgidum ssp. durum ) landraces. Indeed, these untapped genetic resources can be a valuable source of favorable alleles for environmental adaptation and tolerance or resistance to (a)biotic stress. In southern Italy, in addition to the widespread modern and highly productive durum wheat cultivars, various landraces have been rediscovered and reused for their adaptation to sustainable and low-input cropping systems and for their peculiar qualitative characteristics. Sicily is a semiarid area rich in landraces, some of which are independently reproduced by many farmers. Among these, “Timilia” and “Russello” have been independently grown in various areas and are now cultivated, mostly under organic systems, for their hypothetical greater benefits and height, which give them a high level of competitiveness against weeds despite their low yield potential. So far, there is little information on the genetic variations of “Timilia” and “Russello” despite their putative origin from a common funder. This work aims to dissect the genetic variation patterns of two large germplasm collections of “Timilia” and “Russello” using SNP genotyping. The analysis of intra- and inter-population genetic variation and the identification of divergent loci between genetic groups showed that (i) there are two “Russello” genetic groups associated with different Sicilian geographical areas, which differ in important traits related to gluten quality and adaptation, and (ii) the individuals of “Timilia”, although presenting wide genetic variation, have undergone a conservative selection, likely associated with their distinctive traits. This work paves the way for a deeper exploration of the wide genetic diversity in Sicilian landraces, which could be conveniently exploited in future breeding programs, and points out that intra-population genetic diversity should be taken into account when ‘conservation varieties’ are to be registered in national registers of crops. Keywords: Triticum turgidum ssp. durum ; landraces ; divergent loci ; genetic diversity ; Fst ; favorable alleles ; adaptation ; climate change 1. Introduction Durum wheat ( Triticum turgidum ssp. durum , 2n = 28) is a strategic crop for the Italian economy due to its multiple uses in the production of pasta and some traditional breads and ability to provide high yield and profits in marginal lands. In Italy, the first durum wheat breeding program was launched at the beginning of the 20th century with the aim of developing varieties with higher yields, reduced height, early maturity, and, to a lesser extent, tolerance to pathogens. Breeding activities began through the selection of different pure lines within landrace populations cultivated in southern Italy and in other Mediterranean countries [ 1 , 2 ]. Subsequently, the introduction of the Rht-B1 dwarfing gene from the Japanese cultivar “Norin 10” in the Italian germplasm during the ‘green revolution’ led to the release of new cultivars with increased yield and better technological quality of the grain [ 3 ]. The processes of domestication and breeding led to a reduction in genetic variation over time [ 4 ]. In the last century, a narrowing of the genetic basis of the Italian durum wheat germplasm was observed due to the repeated use of a few élite varieties as parents in breeding programs [ 5 ]. This is especially true for cultivars released after the year 2000 [ 6 ]. Meanwhile, old landraces were confined to niche areas, and their conservation was delegated to public research institutes and private farmers. The climate emergency and the increase in the world population have made it urgent to recover genetic variation from underexploited or unexplored landraces [ 7 ]. These untapped resources are known to be a valuable source of useful alleles for environmental adaptation and tolerance to (a)biotic stress [ 8 , 9 ]. Furthermore, consumers’ demand for a range of healthy wheat-based food products is driving processing industries to diversify their products, including the use of ancient wheats, despite the fact that their supposed superior healthy properties have never been demonstrated [ 10 , 11 , 12 ]. In southern Italy, especially in Apulia and Sicily, it is still possible to find old landraces of durum wheat grown in situ, mainly on organic farms [ 6 , 13 , 14 ]. Indeed, many of them are no longer cultivated over large areas due to the spread of new, more productive cultivars. However, in recent years, thanks to their adaptation to sustainable and low-input cropping systems, several landraces have been rediscovered and reused. In Sicily, durum wheat has historically represented, and still represents, one of the main crops. The different pedoclimatic areas where this cereal is grown generated a wide array of well-adapted indigenous landraces, such as “Timilia”, “Russello”, “Perciasacchi”, “Bidi”, “Ciciredda”, “Faricello”, “Francesa”, “Gioia”, “Martinella”, “Paola”, “Scorsonera”, “Tripolino” and “Margherito” [ 14 , 15 , 16 , 17 ]. However, since their seeds are mainly produced, stored, and exchanged among farmers, it is extremely hard to keep each landrace pure. In order to preserve these local resources from genetic erosion, some of them have been registered in the Italian National Register of crop varieties as ‘conservation varieties’, introduced by Council Directive 98/95/EC and improved with Council Directive 08/63/CE. This is the case of durum wheat landraces “Russello” and “Timilia”, released, respectively, in 2014 and 2018. These two landraces, in the last few years, have attracted the interest of both consumers and the scientific community due to their strong link with the territory and their valuable qualitative characteristics, mainly intended for specialty breads [ 18 , 19 ]. “Timilia” was one of the most widespread cereals in the Mediterranean area in the 18th and 19th centuries thanks to its lack of vernalization, in contrast with most of the other landraces. Indeed, it has also been found in Portugal, North Africa, France, and particularly in Seville, Spain [ 20 ]. Its synonym “Triminia” indicates the ability that this wheat has to complete its crop cycle in three months because it was normally sown in the late winter or early spring and harvested in June [ 13 ]. Its cultivation has been widespread for centuries throughout Sicily but has never been very intense, as its low crop cycle, tall size, and late spiking date are major constraints to its productivity. At the beginning of the 20th century, the breading activity of within-population selection led to the release of new pure lines such as “Timilia with white awns”, “Timilia with black awns”, and “Timilia SG3”, which are more productive and have a better ability to adapt [ 15 ]. “Timilia” is still used to produce local and traditional breads that are much appreciated by consumers, such as ‘Castelvetrano black bread’ [ 18 , 21 ] and ‘Monreale bread’ [ 22 , 23 ] which have been labeled as traditional agri-food products. Similarly, “Russello” was one of the most cultivated landraces in Sicily in the early 1900s, especially in the western areas of Agrigento, Caltanissetta, and Palermo. In the Hyblaean area (the eastern districts of Ragusa, Syracuse, and Catania), “Russello” was often confused with the landrace “Ruscìa” [ 15 , 23 ]. Over time, different populations were referred to as “Russello” even though they have different morpho-physiological and agronomic traits [ 24 ]. Given the growing interest of farmers and consumers, many efforts were made to preserve and enhance Sicilian durum wheat landraces and their end-products, leading to the development of traceability methods based on morphological descriptors, storage protein composition, digestibility of starch, and concentration of secondary compounds [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. In contrast, the genetic diversity of Sicilian landraces was poorly explored using molecular markers. Some studies analyzed the genetic variation of a few accessions of “Russello” and “Timilia” as pure lines, using amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers [ 5 , 30 , 31 , 32 ]. Advances in high-throughput next-generation sequencing (NGS)-based genotyping offer the opportunity to generate a large panel of single nucleotide polymorphism (SNP) markers for use in genetic studies [ 33 , 34 ]. Using these new technologies, several studies on durum wheat were performed to dissect the patterns of genetic variation between landraces and old/modern varieties [ 6 , 14 , 35 , 36 , 37 , 38 ]. Unfortunately, no studies have ever been performed on large collections of Sicilian durum wheat landraces using SNP genotyping. This work explored intra- and inter-population genetic variation of two large collections (including over 350 individuals) of “Russello” and “Timilia” with the aim of (i) identifying and removing duplicate individuals, (ii) defining patterns of genetic diversity within and between populations, (iii) estimating the pattern and extent of linkage disequilibrium and identifying haplotype blocks, and (iv) searching for divergent loci that may contribute to phenotypic differentiation. 2. Materials and Methods 2.1. Plant Material, Genotyping, and SNP Filtering The durum wheat germplasm under investigation included 357 individuals collected from farmers’ fields that belong to two Sicilian durum wheat landraces, namely “Russello” and “Timilia”. The whole collection (RTC) consisted of 5 “Russello” populations (Pop-R) with 30 individuals each and 7 “Timilia” populations with black awns (Pop-T), 5 of which with 30 individuals, 1 with 29, and 1 with 28 individuals. The populations were sampled in different Sicilian geographical areas ( Figure 1 ), advanced by three generations using the Single Seed Descendent (SSD) method, and conserved at the Research Centre for Cereal and Industrial Crops (CREA-CI), Foggia, Italy, up to the time of this study. DNA was extracted from the leaf tissue of each sample according to [ 39 ]. DNA was genotyped using the Illumina iSelect 15K wheat SNP array (TraitGenetics GmbH, Gatersleben, Germany), which includes 13,006 markers distributed along the durum wheat genome. The physical location of each SNP was assigned based on the physical map of the Svevo durum wheat cultivar, available at https://www.interomics.eu/durum-wheat-genome (accessed on 10 May 2022) [ 4 ]. SNP markers with unknown chromosomal positions were arbitrarily assigned to chromosome 0. For all downstream analyses, the following groups of individuals were considered: (i) the individual “Russello” and “Timilia” populations (Pop-R and Pop-T); (ii) two collections, grouping either the “Russello” (RC) or the “Timilia” (TC) populations; (iii) the entire collection, combining all the “Russello” and “Timilia” (RTC). SNP markers with minor allele frequency (MAF) < 5%, minimum site count < 10%, and individuals with missing call rate > 10% were filtered out. Finally, each dataset was LD (linkage disequilibrium) pruned (r 2 = 0.20) using the SNP and Variation suite (SVS) v.8.4.0 (Golden Helix Inc., Bozeman, MT, USA). The filtering procedure and LD pruning resulted in datasets of high-quality SNP markers that were used to calculate the pairwise identical-by-state (IBS) distance matrix among all individuals using PLINK (v. 1.90). Duplicated individuals were inferred for a percentage of shared alleles ≥0.99. Once duplications were found, only one individual (the one with the highest call rate) was used for downstream analyses. The R ggplot2 package [ 40 ] was used to generate bar charts showing the frequency distribution of the IBS values and the number of high-quality SNPs per chromosome. 2.2. Population Genetics and Diversity Genetic structure was evaluated by MultiDimensional Scaling (MDS) on the basis of the IBS distance and by constructing a neighbor-joining tree with 1000 bootstrap replicates using Mega X [ 41 ]. FigTree v.1.4.3 was used for tree visualization. GenAlEx 6.5 [ 42 ] was used to estimate the number of observed alleles (Na), Nei’s genetic distance index (He), Shannon’s index (I), the percentage of private alleles (PA), and to run the analysis of molecular variance (AMOVA) test. SVS was used to estimate the pairwise fixation index ( F ST ) between populations. Finally, the R ComplexHeatmap [ 43 ] and circlize [ 44 ] packages were used to obtain heatmaps based on pairwise F ST values. 2.3. Divergent Loci and Putative Genes under Selection The identification of divergent loci was performed by applying the Weir and Cockerham formula [ 45 ] implemented in SVS. F ST values at individual loci were computed by pairwise comparison between groups in RC, TC, and RTC. The 95% confidence interval around the F ST value was calculated using the percentile -t bootstrapping technique [ 46 ]. A significance threshold >0.25 was fixed. All divergent loci with F ST > 0.50 were then used to construct the haplotype network using the minimum spanning method in PopART [ 47 ]. The LD Adjacent Pairs Analysis function in SVS was used to calculate the average decay of LD in the RC, TC, and RTC collections. The average LD decay distance was used to define the size of the region containing each divergent marker, thus including putative QTLs or genes under selection. 3. Results 3.1. IBS Analysis Out of 13,006 SNPs spotted onto the 15K Infinium iSelect array, 4624 high-quality SNPs were retained after filtering, which were physically mapped onto the 14 chromosomes of the durum “Svevo” genome ( Figure 2 ). A total of 1970 and 2654 SNPs were located on the genomes A and B, respectively, ranging from 178 (4B) to 525 (5B) ( Figure S1 ). IBS matrices were used to identify duplicated samples by setting a percentage of shared alleles ≥ 0.99 as the threshold. The frequency distribution of IBS values ranged between 0.5 and 1 for Pop-R1, Pop-R3, and Pop-R5. No duplicated samples were found in Pop-R1 and Pop-R5, whereas Pop-R3 included a single pair of duplicated samples ( Table S1 ). Estimates of pairwise IBS ranged from 0.4 to 1 in the case of Pop-R2 and Pop-R4. A total of 8 and 17 duplicated samples were found in Pop-R2 and Pop-R4, respectively ( Tables S1 and S2 ). The 7 populations of “Timilia” had a very similar IBS frequency distribution. Most pairwise IBS values fell within a range of 0.5 to 0.8. At least three duplicated samples were identified in each population. A total of 10 and 8 duplicated samples were detected in Pop-T8 and Pop-T11, respectively. As for RC, the frequency distribution of the pairwise IBS estimates was bimodal ( Figure S2A ). Based on the threshold value, only one pair of duplicated samples was found ( Tables S1 and S2 ). In TC, most IBS values were between 0.6 to 0.8 ( Figure S2B ), and 31 pairs of duplicated samples were found. Finally, a total of 8 duplicated samples were found in RTC ( Supplementary Table S1 ). The duplicated samples were discarded to avoid affecting the genetic diversity analysis ( Tables S1 and S2 ). 3.2. Genetic Relationships and Differentiation The genetic relationship of each population, cleaned of duplicate samples based on IBS values, was described by an MDS scatterplot and an NJ tree. Both approaches returned the same results. In RC, it was possible to clearly distinguish two groups: the first included the R1, R3, and R5 populations, and the second included R2 and R4 ( Figure S3A,B ). In contrast, the NJ and MDS did not indicate any clustering patterns for the populations of “Timilia” ( Figure S3C,D ). MDS and NJ analyses performed on the entire collection (RTC) supported the genetic structure described above, as “Timilia”, R1-3-5 and R2-4 were separated into three clusters ( Figure 3 A,B), except for three individuals belonging to R2 which were included in the cluster together with all those R1-3-5. The fixation index ( F ST ) between pairs of populations was computed to assess their degree of differentiation ( Figure 3 C). An F ST value < 0.05 (low differentiation) was observed among the R1, R3, and R5 populations, as well as between the R2 and R4 populations. On the other hand, large genetic differentiation ( F ST > 0.40) was observed by comparing the two groups (i.e., R1-3-5 vs. R2-4). As previously suggested by AMOVA, F ST values obtained by comparing the populations of “Timilia” in pairs were close to 0, thus indicating an almost absent genetic differentiation among the populations. In addition, a strong differentiation was found when comparing “Timilia” vs. R1-3-5 ( F ST = 0.59) and “Timilia” vs. R2-4 ( F ST = 0.60). 3.3. Genetic Diversity Analysis Genetic diversity analysis was first performed by comparing the Pop-R and Pop-T populations with each other. Based on genetic relationships, the RC collection was also divided into two groups, RC1-3-5 and RC2-4. Then, for RTC, the three groups (RC1-3-5, RC2-4, and TC) were compared in pairs. A large genetic variation was observed within all the “Russello” and “Timilia” populations ( Table 1 ). Indeed, Shannon and Nei’s indices changed slightly in Pop-R and Pop-T populations, with the highest values in Pop-T7 (I = 0.602, He = 0.355). As for “Russello”, Pop-R2 and Pop-R4 showed the lowest average number of observed alleles (Na = 1.913 and 1.734, respectively). The same trend was observed for the frequency of private alleles (PA ≤ 0.012). As for “Timilia”, the lowest values of Na (2.179), I (0.485), and He (0.304) were found in Pop-T8. The genetic diversity parameters estimated for RC and TC revealed that all the “Russello” (RC) had higher variability than “Timilia” (TC). In addition, the RC1-3-5 group was characterized by greater genetic diversity than RC2-4 and TC ( Table 1 ). Within RTC, RC1-3-5 and RC2-4 showed a higher Shannon’s index (I = 0.419 and I = 0.396, respectively) and Nei’s index (He = 0.246 and He = 0.258, respectively) than TC (I = 0.288 and He = 0.167) ( Table 1 ). Conversely, TC had a larger number of private alleles than the other two groups ( Table 1 ). AMOVA was used to describe population differentiation. The test revealed that there was greater genetic variation within (76%) than among populations (24%) in RC. In TC, 100% within-population variation was observed. As for RTC, within-population variation (54%) was slightly higher than among-populations variation (46%). 3.4. Divergent Loci and Haplotype Network The genetic differentiation between the three groups mentioned above was further investigated by analyzing the F ST index at individual loci, using F ST > 0.50 as the threshold. A total of 1126, 1673, and 1968 divergent markers were detected in RC1-3-5 vs. R2-4, TC vs. R1-3-5, and TC vs. R2-4, respectively. Figure 4 shows the distribution of divergent loci along all chromosomes (A) and a Venn diagram (B) reporting the number of unique and common divergent markers among the three groups. Divergent loci were identified along all chromosomes, with the lowest values in the R1-3-5 vs. R2-4 comparison ( Figure 3 ). When comparing TC vs. R1-3-5 and TC vs. R2-4, the chromosomes with the largest number (n) of divergent SNP markers were chromosomes 5B (n = 203) and 6B (n = 191). In contrast, chromosome 4A showed the smallest number of divergent SNPs in TC vs. R1-3-5 and TC vs. R2-4 (82 and 44, respectively). The largest and smallest number of divergent SNPs between the groups R1-3-5 and R2-4 were on chromosomes 5B (n = 129) and 4B (n = 19). All the divergent loci were then used to construct the haplotype network shown in Figure 5 , further confirming the genetic relationships among “Russello” and “Timilia” individuals ( Figure 3 ). Indeed, most individuals of “Timilia” were arranged into a large haplotype group, which exhibited high genetic conservation. The remaining two groups (R1-3-5 and R2-4) showed greater haplotype variability. The analysis indicated that R1-3-5 appears to be closer to the “Timilia” haplotype than R-2-4. The latter had a lower and more distant number of haplotypes. 3.5. Patterns of Linkage Disequilibrium and Candidate Genes Associated with Divergent Loci In order to identify the genes putatively associated with differences among the three groups, the decay of linkage disequilibrium within each group was estimated ( Figure S4 ). Average genome-wide LD decay at which r 2 fell to 0.20 was ∼11.5 Mb, 24 Mb, and 11 Mb for RC, TC, and RTC, respectively. In addition, the LD decay was also calculated considering TC+R1-3-5 (∼10 Mb) and TC+R2-4 (∼14 Mb); these LD decay values were then used as confidence intervals around each divergent SNP marker ( F ST > 0.80). Candidate genes in the confidence interval around each divergent SNP, returned from the comparison among the three groups, suggested a high level of divergence between populations, mostly in genomic regions where the genes controlling wheat grain quality traits are ( Table 2 ). The differences between “Timilia” and the two “Russello “groups are mostly related to genes encoding storage proteins (i.e., gliadins and glutenins) and genes responsible for grain color, such as those related to the browning reaction (i.e., polyphenol oxidase enzymes), and those belonging to the biosynthetic pathways of carotenoids and anthocyanins. However, comparisons did not always return the same loci but rather different genes on different chromosomes, as shown below. Divergent loci between the two RC groups were associated with qualitative traits such as γ-gliadin and glutenin on chromosome 1A and sucrose synthase (SUS3) on chromosome 2A; terpene synthase , terpene cyclase/mutase , 9-cis-epoxycarotenoid dioxygenase and carotenoid isomerase on chromosomes 3A, 3B, 5A, 6A and 7A, which are involved in the primary and part of the secondary metabolism, and starch biosynthesis on chromosome 3A. Comparisons of TC vs. R1-3-5 and TC vs. R2-4 returned some common genes, such as those encoding the polyphenol oxidase enzymes Ppo-A1 , Ppo-A2, and Ppo-B2 on homeologous chromosome 2 and the lipoxygenase enzyme on chromosome 5A. The analysis also revealed genes involved in starch metabolism ( starch synthase , α and β amylase and maltase , sucrose synthase ) on chromosomes 1B, 2A, 2B, 5A, and 7A; the gene that codes for the 15-cis-zeta-carotene-isomerase involved in the biosynthesis of carotenoids and the gene that codes for a high molecular weight glutenin and gliadin on chromosome 1A, 1B, and 5B. In the TC vs. R1-3-5 comparison, we identified genes such as: α, γ- gliadin, and glutenin ( hmw ) located on chromosomes 1A, 1B, and 6B; genes involved in starch metabolism, such as α and β amylase on chromosomes 2B and 5A, starch synthase on chromosomes 1B and 2B, granule-bound starch synthase ( GBSSI ) on chromosome 7A, and genes for maltose transport on chromosomes 2B, 4B and 6B. In addition, lipoxygenase genes were also detected on chromosome 2A. In the TC vs. R2-4 comparison, we identified the genes that influence the quality of durum wheat, such as: α, γ- gliadin, and glutenin ( hmw ) on chromosomes 1A, 1B, and 6A; α and β amylase on chromosomes 2B, 3A, 4B, 6B, and 7A; genes involved in the biosynthesis of carotenoids ( 9-cis-epoxycarotenoid dioxygenase , carotenoid oxugenase, and carotenoid isomerase ) on chromosomes 2B and 7A; a lipoxygenase (lpx) gene on chromosome 5B; genes encoding anthocyanin 5-aromatic acyltransferase and anthocyanin 5,3-O-glucosyltransferase on chromosomes 1B, 2A, 3A, 4B, 6A, and 6B. Regions that include genes known to be related to the most renowned morpho-agronomic traits important during the durum wheat breeding process were identified mainly in “Timilia” vs. “Russello” (both R1-3-5 and R2-4) comparison. Genes associated with other important traits associated with durum wheat artificial selection were detected, such as those controlling grain size and weight, i.e., MEI2-LIKE PROTEIN 4 ( OML4 ) and GW2-B1 , which included the divergent markers tplb0025b13_1721 (chr.1A) and Tdurum_contig85266_280 (chr.7B), respectively. In this latter region (chr.7B), a cluster of Agamous MADS-box transcription factor MADAGL17 was also found in TC vs. R2-4. Genes involved in the nitrogen metabolism were in regions harboring divergent SNP markers. In detail, the markers wsnp_CAP11_rep_c8768_3788007 and CAP7_c7415_267 fell into the sequence of glutamate synthase ( FD-GOGAT ) and nitrite reductase ( Nir ) genes on chromosomes 2A and 6A, respectively, the asparagine synthetase ( ASN ) and histone H3 were in a region with divergent SNPs spanning ~6 Mb on chr. 5A. Nitrate reductase ( NR) and nitrilase were in a region with divergent loci on chromosome 6A. Divergent loci were in LD in the regions including genes involved in nitrogen metabolism (nitrilase and nitrate transporter) as well as the Lipoxigenase 1 ( Lpx 1 ) and genes controlling plant height ( Rht ), such as Rht-A1 , Rht-B1, and Rht-14 on chromosomes 4A, 4B, and 6A, respectively. Other SNP markers were proximal to Ppd-A1 , Vrn-A1, and Vrn-B1 . The latter gene was also adjacent to the gene TdHMA3-B1, responsible for cadmium accumulation and considered a signature of selection from wild emmer to durum wheat. Finally, divergent genes involved in response to abiotic stresses such as the cold-responsive WCOR15 and the late embryogenesis abundant (LEA) hydroxyproline-rich glycoprotein were detected on chromosomes 1A and 3A, respectively. Furthermore, genes implicated in the signaling pathway of the rapamycin target (TOR) such as PP2A regulatory subunit TAP46 , Telo2 interacting protein2 , Kinase family protein , NAC , Phenylalanine--tRNA ligase beta subunit were detected. 4. Discussion In the current scenario of severe climate change, it is urgent to broaden the genetic basis of élite varieties through the introduction of favorable alleles conferring tolerance to (a)biotic stress. Landraces and old cultivars represent a precious resource for traits linked to adaptation to different pedoclimatic conditions [ 14 , 48 ]. Presently, thanks to the efforts of farmers and scientists, several wheat landraces and old cultivars have been collected and conserved on-farm and/or in ex situ genebanks [ 49 , 50 ]. However, within-population genetic variability is rarely studied by comparing a large number of individuals. Within this context, our work aimed to assess the intra- and inter-population genetic diversity of two large germplasm collections of the landraces “Timilia” and “Russello” and to identify the distinguishing SNP loci. The AMOVA and the assessment of the percentage of private alleles indicated very low genetic distance among seven populations of “Timilia” and moderately high intra-population variability. The five “Russello” populations were instead clearly separated into two distinct groups, respectively, R1-3-5 and R2-4. Inter-population variability was greater in the R1-3-5 populations than in R2-4. This is in accordance with the identification of several cases of duplicated individuals in R2 and R4. The identification of two “Russello” populations was in accordance with their geographical origin, as the R1-3-5 populations were collected from the Hyblaean mountains in south-eastern Sicily, which are characterized by different pedoclimatic conditions compared to central-western Sicily, where the R2-4 populations were sampled. The existence of two different “Russello” groups could also be explained by the fact that with the name “Russello”, farmers have indicated different durum wheat populations over time, even with different morpho-agronomic traits [ 24 , 51 ]. Our work evidenced the existence of two groups of “Russello” in Sicily and revealed how these remained distinct over time, probably due to geographical isolation, and have adapted to the different pedoclimatic conditions of the two cultivation areas [ 26 ]. Our results based on SNP markers agree with those by [ 23 ], who pointed out that all the “Timilia” individuals they sampled in different areas showed a single electrophoretic profile (HMW-GS, Bx6 + By8) of glutenins. In contrast, the same authors found two profiles for “Russello” (HMW-GS, Bx13 + By16 and Bx6 + By8), thus suggesting that the “Russello” grown between the two districts of Palermo and Agrigento has distinct characteristics compared with that grown in the Hyblaean area, where it is also referred to as “Ruscìa” [ 23 , 51 ]. The differentiation between the two “Russello” groups was also supported by the identification of divergent loci associated with genes encoding storage proteins. This difference may also be due to selection driven by contrasting temperatures during the grain filling stage in these areas [ 52 ]. Finally, our findings are also corroborated by the previous work by [ 6 ], in which single individuals randomly taken from each of the five “Russello” populations analyzed in this study were compared with a large collection of Italian landraces, ancient, and modern cultivars. Taranto [ 6 ] reported that individuals belonging to the R1-3-5 populations grouped with “Ruscìa”, while the individuals taken from the R2-4 populations were more similar to the ancient variety “Tangarog”, from which “Russello” could have originated [ 2 ]. The study of LD decay within the populations of “Timilia” and “Russello” further validated the genetic structure of the groups. Indeed, the slower decay of LD in TC confirmed the presence of larger haplotype blocks, probably due to the conservative selection made by farmers [ 6 ]. Indeed, although “Timilia” seeds have been exchanged among farmers even outside Sicily, as demonstrated by [ 6 ], it has maintained its genetic integrity for its exclusive use in spring sowing. The haplotype and the F ST analysis clearly show that although “Timilia” and “Russello” are two Sicilian landraces, they are genetically different. Furthermore, the R2 and R4 populations are the most variable and distant from “Timilia”, probably because they have been crossed with other cultivars, either other ancient Sicilian varieties or not, or erroneously referred to as “Russello” [ 24 ]. The analysis of the divergent loci supports and corroborates the genetic differences between the two “Russello” groups and between “Russello” and “Timilia”. It is known that these two landraces differ in the traits related to the quality of the grain. The comparison between TC and R1-3-5/R2-4 allowed identifying key genes that influence the composition of gluten, in accordance with the distinct electrophoretic profiles identified in several studies [ 3 , 23 , 25 , 26 ]. Another important aspect emerging from the present analysis is related to the genes encoding for the polyphenol oxidase (PPO) enzymes, which are involved in the oxidation of phenolic compounds, giving rise to the browning reactions of the kernels. Taranto [ 53 ] demonstrated that the PPO activity was positively correlated with the brown index of wholemeal flour and dough, and both were very high in “Timilia” (giving a typical brown color to kernels) compared with both “Russello” and modern varieties [ 54 , 55 ]. Significant differences in phenolic compounds were found between “Timilia” and other old and modern varieties analyzed by Lo Bianco [ 56 ], who suggested these molecules as markers for the traceability of “Timilia”. Although PPO genes located on homeologous chromosome 2 have been extensively studied for browning and discoloration of wheat flour [ 55 , 57 , 58 , 59 , 60 , 61 ], they may also be involved in adaptation mechanisms, like peroxidase and lipoxygenase genes [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ]; they could therefore be involved in conferring unique characteristics to “Timilia”, which is particularly suitable for hot-arid Mediterranean climates [ 28 , 65 ]. This is further corroborated by its late sowing (in the late winter), which forces it to withstand the late spring heat spells and drought in the area during the grain filling stage. This result is also consistent with the fact that “Timilia” showed a higher level of expressions of genes involved in response to attacks by fungi, herbivores, and pathogens, as well as wounds and other abiotic stresses than “Russello” [ 28 ]. All these results suggested that “Timilia” should be explored more carefully as a potential source of favorable alleles to counteract the direct and indirect effects of climate change and that a preservation plan is needed to avoid its genetic contamination. In this context, PPOs could play a key role both in “Timilia“ traceability and in the study of traits related to the adaptation mechanisms of the plant. Divergent loci have also been identified as linked to other qualitative characteristics of the flours, in particular to the biosynthesis of starch and carotenoids concentration in the grain. Again, the divergence in the genes associated with the biosynthesis of carotenoids agreed with previous results by [ 3 , 14 , 66 ], showing a higher content of carotenoids in “Russello” grain than in “Timilia”. Several genes related to starch metabolism seem to differentiate “Russello” from “Timila”. This finding agrees with the work by [ 28 ], who reported the quantitative label-free comparison of the metabolic protein fraction in “Russello”, “Timilia”, and the modern variety “Simeto”. Their results suggest that “Russello” and “Timilia” differ in genes related to starch compositions, such as SUS1 and SUS3 , which also affect grain size and grain yield. In our work, we found divergent SNP loci associated with SUS1 , SUS3, and other key genes controlling grain size and weight; these findings explain the genetic distance between “Russello” and “Timilia”, as evidenced in previous studies [ 14 , 25 , 66 , 67 ]. Indeed, in all these studies, “Timilia” showed a thousand kernel weight (TKW) lower than “Russello” (on average 35–45 g vs. 45–55 g, respectively). Another aspect that affects the grain yield and the physiology of the plant is the role of source and sink mechanisms of nitrogen transport and use. Here we found that several divergent SNP loci were associated with genes involved in nitrogen metabolism and plant adaptations. Finally, due to the use of the durum wheat genome (cv. Svevo) as the reference for the identification of candidate genes responsible for phenotypic differentiation, some genes fall into regions harboring Rht genes. However, the “Russello” and “Timilia” landraces are known to be ancient and tall grains and therefore do not contain the semi-dwarfing Rht gene, as on the contrary observed in Polish wheat by [ 68 ]. Those regions are rich in nitrogen metabolism-related genes and lipoxygenases, which played a key role in the domestication process of tetraploid wheat [ 6 , 55 ]. The combined effect of these genes should explain the genetic basis that differentiates the two Sicilian landraces and deserve further study. 5. Conclusions Landraces and obsolete cultivars are an important reservoir of genes/alleles to be used in durum wheat breeding to counteract the effects of climate change. The recovery and characterization of landraces are the first steps towards promoting and restoring the conservation and sustainable use of agricultural biodiversity, as well as the protection of marginal areas. In this work, large populations of two Sicilian landraces, namely “Russello” and “Timilia”, were analyzed using approximately 5000 high-quality SNP markers with the aim of revealing intra- and inter-populations genetic diversity and identifying divergent loci between genetic groups. Our findings demonstrated a wide variability within and between populations, evidenced by the fact that there are two different types of “Russello” scattered throughout Sicily, which differ in important traits associated with the adaptation and quality of gluten. On the other hand, the accessions of “Timilia”, although cultivated throughout Sicily, showed a great genetic distance from the two Russello groups, maintaining its genetic integrity probably due to its exclusive destination for spring sowing. For this reason, farmers managed these landraces separately, retaining some distinctive characteristics (i.e., polyphenol oxidases, carotenoids, TKW). This work paves the way for a greater exploration of the broad genetic diversity that characterizes Sicilian landraces and points out that intra-population genetic diversity should be taken into account when ‘conservation variety’ are to be registered in National Registers of crops. Supplementary Materials The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/agronomy12061326/s1 . Figure S1: Bar chart showing the number of high-quality SNPs per chromosome. Figure S2: Distribution of identity-by-state (IBS) allele sharing values amongst (A) “Russello” (RC), “Timilia” (TC), and C) “Russello” + “Timilia” (RTC) populations determined by the analysis of 4624 unlinked single nucleotide polymorphisms. Figure S3: Genetic diversity assessment of “Russello” and “Timilia” populations using 4624 high-quality SNP markers. (A–C) Neighbor-joining tree based on the genetic distances for “Russello” and “Timilia” individuals, respectively. (B–D) Multidimensional scaling (MDS) plot representing relationships between the” Russello” and “Timilia” individuals, respectively. Individuals are colored according to different populations. Figure S4: Intra-chromosomal LD decay distance (kb) evaluated for each “Russello” (RC) and “Timilia” (TC) population, and for the whole population (RTC). LD decay was also calculated considering two other collections composed of TC+R1-3-5 and TC+R2-4. Red lines indicate the r2 threshold at 0.20. The intersection point between the decay LD curve and the LD threshold was indicated by “+”. Table S1: Initial of individuals for the “Russello” and “Timilia” populations, duplicated individuals (IBS > 0.99), discarded individuals, and the final number of individuals used in downstream analysis. Table S2: List of pairs of individuals with identity-by-state (IBS) allele-sharing estimates >0.99. Stars indicate the individuals retained. Table S3: Divergent SNP loci detected by pairwise comparisons between the populations R1-3-5, R2-4, and TC using F ST (>0.50). SNP name, physical position on “Svevo” (chromosome and bp), and F ST values were reported. Author Contributions Conceptualization, F.T., P.D.V. and N.D.; methodology, F.T., S.P. and N.D.; formal analysis, F.T., E.D.S., M.M.M. and N.D.; investigation, F.T. and N.D.; genetic resources, P.D.V. and S.S.; data curation, F.T., E.D.S., M.M.M. and N.D.; writing—original draft preparation, F.T.; writing—review and editing, F.T., P.D.V. and N.D.; funding acquisition, F.T. All authors have read and agreed to the published version of the manuscript. Funding This work was partially funded by the Italian Ministry of Agricultural, Food, and Forestry Policies (MIPAAF) project RGV-FAO. Informed Consent Statement Not applicable. Data Availability Statement Not applicable. Conflicts of Interest The authors declare no conflict of interest. References Bozzini, A.; Scarascia-Mugnozza, G.T. Relative frequency of chlorophyll to morphological and sterility mutations induced in durum wheat by radiations and chemicals. Mutat. Res.-Fundam. Mol. Mech. Mutagen. 1970 , 9 , 589–597. 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( A ) Neighbor-joining tree; ( B ) MDS scatterplot based on the identity-by-state (IBS) matrix of the entire collection (RTC). Different colors in the NJ tree and in the MDS scatterplot distinguish the 3 RTC groups. TC (blue), R1-3-5 (red) and R2-4 (green); ( C ) Heatmap of pairwise F ST values. Color scale ranges from yellow ( F ST = 0) to red ( F ST = 1). Figure 3. ( A ) Neighbor-joining tree; ( B ) MDS scatterplot based on the identity-by-state (IBS) matrix of the entire collection (RTC). Different colors in the NJ tree and in the MDS scatterplot distinguish the 3 RTC groups. TC (blue), R1-3-5 (red) and R2-4 (green); ( C ) Heatmap of pairwise F ST values. Color scale ranges from yellow ( F ST = 0) to red ( F ST = 1). Figure 4. ( A ) Distribution of divergent loci ( F ST > 0.50) along the 14 chromosomes of durum wheat. ( B ) Venn diagram showing the number of divergent SNP markers detected in TC vs. R1-3-5, TC vs. R2-4 and R1-3-5 vs. R2-4. Figure 4. ( A ) Distribution of divergent loci ( F ST > 0.50) along the 14 chromosomes of durum wheat. ( B ) Venn diagram showing the number of divergent SNP markers detected in TC vs. R1-3-5, TC vs. R2-4 and R1-3-5 vs. R2-4. Figure 5. Minimum spanning networks using the three groups: TC (blue), R1-3-5 (red), and R2-4 (green). Each circle represents a haplotype; the circle sizes correspond to abundances. Bars indicate the number of mutations between haplotypes. Figure 5. Minimum spanning networks using the three groups: TC (blue), R1-3-5 (red), and R2-4 (green). Each circle represents a haplotype; the circle sizes correspond to abundances. Bars indicate the number of mutations between haplotypes. Table 1. Summary of genetic diversity and nucleotide variation indices calculated for each ”Russello” and “Timilia” populations and for the 3 RTC groups, after the removal of duplicate samples based on IBS values. Na = number of average alleles, I = Shannon’s index, PA = frequency of private alleles, He = Nei’s index. Table 1. Summary of genetic diversity and nucleotide variation indices calculated for each ”Russello” and “Timilia” populations and for the 3 RTC groups, after the removal of duplicate samples based on IBS values. Na = number of average alleles, I = Shannon’s index, PA = frequency of private alleles, He = Nei’s index. Population #Individuals Na PA I He Russello R1 28 2.167 0.064 0.422 0.255 R2 21 1.913 0.002 0.455 0.300 R3 27 2.304 0.187 0.458 0.273 R4 15 1.734 0.012 0.384 0.255 R5 29 2.139 0.066 0.407 0.244 Timilia T3 25 2.202 0.004 0.534 0.342 T5 24 2.313 0.009 0.559 0.355 T7 24 2.601 0.053 0.602 0.355 T8 21 2.179 0.006 0.485 0.304 T9 22 2.557 0.041 0.575 0.340 T11 21 2.350 0.02 0.564 0.352 T12 20 2.228 0.009 0.505 0.315 RT Collection TC 157 2.233 0.301 0.288 0.167 RC 120 2.597 0.665 0.515 0.319 RC1-3-5 84 2.481 0.265 0.419 0.246 RC2-4 36 1.871 0.048 0.396 0.258 Table 2. Major genes detected in the flanking region of divergent SNPs exceeding the significant threshold of F ST > 0.80. SNP name, chromosome, and position on “Svevo” genomes, distance (Mb) between divergent SNP and genes, transcript ID, and pairwise comparison are reported. Table 2. Major genes detected in the flanking region of divergent SNPs exceeding the significant threshold of F ST > 0.80. SNP name, chromosome, and position on “Svevo” genomes, distance (Mb) between divergent SNP and genes, transcript ID, and pairwise comparison are reported. SNP Marker Gene Transcript ID Distance (~Mb) Comparison tplb0025b13_1721 MEI2-4 (OML4) TRITD1Av1G001750 0 R1-3-5 vs. R2-4 - TC vs. R2-4 tplb0025b13_1721; TA001286-0611-w Gamma-gliadin TRITD1Av1G002070 0.50; 0 R1-3-5 vs. R2-4; TC vs. R1-3-5 - TC vs. R2-4 tplb0025b13_1721; Excalibur_c35919_107 glutenin (LMW) TRITD1Av1G002310 0.33; 0.01 R1-3-5 vs. R2-4; TC vs. R1-3-5 - TC vs. R2-4 Excalibur_c77035_156 WCOR15 TRITD1Av1G021590 0.55 R1-3-5 vs. R2-4 IAAV8147 PP2A regulatory subunit TAP46 TRITD1Av1G125250 0.18 TC vs. R1-3-5 RAC875_c6338_2719 TELO2 TRITD1Av1G127160 0.68 TC vs. R1-3-5 RAC875_c30138_595; IACX2941 Gamma-gliadin TRITD1Bv1G001870 0.27; 0.07 TC vs. R1-3-5; TC vs. R2-4 BS00004903_51 Anthocyanin 5-aromatic acyltransferase TRITD1Bv1G004660 0.38 TC vs. R1-3-5 BS00021975_51; CAP8_rep_c7343_88 glutenin (HMW) TRITD1Bv1G177800 0.18; 0 TC vs. R1-3-5: R1-3-5 vs. R2-4 - TC vs. R2-4 wsnp_Ex_c19556_28530231 Ppd-A1 TRITD2Av1G019250 0.27 TC vs. R1-3-5; TC vs. R2-4 wsnp_CAP11_rep_c8768_3788007 FD-GOGAT TRITD2Av1G036960 0 TC vs. R1-3-5 - TC vs. R2-4 wsnp_Ex_c12219_19526749 SUS3 TRITD2Av1G053920 3.9 R1-3-5 vs. R2-4; TC vs. R1-3-5 Kukri_c44442_274 Lpx TRITD2Av1G054540 0.62 R1-3-5 vs. R2-4; TC vs. R1-3-5 wsnp_be471201A_Ta_1_1 Anthocyanin 3’-O-beta-glucosyltransferase TRITD2Av1G252600 1.2 TC vs. R2-4 wsnp_be471201A_Ta_1_1 Anthocyanin 5-aromatic acyltransferase TRITD2Av1G253600 1.12 R1-3-5 vs. R2-4; TC vs. R2-4 RAC875_c110838_165; Ku_c13700_1196 Ppo-A1 TRITD2Av1G261300 0.62 TC vs. R1-3-5; TC vs. R2-4 RAC875_c110838_165; Ku_c13700_1196 Ppo-A2 TRITD2Av1G261390 0.4 TC vs. R1-3-5; TC vs. R2-4 RAC875_c110838_165; Ku_c13700_1196 starch synthase TRITD2Av1G261450 0.14 TC vs. R1-3-5; TC vs. R2-4 RAC875_c35438_474 Beta-amylase TRITD2Bv1G043100 1.2 TC vs. R1-3-5; TC vs. R2-4 BS00011630_51 Ppo-B2 TRITD2Bv1G224170 0.46 TC vs. R1-3-5; TC vs. R2-4 RAC875_c19534_68 9-cis-epoxycarotenoid dioxygenase TRITD3Av1G020620 0.46 R1-3-5 vs. R2-4 BS00024548_51 LEA TRITD3Av1G260240 0 R1-3-5 vs. R2-4 BS00036352_51 Carotenoid cleavage dioxygenase TRITD3Bv1G162510 1.9 TC vs. R2-4 BobWhite_c1196_297 Anthocyanin 3’-O-beta-glucosyltransferase TRITD3Bv1G163770 0 TC vs. R2-4 Jagger_rep_c10288_53 Rht-A1 TRITD4Av1G194130 7.5 TC vs. R2-4 Jagger_rep_c10288_53 NRT1/PTR TRITD4Av1G198820 0.53 TC vs. R2-4 Tdurum_contig82378_264 Rht-B1 TRITD4Bv1G012280 4.5 R1-3-5 vs. R2-4 - TC vs. R2-4 Tdurum_contig82378_264 Lpx1 TRITD4Bv1G010710 7.8 R1-3-5 vs. R2-4 - TC vs. R2-4 Tdurum_contig82378_264 Teosinte branched 1 protein TRITD4Bv1G012050 4.5 R1-3-5 vs. R2-4 - TC vs. R2-4 wsnp_Ex_c6117_10704945 Histone H3 TRITD5Av1G041920 6 TC vs. R1-3-5 wsnp_Ra_c10053_16636851 ASN TRITD5Av1G043240 6 TC vs. R1-3-5 BS00076246_51 Lpx TRITD5Av1G200190 1.7 TC vs. R1-3-5; TC vs. R2-4 GENE-3601_145 Vrn-A1 TRITD5Av1G204680 10 TC vs. R2-4 BS00066456_51 15-cis-zeta-carotene isomerase TRITD5Bv1G013720 5.7 TC vs. R1-3-5; TC vs. R2-4 GENE-3383_710 9-cis-epoxycarotenoid dioxygenase TRITD5Bv1G192230 3.4 R1-3-5 vs. R2-4 wsnp_Ex_c5155_9140608 Lpx TRITD5Bv1G195300 1.7 TC vs. R2-4 Excalibur_c24051_502 TdHMA3-B1 TRITD5Bv1G197370 1 TC vs. R1-3-5 Excalibur_c24051_502 Vrn-B1 TRITD5Bv1G200510 10 TC vs. R2-4 BS00071573_51 Terpene cyclase/mutase TRITD6Av1G000890 0.08 TC vs. R1-3-5; TC vs. R2-4 BS00022660_51 Terpene synthase TRITD6Av1G008120 0.04 TC vs. R2-4 IACX5772 Alpha-gliadin TRITD6Av1G009340 1.6 TC vs. R2-4 IACX203 Rht-14 TRITD6Av1G140910 24 TC vs. R2-4 IACX203 Nitrilase TRITD6Av1G150150 0.17 TC vs. R2-4 BS00065082_51 Nrt TRITD6Av1G196930 0.56 TC vs. R1-3-5 - TC vs. R2-4 CAP7_c7415_267 Nir TRITD6Av1G199660 0 TC vs. R2-4 BS00109708_51 Alpha-gliadin TRITD6Bv1G014640 0.27 TC vs. R1-3-5 GENE-3945_245 Anthocyanin 3’-O-beta-glucosyltransferase TRITD6Bv1G159080 1.2 R1-3-5 vs. R2-4; TC vs. R1-3-5 BS00109912_51; RFL_Contig3621_1157 Terpene cyclase/mutase TRITD7Av1G000490 0.79 R1-3-5 vs. R2-4; TC vs. R2-4 BS00109912_51; RFL_Contig3621_1157 Terpene synthase TRITD7Av1G000650 0.84 R1-3-5 vs. R2-4; TC vs. R2-4 Excalibur_c25891_1402 SUS1 TRITD7Av1G009720 0.75 TC vs. R1-3-5; TC vs. R2-4 RAC875_c63822_185 Anthocyanin 5-aromatic acyltransferase TRITD7Av1G013740 0.94 R1-3-5 vs. R2-4; TC vs. R2-4 BS00062724_51 GBSSI TRITD7Av1G018110 0.82 TC vs. R1-3-5 Excalibur_c96483_102 Beta-carotene isomerase TRITD7Av1G226310 0.24 TC vs. R1-3-5 Jagger_c5275_99 MADAGL17 TRITD7Bv1G002790 0.56 TC vs. R2-4 Tdurum_contig85266_280 GW2-B1 TRITD7Bv1G002890 0 R1-3-5 vs. R2-4 Taranto, F.; Di Serio, E.; Miazzi, M.M.; Pavan, S.; Saia, S.; De Vita, P.; D’Agostino, N. Intra- and Inter-Population Genetic Diversity of “Russello” and “Timilia” Landraces from Sicily: A Proxy towards the Identification of Favorable Alleles in Durum Wheat. Agronomy 2022, 12, 1326. https://doi.org/10.3390/agronomy12061326 AMA Style Taranto F, Di Serio E, Miazzi MM, Pavan S, Saia S, De Vita P, D’Agostino N. Intra- and Inter-Population Genetic Diversity of “Russello” and “Timilia” Landraces from Sicily: A Proxy towards the Identification of Favorable Alleles in Durum Wheat. Agronomy. 2022; 12(6):1326. https://doi.org/10.3390/agronomy12061326 Chicago/Turabian Style Taranto, Francesca, Ermanno Di Serio, Monica Marilena Miazzi, Stefano Pavan, Sergio Saia, Pasquale De Vita, and Nunzio D’Agostino. 2022. "Intra- and Inter-Population Genetic Diversity of “Russello” and “Timilia” Landraces from Sicily: A Proxy towards the Identification of Favorable Alleles in Durum Wheat" Agronomy12, no. 6: 1326. https://doi.org/10.3390/agronomy12061326 Taranto, F.; Di Serio, E.; Miazzi, M.M.; Pavan, S.; Saia, S.; De Vita, P.; D’Agostino, N. Intra- and Inter-Population Genetic Diversity of “Russello” and “Timilia” Landraces from Sicily: A Proxy towards the Identification of Favorable Alleles in Durum Wheat. Agronomy 2022, 12, 1326. https://doi.org/10.3390/agronomy12061326
https://www.mdpi.com/2073-4395/12/6/1326/xml
Browse Digital Heritage | The Ethno-ornithology World Atlas Explore Browse Digital Heritage pandemic Apus apus Cyanistes caeruleus Browse Digital Heritage Browse Digital Heritage Search Reset Sort Search Relevance Date Changed Date Added Newest Oldest Alphabetical Featured Apply Featured filter Featured (1) Apply Featured filter Community Apply People + Birds Around the World filter People + Birds Around the World (1) Apply People + Birds Around the World filter Collection Apply Resources for teaching and learning filter Resources for teaching and learning (1) Apply Resources for teaching and learning filter Bird And Other Animal Species Remove <span class="notranslate"><i>Apus apus</i></span> filter (-) Remove <span class="notranslate"><i>Apus apus</i></span> filter Apus apus Remove <span class="notranslate"><i>Cyanistes caeruleus</i></span> filter (-) Remove <span class="notranslate"><i>Cyanistes caeruleus</i></span> filter Cyanistes caeruleus Apply <span 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Apply Naming filter Naming (1) Apply Naming filter Apply Preferred habitats filter Preferred habitats (1) Apply Preferred habitats filter Keywords Remove pandemic filter (-) Remove pandemic filter pandemic Apply common species filter common species (1) Apply common species filter Apply covid-19 filter covid-19 (1) Apply covid-19 filter Apply Oxford filter Oxford (1) Apply Oxford filter 1 + - roadmap terrain Leaflet | Map data © Google List Grid Learn some Oxford birds while in lockdown Digital Heritage Community People + Birds Around the World Category Educational materials, Europe, Bird song & calls, Preferred habitats, Naming, Names Summary A short movie featuring 31 species local to Oxford with habitat and song to help people learn to recognise the songs they hear Animals Turdus merula (Eurasian Blackbird), Erithacus rubecula (European Robin), Troglodytes troglodytes (Northern Wren), Columba palumbus (Common Woodpigeon), Fringilla coelebs (Common Chaffinch), Parus major (Great Tit), Cyanistes caeruleus (Eurasian Blue Tit), Periparus ater (Coal Tit), Prunella modularis (Dunnock), Cuculus canorus (Common Cuckoo), Pyrrhula pyrrhula (Eurasian Bullfinch), Dendrocopos major (Great Spotted Woodpecker), Picus viridis (Eurasian Green Woodpecker), Carduelis carduelis (European Goldfinch), Sylvia atricapilla (Eurasian Blackcap), Passer domesticus (House Sparrow), Certhia familiaris (Eurasian Treecreeper), Strix aluco (Tawny Owl), Milvus milvus (Red Kite), Buteo buteo (Eurasian Buzzard), Alauda arvensis (Eurasian Skylark), Streptopelia decaocto (Eurasian Collared-dove), Regulus regulus (Goldcrest), Phylloscopus collybita (Common Chiffchaff), Sylvia communis (Common Whitethroat), Sitta europaea (Eurasian Nuthatch), Turdus philomelos (Song Thrush), Delichon urbicum (Northern House Martin), Apus apus (Common Swift), Pica pica (Eurasian Magpie), Garrulus glandarius (Eurasian Jay)
https://ewatlas.net/digital-heritage/water-rail-pic/keywords/pandemic/animals/apus-apus-193109/animals/cyanistes-caeruleus-219068
Adding Science to the Decision to Extubate Children | Anesthesiology | American Society of Anesthesiologists Adding Science to the Decision to Extubate Children David J. Murray, M.D. David J. Murray, M.D. From the Division of Pediatric Anesthesiology, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri. Address correspondence to Dr. Murray: murrayd@wustl.edu Author and Article Information Accepted for publication July 9, 2019. Address correspondence to Dr. Murray: murrayd@wustl.edu Anesthesiology October 2019, Vol. 131, 769–770. https://doi.org/10.1097/ALN.0000000000002921 Topics: child , extubation “[E]xpert judgments are challenging to study [objectively] because most decisions are based on an expert’s ability to integrate their knowledge and experience in a timely manner.” Practitioners develop expertise in deciding when to extubate children through experience. The clinical acumen to make this decision is difficult to learn and is a skill that many consider more art than science. In this issue of Anesthesiology, Templeton et al. report the relationship between a number of clinical signs frequently used by practitioners to make a decision to extubate children and how these signs correlate with “success.” 1One of the most important contributions of the study is that by applying the signs selected for extubation “readiness,” the less experienced practitioner could acquire the expertise in deciding when to extubate more quickly and with a lower frequency of, as this study reports, either the need for a “major” or “minor” airway intervention after extubation. 1A second important finding of Templeton et al.’s study is that children who exhibited more of the selected clinical signs used to guide extubation had a greater likelihood of successful extubation, suggesting the utility of the cues selected by the authors to include in their study design. Finally, the study identified additional signs (elevated end-tidal carbon dioxide) and perioperative factors (upper respiratory infection and midazolam premedication) that, when present, impact extubation success. 1 Similar to the findings in many other clinical studies, there are numerous caveats that need to be considered when interpreting the study results and, more importantly, when applying the approach to clinical practice. The first and foremost is that the findings apply only to those children who were emerging from inhalation anesthesia and judged to be ready for extubaton. The study excluded children for whom the plan was to extubate deep before their emergence from anesthesia. The study also excluded children who received intravenous anesthetic techniques or a dose of Propofol in the period before emergence. The study is observational, and the perioperative anesthetic management was left to the discretion of the anesthesiologist. This led to variation in the use of midazolam premedication and the type, timing, and dose of narcotic administered during the procedure. The study also was limited to children who were less than 7 yr old, and a large proportion of those children were infants less than 1 yr of age (more than 30%). Despite these many study qualifications that could limit the application of the findings, infants and young children most commonly receive primarily volatile anesthesia and in this younger age group the decision to extubate is often based on clinical signs rather than the child’s ability to respond to verbal stimuli. More than 92% of the children met the author’s definition of extubation success. These children required brief airway support (continuous positive airway pressure less than 30 s) and maintained an oxygen saturation greater than 92%. In a study that directed practitioner’s attention to clinical signs of emergence, this extubation success rate might be better than that observed in practice settings when practitioners might not assess clinical criteria as thoroughly before extubation or be as attentive to apnea, breath-holding, and desaturation as this study required after extubation. The finding that 44 of the 600 children (7%) required an experienced practitioner to recognize and manage either apnea or breath-holding for an extended time period after extubation is not surprising. The study confirms that skill in airway management and vigilance are required in managing emergence. 2The results reaffirm the need for advanced airway training for recovery room personnel, if extubation is to be deferred to postanesthesia care unit settings. 3 The study design included nine signs that were evaluated before extubation. The clinical signs selected in the study are time honored, and pediatric anesthesia practitioners around the world use similar signs or variants of these signs to determine extubation readiness. In general, the results indicate that the more signs that were present, the greater likelihood of success. Some signs often used in older children and adults, such as eye opening and purposeful movement, although predictive of success, were often not present at the time the decision was made to extubate. The relationship between many of the central nervous system events surrounding recovery from anesthesia, such as movement, purposeful movement, and eye opening, are being investigated using a combination of brain function monitoring, neuroimaging, and neural network research. 4As this research continues to provide additional insight about the return of consciousness after anesthesia and the relationship of these clinical signs to consciousness, the potential exists to add considerably more scientific rigor to this decision-making process in the future. 4 References 1. Templeton TW , Goenaga-Díaz EJ , Downard MG , McLouth CJ , Smith TE , Templeton LB , Pecorella SH , Hammon DE , O’Brien JJ , , Lawrence AE , Tennant PR , Ririe DG : . Assessment of common criteria for awake extubation in infants and young children. A nesthesiology . 2019 ; 131 : 801 – 8 , Chandrakantan A : . Nursing initiated tracheal extubation in PACU, the risk of delegating critical anesthesiology tasks in the interest of speed. Paediatr Anaesth . 2017 ; 27 : 1165 – 6 3. Kako H , Corridore M Image: S. Suresh, Lurie Children’s Hospital. Image: S. Suresh, Lurie Children’s Hospital.
https://pubs.asahq.org/anesthesiology/article-split/131/4/769/914/Adding-Science-to-the-Decision-to-Extubate
Ethnic/Traditional Snacks (Savory Snacks) Market in Mexico - Outlook to 2024; Market Size, Growth and Forecast Analytics (updated with COVID-19 Impact) Ethnic/Traditional Snacks (Savory Snacks) Market in Mexico - Outlook to 2024; Market Size, Growth and Forecast Analytics (updated with COVID-19 Impact) Ethnic/Traditional Snacks (Savory Snacks) - Market research report and industry analysis - 13760529 Ethnic/Traditional Snacks (Savory Snacks) Market in Mexico - Outlook to 2024; Market Size, Growth and Forecast Analytics (updated with COVID-19 Impact) Best Price Guarantee Price from $500 Length 19 Pages Publisher GlobalData Published Date October, 2020 SKU GBDT16397244 Table of Contents Description Ethnic/Traditional Snacks (Savory Snacks) Market in Mexico - Outlook to 2024; Market Size, Growth and Forecast Analytics (updated with COVID-19 Impact) SummaryEthnic/Traditional Snacks (Savory Snacks) Market in Mexico - Outlook to 2024; Market Size, Growth and Forecast Analytics (updated with COVID-19 Impact) is a broad level market review of Ethnic/Traditional Snacks market in Mexico.Ethnic/Traditional Snacks - Snacks from non-western cultures, usually Asian specialties e.g. Bombay mixEthnic/Traditional Snacks market in Mexico registered a positive compound annual growth rate (CAGR) of 5.02% during the period 2014 to 2019 with a sales value of MXN 1,701.59 Million in 2019, an increase of 4.52% over 2018. The market achieved its strongest performance in 2017, when it grew by 7.64% over its previous year and its weakest performance in 2018, when it increased by 4.02% over 2017.The research handbook provides up-to-date market size data for period 2014-2019 and illustrative forecast to 2024 premised on Covid-19 hit, covering key market aspects like Sales Value and Volume for Ethnic/Traditional Snacks and its variants .Furthermore, the research handbook details overall market sales by Distribution Channel (Dollar Stores, Variety Store & General Merchandise Retailers, Cash & Carries and Warehouse Clubs, Convenience Stores & Gas Stations, Department Stores, Drug Stores & Pharmacies, Chemists/Pharmacies, Parapharmacies/Drugstores, eRetailers, Food & Drinks Specialists, Health & Beauty Stores, Hypermarkets & Supermarkets, Direct Sellers, Others, On Trade, Vending Machines, Other Specialist Retailers, Tobacco Specialists) where ever applicable.Due to on going large scale uncertainties in the market due to COVID-19 pandemic, the research handbook acts as an essential tool for companies active or planning to venture in to Mexico's Ethnic/Traditional Snacks (Savory Snacks) market. The comprehensive statistics within the research handbook provides insight into the operating environment of the market and also ensures right business decision making based on historical trends and industry model based forecasting.Sales Values in the handbook are depicted in USD ($) and local currency of country and Volumes are represented in M Kilograms. *Note:Certain content / sections in the research handbook may be removed or altered based on the availability and relevance of data. Scope Overall Ethnic/Traditional Snacks (Savory Snacks) market value and volume analytics with growth analysis from 2014 to 2024. Distribution channel sales analytics from 2016-2019. Reasons to Buy Get access to authoritative and granular data on the Ethnic/Traditional Snacks (Savory Snacks) market and fill in the gaps in understanding of trends and the components of change behind them. Enhance your understanding of the market to update your strategic and tactical plans based on volume and value changes and distribution trends. Analyze the components of change in the market by looking at historic and future growth patterns. Use the data to understand future patterns of the market trends from winners and losers to category dynamics and thereby quickly and easily identify the key areas in which you want to compete in the future. 1 Ethnic/Traditional Snacks Market Overview 2 Mexico Ethnic/Traditional Snacks Market Analytics, 2014-24 2.1 Ethnic/Traditional Snacks Value Analytics, 2014-24 2.1.1 Ethnic/Traditional Snacks Market by Value, 2014-24 Table 5: Mexico Ethnic/Traditional Snacks Market Value by Brands (USD m), 2016-19 Table 6: Mexico Ethnic/Traditional Snacks Market Volume by Brands (Kg m), 2016-19 Table 7: Mexico Ethnic/Traditional Snacks Market Value by Distribution Channel (MXN m), 2016-19 Table 8: Mexico Ethnic/Traditional Snacks Market Value by Distribution Channel (USD m), 2016-19 Table 9: Category Definitions - Ethnic/Traditional Snacks Market Table 10: Distribution Channel Definitions Ethnic/Traditional Snacks Market Table 11: Volume Units for Ethnic/Traditional Snacks Market Table 12: Mexico Exchange Rate MXN - USD (Annual Average), 2014 - 2019 Table 13: Mexico Exchange Rate MXN - USD (Annual Average), 2020 - 2024 Forecast List of Figures Figure 1: Mexico Ethnic/Traditional Snacks Market Value (MXN m) and Growth (Y-o-Y), 2014-24 Figure 2: Mexico Ethnic/Traditional Snacks Market Volume (Kg m) and Growth (Y-o-Y), 2014-24 Figure 3: Mexico Ethnic/Traditional Snacks Market Value by Brands (MXN m), 2016-19 Figure 4: Mexico Ethnic/Traditional Snacks Market Volume by Brands (kgm), 2016-19 Figure 5: Mexico Ethnic/Traditional Snacks Market Value by Distribution Channel (MXN m), 2016-19 $500
https://www.marketresearch.com/GlobalData-v3648/Ethnic-Traditional-Snacks-Savory-Mexico-13760529/
The Oxford Oratory A sanctuary in the midst of the city The Oxford Oratory is a vibrant centre of Catholic life. Our church is open every day: join us for Mass, pop in for some quiet prayer, or come and discover more at one of our groups. Our historic church of St Aloysius has been a key feature in the lives of the city’s Catholics for 150 years, attracting people of all ages and from every walk of life. We use beauty to raise hearts and minds to God, faithful to the traditions of St Philip Neri and St John Henry Newman. Heart of Jesus, all-holy! Fountain of all blessings, I adore thee, I love thee, and with a lively sorrow for my sins, I offer thee this poor heart of mine. Make me humble, patient, pure, and wholly obedient to thy will. Good Jesus, grant that I may live in thee and for thee. Protect me in the midst of danger; comfort me in my afflictions; give me health of body, assistance in my temporal needs, thy blessing on all that I do, and the grace of a holy death. Amen. A photo from Sunday’s Solemn Mass for Corpus Christi. #oxfordoratory June Music Sunday 4 JuneSolemn Mass 11:00The Most Holy TrinityKyrie MundyMissa Euge bone TyeLibera nos SheppardHonor, virtus et potestas Tallis Sunday 11 JuneSolemn Mass 11:00Corpus ChristiMissa Pange lingua JosquinLauda Sion PalestrinaOculi omnium Byrd Friday 16 JuneSolemn Mass 18:00The Most Sacred Heart of JesusMissa Dormendo un giorno GuerreroImproperium PalestrinaSancte Deus Tallis Sunday 18 JuneSolemn Mass 11:0011th Sunday of the YearMissa Brevis in F Op.117 RheinbergerBenedicam Dominum VictoriaSalve Regina Poulenc Wednesday 21 JuneSolemn Mass 18:00St Aloysius GonzagaMissa O quam gloriosum VictoriaJustitiae Domini A ScarlattiO bone Jesu Anchieta Sunday 25 JuneSolemn Mass 11:0012th Sunday of the YearMissa Repleatur os meum PalestrinaPerfice gressus meos LassusHomo quidam fecit coenam magnam Mouton Thursday 29 JuneSolemn Mass 18:00St Peter and St PaulMissa Petre ego pro te rogavi LoboPetre ego pro te rogavi GuerreroJanitor caeli Ortiz The Sacred Heart Love is a funny thing. Materialists will tell us that it is purely the result of a series of electro-chemical responses in the brain, and yet others will tell us that it is the result of fate, the conspiracy of the alignment of the planets or the times we find ourselves in. The heart has long been understood as the centre of a person, a place of knowledge as much as will. It makes us do unreasonable things like acts of unwarranted kindness and altruism and by the edge of its blade we can be hurt in ways that we just can’t speak about. And yet none of these express what love is in itself — only God does that. On Friday we venerate the Heart of our Lord as the symbol of his human love in which God’s divine love is revealed to us. In most of the prayers to or the meditations on the Sacred Heart, even those very ancient prayers, the woundedness of our Lord’s heart comes to the fore. That heart pierced with a lance and bruised with outrages and blasphemies is a stark and realistic image of the extent to which Christ loves us. Christ, who is the image of the unseen God, the Icon of the Father, shows us precisely what God’s love for us looks like. And it looks like a heart pierced and bruised on account of our sins, yet burning with ardent love for you and for me. This divine love is not for softies. The time when we celebrate this feast is very fitting. We have come to the end of the Church’s celebration of the mysteries of our redemption: the Passion, the Cross, the Resurrection, the Ascension, Pentecost, the Feast of the Blessed Trinity and Corpus Christi. But today we commemorate the divine-human love which motivated them all. In adoring the Sacred Heart, we adore the totality of Christ’s saving work — it represents the way in which God holds nothing back from us. And in order to share his divine life with us, he reaches down into the very depths of our life, even — and especially — where it is painful, difficult to speak of, hidden. By taking it all and joining it to himself, he scoops us up, he enables us to become like him. By sharing our life, and by sharing our pains, he heals us, he sanctifies us, and he strengthens us. It is also true that his heart welcomes us precisely so that we might become like it. The whole thrust of our Christian life is that we might be conformed to our Saviour, that we might resemble him, and in this sense, in the life of faith, we should ask ourselves continually whether our heart resembles his. His Sacred Heart is both the example and the cause of our becoming like him. His love is attractive. The more we consider the love with which Jesus acted, and spoke and gave of himself for us, the more we can begin, by his grace, to imitate him — it is truly the school of Christian perfection. And we begin in that school by prayer. When St John Henry Newman, our Cardinal, chose his motto, he looked to St Francis de Sales’ Treatise on the Love of God. The phrase he chose and paraphrased, Cor ad Cor loquiturrepresents for us the central mystery of the prayer that can begin to transform us. St Francis de Sales wrote: Truly the chief exercise in mystical theology is to speak to God and to hear God speak in the bottom of the heart; and because this discourse passes in most secret aspirations and inspirations, we term it a silent conversing. Eyes speak to eyes, and heart to heart, and none understand what passes save those who speak. We may be no great shakes at the spiritual life, or prayer, or we may feel that excelling in virtue is beyond us, but if we can in the simplest of ways open our poor heart to his Sacred Heart, and speak to him as to a friend, if we can entrust our lives to him and ask him devoutly and sincerely to shape us after the model of his Heart, then our Christian life will be all the more graced. The Corpus Christi procession concluded with Benediction at the University Chaplaincy. #oxfordoratory The procession finished at the University’s Catholic Chaplaincy. #oxfordoratory The numbers caught the attention of the local media: https://www.oxfordmail.co.uk/news/23582016.oxfords-catholic-congregations-take-part-corpus-christi-procession/ #oxfordoratory Children scattered flower petals before the Blessed Sacrament all the way. #oxfordoratory Our route now passes through the city in a straight line, taking us directly through the busiest shopping areas. #oxfordoratory The canopy was carried by members of the University of Oxford wearing their academic dress. #oxfordoratory Fr Robert Ombres OP preached a sermon. #oxfordoratory We paused at Blackfriars. #oxfordoratory We were joined by local clergy and religious orders as we processed through the streets to the Dominican Priory at Blackfriars. #oxfordoratory The processions sets off… #oxfordoratory We had record numbers for the procession this year. There wasn’t space in church for everyone at the beginning! There were more people outside too. #oxfordoratory The beginning of our Corpus Christi procession last Sunday.#oxfordoratory The Oratory Prayer Book is now shipping internationally! We’ve made it even easier to buy the Oratory Prayer Book from anywhere in the world. And we’ve made it easier to order multiple copies too — in the UK and worldwide. Order your copy here:https://tinyurl.com/opb-buy If you have one, we’d love to hear what you think about it. Let us know in the comments, or tag a photo of your prayer book in the wild with #oratoryprayerbook Thanks to @acatholicinoxford for the photo. #oxfordoratory Worship What does it actually mean to worship God? In the New Testament, the word we most often translate as ‘worship’ doesn’t mean to reverence another in some abstract sense. It always involves some kind of bodily action. When we think about the magi visiting the Holy Family, we sometimes convey this motion by describing them — after they fall to their knees — as ‘doing homage’. But it’s actually that same word here we might translate elsewhere as ‘worship’. It’s just that we recognise the need to describe the bodily sign of their submission and adoration of the new born King with something that sounds a bit more physical. The word we usually translate as ‘worship’ ( proskuneo) comes literally from a root meaning ‘to make yourself like a dog before the other person’. It originally meant prostrating yourself on the floor to show your humble submission before another. By the time of the New Testament, people wouldn’t necessarily have had the root of this word in mind whenever they used it,* but the word still carries with it the idea of doing something with your body to express your worship. The feast of Corpus Christi is all about this kind of bodily worship. It’s tied to the fact that we are not pure spirits, but that we are human beings, body and soul. To worship God is not just a spiritual act. The right worship of God does not consist in simply having the right kinds of thoughts towards him. But the worship of God involves the humble submission of our entire human being, body and soul, before the God who is greater than all of us. And ever since the Incarnation, we do this not just before an abstract spirit. Because, from the moment of the Incarnation, God really does have a human body, that we can worship, that we fall down on our knees before, like the magi and the Canaanite woman, and so many others in the Gospel who kneel down and worship Christ. When we worship God, we kneel before God who is present in the flesh, under the appearances of bread and wine, in our churches all over the world. Corpus Christi is a joyful celebration of Christ’s presence among us, and it gives us an opportunity to think about how we respond to that gift. All this talk of kneeling and worship might not sound so joyful, but one of the great paradoxes of Christianity is that we find our greatest freedom in the humble service of God. Our greatest joy really should be found in finding ways to express this loving worship. So at least once a year, it is no bad thing to think about how we express with our own bodies that worship of God’s body, and what ways we can find to worship him even more perfectly. This Sunday, we will carry Christ’s Body through the streets of our city. We have a chance to demonstrate to the world our love, our joyful service, our worship of him, through our presence. The procession leaves our church at 2:30pm. Make sure you are there. But we should also think about the more ordinary things, like making sure we show that worship whenever we are in his presence. We should show through our behaviour in church that we believe him to be there: by genuflecting before him in the tabernacle of the church, and by keeping the church quiet and prayerful. We show our worship above all by kneeling down before him — like all those people in the Gospel — for the moment of Holy Communion. And we allow the priest to place the Host on our tongues, so that we don’t handle unnecessarily what is holy and precious, and no particles of Our Lord’s Body are ever dropped or lost through carelessness. We continue that worship in our prayers of thanksgiving after Communion and once the Mass has ended. We certainly never leave church during Communion. And we might think of ways of extending the time we spend with Christ present in the Blessed Sacrament: by attending Mass during the week sometimes, or visiting him during the times each week when his Body is exposed solemnly on the altar for Adoration, or even just by visiting an empty church, where he is waiting for us to show him our worship. Our Lord is hidden there, waiting for us to come and visit him, and make our request to him. See how good he is! He is there in the Sacrament of his love, sighing and interceding incessantly with his Father for sinners. To what outrages does he not expose himself, that he may remain in the midst of us! He is there to console us; and therefore we ought often to visit him. How pleasing to him is the short quarter of an hour that we steal from our occupations, from something of no use, to come and pray to him, to visit him, to console him for all the outrages he receives! When he sees pure souls coming eagerly to him, he smiles upon them. They come with that simplicity which pleases him so much, to ask his pardon for all sinners, for the outrages of so many ungrateful men. What happiness do we not feel in the presence of God, when we find ourselves alone at his feet before the holy tabernacles! ‘Come, my soul, redouble thy fervour; thou art alone adoring thy God. His eyes rest upon thee alone.’ — St John Mary Vianney * One exception is that I do think Christ had this root meaning in mind when he spoke to the Canaanite woman in Matthew 15:21–28. He wasn’t randomly insulting her by comparing her to a dog, but drawing attention to the fact that she was making herself like a dog before him — i.e. worshipping him — because she recognised him to be God. In other words, he was acknowledging her worship as proof of her faith and humility. These reflections are sent out each Wednesday to all those on our mailing list. Click here to sign up to our mailing list , and receive our Sunday E-newsletter and these reflections straight to your inbox. Monday 5 June 2023 On Saturday, Fr Rupert led Men’s Oratory on a walking pilgrimage to Islip, birthplace of St Edward the Confessor. #oxfordoratory Thursday 1 June 2023 Congratulations to Elizabeth who was received into the Church yesterday evening on the Feast of the Visitation. #oxfordoratory The Oratory 25 Woodstock Road Oxford OX2 6HA Getting here Privacy Policy © 2023 Oxford Oratory. All rights reserved. The Oxford Oratory of St Philip Neri is a Registered Charity number 1018455
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Antivaxers are collecting stories of "vaccine injury" to send to Donald Trump to change federal vaccine policy | ScienceBlogs I've written quite a bit about how our soon-to-be President Donald Trump has consistently expressed antivaccine views over the years, such as his oft-stated (on Twitter and elsewhere) beliefs that it's a " monster" shot that causes autism and infants get " too many" vaccines " too soon." I've heard Trump supporters who are pro-vaccine pooh-pooh these statements and claim that Trump won't be doing anything about vaccine policy because it's not a priority, an observation I counter by pointing out that Trump met with two of the biggest antivaccine " icons" there are: Antivaxers are collecting stories of "vaccine injury" to send to Donald Trump to change federal vaccine policy I've written quite a bit about how our soon-to-be President Donald Trump has consistently expressed antivaccine views over the years, such as his oft-stated (on Twitter and elsewhere) beliefs that it's a "monster" shot that causes autism and infants get "too many" vaccines "too soon." I've heard Trump supporters who are pro-vaccine pooh-pooh these statements and claim that Trump won't be doing anything about vaccine policy because it's not a priority, an observation I counter by pointing out that Trump met with two of the biggest antivaccine "icons" there are:Andrew Wakefieldand, just last week,Robert F. Kennedy, Jr. RFK Jr. even claimed that Trump asked him to chair a vaccine safety commission, although the Trump team later said that no decision had been made and that the commission would be about autism. Not surprisingly, Ididn't find that reassuring, given that RFK Jr. has no qualifications to chair an autism commission other than his antivaccine views. Not surprisingly, antivaccine ideologues are ecstatic, with the cranks at Age of Autism practicallybeside themselves with gleeand our old friend Lawrence Solomon (whom we've met before)celebrating the meeting with RFK Jr.: In the September debate and on numerous earlier occasions, Trump has referred to his personal experiences with those he’s known. “I’ve seen people where they have a perfectly healthy child, and they go for the vaccinations, and a month later the child is no longer healthy,” he told Fox News in 2012. “It happened to somebody that worked for me recently. I mean, they had this beautiful child, not a problem in the world. And all of a sudden, they go in, they get this monster (sized) shot. You ever see the size of it? It’s like they’re pumping in — you know, it’s terrible, the amount. And they pump this into this little body. And then all of the sudden, the child is different a month later.” Others very important to Trump — his voters — also help explain Trump’s enthusiasm for a commission into vaccine safety. According to an Economist/YouGov poll taken in December, 31 per cent of Trump voters believe that vaccines can cause autism and only 21 per cent reject that view outright. Other voters doubtless worried about vaccines for reasons other than autism. Many of those vaccine-issue voters would have been highly motivated, since the health of their children was at stake. Trump believes his presidency places him at the head of an historic movement, “a beautiful movement. We are going to make America safe and great again.” Making America safe doesn’t just involve building a wall to keep out criminals and terrorists, he believes. To Trump, it also includes making sure that there’s safety in America’s vaccines. I noted how, shortly after the election, antivaccinationists were practicallysalivating at the prospect of what Donald Trump might dowith respect to federal vaccine policy. I now note that they are now doing their best to get their message to what they see as a sympathetic President-Elect. I first learned of this the other day while seeing responses to the not-so-Thinking Moms' Revolution (TMR) on Twitter. (TMR, of course, has blocked me.) For example: The#Vaxxedteam is asking for your vaccine injury stories, they will deliver them to PEOTUS soon! Do it today!...https://t.co/vv2qPLs7D8 — thinkingmoms (@thinkingmomsrev)January 12, 2017 And a reminder just yesterday: Have you turned in your vaccine story for PEOTUS?#vaxxedhttps://t.co/P9KLwYPNAB — thinkingmoms (@thinkingmomsrev)January 16, 2017 And who is behind this effort? Whom do you think? That's right, it's the team behind theantivaccine propaganda film VAXXED, which wasproduced by Del Bigtree and directed by—who else?—Andrew Wakefield: There's a link to theVAXXED story submission form, which looks like this: The video is basically Polly Tommey telling VAXXED viewers and believers that vaccines cause autism exactly how to tell Donald Trump their child's story, using her own child's anecdote as a basis, stating that her son was "injured by the MMR vaccine at 13 months" and how she "trusted that vaccines are safe." She's also asking for stories from around the world. Basically she tells the audience to tell about their "beautiful child" before vaccines and what vaccines did to him or her. In other words, she's trying to make the stories as similar as possible, and, make no mistake, many of these stories do sound a lot a like because, at their source, they involve confusing correlation with causation and using the post hoc ergo propter hocfallacy. I also note that this video is form yesterday, and Tommey is claiming that "something" will happen with these stories in 48 hours. She also says that there are other organizations working together to gather these stories and send them to President-Elect Trump. As Polly Tommey puts it at one point, "I want to hear about babies who died" and everything. One odd thing I noted about this whole thing is how coy, how seemingly mysterious about what, exactly, is going to be done with these letters. AT some points, they So basically, antivaccine activists, led by Polly Tommey, who also co-produced VAXXED, are collecting stories of "vaccine injury." One could say that the movie VAXXED consists, to a large degree, of stories of "vaccine-induced" autism, and the VAXXED team has been busy collecting such stories and posting videos to itswebsite, grouped by state. For instance,here is Michigan, which as of last night included six videos. Not surprisingly,California has many more. So far, theVAXXED team claimsit's received over 650 e-mails from people who have submitted their stories. Given the coyness of the appeal, it's not clear to me what Tommey and company are planning to do with all these stories, other than send them to President-Elect Trump. If that's all they were planning on doing, why all the mystery? I rather suspect we're about to see some sort of publicity stunt. Advocates of science need to be on guard this week and throughout the next four years. I get the feeling that stunts like this and antivaccine activities like the meeting with RFK Jr. will be a regular occurrence. Tags Antivaccine nonsense autism complementary and alternative medicine medicine Politics Pseudoscience Quackery Skepticism/Critical Thinking andrew wakefield antivaccine Autism Speaks Donald Trump Polly Tommey Robert F. Kennedy Jr. vaccine Vaxxed complementary and alternative medicine medicine Politics I have noticed before that for this group of people, vaccine injury is a synonym for autism. There's no room for uncertainty or debate. Autism is vaccine injury, vaccine injury is autism (and anything else they can think of). I have no idea how to even begin challenging this: it's a religious conviction and by questioning it you are denying their suffering. AVers have been ramping up their publicity stunts this last week already, between the "Vaccines Revealed docu-series" (where apparently the editors think everyone has two hours a night x 9 nights in a row to watch the usual crop of AVers drone on and on) to those AVers "The Drs. Wolfson" with their "Wide Awake" fakeumentary, which is rife with errors, lies and stupidity. OT and almost off-topic: Frankly a straight advertisement. We need family physicians in various parts of Canada especially in rural and semi-rural areas. Oh, we have a single-payer insurance system. Co-pay is not a word here. The problem in many instances is not establishing a practice as it is beating off off the patients as they storm the doors. How about stories like mine? Three kids, all fully vaccinated. Nothing happened. So...what could actually happen with this kind of thing? Can the president really influence the vaccine schedule? Don't there have to be actual scientists in charge of this stuff, or am I being naive? According to an Economist/YouGov poll taken in December, 31 per cent of Trump voters believe that vaccines can cause autism and only 21 per cent reject that view outright. Oh, look, somebody's playing mix and match with the "probably" and "definitely" categories while omitting the actual survey item. Autism is vaccine injury, vaccine injury is autism Can you say cherry picking, boys and girls? I knew you could. Sadly, there are instances (however rare) of vaccine injury. These injuries are most definitely NOT autism. And remember that the whole thing goes back to a paper that was actually found to be fraudulent. There never was a link between vaccines and autism. it’s a religious conviction And here's where it gets worse: there is established legal precedent in the US (Hobby Lobby v. Burwell) that "sincerely held" religious beliefs must be taken into account, no matter if they are not based in reality. The precedent case involved a privately held company that did not wish to provide coverage for contraceptives in the policies offered to its employees because of the company's owners' "religious beliefs". IANAL, but I don't see how TMR's position is any more legally ridiculous than Hobby Lobby's was. TMR can point to an actual (albeit retracted) refereed journal article in support of their position. Narad@5: It's even worse than that. They are attempting an argumentum ad populam, and are botching it. They don't tell us anything about the opinions of Clinton's voters (let alone Johnson's or Stein's), and Clinton got more votes than Trump. Even among Trump voters, 31 + 21 = 52. Where are the other 48%? jrkrideau: how does Canada feel about nurse practitioners? Because I swear . . . . I'm really feeling tempted. I lived in North Dakota for two years, and visited Saskatchewan Province many times . . . in winter. So I have an idea what it's like there. And I swear, it's sounding better and better. Orac writes, Advocates of science need to be on guard this week and throughout the next four years. MJD says, https://www.abebooks.com/Allergies-Autism-Michael-Dochniak-Denise-Dunn/… In the book, I wrote a science based mechanism-of-action on how a potential contaminant in vaccines may have caused my beautiful son's regressive autism. Here's my dilemma, if I submit the books vaccine-injury story to Polly Tommey, et al., will I need to get permission from the publisher to avoid copy right infringement? Please advise... Just wanted to congratulate Orac on making the Health Deranger's top ten list of feared health and science advocates (at #4). He's in mostly good company along with promoters of sanity on the biotech front (Kevin Folta and Jon Entine). Nothing really new in the anti-Orac drool, except maybe for the speculation that his patients don't really have cancer at all. Rest assured droogies, real live breast cancer patients do get referred to his cancer center (don't ask me how I know). It is rather humbling to have been included with luminaries such as Bill Nye, Neil deGrasse Tyson, Kevin Folta, and Bill Gates. It is, however, rather telling how Adams thinks we're all equivalent to the evil Dr. Farid Fata, who bilked Medicare and Medicaid for millions of dollars by administering chemotherapy to cancer patients who didn't need it and, in some cases, to patients who didn't have cancer at all. @Panacea Vancouver, BC is much milder and very beautiful as well--not to detract from the beauty of The Prairies! I know of a number of nurses and NP’s who have quite easily been accepted to Canada. Alas, I have no such skills and am old to boot, so I’m going to have to settle for a border town. Stories allow hyperbole and histrionics hidden in research. @ Dangerous Bacon: I am - and will always be - your 'droogie" Assuming this is accurate (http://www.bbc.com/news/science-environment-38640413), and I generally trust the BBC. It seems to me that if someone with in-depth knowledge about vaccine safety and side-effects were to write something that explained the reality of the situation in simple understandable terms, around a grade 6-8 level would be appropriate, with links and synopsis of the backing studies, there is a real chance to change Trump's mind. I realize that climate-change and vaccine safety are different beasts, but seems to me that you or you and your compatriots at the super-secret other site would be perfect for the job. There is also a number of regular posters on here who would be good collaborators. Then again, it is much easier to complain about the problem, vice attempting to fix it. I refuse to believe that he is too stupid to be educated. He is definitely has a motivated view-point, but any business man who refused to change his mind would be dirt poor, ex-business man. @8 Panacea:In Ontario Nurse Practitioners can be your primary health-care provider. I don't know what other provinces have accredited them in this manner however. Since they are less expensive then doctors, I imagine that most provinces have or will accredit them as primary care providers. One thing people can do in response, if they're looking for a positive action, is submit their story of why they support vaccines through the form created by Voices for Vaccines and Every Child by Two, who can then share that information with state and national legislators. Here is the link to do that: https://goo.gl/forms/anLDzJYTaXMXpRIH2 Here is the Facebook prompt:https://www.facebook.com/VoicesForVaccines/posts/1190551414398131 @Panacea: I'd be wary of moving to Alberta, which is basically the Canadian equivalent of Texas (Stephen Harper's riding is/was in the Calgary area). But I can confirm that coastal BC is much milder than other places in Canada, and even southeastern BC isn't too bad--there is a small wine industry in the Okanagan Valley. Parts of Atlantic Canada are also relatively mild, although they can have stormy winters. Lots of beautiful countryside in Quebec, although you would need to have some knowledge of French to work there or in parts of New Brunswick. I have made several extended visits to Fairbanks in winter, so I could probably handle the winters in most of Canada--maybe not parts of Nunavut, the Northwest Territories, or the Hudson Bay watershed, but most of the rest would be within my experience. Alas, I also don't have any such skills, but my current abode is about a five hour drive from Montreal, and my mother is about three hours from Vancouver. Perfect - remember that this is the guy who repeats fake news stories on live TV and when it's pointed out that they've already been debunked just shrugs and says, "Am I going to check out every story?" I can't even wrap my head around that degree of indifference to veracity. Trump and anti-vaxxers are a match made in heaven the other place. @jrkrideau - I'm interested in your inside opinion of the Canadian health care system, since there's a lot of debate in the U.S. over whether we should adopt something like it. For example, I can already hear the anti-gov't healthcare people taking your comment about needing more doctors as evidence that a single-payer system will drive people out of medicine because they won't get paid enough. Is that what's happening? @Sarah: I can't speak to the Canadian situation, but the shortage of qualified medical practitioners in rural and semi-rural areas is also a thing in the US. If anything, it's probably worse here, because in addition to the reduced cultural opportunities of living in the boonies, there is the not-so-small problem that these days, it's difficult to repay US student loans on the salary of a simple country doctor. The Supreme Court made it worse when they ruled that the Medicaid expansion part of PPACA was merely optional--in states that chose not to expand Medicaid, many rural hospitals that needed those subsidies (which were intended to replace subsidies that were repealed in passing PPACA) were forced to close. I have heard anecdotally of underserved towns in the US offering to pay the student loans of any doctor who agreed to settle there for a minimum amount of time (even before PPACA). I have no idea how widespread such programs are, or even if there are any currently in existence. I have heard anecdotally of underserved towns in the US offering to pay the student loans of any doctor who agreed to settle there for a minimum amount of time (even before PPACA). Indeed, this is the premise of Northern Exposure, pretty much my favorite TV show of all time. Well he's not going to vaccines or GMOs, these issues being "obvious" where it's " fair to criticize people for denying compounding evidence." Nope, the conclusion is an appeal for tolerance of climate-change denialists: Accepting major claims like global warming should require a lot of time and mental work to sift through the evidence. And in the event that we don’t have a clear answer to a question, we should be more open to the idea of refusing to have an opinion. OK, here's the admittedly somewhat loose connection to Mikey's Ass Hat list. Since I thought it odd indeed that Gabelhoff put GMO critics in the 'obviously fair to criticize' category, but not climate change deniers, I asked my 'who is this guy', and Googled his name. On the first page of hits: "Robert Gebelhoff Archives | Genetic Literacy Project". So he's 'buddies' with Jon Entine. Not remembering that much about Entine, I Googled again. My main discoveries: Anyway, it seems Entine has some actual shill cred, and gets some significant financial support from Big Oil. Whether that fully explains Gabelhoff singling out climate change denials for admittance into the circle of commendable scepticism or not, it's an interesting coincidence if nothing else.
https://scienceblogs.com/comment/1350689
B727 flight crew descends below assigned altitude while looking for traffic indicated on TCASII. - NASA ASRS B727 flight crew descends below assigned altitude while looking for traffic indicated on TCASII. B727 flight crew descends below assigned altitude while looking for traffic indicated on TCASII. <table><tbody><tr><td colspan=2> Attributes</td></tr><tr><td> ACN</td><td> 332179</td></tr><tr><td colspan=2> Time</td></tr><tr><td> Date</td><td> 199603</td></tr><tr><td> Day</td><td> Fri</td></tr><tr><td> Local Time Of Day</td><td> 1201 To 1800</td></tr><tr><td colspan=2> Place</td></tr><tr><td> Locale Reference</td><td> atc facility : las</td></tr><tr><td> State Reference</td><td> NV</td></tr><tr><td> Altitude</td><td> msl bound lower : 23200msl bound upper : 24000</td></tr><tr><td colspan=2> Environment</td></tr><tr><td> Flight Conditions</td><td> VMC</td></tr><tr><td> Light</td><td> Daylight</td></tr><tr><td colspan=2> Aircraft 1</td></tr><tr><td> Controlling Facilities</td><td> artcc : zlatower : mia</td></tr><tr><td> Operator</td><td> common carrier : air carrier</td></tr><tr><td> Make Model Name</td><td> B727 Undifferentiated or Other Model</td></tr><tr><td> Operating Under FAR Part</td><td> Part 121</td></tr><tr><td> Flight Phase</td><td> descent other</td></tr><tr><td> Flight Plan</td><td> IFR</td></tr><tr><td colspan=2> Aircraft 2</td></tr><tr><td> Operator</td><td> common carrier : air carrier</td></tr><tr><td> Make Model Name</td><td> Commercial Fixed Wing</td></tr><tr><td> Operating Under FAR Part</td><td> Part 121</td></tr><tr><td> Flight Plan</td><td> IFR</td></tr><tr><td colspan=2> Person 1</td></tr><tr><td> Affiliation</td><td> company : air carrier</td></tr><tr><td> Function</td><td> flight crew : captainoversight : pic</td></tr><tr><td> Qualification</td><td> pilot : atp</td></tr><tr><td> Experience</td><td> flight time last 90 days : 190flight time total : 12700flight time type : 2000</td></tr><tr><td> ASRS Report</td><td> 332179</td></tr><tr><td colspan=2> Person 2</td></tr><tr><td> Affiliation</td><td> company : air carrier</td></tr><tr><td> Function</td><td> flight crew : first officer</td></tr><tr><td> Qualification</td><td> pilot : instrumentpilot : commercial</td></tr><tr><td colspan=2> Events</td></tr><tr><td> Anomaly</td><td> altitude deviation : overshootnon adherence : clearanceother anomaly other</td></tr><tr><td> Independent Detector</td><td> aircraft equipment other aircraft equipment : unspecifiedother flight crewa</td></tr><tr><td> Resolutory Action</td><td> controller : issued new clearanceother</td></tr><tr><td> Consequence</td><td> Other</td></tr><tr><td> Miss Distance</td><td> vertical : 1500</td></tr><tr><td colspan=2> Supplementary</td></tr><tr><td> Primary Problem</td><td> Flight Crew Human Performance</td></tr><tr><td> Air Traffic Incident</td><td> Pilot Deviation</td></tr><tr><td colspan=2></td></tr></tbody></table> Narrative: On a scheduled flight from stl to las, we were cleared, pilot's discretion, to descend to FL240. At 90 DMEfrom las, first officer began his descent and I reported leaving FL310. At about FL260, I saw a bogie on TCASIIat 11 O'clock about 12 mi, 3000 ft low. Our altitudes were closing but it appeared that his trajectory would take him slightly left of our course, so I was not concerned. Shortly later, at about FL255, the TCASIIgave us a TA. I checked the TCASIIwhere the bogie was now at 10:30 O'clock and about 5 mi. I immediately looked out the window and began a rapid scan for traffic. I repeatedly checked TCASIIdisplay and out the window, but never saw the traffic. I kept this up until the bogie passed our 9 O'clock position. I was just resuming my normal instrument scan when ATCasked us what our altitude was. I checked, saw that it was FL232and reported that to ATC. He then cleared us for further descent. This incident had several contributing factors: 1) the flight engineer was occupied copying ATISinformation which had just become legible. 2) first officer had planned his descent point based on an optimum descent profile for landing, and was clearly anticipating further descent clearance. 3) at 1000 ft above our assigned altitude, where I should have made a callout, I was busy looking for traffic. 4) ATCnever mentioned the traffic, although in retrospect, it's obvious that he was waiting for that traffic to pass before issuing further descent clearance. 5) TCASII, which is generally of great value to flcs, this time contributed to a loss of separation by distracting me enough to interfere with normal cockpit procedures. Original NASA ASRS Text Title: B727 FLC DSNDS BELOW ASSIGNED ALT WHILE LOOKING FOR TFC INDICATED ON TCASII. Narrative: ON A SCHEDULED FLT FROM STL TO LAS, WE WERE CLRED, PLT'S DISCRETION, TO DSND TO FL240. AT 90 DME FROM LAS, FO BEGAN HIS DSCNT AND I RPTED LEAVING FL310. AT ABOUT FL260, I SAW A BOGIE ON TCASII AT 11 O'CLOCK ABOUT 12 MI, 3000 FT LOW. OUR ALTS WERE CLOSING BUT IT APPEARED THAT HIS TRAJECTORY WOULD TAKE HIM SLIGHTLY L OF OUR COURSE, SO I WAS NOT CONCERNED. SHORTLY LATER, AT ABOUT FL255, THE TCASII GAVE US A TA. I CHKED THE TCASII WHERE THE BOGIE WAS NOW AT 10:30 O'CLOCK AND ABOUT 5 MI. I IMMEDIATELY LOOKED OUT THE WINDOW AND BEGAN A RAPID SCAN FOR TFC. I REPEATEDLY CHKED TCASII DISPLAY AND OUT THE WINDOW, BUT NEVER SAW THE TFC. I KEPT THIS UP UNTIL THE BOGIE PASSED OUR 9 O'CLOCK POS. I WAS JUST RESUMING MY NORMAL INST SCAN WHEN ATC ASKED US WHAT OUR ALT WAS. I CHKED, SAW THAT IT WAS FL232 AND RPTED THAT TO ATC. HE THEN CLRED US FOR FURTHER DSCNT. THIS INCIDENT HAD SEVERAL CONTRIBUTING FACTORS: 1) THE FE WAS OCCUPIED COPYING ATIS INFO WHICH HAD JUST BECOME LEGIBLE. 2) FO HAD PLANNED HIS DSCNT POINT BASED ON AN OPTIMUM DSCNT PROFILE FOR LNDG, AND WAS CLRLY ANTICIPATING FURTHER DSCNT CLRNC. 3) AT 1000 FT ABOVE OUR ASSIGNED ALT, WHERE I SHOULD HAVE MADE A CALLOUT, I WAS BUSY LOOKING FOR TFC. 4) ATC NEVER MENTIONED THE TFC, ALTHOUGH IN RETROSPECT, IT'S OBVIOUS THAT HE WAS WAITING FOR THAT TFC TO PASS BEFORE ISSUING FURTHER DSCNT CLRNC. 5) TCASII, WHICH IS GENERALLY OF GREAT VALUE TO FLCS, THIS TIME CONTRIBUTED TO A LOSS OF SEPARATION BY DISTRACTING ME ENOUGH TO INTERFERE WITH NORMAL COCKPIT PROCS. Data retrieved from NASA's ASRS site as of July 2007 and automatically converted to unabbreviated mixed upper/lowercase text. This report is for informational purposes with no guarantee of accuracy. See NASA's ASRS site for official report.
http://www.37000feet.com/report/332179/B727-flight-crew-descends-below-assigned-altitude-while-looking-for-traffic-indicated
81 FR 18940 - Agency Information Collection Activities; Information Collection Renewal; Submission for OMB Review; Leasing 81 FR 18940 - Agency Information Collection Activities; Information Collection Renewal; Submission for OMB Review; Leasing : The OCC, as part of its continuing effort to reduce paperwork and respondent burden, invites the general public and other Federal agencies to take this opportunity to comment on a continuing information collection, as required by the Paperwork Reduction Act of 1995 (PRA). In accordance with the requirements of the PRA, the OCC may not conduct or sponsor, and the respondent is not required to respond to, an information collection unless it displays a currently valid Office of Management and Budget (OMB) control number. The OCC is soliciting comment concerning the renewal of its information collection titled, ``Leasing.'' The OCC also is giving notice that it has sent the collection to OMB for review. DEPARTMENT OF THE TREASURY Office of the Comptroller of the Currency Federal Register Volume 81, Issue 63 (April 1, 2016) Page Range 18940-18941 FR Document 2016-07351 The OCC, as part of its continuing effort to reduce paperwork and respondent burden, invites the general public and other Federal agencies to take this opportunity to comment on a continuing information collection, as required by the Paperwork Reduction Act of 1995 (PRA). In accordance with the requirements of the PRA, the OCC may not conduct or sponsor, and the respondent is not required to respond to, an information collection unless it displays a currently valid Office of Management and Budget (OMB) control number. The OCC is soliciting comment concerning the renewal of its information collection titled, ``Leasing.'' The OCC also is giving notice that it has sent the collection to OMB for review. [Federal Register Volume 81, Number 63 (Friday, April 1, 2016)] [Notices] [Pages 18940-18941] From the Federal Register Online [ www.thefederalregister.org ] [FR Doc No: 2016-07351] ----------------------------------------------------------------------- DEPARTMENT OF THE TREASURY Office of the Comptroller of the Currency Agency Information Collection Activities; Information Collection Renewal; Submission for OMB Review; Leasing AGENCY: Office of the Comptroller of the Currency (OCC), Treasury. ACTION: Notice and request for comment. ----------------------------------------------------------------------- SUMMARY: The OCC, as part of its continuing effort to reduce paperwork and respondent burden, invites the general public and other Federal agencies to take this opportunity to comment on a continuing information collection, as required by the Paperwork Reduction Act of 1995 (PRA). In accordance with the requirements of the PRA, the OCC may not conduct or sponsor, and the respondent is not required to respond to, an information collection unless it displays a currently valid Office of Management and Budget (OMB) control number. The OCC is soliciting comment concerning the renewal of its information collection titled, ``Leasing.'' The OCC also is giving notice that it has sent the collection to OMB for review. DATES: Comments must be received by May 2, 2016. ADDRESSES: Because paper mail in the Washington, DC area and at the OCC is subject to delay, commenters are encouraged to submit comments by email, if possible. Comments may be sent to: Legislative and Regulatory Activities Division, Office of the Comptroller of the Currency, Attention: 1557-0206, 400 7th Street SW., suite 3E-218, mail stop 9W-11, Washington, DC 20219. In addition, comments may be sent by fax to (571) 465-4326 or by electronic mail to prainfo@occ.treas.gov . You may personally inspect and photocopy comments at the OCC, 400 7th Street SW., Washington, DC 20219. For security reasons, the OCC requires that visitors make an appointment to inspect comments. You may do so by calling (202) 649-6700 or, for persons who are deaf or hard of hearing, TTY, (202) 649-5597. Upon arrival, visitors will be required to present valid government-issued photo identification and submit to security screening in order to inspect and photocopy comments. All comments received, including attachments and other supporting materials, are part of the public record and subject to public disclosure. Do not include any information in your comment or supporting materials that you consider confidential or inappropriate for public disclosure. Additionally, please send a copy of your comments by mail to: OCC Desk Officer, 1557-0206, U.S. Office of Management and Budget, 725 17th Street NW., #10235, Washington, DC 20503, or by email to: oira_submission@omb.eop.gov . FOR FURTHER INFORMATION CONTACT: Shaquita Merritt, Clearance Officer, (202) 649-5490 or, for persons who are deaf or hard of hearing, TTY, (202) 649-5597, Legislative and Regulatory Activities Division, Office of the Comptroller of the Currency, 400 7th Street SW., Washington, DC 20219. SUPPLEMENTARY INFORMATION: The OCC is proposing to extend OMB approval of the following information collection: Title: Leasing. OMB Control No.: 1557-0206. Description: This submission requests the renewal of PRA clearance for an existing regulation and involves no change to the regulation or to the information collection requirements. Under 12 CFR 23.4(c), national banks must liquidate or release property that is no longer subject to lease (off-lease property) within five years from the date of the lease expiration. If a national bank wishes to extend the five-year holding period for up to an additional five years, it must obtain OCC approval. Permitting a national bank to extend the holding period may result in cost savings. It also may provide flexibility for a national bank that experiences unusual or unforeseen conditions that would make it imprudent to dispose of the off-lease property prior to the expiration of the five-year holding period. Section 23.4(c) requires a national bank seeking an extension to provide a clearly convincing demonstration as to why any additional holding period is necessary. In addition, a national bank must value off-lease property at the lower of current fair market value or book value promptly after the property comes off-lease. These requirements enable the OCC to ensure that a national bank is not holding the property for speculative reasons and that the value of the property is recorded in accordance with generally accepted accounting principles (GAAP). Under 12 CFR 23.6, leases are subject to the lending limits prescribed by 12 U.S.C. 84, as implemented by 12 CFR part 32, or, if the lessee is an affiliate of the national bank, to the restrictions on transactions with affiliates prescribed by 12 U.S.C. 371c and 371c-1. Twelve U.S.C. 24 contains two separate provisions authorizing a national bank to acquire personal property for purposes of lease financing. Twelve U.S.C. 24(Seventh) authorizes leases of personal property (Section 24(Seventh) Leases) if the lease is a conforming lease as defined in 12 CFR 23.2(d)(2) and represents a noncancelable obligation of the lessee (i.e., the lease serves as the functional equivalent of a loan). See 12 CFR 23.20. A national bank also may acquire personal property for purposes of lease financing under the authority of 12 U.S.C. 24(Tenth) (CEBA Leases). Section 23.5 requires that if a national bank enters into both types of leases, its records must distinguish between the two types of leases. This information is required to establish that the national bank is complying with the limitations and requirements applicable to the two types of leases. National banks use the information to ensure their compliance with applicable [[Page 18941]] Federal banking law and regulations and accounting principles. The OCC uses the information in conducting examinations and as an auditing tool to verify compliance with laws and regulations. In addition, the OCC uses national bank requests for permission to extend the holding period for off-lease property to ensure national bank compliance with relevant laws and regulations and to ensure bank safety and soundness. Type of Review: Regular. Affected Public: Individuals; Businesses or other for-profit. Frequency of Response: On occasion. Estimated Number of Respondents: 345. Estimated Total Annual Burden: 678. The OCC published a notice for 60 days of comment on January 20, 2016, 81 FR 3236. No comments were received. Comments continue to be requested on: (a) Whether the information collections are necessary for the proper performance of the OCC's functions, including whether the information has practical utility; (b) The accuracy of the OCC's estimates of the burden of the information collections, including the validity of the methodology and assumptions used; (c) Ways to enhance the quality, utility, and clarity of the information to be collected; (d) Ways to minimize the burden of information collections on respondents, including through the use of automated collection techniques or other forms of information technology; and (e) Estimates of capital or start up costs and costs of operation, maintenance, and purchase of services to provide information. Dated: March 28, 2016. Mary Hoyle Gottlieb, Regulatory Specialist, Legislative and Regulatory Activities Division. [FR Doc. 2016-07351 Filed 3-31-16; 8:45 am] BILLING CODE 4810-33-P
https://thefederalregister.org/81-FR/18940
Facts about "Casablanca" : Classic Movie Hub (CMH) Browse Fun Facts and Trivia about at Classic Movie Hub (CMH). <here is a image bf78f8e36794dad7-ec58925fe0d64af1> Casablanca "As Time Goes By" was written by lifelong bachelorHerman Hupfeldand debuted in 1931's Broadway show "Everybody's Welcome", sung byFrances Williams, It had been a personal favorite of playwright and high school teacherMurray Burnettwho, seven years later, visited Vienna just after the Nazis had entered. Later, after visiting a café in south France where a black pianist had entertained a mixed crowd of Nazis, French and refugees, Burnett was inspired to write the melodrama "Everybody Comes to Rick's", which was optioned for production byMartin GabelandCarly Wharton, and later, Warners. After the film's release, "As Time Goes By" stayed on radio's "Hit Parade" for 21 weeks. However, because of the coincidental musicians' union recording ban, the 1931Rudy Valleeversion became the smash hit. (It contains the rarely-sung introductory verse, not heard in the film.)Max Steiner, in a 1943 interview, admitted that the song "must have had something to attract so much attention". "Here's looking at you, kid" was improvised by Humphrey Bogart in the Parisian scenes and worked so well that it was used later on again in the film. He originally used the same line in Midnight . It is also rumored that during breaks, Ingrid Bergman would play poker with other cast members. Since she was still learning English, Bogart would occasionally watch the game, and he added "Here's looking at you" to her poker repertoire. "Rick's Café Américain" was modeled after Hotel El Minzah in Tangiers. Humphrey Bogarthad to wear platform shoes to play alongsideIngrid Bergman. Humphrey Bogart , Ingrid Bergman and Paul Henreid later reprised their roles for a radio performance of on the CBS radio program "The Screen Guild Players", a war benefit show on April 26, 1943. Humphrey Bogart 's wife Mayo Methot continually accused him of having an affair with Ingrid Bergman , often confronting him in his dressing room before a shot. Bogart would come onto the set in a rage. In fact, despite the undeniable on-screen chemistry between Bogart and Bergman, they hardly spoke, and the only time they bonded was when the two had lunch with Geraldine Fitzgerald . According to Fitzgerald, "the whole subject at lunch was how they could get out of that movie. They thought the dialogue was ridiculous and the situations were unbelievable... I knew Bogart very well, and I think he wanted to join forces with Bergman, to make sure they both said the same things." For whatever reasons, Bogart and Bergman rarely spoke after that. S.Z. Sakall, who plays the maitre d' at Rick's Cafe, actually has more screen time thanPeter LorreorSydney Greenstreet. Madeleine Lebeau , who plays Yvonne, and Marcel Dalio , who plays croupier Emil, were husband and wife at the time of filming. They had not long before escaped the Nazis by fleeing their native France. Dooley Wilson (Sam) was a professional drummer who faked playing the piano. As the music was recorded at the same time as the film, the piano playing was actually a recording of a performance by Elliot Carpenter who was playing behind a curtain but who was positioned such that Dooley could watch, and copy, his hand movements. Dooley Wilsonwas borrowed from Paramount at $500 a week. Dooley Wilsonwas, in fact, the only member of the cast to have ever actually visited the city of Casablanca. Joy Page , who played the young Bulgarian wife, was the stepdaughter of studio head Jack L. Warner . She, Humphrey Bogart and Dooley Wilson were the only American-born people in the credited cast. This film was her debut. Hal B. Wallisdidn't wantHumphrey Bogartwearing a hat too often in the film, as he thought it made Bogart look like a gangster. Hal B. Wallis's first choice for director wasWilliam Wyler. Sydney Greenstreet wanted to wear something more ethnic to show that his character had assimilated into the Moroccan lifestyle. This idea was nixed by producer Hal B. Wallis who insisted that he wear his now-iconic white suit. Ingrid BergmanandPaul Henreidmake their first appearance 24 minutes into the film. Ingrid Bergman considered her left side as her better side, and to the extent possible that was the side photographed throughout the film, so she is almost always on the right side of the screen looking towards the left regardless of who is in the shot with her. However, there are several shots where she is to the left and Humphrey Bogart is on the right, including the flashbacks to the street scene in Paris (0:41:50) and the scene at the window (0:43:40). There are also several scenes where Bergman is centered between Paul Henreid and Bogart, suggesting the triangle nature of their relationship; in these shots Henreid is usually to the left and Bogart is usually on the right, including the scene where she and Henreid enter the café at just before the famous "Battle of the Anthems" (1:07:40); the scene where Captain Renault arrests Victor Laszlo (1:34:00); and at the end of the final airport scene (1:39:00). Ingrid Bergman's contract was owned by producerDavid O. Selznick, and producerHal B. Wallissent the film's writers,Philip G. EpsteinandJulius J. Epstein, to persuade Selznick to loan her to Warner Bros. for the picture. After 20 minutes of describing the plot to Selznick, Julius gave up and said, "Oh, what the hell! It's a lot of shit likeAlgiers!" Selznick nodded and agreed to the loan. Ingrid Bergman 's line "Victor Laszlo is my husband, and was, even when I knew you in Paris" was almost cut from the film because during that time it was deemed inappropriate for a film to depict or suggest a woman romancing with another man if she were already married. However, it was pointed out that later in the film she explains that she had thought Laszlo was dead at the time, and the censors allowed the line to stay in. Howard Hawks had said in interviews that he was supposed to direct Casablanca and Michael Curtiz was supposed to direct Sergeant York . The directors had lunch together, where Hawks said he didn't know how to make this "musical comedy", while Curtiz didn't know anything about "those hill people." They switched projects. Hawks struggled on how to direct the scenes that involved singing, namely the "La Marseillaise" scene. It is ironic to note that most of his other films involved at least one singing scene.
https://www.classicmoviehub.com/facts-and-trivia/film/casablanca-1942/?lv=true%2Fpage%2F1%2F%2Fpage%2F2%2F%2Fpage%2F6%2F%2Fpage%2F1%2F%2Fpage%2F5%2F%2Fpage%2F5%2F%2Fpage%2F1%2F%2Fpage%2F4%2F
e claims of Latif Pasha, and then arrested him, and had him publicly executed. From this moment the real reign of Mehemet Ali begins. Possessed of a fertile country, he promptly began to consider the ways and means of improving the deplorable state of its finances, and to grasp all the resources which agriculture and commerce could yield for the realisation of his ambitious schemes. Nothing must be neglected in the government of a country for so many years the scene of incessant warfare; the labourer must be made to return to the field he had deserted during the time of trouble; political and civil order must be reestablished so as to reassure the inhabitants, and secure the resumption of long abandoned industries. The most important matter was to restrain the depredations of the Bedouins, and, to assure the obedience of these hitherto unsubdued tribes, he kept their sheikhs as hostages: at the same time he checked the delinquencies of the Kopts, in whose hands the government of the territories had been from time immemorial. A sure and certain peace thus having been ensured to the interior of the country, the pasha turned his attention to another enterprise, the accomplishment of which is always somewhat difficult after a lengthy crisis. He wished to encourage and regulate the payment of taxes without hindering the financial operations of private individuals. To this end, he re-established the custom of receiving tribute in kind, and to support the payment of this tribute he organised the export trade. A thousand vessels built at his own expense ploughed the waters of the Nile in all directions, and conveyed Egyptian produce to the shores of the Mediterranean, where huge warehouses stored the goods destined for foreign countries. Mehemet Ali preserved a continual intercourse with foreign merchants, and the country owed many fortunate innovations to these relations: agriculture was enriched by several productions hitherto unknown. A Frenchman, M. Jumel, introduced improvements in the production of cotton, whilst M. Drovetti, the pasha’s tried friend, helped to further the establishment of manufactories by his advice and great experience of men and things. Before long, cotton mills were built, cloth factories, a sugar refinery, rum distillery, and saltpetre works erected. The foreign trade despatched as much as seven million _ardebs_ of cereals every year, and more than six hundred thousand bales of cotton. In return, European gold flowed into the treasury of this industrious pasha, and the revenues of Egypt, which hitherto had never exceeded $150,000,000, were more than doubled in 1816. The very slight success which Mehemet Ali had obtained when commanding the irregular forces during the expedition against the Wahabis decided him to put a long-cherished idea into execution, namely, to organise an army on European lines. Henceforth this became the sole occupation of the enterprising pasha and the exclusive goal of his perseverance. The Nizam-Jedyd was proclaimed in the month of July, 1815, and all the troops were ordered to model themselves after the pattern of the French army. This large undertaking, which in 1807 had cost Selim III. his life, proved almost as fatal to Mehemet Ali. A terrible insurrection broke out amongst the alien soldiers, who principally composed the army; the infuriated troops rose against the tyrant and the unbeliever, the palace was pillaged, and the pasha had scarcely time to seek the shelter of his citadel. His only means of saving his life and recovering his authority was solemnly to promise to abandon his plan. Mehemet Ali therefore deferred his military schemes and awaited the opportunity to test its success upon the natives, who would be far more easily managed than the excitable strangers, brought up as they were on the old traditions of the Okaz and the Mamluks. The war which still raged in Arabia gave him the means of ridding himself of the most indomitable men, whom he despatched to Hedjaz under the command of Ibrahim Pasha, his eldest son. Now came success to console Mehemet Ali for the failure of his reformatory plans. After a long series of disasters, Ibrahim succeeded, in the year 1818, in taking Abd Allah Ibn-Sonud, the chief of the Wahabis, prisoner. He sent him to the Great Pasha, a name often applied to Mehemet Ali in Egypt, at Cairo, bearing a portion of the jewels taken from the temple at Mecca. The unfortunate man was then taken to Constantinople, where his punishment bore testimony to the victory rather than the clemency of his conquerors. In reward for his services, the sultan sent Ibrahim a mantle of honour and named him Pasha of Egypt, which title conferred on him the highest rank among the viziers and pashas, and even placed him above his own father in the hierarchy of the dignitaries of the Turkish Empire. At the same time Mehemet Ali was raised to the dignity of khan, an attribute of the Ottomans, and the greatest distinction obtainable for a pasha, inasmuch as it was formerly exclusively reserved for the sovereigns of the Crimea. [Illustration: 157.jpg THE COTTON PLANT] After destroying Daryeh, the capital of Nedj, Mehemet Ali conceived the idea of extending his possessions in the interior of Africa, and of subduing the country of the negroes, where he hoped to find much treasure. He accordingly sent his son, Ishmail Pasha, with five thousand men, upon this expedition, which ended most disastrously with the murder of Ishmail and his guard by Melek Nemr, and the destruction of the remainder of his forces. In the year 1824, Sultan Mahmud, realising the impossibility of putting down the Greek insurrection by his own unaided forces, bent his pride sufficiently to ask help of his vassal Mehemet Ali. Mehemet was now in possession of a well-drilled army and a well-equipped fleet, which were placed at the service of the sultan, who promised him in return the sovereignty of Crete, the pashalic of Syria, and possibly the reversion of Morea for his son Ibrahim. The Greeks, deceived by their easy successes over the undisciplined Turkish hosts, failed to realise the greatness of the danger which threatened them. The Egyptian fleet managed, without serious opposition, to enter the Archipelago, and, in December, 1824, Ibrahim, to whom Mehemet Ali had entrusted the supreme command of the expedition, established his base in Crete, within striking distance of the Greek mainland. The following February he landed with four thousand regular infantry and five hundred cavalry at Modon, in the south of Morea. The Greeks were utterly unable to hold their own against the well-disciplined fellaheen of Ibrahim Bey, and, before the end of the year, the whole of the Peloponnesus, with the exception of a few strongholds, was at the mercy of the invader, and the report was spread that Ibrahim intended to deport the Greek population and re-people the country with Moslem negroes and Arabs. The only barrier opposed to the entire extinction of the Greek population was their single stronghold of Missolonghi, which was now besieged by Rashid Pasha and the Turks. If Ibrahim had joined his forces with the besieging army of the Turks, Missolonghi could hardly have resisted their combined attack, and the Greek race would have been in danger of suffering annihilation. Meanwhile the Great Powers of Europe were seriously concerned with this threatened destruction of the Greeks. England proposed a joint intervention in defence of Greece on the part of the Powers, but Russia desired to act alone. A huge army was gradually concentrated upon the Turkish frontier. The Greek leaders now offered to place Greece under British protection, and the Duke of Wellington was sent to St. Petersburg to arrange the terms of the proposed joint intervention. A protocol was signed at St. Petersburg April 4, 1826, whereby England and Russia pledged themselves to cooperate in preventing any further Turco-Egyptian agression. A more definite agreement was reached in September, aiming at the cutting off of Ibrahim in Morea by a united European fleet, thus forcing the Turks and Egyptians to terms. On July 6,1827, a treaty was signed at London, between England, France, and Russia, which empowered the French and English admirals at Smyrna to part the combatants--by peaceful means if possible, and if not, by force. Admiral Codrington at once sailed to Nauplia. The Greeks were willing to accept an armistice, but the Turks scorned the offer. At about this time an Egyptian fleet of ninety-two vessels sailed from Alexandria and joined the Ottoman fleet in the bay of Navarino (September 7th). Five days later Admiral Codrington arrived and informed the Turkish admiral that any attempt to leave the bay would be resisted by force. French vessels had also arrived, and Ibrahim agreed not to leave the bay without consulting the sultan. A Greek flotilla having destroyed a Turkish flotilla, Ibrahim took this as a breach of the convention and sailed out to sea, but Codrington succeeded in turning him back. Ibrahim now received instructions from the Porte to the effect that he should defy the Powers. A new ultimatum was at once presented and the allied fleet of the European Powers entered the bay of Navarino. The Turco-Egyptian fleet was disposed at the bottom of the bay in the form of a crescent. Without further parleying, as the fleet of the English and their allies approached, the Turks and Egyptians began to fire, and a battle ensued, apparently without plan on either side: the conflict soon became general, and Admiral Codrington in the _Asia_ opened a broadside upon the Egyptian admiral, and quickly reduced his vessel to a wreck. Other vessels in rapid succession shared the same fate, and the conflict raged with great fury for four hours. When the smoke cleared off, the Turks and Egyptians had disappeared, and the bay was strewn with fragments of their ships. [Illustration: 161.jpg A DISTINGUISHED EGYPTIAN JEW] Admiral Codrington now made a demonstration before Alexandria, and Mehemet Ali gladly withdrew his forces from co-operating with such a dangerous ally as the sultan had proved himself to be. Before the French expedition, bound for the Morea, had arrived, all the Egyptian forces had been withdrawn from the Peloponnesus, and the French only arrived after the Anglo-Egyptian treaty had been signed August 9, 1828. Mehemet Ali’s chief ambition had always been to enlarge the circle of regeneration in the East. In Morea he had failed through European intervention. He felt that his nearer neighbour, Syria, which he had long coveted, would be an easier conquest, and he made the punishment of Abdullah Pasha of Acre, against whom he had many grievances, his excuse to the Porte. In reality it was a case of attacking or being attacked. Through a firman of the Divan of Constantinople, which had been published officially to the European Powers, he knew that his secret relations with Mustapha Pasha of Scodra had become known. He knew also that letters had been intercepted in which he offered this pasha money, troops, and ammunition, while engaging himself to march on the capital of the empire, and that these letters were now in the hand of the Sultan Mahmud. He wras also informed that the Porte was preparing to send a formidable army to Egypt; and his sound instinct taught him what to do in this position. Ibrahim Pasha was appointed commander-in-chief of the invading army, which was composed of six regiments of infantry, four of cavalry, forty field-pieces, and many siege-pieces. Provisions, artillery, and ammunition were on board the men-of-war. Thousands of baggage camels and ambulances were being collected ready for departure when cholera broke out. Coming from India, after having touched along the coasts of the Persian Gulf, it had penetrated into the caravan to Mecca, where the heat and dearth of water had given it fresh intensity. It raged in the Holy Town, striking down twenty thousand victims, and touched at Jeddah and Zambo, where its effects were very dire. Passing through Suez, it decimated the population, and in August it reached Cairo and spread to Upper and Lower Egypt. The army did not escape the common scourge, and when about to invade Syria was overtaken by the epidemic. Five thousand out of ninety thousand perished. All preparations for the expedition were abandoned until a more temperate season improved the sanitary conditions. About the beginning of October, 1831, the viceroy gave orders to his son to prepare for departure, and on November 2d the troops started for El Arish, the general meeting-place of the army. Ibrahim Pasha went to Alexandria, whence he embarked with his staff and some troops for landing. Uniting at El Arish, the army marched on Gaza and took possession of that town, dispersing some soldiers of the Pasha of Acre. Thence it turned to Jaffa, where it met with no resistance, the Turkish garrison having already evacuated the town. At this time the army which had sailed from Alexandria was cruising about the port of Jaffa, and Ibrahim Pasha landed there and took over the command of the army, which advanced slowly on St. Jean d’Acre, seizing Caiffa to facilitate the anchoring of the fleet, which had landed provisions, artillery, and all kinds of ammunition. After six months’ siege and ten hours’ fighting, Ibrahim Pasha obtained possession of St. Jean d’Acre, under whose walls fell so many valiant crusaders, and which, since the repulse of Napoleon, had passed for all but impregnable. Abdullah Pasha evinced a desire to be taken to Egypt, and he landed at Alexandria, where he was warmly welcomed by the viceroy, who complimented him on his defence. Hostile in everything to Mehemet Ali, the Porte seized every opportunity of injuring him. When Sultan Mahmud learned of the victory of the viceroy’s troops in Syria, he sent one of his first officers to enquire the reason of this invasion. The viceroy alleged grievances against the Pasha of Acre, to which his Highness replied that he alone had the right to punish his subjects. The eyes of Europe were now fixed upon the Levant, where a novel struggle was going on between vassal and suzerain. Authority and liberty were again opposing each other. The Powers watched the struggle with intense interest. The viceroy protested against bearing the cost of the war, and demanded the investiture of Syria. Mehemet Ali was then declared a rebel, and a firman was issued against him, in support of which excommunication an army of sixty thousand men advanced across Asia Minor to the Syrian boundaries, while a squadron of twenty-five sail stood in the Dardanelles ready to weigh anchor. [Illustration: 165.jpg MOSQUE OF MUAD AT CAIRO] The Porte forbade the ambassadors of the Powers to import ammunition into Egypt, for it feared that the viceroy might find a support whose strength it knew only too well. But the viceroy had no need of this, for his former connections with Europe had put him in a position of independence, whereas the Porte itself was obliged to fall back on this support. Russia, the one of the three Great Powers whose disposition it was to support the authority of the sultan, lent him twenty thousand bayonets, whilst Ibrahim Pasha made his advance to the gates of Constantinople. Immediately after the taking of St. Jean d’Acre Ibrahim Pasha, following up his successes, had turned towards Damascus, which town he entered without a blow being struck, the governor and the leading inhabitants having taken flight. The commander-in-chief established his headquarters under the walls of the conquered country, and then marched in three columns on Horns. The battle of Horns (July 8, 1832) demonstrated the vast superiority of the Egyptian troops. On both sides there were about thirty thousand regular soldiers, but the Egyptians were the better organised, the better disciplined, and the more practised in the arts of war. When it is remembered that at Horns the Turks lost two thousand men killed, and 2,500 taken prisoners, while the Egyptian casualties were only 102 k
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Debate: West Papua: Human Rights - 8th May 2019 - Robert Courts extracts Wed 8th May 2019 - Commons - West Papua: Human Rights debate Robert Courts contributions to the 8th May 2019 West Papua: Human Rights debate West Papua: Human Rights Debate Full Debate: Read Full Debate Department: Foreign, Commonwealth & Development Office West Papua: Human Rights Robert Courts Excerpts Wednesday 8th May 2019 (4 years, 1 month ago) Westminster Hall Robert Courts (Witney) (Con)- Hansard- Copy Link- I beg to move, That this House has considered human rights in West Papua. It is an honour to serve under your chairmanship, Mr Hollobone. I am delighted to have been granted this extremely important debate about human rights in West Papua. As I understand it, this is the first ever debate in the House of Commons on this topic. I am pleased to welcome colleagues from across the House who have come to support the debate, and I am grateful to them. There have been a couple of brief debates in the other place over the years, but this is the first time that we, as elected representatives, have debated West Papua, despite having held some 3,455 debates in the last 50 years on issues great and small, of national and local significance. That is illustrative of the lack of attention this issue has received, when it ought to have had attention both at home and from the international community. I hope that today, in our small way, we can start to shine a light on the West Papuan cause and to give a voice to the people of West Papua. I referenced the last 50 years, and there is a significance to that, as 2019 marks the 50th anniversary of the so-called Act of Free Choice. That Act is a defining moment in the West Papuan story and forms the context within which the current situation in West Papua must be viewed. I will set out some of that context and give a brief history of West Papua, before discussing the current situation. I will conclude with two key actions I suggest the UK Government consider taking to help improve the human rights situation in West Papua. John Howell (Henley) (Con)- Hansard- Copy Link-- Excerpts I thank my hon. Friend for giving way before he starts on his historical exposé. I want to set the current situation in context, as he is coming on to describe it. Is he aware of two human rights situations? The first was illustrated in a video that went viral, which showed a West Papuan freedom fighter being tortured with a snake by the Indonesian army. Is he also aware that, as a result of Indonesian activities in Nduga, 30,000 refugees have been created in just that area? Robert Courts- Hansard- Copy Link- I am grateful to my hon. Friend for that intervention. I am aware of both the fact and the incident; they illustrate, in microcosm, the importance of this debate and are vivid examples of what is happening this very day in West Papua. West Papua is the western half of New Guinea, which is the second largest island on earth and one of many thousands of south Pacific islands that are collectively known as Melanesia. Papuan people have inhabited the West Papua region for over 40,000 years. It was slowly drawn into the Dutch sphere of influence, and by the end of the 19th century the Dutch had established permanent administrative centres in the region as part of the Dutch East Indies. When Indonesian nationalists declared independence from the Dutch empire in 1945, they included West Papua in the list of territories that would form the newly born country. That declaration sparked a four-year-long war between the Indonesians and the Dutch, which ended in 1949, when Indonesia was granted international recognition as an independent state at TheHague roundtable conference. However, this only heightened the divisions that existed on the status of the West Papua region. Indonesia argued that the region should be included in its new independent state, but the Dutch refused to cede the territory. At this point, I ought to mention that the West Papua region is home to the largest gold mine and the second largest copper mine in the world. No compromise was found in the years that followed Indonesian independence, leading to a further fraying of tensions between Indonesia and the Netherlands. That led to Indonesia building up its military capacity, largely from weapons acquired from the Soviet Union. In the conflict that ensued, the United States, although originally supportive of the Dutch cause, eventually changed its position to ensure that Indonesia would not be driven towards the Soviet Union, in the context of the cold war. Talks between Indonesia and the Netherlands followed in 1962, with the UN acting as the official mediating power. This resulted in the signing of the New York agreement, according to which the administration of West Papua would be assigned to the United Nations for a minimum of seven months, before being passed to Indonesia. Crucially, article 18 of that agreement stipulated: “Indonesia will make arrangements, with the assistance and participation of the United Nations Representative and his staff, to give the people of the territory the opportunity to exercise freedom of choice.” It went on: “Such arrangements will include...formulations of the questions in such a way as to permit the inhabitants to decide (a) whether they wish to remain with Indonesia; or (b) whether they wish to sever their ties with Indonesia.” Article 18 also noted that the consultation had to ensure the “eligibility of all adults, male and female, not foreign nationals to participate in the act of self-determination to be carried out in accordance with international practice.” Jonathan Edwards (Carmarthen East and Dinefwr) (PC)- Hansard- Copy Link-- Excerpts I thank the hon. Member for securing this important debate. I have long held an interest in West Papua, going back 15 or 16 years into my previous life. Is not the root issue self-determination, which is an international human right? Having an ethical foreign policy that protects that vital human right is important for any Government, including the British Government. Robert Courts- Hansard- Copy Link- Self-determination is a fundamental human right. That has been the case for many hundreds of years, as most famously enunciated at the beginning of the 20th century, after the first world war. It is a guiding principle in foreign policy for all countries, but particularly for the United Kingdom since that time. Self-determination is at the heart of the issue we are discussing, and I am grateful to the hon. Gentleman for making that point. It is difficult to say that what happened in 1969—the so-called Act of Free Choice—was carried out in accordance with international practice or captured the true democratic will of the West Papuan people. Despite the New York agreement explicitly requiring Indonesia to “guarantee fully the rights, including the rights of free speech, free movement and of assembly, of the inhabitants of the area”, that guarantee was not fulfilled, because Papuan political parties were banned at the time of the Act of Free Choice. A one person, one vote system, which is international practice, was not granted. Instead 1,025 representatives were selected by the Indonesian military to vote on behalf of the Papuan people. The representatives voted unanimously in favour of Papua becoming part of Indonesia. However, numerous reports from foreign observers and Papuans suggest that it was not a free consultation. It is claimed that those who were selected for the vote were blackmailed into voting against independence by means of threats of violence against their person and their families. Representatives were taken away from their families and communities for several weeks before the consultation. Diplomatic cables from the US ambassador to Indonesia reported at the time that the Act of Free Choice in West Papua “is unfolding like a Greek tragedy, the conclusion preordained.” The ambassador went on to say that the Indonesians “cannot and will not permit any resolution other than continued inclusion” of West Papua “in Indonesia. Dissident activity is likely to increase as the climax is reached but the Indonesian armed forces will be able to contain it and, if necessary, suppress it.” The ambassador continued by saying that the Indonesian armed forces had “no intention of allowing” West Papuan choice “other than incorporation into Indonesia. Separation is unthinkable.” British diplomats in the region took similar views and drew similar conclusions at the time. In a House of Lords debate in 2004, the then Foreign Office Minister, Baroness Symons, made this admission in responding to the then Bishop of Oxford: “He is right to say that there were 1,000 handpicked representatives and that they were largely coerced into declaring for inclusion in Indonesia.” —[ Official Report, House of Lords,13 December 2004; Vol. 667, c. 1084.] I would be interested to hear in due course from the Minister whether that is still the position of the UK Government, although I see no reason for it to have changed at this stage. After making that admission, Baroness Symons went on to say that these things had occurred many decades ago and that, rather than dwelling on the past, it was important to look to the future and improve matters in the here and now. While I have some sympathy with that sentiment, it does perhaps miss the key point—that in the eyes of many West Papuans, the fundamental questions about the legitimacy of the so-called Act of Free Choice undermine the very legitimacy of Indonesian rule in West Papua. We are now in the 50th anniversary year of the Act of Free Choice, which is understandably seen as an act of great injustice by the people of West Papua, who refer to it ironically as the “Act of No Choice”. In the past 50 years, the West Papuan people have been subjected to serious human rights violations, which have only fuelled and heightened that sense of injustice. Those human rights violations include the repression of freespeech and peaceful assembly, impediments to a free press, arbitrary arrest, and even cases of torture and killings, as we have heard. The human rights abuses in West Papua are in large part down to the fact that the region is de facto controlled by the Indonesian military. The University of Sydney has estimated that around 15,000 troops are currently deployed in the region. When human rights violations occur, there are inadequate systems of redress for Papuans, so violations often go unpunished. An Amnesty International report on West Papua noted that there is a lack of effort to investigate accusations of human rights violations and to try before civilian courts police officials accused of violations. Furthermore, it noted that allegations of human rights abuses committed by the military in West Papua often go unchecked or are dealt with before military tribunals with no transparency, leaving many victims of human rights violations awaiting justice. We will all be aware of the case from earlier this year, which we heard about from my hon. Friend the Member for Henley (John Howell). Footage emerged of Indonesian police interrogating a young Papuan boy, who was on the floor and in handcuffs while officers wrapped a large snake around him. The child was alleged to have stolen a mobile phone. In the video, he is heard screaming in fear as officers laugh and push the snake’s head towards his face. In responding to the incident, a UN panel of human rights experts stated that it “reflects a widespread pattern of violence, alleged arbitrary arrests and detention as well as methods amounting to torture used by the Indonesian police and military in Papua”. They went on to explain that those tactics are often used against indigenous Papuans and that the incident is “symptomatic” of the discrimination West Papuans face from the Indonesian authorities. Papuans are regularly arrested for peacefully expressing their opinions on the political status of West Papua, including through peaceful demonstrations or attending meetings in which the matter is discussed. The simple act of raising the symbol of West Papuan independence, the Morning Star flag, carries a prison sentence of up to 15 years. Pro-independence political leaders have routinely faced persecution and even assassination at the hands of the Indonesian authorities. At this point, I would like to introduce someone who, I am pleased to say, is in attendance today—Benny Wenda, leader of the United Liberation Movement for West Papua, who came to see me recently, along with my constituent Richard Samuelson, who was the first person to bring the situation in West Papua to my attention, and his fiancée Elaine, who are also in attendance. I thank them. I pay tribute to Richard for bringing this issue to my attention; without going off on too much of a tangent, it shows one of the greatest things about our parliamentary system. Many of us, when we raise issues in the House, do so because they are brought to our attention by constituents in our surgeries, and this is one such case. Richard and Benny made a powerful, moving case to me, and I am only too pleased to raise this issue before Parliament today. I make that point during this debate as a reminder of the democratic rights and freedoms we enjoy in this country. Richard and Benny could come to see me and make their point freely, knowing they would not bepersecuted and that their representative could and would take up the matter on their behalf. Those are rights and freedoms that, sadly, are not enjoyed by too many people around the world. Benny’s story would bring a tear to the stoniest eye. Benny’s father was, in fact, one of the representatives hand-picked in 1969 to vote in the Act of Free Choice. Benny says that he still remembers his father telling him how he had been threatened and told that he and his whole family would be killed if he voted for Papuan independence. During our meeting, Benny told me the tragic story, which he says is permanently fixed in his memory, of when, at just three years old, he saw many of his fellow villagers, including most of his family, killed during an Indonesian military operation. Years later, Benny became the leader of the Papuan student independence movement. After being imprisoned, he was able to escape to Oxford, where he was duly granted political asylum by the United Kingdom. When I met Benny, he expressed with great emotion the gratitude he felt to the United Kingdom, and he spoke with admiration of our values of freedom and the rule of law—principles he said he was determined to see his people in West Papua enjoy. Benny was the one who, earlier this year, presented a petition to the United Nations calling for an independence referendum in West Papua. The petition contained the signatures and thumbprints of some 1.8 million West Papuans, which represents approximately 70% of the entire population. I turn now to the Minister. What can the UK Government do? I have explained the history and set out the present situation. The question is, what can we do to ensure that the human rights situation improves in West Papua and that the future is brighter for the Papuan people? I accept that the United Kingdom’s power is limited, but I think there are two key areas where we could—and should—apply diplomatic pressure. We should not downplay our influence. The United Kingdom is a close and important friend of Indonesia. A recent BBC poll found that over 65% of Indonesians take a positive view of the UK’s influence, making Indonesia the country with the second most favourable perception of the United Kingdom in Asia. Therefore, we have a role to play in having these conversations with our Indonesian friends, difficult though they may be. The first thing I ask the Minister to consider doing is to push for the Office of the UN High Commissioner for Human Rights to visit West Papua. That should not be controversial; indeed, in a February 2018 meeting with the then UN High Commissioner, Zeid Ra’ad Al Hussein, Indonesian President Jokowi invited his office to visit West Papua. Sadly, some 15 months on, that visit has not taken place, and the former UN High Commissioner expressed concern about that in his update to the 38th session of the Human Rights Council. The Foreign Office, and our representatives in the United Nations, should encourage their Indonesian counterparts to honour that invitation and permit the Office of the UN High Commissioner for Human Rights to visit West Papua. The UN High Commissioner’s assessment of human rights in West Papua will be critical to informing the world of the situation on the ground and bringing about positive change in the region. I ask the Minister today if he would please commit to raising the issue of this invitation with his Indonesian counterpart and encouraging them to honour it. The second area where I would suggest the United Kingdom could have a positive influence is in pushing for increased press freedom in West Papua and particularly for greater access for foreign journalists to the region. At present, foreign journalists are essentially banned from West Papua. The few who are granted access are closely monitored by the Indonesian military and by no means allowed to report freely. The BBC’s Indonesia editor, Rebecca Henschke, was granted a special permit to report on a malnutrition crisis in the region last year but was expelled shortly after arriving after posting tweets that “hurt the feelings” of soldiers. It is therefore unsurprising that Indonesia ranks 124th out of 180 countries in the 2019 World Press Freedom Index of the press freedom charity Reporters Without Borders. The charity concludes that President Jokowi did not keep his campaign promise to address media freedom in West Papua, with his presidency instead seeing drastic restrictions on access for foreign journalists and growing violence against local journalists who seek to report abuses by the Indonesian military. A free press nurtures free societies. Now, more than ever, we must defend it. That was the message of the Foreign and Commonwealth Office last week as we marked World Press Freedom Day. Never has that been more true than in the case of West Papua. We simply must ensure that journalists are able to report freely in the region, shining a light on wrongdoings when they occur, and generally scrutinising the actions of the authorities in West Papua. Ensuring that that happens will go a long way towards helping to protect the human rights of the West Papuan people. The UK is in an ideal position to take action on this issue. Last month, the UK Government announced that Amal Clooney had been made a special envoy on media freedom by the FCO and would head up a panel of legal experts looking to repeal anti-press freedom laws abroad and ensure that journalists across the world are free to report the truth. I therefore urge the Minister and the Foreign Secretary to ensure that this important panel, when it is established, investigates the situation in West Papua as a top priority. The panel, which is a wonderful initiative, can look at the restrictive laws that the Indonesian Government have put in place in West Papua, which have essentially created a media blackout in the region, and press the Indonesian Government to repeal them, enabling a free press, transparency and accountability in West Papua. The simple fact is that the human rights situation in West Papua cannot improve until President Jokowi delivers on his promise to allow greater press freedom in the region, which has thus far failed to happen. The panel therefore represents a golden opportunity to hold the Indonesian Government to their promises, ensuring that their warm words turn into hard action. Ultimately, a free media can prevail in West Papua, and I therefore hope that the Minister will assure me that he will make strong representations to the Foreign Secretary and Amal Clooney that West Papua must be an area of focus for the Defend Media Freedom panel. Jonathan Edwards- Hansard- Copy Link-- Excerpts I am grateful to the hon. Gentleman for giving way again; he is extremely generous. Will he add to his wish list the suggestion that the BritishGovernment use all their efforts and influence in Indonesia to secure access to West Papua for non-governmental organisations such as Amnesty International and the Red Cross? They have had difficulty visiting the area to see what is going on. Robert Courts- Hansard- Copy Link- That is a very sensible suggestion. I wonder whether the Minister will add that. Ultimately, I think the hon. Gentleman and I are looking for transparency, access and freedom, all of which are tied together. John Howell- Hansard- Copy Link-- Excerpts I wonder whether my hon. Friend will add to his list of things that could be done something that the University of Sydney has called for: a comprehensive investigation into the killing of Papuans by Indonesian forces. At the moment, we are left with the Asian Human Rights Commission, which produced a report in 2013 showing the savagery of Indonesian forces in dealing with this situation. Robert Courts- Hansard- Copy Link- I am grateful for that suggestion. I am keen that the Minister takes away two or three things that we may be able to achieve in the near future, and I am of course happy to add that request to the list. Ultimately, I think we are all making the same point, which is that an investigation carried out by an NGO or the press will achieve largely the same ends: transparency, clarity and an understanding of what is taking place in West Papua. I am grateful to my hon. Friend for adding that suggestion to the list. In conclusion, I leave the Minister with two modest requests from myself—and two from hon. Members—which, if followed through and achieved, could be immensely significant. They ought not to be controversial, as they essentially ask the Indonesian Government to honour promises they have already made. The first request is that the Minister encourages his counterparts in the Indonesian Government to honour that February 2018 invitation to the Office of the UN Commissioner for Human Rights to visit West Papua, and the second is that he ensures that the new FCO panel for press freedom investigates the situation in West Papua as a top priority. If we can ensure the free access of international media and independent human rights observers to West Papua, we will have taken an enormous step forward in protecting the human rights of the Papuan people, putting the region on the road towards a more free and prosperous future. I hope the Minister will be able to assure me and all others who have attended the debate—I note that the chairman of the all-party parliamentary group on West Papua, the hon. Member for Leeds North West (Alex Sobel), is here, and I welcome him—that he will take up these issues on behalf of the people of West Papua, whose cries for help have for far too long gone unanswered. The debate has helped give a voice to the voiceless. I hope the Foreign and Commonwealth Office will be able to help too. Mr Philip Hollobone (in the Chair)- Hansard- Copy Link-- Excerpts The debate can last until 5.30 pm. I am obliged to call the Front-Bench spokespeople no later than 5.8 pm. The guideline limits are five minutes for the Scottish National party spokesperson, five minutes for Her Majesty’s Opposition’s spokesperson and 10 minutes for the Minister. If the Minister will allow Robert Courts two minutes at theend to sum up the debate, that would be fantastic. Until 5.8 pm is Back-Bench time. Two Members are seeking to contribute, so there will be a time limit of six minutes each. Robert Courts- Hansard- Copy Link- I thank the Minister for his full and comprehensive response, and every hon. Member for taking part. Once again, I welcome Benny Wenda and my constituent Richard Samuelson to the Public Gallery. I thank them for having initiated the debate and I hope that they think it has advanced the cause of human rights in West Papua. I am grateful to all hon. Members for their points. I thank the hon. Member for Leeds North West (Alex Sobel) for what I will summarise as his robust response to the Foreign and Commonwealth Office; the hon. Member for Strangford (Jim Shannon) for his point about access to justice; the hon. Member for North East Fife (Stephen Gethins) for underlining my points about the visit of the UN High Commissioner for Human Rights and press freedom; and the hon. Member for Bishop Auckland (Helen Goodman) for making the point about political prisoners. I assure the Minister that I have heard everything he has said and I am glad that the FCO regularly raises the issue of press freedom. I underline the point that the Act of Free Choice lies at the heart of the real repression and the feeling of ill-justice, which are central to the cause. In the 70th year of diplomatic relations, I hope that the Minister and the FCO will continue and redouble their efforts, having heard how strongly hon. Members feel. On the panel to defend media freedoms, I understand its independence; I do not ask that the UK Government dictate to it but merely make suggestions. We have made great strides today. I am grateful to you for having listened to us in detail, Mr Hollobone. We have cast a searching gaze on the human rights situation in West Papua. We must ensure that we do not look away. Question put and agreed to. Resolved, That this House has considered human rights in West Papua.
https://www.parallelparliament.co.uk/mp/robert-courts/debate/2019-05-08/commons/westminster-hall/west-papua-human-rights
Telmitrust Ln: Uses, Price, Dosage, Side Effects, Substitute, Buy Online Find out about Telmitrust Ln benefits, side effects, price, dose, how to use Telmitrust Ln, interactions and contraindications <here is a image b9443e8cdad693c3-fa1cd1e2c2fe75ce> Telmitrust LN ☆ ☆ ☆ ☆ ☆ 5.0/5.0 (1 Ratings & 0 Reviews) 10 Tablet in 1 Strip ₹ 73 Telmitrust LN Tablet 10 TABLET 1 Strip ₹ 73 Out of Stock Manufactured by: Centaur Pharmaceuticals Pvt Ltd Contains / Salt: Cilnidipine (10 mg) + Telmisartan (40 mg) Telmitrust Ln Information Telmitrust Ln, a prescription drug, is manufactured in various forms such as Tablet. Telmitrust Ln also has some secondary and off-label uses. These are listed below. Medical history of the patient along with age and gender determines the dosage of Telmitrust Ln. The condition it has been prescribed for, and the route of administration also determine the right dosage. For detailed information on this, read through the dosage section. 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In addition to the above precautions for Telmitrust Ln, it is important to know that it is not safe while driving, and is not habit-forming. Telmitrust Ln Benefits & Uses Telmitrust Ln Dosage & How to Take Telmitrust Ln Side Effects Telmitrust Ln Related Warnings Severe Interaction of Telmitrust Ln with Other Drugs Telmitrust Ln Contraindications Frequently asked Questions about Telmitrust Ln Telmitrust Ln Interactions with Food and Alcohol Telmitrust Ln Benefits & Uses Telmitrust Ln is used to treat the following - Other Benefits High BP(Read More -Home Remedies for High Blood Pressure) <here is a image 3e9916784ef10738-e26bf04f7291504d> Telmitrust Ln Dosage & How to Take This is the usual dosage recommended in most common treatment cases. Please remember that every patient and their case is different, so the dosage can be different based on the disease, route of administration, patient's age and medical history. <table><tbody><tr><td> Age Group</td><td> Dosage</td></tr><tr><td>Adult</td><td> Disease:High Blood Pressure Before or After Meal:Either Single Maximum Dose:1 Tablet Dosage Form:Tablet Dosage Route:Oral Frequency:1 daily Course Duration:As directed by the doctor Special Instructions:strength 40 mg telmisartan and 10 mg cilnidipine</td></tr><tr><td>Geriatric</td><td> Disease:High Blood Pressure Before or After Meal:Either Single Maximum Dose:1 Tablet Dosage Form:Tablet Dosage Route:Oral Frequency:1 daily Course Duration:As directed by the doctor Special Instructions:strength 40 mg telmisartan and 10 mg cilnidipine</td></tr></tbody></table> Telmitrust Ln Side Effects Based on research, the following side effects have been observed when Telmitrust Ln is used - Severe Dizziness Tachycardia Bradycardia Moderate Ankle Swelling Flushing Edema Mild Fatigue Drowsiness Headache Nausea or vomiting पेट दर्द Weakness Stomach ache(Read More -Home remedies for stomach pain) Common Back Pain <here is a image ffab78ed4e578db7-acef09b9a46b877d> Telmitrust Ln Related Warnings Is the use of Telmitrust Ln safe for pregnant women? Pregnant women may get severe side effects after taking Telmitrust LN. If you are pregnant, do not take Telmitrust LN without a doctor's advice. Is the use of Telmitrust Ln safe during breastfeeding? Side effects of Telmitrust LN for breastfeeding are little to none, so you can take it without doctor's advice. What is the effect of Telmitrust Ln on the Kidneys? Telmitrust LN does not damage the kidneys. What is the effect of Telmitrust Ln on the Liver? Telmitrust LN is rarely harmful for the liver. What is the effect of Telmitrust Ln on the Heart? Very few cases of side effects of Telmitrust LN on the heart have been reported. Severe Interaction of Telmitrust Ln with Other Drugs Telmitrust Ln should not be taken with following medicines due to severe side effects it may cause to patients - Amlodipine Amlodac 2.5 Tablet Amlodac 5 Tablet Amlogard 10 Tablet (30) Amlogard 2.5 Tablet (30) Telmitrust Ln Contraindications If you are suffering from any of the following diseases, you should not take Telmitrust Ln unless your doctor advises you to do so - Aortic Stenosis Angina Heart Disease Allergy Low Blood Pressure Angioedema Hyperkalemia Drug Allergy Frequently asked Questions about Telmitrust Ln Is this Telmitrust Ln habit forming or addictive? Telmitrust Ln does not cause addiction. Telmitrust Ln Interactions with Food and Alcohol Interaction between Food and Telmitrust Ln Telmitrust Ln may take longer to act if you eat some foods while taking it. Follow your doctor's advice on this. Interaction between Alcohol and Telmitrust Ln Consumption of alcohol and Telmitrust Ln together may have severe effects on your health. Vikas Chauhan References April Hazard Vallerand, Cynthia A. Sanoski. [link]. Sixteenth Edition. Philadelphia, China: F. A. Davis Company; 2019: Page No 169-173 KD Tripathi. [link]. Seventh Edition. New Delhi, India: Jaypee Brothers Medical Publishers; 2013: Page No 507 US Food and Drug Administration (FDA) [Internet]. Maryland. USA;Package leaflet information for the user; Micardis® (telmisartan) US Food and Drug Administration (FDA) [Internet]. Maryland. USA;Package leaflet information for the user; Twynsta® (telmisartan/amlodipine)
https://www.myupchar.com/en/medicine/telmitrust-ln-p37115070?ref=raisan-21
Polymers | Free Full-Text | Crosslinked Polyethylene (XLPE) Recycling via Foams Efficient recycling of crosslinked polyethylene has been challenging due to manufacturing difficulties caused by chemical crosslinking. This study focuses on simple processing via solid waste powder generation and particle fining for the subsequent crosslinked polyethylene inclusion and dispersion in rigid polyurethane foam. In addition, the concentration effects of crosslinked polyethylene in polyurethane were studied, showing a well-controlled foam microstructure with uniform pores, retained strength, better thermal degradation resistance, and, more importantly, increased thermal capabilities. Thus, the simple mechanical processing of crosslinked polyethylene and chemical urethane foaming showed the massive potential of recycling large amounts of crosslinked polyethylene in foams for broad applications in food packaging, house insulation, and sound reduction. Crosslinked Polyethylene (XLPE) Recycling via Foams Mohammed Bawareth 1 , Weiheng Xu 2 , Dharneedar Ravichandran 2 , Yuxiang Zhu 2 , Sayli Jambhulkar 2 , Nathan Fonseca 1 , Guillaume Miquelard-Garnier 3 , Visnansky Camille 4 , Kenan Song 6,* 1 Mechanical Systems Engineering, The Polytechnic School (TPS), Ira A. Fulton Schools for Engineering, Arizona State University, Mesa, AZ 85212, USA 2 Systems Engineering, The Polytechnic School (TPS), Ira A. Fulton Schools of Engineering, Arizona State University, Mesa, AZ 85212, USA 3 Laboratoire PIMM, UMR 8006, Arts et Métiers Institute of Technology, CNRS, CNAM, Hesam University, 151 boulevard de L’Hôpital, 75013 Paris, France 4 Salt River Project (SRP), 1500 N. Mill Ave., Tempe, AZ 85281, USA 5 Rob and Melani Walton Sustainability Solutions Service, Arizona State University, Tempe, AZ 85287-8009, USA 6 The Polytechnic School (TPS), The School of Engineering of Matter, Transport and Energy (SEMTE), Ira A. Fulton Schools of Engineering, Arizona State University, Mesa, AZ 85212, USA * Author to whom correspondence should be addressed. Polymers 2022 , 14 (13), 2589; https://doi.org/10.3390/polym14132589 Received: 1 May 2022 / Revised: 12 June 2022 / Accepted: 23 June 2022 / Published: 26 June 2022 (This article belongs to the Section Polymer Processing and Engineering ) Versions Notes Abstract : Efficient recycling of crosslinked polyethylene has been challenging due to manufacturing difficulties caused by chemical crosslinking. This study focuses on simple processing via solid waste powder generation and particle fining for the subsequent crosslinked polyethylene inclusion and dispersion in rigid polyurethane foam. In addition, the concentration effects of crosslinked polyethylene in polyurethane were studied, showing a well-controlled foam microstructure with uniform pores, retained strength, better thermal degradation resistance, and, more importantly, increased thermal capabilities. Thus, the simple mechanical processing of crosslinked polyethylene and chemical urethane foaming showed the massive potential of recycling large amounts of crosslinked polyethylene in foams for broad applications in food packaging, house insulation, and sound reduction. Keywords: crosslinked ; polyethylene ; polyurethane ; recycling ; foam ; thermal insulator 1. Introduction Cable recycling traditionally focuses on metal recovery (i.e., copper, aluminum), and the plastic cover is usually overlooked. For example, the Salt River Project (SRP) facility (Arizona, USA) annually produces ~540 tons of crosslinked polyethylene (XLPE) plastic waste from electricity wires, and most of this plastic material is currently sent to either landfill or incineration, resulting in land pollution or CO 2 generation (e.g., every ton of XLPE burnt for heating would generate three tons of CO 2 ) [ 1 ]. However, commercial XLPE recycling is challenging due to technical and economic reasons. First, a chemical or irradiation process for synthesizing polyethylene (PE) networks achieves high-density crosslinking at the molecular level [ 2 ]. Crosslinking substantially improves compression strength, compression set, tensile strength, thermal stability, and water absorption resistance [ 3 ]. However, due to covalent bonds forming the network, XLPE behaves as a thermoset that would degrade before melting, posing challenges in mechanical and physical recyclability [ 4 , 5 , 6 ]. Second, there are currently a few methods of decrosslinking, but their involvement of supercritical fluids or cryogenic gases far exceeds the cost of landfill or incineration [ 7 ]. So far, repurposing of XLPE without any chemical modification has only been achieved in a few cases, such as polymer-reinforced concrete pavement [ 4 ]. Adding shredded XLPE waste replaces medium-size natural aggregates, enhancing cement mechanical performance [ 4 ]. However, the thermal stability of plastics in cement and their potential degradation with the release of toxic gas can raise questions regarding environmental safety and human health. Therefore, there is an urgent need to find an efficient recycling method for turning recycled XLPE into new applications with higher-end values. Foams are usually a disordered mixture of air cells or bubbles with monodisperse structure or non-uniform pore size and dispersions [ 8 ]. The foaming processes have three classifications: mechanical foaming, physical foaming, and chemical foaming [ 9 ]. Mechanical foaming occurs by mixing air with polymer resins during or after mechanical stirring. Physical foaming involves thermodynamics regulations due to adjusting temperature and pressure to control polymer microstructures. Chemical foaming is mixing a blowing agent or polymer additive with a matrix to initiate reaction-induced pores. The control over pore size, porosity, and open-/closed-cell morphologies offering reduced weights and superior performance can broaden the foam applications in structural supports, thermal insulators, sound reductions, and biomedical devices. Among all cellular solid materials, the XLPE and rigid polyurethane foam (RPUF) are two primary foaming materials due to their facile processing, low cost, and similar thermal conductivity for insulation purposes [ 10 , 11 ]. The PU foams are obtained by mixing a polyester diol and a diisocyanate, during which procedure the polyol hydroxyl (-OH) and isocyanate functional (-NCO) groups create a urethane linkage reaction [ 12 , 13 ]. These fast-curing and simple reactions without organic solvents are potentially transferrable in XLPE processing as cost-efficient, scalable recycling for thermal barrier or heat dissipation usages [ 14 ]. This research explored the possibility of including XLPE in RPUF as a microparticle filler and using them for scalable foams as household insulators. In addition to studies of the mechanical properties, this project mainly explored the thermal behaviors of RPUF/XLPE as a function of compositions and morphologies. This project has leveraged the simple processing of physical separation, pelletizing, and foaming to alter porous microstructures and improve thermal behaviors. As a result, the RPUF/XLPE foams have shown different pore sizes, porosity/density, mechanical behaviors, and thermal properties, with a high potential to serve as thermal insulators. 2. Materials and Methods 2.1. Materials and Foam Processing XLPE solid waste from insulated stranded cable was provided by Salt River Project (SRP) ( Figure 1 a,b). These solid wastes in the form of large pellets mainly contain XLPE and metal powders (e.g., copper, aluminum). Subsequently, soaking these mixtures in water via the floating method separated metals from the polymer. In addition, a tip sonicator (SFX250 Sonifier, Branson, Missouri, MO, US) was added to the system to agitate the aluminum particles at 80 °C. The sonication setting was in pulse mode with the on/off frequency of 20/30 s during 2 h and a power amplitude of 175 W ( Figure 1 c,f). The washed XLPE was stored for 24 h inside a hood with a ventilation system to dry out completely. Then, the dried XLPE was inserted inside a continuous process grinder (Reclaimer, FILABOT, Barre, VT, US) for 1–2 min at 0.75 kW to reduce the particle size ( Figure 1 d,g) before being inserted into a batch process miller (High-Speed Multi-Function Comminutor, Zhejiang Wanji Plastic Industry Co., Ltd., Zhejiang, China) for 5 min at 2.3 kW, thus forming polymer microparticles ( Figure 1 e,h). RPUF was obtained from Smooth-On as the product of FOAM-iT™ 5, which includes two separate components of parts A and B for the foaming reaction. Part A is a composite of s 4,4′ methylene bis(phenyl isocyanate) (MDI) [ 15 ], and part B is a composite of ether polyols with silicone surfactant and water [ 16 ]. The RPUF/XLPE blend foams were prepared via the following steps. First, the MDI, ether polyols, and XLPE were mixed with mechanical stirring for 45 s. Then, the viscous mixture was poured into different silicon molds with a curing time of 2 h. Consequently, the XLPE microparticles were dispersed during the RPUF foaming reaction. The molds were ( i ) a parallelepiped shape with 30 × 30 mm 2 , ( ii ) a parallelepiped shape with 50 × 50 mm 2 , and ( iii ) a cylindrical shape with 50 mm diameter. After curing, the samples were cut (i.e., a size of ( i ) 8 ± 0.5 mm, ( ii ) 30 ± 0.5 mm, and ( iii ) 40 ± 0.5 mm) with a bandsaw. As a result, the samples were created with XLPE concentrations of 0 wt%, 16.67 wt%, 33.33 wt%, and 47.37 wt%. ( i ) Samples were used to determine the density and thermal properties. ( ii ) Samples were used to assess the thermal response. ( iii ) Samples were used to measure the mechanical properties—other experiments were required to reduce the sample size, such as morphology and thermogravimetric analysis. 2.2. Characterization Methods XLPE Particle Size: Optical images were recorded using a 3D Measurement System (VR-3000 Wide-Area 3D Measurement System, KEYENCE, Japan), with a camera brightness of 200–250 and a magnification of 12×. The images were analyzed by the ImageJ software tool to determine the particle size and size distributions. Then, the data were analyzed statistically to eliminate the outliers by whisker plot before determining the average size and standard deviations. Foam Density: Twelve samples with four different concentrations were used to measure the foam density. The foam density was obtained from the gravimetric method (Equation (1)), measuring the foam weight via an analytical balance (AB54-S, Mettler Toledo, Columbus, OH, USA) and volume via electronic calipers (Ultra-Cal V, Fowler, Newton, MA, USA). The foam density ( ρ ) was based on a bulk-sized dimension (i.e., l is the foam length, w is the width, and t avg is the average thickness) [ 17 ]. ρ = m n / ( l × w × t a v g ) (1) Foam Morphology: Four samples with four different concentrations were used to capture the foam morphology. The foam morphology was captured from a scanning electron microscope (SEM) (Auriga, Zeiss, Jena, Germany) with the foam surfaces coated with a 15 nm Au/Pd layer to increase conductivity. Mechanical Properties: Sixteen samples with four different concentrations were used to determine the mechanical properties. The mechanical properties were measured by following the ASTM D1621-16 (i.e., Standard Test Method for Compressive Properties of Rigid Cellular Plastics) standard at a speed rate of 0.0416 mm/s using a universal test machine (5985 Testing Mechanics, Instron, Norwood, MA, USA). Degradation Analysis: Eight samples with four concentrations were used for thermogravimetric analysis. Degradation starting points were evaluated by a thermogravimetric analyzer (TGA, TA Instruments, New Castle, DE, USA). The tests started from 0 °C to 900 °C with a 10 min/°C heating ramp rate in two environments of air and nitrogen. Thermal Conductivity: Eight samples with four concentrations were used to quantify the thermal properties. Each sample had four runs. The thermal conductivity ( K ), diffusivity ( α ), and volumetric specific heat ( Q v ) were measured by a thermal analyzer (TPS 2500 S, Hot Disk, Gothenburg, Sweden). The disk sensor type was Kapton 5501 with a transient plane source of 4.67 × 10 −3 K −1 and thermal resistance of 6.74 Ω. The probing depth was 6.403 mm, and the measurement time was 40 s. Based on the temperature transient response and residual temperature response, each sample’s heat flow was adjusted to 15–40 mW [ 18 ]. Then, the specific heat capacity ( C P ) was calculated by Equation (2). C p = Q v / ρ (2) Thermal Responses: The thermal responses were used to calculate the theoretical conductive heat to change temperature. The analysis was based on Fourier’s Law [ 19 , 20 ]. Equation (3) expresses linear conductive heat transfer, q ( x ), where A is the heated cross-sectional area, t is the sample thickness, and dT = T 2 − T 1 is temperature variation between two measurement points. Equation (4) expresses the transient heat transfer as a function of time in any localized point, q ( t ), where m is the sample mass and [ T ( t ) − T 0 ] is the temperature change at the localized point as a function of time. q ( x ) = K A ( d T ) / t (3) [ T ( t ) − T 0 ] = q ( t ) / ( m C p ) (4) The thermal responses were measured and recorded by two methods to collect numerical data and thermal images on two samples, RPUF and RPUF/XLPE 33.33 wt%. Each sample had three runs. First, the temperature response data were measured by a digital multimeter (DMM7510, Keithley, Cleveland, OH, USA). Next, the samples were heated by a rheometer (HR-2, TA Instruments, New Castle, DE, USA) ( Figure 2 a). The test had two configurations: a steady-state environment and fluctuating environment. ( i ) In the steady-state environment, the temperature started at 0 °C with a soaking time of 20 min. Then, the temperature increased to 100 °C at 5 min/°C. Next, the temperature remained constant for 20 min. After that, the temperature decreased to 0 °C by 20 min/°C. The cycle was repeated four times with four different heating increments of 5, 10, 15, and 20 min/°C. ( ii ) In the fluctuating environment configuration, the same procedure of the steady-state configuration was followed but with only one initial soaking time at the first cycle. The thermal images were recorded in heating and cooling by an infrared digital camera (E8, Teledyne FLIR, Wilsonville, OR, USA) ( Figure 2 b). During heating, all samples were placed simultaneously on a hot plate at 100 °C. During cooling, both samples were placed on a hot plate for 15 min. Then, they were placed on a white non-reflective surface. For every 45 s cycle, thermal images were acquired for heating and cooling experiments. 3. Results and Discussion 3.1. XLPE Particulate Fining Foams from extrusion, injection molding, and multilayering usually have the pore sizes distributed at the microscale [ 21 , 22 , 23 ]. The obtained XLPE wastes have large pellets (i.e., 5–10 mm) that would be hard to include in porous media. Therefore, a series of preprocessing steps were used for fine powder generation. As stated previously, the mechanical treatment used in this study includes metal separation ( Figure 1 c,f), grinding ( Figure 1 d,g), and shredding/milling ( Figure 1 e,h). Optical imaging of samples after these processing steps ( Figure 3 a–c) and the ImageJ analyses show the efficient XLPE size reduction from 8.0 ± 2.3 mm to 9.4 ± 7.0 µm ( Figure 3 d,e) [ 24 ]. 3.2. Foam Density Conventional RPUF and XLPE have a density of 0.05–1 g/cm 3 and 0.91–0.94 g/cm 3 [ 25 , 26 ], respectively. The RPUF/XLPE foam density increased with a higher XLPE weight percentage ( Figure 4 a). The digital photos of these foams also show the contrast between RPUF and XLPE ( Figure 4 b–e), with varying XLPE concentrations exhibiting distinct pores among samples. 3.3. Foam Morphology The foam microstructure influences its mechanical and thermal behaviors, with the SEM images ( Figure 5 a–d) showing the foam morphology as a function of XLPE addition. Adding XLPE content did not change the foam formability and decreased the pore size ( Figure 5 e). Additionally, these SEM images show a closed-cell structure consistently, providing unique advantages in insulating heat and enclosing sound waves [ 27 ]. Lastly, there is a critical point where the foam morphology loses its pore size uniformity to an undesirable point due to the loss of structural integrity with specific XLPE content (e.g., Figure 5 d). 3.4. Mechanical Properties The mechanical compression tests in Figure 6 show the XLPE influences on compressive modulus and strength up to a compression strain of 95% ( Figure 6 a). An increase in XLPE addition decreased the modulus (i.e., 15.8 kPa in RPUF vs. 12.5 kPa in RPUF/XLPE 33.33 wt% XLPE, Figure 6 b) but significantly improved the compressive strength under large strains (i.e., 23.8 MPa in RPUF vs. 73.6 MPa in RPUF/XLPE 33.33 wt% XLPE at a strain of 95%) ( Figure 6 a,b). Experimentally, a higher than 47.37 wt% XLPE in RPUF will disrupt the porous media and degrade the mechanical integrity (e.g., a modulus drop from 15.8 MPa in RPUF foams to 8.3 MPa with a 47.37 wt% XLPE), which is consistent with the morphology ( Figure 5 d). Furthermore, cell density’s uniformity and circular cell aspect ratio were reconstructed in the foam structure by adding XLPE microparticle fillers to non-uniform cell density and ellipsoidal cell aspect ratio. As a result, the Young’s modulus decreases [ 28 ]. 3.5. Degradation Points TGA tests show the thermal degradation starting points in an atmosphere of air ( Figure 7 a) and nitrogen ( Figure 7 b). The transition temperatures at a 10 wt% loss (i.e., Temp at 90%) are listed in Figure 7 . XLPE showed higher thermal resistance than RPUF (e.g., ~381 °C for XLPE and ~274 °C for RPUF for the initial thermal degradation in air, Figure 7 a); thus, the increase of XLPE in RPUF showed enhanced degradation starting point resistance as compared to RPUF ( Figure 7 a,b). The air fully degraded the foams to amorphous carbon while the N 2 retained the foam shape, consistent with the carbon residue ~10 wt% in RPUF/XLPE ( Figure 7 b L ). For minimal thermal degradations, the thermal conductivity and response tests were at temperatures < 100 °C. 3.6. Thermal Conductivity and Diffusivity Properties The thermal dissipation of the foams plays an essential role in their applications as thermal barriers. The thermal conductivity increased slightly and quasi-linearly with increasing XLPE ratios (i.e., ~0.04 in RPUF to ~0.06 in RPUF/47.37 wt% XLPE, Figure 8 a), showing their potential as thermal insulators that in many applications require K under 0.1 W/mK [ 29 ]. The thermal conductivity of RPUF/XLPE increases with increasing XLPE content due to the high thermal conductivity of XLPE. Polyethylene’s thermal conductivity could be as high as 20 W m −1 K −1 [ 30 ]. The dispersed XLPE microparticles behaved as energy storage units inside the RPUF. Thermal diffusivity, defined by the thermal conductivity divided by density and specific heat capacity at constant pressure, measures the heat propagation rate from the hot end to the cold end. With increasing XLPE, α decreased, confirming the foam’s capability to prevent quick thermal energy loss (e.g., it is more time-consuming for specific heat to dissipate in RPUF/XLPE than pure RPUF, Figure 8 b). The volumetric specific heat and specific heat capacity increased, which shows the amount of heat needed to change the temperature at a specific volume ( Figure 8 c) and mass ( Figure 8 d). 3.7. Thermal Response An in-house setup was built to detect the temperature change as a function of temperature and time in fluctuating-state ( Figure 9 a) and steady-state ( Figure 9 b) ( Figure 2 ). In both cases, the RPUF/XLPE 33.33 wt% showed lower temperature changes than the RPUF, consistent with the thermal properties (i.e., K , α , Q v , and C p ) in Figure 9 . The temperature change in steady-state does not show sufficient improvement in thermal stability relative to fluctuating-state. However, thermal barrier applications such as house insulators and wind turbine nacelle operate in fluctuating-state [ 31 , 32 , 33 ]. The lower surface temperature within the same heating range ( Figure 9 c) and the slower cooling rate ( Figure 9 d) in RPUF/XLPE 33.33 wt% suggested their advantage as a thermal barrier, e.g., in food packaging applications. Concurrently, the theoretical thermal predictions from Equations (3) and (4) indicate that higher thermal conductivity or specific heat capacity leads to lower temperature variations ( dT ) (i.e., with constant thermal energy in the system of 0.173 W, Figure 9 e). 4. Conclusions XLPE recycling methods usually require supercritical decrosslinking techniques, which are not yet economically feasible for industrial processing. Our proposed recycling method aimed to optimize the thermal properties, mechanical integrities, manufacturing scalability, and cost-efficiency via simple plastic particle size control and urethane-based foam engineering. The XLPE microparticles were included in RPUF for thermal purposes by reducing the size via mechanical shredding and milling. The initial average XLPE particle size was ~8 mm, reduced to the final XLPE particle size of ~9 µm with enhanced dispersion quality in foams. In addition, the XLPE concentration effects were studied, showing fine morphology control (e.g., pore size and surface roughness), retained mechanical robustness, higher thermal resistance, and better diffusivity parameters. For example, the RPUF/XLPE 33.33 wt% showed a 10% weight loss temperature of ~296 °C, as compared to the 10% weight loss temperature of ~275 °C in RPUF. Similarly, it exhibited a temperature variation of ~12 °C during the fluctuating configuration control, while the RPUF sample was ~22 °C. Thus, this research demonstrated the foaming strategies of RPUF/XLPE compounds as a simple and cost-efficient method of recycling XLPE for thermal applications (e.g., house insulators, automotive headliners, or wind turbine nacelle). Informed Consent Statement Not applicable. 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Thermal Analysis of Wind Turbine Nacelle Operating in Algerian Saharan Climate. Energy Procedia 2012 , 18 , 187–196. [ Google Scholar ] [ CrossRef ][ Green Version ] Figure 1. ( a ) XLPE pellets, ( b ) zoom-in with 40 mm scale bar of the XLPE solid waste pellets, plastic waste fining processes for powders and microparticles via ( a ) metal separation from plastics, ( b ) grinding, ( c ) shredding and milling, and ( d – h ) the corresponding processing instruments. Figure 1. ( a ) XLPE pellets, ( b ) zoom-in with 40 mm scale bar of the XLPE solid waste pellets, plastic waste fining processes for powders and microparticles via ( a ) metal separation from plastics, ( b ) grinding, ( c ) shredding and milling, and ( d – h ) the corresponding processing instruments. Figure 2. Experiment setups for ( a ) collecting numerical temperature response data and ( b ) thermal images for temperature change. Figure 2. Experiment setups for ( a ) collecting numerical temperature response data and ( b ) thermal images for temperature change. Figure 3. ( a – c ) the optical images of fining XLPE to powders for each process and ( d , e ) the final particle size distributions. Figure 3. ( a – c ) the optical images of fining XLPE to powders for each process and ( d , e ) the final particle size distributions. Figure 4. ( a ) RPUF/XLPE density measurements for samples ( b ) RPUF, ( c ) RPUF/XLPE 16.67 wt%, ( d ) RPUF/XLPE 33.33 wt%, and ( e ) RPUF/XLPE 47.37 wt%. Figure 4. ( a ) RPUF/XLPE density measurements for samples ( b ) RPUF, ( c ) RPUF/XLPE 16.67 wt%, ( d ) RPUF/XLPE 33.33 wt%, and ( e ) RPUF/XLPE 47.37 wt%. Figure 5. The SEM images for foams of the ( a ) RPUF, ( b ) RPUF/XLPE 16.67 wt%, ( b g ) XLPE microparticle fillers with 100 µm scalebar, ( c ) RPUF/XLPE 33.33 wt%, ( c g ) XLPE microparticles, and ( d ) RPUF/XLPE 47.37 wt%, ( e ) whisker box plot of pore size area vs. XLPE content. Figure 5. The SEM images for foams of the ( a ) RPUF, ( b ) RPUF/XLPE 16.67 wt%, ( b g ) XLPE microparticle fillers with 100 µm scalebar, ( c ) RPUF/XLPE 33.33 wt%, ( c g ) XLPE microparticles, and ( d ) RPUF/XLPE 47.37 wt%, ( e ) whisker box plot of pore size area vs. XLPE content. Figure 6. ( a ) Compression tests following the standard ASTM D1621-16 (i.e., Standard Test Method for Compressive Properties of Rigid Cellular Plastics), with the ( b ) zoomed-in elastic regions and ( c ) Young’s modulus as a function of the XLPE content. Figure 6. ( a ) Compression tests following the standard ASTM D1621-16 (i.e., Standard Test Method for Compressive Properties of Rigid Cellular Plastics), with the ( b ) zoomed-in elastic regions and ( c ) Young’s modulus as a function of the XLPE content. Figure 7. Thermogravimetric (TGA) tests of RPUF with XLPE additions and pure XLPE with the temperature at 10% weight loss in an atmosphere of ( a ) air, ( b ) N 2 , and ( b L ) the residue of RPUF/XLPE 47.37 wt%. Figure 7. Thermogravimetric (TGA) tests of RPUF with XLPE additions and pure XLPE with the temperature at 10% weight loss in an atmosphere of ( a ) air, ( b ) N 2 , and ( b L ) the residue of RPUF/XLPE 47.37 wt%. Figure 8. Result of thermal properties of RPUF with varying XLPE percentages: ( a ) thermal conductivity, ( b ) thermal diffusivity, ( c ) volumetric heat capacity, and ( d ) specific heat capacity. Figure 9. The result of the thermal response between 0 wt% and 33.33 wt% RPUF in XLPE: ( a ) fluctuating-state, ( b ) steady-state; thermal imaging for detecting ( c ) heating, ( d ) cooling history, and ( e ) the theoretical temperature change by conduction. Figure 9. The result of the thermal response between 0 wt% and 33.33 wt% RPUF in XLPE: ( a ) fluctuating-state, ( b ) steady-state; thermal imaging for detecting ( c ) heating, ( d ) cooling history, and ( e ) the theoretical temperature change by conduction.
https://www.mdpi.com/2073-4360/14/13/2589
Why Shakespeare is Julie Taymor’s Superhero | Arts & Culture| Smithsonian Magazine For the renowned director of the screen and stage, the Bard is a fantasy and a nightmare ARTS & CULTURE Why Shakespeare is Julie Taymor’s Superhero Marco Grob / Trunk Archive For such a physically slight, ballerina-like figure, Julie Taymor is metaphysically fierce. The fact that she arrives at our rendezvous in a New York bistro buzzing with adrenaline, having just come from the first rehearsal of her new production of A Midsummer Night’s Dream, only intensifies the impression. She’s on a Shakespeare high, and her enthusiasm for the relevance of Shakespeare is contagious. Most of the world knows Julie Taymor as the director of The Lion King, the epic, viral Broadway smash that has circled the globe. It’s become a modern myth, virtually Homeric. A wild spectacle that, as she puts it, “got to the DNA” of a vast audience and wrapped their double helixes around her finger. But there’s another Julie Taymor, lesser known and more surprising: the one who took one of Shakespeare’s most obscure, most brutal, haunting and mystifying tragedies— Titus Andronicus—and turned it into one of the greatest Shakespearean films ever. She made Titusin 1999 on a big budget with Anthony Hopkins playing the tragic title character and Jessica Lange playing Tamora, Queen of the Goths. Taymor took what had seemed to me a play that was a bit stilted on the page and blew it up into a magnificent Fellini/Scorsese fusion of raw bloody Shakespearean fury. I’m not exaggerating: I watched it again recently at a screening at the Museum of Modern Art and felt like I had been given a metaphysical punch to the gut. I say this as someone who has watched virtually every major Shakespearean film in the course of writing a book on Shakespearean scholars and directors. Tituscreates an intensity so breathtaking it makes you forget the rest of the world. It made me rethink human nature, made me rethink Shakespeare’s nature. How could he have harbored such a horrific and merciless vision so early (he wrote Titus Andronicuswhen he was not yet 30, at least six years before Hamlet). It also made me rethink Julie Taymor’s nature. How could the person who created The Lion King, with the theme of “The Circle of Life,” also create a Titus, which might well be called “The Circle of Death”? My mission, I decide even before meeting her, is to get people to see Titus and recognize just how utterly contemporary and relevant it is to the war-torn, terror-ridden world we live in today. “It was massive!” I say to her as we sit down. “It was massive!” she agrees. “My first feature. And it was so exciting.” She takes a sip of prosecco. She reminds me of that line in A Midsummer Night’s Dream: “Though she be but little, she is fierce!” (Well, she’s not thatlittle, but she radiates furious, focused energy.) The wild stories she tells in the big book about her work, aptly titled Playing With Fire, testify to that ferocity: about her time on a fellowship in Indonesia, putting together a theater troupe in the wild outback of Bali, daring the fires of live volcanoes, developing the unique Javanese and Balinese-influenced huge-mask-and-giant-puppet-based theater art that eventually made The Lion Kingsuch a spectacle. “Oh, it’s the best!” she declares with utter finality. “I love to do musicals and operas, but that’s because they take you to another plane of existence. But for me Shakespeare is the most challenging. He’s the most far-out, the most wicked and spiritual, and demonic and philosophical. In one play!” Of course Titusis not the only Shakespeare Taymor has done. She’s directed four versions of The Tempest, the last a brilliant film featuring Helen Mirren playing “Prospera,” the traditionally male Prospero role, in an extraordinarily revealing way. And now she’s doing A Midsummer Night’s Dreamoff Broadway. She describes for me her primal experience with Shakespeare’s Dream. “I remember being at Oberlin College and taking a bus 15 hours with my fellow schoolmates to New York to see Peter Brook’s Dream,” she says. It was a historic production, a production I also saw, that changed the way Shakespeare was done on both sides of the Atlantic. “It had a powerful effect on me. And I don’t think I’ve seen a good one since, so I’ve pretty much avoided it for years. Partly because after The Lion KingI did Titusand that’s the natural way to go—you do The Lion Kingand then you do Titus.” Circle of Life, Circle of Death. “A bare stage—” I began to describe Brook’s set design, a kind of luminescent white box. “Not a bare stage,” she counters. “The Globe [Shakespeare’s main venue] was a bare stage. It’s interesting because the Brook was revolutionary for our time, but not really for Shakespeare’s day, because in Shakespeare’s day it was just an empty stage and empty space—and you used your imagination.” She tells me she’s devised a different kind of box for her Dreamstage. “The audience is on three sides and it’s basically a magic black box, like a Japanese lacquered black box, that has holes and windows and traps. But we’re using the idea there’s a prologue which is a bed.” A bed as a prologue? “This character [who turns out to be Puck, the chief instigator of mischief among the lovers in the play] is sleeping in a bed and from out of the earth trees push the mattress up and it floats, and then the bedsheets get attached and the mechanicals—the real mechanicals, my workmen—pull out the sheet and it becomes a canopy which becomes the sky. What I’m trying to do is what I think the play does so brilliantly—it goes from the poetic to the mundane, from the magical to the banal, kind of gossamer and intangible to the concrete and, you know, gaudy and real.” She speaks almost as if possessed. “It’s earthiness and concrete,” she goes on, “it’s there, you can touch it. A person sleeping in a bed dreams...trees grow, the bed floats, then these kind of New York guys come out and attach a hook and you see them pulling a light circuit, they pull the bedsheet up and it’s a sky! It’s a sky!” The bedsheet/sky she says is her “ideograph” for this production, a word she uses for an emblematic design element—the play is about love and sex, after all—and everything else in her visual scheme grows out of it. Taymor started off as a theater set designer and she’s always found her way into a play through visual concepts. (Her ideograph for The Lion King, she says, was the wheel, from the Circle of Life to the bicycles the antelopes rode.) “So from the bed, they start to make the trestle table for the wedding,” she says. “They do what I feel we as humans do—we take nature, we take a tree, and we make chairs, we make tables, we make concrete things out of natural ones. So we’re constantly reforming and reshaping what is nature into something practical, mechanical, useful. Weddings, marriages are useful because they control our inner natures. They put boundaries and handcuffs on our natural instincts.” She speaks about the spirituality she finds in her productions. “There’s a certain point of divine spirit that is inexplicable. You either feel it or you don’t. It takes you to another level. It happened in The Lion King—people don’t know why they cry. They don’t know! Something in the art of it touched them in a deep DNA way. And I’ve been able to be involved in productions that have had that effect on me, on the performers, on the audience....” She takes a breath. “That’s what I strive for.” And she finds it over and over again in Shakespeare. For instance, the eternal question of love at first sight, the bewitching focus of A Midsummer Night’s Dream. “What does the play do with that? What do we learn?” “We usually think that if we see with the eye, it’s superficial,” she says, “but in this play it’s kind of opposite. You can see with the mind or heart. That I find a tough concept that Shakespeare’s bringing out...that he’s on a whole other level of what ‘seeing’ and ‘loving’ means.” “Do you mean he sees love at first sight as something arbitrary?” She’s read this too in her research, she says, but she begs to differ: “Are they out of their minds?! These are extremely well-etched and differentiated characters. Lysander is like a hippie, a poet. He’s not loved by Egeus [the father] because he is an artist. And that’s what little Hermia falls in love with. Demetrius is Wall Street....They’re unbelievably opposite.” Lysander and Hermia go into the forest and Puck mistakenly puts drops of the play’s love potion in Lysander’s eyes, a potion made from the distillation of a flower called “love in idleness.” “It’s a psychedelic!” Taymor exclaims. “The humor is obviously with the herb, because when Lysander wakes up with the drops in his eyes, he just dumps Hermia and easily falls in love with Helena, the first person to cross his path. But it’s not a true love, is it?” “A potion is a juice, but the emotions—” I start to say. “The emotion is unleashed!” she says, “and I think that Shakespeare’s saying that’s how easily we can switch our passions. A little thing can do it. Whether it’s love juice, a psychedelic drug or somebody swishes by in a different way—that love is extremely fickle. I think a lot of this is about all different levels of love, just like Titusis about every single aspect of violence.” Circle of Love. Circle of Death. This brings her to a hole she’s spotted in the plot. It involves Demetrius, the Wall Street type, who is spurned by Hermia but loved by Helena, whom he spurns. Until, Taymor says, he wakes up with the juice in his eyes and says, “‘And now Helena who I always loved’ and you have to think—he’s on a drug.” But she says, unlike the other youth—the poetic Lysander who gets the antidote for his drug and switches his affections back from Helena to Hermia—Demetrius “never gets off the drug,” Taymor says. “Because at the end [Shakespeare] didn’t take the drug off,” Taymor says. Perhaps he didn’t have the time. Or he forgot. “He probably wrote it over a weekend,” she says. “Demetrius is still in love with Helena. We have no idea if he had an antidote to the drug or that the drug didn’t wear off and he found his true self.” In other words this “hole,” this apparent neglect by Shakespeare to tell us what happened to Demetrius—is he still juiced or has he found a new truth—ends up posing the question at the center of the play: What is one’s true self, what is true love? How dowe know? “There are many things in this play, more than other Shakespeare that I’ve directed, where we have to decide what we feel about it, it’s not answered in the play.” So where does that leave love at first sight? “I don’t think he believes in love at first sight,” she says. She starts singing lyrics from a Beatles song, “Would you believe in a love at first sight / Yes I’m certain that it happens all the time.” Which reminds me—it’s so hard to keep track of everything this woman has done—that she directed a movie, Across the Universe, that was a surprisingly moving adaptation of a slew of Beatles songs, a project she made with her longtime collaborator and significant other, Elliot Goldenthal. And yes there was a much-praised film she directed about Frida Kahlo the artist and feminist icon of the ’30s and ’40s. And a number of operas and, oh yes, there was Spider-Man: Turn Off the Dark. The ambitious big budget Broadway superhero extravaganza that she collaborated on with Bono and The Edge, until “creative differences,” as they say, ended up with her leaving the production after two months of previews and some contentious litigation that has finally been settled, terms undisclosed. She said she just wouldn’t talk about it. Let’s face it: Shakespeare is her real superhero, not some spider. I returned to the question that preoccupied Shakespeare—and her—throughout their careers. The nature of love and love at first sight. “Was it love at first sight between you and Elliot?” I ask her. “No, we worked together five years. So it wasn’t ‘some enchanted evening.’ [It’s been] 30 years now. But it was love at first sight as collaborators,” she says. “I love working with him. He’s a genius!” Especially working on Shakespeare, she says. “We eat dinner going, ‘Oh my god, can you believe this piece of Shakespeare?’ this line, that line—so it continually feeds you to do Shakespeare because you’re always discovering something new.” How many people still feel this way about Shakespeare after 400 or so years? I recall a dinner I had with the founder of the Royal Shakespeare Company, Sir Peter Hall, when he said he was worried that people were losing their grip on Shakespearean language. “Are you kidding?” Taymor says. “What are there now, seven, ten productions going on in this city?” And it is true. The New York Timeshas called it a “feast of Shakespeare.” I ask if the “feast of Shakespeare” has something to do with the sense of being out of control—chaos at home, terror spreading around the world—and the need for wisdom and perspective from the Bard. She doesn’t think so. She sees it more practically, as “a dearth of good writing for the stage” because many of the best writers are doing quality long-form TV. In addition, she says people have gotten over the idea that British Shakespeare is somehow more stodgy. (Many of the “feast of Shakespeare” productions are British imports.) “Was there something about our situation today that makes Shakespeare more relevant?” I ask Jeffrey Horo­witz, the founder of the Theatre for a New Audience, who put on the stage version of Taymor’s Titusback in 1994 and is highly regarded in his own right as a Shakespeare producer/director and thinker. He’s also a producer of her new Dream. He thought it might have something to do with “America as a struggling empire. When Shakespeare wrote,” he pointed out, “England was dealing with the question of what it means to be English, and what political system should we have? America is losing its uncontested power in the world. Shakespeare is a writer who expresses an understanding of wrenching change and loss.” Of course, he adds, there is also the star factor: “American stars playing Shakespeare—Al Pacino, F. Murray Abraham, Kevin Kline, Meryl Streep, Liev Schreiber, Ethan Hawke—all have great skills with Shakespeare and build audiences.” The Shakespeare plays revived today, though, are mainly familiar ones— Romeo, Hamlet, Macbeth, even Taymor’s own Midsummer Night’s Dream. It had been Taymor’s daring to reach outside the famous Shakespeare plays and revive Titus(now available on YouTube as well as DVD). I say daring not just because it’s relatively obscure, but also because it’s so bloody and terrifying. Titusis the story of a Roman general, Titus Andronicus, who ends up in a death spiral of murder, mutilation, rape and the most grisly revenge in the history of revenge. “How do you explain all this—?” I start to ask about the sensational, horrific material. “I think that part of civilization—similar to Midsummer—is to harness the darker aspects of our nature. When you come to Tamora...” Tamora is the queen of the conquered Goths, whose son is slaughtered in front of her by Titus. “When Tamora sees her firstborn murdered, she says, ‘Cruel, irreligious piety.’” For Taymor, these are “the most extraordinary three words. They represent our day and age better than any I know. Because it is [filled with] ‘cruel, irreligious piety’—in the name of which we bomb these people or we kill those people. “My favorite play is Titusand it will always be Titus,” she says. “I think it contains the truth of human nature. Especially about evil, about violence, about blood. It investigates every aspect of violence that exists. It is the most terrifying play or movie that exists.” When I ask why, she gives a terrifying answer: “Because what Shakespeare’s saying is that anybody can turn into a monster. That is why I think Titusis way beyond Hamlet." Marco Grob / Trunk Archive A poster promotes Taymor's latest work, which opened in Brooklyn this fall. Poster design by Julie Taymor, Photography by Josef Astor, Graphic Design by Milton Glaser Inc
https://www.smithsonianmag.com/arts-culture/why-shakespeare-is-julie-taymors-superhero-180947631/?page=2
(PDF) Cardiovascular biomarkers predict post‐discharge re‐hospitalization risk and mortality among Swedish heart failure patients PDF | Aim: The aim of this study was to assess the predictive role of biomarkers, associated with cardiovascular stress and its neuroendocrine response... | Find, read and cite all the research you need on ResearchGate Cardiovascular biomarkers predict post‐discharge re‐hospitalization risk and mortality among Swedish heart failure patients July 2019 ESC Heart Failure 6(5) DOI: 10.1002/ehf2.12486 License CC BY-NC 4.0 inst of Clinical Sciences Hypertension and Cardiovascular Disease Show all 9 authors Hide Abstract and Figures Aim: The aim of this study was to assess the predictive role of biomarkers, associated with cardiovascular stress and its neuroendocrine response as well as renal function, in relation to mortality and risk of re-hospitalization among consecutive patients admitted because of heart failure (HF). Methods and results: A total of 286 patients (mean age, 75 years; 29% women) hospitalized for newly diagnosed or exacerbated HF were analysed. Associations between circulating levels of mid-regional pro-adrenomedullin (MR-proADM), copeptin, C-terminal pro-endothelin-1, N-terminal pro-brain natriuretic peptide (NT-proBNP), cystatin C, and all-cause mortality as well as risk of re-hospitalization due to cardiac causes were assessed using multivariable Cox regression models. A two-sided Bonferroni-corrected P-value of 0.05/5 = 0.010 was considered statistically significant. All biomarkers were related to echocardiographic measurements of cardiac dimensions and function. A total of 57 patients died (median follow-up time, 17 months). In the multivariable-adjusted Cox regression analyses, all biomarkers, except C-terminal pro-endothelin-1, were significantly associated with increased mortality: NT-proBNP [hazard ratio (HR) 1.85, 95% confidence interval (CI) 1.17-2.17; P = 4.0 × 10-4 ], MR-proADM (HR 1.94, 95% CI 1.36-2.75; P = 2.2 × 10-4 ), copeptin (HR 1.70, 95% CI 1.22-2.36; P = 0.002), and cystatin C (HR 2.11, 95% CI 1.56-2.86; P = 1.0 × 10-6 ). A total of 90 patients were re-hospitalized (median time to re-hospitalization, 5 months). In multivariable Cox regression analyses, NT-proBNP was the only biomarker that showed significant association with risk of re-hospitalization due to cardiac causes (HR 1.43, 95% CI 1.10-1.87; P = 0.009). Conclusions: Among patients hospitalized for HF, elevated plasma levels of NT-proBNP, MR-proADM, copeptin, and cystatin C are associated with higher mortality after discharge, whereas NT-proBNP is the only biomarker that predicts the risk of re-hospitalization due to cardiac causes. Baseline characteristics of the study population … Cardiac biomarkers and risk of all-cause mortality … Cardiac biomarkers and risk of re-hospitalization … Figures - available via license: Creative Commons Attribution-NonCommercial 4.0 International 160+ million publication pages Cardiovascular biomarkers predict post-discharge re- hospitalization risk and mortality among Swedish heart failure patients John Molvin 1 , 2 * , Amra Jujic 1 , 2 , Erasmus Bachus 1 , 3 , Widet Gallo 1 , Gordana Tasevska-Dinevska 2 , Hannes Holm 1 , Olle Melander 1 , 3 , Artur Fedorowski 1 , 2 and Martin Magnusson 1 , 2 , 4 1 Department of Clinical Sciences, Lund University, Malmö, Malmö, Sweden; 2 Department of Cardiology, Skåne University Hospital, Malmö, Carl-Bertil Laurells gata 9 , 214 28 , Malmö, Sweden; 3 Department of Internal Medicine, Skåne University Hospital, Malmö, Malmö, Sweden; 4 Wallenberg Centre for Molecular Medicine, Lund University, Lund, Lund, Sweden Aim The aim of this study was to assess the predictive role of biomarkers, associated with cardiovascular stress and its neuroendocrine response as well as renal function, in relation to mortality and risk of re-hospitalization among consecutive patients admitted because of heart failure (HF). Methods and results A total of 286 patients (mean age, 75 years; 29 % women) hospitalized for newly diagnosed or exacer- bated HF were analysed. Associations between circulati ng levels of mid-regional pro-adrenomedullin (MR-pro ADM), copeptin, C-terminal pro-endothelin- 1 , N-terminal pro-brain natriuretic peptide (NT-proBNP), cystatin C, and all-cause mortality as well as risk of re-hospitalization due to cardiac causes were assessed using multivariable Cox regression models. A two-sided Bonferroni-corrected P -value of 0 . 05 / 5 = 0 . 010 was considered statistically signi fi cant. All biomarkers were related to echocar- diographic measurements of cardiac dimensions and function. A total of 57 patien ts died (median follow-up time, 17 months). In the multivariable-adjusted Cox regression analyses, all biomarkers, except C-term inal pro-endothelin- 1 , were signi fi cantly associated with increased mortality: NT-proBNP [hazard ratio (HR) 1 . 85 , 95 % con fi dence interval (CI) 1 . 17 – 2 . 17 ; P = 4 . 0 × 10  4 ], MR-proADM (HR 1 . 94 , 95 %C I 1 . 36 – 2 . 75 ; P = 2 . 2 × 10  4 ), copeptin (HR 1 . 70 , 95 %C I 1 . 22 – 2 . 36 ; P = 0 . 002 ), and cystatin C (HR 2 . 11 , 95 %C I 1 . 56 – 2 . 86 ; P = 1 . 0 × 10  6 ). A total of 90 patients were re-hospitalized (median time to re- hospitalization, 5 months). In multivariable Cox regression analyses, NT-proBN P was the only biomarker that showed signi fi - cant association with risk of re-hospitalization due to cardiac causes (HR 1 . 43 , 95 %C I 1 . 10 – 1 . 87 ; P = 0 . 009 ). Conclusions Among patients hospitalized for HF, elevated plasma levels of NT-proBNP , MR-proADM, copeptin, and cystatin C are associated with higher mortality after discharge, whereas NT-proBNP is the only biomarker that predicts the risk of re- hospitalization due to cardiac causes. Keywords Heart failure (HF); Mid-regional pro-adrenomedullin (MR-proADM); Copeptin; C-terminal pro-endothelin-1 (CT-pro-ET-1); N-terminal pro-brain natriuretic peptide (NT-proBNP); Cystatin C Received: 23 April 2019 ; Accepted: 1 June 2019 *Correspond ence to: John Mo lvin, Depar tment of Cardi ology, SkåneUniversity Hospital , Malmö, Carl- Bertil Laur ells gata 9 , 214 28 Malmö, Sweden . Email: john.mo lvin@med.l u.se Introduction Heart failure (HF) is not only one of our deadliest and most widespread diseases but also one of the most common causes of hospitalization and re-hospitalization. 1 Although the care of patients with HF has improved over the last de- cades, physicians need better tools to predict adverse events and risk stratify patients hospitalized for HF. Biomarkers have been shown to have limited value for clinical assessment in addition to traditional risk factors in regard to prediction of cardiovascular disease. 2 However, bio- markers related to in fl ammation and haemodynamic stress have recently been shown to predict or rule out early post - discharge events in patients hospitalized for acute HF. 3 In particular, creatinine, brain natriuretic peptides (BNPs), pro- adrenomedullin, and endothelin 1 (ET- 1 ) were all signi fi cantly ORIGINAL RESEARCH ARTICLE © 2019 The Authors. ESC Heart Failure published by Jo hn Wiley & Sons Ltd on behal f of the European Soci ety of Cardiology. ESC HEART FAILURE ESC Heart Failure ( 2019 ) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10 . 1002 /ehf 2 . 12486 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any me- dium, provided the original work is properly cited and is not used for commercial purposes. higher in subjects that died because of HF. Furthermor e, these four biomarkers also showed additive value in low-risk vs. high-risk prediction of early post-discharge death or HF re- admission in patients hospitalized for acute HF. 3 In this study, we analysed the following biomarkers: mid-regional pro-adrenomedullin (MR-proADM), copeptin, C-terminal pro-endothelin- 1 (CT-pro-ET- 1 ), N-terminal pro- brain natriuretic peptide (NT-proBNP), and cystatin C; these are biomarkers associated with cardiovascular stress and the neuroendocrine response it incites as well as renal func- tion to assess their predictive role in relation to mortality and risk of re-hospitalization in a Swedish prospective HF co- hort. Finally, because echocardiography is the most common modality to diagnose and grade severity of HF, the plasma levels of the biomarkers were related to echocardiographic measurements of cardiac dimension and function. Methods Study population The HeARt and Brain Failure inVESTigation project in Malmö, Sweden (HARVEST — Malmö), is an ongoing study undertaken in patients hospitalized for HF (ICD- 10 :I 50 -) in Skåne Univer- sity Hospital, Malmö. 4 , 5 The inclusion criteria for the HARVEST study are admission to the Department of Cardiolog y or In- ternal Medicine for treatment of newly diagnosed or exac er- bated HF. The only exclusion criterion is the inability to give informed consent. In case of severe cognitive impairment, in- formed consent has been collected from relatives. Between March 2014 and October 2017 , a total of 283 consecutive patients hospitalized for HF were included and underwent clinical examination. Of these, 268 patients had complete dataset on all covariates and were included in the present analysis. The study was approved by the ethical re- view board at Lund University, Sweden. A written informed consent was obtained from all participants. Clinical examination After admission to the clinical ward, study participants were examined with anthropometric measurements, and blood samples were drawn after overnight fast. Body mass index was calculated as kg/m 2 , and data regarding the study partic- ipants ’ medication were collected. Prevalent diabetes was de- fi ned as either self-reported diagnosis of type 2 diabetes or use of antidiabetic medication. Hypertension was de fi ned as either systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg. 6 A diagnosis of atrial fi brillation was based on previous hospital records or on admission electro- cardiography. Information about patients ’ medication was re- trieved at discharge. Laboratory assays Analyses of high-density lipoprotein and plasma cholesterol were carried out upon admission at the Department of Clini- cal Chemistry, Skåne University Hospital, Malmö, participat- ing in a national standardization and quality control system. For the biomarker analyses, blood samples were collected after admission within 24 h in a fasting condition. Blood sam- ples were stored at  80 °C. N-terminal pro-brain natriuretic peptide N-terminal pro-brain natriuretic peptide was analysed at the Department of Clinical Chemistry, Skåne University Hospital, Malmö, participating in a national standardization and quality control system using ElectroChemiLuminiscenceImmunoassay (Cobas NPU 21571 ). Cystatin C Cystatin C was analysed at the Department of Clinica l Chem- istry, Skåne University Hospital, using an automated particle- based immunoassay (Hitachi Modular P analysis system; Roche, Basel, Switzerland). Copeptin Copeptin was measured at baseline using an ultrasensitive as- say on KRYPTOR Compact Plus analyzers and a commercial sandwich immunoluminometric assay (Thermo Fisher Scien- ti fi c, B.R.A.H.M.S Biomarkers) as previously described. 7 The lower detection limit was 0 . 4 pmol/L, and the functional as- say sensitivity ( < 20 % inter-assay coef fi cient of variation) was less than 1 pmol/L. Mid-regional pro-adrenomedullin The MR-proADM levels were analysed at baseline via speci fi c sandwich immunoluminometric assays (KRYPTOR, B.R.A.H.M. S, Berlin, Germany) in EDTA-treated plasma. 8 Mean inter- assay coef fi cient of variation was < 10 %. 9 C-terminal pro-endothelin-1 C-terminal pro-endothelin- 1 was measured at baseline using Thermo Fisher Scienti fi c B.R.A.H.M.S CT-pro-ET- 1 KRYPTOR. The analytical detection limit of CT-pro-ET- 1 was 0 . 4 pmol/L, and inter-laboratory coef fi cient of variation was < 10 % for values > 10 pmol/L. 10 Echocardiography Conventional transthoracic echocardiograms were obtained using a Philips IE 33 (Philips, Andover, MA, USA) with a 1 – 5 MHz transducer (S 5 - 1 ) or with a GE Vingmed Vivid 7 Ul- trasound (GE, Vingmed Ultrasound, Horten, Norway) with a 1 – 4 MHz transducer (M 3 S). All studies were performed by ex- perienced sonographers. Cine loops were obtained from standard views (parasternal long axis and apical four chamber 2 J. Molvin et al . ESC Heart Failure ( 2019 ) DOI: 10 . 1002 /ehf 2 . 12486 and two chamber). Measurements were performed of fl ine using Xcelera 4 . 1 . 1 (Philips Medical Systems, The Netherlands) according to the recommendations of the American Society of Echocardiography. 11 Internal left and right ventricular dimensions were measured from parasternal long-axis view at end diastole. Measurements of wall thick- ness were obtained in two-dimensional end-diastolic parasternal long-axis view. Left ventricular mass (LVM) was calculated according to the Devereux formula: LVM (g) 0 . 8 ( 1 . 04 [([LVEDD + IVSd + PWd] 3  LVEDD 3 )) + 0 . 6 . 12 Left ventricular volumes were calculated using the biplane Simpson method of discs, by manual tracing (papillary mus- cles included in the cavity) in two-dimensional end-diastolic and end-systolic frames de fi ned as the largest and smallest left ventricular cavities, respectively, in apical four-chamber and two-chamber projections. Ejection fraction (EF) was calculated automatically from end-diastolic volume (EDV) and end-systolic volume (ESV) using the following formula: EF = (EDV  ESV) EDV. For assessment of left atrium (LA) volumes, the biplane area – length method was used: LA volume=( 0 . 85 × LA Area 4 ch x LA Area 2 ch)/(Longest atrial length). The values were indexed to body surface area. The LA endocardial borders were manually traced in both apical four-chamber and two-chamber views. Right atrium volumes were obtained using a single-plane disc summation technique in a dedicated apical four-chamber view. the study subjects with full data on age, sex, and biomarkers. Endpoint assessment Mortality was de fi ned as all-cause mortality during the follow-up and was retrieved from the Swedish National Board of Health and Welfare ’ s Cause of Death Register. Data regard- ing the re-hospitalization due to cardiac causes were re- trieved from the individual electronic medical records of the Skåne Health Care Region (Melior, Siemens Health Services, Solna, Sweden), which cover all the citizens in the study catchment area. Statistics The variables are presented as means (± standard deviation) or median [ 25 th – 75 th inter-quartile range (IQR)]. All variables that were not normally distributed were log trans formed (NT- proBNP, cystatin C, copeptin, MR-proADM, and CT-pro-ET- 1 ). Multivariable-adjusted Cox regression models were applied and log transformed, and standardized values of NT-proBNP, cystatin C, copeptin, MR-proADM, and CT-pro-ET- 1 were en- tered as independent variables. Model 1 included age and sex, whereas Model 2 included age, sex, body mass index, di- abetes status, smoking, presence of atrial fi brillation, systolic blood pressure at admission, total cholesterol, high-density li- sion. The time variable was calculated as follow-up time between screening and date of the fi rst re-hospitalization, death, or end of follow-up through 1 October 2017 . All anal- yses were performed using SPSS Windows Version 23 . 0 , and a two-sided Bonferroni-corrected P -value of 0 . 05 / 5 = 0 . 010 was considered statistically signi fi cant in the Cox regression analysis. Echocardiographic measurements of cardiac dimensions and hypertrophy (eight different modalities) were tested for possible associations with the fi ve biomarkers in age-adjusted and sex-adjusted linear regression analysis, and a two-sided Bonferroni-corrected P -value of 0 . 05 / 13 = 0 . 0038 was consid- ered statistically signi fi cant. Results The study population had a mean age of 75 years, were predominantly male ( 71 %), 39 % had diabetes, and 59 % had previous or prevalent atrial fi brillation at inclusion. A high percentage of the patients received treatment with beta-blockers ( 92 %) and angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists ( 78 %) ( Table 1 ). 29 ]), a total of 57 patients died. The most frequent cause of death was HF ( n = 21 ) followed by cardiac arrest ( n = 7 ), can- cer ( n = 2 ), and stroke ( n = 2 ). The remaining death causes ( n = 21 ) consisted of different diagnoses and were de fi ned as ‘ other ’ in the database. A total of 90 patients were re-hospitalized (median follow- up time, 5 months; IQR [ 1 – 12 ]) because of cardiac causes. The most common cardiac causes of re-hospitalization were HF ( n = 79 ) followed by cardiac arrhythmia ( n = 10 ) and myo- cardial infarction ( n = 1 ). Biomarkers and mortality In the Cox regression analyses adjusted for age and sex, all fi ve biomarkers were signi fi cantly associated with increased post-discharge mortality ( Table 2 ). In the multivariable analy- ses, all biomarkers, except CT-pro-ET- 1 , were signi fi cantly associated with mortality: cystatin C [hazard ratio (HR) 2 . 11 , 95 % con fi dence interval (CI) 1 . 56 – 2 . 86 ; P = 1 . 0 × 10  6 ], NT- GFR (mL/min) 45.9 (16.8) AF, n (%) 157 (58.6) Newly diagnosed HF, n (%) 85 (32) NT-proBNP (pmol/L) 4077.5 [2175.0 – 8125.8] Cystatin C 1.6 [1.3 – 2.1] Copeptin 30.9 [14.7 – 49.2] MR-proADM 1.6 [1.1 – 2.2] CT-pro-ET-1 149.3 [118.9 – 200.0] LVEF, n (%) 39.1 (16.2) ACEi, angiotensin-converting enzyme inhibitor; AF, atrial fi brilla- tion; AHT, antihypertensive treatment; ARB, angiotensin II receptor antagonist; BMI, body mass index; CT-pro-ET-1, C-terminal pro- endothelin-1; DBP, diastolic blood pressure; GFR, glomerular fi ltra- tion rate; HDL, high-density lipoprotein; HF, heart failure; HT, hy- pertension; LVEF, left ventricular ejection fraction; MR-proADM, mid-regional pro-adrenomedullin; NT-proBNP, N-terminal pro- brain natriuretic peptide; SBP, systolic blood pressure. Values are means (± standard deviation) or median [25th – 75th in- ter-quartile range]. Table 2 Cardiac biomarkers and risk of all-cause mortality Total mortality HR (95% CI) P -value Model 1 1.99 (1.52 – 2.62) 5.8 × 10  7 Model 2 2.11 (1.56 – 2.86) 1.0 × 10  6 NT-proBNP ( n = 262; 55 events) Model 1 1.88 (1.37 – 2.57) 8.2 × 10  5 Model 2 1.85 (1.32 – 2.61) 4.0 × 10  4 Copeptin ( n = 259; 57 events) Model 1 1.63 (1.20 – 2.20) 0.002 Model 2 1.70 (1.22 – 2.36) 0.002 MR-proADM ( n = 250; 53 events) Model 1 1.78 (1.32 – 2.41) 1.9 × 10  4 Model 2 1.94 (1.36 – 2.75) 2.2 × 10  4 CT-pro-ET-1 ( n = 260; 57 events) Model 1 1.45 (1.08 – 1.95) 0.014 Model 2 1.42 (1.03 – 1.95) 0.034 CI, con fi dence interval; CT-pro-ET-1, C-terminal pro-endothelin-1; HR, hazard ratio; MR-proADM, mid-regional pro-adrenomedullin; Cox regressions: Model 1: adjusted for age and sex; Model 2: ad- justed for age, sex, body mass index, diabetes status, smoking, atrial fi brillation, systolic blood pressure at admission, total choles- terol, high-density lipoprotein, and New York Heart Association class at admission. 4 J. Molvin et al . ESC Heart Failure ( 2019 ) DOI: 10 . 1002 /ehf 2 . 12486 However, although these studies indicate that cystatin C might serve as a marker of disease susceptibility, a causal in- volvement has been repeatedly counter-proven in Mendelian randomization analyses. 16 , 17 Hence, high levels of cystatin C are only regarded as robust markers of kidney function. In this context, it is not unexpected to see that higher levels of cystatin C are strongly associated with mortality in our study. Poor renal function has been shown to increase risk of cardiac remodelling (e.g. left ventricular hypertrophy), 18 and indeed, we found an association between cystatin C and left ventricular hypertrophy, which in itself is a strong 19 Moreover, the median glomerular fi l- tration rate value in our cohort was low (mean 45 mL/min), and left ventricular EF was 39 %, further implying an interplay between cardiac and renal dysfunction, often referred to as the cardio-renal syndrome. N-terminal pro-brain natriuretic peptide N-terminal pro-brain natriuretic peptide is an established bio- marker re fl ecting HF severity and has earlier been associated with adverse outcomes in various HF populations. 20 In our study, NT-proBNP was the only biomarker that predicted re- hospitalization. Our results are in line with previous reports where elevated mature BNP levels predicted 30 day readmis- sion for HF in over 50 000 subjects. 21 Our fi nding that NT- proBNP is associated with reduced left ventricular func tion is concordant with previous studies. 22 Table 4 Biomarkers associated with echocardiographic measurements Mockel M, Hogan C, Wu AH, Richards M, Clopton P, Filippat os GS, Di Somma S, Anand IS, Ng L, Daniels LB, Neath SX, Christenson R, Potocki M, McCord J, Terracciano G, Kremastinos D, Hartmann O, von Haehling S, Bergmann A, Morgenthaler NG, Anker SD. In- creased 90-day mortality in patients with acute heart failure with elevated copeptin: secondary results from the Biomarkers in Acute Heart Failure (BACH) study . Circ Heart Fail 201 1; 4 : 613 – 620. 28. Zhong Y, Wang R, Y an L, Lin M, Liu X, You T . Copeptin in heart failure: review and meta-analysis. Clin Chim Acta 201 7; 475 :3 6 – 43. 29. Jougasaki M, Burnett JC Jr. Adrenomedullin: potential in physiology and pathophysiology. Life Sci 2000; 66 : 855 – 872. 30. Maisel A, Mueller C, Nowak R, Peacock WF, Landsberg JW , Ponikowski P , Mockel M, Hogan C, Wu AH, Richards M, Clopton P, Fi lippatos GS, Di Somma S, Anand I, Ng L, Daniels LB, Neath SX, Christenson R, Potocki M, McCord J, Terracciano G, Kremastinos D, Hartmann O, von Haehling S, Bergmann A, Morgenthaler NG, Anker SD. Mid-re- gion pro-hormone markers for diagnosis and prognosis in acute dyspnea. JA m Coll Cardiol 201 0; 55 : 2062. 31. Yoshihara F , Nishikimi T, Horio T , Yutani C, Takishita S, Matsuo H, Ohe T , Kangawa K. Chronic infusion of adrenomedullin reduces pulmonary hy- pertension and lessens right ventricular hypertrophy in rats administered mono- crotaline. Eur J Pharmacol 1998; 355 : 33 – 39. 32. Tomoda H. Plasma endothelin-1 in acute myocardial infarction with heart failure. Am Heart J 1993; 125 :6 6 7 – 672. 33. Schif frin EL. Role of endothelin-1 in hy- pertension and vascular disease. Am J Hypertens 2001; 14 : 83S – 89S. 34. W ei CM, Lerman A, Rodeheffer RJ, McGregor CG, Brandt RR, Wright S, Heublein DM, Kao PC, Edwards WD, Burnett JC Jr. Endothelin in human con- gestive heart failure. Circulation 1994; 89 : 1580 – 1586. 35. Zhang C-L, Xie S, Qiao X, An Y-M, Zhang Y, Li L, Guo XB, Zhang FC, Wu LL. Plasma endothelin-1-related peptides as the prognostic biomarkers for heart failure: a PRISMA-compliant meta- analysis. Medicine 201 7; 96 : e9342-e. 8 J. Molvin et al . ESC Heart Failure ( 2019 ) DOI: 10 . 1002 /ehf 2 . 12486 ... Other studies reported different outcomes. One described copeptin as inferior to BNP in prediction of HF re-hospitalization in chronic HF (Stoiser et al. 2006) Another study reported NT-proBNP as the only independent predictor of re-hospitalization due to cardiac causes in patients with de novo HF (Molvin et al. 2019 ). Although we found copeptin to be useful in the prediction of HF-re-hospitalization, its independency for this calculation remains unclear. ... ... Therefore, copeptin, as marker of hemodynamic status, may be superior to NPs in predicting short-term mortality (Peacock et al. 2011, Jia et al. 2017. Overall, use of copeptin in prediction of adverse events was proven to increase the prognostic value of NPs (Maisel et al. 2011, Pozsonyi et al. 2015, Duengen et al. 2018, thus multi-marker approach was recommended (Dieplinger et al. 2009, Yan et al. 2017 , Molvin et al. 2019 . ... Role of copeptin in diagnosis and outcome prediction in patients with heart failure: a systematic review and meta-analysis Article Sep 2022 BIOMARKERS Jakub M. Zimodro Aleksandra Gasecka Milosz J. Jaguszewski Łukasz Szarpak Background/context: Heart failure (HF) is a heterogeneous condition characterized by increased morbidity and mortality. Objective: This systematic review and meta-analysis of 19 studies was conducted to evaluate the role of copeptin in diagnosis and outcome prediction in HF patients. Materials and methods: A systematic literature search for clinical trials reporting copeptin levels in HF patients was performed using EMBASE, PubMed, Cochrane Register of Controlled Trials, and Google Scholar. Articles from databases published by 2 January 2022, that met the selection criteria were retrieved and reviewed. The random effects model was used for analyses. Results: Pooled analysis found higher mean copeptin levels in HF vs. non-HF populations (43.6 ± 46.4 vs. 21.4 ± 21.4; MD= 20.48; 95% CI: 9.22 to 31.74; p < 0.001). Pooled analysis of copeptin concentrations stratified by ejection fraction showed higher concentrations in HFrEF vs. HFpEF (17.4 ± 7.1 vs. 10.1 ± 5.5; MD= -4.69; 95% CI: -7.58 to -1.81; p = 0.001). Copeptin level was higher in patients with mortality/acute HF-related hospitalization vs. stable patients (31.3 ± 23.7 vs. 20.4 ± 12.8; MD= -13.06; 95% CI: -25.28 to -0.84; p = 0.04). Higher copeptin concentrations were associated with mortality and observed in all follow-up periods (p < 0.05). Conclusions: The present meta-analysis showed that elevated copeptin plasma concentrations observed in HF patients are associated with an increased risk of all-cause mortality, thus copeptin may serve as predictor of outcome in HF. ... ET-1 or its surrogate CT-proET-1 were associated with the metabolic syndrome and impaired glucose tolerance in the general population, 7,8 and with increased inflammation, cardiovascular disease and mortality in studies involving critically ill patients, 9 participants with heart failure, 10,11 acute myocardial infarction [12][13][14] and chronic kidney disease. 15 However, these results were not confirmed by all studies, [16][17][18] [19] and the association of CT-proET-1 with cardiovascular events, mortality and (subclinical) inflammation is less well studied in the general population. ... ... 10,11 Regarding population-based studies, CT-proET-1 was recently shown to be associated with all-cause mortality in a Swedish population. 31 However, other studies showed no association of ET-1/CT-proET-1 with adverse outcomes after ischemic stroke, 16 in patients on hemodialysis 17 and in patients with heart failure, 19 or even an inverse association of CT-proET-1 with mortality in heart failure patients, 32 emphasizing the heterogeneity of the literature regarding the association of ET-1/CT-proET-1 with mortality. ... Association of C-Terminal Pro-Endothelin-1 with Mortality in the Population-Based KORA F4 Study Article Full-text available May 2022 Vasc Health Risk Manag Introduction: Endothelin-1 and its prohormone C-terminal pro-endothelin-1 (CT-proET-1) have been linked to metabolic alterations, inflammatory responses and cardiovascular events in selected study populations. We analyzed the association of CT-proET-1 with cardiovascular events and mortality, carotid intima-media-thickness as surrogate for early atherosclerotic lesions, biomarkers of subclinical inflammation and adipokines in a population-based study. Methods: The cross-sectional and prospective analyses used data from the KORA F4 study with a median follow-up time of 9.1 (8.8-9.4) years. Data on CT-proET-1 and mortality were available for 1554 participants, data on the other outcomes in subgroups (n = 596-1554). The associations were estimated using multivariable linear regression and Cox proportional hazard models adjusted for sex, age, body mass index, estimated glomerular filtration rate, arterial hypertension, diabetes, low-density and high-density lipoprotein cholesterol, current and former smoking and physical activity. The Bonferroni method was used to correct for multiple testing. Results: In the fully adjusted model, CT-proET-1 was associated with cardiovascular (hazard ratio (HR) per standard deviation increase: 1.66; 95% confidence interval (CI): 1.10-2.51; p = 0.017) and all-cause mortality (HR: 2.03; 95% CI 1.55-2.67; p < 0.001), but not with cardiovascular events, and was inversely associated with the intima-media thickness (β: -0.09 ± 0.03; p = 0.001). CT-proET-1 was positively associated with five out of ten biomarkers of subclinical inflammation and with two out of five adipokines after correction for multiple testing. After inclusion of biomarkers of subclinical inflammation in the Cox proportional hazard model, the association of CT-proET-1 with all-cause mortality persisted (p < 0.001). Conclusion: These results emphasize the complexity of endothelin-1 actions and/or indicator functions of CT-proET-1. CT-proET-1 is a risk marker for all-cause mortality, which is likely independent of vascular endothelin-1 actions, cardiovascular disease and inflammation. ... Biomarkers are objective measurements of the severity of HF and in this sense, they predict mortality and readmission among patients aged 65 years old. 30 It seems that the situation of myocardial and remodeling stress marked by troponin and NT-proBNP has an impact on frailty, 31 that is the probable reason why the frail patients which have higher values of NT-proBNP had also worse values of NYHA (more prevalence of NYHA classes II, III and IV). The plasmatic levels of biomarkers, such as NT-proBNP, increase with the HF stage and predict mortality and readmission. ... Fast systematic geriatric assessment in acute heart failure patients admitted in Cardiology Background: Heart failure prevalence is increasing in elder adults. These patients usually present geriatric syndromes, especially frailty. The effect of frailty on heart failure is under discussion but there are few data about the clinical characterization of frail patients who are admitted for acute heart failure decompensation. Objective: The purpose of this study was to study the differences in clinical baseline variables and geriatric scales between frail and non-frail patients admitted to the Cardiology unit via the Emergency Department for acute heart failure. Methods: We enrolled all patients with acute heart failure who were admitted to the Cardiology unit from the Emergency Department of our hospital from July 2020 through May 2021. A multidimensional and comprehensive geriatric assessment was performed at the moment of admission. We studied differences in baseline variables and geriatric scales according to the frailty status determined by the FRAIL scale. Results: A total of 202 patients were included. In the whole population, 68 (33.7%) patients presented frailty defined by a FRAIL score ≥ 3. The frail patients were older (80±9 vs. 69±12 years; p<0.001), and had a worse quality of life (58.31±12.18 vs.39.26±13.71 points; p<0.001) according to the Minnesota scale, presented high comorbidity (47 (69.1%) vs. 67 (50.4%) patients; p = 0.011) defined as ≥3 points according to the Charlson scale and were more dependent (40 (58.8%) vs. 25 (18.8%) patients; p<0.001) according to the Barthel scale. The frail patients presented higher MAGGIC risk scores (24.09±4.99 vs. 18.89±6.26; p<0.001). Despite this adverse profile, the treatments prescribed during the admission and at the hospital discharge were similar. Conclusions: The prevalence of geriatric syndromes, especially frailty, is very high in patients admitted for acute heart failure. Frail patients with acute heart failure had an adverse clinical profile with more prevalence of concomitant geriatric syndromes. Therefore, we consider that a geriatric assessment should be performed during the admission of acute heart failure patients to improve care and attention. ... More than 1 patient over 4 were readmitted to the hospital in our study population after 30 days. Our readmission rate was more frequent than those observed in some previous studies (37)(38)(39) over the same follow-up time, yet the discrepancies could be explained by the age of the patients (much older in our population than in the others (37)(38)(39), high comorbidity burden (which was evaluated in our study, whether not entirely specified in other ones), and in line with Molvin et al. who observed a 33.5% readmission rate, in a Swedish cohort of 268 patients (mean age 75 years) over a follow-up time of 5 months (40) . ... Arterial Stiffness, Subendocardial Impairment, and 30-Day Readmission in Heart Failure Older Patients Arterial stiffness and subendocardial perfusion impairment may play a significant role in heart failure (HF) outcomes. The aim of the study was to examine the main predictors of 30-day readmission in geriatric patients, hospitalized with HF, explore hemodynamical parameters, arterial stiffness indexes, and subendocardial viability ratio (SEVR). In total, 41 hospitalized patients, affected by HF, were included; they underwent clinical evaluation, routine laboratory testing, and echocardiography. At the time of admission, after the achievement of clinical stability (defined as switching from intravenous to oral diuretic therapy), and at discharge, arterial tonometry was performed to evaluate carotid-femoral pulse wave velocity (PWVcf) and SEVR (then corrected for hemoglobin concentration and oxygen saturation). Through the evaluations, a significant progressive decrease in PWVcf was described (17.79 ± 4.49, 13.54 ± 4.54, and 9.94 ± 3.73 m/s), even after adjustment for age, gender, mean arterial pressure (MAP) variation, and left ventricular ejection fraction (LVEF). A significant improvement was registered for both SEVR (83.48 ± 24.43, 97.94 ± 26.84, and 113.29 ± 38.02) and corrected SEVR (12.74 ± 4.69, 15.71 ± 5.30, and 18.55 ± 6.66) values, and it was still significant when adjusted for age, gender, MAP variation, and LVEF. After discharge, 26.8% of patients were readmitted within 30 days. In a multivariate binary logistic regression analysis, PWVcf at discharge was the only predictor of 30-day readmission (odds ratio [OR] 1.957, 95% CI 1.112–3.443). In conclusion, medical therapy seems to improve arterial stiffness and subendocardial perfusion in geriatric patients hospitalized with heart failure. Furthermore, PWVcf is a valid predictor of 30-day readmission. Its feasibility in clinical practice may provide an instrument to detect patients with HF at high risk of rehospitalization. ... In the older group of patients, only NT-proBNP was related to frailty. The plasmatic levels of this biomarker increase with the HF stage and predict mortality and readmission among patients aged ≥65 years who have been hospitalized for HF [24] . Previous data have shown a relationship between NT-proBNP with muscle weakness [25] and functional disability [26]. ... Differences According to Age in the Diagnostic Performance of Cardiac Biomarkers to Predict Frailty in Patients with Acute Heart Failure Frailty has traditionally been studied in the elderly population but scarcely in younger individuals. The objective of the present study is to analyze differences according to age in the diagnostic performance of cardiac biomarkers to predict frailty in patients admitted to the hospital for acute heart failure (AHF). A frailty assessment was performed with the SPPB and FRAIL scales (score > 3). We included 201 patients who were divided according to age: those older and younger than 75 years. In the younger group, no biomarker was related to the presence of frailty. This was mainly determined by age and comorbidities. In the elderly group, NT-proBNP was significantly related to the presence of frailty, but none of the baseline characteristics were. The best cut-off point in the elderly group for NT-proBNP was 4000 pg/mL. The area under the curve (AUC) for proBNP for frailty detection was 0.62 in the elderly. Another similar frailty scale, the SPPB, also showed a similar AUC in this group; however, adding the NT-proBNP (one point if NT-proBNP < 4000 pg/mL), it showed a slightly higher yield (AUC 0.65). The addition of biomarkers could improve frailty detection in members of the elderly population who are admitted to the hospital for AHF. ... Our study found that NT-proBNP is an important predictor of prognosis in patients with CHF comorbid with AF. The NT-proBNP level is positively correlated with the severity of heart failure, and is closely related to NYHA class, end-diastolic pressure, and degree of hemodynamic disturbances, and can be used as an effective means of prognostic evaluation [12, 13] . Abnormal liver enzymes often appear in patients with heart failure, with a prevalence of 30-60% [14]. ... Time-to-event prediction analysis of patients with chronic heart failure comorbid with atrial fibrillation: a LightGBM model Abstract Background Chronic heart failure (CHF) comorbid with atrial fibrillation (AF) is a serious threat to human health and has become a major clinical burden. This prospective cohort study was performed to design a risk stratification system based on the light gradient boosting machine (LightGBM) model to accurately predict the 1- to 3-year all-cause mortality of patients with CHF comorbid with AF. Methods Electronic medical records of hospitalized patients with CHF comorbid with AF from January 2014 to April 2019 were collected. The data set was randomly divided into a training set and test set at a 3:1 ratio. In the training set, the synthetic minority over-sampling technique (SMOTE) algorithm and fivefold cross validation were used for LightGBM model training, and the model performance was performed on the test set and compared using the logistic regression method. The survival rate was presented on a Kaplan–Meier curve and compared by a log-rank test, and the hazard ratio was calculated by a Cox proportional hazard model. Results Of the included 1796 patients, the 1-, 2-, and 3-year cumulative mortality rates were 7.74%, 10.63%, and 12.43%, respectively. Compared with the logistic regression model, the LightGBM model showed better predictive performance, the area under the receiver operating characteristic curve for 1-, 2-, and 3-year all-cause mortality was 0.718 (95%CI, 0.710–0.727), 0.744(95%CI, 0.737–0.751), and 0.757 (95%CI, 0.751–0.763), respectively. The net reclassification index was 0.062 (95%CI, 0.044–0.079), 0.154 (95%CI, 0.138–0.172), and 0.148 (95%CI, 0.133–0.164), respectively. The differences between the two models were statistically significant (P ... 21 Studies in patients with established HF also demonstrate increased risk of hospitalisation and mortality. A recent Swedish study of hospitalised patients, 22 and an older UK study of patients in the community, 9 both demonstrated increased risks of hospitalisation and mortality with raised NT-proBNP. A 2015 systematic review also showed an increased risk of death associated with raised BNP. ... Natriuretic peptide level at heart failure diagnosis and risk of hospitalisation and death in England 2004–2018 Article Full-text available Objective Heart failure (HF) is a malignant condition requiring urgent treatment. Guidelines recommend natriuretic peptide (NP) testing in primary care to prioritise referral for specialist diagnostic assessment. We aimed to assess association of baseline NP with hospitalisation and mortality in people with newly diagnosed HF. Methods Population-based cohort study of 40 007 patients in the Clinical Practice Research Datalink in England with a new HF diagnosis (48% men, mean age 78.5 years). We used linked primary and secondary care data between 1 January 2004 and 31 December 2018 to report one-year hospitalisation and 1-year, 5-year and 10-year mortality by NP level. Results 22 085 (55%) participants were hospitalised in the year following diagnosis. Adjusted odds of HF-related hospitalisation in those with a high NP (NT-proBNP >2000 pg/mL) were twofold greater (OR 2.26 95% CI 1.98 to 2.59) than a moderate NP (NT-proBNP 400–2000 pg/mL). All-cause mortality rates in the high NP group were 27%, 62% and 82% at 1, 5 and 10 years, compared with 19%, 50% and 77%, respectively, in the moderate NP group and, in a competing risks model, risk of HF-related death was 50% higher at each timepoint. Median time between NP test and HF diagnosis was 101 days (IQR 19–581). Conclusions High baseline NP is associated with increased HF-related hospitalisation and poor survival. While healthcare systems remain under pressure from the impact of COVID-19, research to test novel strategies to prevent hospitalisation and improve outcomes—such as a mandatory two-week HF diagnosis pathway—is urgently needed. Copeptin as a Diagnostic and Prognostic Biomarker in Cardiovascular Diseases Copeptin is the carboxyl-terminus of the arginine vasopressin (AVP) precursor peptide. The main physiological functions of AVP are fluid and osmotic balance, cardiovascular homeostasis, and regulation of endocrine stress response. Copeptin, which is released in an equimolar mode with AVP from the neurohypophysis, has emerged as a stable and simple-to-measure surrogate marker of AVP and has displayed enormous potential in clinical practice. Cardiovascular disease (CVD) is currently recognized as a primary threat to the health of the population worldwide, and thus, rapid and effective approaches to identify individuals that are at high risk of, or have already developed CVD are required. Copeptin is a diagnostic and prognostic biomarker in CVD, including the rapid rule-out of acute myocardial infarction (AMI), mortality prediction in heart failure (HF), and stroke. This review summarizes and discusses the value of copeptin in the diagnosis, discrimination, and prognosis of CVD (AMI, HF, and stroke), as well as the caveats and prospects for the application of this potential biomarker. A year in heart failure: an update of recent findings Full-text available Dec 2021 Major changes have occurred in these last years in heart failure (HF) management. Landmark trials and the 2021 European Society of Cardiology guidelines for the diagnosis and treatment of HF have established four classes of drugs for treatment of HF with reduced ejection fraction: angiotensin-converting enzyme inhibitors or an angiotensin receptor-neprilysin inhibitor, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors, namely, dapagliflozin or empagliflozin. These drugs consistently showed benefits on mortality, HF hospitalizations, and quality of life. Correction of iron deficiency is indicated to improve symptoms and reduce HF hospitalizations. AFFIRM-AHF showed 26% reduction in total HF hospitalizations with ferric carboxymaltose vs. placebo in patients hospitalized for acute HF (P = 0.013). The guanylate cyclase activator vericiguat and the myosin activator omecamtiv mecarbil improved outcomes in randomized placebo-controlled trials, and vericiguat is now approved for clinical practice. Treatment of HF with preserved ejection fraction (HFpEF) was a major unmet clinical need until this year when the results of EMPEROR-Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic HFpEF) were issued. Compared with placebo, empagliflozin reduced by 21% (hazard ratio, 0.79; 95% confidence interval, 0.69 to 0.90; P < 0.001), the primary outcome of cardiovascular death or HF hospitalization. Advances in the treatment of specific phenotypes of HF, including atrial fibrillation, valvular heart disease, cardiomyopathies, cardiac amyloidosis, and cancer-related HF, also occurred. Coronavirus disease 2019 (COVID-19) pandemic still plays a major role in HF epidemiology and management. All these aspects are highlighted in this review. Depression and Hospital Readmissions in Patients with Heart Failure Depression increases the risk of mortality in patients with heart failure (HF). Less is known about whether depression predicts multiple readmissions or whether multiple hospitalizations worsen depression in patients with HF. This study aimed to test the hypotheses that depression predicts multiple readmissions in patients hospitalized with HF, and conversely that multiple readmissions predict persistent or worsening depression. All-cause readmissions were ascertained over a 2-year follow-up of a cohort of 400 patients hospitalized with HF. The Patient Health Questionnaire-9 was used to assess depression at index and 3-month intervals. At enrollment in the study, 21% of the patients were mildly depressed and 22% were severely depressed. Higher Patient Health Questionnaire-9 depression scores predicted a higher rate of readmissions (adjusted hazard ratio 1.02, 95% confidence interval 1.00 to 1.04, p = 0.03). The readmission rate was higher in those who were severely depressed than in those without depression (p = 0.0003), but it did not differ between patients who were mildly depressed and patients without depression. Multiple readmissions did not predict persistent or worsening depression, but younger patients in higher New York Heart Association classes were more depressed than other patients. Depression is an independent risk factor for multiple all-cause readmissions in patients hospitalized with HF. Severe depression is a treatable psychiatric co-morbidity that warrants ongoing clinical attention in patients with HF.
https://www.researchgate.net/publication/334661217_Cardiovascular_biomarkers_predict_post-discharge_re-hospitalization_risk_and_mortality_among_Swedish_heart_failure_patients
Shelf Life Determination of Picralima Nitida, Glibenclamide, Ciprofloxacin and Pefloxacin using UV Spectrometry Physicochemical Technique Shelf life is one of the important property of a drug for safety and quality. The shelf life of Picralima nitida (herbal drug) and three orthodox drugs (glibenclamide, ciprofloxacin, and pefloxacin) has been investigated. The stability study was done using UV spectrometry method. Their shelf life was determined by accelerated stability studies on the basis of first-order degradation kinetics and t10% (the time required to degrade 10% of a drug at 27°C). The stability was studied at temperatures of 45°C, 60°C and 70°C during the course of one month at one-week interval (1, 2, 3 and 4 weeks). The initial concentration of 5, 2.5, 25 and 100 mg/ml was used for Picralima nitida, glibenclamide, ciprofloxacin, and pefloxacin, respectively in the study. Influence of storage time and temperature on the drug samples were investigated. The half-life was also evaluated. All experiments were carried out in the year 2012. The concentrations of the drug samples were found to decrease with increase in storage time and temperature. The shelf life of ciprofloxacin, pefloxacin, and glibenclamide were found to be 535.18, 298.17 and 134.31 weeks, respectively. The half-life of ciprofloxacin, pefloxacin and glibenclamide were also found to be 3553.85, 1980 and 891.89 weeks, respectively. The shelf life and half-life of Picralima nitida could not be determined using UV spectrometry technique because of the presence of complex metabolites, which results in the irregular increase in absorbance and instability. Storage time and temperature was found to have a great influence on the concentration of the drug substances. Research Article - Der Pharma Chemica ( 2018) Volume 10, Issue 6 Shelf Life Determination of Picralima Nitida, Glibenclamide, Ciprofloxacin and Pefloxacin using UV Spectrometry Physicochemical Technique Kenechukwu Keluo Onyechi 1and Chinenye Adaobi Igwegbe 2 * 1Department of Pharmaceutics and Pharmaceutical Technology, Nnamdi Azikiwe University, Awka, Nigeria 2Department of Chemical Engineering, Nnamdi Azikiwe University, Awka, Nigeria *Corresponding Author: Chinenye Adaobi Igwegbe Department of Chemical Engineering Nnamdi Azikiwe University Awka, Nigeria Abstract Shelf life is one of the important property of a drug for safety and quality. The shelf life of Picralima nitida(herbal drug) and three orthodox drugs (glibenclamide, ciprofloxacin, and pefloxacin) has been investigated. The stability study was done using UV spectrometry method. Their shelf life was determined by accelerated stability studies on the basis of first-order degradation kinetics and t 10%(the time required to degrade 10% of a drug at 27°C). The stability was studied at temperatures of 45°C, 60°C and 70°C during the course of one month at one-week interval (1, 2, 3 and 4 weeks). The initial concentration of 5, 2.5, 25 and 100 mg/ml was used for Picralima nitida, glibenclamide, ciprofloxacin, and pefloxacin, respectively in the study. Influence of storage time and temperature on the drug samples were investigated. The half-life was also evaluated. All experiments were carried out in the year 2012. The concentrations of the drug samples were found to decrease with increase in storage time and temperature. The shelf life of ciprofloxacin, pefloxacin, and glibenclamide were found to be 535.18, 298.17 and 134.31 weeks, respectively. The half-life of ciprofloxacin, pefloxacin and glibenclamide were also found to be 3553.85, 1980 and 891.89 weeks, respectively. The shelf life and half-life of Picralima nitidacould not be determined using UV spectrometry technique because of the presence of complex metabolites, which results in the irregular increase in absorbance and instability. Storage time and temperature was found to have a great influence on the concentration of the drug substances. Keywords Accelerated stability study, Ciprofloxacin, Degradation kinetics, Glibenclamide, Pefloxacin, Picralima nitida, Shelf life determination Introduction Shelf life/stability studies are usually carried out on a drug substance in order to determine the degradation of its active ingredient [1]. Stability is defined as the capacity of a drug material to retain its specifications of its active ingredient at a period time to ensure its quality and safety. Stability testing of drug substances gives information of the drug variation with time under the influence of environmental conditions such as humidity, temperature, and light [2,3]. Stability of a drug product provides additional information on the possible storage conditions during the line processing of raw materials, the intermediate and finished product; and the shelf-life and expiration date of a pharmaceutical product. The two common types of stability tests employed to estimate shelf life are real-time stability tests and accelerated stability tests [4]. In real-time stability testing, a product is stored at recommended storage conditions and monitored until it fails the specification. In accelerated stability tests, a product is stored at elevated stress conditions such as temperature, humidity, and pH [4]. Herbal drugs have been used in decades for the treatment of diseases and revitalization of body systems. WHO stated that about 80% of the world populates depend on herbal drugs [5], due to its economic importance and ease of reach. Therefore, the need for the study of their safety. Picralima nitidaextracts have been reported to be effective as cough suppressant [6], antibacterial effect [7,8], treatment of viral infections [9], anti-inflammatory and antipyretic activity [10], analgesic activity [11,12] and anti-parasitic effect including malaria parasite [13,14]. Ciprofloxacin {1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3 quinolinecarboxylic acid} and Pefloxacin {1-ethyl-6-fluoro-7-(4- methyl piperazin-1-yl)-4-oxo-quinoline-3-carboxylic acid} are synthetic broad-spectrum antibiotic active against both gram-positive and gram-negative bacteria [15]. Pefloxacin, an analog of norfloxacin is a synthetic chemotherapeutic agent used to treat severe and life-threatening bacterial infections [16]. Glibenclamide {5-chloro-N-(4-[N-(cyclohexyl carbamoyl) sulfamoyl] phenethyl)-2-methoxybenzamide} also known as glyburide is an antidiabetic drug. Glibenclamide is one of only two oral antidiabetics in the World Health Organization model list of essential medicines [17,18]. Also, glibenclamide has been reported to improve the outcome in animal stroke models by preventing brain swelling [19]. The objective of this study is to estimate the shelf life of Picralima nitida(herbal drug) and three orthodox drugs (glibenclamide, ciprofloxacin and pefloxacin) at different storage times and temperatures using UV spectrometry method. Materials and Methods 2.1 Collection and Preparation of the Drug Samples Picralima nitida(Apocynaceae) seeds known as akuamma seed in Ghana and Osuigwe in Igboland (Eastern, Nigeria) were collected from Ihembosi, Anambra state, Nigeria. The pods were washed with clean water to remove dirt, dried and dissected longitudinally to expose the interior component. The seeds were isolated from the pulp into a clean stainless steel bowl. The seeds obtained from the pods were allowed to dry at room temperature for one week and the testa manually removed. Further drying of the cotyledons was done until they turned dark brown and hard. The seeds were pulverized into coarse particles using a manual grinder and further size reduction was done manually in a porcelain mortar. The resulting powder was screened through a 0.25 μm sieve and packed in an air tight bottle. 200 g of the seed powder was defatted by maceration in n-hexane and dried. The powder was then packed in a glass container and methanol of 1 l added to cover two thirds the volume of the container. The maceration was allowed to continue for 48 h with occasional agitation. The mixture was filtered through a filter paper into a glass beaker and the filtrate allowed to dry at room temperature. The resinous extract obtained was weighed, packed, covered and stored in a refrigerator for further usage. The orthodox drugs used in the study were: (1) Ciprofloxacin hydrochloride (antibacterial drug) tablets USP 500 mg (gecip®) manufactured in 2010 by MICRO lab limited, Bangalore, India and marketed by Geneith Pharm LTD, Oshodi, Lagos State, Nigeria. (2) Glibenclamide (hypoglycaemic drug) tablets BP 5 mg (diatab®) manufactured in 2009 by Mayer and Baker, Nigeria PLC, Ikeja, Lagos State, Nigeria. (3) Pefloxacin (antibacterial drug) tablets 400 mg (peflomed®) manufactured in 2011 by Bharat Parenterals LTD, Barode Gujarat, India and marketed by Evans medical PLC, Agbara, Ogun State, Nigeria. All drugs (tablets) were obtained from a pharmaceutical store in Awka, Anambra State, Nigeria on February 19, 2012. 2.2 Stability Study using UV Absorption Spectra Standard plot of absorbance against concentrations for Picralima nitida, ciprofloxacin, pefloxacin, and glibenclamide were determined using UV-Vis spectrophotometer (Shimadzu model 1800) by two-fold serial dilution of the stock solutions (ciprofloxacin hydrochloride-25 mg/ml in distilled water, pefloxacin-100 mg/ml in distilled water, glibenclamide-2.5 mg/ml in methanol and Picralima nitidaseed extract-5 mg/ml in methanol) into four different concentrations. Their absorbance at different concentrations was obtained at their various characteristic wavelengths of 429, 433, 370 and 425 nm for ciprofloxacin, pefloxacin, glibenclamide, and Picralima nitidarespectively. All reagents used in the study were of analytical grade. The stock solutions of the drugs were then subjected to different temperatures (45°C, 60°C and 70°C) and the samples collected at one-week interval for one month to obtain their absorbance in which their coresponding final concentrations were evaluated from the regression equations of their standard plots. All experiments were carried out in the year 2012. Results and Discussion 4.1 Standard Plots of Ciprofloxacin, Pefloxacin, Glibenclamide, and Picralima nitida The standard plots (absorbance against concentration) of ciprofloxacin, pefloxacin, glibenclamide, and Picralima nitidaat different dilution concentrations with their respective absorbance are presented infigures 1-4. The regression equations of their standard plots were used further to evaluate the final concentrations of the drug samples after the accelerated stability studies at different storage times and temperatures. Figure 1:Standard plot of ciprofloxacin Figure 2:Standard plot of pefloxacin Figure 3:Standard plot of glibenclamide Figure 4:Standard plot of Picralima nitida 4.2 Effect of Storage Time and Temperature on Drug Concentration Accelerated stability tests was investigated by stressfully conditioning the drug for a period of time at high or elevated temperatures. The concentration of ciprofloxacin, pefloxacin, glibenclamide, and Picralima nitidaremaining after storage times of 0, 1, 2, 3 and 4 weeks at different storage temperatures of 45, 60 and 70°C was determined using an initial concentration of 5, 2.5, 25 and 100 mg/ml for Picralima nitida, glibenclamide, ciprofloxacin, and pefloxacin, respectively. The concentration of the drug substances remaining was plotted against time (Figures 5-8). Fromfigures 5-8, it can be seen that the concentrations of ciprofloxacin, pefloxacin, glibenclamide, and Picralima nitidadecreased with increase in storage time. Increase in temperature increased the decomposition of ciprofloxacin, pefloxacin, and glibenclamide since the molecules tend to move faster with increased kinetic energy [20] but for Picralima nitidasample, its concentration was increased. This implies that the storage time and temperature have a great influence on the concentration of the drug substances. Figure 5:Effect of storage time and temperature on ciprofloxacin concentration Figure 6:Effect of storage time and temperature on pefloxacin concentration Figure 7:Effect of storage time and temperature on glibenclamide concentration Figure 8:Effect of storage time and temperature on Pricralima nitida concentration 4.3 Kinetics of Degradation The accelerated degradation kinetics was done at elevated temperatures of 45°C, 60°C and 70°C. The degradation kinetic constant, k was evaluated by using the first order rate equation: ln C= ln C 0- k it (1) Where Cand C 0is the concentration of drug remaining at a time (t = t) and drug concentration at time (t = 0), respectively. k iis the degradation rate constant which can be evaluated from the slopes of the linear plot In Cof and t (Figures 9-12). The average k can be calculated k iat each week at temperatures of 45, 60 and 70°C. The degradation rate constant, k obtained at various temperatures for the drug substances are presented inTable 1. The correlation coefficients (R2 > 0.95) shows that the degradation experimental data of ciprofloxacin and pefloxacin fitted into the first-order plot at all temperatures (Figures 9,10) but that of glibenclamide fitted the plot only at 45°C (Figure 11). From,Figure 12, it can be seen that the experimental data gotten from the degradation of Picralima nitidadidn’t fit into the first-order model at all temperatures. Drug substance Temperature (°C) k (week-1) Absolute Temperature (K) 1/T In k Activation energy, E a ( kJ/mol.K) Shelf-life at 27°C (weeks) Half-life at 27°C (weeks) Ciprofloxacin 27 0.000195 300 0.00333 -6.24038 97.1574 535.18 3553.85 45 0.0221 318 0.00315 -3.81218 60 0.0361 333 0.003 -3.32146 70 0.432 343 0.00292 -0.83933 Pefloxacin 27 0.00035 300 0.00333 -5.655048 72.21208 298.17 1980 45 0.0167 318 0.00315 -4.09235 60 0.0617 333 0.003 -2.78547 70 0.123 343 0.00292 -2.09557 Glibenclamide 27 0.000777 300 0.00333 -4.85787 106.74345 134.31 891.89 45 0.077 318 0.00315 -2.56395 60 0.5624 333 0.003 -0.57554 70 1.4549 343 0.00292 0.374937 Picralima nitida 27 - 300 0.00333 - - - - 45 -0.1282 318 0.00315 - 60 -0.1409 333 0.003 - 70 -0.176 343 0.00292 - Table 1:Degradation rate constants calculated at different temperatures, shelf life and half-life of ciprofloxacin, pefloxacin, glibenclamide, and Picralima nitida Figure 9:Degradation kinetics of ciprofloxacin Figure 10:Degradation kinetics of pefloxacin Figure 11:Degradation kinetics of glibenclamide Figure 12:Degradation kinetics of Picralima nitida 4.4 Shelf-Life Determination The effect of temperature on the degradation kinetics was also determined using Arrhenius equation. Arrhenius establishes a relationship between temperature and rate of reaction. Arrhenius plot was made by plotting ln kvalues against 1/T (Figures XIII-XVI). The value of k at 27°C ( k 27) was extrapolated from the Arrhenius plot using equation 2 [21]: Figure 13:Arrhenius plot for ciprofloxacin Figure 14:Arrhenius plot for pefloxacin Figure 15:Arrhenius plot for glibenclamide Figure 16:Arrhenius plot for Picralima nitida (2) Where k is the degradation rate constant, A is the frequency of molecular collisions occurring between the molecules or Arrhenius factor, E ais the energy of activation (kJ/mol.K), T is the absolute temperature (K) and R is the ideal gas constant (8.314 J/mol.K). The degradation rate also depends on the activation energy of the chemical reaction [4]. The activation energy was evaluated from the slope of the plot (Figures 13-16) using: (3) The activation energies E afor the degradation of each drug samples were found to be high ( E a> 50 kJ/mol.K), which were calculated as shown intable 1. The higher E ais, the less the degradation reaction is influenced by temperature; the result indicated that temperature contributed to the degradation of the drugs [22]. The shelf-life of the drug substances were estimated by substituting the values of k 27in the equation: (4) Where t 10%is the shelf life (the time required for 10% degradation of the drug) and k 27is the degradation rate constant at 27°C. The shelf life of the drug substances is presented inTable 1. The shelf life of ciprofloxacin, pefloxacin, and glibenclamide were found to be 535.18, 298.17 and 134.31 weeks, respectively. The shelf life of Picralima nitida(herbal drug) could not be determined because of the presence of complex metabolites, which results in the irregular increase in absorbance and instability. Half-life, t 1/2of the drug substances (the period of time required for the concentration of drug to be reduced by one-half of a given concentration) were also estimated at 27°C as follows: (5) The half-life of the drug substances is stated inTable 1. The half-life of ciprofloxacin, pefloxacin and, glibenclamide were found to be 3553.85, 1980 and 891.89 weeks, respectively while that of Picralima nitidacould not be determined because of its complexity. Conclusion The shelf life of Picralima nitida(herbal drug) and three orthodox drugs (glibenclamide, ciprofloxacin, and pefloxacin) have been investigated. The stability/shelf life study was done using UV spectrometry. The shelf life, t 10%(the time required to degrade 10% of a drug at 27°C) was determined by accelerated stability studies. The stability studies were done at temperatures of 45°C, 60°C and 70°C at 1, 2, 3 and 4 weeks. The initial concentration of 5, 2.5, 25 and 100 mg/ml was used for Picralima nitida, glibenclamide, ciprofloxacin, and pefloxacin, respectively for the stability study. The effects of storage time and temperature on the concentration of the drug samples were also investigated. First-order degradation kinetics constant, k and half-life, t 1/2were also evaluated. All experiments were carried out in the year 2012. The concentrations of the drug samples were found to decrease with increase in storage time and temperature. The shelf life of ciprofloxacin, pefloxacin, and glibenclamide were found to be 535.18, 298.17 and 134.31 weeks, respectively. The half-life of ciprofloxacin, pefloxacin and, glibenclamide were also found to be 3553.85, 1980 and 891.89 weeks, respectively. The shelf life and half-life of Picralima nitida(herbal drug) could not be determined because of its complexity (presence of complex metabolites, which results in the irregular increase in absorbance and instability). Storage time and temperature were found to have a great change in the concentration of the drugs. Acknowledgement The authors wish to acknowledge the Department of Pharmaceutics and Pharmaceutical Technology, Nnamdi Azikiwe University, Awka, Nigeria and National Agency for Food and Drug Administration and Control (NAFDAC), Agulu, Nigeria. References W. Liu, J.C. Hsu, F. Bretz, A.J. Hayter, Y. Han, Journal of Applied Statistics. , 2014, 41(9), 1989-2000. A. Uzunović, E. Vranić, Bosnian Journal of Basic Medical Sciences. , 2008, 8(1), 93-97. E. Koleva, T. Paneva, V. Tzotchev, Science, Engineering & Education. , 2016, 1(1), 106–112. R.T. Magari, BioPharm International. , 2003, 16(11), 36-48. WHO, Final report of the seminar on the use of medicinal plants in health care, WPRO Publication, Tokyo, 1996. H.M. Burkhill, The useful plants of West Tropical Arica. Royal botanic gardens, United Kingdom, 1985, 1(2), 28. C.K. Nkere, C.U. Iroegbu, Afr. J. Biotech. , 2005, 4(6), 522-526. T.O. Fakeye, O.A. Itiola, H.A. Odehla, Phythother. Res. , 2000, 14, 368-370. E.J. Akpan, I.B. Umoh, Nig. Soc. Exptl. Bio. , 2004, 16(2), 72-78. I.C. Ezeamuzie, M.C. Ojinnaka, E.O. Uzogara, S.E. Oji., J. Ethanopharmacol. , 1994, 54(2-3), 113-117. M. Duwiejua, E. Woode, D.D. Obiri, J. Ethnopharmacol ., 81(1), 2002, 73-79. M.M. Iwu, D.L. Klayman, J. Ethanopharmacol. , 1992, 36(2), 133-135. J. Bickii, G.R.F. Tchouya, J.C. Tchouankeu, E. Tsamo, Afr. J. Trad. Comp. Alter. Med. , 2007, 4(1), 107 - 111. E.C. Ibezim, C.O. Esimone, P.O. Nnamani, I.V. Onyishi, S.A. Brown, C.E. Obodo, Afr. J. Biotechnol. , 2006, 5(19), 1781-1784. J.P. Gonzalez, J.M. Henwood, Drugs. , 1989, 37(5), 628-68. WHO Expert Committee, The selection and use of essential medicines, WHO Tech Rep Ser. , 2011, 965, 1-249. L.E. Taha., S.M.A. Bakhit., J.A.A. Al-Sa’aidi, A.B.O. Uro, AL-Qadisiya J. Vet. Med. Sci ., 2014, 13(2), 113-117. H. Kunte, S. Schmidt, M. Eliasziw, G.J. de Zoppo, J.M. Simard, F. Masuhr, M. Weih, U. Dirnagl Stroke. , 2007, 38(9), 2526-2530. A.H. Moreno, H.R.N. Salgado, Adv. Anal. Chem. , 2016, 2(1), 1-5. V. Agrahari, S. Putty, C. Mathes,, J.B. Murowchick, B.C. Youan, Drug Test. Anal ., 2015, 7(3), 207-213. X. Lianga, Z. Liub, H. Shia, Y. Zhanga, S. Wanga, K. Bia and X. Chen, J Pharm Anal. , 2017, 7, 118-122.
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GtR The Gateway to Research: UKRI portal onto publically funded research MY-STORE: Multi-energY storage-Social, TechnO-economic, Regulatory and Environmental assessment under uncertainty Lead Research Organisation: University of Manchester Department Name: Electrical and Electronic Engineering Overview Organisations People Publications Outcomes Abstract The UK has a commitment to reduce its greenhouse gas emissions by at least 80% by 2050 relative to 1990 levels. While the potential role of energy storage to support integration of RES and help meet these challenging targets is well recognised, development of suitable frameworks that could facilitate energy storage rollout is still lacking. This is due to multiple factors that can be reflected in relevant Research Challenges that this project aims to address. These include: - An adequate understanding of commercial, regulatory, and institutional settings that can facilitate storage deployment; - Gaining insights into the true value streams that individual storage devices and coordinated portfolios of different technologies can generate for different parties across different markets; - Modelling interactions and maximising synergies among different energy vectors, and in particular heat and gas besides electricity, in order to unlock the flexibility of multi-energy forms of storage; - Developing suitable techno-economic models that can cater for the relevant operational and investment uncertainties that affect storage operators and owners and properly consider network and market constraints; - Understanding of wider impacts and social responses of different storage technologies, including public perceptions and environmental impacts. Our Vision is to develop a comprehensive framework, supported by innovative techno-economic modelling techniques capable to deal with different types of operational and planning uncertainties as well as network constraints, aimed at fostering sustainable business cases for different types of energy storage. Our analyses will assess how individual energy storage devices or aggregated portfolios of devices connected to different network levels can provide multiple simultaneous steady-state, dynamic services and power quality services and assess the relevant impact and value arising from these services for different market parties. We will consider explicitly multi-energy forms of storage, and in particular different types of electrical energy storage and thermal energy storage technologies, as well as innovative technologies such as power-to-gas. Our models will be tested in various technical, commercial and regulatory environments and taking into account socio-economic and environmental aspects, including public perceptions to different technologies. The MY-STORE project will strategically supplement the current research and bring a new perspective by providing much broader context, understanding and responses to the wide-scale deployment of energy storage. Our Ambition is to be the first in the world to provide such a comprehensive framework that can inform policy debates and the business community on the value and role of any storage technology in the transition towards more sustainable energy networks. Notwithstanding the generality of the framework put forward, the studies will focus on the UK situation, with time horizons from short to medium term (around 2035) and then opening up to 2050 and beyond. In fact, part of our ambitious plan is to bring out the value and role of energy storage and demonstrate how it could be possible to build business cases already in the shorter term and even for technologies that are commercially available today (e.g., thermal energy storage and different types of batteries), and then to facilitate development of appropriate regulatory and market environments for wider scale storage deployment (and possibly based on new technologies) to deal with the challenges of developing a truly low-carbon energy system. Our research will put the UK at the international forefront in this important field and provide a secure platform for future developments, also based on close collaboration with our industrial partners which represent a variety of established and emerging multi-energy storage technologies that are being already deployed or trialled in the UK. Planned Impact This project will be the first in the UK to compare a wide range of multi-energy storage options, and electrical and thermal storage in particular, using a consistent interdisciplinary framework, with a key objective to inform on new business case opportunities already from the end of the project (2019). The interdisciplinary methodologies applied have significant value for a wide range of stakeholders. The project has in fact been informed through discussions with key players we have already done significant Smart Grid-related research work with, including on storage technologies, namely, ENWL, E.On, and Hitachi. In addition, other partners have clearly expressed interest in our innovative approach by participating in the project, as indicated in the enclosed letters of support. Thus, the outputs of this project will be extremely relevant to network operators such as ENWL, internationally leading technical consultants such as ARUP and EA Technology, energy companies such as E.On, providers of different types of energy storage technology such as S&C Electric (electric storage), Hitachi (electric and thermal storage), ITM Power (power-to-gas storage), Highview Power (liquefied air energy storage), and SMEs such as Upside. We also anticipate that other industrial partners will join the project as it progresses. Knowledge transfer and impact on industrial partners will be achieved through a range of mechanisms including their attendance at review meetings, workshops, and ongoing inputs and feedback from their side also based on the use of specific technology data and case studies that they will provide during the project. We will also work with trade associations, policy makers, planners and regulators. In fact, energy storage technologies are frequently advocated as the game changer to address the energy trilemma of sustainability, affordability and security, which underpins the UK's economic and social well-being. Hence, if the system benefits of storage to address the trilemma are to be delivered, it will be essential that these groups understand the benefits and financial value of multi-energy storage portfolios so that appropriate commercial and regulatory frameworks are implemented. In order to do so, we will exploit our links with institutional bodies, the regulator Ofgem, the Department of Energy and Climate Change (DECC), the Committee for Climate Change (CCC), the Association of Greater Manchester Authority, and social housing providers (due to carbon emissions and fuel poverty) to ensure maximum impact. The project outputs will aid UK government agencies such as DECC and CCC in developing future energy storage support and related policy strategies. For policy makers and statutory bodies, this research will provide the evidence base upon which to design public policies and national legislation that can maximise the potential value of storage technologies; we will produce a report for policy makers and regulators at the end of the project to summarize our findings in this direction. The general public will benefit from increased awareness and knowledge of energy storage, besides the economic and environmental system level benefits that can be achieved. In this light, we will explicitly explore the public perceptions of these technologies and the context within which they may be used, which will inform how organisations should deliver new energy storage. The assessment metrics to compare technologies and designed in collaboration with industry and public sector parties will also ensure the direct relevance and utility of the research outputs to the widest possible stakeholders. This will be facilitated by different stakeholder workshops that will include a broader range of interested parties. These activities will thus eventually enable the co-production of knowledge with academia, industry and regulators and ensure that all end-users and market actors receive maximum benefit from our research. Funded Value: £1,268,165 Funded Period: Jan 16 - Nov 19 Funder: EPSRC Project Status: Closed Project Category: Research Grant Project Reference: EP/N001974/1 Principal Investigator: Pierluigi Mancarella Research Subject: Energy (100%) Research Topic: Energy Storage (100%) If populated the following is a graphic depicting where in the UK the given postcode is located. Organisations University of Manchester, Manchester, United Kingdom (Lead Research Organisation) ITM Power, United Kingdom (Collaboration) Energy Systems Catapult Ltd (Collaboration) redT energy plc (Collaboration) Highview Power Storage, United Kingdom (Collaboration, Project Partner) University of Melbourne, Australia (Collaboration) Arup Group Ltd, United Kingdom (Project Partner) Hitachi Europe Ltd, United Kingdom (Project Partner) S&C Electric Europe Limited, United Kingdom (Project Partner) ITM Power plc, United Kingdom (Project Partner) Upside Energy Ltd (Project Partner) Electricity North West, United Kingdom (Project Partner) E.On UK Plc, United Kingdom (Project Partner) E A Technology Ltd, United Kingdom (Project Partner) Birgitte Bak-Jensen (2022) Multi-energy System Interactions in Distribution Grids Clegg S (2016) Integrated Electrical and Gas Network Flexibility Assessment in Low-Carbon Multi-Energy Systemsin IEEE Transactions on Sustainable Energy Clegg S (2016) Assessment of the impact of heating on integrated gas and electrical network flexibility Corsetti E (2021) Modelling and deploying multi-energy flexibility: The energy lattice frameworkin Advances in Applied Energy Dai Y (2018) Integrated Dispatch Model for Combined Heat and Power Plant With Phase-Change Thermal Energy Storage Considering Heat Transfer Processin IEEE Transactions on Sustainable Energy Dai Y (2018) A General Model for Thermal Energy Storage in Combined Heat and Power Dispatch Considering Heat Transfer Constraintsin IEEE Transactions on Sustainable Energy Good N (2016) A business case modelling framework for smart multi-energy districts Good N (2017) Techno-economic assessment of community energy solutions to network capacity issues Good N (2016) Modelling and assessment of business cases for smart multi-energy districts Good N (2017) Ten questions concerning smart districtsin Building and Environment Good N (2019) Flexibility in Multi-Energy Communities With Electrical and Thermal Storage: A Stochastic, Robust Approach for Multi-Service Demand Responsein IEEE Transactions on Smart Grid Good N (2019) A transactive energy modelling and assessment framework for demand response business cases in smart distributed multi-energy systemsin Energy Gutierrez L (2019) CVR in PV-rich distribution networks: A customer perspective Gutierrez L. (2020) Quantifying the Effects of MV-LV Distribution Network Constraints and DER Reactive Power Capabilities on Aggregatorsin IEEE Transactions on Power Systems Gutierrez-Lagos L (2019) Implementable Three-Phase OPF Formulations for MV-LV Distribution Networks: MILP and MIQCP Gutierrez-Lagos L (2020) On the Inadequacy of the CVR Factor for Active Schemesin IEEE Transactions on Power Delivery Haas J (2017) Challenges and trends of energy storage expansion planning for flexibility provision in low-carbon power systems - a reviewin Renewable and Sustainable Energy Reviews
https://gtr.ukri.org/project/C52EF173-39D7-4823-B384-6C8052365B96?fetchSize=25&pn=0&selectedSortOrder=ASC&selectedSortableField=firstAuthorName
ANZCTR - Registration Trial Review We have now released the latest update to our report on the clinical trials landscape in Australia (2006 – 2020) , which outlines key characteristics of clinical trials over time. Registering a new trial? Videos on how to complete Step 3: Intervention , Step 4: Outcomes and Step 11: Data sharing are available. To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers Trial details imported from ClinicalTrials.gov For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03347253 Registration number NCT03347253 Ethics application status Date submitted Date registered Date last updated Titles & IDs Public title STRIDE Study - A Study in Subjects With LOPD Who Are Currently Being Treated With ERT Scientific title A Prospective Study in Subjects With Late Onset Pompe Disease Who Are Currently Being Treated With Enzyme Replacement Therapy Secondary ID [1] 0 0 POM-003 Universal Trial Number (UTN) Trial acronym Linked study record Health condition Health condition(s) or problem(s) studied: Late-onset Pompe Disease Condition category Condition code Metabolic and Endocrine Metabolic disorders Metabolic and Endocrine Other metabolic disorders Human Genetics and Inherited Disorders Other human genetics and inherited disorders Intervention/exposure Study type Observational Patient registry Target follow-up duration Target follow-up type Description of intervention(s) / exposure Comparator / control treatment Control group Outcomes Primary outcome [1] 0 0 Evaluate degree of change in muscle function and respiratory endpoints over time - To evaluate the degree of change in muscle function and respiratory endpoints over time in patients with Late Onset Pompe disease Timepoint [1] 0 0 6-15 month Eligibility Key inclusion criteria 1. Subject has a diagnosis of Pompe disease based on documented deficiency of GAA activity and a documented GAA mutation. 2. Male and female subjects between 18 years and 75 years, inclusive and = 50 kg. 3. Subject must be currently receiving standard-of-care ERT (alglucosidase alfa) at a dose of 20 mg/kg dose every other week. 4. Subject must have been on ERT for the preceding 2 years or more. 5. Subject must have an upright forced vital capacity (FVC) within 35 to 90% of predicted normal (NHANES III reference values), based on the higher of the screening or baseline value, if their 6 minute walk distance (6MWD) is > 200 m. Subject must have an upright FVC within 40 to 90% of predicted normal (NHANES III reference values), based on the higher of the screening or baseline value, if their 6MWD is = 200 m. If FVC is between 80 and 90% of predicted normal, the subject may enter the study if the percent predicted FVC value drops by 10% predicted or more in supine position 6. Subject is able to walk at least 100 m in the 6MWT and the assessment is noted as valid. Minimum age 18 Years Maximum age 75 Years Gender Both males and females Can healthy volunteers participate? No Key exclusion criteria 1. Subject has received any investigational therapy or pharmacological treatment for Pompe disease, other than alglucosidase alfa within 30 days or 5 half lives, whichever is shorter, prior to the Baseline Visit or is anticipated to do so during the course of the study 2. Subject is on any of the following prohibited medications within 30 days of baseline: - miglitol (eg, Glyset) - miglustat (eg, Zavesca) - acarbose (eg, Precose, Glucobay) - voglibose (eg, Volix, Vocarb, Volibo) 3. Subject requires use of invasive or non-invasive ventilatory support for > 6 hours a day while awake. 4. Subject has a medical or any other extenuating condition or circumstance that may, in the opinion of the investigator, pose an undue safety risk to the subject or compromise his/her ability to comply with protocol requirements. This includes clinical depression (as diagnosed by a psychiatrist or other mental health professional) with uncontrolled or poorly controlled symptoms. 5. Subject is breastfeeding, or is pregnant or planning to become pregnant within the next 2 years. 6. Other exclusion criteria according to the Lumizyme/Myozyme instructions for use. Study design Purpose Duration Selection Timing Prospective Statistical methods / analysis Recruitment Recruitment status Terminated Data analysis Reason for early stopping/withdrawal Other reasons Date of first participant enrolment Anticipated Actual Date of last participant enrolment Anticipated Actual Date of last data collection Anticipated Actual Sample size Target Accrual to date Final 12 Recruitment in Australia Recruitment state(s) Recruitment hospital [1] 0 0 Royal Adelaide Hospital - Adelaide Recruitment postcode(s) [1] 0 0 5000 - Adelaide Recruitment outside Australia Country [1] 0 0 United States of America State/province [1] 0 0 California Country [2] 0 0 United States of America State/province [2] 0 0 Florida Country [3] 0 0 United States of America State/province [3] 0 0 Georgia Country [4] 0 0 United States of America State/province [4] 0 0 Kansas Country [5] 0 0 United States of America State/province [5] 0 0 Massachusetts Country [6] 0 0 United States of America State/province [6] 0 0 Minnesota Country [7] 0 0 United States of America State/province [7] 0 0 New Jersey Country [8] 0 0 United States of America State/province [8] 0 0 New York Country [9] 0 0 United States of America State/province [9] 0 0 North Carolina Country [10] 0 0 United States of America State/province [10] 0 0 Ohio Country [11] 0 0 United States of America State/province [11] 0 0 Oregon Country [12] 0 0 United States of America State/province [12] 0 0 Pennsylvania Country [13] 0 0 United States of America State/province [13] 0 0 Texas Country [14] 0 0 Belgium State/province [14] 0 0 Edegem Country [15] 0 0 Canada State/province [15] 0 0 Alberta Country [16] 0 0 Canada State/province [16] 0 0 Primary sponsor type Name Address Country Brief summary Trial website Principal investigator Summary results For IPD and results data, please see https://clinicaltrials.gov/show/NCT03347253
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=7155&isClinicalTrial=True
Surgical Site Infection With 0.05% Chlorhexidine (CHG) Compared to Triple Antibiotic Irrigation - Full Text View - ClinicalTrials.gov Surgical Site Infection With 0.05% Chlorhexidine (CHG) Compared to Triple Antibiotic Irrigation The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. ClinicalTrials.gov Identifier: NCT02395614 Recruitment Status : Completed First Posted : March 23, 2015 Results First Posted : January 26, 2022 Last Update Posted : January 26, 2022 Sponsor: Vanderbilt University Medical Center Information provided by (Responsible Party): Kent Higdon, Vanderbilt University Medical Center Study Details Study Description Brief Summary: The investigators intend to perform a prospective randomized study and compare the incidence of surgical wound infection between mastectomy wounds irrigated with triple antibiotic solution (one side) and 0.05% CHG (opposite side) in patients undergoing bilateral breast reconstruction. Each patient will receive triple antibiotic solution on one breast and the CHG on the other breast. Condition or disease Intervention/treatment Phase Breast Cancer Drug: Chlorhexidine irrigation Drug: triple antibiotic irrigation Not Applicable Detailed Description: Breast reconstruction with tissue expander (TE) remains the gold standard of breast restoration after mastectomy. During the first stage of reconstruction, a TE is placed under chest muscles and slowly inflated postoperatively over the period of several weeks. After desired volume of TE is achieved it is exchanged for permanent breast prosthesis during another surgery (second stage of reconstruction). Postoperative wound infection after placement of TE can lead to devastating consequences both for patients and a surgeon. Frequently, surgical site infection requires additional surgeries and resulting in the removal of TE and long term IV antibiotic therapy. Therefore, during breast reconstruction procedures all possible measures are implemented to reduce postoperative infection rate. Several studies demonstrated that intra-operative irrigation of surgical wounds with antibiotic containing solution before insertion of breast TE decreases postoperative infection rate. This approach is currently adopted as a standard of care within plastic surgery clinical community. The investigators intend to perform a prospective randomized study and compare the incidence of surgical wound infection between mastectomy wounds irrigated with triple antibiotic solution (one side) and 0.05% CHG (opposite side) in patients undergoing bilateral breast reconstruction. Study Design Layout table for study information Study Type : Interventional  (Clinical Trial) Actual Enrollment : 88 participants Allocation: Randomized Intervention Model: Single Group Assignment Masking: Double (Participant, Outcomes Assessor) Primary Purpose: Treatment Official Title: Post-Mastectomy Surgical Pocket Irrigation With Triple Antibiotic Solution vs Chlorhexidine Gluconate: A Randomized Controlled Trial Assessing Surgical Site Infections in Immediate Tissue Expander Breast Reconstruction Study Start Date : December 2015 Actual Primary Completion Date : December 2020 Actual Study Completion Date : December 2020 Resource links provided by the National Library of Medicine MedlinePlus Genetics related topics: Breast cancer MedlinePlus related topics: Antibiotics Drug Information available for: Chlorhexidine Chlorhexidine acetate Bacitracin Chlorhexidine hydrochloride Chlorhexidine gluconate Hibiclens U.S. FDA Resources Arms and Interventions Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Arm Intervention/treatment Experimental: Chlorhexidine irrigation 0.05% chlorhexidine solution (IrriSept®) commercially prepared in 450 ml bottles for irrigation. Each patient will receive triple antibiotic solution on one breast and the CHG on the other breast. Drug: Chlorhexidine irrigation - 0.05% chlorhexidine solution (IrriSept®) commercially prepared in 450 ml bottles will be used to irrigate one breast pocket. Each patient will receive triple antibiotic solution on one breast and the CHG on the other breast. Other Name: CHG Active Comparator: triple antibiotic irrigation triple antibiotic solution will contain 1 g of cefazolin, 50,000 U of bacitracin, and 80 mg of gentamicin in 500 mL of normal saline (NS). If the patient is allergic to either component - the allergen will not be used in the solution - for irrigation. Each patient will receive triple antibiotic solution on one breast and the CHG on the other breast. Drug: triple antibiotic irrigation-triple antibiotic solution will contain 1 g of cefazolin, 50,000 U of bacitracin, and. Each patient will receive triple antibiotic solution on one breast and the CHG on the other breast.80 mg of gentamicin in 500 mL of NS. If the patient is allergic to either component - the allergen will not be used in the solution - to irrigate one breast pocket Other Name: gentamicin, cefazolin and bacitracin Outcome Measures Primary Outcome Measures : Number of Participants With Surgical Site Infection [ Time Frame: 6 months ] At all postoperative visits with the reconstructive surgeon, patients were thoroughly examined for presence of SSI (cellulitis, purulent drainage). SSI was defined as any instance where antibiotics were restarted or where erythema, cellulitis, warmth, purulent drainage, or fever occurred. SSI was further classified in 3 categories: minor when requiring oral antibiotics, major when requiring inpatient intravenous antibiotics or operative washout, and finally, explantation. Secondary Outcome Measures : Number of Participants With Flap Necrosis, Hematoma, and Seroma [ Time Frame: 6 months ] At all postoperative visits with the reconstructive surgeon, patients were thoroughly examined for presence of necrosis, seroma, or hematoma. Eligibility Criteria Layout table for eligibility information Ages Eligible for Study: 18 Years to 81 Years   (Adult, Older Adult) Sexes Eligible for Study: Female Accepts Healthy Volunteers: No Criteria Inclusion Criteria: females between 18 - 81 years of age and are undergoing bilateral mastectomy and are candidates for immediate breast reconstruction with tissue expanders. Exclusion Criteria: females younger than 18 and older than 81 years of age; undergoing unilateral mastectomy and reconstruction; bilateral reconstruction using other techniques, patients allergic to one or more components of the antibiotic solution; allergy to CHG Locations Layout table for location information United States, Tennessee Vanderbilt University Medical Center Nashville, Tennessee, United States, 37232 Sponsors and Collaborators Vanderbilt University Medical Center Investigators Layout table for investigator information Principal Investigator: Kent Higdon, MD Vanderbilt University Medical Center Study Documents (Full-Text) Documents provided by Kent Higdon, Vanderbilt University Medical Center: Study Protocol and Statistical Analysis Plan [PDF] April 1, 2014 Informed Consent Form [PDF] June 20, 2018 Layout table for additonal information Responsible Party: Kent Higdon, MD, Vanderbilt University Medical Center ClinicalTrials.gov Identifier: NCT02395614 History of Changes Other Study ID Numbers: 140231 First Posted: March 23, 2015 Key Record Dates Results First Posted: January 26, 2022 Last Update Posted: January 26, 2022 Last Verified: January 2022 Individual Participant Data (IPD) Sharing Statement: Plan to Share IPD: No Keywords provided by Kent Higdon, Vanderbilt University Medical Center: tissue expander breast reconstruction
https://clinicaltrials.gov/show/NCT02395614
Factories Act - Singapore Statutes Online Singapore Statutes Online is provided by the Legislation Division of the Singapore Attorney-General's Chambers A Singapore Government Agency Website Home Browse Acts Current Repealed/Spent Uncommenced Subsidiary Legislation Current Revoked/Spent Uncommenced AS PUBLISHED Acts Supplement Bills Supplement Subsidiary Legislation Supplement Revised Editions of Acts Revised Editions of Subsidiary Legislation QUICK LINKS Constitutional Instruments Basic Acts Subsidiary Legislation Interpretation Act Private Acts English Acts Imperial Acts Honours/Awards Frequently Accessed Legislation What's New Announcements Courses New Legislation Help FAQs SSO Guide Video Guides About Us FAQs Feedback My Collections Search within My Collections | Help My Collections Search within My Collections | Help My Collections allows you to create your personal lists of current legislation for quick access and search. 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Search Advanced Search | Saved Searches | Help All of these words Current Acts and Subsidiary Legislation Title / No. Content Title / No. Content All of these words Current Acts and Subsidiary Legislation Factories Act (CHAPTER 104) Status: Not current version (effective from 01 Jun 1989 to 31 Mar 1995) Print Select the provisions you wish to print using the checkboxes and then click the relevant "Print" Select All Clear All Print - HTML Print - PDF Print - Word Factories Act (CHAPTER 104) Table of Contents Long Title Part I SHORT TITLE AND APPLICATION 1 Short title 2 General application of this Act 3 Application to factories belonging to Government 4 Power to exempt in case of public emergency 5 Power to exempt Part II INTERPRETATION 6 Interpretation of "factory" 7 General interpretation Part III REGISTRATION OF FACTORIES 8 Register of factories 9 Registration of factories 10 Notification by inspector of defects in factory 11 Interpretation Part IV HEALTH (GENERAL PROVISIONS) 12 Cleanliness 13 Overcrowding 14 Ventilation 15 Lighting 16 Drainage of floors 17 Sanitary conveniences Part V SAFETY (GENERAL PROVISIONS) 18 Prime movers 19 Electric generators and motors 20 Electrical installations and equipment 21 Transmission machinery 22 Other machinery 23 Provisions as to unfenced machinery 24 Construction and maintenance 25 Construction and disposal of new machinery 26 Dangerous substances 27 Self-acting machines 28 Training and supervision of inexperienced workers 29 Hoists and lifts 30 Lifting gear 31 Lifting appliances and lifting machines 32 Register of lifting gear, etc. 33 Safe means of access and safe place of employment 34 Dangerous fumes and lack of oxygen 35 Precautions with regard to explosive or inflammable dust, gas, vapour or substance 36 Steam boilers 37 Steam receivers and steam containers 38 Cast-iron underfired vulcanisers 39 Air receivers 40 Refrigerating plant pressure receivers 41 Pressure vessels containing corrosive, toxic, explosive or inflammable substance 42 Pipelines and equipment conveying certain substances 43 Exemptions from sections 36, 37, 38, 39 and 40 44 Gas plants 45 Repair of pressure vessel 46 Prevention of fire 47 Safety provisions in case of fire 48 Power of Chief Inspector to make orders 49 Power to prohibit work or processes in certain circumstances 50 Appeal from order made by Chief Inspector 51 Notification of accidents and dangerous occurrences 52 Investigation into accidents and dangerous occurrences 53 Alteration or addition to machinery, equipment, etc. 54 Minister may direct inquiry to be held into accident and dangerous occurrence Part VI WELFARE (GENERAL PROVISIONS) 55 Supply of drinking water 56 Washing facilities and accommodation for clothing 57 Exemption as to washing facilities 58 First-aid Part VII HEALTH, SAFETY AND WELFARE (SPECIAL PROVISIONS AND REGULATIONS) 59 Removal of dust or fumes 60 Poisonous substances 61 Meals in certain dangerous trades 62 Protective clothing and appliances 63 Protection of eyes in certain processes 64 Reduction of noise or vibration 65 Protection against harmful processes or substances 66 Power of Chief Inspector to require separate changing and washing facilities 67 Notification of industrial diseases 68 Power to make regulations 69 Medical supervision 70 Power to take samples 71 Safety officers 72 Safety committees Part VIII SPECIAL APPLICATIONS AND EXTENSIONS 73 Premises where part of building is separate factory 74 Docks, etc. 75 Ships 76 Premises in which steam boilers and air receivers are used 77 Regulations in respect of building operations, etc. Part IX MISCELLANEOUS 78 Periodical examinations when a boiler inspector or an approved person not available 79 Factory records 80 Duties of persons employed 81 Persons employed not to cause danger 82 Prohibition of deductions from wages Part X ADMINISTRATION 83 Administration of this Act 84 Appointment of inspectors 85 Powers of inspectors 86 Power of inspector to conduct proceedings before a Magistrate’s Court or District Court 87 Persons not to reveal secrets Part XI OFFENCES, PENALTIES AND LEGAL PROCEEDINGS 88 Offences 89 Penalty for offences for which no express penalty is provided 90 Power of court to order cause of contravention to be remedied 91 Forgery of certificates, false entries and false declarations 92 Penalty on persons actually committing offence for which other person is liable 93 Power of person primarily liable to exempt himself from liability 94 Proceedings against persons not primarily liable 95 Owner of machine liable in certain cases instead of occupier 96 Prosecution of offences 97 Power to compound offences 98 Special provisions as to evidence 99 Service and sending of documents, etc. 100 Power to modify agreements 101 Power to apportion expenses Part XII GENERAL 102 Regulations 103 Advisory Council for Industrial Health and Safety 104 Power of Minister to amend Schedules 105 Saving 106 Transitional provisions FIRST SCHEDULE SECOND SCHEDULE THIRD SCHEDULE FOURTH SCHEDULE Classes of dangerous occurrences FIFTH SCHEDULE Processes requiring provision of suitable goggles or effective screens SIXTH SCHEDULE Notifiable Industrial Diseases SEVENTH SCHEDULE Occupations involving special risks to health EIGHTH SCHEDULE Particulars to be submitted by occupiers of premises (other than factories) in which a steam boiler or air receiver is used NINTH SCHEDULE TENTH SCHEDULE ELEVENTH SCHEDULE Legislative History Select All Clear All Print HTML PDF Word Factories Act Status: Not current version (effective from 01 Jun 1989 to 31 Mar 1995) Please check the legislation timeline to ensure that you are viewing the correct legislation version. See also FAQ B3 . Factories Act ... Hide Amendment Annotation Amendments RSS Feed Print Help Timeline Document Provision Versions 01 Jun 1989 or find current version as at 01 Jun 1989 01 Mar 2006 Repealed by Act 7 of 2006 01 Apr 2005 Amended by Act 47 of 2004 01 Mar 2003 Amended by S 672/2002 01 Apr 2001 Amended by Act 4 of 2001 01 Mar 2000 Amended by Act 1 of 2000 30 May 1998 1998 RevEd 01 Feb 1997 Amended by S 20/1997 01 Apr 1996 Amended by Act 1 of 1996 01 Apr 1995 Amended by S 145/1995 01 Jun 1989 Amended by S 136/1989 01 Apr 1988 Amended by S 34/1988 30 Mar 1987 1985 RevEd Table of Contents Factories Act (CHAPTER 104) Long Title Part I SHORT TITLE AND APPLICATION 1 Short title 2 General application of this Act 3 Application to factories belonging to Government 4 Power to exempt in case of public emergency 5 Power to exempt Part II INTERPRETATION 6 Interpretation of "factory" 7 General interpretation Part III REGISTRATION OF FACTORIES 8 Register of factories 9 Registration of factories 10 Notification by inspector of defects in factory 11 Interpretation Part IV HEALTH (GENERAL PROVISIONS) 12 Cleanliness 13 Overcrowding 14 Ventilation 15 Lighting 16 Drainage of floors 17 Sanitary conveniences Part V SAFETY (GENERAL PROVISIONS) 18 Prime movers 19 Electric generators and motors 20 Electrical installations and equipment 21 Transmission machinery 22 Other machinery 23 Provisions as to unfenced machinery 24 Construction and maintenance 25 Construction and disposal of new machinery 26 Dangerous substances 27 Self-acting machines 28 Training and supervision of inexperienced workers 29 Hoists and lifts 30 Lifting gear 31 Lifting appliances and lifting machines 32 Register of lifting gear, etc. 33 Safe means of access and safe place of employment 34 Dangerous fumes and lack of oxygen 35 Precautions with regard to explosive or inflammable dust, gas, vapour or substance 36 Steam boilers 37 Steam receivers and steam containers 38 Cast-iron underfired vulcanisers 39 Air receivers 40 Refrigerating plant pressure receivers 41 Pressure vessels containing corrosive, toxic, explosive or inflammable substance 42 Pipelines and equipment conveying certain substances 43 Exemptions from sections 36, 37, 38, 39 and 40 44 Gas plants 45 Repair of pressure vessel 46 Prevention of fire 47 Safety provisions in case of fire 48 Power of Chief Inspector to make orders 49 Power to prohibit work or processes in certain circumstances 50 Appeal from order made by Chief Inspector 51 Notification of accidents and dangerous occurrences 52 Investigation into accidents and dangerous occurrences 53 Alteration or addition to machinery, equipment, etc. 54 Minister may direct inquiry to be held into accident and dangerous occurrence Part VI WELFARE (GENERAL PROVISIONS) 55 Supply of drinking water 56 Washing facilities and accommodation for clothing 57 Exemption as to washing facilities 58 First-aid Part VII HEALTH, SAFETY AND WELFARE (SPECIAL PROVISIONS AND REGULATIONS) 59 Removal of dust or fumes 60 Poisonous substances 61 Meals in certain dangerous trades 62 Protective clothing and appliances 63 Protection of eyes in certain processes 64 Reduction of noise or vibration 65 Protection against harmful processes or substances 66 Power of Chief Inspector to require separate changing and washing facilities 67 Notification of industrial diseases 68 Power to make regulations 69 Medical supervision 70 Power to take samples 71 Safety officers 72 Safety committees Part VIII SPECIAL APPLICATIONS AND EXTENSIONS 73 Premises where part of building is separate factory 74 Docks, etc. 75 Ships 76 Premises in which steam boilers and air receivers are used 77 Regulations in respect of building operations, etc. Part IX MISCELLANEOUS 78 Periodical examinations when a boiler inspector or an approved person not available 79 Factory records 80 Duties of persons employed 81 Persons employed not to cause danger 82 Prohibition of deductions from wages Part X ADMINISTRATION 83 Administration of this Act 84 Appointment of inspectors 85 Powers of inspectors 86 Power of inspector to conduct proceedings before a Magistrate’s Court or District Court 87 Persons not to reveal secrets Part XI OFFENCES, PENALTIES AND LEGAL PROCEEDINGS 88 Offences 89 Penalty for offences for which no express penalty is provided 90 Power of court to order cause of contravention to be remedied 91 Forgery of certificates, false entries and false declarations 92 Penalty on persons actually committing offence for which other person is liable 93 Power of person primarily liable to exempt himself from liability 94 Proceedings against persons not primarily liable 95 Owner of machine liable in certain cases instead of occupier 96 Prosecution of offences 97 Power to compound offences 98 Special provisions as to evidence 99 Service and sending of documents, etc. 100 Power to modify agreements 101 Power to apportion expenses Part XII GENERAL 102 Regulations 103 Advisory Council for Industrial Health and Safety 104 Power of Minister to amend Schedules 105 Saving 106 Transitional provisions FIRST SCHEDULE SECOND SCHEDULE THIRD SCHEDULE FOURTH SCHEDULE Classes of dangerous occurrences FIFTH SCHEDULE Processes requiring provision of suitable goggles or effective screens SIXTH SCHEDULE Notifiable Industrial Diseases SEVENTH SCHEDULE Occupations involving special risks to health EIGHTH SCHEDULE Particulars to be submitted by occupiers of premises (other than factories) in which a steam boiler or air receiver is used NINTH SCHEDULE TENTH SCHEDULE ELEVENTH SCHEDULE Legislative History Reset Get Provisions Whole Document Factories Act Status: Not current version (effective from 01 Jun 1989 to 31 Mar 1995) Timeline Amendment Annotation Loading... Actions Amendments RSS Feed Document Provision 30 Mar 1987 1985 RevEd 01 Apr 1988 Amended by S 34/1988 01 Jun 1989 Amended by S 136/1989 01 Apr 1995 Amended by S 145/1995 01 Apr 1996 Amended by Act 1 of 1996 01 Feb 1997 Amended by S 20/1997 30 May 1998 1998 RevEd 01 Mar 2000 Amended by Act 1 of 2000 01 Apr 2001 Amended by Act 4 of 2001 01 Mar 2003 Amended by S 672/2002 01 Apr 2005 Amended by Act 47 of 2004 01 Mar 2006 Repealed by Act 7 of 2006 Versions 01 Jun 1989 30 Mar 1987 1 Apr 1988 1 Jun 1989 1 Apr 1995 1 Apr 1996 1 Feb 1997 30 May 1998 1 Mar 2000 1 Apr 2001 1 Mar 2003 1 Apr 2005 1 Mar 2006 or find current version as at Go Search within Legislation Exit Search Search Results NINTH SCHEDULE Section 51. [19/78] Singapore Statutes Online FAQs Feedback Site Map Privacy Statement Terms of Use Report Vulnerability
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JFK Assassination Records - 2018 Additional Documents Release | National Archives Have a question about JFK Assassination Records? Ask it on HistoryHub! The National Archives is releasing documents previously withheld in accordance with the JFK Assassination Records Collection Act. The vast majority of the Collection (88%) has been open in full and released to the public since the late 1990s. The records at issue are documents previously identified as JFK Assassination Records - 2018 Additional Documents Release The National Archives is releasing documents previously withheld in accordance with the JFK Assassination Records Collection Act.  The vast majority of the Collection (88%) has been open in full and released to the public since the late 1990s. The records at issue are documents previously identified as assassination records, but withheld in full or withheld in part.Learn more These releases include FBI, CIA, and other agency documents (both formerly withheld in part and formerly withheld in full) identified by the Assassination Records Review Board as assassination records. The releases to date are as follows: July 24, 2017: 3,810 documents (read press release ) October 26, 2017: 2,891 documents (read press release ) November 3, 2017: 676 documents (read press release ) November 9, 2017: 13,213 documents (read press release ) November 17, 2017: 10,744 documents (read press release ) December 15, 2017: 3,539 documents * (read press release ) April 26, 2018: 18,731 documents * (read press release ) * Note: There are instances where multiple record identification numbers are associated with the same pdf. This is due to the fact that the files were scanned in batches. Accessing the Release Files The table below displays metadata about all the released documents. You can alsodownload the spreadsheet as an Excel file(4.7MB). To view or download a specific document, follow the link in the "Doc Date" column. The files are sorted by NARA Release Date, with the most recent files appearing first. The previous withholding status (i.e., formerly withheld in part or formerly withheld in full) is identified in the “Formerly Withheld Status” column. JFK Table Search: Search Reset Row Num Record Num NARA Release Date Formerly Withheld Agency Doc Date Doc Type File Num To Name From Name Title Num Pages Originator Record Series Review Date Comments Pages Released Row Num Record Num NARA Release Date Formerly Withheld Agency Doc Date Doc Type File Num To Name From Name Title Num Pages Originator Record Series Review Date Comments Pages Released 49351 124-10250-10287 07/24/2017 In Part FBI 12/15/1964 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-38431-1286, 1287 SAC, NY DIRECTOR, FBI FBI NY 06/01/2017 INC LHM, MEMO 49352 124-10250-10314 07/24/2017 In Part FBI 10/04/1965 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-38431-1340, 1341 SAC, NY DIRECTOR, FBI FBI NY 05/22/2017 INC MEMO, LHM 49353 124-10250-10338 07/24/2017 In Part FBI 01/06/1964 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-38431-372 HALLERON, JAMES P. SAC, NY FBI NY 05/22/2017 49354 124-10250-10392 07/24/2017 In Part FBI 07/16/1964 [ PDF ] PAPER, TEXTUAL DOCUMENT 89-69-1282A GEMBERLING, ROBERT P. DIRECTOR, FBI FBI NO 05/22/2017 49355 124-10251-10033 07/24/2017 In Part FBI 07/18/1967 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-8342-1274, 1275 SAC, NO DIRECTOR, FBI FBI MM 05/18/2017 INC LHM, A/T 49356 124-10251-10074 07/24/2017 In Part FBI 03/17/1964 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-38431-663, 664 SAC, LA DIRECTOR, FBI FBI NY 05/22/2017 INC LHM, A/T 49357 124-10251-10316 07/24/2017 In Part FBI 07/18/1967 [ PDF ] PAPER, TEXTUAL DOCUMENT 89-69-3343, 3344 SAC, NO DIRECTOR, FBI FBI NO 05/22/2017 INC LHM, A/T 49358 124-10251-10336 07/24/2017 In Part FBI 12/16/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-2758-154 ESTEP, THOMAS B. DIRECTOR, FBI FBI CI 05/22/2017 49359 124-10251-10337 07/24/2017 In Part FBI 12/18/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-2758-155 ESTEP, THOMAS B. DIRECTOR, FBI FBI CI 05/22/2017 49360 124-10251-10355 07/24/2017 In Part FBI 12/08/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-2758-173 HOPKINS, EMIL E. FBI CI 05/22/2017 49361 124-10251-10356 07/24/2017 In Part FBI 12/08/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-2758-174 HOPKINS, EMIL E. FBI CI 05/22/2017 49362 124-10251-10399 07/24/2017 In Part FBI 11/30/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-2758-221 HOPKINS, EMIL E. FBI CI 05/22/2017 49363 124-10252-10005 07/24/2017 In Part FBI 11/25/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 100-18158-8 SLIFKA, STEPHEN J. JR. SAC FBI NH 05/18/2017 49364 124-10252-10015 07/24/2017 In Part FBI 11/26/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 100-18158-20 ROBERTSON, ROBERT E. SAC, NH FBI NH 05/18/2017 49365 124-10253-10005 07/24/2017 In Part FBI 00/00/0000 [ PDF ] PAPER, TEXTUAL DOCUMENT, OTHER NON-TEXTUAL 105-38431-SEE COMMENTS SAC, NY FBI NY 05/22/2017 105-38431-1B4,1B5,1B6,1B7,1B4-1,1B4-2,1B4-3, BULKY ENC, INC EXH, PHOTOSTATS 49366 124-10253-10007 07/24/2017 In Part FBI 00/00/0000 [ PDF ] PAPER, TEXTUAL DOCUMENT, PHOTO, PHOTO NEG, NON-TEXTUAL 105-38431-SEE COMMENTS SAC, NY FBI NY 05/22/2017 105-38431-1B4-7,1B5-1,1B5-2,1B5-3,1B5-4,1B5-5 ,1B5-6,1B5-7,1B6-1,1B6-2,1B6-3,1B6-4,1B6-5, 1B6-6,1B6-7,1B6-8,1B7-1, BULKY ENC, INC EXH, PHOTOSTATS, SOUND RECORDING TAPES 49367 124-10253-10026 07/24/2017 In Part FBI 11/12/1968 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-16814-31 SMITH, JOSEPH F. FBI SF 05/22/2017 49368 124-10254-10013 07/24/2017 In Part FBI 12/01/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-620-18 TWINER, GROVER C. DIRECTOR, FBI FBI LS 05/18/2017 49369 124-10254-10093 07/24/2017 In Part FBI 00/00/0000 [ PDF ] PAPER, TEXTUAL DOCUMENT, PHOTO 105-37111-C-1A1, 1A2, 1A3 SAC, WMFO FBI WMFO 05/22/2017 INC ENV, PHOTO, LTRS, INVOICE, POSTCARD 49370 124-10254-10107 07/24/2017 In Part FBI 04/16/1964 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-37111-324 NORRIS, JOSEPH K. SAC, WMFO FBI WMFO 05/22/2017 49371 124-10254-10110 07/24/2017 In Part FBI 04/17/1964 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-37111-329 SAC, WMFO DIRECTOR, FBI FBI WMFO 05/22/2017 49372 124-10254-10147 07/24/2017 In Part FBI 04/30/1964 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-37111-373 KAIER, EDWARD J. SAC, WMFO FBI WMFO 05/22/2017 49373 124-10254-10161 07/24/2017 In Part FBI 12/18/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-38431-299 LAUZIERE, MAURICE H. SAC, NY FBI NY 05/22/2017 49374 124-10254-10173 07/24/2017 In Part FBI 12/27/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-38431-313 SAC, NY SAC, NK FBI NY 05/22/2017 49375 124-10254-10179 07/24/2017 In Part FBI 12/31/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-38431-320 SAC, NY SAC, CG FBI NY 05/22/2017 49376 124-10254-10187 07/24/2017 In Part FBI 12/08/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-38431-328 HOPKINS, EMIL E. FBI NY 05/22/2017 49377 124-10254-10188 07/24/2017 In Part FBI 12/17/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-38431-329 HALDESON, JAMES P. FBI NY 05/22/2017 49378 124-10254-10189 07/24/2017 In Part FBI 12/08/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-38431-330 HOPKINS, EMIL E. FBI NY 05/22/2017 49379 124-10254-10190 07/24/2017 In Part FBI 12/08/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-38431-331 HOPKINS, EMIL E. FBI NY 06/01/2017 49380 124-10254-10196 07/24/2017 In Part FBI 12/31/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-38431-337 SAC, NY SAC, CG FBI NY 05/22/2017 49381 124-10254-10261 07/24/2017 In Part FBI 02/06/1964 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-38431-533 GRUBERT, HERBERT A. SAC, NY FBI NY 05/22/2017 49382 124-10254-10302 07/24/2017 In Part FBI 11/26/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-3060-36 MARLEY, JAMES A. JR. SAC, NK FBI NK 05/22/2017 49383 124-10254-10327 07/24/2017 In Part FBI 11/26/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-3060-61 LIGHT, RALPH D. JR. SAC, NK FBI NK 05/22/2017 49384 124-10254-10335 07/24/2017 In Part FBI 11/26/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-3060-69 BOWMAN, MAURICE T. SAC, NK FBI NK 05/22/2017 49385 124-10254-10337 07/24/2017 In Part FBI 11/26/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-3060-71 CHALIFOUX, OLIVER A. SAC, NK FBI NK 05/22/2017 49386 124-10254-10340 07/24/2017 In Part FBI 11/26/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-3060-74 BOWMAN, MAURICE T. SAC, NK FBI NK 05/22/2017 49387 124-10254-10345 07/24/2017 In Part FBI 11/27/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-3060-80 SUTTON, DALE R. SAC, NK FBI NK 05/22/2017 49388 124-10254-10346 07/24/2017 In Part FBI 11/27/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-3060-81 SUTTON, DALE R. SAC, NK FBI NK 05/22/2017 49389 124-10254-10352 07/24/2017 In Part FBI 11/27/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-3060-87 SUTTON, DALE R. SAC, NK FBI NK 05/22/2017 49390 124-10254-10386 07/24/2017 In Part FBI 12/02/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-3060-126 SAC, NK DIRECTOR, FBI FBI NK 05/22/2017 49391 124-10254-10419 07/24/2017 In Part FBI 01/15/1964 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-3060-169 SAC, NK DIRECTOR, FBI FBI NK 06/01/2017 49392 124-10255-10094 07/24/2017 In Part FBI 04/15/1964 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-2909-641 GEMBERLING, ROBERT P. DIRECTOR, FBI FBI SA 06/01/2017 49393 124-10255-10390 07/24/2017 In Part FBI 07/29/1966 [ PDF ] PAPER, TEXTUAL DOCUMENT CR 105-74540-4 DIRECTOR, FBI SAC, CG FBI WMFO 06/01/2017 49394 124-10255-10401 07/24/2017 In Part FBI 09/13/1965 [ PDF ] PAPER, TEXTUAL DOCUMENT 44-1166-187 DOUGLASS, EUGENE G. FBI ME 05/22/2017 49395 124-10256-10019 07/24/2017 In Part FBI 10/27/1964 [ PDF ] PAPER, TEXTUAL DOCUMENT 105-38431-1244 SAC, NY SAC, DN FBI NY 06/01/2017 49396 124-10256-10132 07/24/2017 In Part FBI 01/04/1967 [ PDF ] PAPER, TEXTUAL DOCUMENT 89-69-1376 SAC, NO DIRECTOR, FBI FBI NO 05/22/2017 49397 124-10256-10146 07/24/2017 In Part FBI 02/01/1967 [ PDF ] PAPER, TEXTUAL DOCUMENT 89-69-1394, 1395 SAC, HO DIRECTOR, FBI FBI NO 05/22/2017 INC LHM, A/T 49398 124-10256-10288 07/24/2017 In Part FBI 03/04/1965 [ PDF ] PAPER, TEXTUAL DOCUMENT 62-3060-227 BARNES, PETER J. JR. SAC, NK FBI NK 05/22/2017 49399 124-10256-10362 07/24/2017 In Part FBI 11/25/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 89-21-17 BARRON, GEORGE A. JR. SAC FBI LR 05/23/2017 49400 124-10256-10365 07/24/2017 In Part FBI 11/26/1963 [ PDF ] PAPER, TEXTUAL DOCUMENT 89-21-20 SCOTT, RALPH D. SAC FBI LR 05/23/2017 Bulk Download of PDF and WAV files You can access individual files by browsing the webpage above and selecting the link in the "Doc Date" column. You may also download the Excel spreadsheet above, which includes links to all of the files. If you need copies of all PDF and WAV files, you can request a compressed bulk download by emailingbulkdownload@nara.govwith “JFK Bulk Download” in the subject line.
https://www.archives.gov/research/jfk/release?Trump=MAGA&order=Num%20Pages&page=987&sort=desc
Molecules | Free Full-Text | Comparison of Phenolic Metabolites in Purified Extracts of Three Wild-Growing Herniaria L. Species and Their Antioxidant and Anti-Inflammatory Activities In Vitro The work is aimed at phytochemical characterization and In Vitro evaluation of antioxidant actions, anti-inflammatory effects, and cytotoxicity of purified extracts from three rupturewort (Herniaria L.) species, i.e., Herniaria glabra (HG), H. polygama (HP), and H. incana herb (HIh). The total phenolic content established in the purified extracts (PEs) of HIh, HP, and HG was 29.6, 24.0, and 13.0%, respectively. Thirty-eight non-saponin metabolites were identified using LC-HR-QTOF-ESI-MS; however, only 9 were common for the studied Herniaria species. The most abundant phenolic compound in HG-PE was narcissin (7.4%), HP-PE shared 3 major constituents, namely cis-2-hydroxy-4-methoxycinnamic acid 2-O-& beta;-glucoside (cis-GMCA, 5.8%), narcissin (5.4%), and rutin (5.3%). Almost half of HIh phenolic content (14.7%) belonged to oxytroflavoside A (7-O-methylkaempferol-3-O-[3-hydroxy-3-methylglutaryl-(1& rarr;6)]-[& alpha;-rhamnopyranosyl-(1& rarr;2)]-& beta;-galactopyranoside). Antioxidant properties of the Herniaria PEs were evaluated employing an experimental model of human blood plasma, exposed to the peroxynitrite-induced oxidative stress. The assays demonstrated significant reduction of oxidative damage to protein and lipid plasma components (estimated by measurements of 3-nitrotyrosine, protein thiol groups, thiobarbituric acid-reactive substances), and moderate protection of its non-enzymatic antioxidant capacity. Anti-inflammatory properties of the Herniaria PEs were evaluated In Vitro as inhibitory effects against cyclooxygenases (COX-1 and -2) and concanavalin A-induced inflammatory response of the peripheral blood mononuclear cells (PBMCs). None of the studied plants showed inhibitory effects on COXs but all purified extracts partly reduced the release of interleukin 2 (IL-2) and tumor necrosis factor-alpha (TNF-& alpha;) from PBMCs, which suggested their prospective ability to up-regulate inflammatory response of the cells. The purified extract from H. glabra turned out to be the most efficient suppressor of PBMCs& rsquo; inflammatory response. Additionally, cytotoxicity of purified Herniaria extracts on PBMCs was ruled out based on In Vitro studies. Comparison of Phenolic Metabolites in Purified Extracts of Three Wild-Growing Herniaria L. Species and Their Antioxidant and Anti-Inflammatory Activities In Vitro by Solomiia Kozachok 1,*,† , Joanna Kolodziejczyk-Czepas 2,*,† , Krzysztof Kamil Wojtanowski 4 , Grażyna Zgórka 4 and Wieslaw Oleszek 1 1 Department of Biochemistry and Crop Quality, Institute of Soil Science and Plant Cultivation—State Research Institute, Czartoryskich 8, 24-100 Puławy, Poland 2 Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland 3 Department of Pharmacognosy and Medical Botany, I Horbachevsky Ternopil National Medical University, Maidan Voli 1, 46001 Ternopil, Ukraine 4 Department of Pharmacognosy with the Medicinal Plant Garden, Medical University of Lublin, 1 Chodzki St., 20-093 Lublin, Poland * Authors to whom correspondence should be addressed. These authors contributed equally to this work. Molecules 2022 , 27 (2), 530; https://doi.org/10.3390/molecules27020530 Received: 23 November 2021 / Revised: 9 January 2022 / Accepted: 11 January 2022 / Published: 14 January 2022 (This article belongs to the Special Issue Natural Plant Substances—Structural and Application Aspects: A Theme Issue in Honor of Professor Wieslaw Oleszek ) Versions Notes Abstract The work is aimed at phytochemical characterization and In Vitro evaluation of antioxidant actions, anti-inflammatory effects, and cytotoxicity of purified extracts from three rupturewort ( Herniaria L.) species, i.e., Herniaria glabra (HG), H. polygama (HP), and H. incana herb (HIh). The total phenolic content established in the purified extracts (PEs) of HIh, HP, and HG was 29.6, 24.0, and 13.0%, respectively. Thirty-eight non-saponin metabolites were identified using LC-HR-QTOF-ESI-MS; however, only 9 were common for the studied Herniaria species. The most abundant phenolic compound in HG-PE was narcissin (7.4%), HP-PE shared 3 major constituents, namely cis -2-hydroxy-4-methoxycinnamic acid 2- O -β-glucoside ( cis -GMCA, 5.8%), narcissin (5.4%), and rutin (5.3%). Almost half of HIh phenolic content (14.7%) belonged to oxytroflavoside A (7- O -methylkaempferol-3- O -[3-hydroxy-3-methylglutaryl-(1→6)]-[α-rhamnopyranosyl-(1→2)]-β-galactopyranoside). Antioxidant properties of the Herniaria PEs were evaluated employing an experimental model of human blood plasma, exposed to the peroxynitrite-induced oxidative stress. The assays demonstrated significant reduction of oxidative damage to protein and lipid plasma components (estimated by measurements of 3-nitrotyrosine, protein thiol groups, thiobarbituric acid-reactive substances), and moderate protection of its non-enzymatic antioxidant capacity. Anti-inflammatory properties of the Herniaria PEs were evaluated In Vitro as inhibitory effects against cyclooxygenases (COX-1 and -2) and concanavalin A-induced inflammatory response of the peripheral blood mononuclear cells (PBMCs). None of the studied plants showed inhibitory effects on COXs but all purified extracts partly reduced the release of interleukin 2 (IL-2) and tumor necrosis factor-alpha (TNF-α) from PBMCs, which suggested their prospective ability to up-regulate inflammatory response of the cells. The purified extract from H. glabra turned out to be the most efficient suppressor of PBMCs’ inflammatory response. Additionally, cytotoxicity of purified Herniaria extracts on PBMCs was ruled out based on In Vitro studies. Keywords: Herniaria glabra L. ; H. polygama J. Gay. ; H. incana Lam. ; Caryophyllaceae ; LC-MS ; phenolic metabolites ; antioxidant ; anti-inflammatory ; cyclooxygenase ; peroxynitrite 1. Introduction Aerial parts of some Herniaria spp. from the family Caryophyllaceae are well documented herbal sources of medicinal substances used for the treatment of urolithiasis and prevention of recurrent kidney stones [ 1 , 2 ]. Their safety and therapeutic effects were confirmed in official monographs published by the European Medicines Agency (EMA) [ 3 ], and Austrian Pharmacopoeia [ 4 ]. The prevalence rate for urinary stones is continuously rising in countries with a high standard of life across the world from 1 to 20% (database from 2001 to 2007) [ 5 , 6 ]. The highest number of cases was reported in Saudi Arabia. It is well documented that the countries with hot, desert climates have the superior risk of urinary tract stone occurrence [ 7 ]. Climate changes (global warming), sedentary lifestyle, dietary habits (consumption of processed food, high content of animal proteins, sodium, sugars, and reduced amount of water) are believed to have a major contribution to an increasing stone prevalence [ 8 ]. Moreover, many sweetened drinks (Pepsi ® , Coca-Cola ® , noncola soda) contain phosphates, sugars, artificial sweeteners promoting the formation of calculi [ 9 ]. Pathophysiology of stone formation is characterized by insufficient urine volume and supersaturation of the urine with stone-forming constituents such as lithogenic ions (e.g., Ca 2+ , NH 4 + , C 2 O 4 2− , PO 4 3− , C 5 H 3 N 4 O 3 − (urate), CO 3 2− ), as well as a low concentration of stone inhibitor ions (Mg 2+ , C 6 H 5 O 7 3− (citrate)). A process of crystallization from solution has the following phases: nucleation, aggregation, and crystal growth [ 10 ]. In the 1st step, lithogenic crystals bind to the renal cells and stay there. Crystals tend to stick easily to the damaged side of the membrane [ 11 ]. Oxidative stress—the result of an imbalance between reactive oxygen species (ROS) and antioxidant capacity, plays a key role in the initiation and progression of damage to kidney cells. The renal deposits may disturb the electron transport chain in mitochondria, thereby triggering the release of mitochondrial ROS and the development of oxidative stress [ 8 ]. In addition, crystal formation, accompanied by free radical damage, stimulates the kidney cells to produce and release of inflammatory mediators. As a result, an acute inflammatory response develops that further exacerbates cell damage [ 7 ]. The next steps in stone formation are aggregation and growth, during which urine crystals adhere and bind to each other through an organic matrix. The latter contains proteins, lipids, polysaccharides, cellular debris, and whole cells, and makes up about 5% of the stone mass. It acts as a binding agent by increasing heterogeneous nucleation and aggregation of crystals [ 7 , 10 , 12 ]. Therefore, to effectively treat and prevent urolithiasis, it is important to use a combination of agents with antiurolithic, antioxidant, and anti-inflammatory properties. In the previous study by Kozachok et al. [ 2 ], the possible antiurolithic mechanism of the main specific metabolites from Herniaria glabra L.—herniariasaponins, their role in stone recurrence, as well as detailed chemical characteristics of the mentioned metabolites were described. Herein, antioxidant and anti-inflammatory potential of purified Herniaria spp. extracts were characterized in the experimental system of human blood plasma exposed to the peroxynitrite-induced oxidative stress and inflammatory activities including cyclooxygenases (COX-1 and -2) inhibitor screening and the response of human peripheral blood mononuclear cells (PBMCs), respectively. Moreover, the cytotoxicity of the studied objects was examined towards PBMCs. The studied Herniaria spp. were H. glabra L. (HG) and H. polygama J. Gay (HP) whole plants, and H. incana Lam. herb (HIh, syn. H. besseri Fisch. ex Hornem). There is a large amount of evidence indicating that phenolic compounds are closely associated with, and responsible for antioxidant and anti-inflammatory activities [ 13 ]. Furthermore, in our previous studies, In Vitro single isolates from HG such as narcissin, licoagroside B, apiorutin as well as rutin, exhibited moderate antioxidant activity [ 14 ], and phenolic fractions from HIh and HP showed profound antioxidant and anti-inflammatory effects [ 15 ]. Thus, the detailed phytochemical characterization and quantification of phenolic metabolites in the purified extracts of HG, HP, and HIh were performed using UHPLC-DAD-QTOF-ESI-HRMS (ultra-high-performance liquid chromatography-diode array detector quadrupole time-of-flight electrospray ionisation high-resolution mass spectrometer) and UPLC-DAD-TQD-MS (TQD, tandem triple-quadrupole) respectively. This is the first study that compares non-triterpenoid profiles of Herniaria spp. and their antioxidant and anti-inflammatory effects In Vitro. 2. Results and Discussion 2.1. Phytochemical Profiles and the Content of Individual Phenolics in HG, HP, and HIh Purified Extracts Water-methanolic Herniaria spp. extracts were defatted and purified from sugar and low molecular organic acids using RP-SPE (reversed-phase-solid phase extraction). The obtained purified extracts (PEs) containing Herniaria specific metabolites (HSM) were subjected to LC-MS analyses and bioassay tests. The major constituents of HSM comprised herniariasaponins [ 2 ] and non-saponin compounds. To estimate the content of the aforementioned compounds in the particular PEs, gel permeation chromatography (GPC) with evaporative light scattering detection (ELSD) was applied. GPC has the advantage of effectively separating triterpene glycosides (with MW > 1000 g/mol) from polyphenolic compounds, especially those with low MW [ 16 ]. Moreover, ELSD and charged-aerosol detector (CAD) are concentration sensitive and can be used to quantify analytes that lack UV chromophores or ionizable groups. They are suitable for saponin detection, unlike semi-volatile compounds [ 17 ]. As a final result, HG-PE, HP-PE, and HIh-PE contained 82%, 62%, and 52% saponins, respectively [ 14 , 15 ]. Commercially available and in-house prepared standards [ 14 , 15 ] were used for the identification and quantification of phenolic compounds in the purified extracts of HG, HP, and HIh. The detailed UV and MS/MS spectra description together with tentative identification of non-triterpenoid constituents in HIh and HP phenolic fractions were presented in our previous work [ 15 ]. Due to LC-HRMS analysis 38 Herniaria -derived non-saponin compounds were identified—10 in HG-PE, 17 in HP-PE, and 31 in HIh-PE ( Figure 1 and Figure 2 and Table 1 ). The studied objects shared only 9 common HSM, namely p -coumaroyl-4- O -hexoside (peak 5), cis -3-feruloyl quinic acid (FerQA, peak 7), licoagroside B (LB, peak 9), trans -4-FerQA (peak 12), rutin (peak 18), quercetin-3- O -hexoside (peak 19), nicotiflorin (peak 25), narcissin (peak 26), and isorhamnetin-3- O -hexoside (peak 29) ( Figure 2 ). It is worth noting, that both HP and HIh possessed unique fingerprints of phenolics within Herniaria species. Namely, HP-PE contained glucosides of 2-hydroxy-4-methoxycinnamic acid ( cis / trans -GMCA, peaks 11 and 15) and 2-hydroxy-4-methoxyphenyl propanoic acid (GMPPA, peak 13), (2 R ,3 R )-benzoyl-tartaric acid (peak 10), 4,4′-dimethoxy-2,2′-di- O -hexoside-truxinate (peak 27). Cis / trans -GMCA are direct precursors of herniarin (peak 30) and truxinate (peak 27). Both cis / trans GMCA and herniarin were the main constituents of ethanolic extract from Chamomilla recutita L. flowers [ 18 ]. Furthermore, trans -GMCA, GMPPA as well as 4,4′-dimethoxy-2,2′-di- O -hexoside-truxinate were previously identified in n -butanol fraction from aerial parts of Lavandula angustifolia Mill. [ 19 ] HIh-PE contained a variety of 3-hydroxy-3-methylglutaric (HMG) acid conjugates with quercetin (peak 22), 7- O -methylquercetin (peak 31), kaempferol (peaks 24, 28), and 7- O -methylkaempferol (peaks 33–37). Three non-phenolic metabolites: maltol derivative (LB), N -malonyl-tryptophan (peak 14), and a trace amount of blumenin isomer (peak 23) were also identified in these extracts. Figure 1. Chemical structures of the main phenolic metabolites in the studied Herniaria purified extracts. Figure 2. UHPLC—diode array detector (DAD) and charged aerosol detector (CAD) profiles of the purified extracts from ( a ) Herniaria glabra ; ( b ) H. polygama ; ( c ) H. incana herb. Table 1. Non-saponin compounds identified and quantified in Herniaria glabra (HG), H. polygama (HP), H. incana herb (HIh) purified extracts using UHPLC-QTOF-MS/MS. Quantification of individual Herniaria phenolics, followed by the UHPLC/PDA analysis, was established using the external standard method. The sum of phenolics in HG-PE, HP-PE, and HIh-PE was 12.95%, 24.03%, and 29.56%, respectively. Flavonoids were the predominant group in HG-PE accounting for 11.15%. The major flavonoid constituents included narcissin—7.34% followed by rutin—1.87%, and apiorutin—1.5% ( Figure 1 , Table 1 ). Moreover, the contents of narcissin, apiorutin, and LB (1.8%), reported in HG, were the highest within three Herniaria spp. The non-terpenoids components of HP-PE comprised of flavonoids—11.69%, cinnamic and benzoic acids derivatives—9.42%, coumarin (herniarin)—1.59%, and LB—1.33%. The significant amounts were documented for cis -GMCA—5.76%, narcissin—5.43%, and rutin—5.27% ( Figure 1 , Table 1 ). The highest concentration of phenolics was established in HIh. The quantitative profile comprised flavonoids—22.06%, hydroxycinnamic acids (HCA)—6.4%, and LB—1.1%. The most abundant metabolite was oxytroflavoside A accounting for 14.73% ( Figure 1 , Table 1 ). This flavonoid is unique among Herniaria spp. and was previously revealed only in Oxytropis falcata Bunge [ 20 ] and Astragalus gombiformis Pomel [ 21 ] from the family Fabaceae. Moreover, rhamnocitrin, a flavonol aglycone, was first time identified in the family Caryophyllaceae [ 22 ]. Among all phenolics in Herniaria spp. examined, the highest content was contributed to flavonoids. Detailed phytochemical analysis, carried out in this study, showed that these Herniaria taxa should not be used interchangeably due to significant differences in polyphenolic patterns and the content of particular non-saponin constituents. 2.2. Evaluation of Antioxidant Effectiveness of the Examined Purified Extracts The exposure of blood plasma to ONOO − action resulted in a significant increase of plasma lipid peroxidation and formation of 3-nitrotyrosine in plasma proteins, accompanied by a decrease of protein thiol groups level. The pre-incubation of blood plasma with the examined Herniaria purified extracts noticeably diminished those harmful effects of ONOO − on blood plasma components. The tested PEs (1–50 μg/mL) significantly reduced nitration of tyrosine residues and oxidation of thiol groups in plasma proteins. The anti-nitrative action of the extracts was dose-dependent and comparable to the effects of a well-known reference antioxidant—i.e., Trolox ( Figure 3 ). In measurements of its ferric reducing ability (the FRAP assay), beneficial effects of the Herniaria PEs on the non-enzymatic antioxidant capacity were also demonstrated (at concentrations of 5–50 µg/mL). Furthermore, the examined purified extracts displayed moderate anti-lipoperoxidative properties and reduced the TBARS (thiobarbituric acid-reactive substances) level in blood plasma exposed to ONOO − , though their actions were not dose-dependent ( Table 2 ). Figure 3. Protective effects of the examined Herniaria glabra (HG-PE), H. polygama (HP-PE) and H. incana herb (HIh-PE) purified extracts on the ONOO − -induced formation of 3-nitrotyrosine in blood plasma proteins. Human plasma was exposed to 100 µM ONOO − in the presence or absence of the tested extracts or a reference compound (Trolox); * p < 0.05, ** p < 0.01, *** p < 0.001; n = 6. Table 2. Determination of antioxidant properties of the examined Herniaria glabra (HG-PE), H. polygama (HP-PE), and H. incana herb (HIh-PE) purified extracts, based on measurements of thiobarbituric acid-reactive substances (TBARS) and protein thiol groups levels as well as on the ferric reducing ability of blood plasma (FRAP), under the ONOO − -induced oxidative stress In Vitro. Statistical significance: # p < 0.05, ## p < 0.001 plasma treated with ONOO − in the absence of examined purified extracts vs. control plasma; * p < 0.05, ** p < 0.01 plasma treated with ONOO − in the absence of examined purified extracts vs. plasma treated with ONOO − in the presence of examined substances. The protective action of the HG-PE, HP-PE, and HIh-PE on blood plasma proteins was additionally confirmed by 1D-electrophoretic analysis ( Figure 4 ). The exposure of fibrinogen to peroxynitrite oxidant resulted in the formation of the high-molecular protein aggregates (HMW), derived from the Aα chain of this protein molecule. Antioxidant effects of all tested extracts were the most evident at a concentration of 50 µg/mL; however, some slight decrease of HMW formation was observed at the concentration of 5 µg/mL ( Figure 4 ). Figure 4. Protective effects of the examined Herniaria glabra , H. polygama and H. incana herb purified extracts on the ONOO − -induced oxidative changes in fibrinogen structure. The figure includes a representative SDS-PAGE pattern of human fibrinogen, obtained from the executed experiments employing 4–20% Mini-PROTEAN ® TGX™ Precast Protein Gels and staining with Coomassie Brilliant Blue R-250 dye ( n = 3). 2.3. Anti-Inflammatory Properties of the Tested Herniaria Purified Extracts The COX inhibitor screening demonstrated that neither of the examined PEs were able to significantly inhibit the activity of COX-1 nor COX-2. At their highest concentrations (of 50 μg/mL), their inhibitory efficiency mostly did not exceed about 15%. For comparison, the reference anti-inflammatory drug, i.e., indomethacin, effectively inhibited both of the isoenzymes with IC 50 values of <1 μg/mL (for COX-1) and 2.43 μg/mL (for COX-2) ( Figure 5 ). Figure 5. Screening of the cyclooxygenase-inhibitory properties of the examined Herniaria glabra (HG-PE), H. polygama (HP-PE), and H. incana herb (HIh-PE) purified extracts. The enzyme activity in control samples (untreated with the extracts or a reference inhibitor) was assumed as 100%; n = 3. However, studies on the concanavalin A (Con A) -stimulated PBMCs clearly indicated that all of the studied Herniaria PEs had some anti-inflammatory potential ( Figure 6 ). At the highest concentration of the purified extracts (50 µg/mL), suppression of the inflammatory response of PBMCs reached up to ≥80%, this was estimated by the release of interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α). At the lower concentrations of the tested objects (i.e., 1 and 5 µg/mL), their effects were slighter (up to about 20–30% of cytokine level reduction), but mostly also statistically significant. Figure 6. Effects of the examined Herniaria glabra (HG-PE), H. polygama (HP-PE) and H. incana herb (HIh-PE) purified extracts on the inflammatory response of the concanavalin A-stimulated human PBMCs. Anti-inflammatory actions of the tested extracts were estimated using ELISA and based on IL-2 (panel ( A )) and TNF-α (panel ( B )) release; * p < 0.05, ** p < 0.01, *** p < 0.001; n = 4–5. 2.4. Cytotoxicity Assay Preliminary assessment of cytotoxicity was based on a direct exposure of PBMCs (suspended in phosphate-buffered saline) on the examined HG-PE, HP-PE, HIh-PE, without protective conditions of any medium components. Under such experimental conditions, a potential cytotoxic action of the tested purified extracts might be quickly detected (after few hours) [ 24 , 25 ]. The initial viability of control PBMCs in samples was 91 ± 4.5%. Measurements of PBMCs viability revealed no toxic actions of the purified extracts from H. glabra , H. polygama, and H. incana herb at concentrations of 5, 25, and 50 µg/mL ( Table 3 ). Table 3. The influence of the examined Herniaria glabra (HG-PE), H. polygama (HP-PE), and H. incana herb (HIh-PE) purified extracts on the viability of peripheral blood mononuclear cells (PBMCs). The viability of control (untreated) PBMCs was assumed as 100%; ** p < 0.01. The above observations were additionally verified by the resazurin-based metabolic viability test, conducted after 24 h of incubation of PBMCs with the Herniaria purified extracts. No cytotoxic effects were found in the vast majority of the analyzed samples, excluding PBMCs treated with the highest concentration (i.e., 50 µg/mL) of H. polygama PE ( Table 3 ). A significant contribution of enhanced generation of ROS and oxidative stress to etiology and pathophysiology of civilization diseases, including cardiovascular disorders has been well established and widely described [ 26 , 27 , 28 , 29 ]. Among natural substances with beneficial effects on human health, ethnomedicinal plants have gained increasing interest as a source of individual bioactive substances, their mixtures, or pharmacophores for the discovery of new drugs [ 30 , 31 ]. Despite the presence in traditional medicine and contemporary herbal therapies, molecular mechanisms and main pathways of biological actions of Herniaria species are poorly recognized. So far, only some aspects of the biological actions of H. glabra and H. hirsuta L. have been described [ 32 , 33 ]. While the most of studies on H. glabra are focused on its diuretic [ 34 ] and anti-urolithiasis activity [ 35 ], other biological actions of different Herniaria species remain inadequately recognized. Several reports are describing in vitro anti-oxidant activity of Herniaria spp. water-organic and water extracts which were mentioned in our previous paper [ 15 ]. As a result, weak (HG, H. hirsuta extracts) or moderate (HIh, H. fontanesii J. Gay extracts) antioxidant capacity was estimated. However, ethyl acetate fraction from an Egyptian species of Herniaria namely H. hemistemon J. Gay showed high DPPH • scavenging activity in vitro [ 36 ]. It caused 88% scavenging in a dose of 125 µg/mL, this effect was comparable with the ascorbic acid. Flavonoids such as quercetin, naringenin, hesperitin, kaempferol, rhamnetin, apigenin, acacetin and their monoglycosides as well as coumarin were responsible for this activity. Contrary to those not very promising literature data, our previous study on narcissin, apiorutin, and licoagroside B isolated from H. glabra indicated their considerable antioxidant effects [ 14 ] and encouraged us to continue work on Herniaria plants. Moreover, our recent publication [ 15 ] shed new light on the antioxidant activity of Herniaria -derived phenolic acid derivatives rich fractions and the 1st one that describes the anti-inflammatory potential of Herniaria spp. Results obtained from the present study indicated that the Herniaria genus may not only be a source of natural antioxidants but also covers species displaying anti-inflammatory effects. Antioxidant activity of the examined Herniaria purified extracts was evaluated in human blood plasma under the 100 µM peroxynitrite-induced oxidative stress. All of the three examined Herniaria -purified extracts (1–50 µg/mL) displayed a considerable antioxidant action in blood plasma. The use of peroxynitrite (ONOO − ) as an inductor of oxidative stress was based on the pathological significance of this ROS. It is one of the main oxidants generated within the cardiovascular system, responsible for both nitrative and oxidative damage to blood cells and blood plasma components [ 37 , 38 , 39 , 40 , 41 , 42 ]. For that reason, natural substances capable of detoxifying (scavenging) ONOO − may be crucial for the prevention of oxidative stress and its functional consequences. The literature data indicate that the bolus addition of 250 µM ONOO − to the experimental system reflects a physiological concentration of 1 µM ONOO − , maintained for 7 min [ 43 ], which is locally achievable at sites of inflammation. Our assays revealed that all of the tested objects diminished the ONOO − -induced plasma lipid peroxidation as well as the formation of 3-nitrotyrosine and oxidation of thiol groups in blood plasma proteins ( Table 2 and Figure 3 ). In vivo, the maintaining of the physiological antioxidant capacity of blood plasma is crucial for intravascular homeostasis; therefore, in this study, the Herniaria PEs effects on this parameter were also determined. For the first time, we have demonstrated that the examined preparations may protect or even strengthen the physiological non-enzymatic antioxidant capacity of blood plasma. Experiments on the isolated fibrinogen demonstrated that the presence of the Herniaria purified extracts (before the exposure to ONOO − ) partly reduced the formation of HMW, derived from the Aα chain of this molecule ( Figure 4 ). The ability of the examined plant preparations to protect fibrinogen, one of the key proteins in the blood coagulation cascade, is very important from the physiological point of view. Due to its spread structure and physiological exposure of protein surface to other molecules, fibrinogen is very prone to undesirable modifications, including oxidative damage. Both oxidative and nitrative alterations in fibrinogen structure may lead to functional consequences, including changes in its clotting ability and interactions with blood platelets [ 44 , 45 , 46 ]. For instance, it has been shown that even very low nitration of fibrinogen molecule (≈45–65 μmol nitrotyrosine/mol tyrosine) may significantly accelerate the formation of a fibrin clot when compared to native fibrin(ogen) [ 44 ]. Moreover, a recent systematic analysis has also confirmed that post-translational modifications of fibrinogen affect both the fibrin clot formation and its structure [ 47 ]. Peroxynitrite is also able to weaken functions of the fibrinolytic proteins [ 48 , 49 ]. It should be also emphasized that the HG-PE, HP-PE, HIh-PE displayed significant antioxidant efficacies at concentrations of 1–5 µg/mL, which are comparable to physiologically achievable levels of plant-derived substances or their metabolites in blood plasma, i.e., ≤5–10 µM [ 50 ]. Antioxidant effects of the investigated Herniaria purified extracts may be attributed to the presence of numerous polyphenolic compounds belonging to different groups of phytochemicals ( Figure 1 and Figure 2 , Table 1 ). Of course, the best known of them is rutin (quercetin-3- O -rutinoside), possessing a wide range of beneficial physiological effects, including the ability to prevent or ameliorate oxidative stress [ 51 , 52 , 53 ]. However, according to our previous studies, also narcissin, apiorutin and licoagroside B have antioxidant properties and might prevent oxidative and nitrative damage caused by peroxynitrite [ 14 ]. Moreover, our studies demonstrated the anti-inflammatory potential of the examined Herniaria purified extracts. It was in line with our previous results on the anti-inflammatory activity of phenolic acid derivatives rich fractions from HP and HIh [ 15 ]. Our preliminary screening involving the exposure of purified COXs (a commercial kit) to the Herniaria PEs did not show the direct inhibitory action of these plant preparations towards the COX-2 enzyme ( Figure 5 ). However, experiments on PBMC cultures showed that their inflammatory response was significantly reduced by all purified Herniaria extracts. Thus, it is likely that the examined phytochemicals may upregulate the activation of pro-inflammatory pathways and act rather as regulators of gene expression than direct inhibitors of pro-inflammatory enzymes. At their physiologically relevant concentrations (1–5 µg/mL), the tested plant preparations reduced the inflammatory response of PBMCs, leading to about a 20% and 30% decrease of IL-2 and TNF-α secretion, respectively ( Figure 6 ). Additionally, cytotoxicity tests confirmed the cellular safety of all tested extracts at these concentrations ( Table 3 ). The purified extract from H. glabra at the lower doses proved to be the most efficient suppressor of PBMCs’ inflammatory response. HG-PE at 1 µg/mL inhibited TNF-α release comparably to the reference compound—indomethacin at the same dose. In contrast, H. polygama purified extract at a dose of 50 µg/mL (the highest dose tested), was the most active among the tested preparations, including positive control. Nevertheless, this dose exceeded the physiologically relevant concentrations and was cytotoxic against PBMCs in the resazurin-based assay. The described effects can be explained by the presence of high amounts of rutin (2.8 times as much in HP-PE as in HG-PE) and narcissin (1.3 times as much in HG-PE as in HP-PE) in both extracts, while H. glabra preparation contains the highest amount of saponins. On the other hand, H. polygama purified extract composed of rare HCA conjugates, namely cis -GMCA (5.76%), tran s-GMCA (1.58%), GMPPA (1.07%) and coumarin derivative—herniarin (1.59%). These metabolites were also isolated from plants with recognized anti-inflammatory properties, i.e., Chamomilla recutita , Lavandula angustifolia , and Artemisia dracunculus L. (Tarragon) [ 54 ]. Although the examined HP-PE showed higher inhibitory activity against IL-2 and TNF-α than the fraction of phenolic acid derivatives from H. polygama (consisting of cis -GMCA 29.7%, GMPPA 5.2%, trans -GMCA 7.59%, herniarin 0.82%, benzoyl tartaric acid 5.5%) [ 15 ]. It may be explained by the synergic and additive effects of the main groups of HSM, i.e., saponins, flavonoids, phenolic acids, and coumarin. The synergistic anti-inflammatory effect of flavonoids mixtures [ 55 ] and additive antioxidant action of flavonoids and cinnamic acid mixes have been described [ 56 ]. The obtained results suggest the ability of the Herniaria PEs-derived metabolites to suppress the activation of pro-inflammatory pathways and are consistent with existing literature data. The pro-inflammatory response of cells involves various signal transduction and metabolic pathways. Thus, inflammation can be diminished at diverse molecular levels, including by direct action on the active COX-2 enzyme or other pro-inflammatory enzymes as well as by modulation of gene expression (i.e., reducing pro-inflammatory genes transcription). One of the key molecular regulators of the cellular pro-inflammatory response is the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) [ 57 ]. The literature indicates that prevention of NF-κB activation is one of the most important mechanisms of anti-inflammatory action of various phytochemicals. For instance, rutin (which is also one of the components of the examined Herniaria extracts, and in the highest content (5.27%) detected in H. polygama ) was found to inhibit NF-κB induction. Blockage of NF-κB activation results in the inhibition of other signaling pathways, dependent on this transcription factor, including cytokine release, pro-inflammatory enzymes synthesis and expression of other molecules involved in the inflammatory response [ 58 ]. The literature also provides data on the NF-κB inhibitory effect of other metabolites found in the studied PEs, i.e., chlorogenic [ 59 ] and neochlorogenic acids [ 60 ]. The recent evidence highlighted the molecular mechanism of anti-inflammatory action of Samoan traditional medicine ( Psychotria insularum homogenate) that was mediated via iron chelation [ 61 ]. Iron chelation is also involved in antioxidant and antibacterial effects. The bioactive principle of the P. insularum homogenate was based on the reduction of the intracellular iron content as well as heme synthesis in yeast ( Saccharomyces cerevisiae ) cells. Bioassay-guided fractionation of the Psychotria insularum homogenate discovered of bioactive iron chelators namely rutin and nicotiflorin. Rutin was more active due to the presence of the catechol group in its structure. Immune response assay of the homogenate as well as bioactive constituent rutin, and the reference drug—ibuprofen, was tested on unstimulated, ConA-stimulated, or LPS-stimulated splenocytes isolated from C57BL/6 mice. Overall, fever-inducing cytokine TNFα and Th1 (T helper cells type 1) -inducing IL12p40 together with proinflammatory cytokines Th1 (interferon γ) and Th17 (IL6, IL17A) were significantly reduced by the tested objects. The anti-inflammatory activity of rutin and the homogenate was consistent with ibuprofen. The mention flavonoids were also detected in the studied Herniaria PE, rutin amount was higher, than nicotiflorin ( Table 1 ). Most of the available evidence concerns the anti-inflammatory action of chlorogenic acid [ 62 ]. For instance, in the lipopolysaccharide-stimulated RAW 264.7 cells, chlorogenic acid was found to inhibit the expression of COX-2 and the inducible nitric oxide synthase (iNOS), and its anti-inflammatory properties were associated with inhibitory action on NF-κB [ 63 ]. The capability of inhibiting NF-κB was also described for kaempferol [ 64 ] and some of its derivatives [ 65 ]. However, the number of papers dealing with activities of other main components of the examined purified extracts, e.g., narcissin, cis -GMCA, and oxytroflavoside A are limited. Besides our previous work on antioxidant properties of narcissin [ 14 ], the biological properties of this compound have been described in a few papers. Some data on antimicrobial and immunomodulatory activities of narcissin were provided by [ 66 ]. According to these authors, this compound reduced the lipopolysaccharide-induced release of IL-1β and IL-6 from human macrophages. The anti-inflammatory potential of the Herniaria -purified extracts may also be explained by the presence of triterpenoid saponins. Herniariasaponins are represented by sapogenins of medicagenic and zanhic acids [ 2 ]. There is a limited number of scientific reports that have described the anti-inflammatory potential of the mentioned saponins. Chen et al. studied the medicagenic acid-3- O -β-D-glucopyranoside (at doses 10, 20, 40 mg/kg) isolated from Dolichos falcata Klein on the models of the monosodium urate crystals-treated monocyte/macrophage cell line RAW 264.7 in vitro for its possible mechanism on gout arthritis [ 67 ]. Anti-inflammatory effect of the studied compound manifested via strong suppression of the pro-inflammatory cytokines production level of TNF-α, IL-1β, and IL-6 in the dose-dependent manners. Another study by Vo et al. revealed the 5-LOX inhibitory activity of medicagenic acid (IC 50 = 30.4 μM) in vitro [ 68 ]. Nevertheless, it did not inhibit COX-1 and very low COX-2 isoenzymes, which is consistent with our results. 3. Materials and Methods 3.1. Chemicals and Biological Material Acetonitrile, methanol (HPLC and LC-MS grade), formic acid (98–100% purity and MS-grade) were purchased from Merck (Darmstadt, Germany). 5-CQA (Aldrich, ≥95%), 4-CQA (Sigma, ≥95%), and herniarin (Roth, 98%) were commercial standards, licoagroside B, apiorutin, rutin, and narcissin were previously isolated from H. glabra L. [ 14 ]. Kaempferol was in-house prepared at the Department of Biochemistry and Crop Quality, IUNG. Ultrapure water was obtained in-house with a purification system (Milli-Q ® Simplicity 185, Millipore Corp., Billerica, MA, USA). Trichloroacetic and thiobarbituric acids, dimethyl sulfoxide (DMSO), phosphate-buffered saline (PBS), tris, Trolox, Sigma Fast OPD substrate for peroxidase, and the resazurin-based in vitro toxicology assay kit were purchased from Sigma-Aldrich (St. Louis, MO, USA). Immunochemical reagents for the enzyme-linked immunosorbent assay (ELISA) such as primary anti-3-nitrotyrosine antibody, biotinylated secondary antibody, and Streptavidin/HRP complex were from Abcam (Cambridge, UK). Peroxynitrite was synthesized according to a method described by Pryor et al. (1995) [ 69 ]. BCA Protein Assay Kit was purchased from ThermoFisher Scientific (Waltham, MA, USA). 4–20% Mini-PROTEAN ® TGX™ Precast Protein Gels and other reagents for SDS-PAGE were provided by BioRad Laboratories (Hercules, CA, USA). COX Colorimetric Inhibitor Screening Assay Kit (item No. 701050) was purchased from Cayman Chemicals (Ann Arbor, MI, USA). Determination of human interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-α) was conducted with the use of Picokine ® ELISA kits (items No. EK0397 and EK0525, respectively) were purchased from BosterBio (Pleasanton, CA, USA). Other analytical reagents were purchased from local or international suppliers. Antioxidant and anti-inflammatory assays were executed based on commercially available blood units (buffy coats), purchased from the Regional Centre of Blood Donation and Blood Treatment in Lodz, Poland. This material was used to isolate blood plasma, fibrinogen, and peripheral blood mononuclear cells (PBMCs). Fibrinogen isolation from blood plasma was carried out with the cold ethanol precipitation technique [ 70 ]. Stock solutions of the examined extracts were prepared with 25% DMSO, providing its final concentration in the assayed samples of ≤0.025%. 3.2. Plant Material The studied plant materials were wild-grown in Ukraine and collected during the flowering stage. The entire herb of Herniaria glabra L. was harvested in July 2016, Ternopil Oblast (GPS-Coordinates: 49°45′23″ N, 25°30′38″ E). The whole plant of H. polygama J. Gay was collected in July 2016, Kyiv Oblast (GPS-Coordinates: 50°26′48.8′′ N, 30°02′38.7′′ E). The mentioned plant objects were harvested by Solomiia Kozachok and identified by Dr. Liudmyla Zavialova (Dept. of Geobotany and Ecology, M.G. Kholodny Inst. of Botany, NAS of Ukraine, Kyiv, Ukraine). The areal parts of H. incana Lam. wild growing in Odesa Oblast (Mayaky village near the Astronomical Observatory) were collected in May 2017 and identified by Dr. Olena Bondarenko (Dept. Botany, Odesa I.I. Mechnikov National Univ., Odesa, Ukraine). Harvested plant materials were naturally dried in a well-ventilated space with no direct sunlight under the gauze. Following, the dried materials were ground using an Ultra Centrifugal Mill ZM 200 (Retsch, Germany) with 0.5 mm sieve pores. The plant’s powder was transferred into tightly closed containers and kept in a dark cold place until the analysis. 3.3. Extraction The preparation method of the Herniaria purified extracts was described in detail in our previous work [ 15 ]. Briefly, extraction was performed using ASE 200 (accelerated solvent extraction) Dionex system with 80% methanol-water solution. Following the obtained extracts were defatted with n -hexane, evaporated up to water phase using a rotary evaporator (Heidolph, Schwabach, Germany), and applied to preconditioned RP-C18 open column (50 mm × 93 mm i.d., Cosmosil 140C18-PREP, 140 μm). HSM were rinsed with 95% methanol solution, evaporated and finally lyophilized using Gamma 2–16 LSC freeze dryer (Martin Christ Gefriertrocknungsanlagen GmbH, Germany). The obtained dried powders were the studied research objects, namely HG-PE, HP-PE, and HIh-PE. 3.4. LC-MS Analysis The purified Herniaria extracts were subjected to LC-MS analysis. The analysis for tentative identification of HSM was run on the Thermo Scientific Ultimate 3000 RS (Thermo Fischer Scientific, Waltham, MS, USA) chromatographic system hyphenated to Bruker Impact II HD (Bruker, Billerica, MA, USA) QTOF-MS (quadrupole-time of flight mass spectrometer), and both a CAD (Thermo Corona Veo RS) and PDA detectors. The separations were performed on an ACQUITY HSS T3 column (100 × 2.1 mm i.d.; 1.8 μm, Waters Corp., Milford, CT, USA) at 60 °C. The settings of MS and chromatographic method were described in detail in our previous publication [ 15 ]. Quantity analysis of the phenolic metabolites in HG-PE, HP-PE, HIh-PE was carried out in triplicate using a Waters ACQUITY UPLC system (Waters Corp., Milford, MA, USA) equipped with a binary pump, and TQD-MS (tandem triple-quadrupole mass spectrometer) and DAD detectors as was recorded earlier [ 15 ]. The purified Herniaria extracts were dissolved in 70% MeOH ( v / v ) at a concentration of 10 mg/mL, centrifuged at 16,000× g (Polygen Sigma 3-16KL, D-37520 Osterode am Harz, Germany), and then subjected to analysis. The amount of individual non-saponin compounds were calculated by the external standard method. Calibration curves for (2 R ,3 R ) benzoyl-tartaric acid, 5-CQA, narcissin, herniarin, and licoagroside B were prepared in six concentrations (5, 50, 100, 150, and 250 μg/mL) and measured at UV 275, 320, 350, 323, and 257 nm respectively. 5-CQA was a group standard for cinnamic acid derivatives, (2 R ,3 R ) benzoyl-tartaric acid—for GMPPA, and narcissin—for flavonoids. Molar absorption coefficients (ε) of trans -GMCA, cis -GMCA, GMPPA, 7- O -methylquercetin-3- O -[HMG-(1→6)]-[α-Rha-(1→2)]-β-galactoside, oxytroflavoside A, rutin, kaempferol, and apiorutin (1845 m 2 /mol at 350 nm), as well as group standards, were calculated [ 15 ]. Their values were used for the correction of chromatographic peaks areas to quantify compounds for which calibration curves were absent. 3.5. Evaluation of Antioxidant Effects in Blood Plasma Plasma was pre-incubated for 15 min at 37 °C with the crude extracts (1–50 μg/mL) or a reference compound, i.e., Trolox (1–50 μg/mL), and then underwent the exposure to ONOO − . For the ferric reducing ability of blood plasma (FRAP) assay, the final concentration of ONOO − was 150 μM, while in other antioxidant assays it was 100 μM. Plasma treated with ONOO − in the absence of the purified extracts or Trolox was also prepared. Control plasma contained neither the examined substances nor ONOO − . Evaluation of antioxidant actions of the Herniaria purified extracts in blood plasma covered measurements of thiobarbituric acid-reactive substances (TBARS, 3-nitrotyrosine, and protein thiol groups levels. TBARS concentration was determined according to the method described previously by Wachowicz and Kustron (1992) [ 71 ]. For the immunodetection of 3-nitrotyrosine, a competitive ELISA was applied [ 72 ]. All results from this assay were expressed as equivalents of a 3-nitrotyrosine-containing protein standard (i.e., nitrated fibrinogen, 3-NT-FG) per mg of blood plasma protein. Thiol groups in blood plasma protein were determined using Ellman’s reagent [ 73 ]. The purified extracts influence of the non-enzymatic antioxidant capacity (NEAC) of blood plasma was measured in the FRAP assay, based on the determination of the capability of the analyzed samples of reducing the ferric ions (Fe 3+ ) to ferrous ions (Fe 2+ ). Plasma samples were assayed according to our previous procedure; the results were calculated from a standard curve and expressed as Fe 2+ equivalents [ 74 ]. 3.6. Evaluation of Anti-Inflammatory Properties Cyclooxygenase (COX-1 and -2) enzymes inhibitor screening of the examined Herniaria purified extracts (1–50 µg/mL) and a reference inhibitor (i.e., indomethacin, 1–50 µg/mL) was executed using a commercial colorimetric kit, based on the oxidation of N,N,N’,N’ -tetramethyl- p -phenylenediamine (TMPD) chromogenic substrate. The method allowed to measure the enzymatic activity of the peroxidase component of COX. Assays were carried out in triplicate. Anti-inflammatory properties of the HG-PE, HP-PE, and HIh-PE were also determined employing PBMCs under the Con A-induced stimulation. The cells were cultured in RPMI 1640 medium (supplemented with 10% fetal calf serum and 0.1% of penicillin-streptomycin), at a density of 1.5 × 10 6 cells/mL. The 1h-preincubation of PBMCs with the examined purified extracts in a laboratory CO 2 incubator was followed by treatment with Con A (at the final conc. of 10 µg/mL), to induce their pro-inflammatory activity. Then, PBMCs were cultured for 24 hrs (in 96-well microplates, at 37 °C, with 5% of CO 2 concentration and 95% humidity). After 24 hrs, microplates were centrifuged to obtain supernatants (cell culture medium) for further analyses, involving immune-enzymatic determinations of interleukin-2 and TNF-α release from the cells. Concentrations of the cytokines were established according to protocols, provided by the manufacturer. 3.7. Cytotoxicity Assays Preliminary evaluation of cellular safety of the examined extracts was based on short-term incubation cytotoxicity tests [ 24 , 25 ]. PBMCs, suspended only in 0.02 PBS (1 × 10 6 PBMCs/mL) were incubated with the extracts (5, 25, and 50 µg/mL) to directly expose the cells to the examined Herniaria preparations and assess the possibility of direct damage to the cell membrane. Cytotoxicity was measured after 6 h of incubation (at 37 °C, with gentle mixing on a rotary shaker) in a micro-chamber automated cell counter, employing the trypan blue excluding test [ 75 ]. Preliminary data on cellular safety of the extracts, derived from trypan blue assays, were additionally confirmed in the resazurin-based cell viability assay. For this assay, PBMCs (1.5 × 10 6 PBMCs/mL) were suspended in the RPMI-1640 medium (supplemented with 10% fetal calf serum and 0.1% of penicillin-streptomycin) and incubated with the Herniaria purified extracts (5, 25 and 50 μg/mL) for 24 h (in 96-well microplates, at 37 °C, with 5% of CO 2 concentration and 95% humidity). After the incubation, the resazurin-based viability tests were carried out. PBMCs viability was determined using a microplate spectrophotometer BMG Labtech SectroStarNano, at λ = 600 nm (690 nm was used as a reference wavelength). 3.8. Determination of Changes in Fibrinogen Structure by 1D-Electrophoresis Analogously to blood plasma samples, human fibrinogen (2 mg/mL, in 0.02 M PBS) was pre-incubated with the tested Herniaria purified extracts or Trolox, and then, exposed to ONOO − (100 μM). The SDS-PAGE [ 76 ] separations were executed under reducing conditions, using 4–20% Mini-PROTEAN ® TGX™ Precast Protein Gels and BioRad MiniProtean Tetra Cell equipment for 1-D vertical gel electrophoresis. Protein bands were visualized using Coomassie Brilliant Blue R-250 dye. 3.9. Statistical Analysis All the values in this work are expressed as mean ± SD; p < 0.05 was assumed as statistically significant; n = number of blood donors. In all experiments on blood plasma and PBMCs, at least two independent incubations of the examined substances with biological material from each donor were performed. Statistical significance of the obtained results was evaluated using the Student’s t-test or ANOVA and Tukey’s post hoc test. 4. Conclusions The performed results describe the composition and concentration levels of single non-saponin constituents in the purified extracts of Herniaria glabra , H. polygama , and H. incana herb. The phenolic metabolites were dominated by narcissin (7.34%) in HG-PE, cis -2-hydroxy-4-methoxycinnamic acid 2- O -β-glucopyranoside (5.76%), narcissin (5.43%), and rutin (5.27%) in HP-PE, and oxytroflavoside A (14.73%) in HIh-PE. The Herniaria purified extracts exhibited considerable anti-oxidant activities in blood plasma under the peroxynitrite-induced oxidative stress in a dose of 1–5 µg/mL. Moreover, the Herniaria -derived preparations partly reduced the formation of the high-molecular aggregates, derived from the Aα chain of this molecule. The studied objects reduced pro-inflammatory response in the peripheral blood mononuclear cells induced with concanavalin A by the suppressive effect on the level of TNF-α, IL-2. The most efficient suppressor of PBMCs response was the purified extract from H. glabra . No toxicity towards PBMCs was revealed for the studied Herniaria purified extracts in vitro. Our results shed new light on phenolic profiles of rupturewort taxa and revealed unique phenolic markers to distinguish H. polygama and H. incana from other Herniaria spp. Moreover, the in vitro bioassay data indicated the anti-oxidant and anti-inflammatory potential of the studied rupturewort species. Based on the obtained results, we intend to examine in detail the saponin profiles of all three Herniaria taxa and revise the view of whether H. glabra can be used interchangeably with H. incana as suggested by the EMA monograph and H. polygama herb as proposed by Ethnobotanical evidence. Author Contributions Conceptualization, S.K., J.K.-C., S.M. and W.O.; methodology, S.K., J.K.-C., G.Z.; formal analysis, S.K., J.K.-C. and K.K.W.; investigation, S.K. and J.K.-C.; data curation, S.K. and J.K.-C.; writing—original draft preparation, S.K. and J.K.-C.; writing—review and editing, S.K., J.K.-C. and G.Z.; supervision, S.K. and J.K.-C.; and funding acquisition, J.K.-C. and W.O. All authors have read and agreed to the published version of the manuscript. Funding This research was partly funded by an internal grant from the University of Lodz, Poland (506/1136). Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement The data supporting the results are present in the manuscript. Acknowledgments The authors would like to thank Mariusz Kowalczyk (Dept. Biochemistry and Crop Quality, Institute of Soil Science and Plant Cultivation) for developing the LC-QTOF-MS analysis method and carrying out LC-MS data acquisition. Also, we would like to thank Pawel Nowak (Dept. Gen. Biochem., University of Lodz) for valuable suggestions and helpful assistance in the analyses of the electrophoresis data. Conflicts of Interest The authors declare no conflict of interest. Sample Availability Samples of the plant materials and the isolated compounds 9 – 11 , 13 , 15 , 16 , 18 , 26 , 31 , 33 – 36 and kaempferol, as well as commercial standards 4 , 6 , 30, are available from the authors. References Chevallier, A. Encyclopedia of Herbal Medicine. 550 Herbs and Remedies for Common Ailments , 3rd ed.; Dorling Kindersley Ltd.: New York, NY, USA, 2016; ISBN 0241282462. [ Google Scholar ] Kozachok, S.; Pecio, Ł.; Orhan, I.E.; Deniz, F.S.S.; Marchyshyn, S.; Oleszek, W. Reinvestigation of Herniaria glabra L. saponins and their biological activity. 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UHPLC—diode array detector (DAD) and charged aerosol detector (CAD) profiles of the purified extracts from ( a ) Herniaria glabra ; ( b ) H. polygama ; ( c ) H. incana herb. Figure 3. Protective effects of the examined Herniaria glabra (HG-PE), H. polygama (HP-PE) and H. incana herb (HIh-PE) purified extracts on the ONOO − -induced formation of 3-nitrotyrosine in blood plasma proteins. Human plasma was exposed to 100 µM ONOO − in the presence or absence of the tested extracts or a reference compound (Trolox); * p < 0.05, ** p < 0.01, *** p < 0.001; n = 6. Figure 4. Protective effects of the examined Herniaria glabra , H. polygama and H. incana herb purified extracts on the ONOO − -induced oxidative changes in fibrinogen structure. The figure includes a representative SDS-PAGE pattern of human fibrinogen, obtained from the executed experiments employing 4–20% Mini-PROTEAN ® TGX™ Precast Protein Gels and staining with Coomassie Brilliant Blue R-250 dye ( n = 3). Figure 5. Screening of the cyclooxygenase-inhibitory properties of the examined Herniaria glabra (HG-PE), H. polygama (HP-PE), and H. incana herb (HIh-PE) purified extracts. The enzyme activity in control samples (untreated with the extracts or a reference inhibitor) was assumed as 100%; n = 3. Figure 6. Effects of the examined Herniaria glabra (HG-PE), H. polygama (HP-PE) and H. incana herb (HIh-PE) purified extracts on the inflammatory response of the concanavalin A-stimulated human PBMCs. Anti-inflammatory actions of the tested extracts were estimated using ELISA and based on IL-2 (panel ( A )) and TNF-α (panel ( B )) release; * p < 0.05, ** p < 0.01, *** p < 0.001; n = 4–5. Table 1. Non-saponin compounds identified and quantified in Herniaria glabra (HG), H. polygama (HP), H. incana herb (HIh) purified extracts using UHPLC-QTOF-MS/MS. t R (min) Compound Neutral Formula Mode m/z Δ * Mσ ** Major Fragments (%) HG,% HP,% HIh,% Ref 1 1.89 3-CQA (Neochlorogenic acid) C 16 H 18 O 9 [M − H] − [2M − H] − 353.0872 707.1820 1.6 0.9 1.5 1.3 191.0558 (100) (C 7 H 11 O 6 ), 179.0342 (80.5) (C 9 H 7 O 4 ), 173.0342 (3.5) (C 7 H 9 O 5 ), 161.0236 (4.8) (C 9 H 5 O 3 ), 135.0439 (14.1) (C 8 H 7 O 2 ) _ _ 1.27 [ 15 ] 2 2.56 Cis -3- p CoQA C 16 H 18 O 8 [M − H] − [2M − H] − 337.0923 675.1926 1.6 0.74 6.8 9.3 191.0559 (7.1) (C 7 H 11 O 6 ), 173.0453 (4.1) (C 7 H 9 O 5 ), 163.0390 (100) (C 9 H 7 O 3 ), 155.0336 (2.3) (C 7 H 7 O 4 ), 119.0487 (8.6) (C 8 H 7 O) _ _ 1.51 [ 15 ] 3 2.64 Trans -3- p CoQA C 16 H 18 O 8 [M − H] − [2M − H] − 337.0921 675.1919 2.5 1.8 4.3 8.6 191.0558 (37.6) (C 7 H 11 O 6 ), 173.0449 (4.4) (C 7 H 9 O 5 ), 163.0392 (100) (C 9 H 7 O 3 ), 155.0343 (2.0) (C 7 H 7 O 4 ), 119.0489 (9.2) (C 8 H 7 O) _ _ 0.31 [ 15 ] 4 2.81 a 5-CQA (Chlorogenic acid) C 16 H 18 O 9 [M − H] − [2M − H] − 353.0871 707.1822 0.7 1.0 1.9 23.5 191.0556 (100) (C 7 H 11 O 6 ), 161.0244 (1.53) (C 9 H 5 O 3 ) _ TA 1.37 [ 15 ] 5 2.99 p CoA-4- O -hexoside C 15 H 18 O 8 [M − H] − [2M − H] − 325.0923 651.1925 1.8 0.8 9.7 11.4 163.0393 (100) (C 9 H 7 O 3 ), 119.0490 (12.6) (C 8 H 7 O) TA TA 0.12 [ 15 ] 6 3.05 a 4-CQA (Cryptochlorogenic acid) C 16 H 18 O 9 [M − H] − [2M − H] − 353.0874 707.1829 1.2 −0.1 3.6 15.3 191.0552 (40.4) (C 7 H 11 O 6 ), 179.0343 (84.5) (C 9 H 7 O 4 ), 173.0446 (100) (C 7 H 9 O 5 ), 161.0231 (2.7) (C 9 H 5 O 3 ), 155.0330 (5.3) (C 7 H 7 O 4 ), 135.0441 (13.9) (C 8 H 7 O 2 ) _ _ 0.20 [ 15 ] 7 3.21 Cis -3-FerQA C 17 H 20 O 9 [M − H] − [2M − H] − 367.1025 735.2128 2.6 1.9 4.0 15.7 193.0500 (100) (C 10 H 9 O 4 ), 173.0450 (4.0) (C 7 H 9 O 5 ), 155.0343 (1.2) (C 7 H 7 O 4 ), 149.0597 (2.0) (C 9 H 9 O 2 ), 134.0363 (C 8 H 6 O 2 ● ) (6.1) TA TA 1.24 [ 15 ] 8 3.31 Trans -3-FerQA C 17 H 20 O 9 [M − H] − [2M − H] − 367.1030 735.2138 1.2 0.6 6.7 36.2 193.0502 (100) (C 10 H 9 O 4 ), 173.0445 (5.5) (C 7 H 9 O 5 ), 155.0338 (1.0) (C 7 H 7 O 4 ), 149.0599 (4.3) (C 9 H 9 O 2 ), 134.0365 (11.8) (C 8 H 6 O 2 ● ) _ _ 0.16 [ 15 ] 9 3.72 # Licoagroside B (maltol-3- O -[HMG-(1→6)]-β-glucoside) C 18 H 24 O 12 [M − H] − [2M − H] − 431.1189 863.2463 1.3 0.9 4.3 7.2 161.0448 (10) (C 6 H 9 O 5 ), 125.0232 (100) (C 6 H 5 O 3 ) 1.80 1.33 1.10 [ 14 ] 10 3.81 # (2 R ,3 R )-Benzoyl-tartaric acid C 11 H 10 O 7 [M − H] − 253.0340 5.4 6.8 130.9969 (26.3) (C 4 H 3 O 5) , 121.0277 (100) (C 7 H 5 O 2 ) _ 1.01 _ [ 15 ] 11 3.87 # Cis -2-hydroxy-4-methoxycinnamic acid 2- O -β-glucoside ( cis -GMCA) C 16 H 20 O 9 [M − H] − 355.1017 5.2 4.9 193.0494 (100) (C 10 H 9 O 4 ), 149.0591 (75.4) (C 9 H 9 O 2 ), 134.0367 (5.5) (C 8 H 6 O 2 ● ) _ 5.76 _ [ 15 ] 12 4.70 Trans -4-FerQA C 17 H 20 O 9 [M − H] − 367.1028 1.9 4.1 193.0501 (21.3) (C 10 H 9 O 4 ), 191.0558 (40.6) (C 7 H 11 O 6 ), 173.0455 (100) (C 7 H 9 O 5 ), 155.0349 (4.0) (C 7 H 7 O 4 ), 134.0372 (2.5) (C 8 H 6 O 2 ● ) TA TA 0.22 [ 15 ] 13 4.77 # 3-(2-glucosyloxy-4- methoxyphenyl)propanoic acid (GMPPA) C 16 H 22 O 9 [M − H] − 357.1174 4.9 0.7 195.0650 (100) (C 10 H 11 O 4 ), 177.0541 (2.8) (C 10 H 9 O 3 ), 151.0748 (10.7) (C 9 H 11 O 2 ), 136.0512 (1.1) (C 8 H 8 O 2 ● ) _ 1.07 _ [ 15 ] 14 5.41 N -Malonyl-tryptophan C 14 H 14 N 2 O 5 [M + H] + 291.0969 2.3 4.6 273.0868 (19.0) (C 14 H 13 N 2 O 4 ), 245.0916 (100) (C 13 H 13 N 2 O 3 ), 227.0807 (24.9) (C 13 H 11 N 2 O 2 ), 188.0702 (21.9) (C 11 H 10 NO 2 ), 130.0647 (18.7) (C 9 H 8 N) _ _ NC [ 15 ] 15 5.52 # Trans -2-hydroxy-4- methoxycinnamic acid 2- O -β-glucoside ( trans -GMCA) C 16 H 20 O 9 [M − H] − 355.1016 5.3 0.7 193.0494 (100) (C 10 H 9 O 4 ), 149.0591 (36.5) (C 9 H 9 O 2 ), 134.0357 (4.7) (C 8 H 6 O 2 ● ) _ 1.58 _ [ 15 ] 16 5.60 # Apiorutin (quercetin-3- O -[β-Api-(1→2)]-[α-Rha-(1→6)]-β-glucoside) C 32 H 38 O 20 [M − H] − 741.1868 2.1 5.9 609.1461 (0.5) (C 27 H 29 O 16 ), 591.1362 (0.3) (C 27 H 27 O 15 ), 300.0269 (100) (C 15 H 8 O 7 ● ), 271.0244 (4.5) (C 14 H 7 O 6 ), 255.0299 (2.0) (C 14 H 7 O 5 ), 178.9986 (2.0) (C 8 H 3 O 5 ), 151.0028 (0.9) (C 7 H 3 O 4 ) 1.50 0.33 _ [ 14 ] 17 5.83 Kaempferol-3- O -(dHex-(1→2))-[dHex-(1→2)]- hexoside C 33 H 40 O 19 [M − H] − 739.2080 1.5 29.0 575.1392 (0.6) (C 27 H 27 O 14 ), 284.0316 (100) (C 15 H 8 O 6 ● ), 255.0291 (7.4) (C 14 H 7 O 5 ), 227.0341 (4.5) (C 13 H 7 O 4 ), 178.9973 (1.2) (C 8 H 3 O 5 ), 151.0024 (1.5) (C 7 H 3 O 4 ) _ _ 0.16 [ 15 ] 18 6.18 # Rutin (quercetin-3- O -[α-Rha-(1→6)]-β-glucoside) C 27 H 30 O 16 [M − H] − 609.1453 1.5 8.3 343.0459 (1.7) (C 17 H 11 O 8 ), 300.0268 (100) (C 15 H 8 O 7 ● ) , 255.0299 (1.0) (C 14 H 7 O 5 ), 178.9986 (2.9) (C 8 H 3 O 5 ), 151.0037 (1.8) (C 7 H 3 O 4 ) 1.87 5.27 0.82 [ 14 ] 19 6.33 Quercetin-3- O - hexoside C 21 H 20 O 12 [M − H] − 463.0874 1.6 4.8 343.0459 (1.4) (C 17 H 11 O 8 ), 300.0267 (100) (C 15 H 8 O 7 ● ), 255.0299 (1.1) (C 14 H 7 O 5 ), 178.9965 (1.8) (C 8 H 3 O 5 ), 151.0035 (1.5) (C 7 H 3 O 4 ) TA 0.22 0.18 20 6.76 Kaempferol-3- O -[dHex-(1→6)]- hexoside C 27 H 30 O 15 [M − H] − 593.1499 1.3 2.1 327.0502 (3.2) (C 17 H 11 O 7 ), 285.0389 (53.9) (C 15 H 9 O 6 ), 284.0317 (100) (C 15 H 8 O 6 ● ), 255.0300 (2.9) (C 14 H 7 O 5 ), 227.0343 (1.7) (C 13 H 7 O 4 ), 151.0035 (2.1) (C 7 H 3 O 4 ) _ _ 0.19 [ 15 ] 21 6.95 Kaempferol-3- O -hexoside C 21 H 20 O 11 [M − H] − 447.0902 2.0 6.5 284.0322 (47.4) (C 15 H 8 O 6 ● ) _ _ TA [ 15 ] 22 6.96 Quercetin- 3- O -[HMG]- hexoside C 27 H 28 O 16 [M − H] − 607.1219 2.4 7.2 545.1280 (8.0) (C 26 H 25 O 13 ), 505.0990 (37.2) (C 23 H 21 O 13 ), 463.0874 (47.5) (C 21 H 19 O 12 ), 300.0268 (100) (C 15 H 8 O 7 ● ), 271.0235 (2.9) (C 14 H 7 O 6 ), 255.0292 (1.5) (C 14 H 7 O 5 ), 178.9978 (3.1) (C 8 H 3 O 5 ), 151.0028 (2.6) (C 7 H 3 O 4 ) _ _ TA [ 15 ] 23 7.00 Blumenin isomer (sesquiterpenoid cyclohexanone-hexuronosyl-hexoside) C 25 H 40 O 13 [M − H] − 547.2383 1.3 12.3 347.2062 (3.7) (C 19 H 31 O 7 ), 209.1529 (1.7) (C 13 H 21 O 2 ), 175.0239 (4.3) (C 6 H 7 O 6 ), 161.0444 (1.5) (C 6 H 9 O 5 ) _ _ TA [ 23 ] 24 7.17 Kaempferol-3- O -[HMG-(1→3/4)]-[dHex-(1→2)]-hexoside C 33 H 38 O 19 [M − H] − 737.1919 2.1 1.5 675.1922 (1.4) (C 32 H 35 O 16 ), 635.1602 (5.7) (C 29 H 31 O 16 ), 593.1528 (8.1) (C 27 H 29 O 15 ), 429.0819 (0.7) (C 21 H 17 O 10 ), 284.0317 (100) (C 15 H 8 O 6 ● ), 255.0293 (4.4) (C 14 H 7 O 5 ), 227.0340 (2.0) (C 13 H 7 O 4 ), 178.9974 (0.8) (C 8 H 3 O 5 ), 151.0027 (0.9) (C 7 H 3 O 4 ) _ _ 1.22 $ [ 15 ] 25 7.19 Nicotiflorin (kaempferol-3- O -[Rha-(1→6)]-glucoside) C 27 H 30 O 15 [M − H] − 593.1501 1.8 4.4 327.0498 (2.4) (C 17 H 11 O 7 ), 285.0392 (100) (C 15 H 9 O 6 ), 255.0291 (1.9) (C 14 H 7 O 5 ), 227.0344 (0.9) (C 13 H 7 O 4 ), 151.0027 (1.2) (C 7 H 3 O 4 ) 0.44 0.44 [ 14 ] 26 7.58 # Narcissin (isorhamnetin-3- O -[α-Rha p -(1→6)]-β-glucoside) C 28 H 32 O 16 [M − H] − 623.1603 2.3 5.1 357.0609 (1.5) (C 18 H 13 O 8 ), 315.0499 (100) (C 16 H 11 O 7 ), 300.0266 (5.9) (C 15 H 8 O 7 ● ), 271.0244 (1.3) (C 14 H 7 O 6 ), 151.0028 (0.7) (C 7 H 3 O 4 ) 7.34 5.43 0.96 [ 14 ] 27 7.77 4,4′-Dimethoxy-2,2′-di- O -hexoside-truxinate (cyclodimer of GMCA) C 32 H 40 O 18 [M − H] − 711.2128 1.9 6. 9 549.1606 (12.9) (C 26 H 29 O 13 ), 531.1497 (8.5) (C 26 H 27 O 12 ), 369.0973 (51.4) (C 20 H 17 O 7 ), 343.1181 (41.6) (C 19 H 19 O 6 ), 299.1284 (23.7) (C 18 H 19 O 4 ), 271.0970 (92.1), 256.0737 (2.7) (C 15 H 12 O 4 ● ), 193.0502 (100) (C 10 H 9 O 4 ), 149.0599 (41.8) (C 9 H 9 O 2 ), 134.0361 (8.2) (C 8 H 6 O 2 ● ) _ TA _ [ 15 ] 28 7.80 Kaempferol-3- O -[HMG-(1→3/4)]-hexoside C 27 H 28 O 15 [M − H] − 591.1344 1.9 5.6 529.1343 (13.8) (C 26 H 25 O 12 ), 489.1031 (39.2) (C 23 H 21 O 12 ), 447.0920 (31.8) (C 21 H 19 O 11 ), 327.0499 (1.8) (C 17 H 11 O 7 ), 284.0318 (100) (C 15 H 8 O 6 ● ), 255.0282 (1.4) (C 14 H 7 O 5 ), 229.0503 (1.1) (C 13 H 9 O 4 ), 151.0025 (0.9) (C 7 H 3 O 4 ) _ _ 0.25 29 7.81 Isorhamnetin-3- O -hexoside C 22 H 22 O 12 [M − H] − 477.1030 1.7 12.8 357.0604 (3.0) (C 18 H 13 O 8 ), 314.0422 (100) (C 16 H 10 O 7 ● ), 299.0195 (1.46) (C 15 H 7 O 7 ), 285.0397 (1.3) (C 15 H 9 O 6 ), 271.0220 (1.6) (C 14 H 7 O 6 ), 151.0034 (2.0) (C 7 H 3 O 4 ) TA TA TA 30 9.10 a Herniarin (7-methoxy- coumarin) C 10 H 8 O 3 [M + H] + 177.0557 −5.8 1.9 177.0537 (100), 133.0659 (4. 3), 121.0658 (2.9) _ 1.59 _ [ 15 ] 31 9.94 # 7- O -Methylquercetin-3- O -[HMG-(1→6)]-[α-Rha-(1→2)]-β-galactoside C 34 H 40 O 20 [M − H] − 767.2035 0.7 17.0 705.2059 (0.4) (C 33 H 37 O 17 ), 665.1726 (1.8) (C 30 H 33 O 17 ), 623.1619 (4.8) (C 28 H 31 O 16 ), 314.0429 (100) (C 16 H 10 O 7 ● ) ; 299.0196 (13.1) (C 15 H 7 O 7 ), 271.0246 (2.4) (C 14 H 7 O 6 ), 193.0145 (0.8) (C 9 H 5 O 5 ), 165.0189 (1.5) (C 8 H 5 O 4 ) _ _ 0.31 [ 15 ] 32 10.20 7- O -Methylkaempferol-3- O -[dHex-(1→2)]-hexoside C 28 H 32 O 15 [M − H] − 607.1672 −0.6 1.6 298.0484 (100) (C 16 H 10 O 6 ● ), 283.0248 (10.2) (C 15 H 7 O 6 ), 271.0610 (0.9) (C 15 H 11 O 5 ), 255.0298 (1.1) (C 14 H 7 O 5 ), 165.0190 (0.7) (C 8 H 5 O 4 ) _ _ 0.51 [ 15 ] 33 10.72 # Oxytroflavoside A (7- O -methylkaempferol-3- O -[HMG-(1→6)]-[α-Rha-(1→2)]-β- galactoside) C 34 H 40 O 19 [M − H] − 751.2089 0.3 14.8 649.1772 (2.2) (C 30 H 33 O 16 ), 607.1666 (4.4) (C 28 H 31 O 15 ), 298.0481 (100) (C 16 H 10 O 6 ● ), 283.0247 (13.5) (C 15 H 7 O 6 ); 271.0610 (0.9) (C 15 H 11 O 5 ), 255.0298 (1.7) (C 14 H 7 O 5 ), 165.0186 (0.7) (C 8 H 5 O 4 ) _ _ 14.73 [ 15 ] 34 11.05 # 7- O -Methylkaempferol-3- O -[HMG-(1→6)]-[α-Rha-(1→2)]-β-glucoside C 34 H 40 O 19 [M − H] − 751.2090 0.2 4.4 649.1788 (1.4) (C 30 H 33 O 16 ), 607.1670 (5.5) (C 28 H 31 O 15 ), 298.0483 (100) (C 16 H 10 O 6 ● ), 283.0247 (13.3) (C 15 H 7 O 6 ), 271.0616 (0.8) (C1 5 H 11 O 5 ), 255.0301 (1.5) (C 14 H 7 O 5 ), 165.0188 (0.8) (C 8 H 5 O 4 ) _ _ 0.91 [ 15 ] 35 11.26 # Oxytroflavoside C (main) (7- O -methylkaempferol-3- O -[HMG-(1→4)]-[α-Rha-(1→2)]-β-galactoside]) Oxytroflavoside B (minor) (7- O -methylkaempferol-3- O -[HMG-(1→3)]-[α-Rha-(1→2)]-β-galactoside) C 34 H 40 O 19 [M − H] − 751.2086 0.6 8.1 649.1779 (1.6) (C 30 H 33 O 16 ), 607.1676 (8.8) (C 28 H 31 O 15 ), 298.0483 (100) (C 16 H 10 O 6 ● ), 283.0249 (11.2) (C 15 H 7 O 6 ), 271.0614 (1.0) (C 15 H 11 O 5 ), 255.0303 (1.2) (C 14 H 7 O 5 ), 165.0189 (0.7) (C 8 H 5 O 4 ) _ _ 1.38 $ [ 15 ] 36 37 11.54 7- O -Methyl-kaempferol-3- O -[HMG-(1→3/4)]-hexoside C 28 H 30 O 15 [M − H] − 605.1515 −0.5 11.4 543.1516 (8.0) (C 27 H 27 O 12 ), 503.1198 (27.1) (C 24 H 23 O 12 ), 461.1093 (22.9) (C 22 H 21 O 11 ), 341.0663 (1.8) (C 18 H 13 O 7 ), 298.0482 (100) (C 16 H 10 O 6 ● ), 283.0247 (6.2) (C 15 H 7 O 6 ); 255.0302 (1.0) (C 14 H 7 O 5 ), 165.0192 (1.3) (C 8 H 5 O 4 ) _ _ 0.32 [ 15 ] 38 11.77 7- O -Methyl-kaempferol-3- O -[dHex-(1→2)]-pentoside C 27 H 30 O 14 [M − H] − 577.1565 −0.5 13.5 413.0888 (1.0) (C 21 H 17 O 9 ), 298.0490 (100) (C 16 H 10 O 6 ● ), 283.0250 (7.3) (C 15 H 7 O 6 ), 255.0302 (1.0) (C 14 H 7 O 5 ), 165.0188 (0.9) (C 8 H 5 O 4 ) _ _ 0.12 [ 15 ] Sum 12.95 24.03 29.56 Notes: a Identification with an analytical standard. # Isolated and NMR confirmed. * Accuracy of mass measurements expressed in parts per million (ppm). ** Isotopic pattern fit factor (mσ). %—Percentage of a compound in the purified extracts. ● Anionradical. $ Co-eluting peaks. CQA—caffeoylquinic acid; p CoQA— p -coumaroylquinic acid; FerQA—feruloylquinic acid; p CoA— p -coumaric acid; dHex—deoxyhexosyl; Rha—rhamnopyranosyl; Api—apifuranosyl; HMG—3-hydroxy-3-methylglutaryl; TA—trace amount; NC—not calculated; Ref.—references. Table 2. Determination of antioxidant properties of the examined Herniaria glabra (HG-PE), H. polygama (HP-PE), and H. incana herb (HIh-PE) purified extracts, based on measurements of thiobarbituric acid-reactive substances (TBARS) and protein thiol groups levels as well as on the ferric reducing ability of blood plasma (FRAP), under the ONOO − -induced oxidative stress In Vitro. Statistical significance: # p < 0.05, ## p < 0.001 plasma treated with ONOO − in the absence of examined purified extracts vs. control plasma; * p < 0.05, ** p < 0.01 plasma treated with ONOO − in the absence of examined purified extracts vs. plasma treated with ONOO − in the presence of examined substances. (µg/ mL) TBARS (nmol/mL of Plasma) ( n = 9) Protein-SH Groups (µmol/mL of Plasma) ( n = 8) FRAP (mM Fe 2+ ) ( n = 9) Control (untreated) plasma 0 0.078 ± 0.011 0.335 ± 0.019 0.460 ± 0.035 Plasma treated with ONOO − 0 0.122 ± 0.015 # 0.229 ± 0.029 ## 0.380 ± 0.027 ## Trolox 1 0.104 ± 0.027 0.267 ± 0.025 * 0.422 ± 0.031 5 0.108 ± 0.027 0.274 ± 0.029 ** 0.462 ± 0.075 ** 50 0.106 ± 0.025 0.288 ± 0.038 ** 0.603 ± 0.060 ** HG-PE 1 0.100 ± 0.022 * 0.260 ± 0.026 * 0.418 ± 0.033 5 0.099 ± 0.023 ** 0.268 ± 0.022 ** 0.429 ± 0.028 * 50 0.102 ± 0.022 ** 0.262 ± 0.024 ** 0.447 ± 0.040 * HP-PE 1 0.101 ± 0.022 * 0.261 ± 0.023 * 0.428 ± 0.029 5 0.093 ± 0.019 ** 0.264 ± 0.029 * 0.442 ± 0.033 ** 50 0.100 ± 0.026 * 0.258 ± 0.027 * 0.458 ± 0.032 ** HIh-PE 1 0.096 ± 0.026 * 0.258 ± 0.031 * 0.425 ± 0.033 5 0.101 ± 0.024 0.262 ± 0.024 ** 0.440 ± 0.028 * 50 0.099 ± 0.022 * 0.264 ± 0.025 ** 0.485 ± 0.091 ** Table 3. The influence of the examined Herniaria glabra (HG-PE), H. polygama (HP-PE), and H. incana herb (HIh-PE) purified extracts on the viability of peripheral blood mononuclear cells (PBMCs). The viability of control (untreated) PBMCs was assumed as 100%; ** p < 0.01. The Examined Extracts (μg/mL) PBMCs Viability (%) the Resazurin-Based Assay ( n = 7) the Trypan Blue Excluding Test ( n = 11) HG-PE 5 93.47 ± 6.83 102.73 ± 11.15 25 95.42 ± 6.82 97.49 ± 8.25 50 93.82 ± 12.51 89.22 ± 14.37 HP-PE 5 93.11 ± 10.27 99.06 ± 11.36 25 95.17 ± 8.46 97.83 ± 10.97 50 68.49 ± 17.29 ** 87.69 ± 12.08 HIh-PE 5 93.52 ± 10.47 101.18 ± 13.86 25 96.85 ± 9.89 101.76 ± 13.29 50 99.98 ± 13.60 92.84 ± 14.54 MDPI and ACS Style Kozachok, S.; Kolodziejczyk-Czepas, J.; Marchyshyn, S.; Wojtanowski, K.K.; Zgórka, G.; Oleszek, W. Comparison of Phenolic Metabolites in Purified Extracts of Three Wild-Growing HerniariaL. Species and Their Antioxidant and Anti-Inflammatory Activities In Vitro. Molecules 2022, 27, 530. https://doi.org/10.3390/molecules27020530 Kozachok S, Kolodziejczyk-Czepas J, Marchyshyn S, Wojtanowski KK, Zgórka G, Oleszek W. Comparison of Phenolic Metabolites in Purified Extracts of Three Wild-Growing HerniariaL. Species and Their Antioxidant and Anti-Inflammatory Activities In Vitro. Molecules. 2022; 27(2):530. https://doi.org/10.3390/molecules27020530 Kozachok, Solomiia, Joanna Kolodziejczyk-Czepas, Svitlana Marchyshyn, Krzysztof Kamil Wojtanowski, Grażyna Zgórka, and Wieslaw Oleszek. 2022. "Comparison of Phenolic Metabolites in Purified Extracts of Three Wild-Growing HerniariaL. Species and Their Antioxidant and Anti-Inflammatory Activities In Vitro" Molecules27, no. 2: 530. https://doi.org/10.3390/molecules27020530
https://www.mdpi.com/1420-3049/27/2/530/xml
Presentations & Reports: Difference between revisions - iDigBio Presentations & Reports: Difference between revisions Revision as of 16:27, 12 March 2013 (view source) Dpaul (talk|contribs) m ( →‎Talks & Reports from Hackathon 1) ← Older edit Latest revision as of 13:12, 13 June 2013 (view source) Pbryan.heidorn (talk|contribs) ( →‎Talks & Reports from Hackathon 1) (4 intermediate revisions by one other user not shown) Line 5: Line 5: ::;Hackathon Metrics - Alex Thompson ::;Hackathon Metrics - Alex Thompson ::;Parsing Dataset 1 - Daryl Lafferty ::; [https://www.idigbio.org/sites/default/files/workshop-presentations/aocr-hackathon/SALIX2.pptParsing Dataset 1 using SALIX 2]- Daryl Lafferty : SALIX is “Semi-Automatic Label Information eXtraction” parsing system, developed and used extensively at Arizona State University. The purpose is to parse OCR'd label data into the respective data fields (e.g. Collector, collection number, etc.). The original SALIX required user intervention with each label to format and proofread. SALIX 2 tries to remove the “Semi” and make it fully automatic. Written in C++ in Windows. Development was focused on Lichen labels. ::;[http://manuscripttranscription.blogspot.com/2013/02/improving-ocr-inputs-from-ocr-outputs.html Improving OCR Inputs from OCR Outputs] - Ben Brumfield: Efforts to improve the quality of OCR by pre-processing images based on the output of 'naive' OCR execution.  Topics included handwriting detection within Dataset 1 ([http://manuscripttranscription.blogspot.com/2013/02/detecting-handwriting-in-ocr-text.html final report]) and label extraction from Dataset 3 ([http://manuscripttranscription.blogspot.com/2013/02/results-of-ocrocrop-approach-to.html final report]). ::;[http://manuscripttranscription.blogspot.com/2013/02/improving-ocr-inputs-from-ocr-outputs.html Improving OCR Inputs from OCR Outputs] - Ben Brumfield: Efforts to improve the quality of OCR by pre-processing images based on the output of 'naive' OCR execution.  Topics included handwriting detection within Dataset 1 ([http://manuscripttranscription.blogspot.com/2013/02/detecting-handwriting-in-ocr-text.html final report]) and label extraction from Dataset 3 ([http://manuscripttranscription.blogspot.com/2013/02/results-of-ocrocrop-approach-to.html final report]). Line 14: Line 14: :::The Lichens, Bryophytes and Climate Change (LBCC) project endeavors to digitize the label information from millions of North American lichen and bryophyte herbarium specimens. These labels are occasionally hand written although usually at least partially typed or printed. When typed or printed a myriad of fonts have been used. Thus far, we have been constrained to use open-source Optical Character Recognition (OCR) software. By most accounts the best of these is Tesseract. While it does not recognize handwriting it is considered to be the best at recognizing typewritten text images. Our workflow involves attaching a barcode to labels, imaging them, assigning the barcode to be the image filename and submitting the images to an FTP server to be entered into Symbiota, a MySQL database designed by Ed Gilbert, with the barcode as the catalog number. Once entered into Symbiota, the images are batch processed with Tesseract and the results entered into the database as well. The next step is to parse the Tesseract output to retrieve the label information in hopes of being able to populate relevant fields in the database. I have been developing code using PHP version 5.3 and its PCRE regular-expression library for this purpose. :::The Lichens, Bryophytes and Climate Change (LBCC) project endeavors to digitize the label information from millions of North American lichen and bryophyte herbarium specimens. These labels are occasionally hand written although usually at least partially typed or printed. When typed or printed a myriad of fonts have been used. Thus far, we have been constrained to use open-source Optical Character Recognition (OCR) software. By most accounts the best of these is Tesseract. While it does not recognize handwriting it is considered to be the best at recognizing typewritten text images. Our workflow involves attaching a barcode to labels, imaging them, assigning the barcode to be the image filename and submitting the images to an FTP server to be entered into Symbiota, a MySQL database designed by Ed Gilbert, with the barcode as the catalog number. Once entered into Symbiota, the images are batch processed with Tesseract and the results entered into the database as well. The next step is to parse the Tesseract output to retrieve the label information in hopes of being able to populate relevant fields in the database. I have been developing code using PHP version 5.3 and its PCRE regular-expression library for this purpose. ::; LabelX- Bryan Heidorn & Qianjin Zhang ::; LABELX- Bryan Heidorn & Qianjin Zhang Label Annotation through Biodiversity Enhanced Learning (LABELX) (Heidorn & Wei, 2008; Heidorn & Zhang, 2013) is a Hidden Markov Model-based system HMM) (Frasconi et al., 2003) with a number of preprocessing and post-processing algorithms added.  HMMs exploit the order of elements in a label and Bayesian conditional probability to predict the proper classification of elements of the label. Because there are millions of scientific names and any individual name is unlikely to be in a training set of 100-200 records used here, for plants the system uses International Plant Name Index (IPNI, 2012) of scientific names and authorities to substitute generic tokens for, genus, species and authority.  Similar substitutions are made for integers and alphanumerics that are used in collector numbers and collection numbers. ::;Parsing Dataset 2 - Dmitry Mozzherin ::;Parsing Dataset 2 - Dmitry Mozzherin ::;[https://www.idigbio.org/sites/default/files/workshop-presentations/aocr-hackathon/Hackathon_InitalResults_Schroeder_final.pptx iDigBio Hackathon:iDigBio OCR Hackathon Initial Results - Rest API]:Services and Workflow UIs - Robin and Paul Schroeder ::;[https://www.idigbio.org/sites/default/files/workshop-presentations/aocr-hackathon/Hackathon_InitalResults_Schroeder_final.pptx iDigBio OCR Hackathon Initial Results - Rest API]:Services and Workflow UIs - Robin and Paul Schroeder ::;Workflows - John Pickering ::;Workflows - John Pickering Talks & Reports from Hackathon 1 Hackathon Overview & Intro to iDigBio- Deborah Paul Overview of the Hackathon goals and introduction to iDigBio for those new to the project. Review this presentation before the other hackathon presentations to learn about the aOCR working group and the talks, presentations, and work being done at this hackathon and after. Hackathon Metrics - Alex Thompson Parsing Dataset 1 using SALIX 2- Daryl Lafferty SALIX is “Semi-Automatic Label Information eXtraction” parsing system, developed and used extensively at Arizona State University. The purpose is to parse OCR'd label data into the respective data fields (e.g. Collector, collection number, etc.). The original SALIX required user intervention with each label to format and proofread. SALIX 2 tries to remove the “Semi” and make it fully automatic. Written in C++ in Windows. Development was focused on Lichen labels. Improving OCR Inputs from OCR Outputs- Ben Brumfield Efforts to improve the quality of OCR by pre-processing images based on the output of 'naive' OCR execution. Topics included handwriting detection within Dataset 1 (final report ) and label extraction from Dataset 3 (final report). Image Segmentation - Phuc Nguyen Parsing Dataset 1: Regular Expression-Based Parsing of Tesseract Output from Lichen Herbarium Labels - Robert Anglin The Lichens, Bryophytes and Climate Change (LBCC) project endeavors to digitize the label information from millions of North American lichen and bryophyte herbarium specimens. These labels are occasionally hand written although usually at least partially typed or printed. When typed or printed a myriad of fonts have been used. Thus far, we have been constrained to use open-source Optical Character Recognition (OCR) software. By most accounts the best of these is Tesseract. While it does not recognize handwriting it is considered to be the best at recognizing typewritten text images. Our workflow involves attaching a barcode to labels, imaging them, assigning the barcode to be the image filename and submitting the images to an FTP server to be entered into Symbiota, a MySQL database designed by Ed Gilbert, with the barcode as the catalog number. Once entered into Symbiota, the images are batch processed with Tesseract and the results entered into the database as well. The next step is to parse the Tesseract output to retrieve the label information in hopes of being able to populate relevant fields in the database. I have been developing code using PHP version 5.3 and its PCRE regular-expression library for this purpose. LABELX - Bryan Heidorn & Qianjin Zhang Label Annotation through Biodiversity Enhanced Learning (LABELX) (Heidorn & Wei, 2008; Heidorn & Zhang, 2013) is a Hidden Markov Model-based system HMM) (Frasconi et al., 2003) with a number of preprocessing and post-processing algorithms added. HMMs exploit the order of elements in a label and Bayesian conditional probability to predict the proper classification of elements of the label. Because there are millions of scientific names and any individual name is unlikely to be in a training set of 100-200 records used here, for plants the system uses International Plant Name Index (IPNI, 2012) of scientific names and authorities to substitute generic tokens for, genus, species and authority. Similar substitutions are made for integers and alphanumerics that are used in collector numbers and collection numbers. Parsing Dataset 2 - Dmitry Mozzherin iDigBio OCR Hackathon Initial Results - Rest API Services and Workflow UIs - Robin and Paul Schroeder Workflows - John Pickering DarwinScore and Apiary - Jason Best
https://www.idigbio.org/wiki/index.php?_Reports&diff=cur&mobileaction=toggle_view_desktop&oldid=3378&title=Presentations_
AGFG1 - Antibodies - The Human Protein Atlas AGFG1 (HRB, RAB, RIP) protein expression summary. Antibody HPA008741 ANTIBODY INFORMATION Provider Atlas Antibodies Sigma-Aldrich Product name HPA008741 Host species Rabbit Clonality iThe antibodies are designated mAB for monoclonal and pAb for polyclonal. pAb Concentration 0.0725 mg/ml Purity Affinity purified using the PrEST-antigen as affinity ligand Released in version iThe release of the Human Protein Atlas in which the antibody was first published. 5.0 Proper citation Atlas Antibodies Cat#HPA008741, RRID:AB_1850752 Validation summary iAll assays through which the antibody has been validated.Assays&annotationprovide a detailed description of the different assays. The pie-charts indicate degree ofvalidation. <here is a image 4cf2cb4ddffafb2e-a2cda0d0977320ea ICC <here is a image 2a94d8f1b2892789-9cf6345435999be5>> <here is a image aa44c70901ac90b4-7eaaed431305a557 IHC <here is a image 52afc12c44ae311c-f54ab43e3b2ebf55>> <here is a image 41b1b25a6bad5753-2e327c7144d0bbda WB <here is a image 2a94d8f1b2892789-9cf6345435999be5>> <here is a image 7ad904cd4290fe28-22164f5be91e0a16 PA <here is a image 2a94d8f1b2892789-9cf6345435999be5>> IMMUNOCYTOCHEMISTRY iImmunocytochemistryis used to validate the antibody staining and for assessing and validating the protein expression pattern in selected human cell lines. Validation iResults of validation by standard or enhanced validation.Standard validation is based on concordance with available experimental gene/protein characterization data in the UniProtKB/Swiss-Prot database. Standard validation results in scores Supported, Approved or Uncertain.Enhanced validation is performed using either siRNA knockdown, tagged GFP cell lines or independent antibodies. For the siRNA validation the decrease in antibody-based staining intensity upon target protein downregulation is evaluated. For the GFP validation the signal overlap between the antibody staining and the GFP-tagged protein is evaluated. For the independent antibodies validation the evaluation is based on comparison of the staining of two (or more) independent antibodies directed towards independent epitopes on the protein.For all cases except the siRNA validation, an image representative of the antibody staining pattern is shown. For the siRNA validation, a box plot of the results is shown.<here is a image 2a94d8f1b2892789-9cf6345435999be5> Supported iReliability scores for antibodies used in immunocytochemistry are set by comparing the staining pattern in cell lines with external experimental evidence for protein localization. The scores are termed Supported, Approved and Uncertain. The subcellular location is supported by literature. <here is a image 4cf2cb4ddffafb2e-a2cda0d0977320ea> Immunofluorescent staining of human cell line A-431 shows localization to vesicles. Antibody dilution Human assay: A-431 fixed with PFA, dilution: 1:36 Human assay: U-251MG fixed with PFA, dilution: 1:36 Human assay: U2OS fixed with PFA, dilution: 1:36 IMMUNOHISTOCHEMISTRY iImmunohistochemistry is used for validating antibody reliability by assessing staining pattern in 44 normal tissues. Validation scores include Enhanced, Supported, Approved and Uncertain. Validation iResults of validation by standard or enhanced validation based on assessment of antibody performance in 44 normal tissues.Standard validation results in scores Supported, Approved or Uncertain. An image representative of the antibody staining pattern is shown.Enhanced validation results in the score Enhanced and includes two methods: Orthogonal validation and Independent antibody validation. For orthogonal validation, representative images of high and low expression are shown. For independent antibody validation, four images of each independent antibody are displayed.<here is a image 52afc12c44ae311c-f54ab43e3b2ebf55> Approved iImmunohistochemistry is used for validating antibody reliability by assessing staining pattern in 44 normal tissues. Validation scores include Enhanced, Supported, Approved and Uncertain. Immunohistochemical staining of human placenta shows strong membranous positivity in trophoblastic cells. <here is a image aa44c70901ac90b4-7eaaed431305a557> Placenta Retrieval iAntigen retrieval is a method used to restore/retrieve the epitope (antibody bidning region) of the target protein, cross-linked, and thus masked, during tissue preserving fixative treatment of the tissues. HIER pH6 Antibody dilution 1:125 Literature conformity iConformance of the expression pattern with available gene/protein characterization data in scientific literature and data from bioinformatic predictions.UniProt is used as the main source of gene/protein characterization data and when relevant, available publications and other sources of information are researched in depth. Extensive or sufficient gene/protein data requires that there is evidence of existence on a protein level and that a substantial quantity of published experimental data is available from literature and public databases. Limited protein/gene characterization data does not require evidence of existence on a protein level and refers to genes for which only bioinformatic predictions and scarce published experimental data is available. Partly consistent with extensive gene/protein characterization data. RNA consistency iConsistency between immunohistochemistry data andconsensus RNA levelsis divided into five different categories: i) High consistency, ii) Medium consistency, iii) Low consistency, iv) Very low consistency, and v) Cannot be evaluated. Low consistency between antibody staining and RNA expression data. WESTERN BLOT iA Western blot analysis is performed on a panel of human tissues and cell lines to evaluate antibody specificity. For antibodies with unreliable result a revalidation using an over-expression lysate is performed. Validation iWestern Blot is used for quality control of the polyclonal antibodies generated in the project. After purification, the antibodies are used to detect bands in a setup of lysate and different tissues. The result is then scored Enhanced, Supported, Approved, or Uncertain.Enhanced validation includes five different methods: Genetic validation, Recombinant expression validation, Independent antibody validation, Orthogonal validation and Capture MS validation. <here is a image 2a94d8f1b2892789-9cf6345435999be5> Supported iThe staining of an antibody is evaluated by Western Blot through analysis of samples from different cell lysates. A supportive score is given if band(s) of predicted size in kDa (+/-20%) is detected. Band of predicted size in kDa (+/-20%) with additional bands present. Analysis performed using a standard panel of samples. 230 130 95 72 56 36 28 17 11 <here is a image 41b1b25a6bad5753-2e327c7144d0bbda> RT-4 U-251MG Human Plasma Liver Tonsil 60.8 58.3 58.1 56.4 25.4 Antibody dilution 1:250 PROTEIN ARRAY Validation iA protein array containing 384 different antigens including the antibody target is used to analyse antibody specificity. Depending on the array interaction profile the antibody is scored as Supported, Approved, or Uncertain.<here is a image 2a94d8f1b2892789-9cf6345435999be5> Supported Pass with single peak corresponding to interaction only with its own antigen. <here is a image 7ad904cd4290fe28-22164f5be91e0a16> Antibody specificity analysis with protein arrays. Predicted and matching interactions are shown in green. Antibody dilution 1:3000 ANTIGEN INFORMATION Antigen Recombinant protein fragment Length (aa) 128 Antigen sequence PQSTATANFANFAHFNSHAAQNSANADFANFDAFGQSSGSSNFGGFPTAS HSPFQPQTTGGSAASVNANFAHFDNFPKSSSADFGTFNTSQSHQTASAVS KVSTNKAGLQTADKYAALANLDNIFSAG Matching transcripts AGFG1-201 - ENSP00000312059 [100%] AGFG1-203 - ENSP00000387218 [100%] AGFG1-204 - ENSP00000387154 [100%] AGFG1-205 - ENSP00000387282 [84%] AGFG1-206 - ENSP00000405429 [80%] Matching mouse transcripts ENSMUSP00000140170 [97%] ENSMUSP00000140785 [97%] ENSMUSP00000109071 [97%] ENSMUSP00000070250 [97%] ENSMUSP00000140473 [81%] ENSMUSP00000141157 [66%] ENSMUSP00000139503 [66%] ENSMUSP00000140678 [44%] ENSMUSP00000021803 [27%] ENSMUSP00000104883 [24%] ANTIGEN VIEW iThe Structure section provides predicted structures from the Alphafold protein structure database and includes structures corresponding to uniprot entries mapped to our gene set with at least one splice variant having 100% identity to the structure sequence. Displaying protein features on the AlphaFold structuresIndividual splice variants can be selected in the top part of the Protein Browser (see below) and both for transcripts matching the whole structure and those corresponding only to a part the full-length AlphaFold structure is shown. Different transcript-related features such as transmembrane regions, InterPro domains and antigen sequences for antibodies can be displayed in the structure by clicking on the respective features in the Protein Browser and then also the part of the structure corresponding to the selected transcript will be shown in lightblue. Clinical and population amino acid variants can be highlighted by using the sliders to the right of the structure, which can also be used to colour the entire structure by residue index or make the structure autorotate.The structures are displayed using theNGL Viewerand can also be zoomed-in and rotated manually. The Protein BrowserThe protein browser displays the antigen location on the target protein(s) and the features of the target protein. The tabs at the top of the protein view section can be used to switch between the different splice variants to which an antigen has been mapped.At the top of the view, the position of the antigen (identified by the corresponding HPA identifier) is shown as a green bar. A yellow triangle on the bar indicates a <100% sequence identity to the protein target.Below the antigens, the maximum percent sequence identity of the protein to all other proteins from other human genes is displayed, using a sliding window of 10 aa residues (HsID 10) or 50 aa residues (HsID 50). The region with the lowest possible identity is always selected for antigen design, with a maximum identity of 60% allowed for designing a single-target antigen (read more).The curve in blue displays the predicted antigenicity i.e. the tendency for different regions of the protein to generate an immune response, with peak regions being predicted to be more antigenic.The curve shows average values based on a sliding window approach using an in-house propensity scale. (read more).If a signal peptide is predicted by a majority of the signal peptide predictorsSPOCTOPUS,SignalP 4.0, andPhobius(turquoise) and/or transmembrane regions (orange) are predicted byMDM, these are displayed.Low complexityregions are shown in yellow andInterProregions in green. Common (purple) and unique (grey) regions between different splice variants of the gene are also displayed (read more), and at the bottom of the protein view is the protein scale. AGFG1-201 AGFG1-203 AGFG1-204 AGFG1-205 AGFG1-206 HPA008741 Protein 1 51 101 151 201 251 301 351 401 451 501 551 HsID 10 HsID 50 100% 60% 0% LC-reg. IP-reg. HPA008741 Protein 1 51 101 151 201 251 301 351 401 451 501 551 HsID 10 HsID 50 100% 60% 0% LC-reg. IP-reg. HPA008741 Protein 1 51 101 151 201 251 301 351 401 451 501 HsID 10 HsID 50 100% 60% 0% Unique LC-reg. IP-reg. HPA008741 84% Protein 1 51 101 151 201 251 301 351 401 451 501 551 HsID 10 HsID 50 100% 60% 0% Unique LC-reg. IP-reg. HPA008741 80% Protein 1 26 51 76 101 126 151 176 201 226 HsID 10 HsID 50 100% 60% 0% Unique LC-reg. IP-reg.
https://www.proteinatlas.org/ENSG00000173744-AGFG1/summary/antibody
Health Professional Training and Capacity Strengthening Through International Academic Partnerships: The First Five Years of the Human Resources for Health Program in Rwanda Background The Rwanda Human Resources for Health Program (HRH Program) is a 7-year (2012-2019) health professional training initiative led by the Government of Rwanda with the goals of training a large, diverse, and competent health workforce and strengthening the capacity of academic institutions in Rwanda. Methods The data for this organizational case study was collected through official reports from the Rwanda Ministry of Health (MoH) and 22 participating US academic institutions, databases from the MoH and the College of Medicine and Health Sciences (CMHS) in Rwanda, and surveys completed by the co-authors. Results In the first 5 years of the HRH Program, a consortium of US academic institutions has deployed an average of 99 visiting faculty per year to support 22 training programs, which are on track to graduate almost 4600 students by 2019. The HRH Program has also built capacity within the CMHS by promoting the recruitment of Rwandan faculty and the establishment of additional partnerships and collaborations with the US academic institutions. Conclusion The milestones achieved by the HRH Program have been substantial although some challenges persist. These challenges include adequately supporting the visiting faculty; pairing them with Rwandan faculty (twinning); ensuring strong communication and coordination among stakeholders; addressing mismatches in priorities between donors and implementers; the execution of a sustainability strategy; and the decision by one of the donors not to renew funding beyond March 2017. Over the next 2 academic years, it is critical for the sustainability of the 22 training programs supported by the HRH Program that the health-related Schools at the CMHS significantly scale up recruitment of new Rwandan faculty. The HRH Program can serve as a model for other training initiatives implemented in countries affected by a severe shortage of health professionals. Health Professional Training and Capacity Strengthening Through International Academic Partnerships: The First Five Years of the Human Resources for Health Program in Rwanda Document Type : Original Article Authors Corrado Cancedda 1 Philip Cotton 2 Joseph Shema 3 Stephen Rulisa 4 Robert Riviello 5 , 6 Lisa V. Adams 7 , 8 Paul E. Farmer 6 , 9 Jeanne N. Kagwiza 10 Donatilla Mukamana 12 Chrispinus Mumena 13 David K. Tumusiime 14 Lydie Mukashyaka 3 Esperance Ndenga 3 Theogene Twagirumugabe 15 Kaitesi B. Mukara 16 Vincent Dusabejambo 17 Timothy D. Walker 17 , 18 , 19 Emmy Nkusi 20 Lisa Bazzett-Matabele 21 Alex Butera 22 Belson Rugwizangoga 23 Jean Claude Kabayiza 24 Simon Kanyandekwe 25 Louise Kalisa 26 Faustin Ntirenganya 27 Jeffrey Dixson 28 Tanya Rogo 29 , 30 Natalie McCall 31 Mark Corden 32 , 33 Rex Wong 34 Agnes Gatarayiha 13 , 35 Egide Kayonga Ntagungira 14 Attila Yaman 9 Juliet Musabeyezu 36 Anne Sliney 37 Tej Nuthulaganti 37 Meredith Kiernan 37 Peter Okwi 38 Joseph Rhatigan 6 , 9 Jane Barrow 39 , 40 Kim Wilson 41 , 6 Adam C. Levine 42 Rebecca Reece 43 Michael Koster 44 Rachel T. Moresky 45 , 46 Jennifer E. O’Flaherty 47 , 48 Paul E. Palumbo 8 , 48 , 49 Rashna Ginwalla 48 , 50 Cynthia A. Binanay 51 Nathan Thielman 52 , 53 , 54 Michael Relf 53 , 55 Deborah Chyun 59 Robin T. Klar 60 Linda L. McCreary 61 Tonda L. Hughes 62 Marik Moen 63 , 64 Valli Meeks 65 Beth Barrows 66 , 67 Marcel E. Durieux 68 Craig D. McClain 6 , 69 Amy Bunts 70 Forrest J. Calland 70 Bethany Hedt-Gauthier 6 Danny Milner 71 , 72 Giuseppe Raviola 6 , 73 Stacy E. Smith 74 Meenu Tuteja 75 Urania Magriples 21 Asghar Rastegar 76 Linda Arnold 31 Ira Magaziner 37 Agnes Binagwaho 6 , 49 , 77 , 78 1Center for Global Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 2Office of the Vice-Chancellor, University of Rwanda, Kigali, Rwanda 3Rwanda Human Resources for Health Program Team, Ministry of Health, Kigali, Rwanda 4Office of the Dean, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 5Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston, MA, USA 6Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA 7Center for Health Equity, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA 8Department of Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA 9Division of Global Health Equity, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA 10Office of the Principal, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 11Department of Surgery, Faculty of Clinical Medicine and Dentistry, Kampala International University - Western Campus, Ishaka, Uganda 12School of Nursing and Midwifery, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 13Office of the Dean and Department of Oral and Maxillofacial Surgery, Oral Pathology and Oral Medicine, School of Dentistry, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 14School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 15Department of Anesthesiology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 16Department of Ear, Nose, and Throat, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 17Department of Internal Medicine, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 18School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW, Australia 19Department of General Medicine, Calvary Mater Hospital, Newcastle, NSW, Australia 20Department of Neurosurgery, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 21Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA 22Department of Orthopedic Surgery, Rwanda Military Hospital, Kigali, Rwanda 23Department of Pathology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 24Department of Pediatrics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 25Department of Mental Health, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 26Department of Radiology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 27Department of Surgery, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 28Yale School of Medicine, New Haven, CT, USA 29Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York City, NY, USA 30Department of Pediatrics, BronxCare Health System, Bronx, NY, USA 31Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA 32Division of Hospital Medicine, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, USA 33Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA 34Global Health Leadership Institute, Yale School of Public Health, New Haven, CT, USA 35Department of Preventive and Community Dentistry, School of Dentistry, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda 36University of Global Health Equity, Kigali, Rwanda 37Clinton Health Access Initiative, Boston, MA, USA 38Clinton Health Access Initiative, Kigali, Rwanda 39Office of Global and Community Health, Harvard School of Dental Medicine, Boston, MA, USA 40Department of Oral Health Policy and Epidemiology, Harvard School of Dental Medicine, Boston, MA, USA 41Department of General Pediatrics, Boston Children’s Hospital, Boston, MA, USA 42Department of Emergency Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA 43Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA 44Department of Pediatrics, Warren Alpert Medical School of Brown University, Providence, RI, USA 45sidHARTe Program, Heilbrunn Department of Population and Family Health, Mailman School of Public Health, Columbia University, New York City, NY, USA 46Department of Emergency Medicine, Columbia University College of Physicians and Surgeons, New York City, NY, USA 47Department of Anesthesiology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA 48Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA 49Department of Pediatrics, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA 50Department of Surgery, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA 51Duke Hubert-Yeargan Center for Global Health, Durham, NC, USA 52Department of Medicine, Duke University School of Medicine, Durham, NC, USA 53Duke Global Health Institute, Durham, NC, USA 54Duke University Medical Center, Durham, NC, USA 55Duke University School of Nursing, Durham, NC, USA 56Department of Obstetrics & Gynecology and Women’s Health, Albert Einstein College of Medicine, New York City, NY, USA 57Obstetrics & Gynecology and Women’s Health, Montefiore Medical Center, New York City, NY, USA 58Division of Nursing, Howard University College of Nursing and Allied Health Sciences, Washington, DC, USA 59University of Connecticut School of Nursing, Storrs, CT, USA 60New York University Rory Meyers College of Nursing, New York City, NY, USA 61University of Illinois at Chicago College of Nursing, Chicago, IL, USA 62Columbia University School of Nursing, New York City, NY, USA 63Department of Family & Community Health, University of Maryland School of Nursing, Baltimore, MD, USA 64Global Education and Mentorship, Office of Global Health, University of Maryland School of Nursing, Baltimore, MD, USA 65Department of Oncology & Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, USA 66Office of Global Health, University of Maryland School of Nursing, Baltimore, MD, USA 67Partnerships, Professional Education, and Practice, University of Maryland School of Nursing, Baltimore, MD, USA 68Department of Anesthesiology, University of Virginia School of Medicine, Charlottesville, VA, USA 69Department of Anesthesiology Perioperative and Pain Medicine, Boston Children’s Hospital, Boston, MA, USA 70Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA 71Center for Global Health, American Society for Clinical Pathology, Chicago, IL, USA 72Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA 73Department of Psychiatry, Boston Children’s Hospital, Boston, MA, USA 74Department of Radiology, Brigham and Women’s Hospital, Boston, MA, USA 75Global Health and Research Programs, Biomedical Research Institute, Brigham and Women’s Hospital, Boston MA, USA 76Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA 77Institute for Health Policy and Clinical Practice, Dartmouth College, Hanover, NH, USA 78Office of the Vice-Chancellor, University of Global Health Equity, Kigali, Rwanda 10.15171/ijhpm.2018.61 Abstract Background The Rwanda Human Resources for Health Program (HRH Program) is a 7-year (2012-2019) health professional training initiative led by the Government of Rwanda with the goals of training a large, diverse, and competent health workforce and strengthening the capacity of academic institutions in Rwanda. Methods The data for this organizational case study was collected through official reports from the Rwanda Ministry of Health (MoH) and 22 participating US academic institutions, databases from the MoH and the College of Medicine and Health Sciences (CMHS) in Rwanda, and surveys completed by the co-authors. Results In the first 5 years of the HRH Program, a consortium of US academic institutions has deployed an average of 99 visiting faculty per year to support 22 training programs, which are on track to graduate almost 4600 students by 2019. The HRH Program has also built capacity within the CMHS by promoting the recruitment of Rwandan faculty and the establishment of additional partnerships and collaborations with the US academic institutions. Conclusion The milestones achieved by the HRH Program have been substantial although some challenges persist. These challenges include adequately supporting the visiting faculty; pairing them with Rwandan faculty (twinning); ensuring strong communication and coordination among stakeholders; addressing mismatches in priorities between donors and implementers; the execution of a sustainability strategy; and the decision by one of the donors not to renew funding beyond March 2017. Over the next 2 academic years, it is critical for the sustainability of the 22 training programs supported by the HRH Program that the health-related Schools at the CMHS significantly scale up recruitment of new Rwandan faculty. The HRH Program can serve as a model for other training initiatives implemented in countries affected by a severe shortage of health professionals. Highlights Commentaries Published on this Paper The Human Resources for Health Program in Rwanda – Reflections on Achievements and Challenges; Comment on “Health Professional Training and Capacity Strengthening Through International Academic Partnerships: The First Five Years of the Human Resources for Health Program in Rwanda” Abstract| PDF Reflections on Health Workforce Development; Comment on “Health Professional Training and Capacity Strengthening Through International Academic Partnerships: The First Five Years of the Human Resources for Health Program in Rwanda” Abstract| PDF Authors ' Response to the Commentaries The Human Resources for Health Program in Rwanda: A Response to Recent Commentaries Abstract| PDF Keywords Health Professional Training Human Resource for Health Institutional Capacity Strengthening Academic Partnerships Rwanda Main Subjects Organisation Studies Full Text " Watch the Video Summary " References Files XML PDF 1.59 M History Statistics PDF Download: 5,048 Cancedda, C., Cotton, P., Shema, J., Rulisa, S., Riviello, R., Adams, L. V., Farmer, P. E., Kagwiza, J. N., Kyamanywa, P., Mukamana, D., Mumena, C., Tumusiime, D. K., Mukashyaka, L., Ndenga, E., Twagirumugabe, T., Mukara, K. B., Dusabejambo, V., Walker, T. D., Nkusi, E., Bazzett-Matabele, L., Butera, A., Rugwizangoga, B., Kabayiza, J. C., Kanyandekwe, S., Kalisa, L., Ntirenganya, F., Dixson, J., Rogo, T., McCall, N., Corden, M., Wong, R., Mukeshimana, M., Gatarayiha, A., Ntagungira, E. K., Yaman, A., Musabeyezu, J., Sliney, A., Nuthulaganti, T., Kiernan, M., Okwi, P., Rhatigan, J., Barrow, J., Wilson, K., Levine, A. C., Reece, R., Koster, M., Moresky, R. T., O’Flaherty, J. E., Palumbo, P. E., Ginwalla, R., Binanay, C. A., Thielman, N., Relf, M., Wright, R., Hill, M., Chyun, D., Klar, R. T., McCreary, L. L., Hughes, T. L., Moen, M., Meeks, V., Barrows, B., Durieux, M. E., McClain, C. D., Bunts, A., Calland, F. J., Hedt-Gauthier, B., Milner, D., Raviola, G., Smith, S. E., Tuteja, M., Magriples, U., Rastegar, A., Arnold, L., Magaziner, I., & Binagwaho, A. (2018). Health Professional Training and Capacity Strengthening Through International Academic Partnerships: The First Five Years of the Human Resources for Health Program in Rwanda. International Journal of Health Policy and Management, 7(11), 1024-1039. doi: 10.15171/ijhpm.2018.61 Corrado Cancedda; Philip Cotton; Joseph Shema; Stephen Rulisa; Robert Riviello; Lisa V. Adams; Paul E. Farmer; Jeanne N. Kagwiza; Patrick Kyamanywa; Donatilla Mukamana; Chrispinus Mumena; David K. Tumusiime; Lydie Mukashyaka; Esperance Ndenga; Theogene Twagirumugabe; Kaitesi B. Mukara; Vincent Dusabejambo; Timothy D. Walker; Emmy Nkusi; Lisa Bazzett-Matabele; Alex Butera; Belson Rugwizangoga; Jean Claude Kabayiza; Simon Kanyandekwe; Louise Kalisa; Faustin Ntirenganya; Jeffrey Dixson; Tanya Rogo; Natalie McCall; Mark Corden; Rex Wong; Madeleine Mukeshimana; Agnes Gatarayiha; Egide Kayonga Ntagungira; Attila Yaman; Juliet Musabeyezu; Anne Sliney; Tej Nuthulaganti; Meredith Kiernan; Peter Okwi; Joseph Rhatigan; Jane Barrow; Kim Wilson; Adam C. Levine; Rebecca Reece; Michael Koster; Rachel T. Moresky; Jennifer E. O’Flaherty; Paul E. Palumbo; Rashna Ginwalla; Cynthia A. Binanay; Nathan Thielman; Michael Relf; Rodney Wright; Mary Hill; Deborah Chyun; Robin T. Klar; Linda L. McCreary; Tonda L. Hughes; Marik Moen; Valli Meeks; Beth Barrows; Marcel E. Durieux; Craig D. McClain; Amy Bunts; Forrest J. Calland; Bethany Hedt-Gauthier; Danny Milner; Giuseppe Raviola; Stacy E. Smith; Meenu Tuteja; Urania Magriples; Asghar Rastegar; Linda Arnold; Ira Magaziner; Agnes Binagwaho. "Health Professional Training and Capacity Strengthening Through International Academic Partnerships: The First Five Years of the Human Resources for Health Program in Rwanda". International Journal of Health Policy and Management, 7, 11, 2018, 1024-1039. doi: 10.15171/ijhpm.2018.61 HARVARD Cancedda, C., Cotton, P., Shema, J., Rulisa, S., Riviello, R., Adams, L. V., Farmer, P. E., Kagwiza, J. N., Kyamanywa, P., Mukamana, D., Mumena, C., Tumusiime, D. K., Mukashyaka, L., Ndenga, E., Twagirumugabe, T., Mukara, K. B., Dusabejambo, V., Walker, T. D., Nkusi, E., Bazzett-Matabele, L., Butera, A., Rugwizangoga, B., Kabayiza, J. C., Kanyandekwe, S., Kalisa, L., Ntirenganya, F., Dixson, J., Rogo, T., McCall, N., Corden, M., Wong, R., Mukeshimana, M., Gatarayiha, A., Ntagungira, E. K., Yaman, A., Musabeyezu, J., Sliney, A., Nuthulaganti, T., Kiernan, M., Okwi, P., Rhatigan, J., Barrow, J., Wilson, K., Levine, A. C., Reece, R., Koster, M., Moresky, R. T., O’Flaherty, J. E., Palumbo, P. E., Ginwalla, R., Binanay, C. A., Thielman, N., Relf, M., Wright, R., Hill, M., Chyun, D., Klar, R. T., McCreary, L. L., Hughes, T. L., Moen, M., Meeks, V., Barrows, B., Durieux, M. E., McClain, C. D., Bunts, A., Calland, F. J., Hedt-Gauthier, B., Milner, D., Raviola, G., Smith, S. E., Tuteja, M., Magriples, U., Rastegar, A., Arnold, L., Magaziner, I., Binagwaho, A. (2018). 'Health Professional Training and Capacity Strengthening Through International Academic Partnerships: The First Five Years of the Human Resources for Health Program in Rwanda', International Journal of Health Policy and Management, 7(11), pp. 1024-1039. doi: 10.15171/ijhpm.2018.61 VANCOUVER Cancedda, C., Cotton, P., Shema, J., Rulisa, S., Riviello, R., Adams, L. V., Farmer, P. E., Kagwiza, J. N., Kyamanywa, P., Mukamana, D., Mumena, C., Tumusiime, D. K., Mukashyaka, L., Ndenga, E., Twagirumugabe, T., Mukara, K. B., Dusabejambo, V., Walker, T. D., Nkusi, E., Bazzett-Matabele, L., Butera, A., Rugwizangoga, B., Kabayiza, J. C., Kanyandekwe, S., Kalisa, L., Ntirenganya, F., Dixson, J., Rogo, T., McCall, N., Corden, M., Wong, R., Mukeshimana, M., Gatarayiha, A., Ntagungira, E. K., Yaman, A., Musabeyezu, J., Sliney, A., Nuthulaganti, T., Kiernan, M., Okwi, P., Rhatigan, J., Barrow, J., Wilson, K., Levine, A. C., Reece, R., Koster, M., Moresky, R. T., O’Flaherty, J. E., Palumbo, P. E., Ginwalla, R., Binanay, C. A., Thielman, N., Relf, M., Wright, R., Hill, M., Chyun, D., Klar, R. T., McCreary, L. L., Hughes, T. L., Moen, M., Meeks, V., Barrows, B., Durieux, M. E., McClain, C. D., Bunts, A., Calland, F. J., Hedt-Gauthier, B., Milner, D., Raviola, G., Smith, S. E., Tuteja, M., Magriples, U., Rastegar, A., Arnold, L., Magaziner, I., Binagwaho, A. Health Professional Training and Capacity Strengthening Through International Academic Partnerships: The First Five Years of the Human Resources for Health Program in Rwanda. International Journal of Health Policy and Management, 2018; 7(11): 1024-1039. doi: 10.15171/ijhpm.2018.61
https://www.ijhpm.com/article_3524.html
Seavey v. Erickson, No. 36356 - Minnesota - Case Law - VLEX 894692683 0: [object Object]. 1: [object Object]. 2: [object Object]. 3: [object Object]. 4: [object Object]. 5: [object Object] Seavey v. Erickson, No. 36356 <table><tbody><tr><td> Court</td><td> Supreme Court of Minnesota (US)</td></tr><tr><td> Writing for the Court</td><td> KNUTSON; FRANK T. GALLAGHER</td></tr><tr><td> Citation</td><td> 244 Minn. 232,52 A.L.R.2d 1144,69 N.W.2d 889</td></tr><tr><td> Parties</td><td> , 52 A.L.R.2d 1144 Gerald SEAVEY, a minor, by Clifford K. Ellis, his guardian ad litem, Respondent, v. Dwayne ERICKSON and Clifford Seavey, defendants and third-party-plaintiffs, Respondents, Farmers Insurance Exchange, third-party defendant, Appellant. Clifford SEAVEY, plaintiff, Respondent, v. FARMERS INSURANCE EXCHANGE, et al., Defendants, Farmers Insurance Exchange, Appellant.</td></tr><tr><td> Decision Date</td><td> 01 April 1955</td></tr><tr><td> Docket Number</td><td> No. 36356</td></tr></tbody></table> Page 889 69 N.W.2d 889 244 Minn. 232, 52 A.L.R.2d 1144 Gerald SEAVEY, a minor, by Clifford K. Ellis, his guardian ad litem, Respondent, v. Dwayne ERICKSON and Clifford Seavey, defendants and third-party-plaintiffs, Respondents, Farmers Insurance Exchange, third-party defendant, Appellant. Clifford SEAVEY, plaintiff, Respondent, v. FARMERS INSURANCE EXCHANGE, et al., Defendants, Farmers Insurance Exchange, Appellant. No. 36356. Supreme Court of Minnesota. April 1, 1955. Rehearing Denied May 12, 1955. Page 890 Syllabus by the Court. 1. Where it has been established that it is the custom and practice of an insurer to give notice of the time of payment of a renewal premium and knowledge of such custom is acquired by an insured in dealings with the insurer, the insured has a right to rely on such notice, and, in the absence thereof, the policy may not be terminated or forfeited without giving the insured notice that such custom has been abandoned. 2. If, in negotiations or transactions with the insured, after knowledge of facts permitting a forfeiture, the insurer recognizes the continued validity of an insurance policy or does acts based thereon, the forfeiture is, as a matter of law, waived. 3. Where an insurer, after knowledge of the total destruction of the insured property, accepts and retains the premium due on the policy, it will be deemed to have waived a forfeiture of the policy. [244 Minn. 233] Freeman, Larson & Peterson and M. W. Gaughan, Minneapolis, Henry M. Gallagher, Waseca, for appellant. Baudler & Baudler, Austin, Moonan, Moonan, Friedel & Senn, Waseca, for respondents. KNUTSON, Justice. These two cases were tried together, and, by stipulation of the parties, they are treated as one appeal here although separate appeals have been taken from orders of the trial court denying new trials in both cases. The appeals in both cases involve the validity of a certain policy of insurance covering liability and property damage and collision on an automobile owned by Clifford Seavey. On November 4, 1950, Clifford Seavey applied for a policy of liability and property damage insurance on a 1941 Mercury automobile. On November 13, 1950, he received such policy bearing No. 7873891, effective as of 2:15 p.m. on November 4, 1950, and good for six months to May 4, 1951. For convenience we shall refer to this policy as policy A. On January 8, 1951, the coverage on this policy was changed to a 1946 Ford automobile, and on July 6, 1951, it was changed to a 1951 Ford. On March 25, 1952, Clifford borrowed some money on the automobile from the First National Bank of Austin, and, upon application Page 891 of the bank, collision and comprehensive coverage was added to the policy. The policy is in the usual form of such insurance and contains, among other things, the following provisions: '(18) Changes 'Notice to any agent or knowledge possessed by any agent or by any other person shall not effect a waiver or a change in any part of this policy or estop the Exchange from asserting any right under [244 Minn. 234] the terms of this policy; nor shall the terms of this policy be waived or changed, except by endorsement issued to form a part of this policy, signed for Farmers Insurance Exchange, by an executive officer of its attorney-in-fact, the Farmers Underwriters Association. '(22) Reciprocal Provisions 'The entire policy shall automatically and immediately become canceled and void upon the expiration date of any current term, if the named insured defaults in making payments of amounts required to maintain the premium deposit.' For some years prior to the issuance of policy A it has been the custom and practice of the insurer to issue three notices in connection with the payment of a renewal premium. The first was mailed to the insured about three weeks to 25 days before the premium was due. The pertinent portions of it read as follows: 'Farmers Insurance Exchange 'Semi-Annual Premium Notice 'St.--Dist. --Local--Policy Number--Comp.or F & T-Collision-Other Cov. PleasePay Correct Amount Due BI & PD 'If all drivers in household are 25 years or older BI & PD rate is: and your Total Premium Due is: 'If you or any driver in household is under 25 years old--BI & PD rate is: and your Total Premium Due is: 'Keep This Copy--It is Your Record of Payment 'Payment of this semi-annual premium at this office on or before the Due Date shown below, renews your insurance for the succeeding six months period. 'Your Cancelled Check or Money Order Stub will be your Receipt 'Renewal Date 'Post Office Box 2179, Kansas City, Missouri.' [244 Minn. 235] The second notice was mailed to the insured about nine days after the renewal premium was due. The material portions of this notice read: 'Farmers Insurance Exchange 'Please return this notice with your payment 'Policy Number-St. -Dist.-Local-Due Date 'If all drivers of your car in household are 25 years or older--your total amount due is: 'Please Pay Correct Amount Page 892 'If you or any driver of your car in household is under 25 years old--your total amount due is: 'Doubtless you will want to be advised that the due date of your premium has passed and payment has not yet been received in this office. Assuming this is due to an oversight, we are extending time for payment as indicated in the next paragraph. If payment is received before midnight of the fifteenth day after the due date shown above, your policy will be reinstated as of its original due date without any interruption. If not, your policy will remain in a lapsed state as of the original premium due date. We believe you will want to take advantage of this provision and remit your premium at once. 'If payment has already been made, please disregard this notice. 'Farmers Insurance Exchange Farmers Underwriters Association, Attorney-in-Fact '(signed) T. E. Leavey President' The third and final notice was sent about three weeks or 25 days after the due date, and it reads as follows: [244 Minn. 236] 'Farmers Insurance Exchange 'To Reinstate: Please Pay Correct Amount 'If all drivers of your car in household are 25 years or older--your total amount due is: 39.24 'If you or any driver of your car in household is under 25 years old--your total amount due is: 39.24 'May we suggest that you contact your agent and arrange for reinstatement of this policy? Reinstatement fee must be added after sixty days. 'Surely you agree that it is extremely hazardous to be without insurance protection. To be provided the opportunity of providing you with maximum protection is the purpose of this organization. 'Sincerely yours, '(signed) P. J. Chrisman. 'P. J. Chrisman Vice President in Charge of Sales.' It is conceded that the first notice mentioned above was not sent to the insured in this case prior to May 4, 1952, the premium date. The insurer claims that such notice was not sent for the reason that, when coverage was changed by the addition of collision coverage, it sent the insured an endorsement showing such change in coverage which also included a statement as to the amount of premium which would be due. Such endorsement was used in place of the usual notice where coverage had been changed within a certain period prior to the due date. The insured claims that he did not receive the second notice. Based on its practice in sending out notices, insurer claims that it did mail such notice. There was no direct evidence that it actually was mailed. A copy of the notice customarily was sent to insurer's agent.He Page 893 could not find such copy in his files. Based on [244 Minn. 237] this evidence, the court found that the notice was not mailed and that the insured did not receive it. The third or final notice was mailed on June 3 and received by the insured on June 5. The home office of the insurance company is in Los Angeles, California. All its business in this area is supervised by its branch office in Kansas City, Missouri. The officers of the company at Kansas City have full authority to act for it in any business transactions in the area under its control. For about 18 years prior to the time here involved, Waldo E. Johannsen was the district agent for the company in Austin, Minnesota. He had authority to collect premiums and to endorse checks made out to the company. It was his practice to deposit checks and other premiums paid and then remit to the company the aggregate collected by a check drawn on the account to which he had deposited the premium payments. The claim office of the company for servicing this area was located in Minneapolis. The insured had done business with the company through Johannsen since about 1947. In addition to policy A he had other policies on other cars and trucks over this period of time and was familiar with the company's practice of sending out notices through his dealings with such policies. The premium due on policy A on May 4, 1951, was paid and accepted by the company on May 22, 1951. The premium due on November 4, 1951, was paid in October prior to the due date. The premium due May 4, 1952, was not paid when due. During the early hours of June 4, 1952, the automobile covered by policy A, while being driven by defendant Dwayne Erickson with the owner's consent, was completely demolished when it was run into a bridge abutment. Shortly after the accident, the insured called Johannsen on the telephone and made arrangements to meet him as soon as he opened his office. The insured then paid Johannsen the sum of $39.24 by check, representing a premium of $15.69 for liability and property damage insurance and $23.55 for collision and comprehensive coverage. The check was deposited in the company account. Johannsen had full knowledge of the accident when he took the check. He gave the insured a receipt reading: 'Farmers Insurance Group 'Receipt No. C832567 'Time 9:15 PM Date 6/4/1952 'Rec'd From Clifford S. Seavey 'Street Address R. R. 1 'City State Austin Minn. 'Due Date 37 practice notes Florsheim v. Travelers Indem. Co. of Illinois, No. 79-87 United States United States Appellate Court of Illinois August 9, 1979 ...Commercial Union Insurance Co. of America v. Great American Insurance Co. (1973), 214 Va. 410, 200 S.E.2d 560; Seavey v. Erickson (1955), 244 Minn. 232, 69 N.W.2d 889.) Nevertheless, to establish an estoppel the insured must show that it was in some manner misled by the acts or statements o...... Sanborn v. Maryland Cas. Co., No. 51175 United States United States State Supreme Court of Iowa January 14, 1964 ...Hanover Ins. Co. v. McLoney & Sons, D.C., 205 F.Supp. 49; Hully v. Aluminum Co. of America, D.C., 143 F.Supp. 508; Seavey v. Erickson, 244 Minn. 232, 69 N.W.2d 889, 52 A.L.R.2d Page 764 Plaintiff, as did the trial court, relies heavily on Seavey v. Erickson, supra. We believe it supports th...... Blazek v. North Am. Life & Cas. Co., No. 37131 United States Supreme Court of Minnesota (US) December 6, 1957 ...Minn. 451, 270 N.W. 150. And see, Engstrom v. Farmers & Bankers Life Ins. Co., 230 Minn. 308, 41 N.W.2d 422. 28 See, Seavey v. Erickson, 244 Minn. 232, 69 N.W.2d 889, 52 A.L.R.2d 1144, and Vorlicky v. Metropolitan Life Ins. Co., 206 Minn. 34, 287 N.W. 109. 29 Lindskog v. Equitable Life Assu...... Oster v. Riley, No. 40042 United States Supreme Court of Minnesota (US) March 31, 1967 ...or otherwise. See, 7 Appleman, Insurance Law and Practice, § 4266; Glens [276 MINN 282] Falls Ind. Co. v. D. A. Swanstrom Co., 203 son, 244 Minn. 232, 69 N.W.2d 889, 52 A.L.R.2d It is our opinion that the decision of the Industrial Commission should be affirmed. Petitioner is allowed $250 a...... 37 cases Florsheim v. Travelers Indem. Co. of Illinois, No. 79-87 United States United States Appellate Court of Illinois August 9, 1979 ...Commercial Union Insurance Co. of America v. Great American Insurance Co. (1973), 214 Va. 410, 200 S.E.2d 560; Seavey v. Erickson (1955), 244 Minn. 232, 69 N.W.2d 889.) Nevertheless, to establish an estoppel the insured must show that it was in some manner misled by the acts or statements o...... Sanborn v. Maryland Cas. Co., No. 51175 United States United States State Supreme Court of Iowa January 14, 1964 ...Hanover Ins. Co. v. McLoney & Sons, D.C., 205 F.Supp. 49; Hully v. Aluminum Co. of America, D.C., 143 F.Supp. 508; Seavey v. Erickson, 244 Minn. 232, 69 N.W.2d 889, 52 A.L.R.2d Page 764 Plaintiff, as did the trial court, relies heavily on Seavey v. Erickson, supra. We believe it supports th...... Blazek v. North Am. Life & Cas. Co., No. 37131 United States Supreme Court of Minnesota (US) December 6, 1957 ...Minn. 451, 270 N.W. 150. And see, Engstrom v. Farmers & Bankers Life Ins. Co., 230 Minn. 308, 41 N.W.2d 422. 28 See, Seavey v. Erickson, 244 Minn. 232, 69 N.W.2d 889, 52 A.L.R.2d 1144, and Vorlicky v. Metropolitan Life Ins. Co., 206 Minn. 34, 287 N.W. 109. 29 Lindskog v. Equitable Life Assu...... Oster v. Riley, No. 40042 United States Supreme Court of Minnesota (US) March 31, 1967 ...or otherwise. See, 7 Appleman, Insurance Law and Practice, § 4266; Glens [276 MINN 282] Falls Ind. Co. v. D. A. Swanstrom Co., 203 son, 244 Minn. 232, 69 N.W.2d 889, 52 A.L.R.2d It is our opinion that the decision of the Industrial Commission should be affirmed. Petitioner is allowed $250 a......
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Midland Radio 710150B VHF Base Station/Repeater User Manual users manual User manual instruction guide for VHF Base Station/Repeater 710150B Midland Radio Corporation. Setup instructions, pairing guide, and how to reset. Midland Radio 710150B VHF Base Station/Repeater User Manual users manual Midland Radio Corporation VHF Base Station/Repeater users manual users manual Download: Mirror Download [FCC.gov] Document ID 134158 Application ID bGt+z6XoGCLgZuv2bwAn0w== Document Description users manual Short Term Confidential No Permanent Confidential No Supercede No Document Type User Manual Display Format Microsoft Word - pdf Filesize 76.35kB (954369 bits) Date Submitted 2001-01-26 00:00:00 Date Available 2001-01-26 00:00:00 Creation Date 2001-01-26 15:09:47 Producing Software Acrobat Distiller 4.0 for Windows Document Lastmod 2001-01-26 15:09:48 Document Title users manual OPERATORS MANUAL KYODO KG510 BASE/REPEATER KYODO KG510 OPERATORS MANUAL CONTENTS SECTION PAGE INTRODUCTION PRODUCT DESCRIPTION 2.1 Features 2.2 Product Description 2.3 Standard Inclusions 134158 DESCRIPTION CONTROLS, INDICATORS, & CONNECTORS 3.1 Front Panel Controls 3.2 Rear Panel Connectors OPERATION 5-7 4.1 Installation and Programming 4.2 Basic Operation 4.2.1 Switch On 4.2.2 Adjust the Volume Setting 4.2.3 Adjust the Squelch Setting 4.2.4 Select the Channel 4.2.5 Receiving 4.2.6 Transmitting 4.3 Front Panel Operation 4.3.1 Keypad Operation 4.3.2 Keypad Operation using the SHIFT Key 10 4.3.3 Changing Channels 11 4.4 Signalling 11 4.4.1 5-Tone Signalling 11 4.4.1.1 Available Tones 11 4.4.1.2 Entering 5-Tone Encoding Sequences 11 4.4.1.3 Recalling the Last Encode Sequence 12 4.4 2 DTMF Signalling 12 4.4.2.1 Available Tones 12 4.4.2.2 DTMF Tone Entry 12 Page #2 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL CONTENTS SECTION 134158 DESCRIPTION PAGE 4.4.2.3 Redialling with DTMF 13 4.4.2.4 Restoring the Last DTMF Numbers to the LCD Display 13 4.4 3 Single Tone Encoding 13 4.4.4 Kill Signalling 14 4.4.4.1 Kill Signalling Operation 14 4.5 Channel Scanning 15 4.5.1 All Channel Scan Operation 15 4.5 2 Program Channel Scan Operation 16 4.5.3 Exiting Scan Modes 16 4.5.4 Priority Scanning 16 4.5.5 Removing Channels from Scan List 17 4.5.6 Restoring Channels to the Scan List 17 4.6 Locking the Key Pad 17 4.7 Changing Tone Signalling Systems 18 4.8 Displaying Channel Information 18 4.9 Displaying Received Tone Frequencies 19 4.10 Bar Graph Displays 20 4.11 LCD Display Back Light 20 4.12 Transmit Power Change 20 4.13 Calling Party ID Display 21 4.14 Displaying any Radio's ID Number 21 4.15 Emergency Caller Display 22 4.16 Automatic Transmit in Repeater Mode 22 4.17 TX Test Mode 23 4.18 Key Pad Test Mode 23 4.19 Frequency Band Test Mode 24 4.20 Starting Message 24 4.21 Serial Number Display 25 4.22 EEPROM Data Check Mode 25 4.23 Hardware Error Detection 26 4.24 RS232C Communications Error Messages 26 Page #3 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 1.0 INTRODUCTION Thank you for purchasing a KYODO KG510 Base or Repeater. We trust that it will operate reliably and give you years of service. If not, or if you wish to suggest ways of improving the KG510's operation, or features, we would welcome your comments. 2.0 FEATURES & PRODUCT DESCRIPTION 2.1 Features Simplex or two frequency Duplex operation EEPROM programmable with a PC computer Single Channel and 99 Channel Versions available Full Dot Matrix Liquid Crystal Display All FM Frequency Bands from 30 to 520 MHz Front Facing Speaker Transmit Time Limiter to prevent channel jamming TX and RX Encryption Two Channel Scanning Modes 5 Tone Encoder & Decoder plus DTMF Encoder & Decoder 22, 26, or 35 MHz switching bandwidth (model dependant) 2.2 Up to 99 channels with Channel Labels Two-Stage Front End allows mixed Simplex and Duplex operation Channel selectable Wide or Narrow channel spacing CTCSS/DCS on a per channel basis 5 X 4 Keypad for Channel Change etc 2RU Equipment Cabinet Step-Up VCO Voltage for Superior Selectivity Low Stand-by Current is ideal for Solar Installations Watch Dog Timer Product Description The Kyodo KG510 transceivers represent a quantum advance on the previous rugged & time proven KG110 transceiver. They comprise of separate modules all housed within one 2RU equipment cabinet. The receiver, the transmitter, and the PA Unit are each enclosed within their own diecast housing, that are then directly mounted on the large upper heat-sink. A µProcessor controlled interface module controls the channel selection, LCD Display, timers, interfaces, and signalling features. Models are available for all FM commercial and military frequency bands from 30 MHz to 520 MHz, with channel selectable 12.5, 20, 25, or 30KHz channel spacing arrangements. The RF Power Output is 1 - 50 Watts on a continuous duty basis. The CTCSS module supports all EIA tones. All tones and different encode and decode tones can be set on a per channel basis during radio programming. The KG510 includes 5 tone Selective Calling encoder/decoder with non-predictive decoder, as well as a DTMF encoder, and voice encryption. It supports normal all channel scanning and programmed channel scanning for base use. The KG510 is fitted with a large full dot matrix LCD that is used to display the Channel Numbers & Names, frequency & tone programmed information, and signalling information. All user interface keys and knobs are conveniently located on the front of the radio. All user entered functions are easily activated in a logical manner via the keypad. The KG510 is supplied with an "N" Type connector for the transmitter, and a TNC Connector for the Receiver to allow easy connection to the diplexer or feeder cables. The rear panel includes a 9 way D sub connector for fitment of an external shared tone panel. Also included is a 25 way D sub connector that enables external interface to other radios or control equipment. 134158 Page #4 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 2.3 Standard Inclusions The KG510 transceiver is supplied complete with the following items: KG510 transceiver DC Cable Operators Manual KD561 Hand Microphone 3.0 CONTROLS, INDICATORS, & CONNECTORS 3.1 134158 Front Panel Controls 1. Headphone Socket This socket is provided to allow users to listen to the KG510 using headphones. Plugging a headphone into this socket will disconnect the built-In speaker. It does NOT include a microphone input, or TX PTT facility. 2. High TX Power This is a service point and is not used by the radio operators 3. Low TX Power This is a service point and is not used by the radio operators 4. Loud Speaker* The receiver audio signals are heard from this speaker (provided that the volume setting is loud enough and provided that the speaker has not been muted by one of the tone signalling formats. 5. Repeater Mode Indicator LED The Repeater Mode Indicator LED will illuminate "REP" in Yellow colour when the selected channel has been programmed for Repeater operation. This LED is NOT illuminated on any channel that is programmed to operate in Base mode. 6. Alarm Mode Indicator LED The Alarm Mode Indicator LED will illuminate (Flashing) "ALM" in Orange colour whenever the transceiver detects a fault in the receiver module, the transmitter module, or the PA module on the selected channel. Page #5 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 7. Transmit Mode Indicator LED The Transmit Mode Indicator LED will illuminate "TX" in Red colour whenever the KG510 is transmitting. 8. Busy Mode Indicator LED The Busy Mode Indicator LED will illuminate "RX" in Green colour whenever the KG510 receives a carrier signal on the selected channel that is greater then the Squelch setting. 9. Keypad* The 5x4 key Keypad is used to enter channel selection, tone information, and other data into the KG510. Specific key sequences are described fully in section 4 of this document. It includes the following keys: CH, SCAN, MON, SHIFT, 1, 2, 3, 4, 5, 6, 7, 8, 9, 0, , #, A, B, C, and D. 10. Volume Control* The Volume Control is used to set the audio output level from the loudspeaker. Rotate this knob clockwise to increase the audio level, or counter-clockwise to reduce the audio level. 11. Squelch Control* The Squelch Control is used to set the squelch threshold. Select a channel that is not being used and slowly rotate this knob clockwise until the annoying background noise ceases. It may be desirable to rotate this knob clockwise slightly past the squelch threshold to compensate for varying background noise levels. 12. Power ON/OFF Switch The Power ON/OFF Switch is used to switch the KG510 "ON" or "OFF". Press this knob to switch the KG510 "ON". Press this knob again to switch the KG510 "OFF". This knob is slightly more depressed when in the "ON" position. 13. Power On Indicator LED The Power ON Indicator LED will illuminate in Green colour whenever the Power ON/OFF switch is switched to the "ON" position. 14. Liquid Crystal Display (LCD)* The LCD comprises of four (4) lines each of which is capable of displaying twenty-one (21) characters. The first line, in normal operating condition, displays the strength of the signal being received on the selected channel as a bar graph. The second line displays the strength of the transmitting power as a bar graph. The third line displays the selected channel number (up to four characters) in the first five left hand character spaces, and displays the channel name (up to eight characters) in the next eight character spaces. The following characters may be used in the channel name: 0-9, A-Z, a-z, / + - # ! $ % ( ) = [ ] < > ? and space This area of the LCD is left blank when channel names are not used. 134158 Page #6 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL The six character spaces on the right hand side of this line are used to display status symbols as follows: a. The monitor status. --- symbol is b. The key lock status. --- symbol is c. The tone encode status. --- symbol is ϕ d. The scan mode status. e. The high power transmit status. --- symbol is f. The [SHIFT] key status. --- symbol is ---This symbol is displayed whenever the [SHIFT] key is held depressed. The fourth line displays (in the left hand four character spaces) the type of tone signalling system selected by the user. e.g. "5TON" means 5 Tone signalling while DTMF means Dual Tone Multi Frequency signalling. The right hand sixteen character spaces are used to display data that the user enters (e.g. 5 Tone calling sequences). These character spaces are also used by the KG510 to display messages and information directed to the user. 15. Microphone Input Socket Connect the supplied Kyodo KD561 microphone into this socket. * Not used on the Single Channel Model 3.2 Rear Panel Connectors 16. 17. 18. 19. 20. 21. 22. 134158 25 way External Options Connector 9 way Programming Connector DC Input Fuse Holder 3 way DC Input Socket TX/Antenna Connector (N type) Ventilation Slots RX Connector (BNC type) Page #7 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.0 OPERATION 4.1 Installation and Programming As the KG510 can be installed to operate as either a Base Station or as a Repeater, some of the instructions in this document may apply to one application only, some may apply in both cases, while others may only apply if the particular function has been enabled during programming of the KG510. The KG510 must be programmed before it will operate correctly. This is best done by the equipment supplier or a competent radio tradesman. They will require the Kyodo 51BS programming software to do this correctly. It is important that the KG510 be correctly installed at its working location. It is recommended that this be done by a competent radio tradesman. As a minimum, it is necessary to: Connect the DC Input power lead to a suitable 13.8 Volt Regulated DC Power supply that • has sufficient capacity. (Ensure that the DC Polarity is correct). Connect the two antenna connectors to suitable antennas. (Ensure that the VSWR of the • antennas is correct). Insert the Kyodo KD561 Microphone into the microphone connector on the front panel. • 4.2 134158 Basic Operation 4.2.1 Switch On Switch the KG510 "ON" by pressing the knob (12) and then check that the LED indicator (13) is illuminated. 4.2.2 Adjust the Volume Setting Rotate the Volume Knob (10) clockwise (from the fully counterclockwise position) until the audio level from the speaker is suitable. 4.2.3 Adjust the Squelch Setting Rotate the Squelch Knob clockwise (from the fully counter clockwise position) slowly until the background noise can no longer be heard. It is wise to slightly rotate the knob further in the clockwise direction (so that variations in the background noise level do not "break" the squelch setting and cause annoying squelch noises to be heard from the speaker). 4.2.4 Select the Channel Select the required channel by pressing the [SHIFT] key followed by the channel number keys within two seconds. E.g. [SHIFT] + [0] + [1] to select channel #1. The LCD Display should now display CH01 and (if programmed with a channel label) the channel name: "CH01 Kyodo-co". 4.2.5 Receiving You should now be able to hear any radio traffic that occurs on channel #1 on the KG510. It may be necessary to further slightly adjust the Volume setting to suit your listening requirements. 4.2.6 Transmitting Depending on the legal requirements in your country, and the operating requirements within your organisation, it may be necessary to announce your Call Sign, and will probably be necessary to announce the Call Sign of the party you are calling at the start of your transmission. When transmitting, it is necessary to hold the microphone about 75mm (3") from your mouth and speak clearly into the grill of the microphone. It is also necessary to press and hold the Press To Talk (PTT) bar on the side of the microphone depressed while speaking into the microphone. Page #8 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.3 Front Panel Operation This section describes most signalling and other advanced features that are available on the KG510 Transceiver. The availability of some features is dependent on the programming of the transceiver. You may find it worthwhile to discuss these features in detail with your radio supplier to obtain a full understanding of their benefits. 4.3.1 Keypad Operation The Keypad is the interface between the user and the KG510 and is used to enable or disable various functions, and to enter the required data for signalling purposes. (5-Tone) or (DTMF) shown after the described feature indicates that the described feature applies to the particular signalling format. The following keys are used for these purposes: 134158 [0] - [9] Entering new channel numbers Entering the "KILL" password Entering signalling encoding numbers (5-Tone) (DTMF) Entering DTMF numbers (DTMF) [A] Advancing the KG510 to the next higher channel Entering the signalling "A" tone (5-Tone) (DTMF) Encodes the "A" Tone (DTMF) [B] Advancing the KG510 to the next lower channel Entering the signalling "B" tone (5-Tone) (DTMF) Encodes the "B" Tone (DTMF) [C] Entering the signalling "C" tone (5-Tone) (DTMF) Encodes the "C" Tone (DTMF) [D] Entering the signalling "D" tone (5-Tone) (DTMF) Encodes the "D" Tone (DTMF) [ ] Displays the previously entered encode numbers (5-Tone) (DTMF) Encodes the " " -Tone (DTMF) [#] Encodes the signalling numbers that are displayed in the LCD display (5-Tone) (DTMF) Encodes the "#"-Tone (DTMF) [CH] Used with two channel numbers [0] - [9] to change the active channel on the KG510. E.g. [CH]+[9]+[0] will change the active channel to Channel 90 (provided Ch 90 has been programmed into the KG510. [SCN] Used to place the KG510 into the "All-Scan" mode where the KG510 will scan all programmed channels. Pressing the [SCN] key again will cause the KG510 to exit from the "All-Scan" mode. [MON] Switches the KG510 between "Monitor ON" mode and "Monitor OFF" mode and is used to "Un-mute" the radio when using selective calling (depending on the programming of the KG510 transceiver). Page #9 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.3.2 Keypad Operation using the [SHIFT] Key Some of the KG510's features and how it operates can be changed by using the [SHIFT] key. To make these changes, it is necessary to firstly press the [SHIFT] key followed by the other keys within a two second timeframe. The following key sequences are used for these purposes: [SHIFT]+[0] Toggles the tone system between 5-Tone signalling and DTMF signalling. [SHIFT]+[1] Switches the LCD back-light ON or OFF. [SHIFT]+[2] Toggles the transmitting power between High power and Low power. [SHIFT]+[3] Invalid Key. [SHIFT]+[4] Toggles between "Single Tone Encoding" mode and "5-Tone" or "DTMF" signalling mode. [SHIFT]+[5] Invalid Key [SHIFT]+[6] Enters the KILL mode to allow entry of the KILL password. [SHIFT]+[7] Displays the programmed information for the selected (active) channel in the LCD display. [SHIFT]+[8] Locks or Unlocks the KG510's Keypad. [SHIFT]+[9] Toggles the KG510 between "Normal Channel Scanning" mode and "Priority Channel Scanning" mode. [SHIFT]+[A] Restores a channel to the Channel Scanning List. (The user must firstly select the channel to be restored as the active channel). [SHIFT]+[B] Invalid Key [SHIFT]+[C] Indicates to the KG510 that you have entered the last number of a DTMF encoding sequence. [SHIFT]+[D] Invalid Key [SHIFT]+[ ] Deletes the active channel from the Channel Scanning List. [SHIFT]+[#] Will attach the "R-Number" data to the active encode number and transmit the whole sequence. [SHIFT]+[CH] Will start or stop the display of the TX and RX bar graphs in the LCD display. [SHIFT]+[SCN] Will place the KG510 in the Program Scan mode or exit from the Program Scan mode. [SHIFT]+[MON] Invalid Key. 134158 Page #10 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.3.3 Changing Channels To change to another channel, simply press the [CH] key followed by the number of the required channel within two seconds. e.g. To select Channel # 8, press [CH] [0] [8] To select Channel # 99, press [CH] [9] [9] Note that it is always necessary to enter two digits for the Channel Number. The channel # location displayed in the LCD will become blank as soon as the [CH] key is pressed, and the cursor will blink at the location of the channel number, and display the new numbers as they are entered. It is also possible to change channels by using the [A] and [B] keys instead of entering the channel numbers. Pressing the [A] key will advance the channel to the next higher programmed channel, while pressing [B] will advance the channel to the next lower programmed channel. Note that this action will ignore channels that have not been programmed into the KG510. Accordingly, the LCD display may appear to advance more than one channel if the missed channel is not programmed into the KG510. 4.4 Signalling The KG510 includes some very sophisticated signalling capabilities. We suggest that you have your radio supplier conduct some training on the use of these capabilities prior to using them. While it is possible to use these signalling capabilities in both repeater mode, and in base station mode, many will only be useful in practice when the KG510 is used in base station configuration. The KG510 supports the 5-Tone sequential, and/or the DTMF, and the Single Tone signalling formats. The required signalling format(s) must be enabled when the KG510 is programmed. 4.4.1 5-Tone Signalling 4.4.1.1 Available Tones 5-Tone signalling is commonly referred to as Selective Calling (or Selcall) and usually comprises of a series of 5 tones sequentially transmitted or received in accordance with certain international standards. It is possible to use longer sequences to enhance the signalling capabilities and to provide further functions. Accordingly, the KG510 will encode up to sixteen (16) tones and decode up to eight (8) tones. These tones can be any of the following: [0] - [9], and [A] - [D] The most recently entered tone can be recalled and deleted by pressing the [ ] key repeatedly. 4.4.1.2 Entering a 5-Tone Encode Sequence When switched "ON", the KG510 carries out its self-test routine, and then waits ready to accept 5-Tone encode numbers. Accordingly, it is only necessary to enter the required 5Tone digits directly using the keypad, and then pressing the [#] key to transmit the 5-Tone sequence. (Up to sixteen digits can be entered). If it is necessary to enter the "R" number sequence to activate the repeater, the [SHIFT] key must be pressed before pressing the [#] key. If a 5-Tone number is NOT displayed in the LCD, and the [#] key is pressed, then the KG510 will recall the most recent 5-Tone number and transmit it. 134158 Page #11 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.4.1.3 Recalling the last encode sequence Pressing the [ ] will recall the most recent 5-Tone encode sequence and display the sequence in the LCD display. Further presses of the [ ] key will delete the last digit of the sequence until all digits are deleted. In practice users will usually delete the last one or two digits before entering the new digits. 4.4.2 DTMF Signalling 4.4.2.1 Available Tones The following DTMF tones can be used: [0] - [9], [A] - [D], [ ], and [#] NOTE: Tone [B] is NOT available if the "Attach Decode No" field in the DTMF Encode Menu has been set to "ON". Up to sixteen (16) DTMF digits can be encoded in one calling sequence. 4.4.2.2 DTMF Tone Entry There are two methods of entering DTMF tones. The specific tone encoding format is selected during the programming of the KG510 transceiver in the field. 4.4.2.2.1 Attach Decode No. "OFF" format Pressing the PTT lever first automatically selects the DTMF encoding format and allows direct entry of DTMF tones. Hold the PTT lever on the microphone depressed while pressing the required DTMF tones. The tones will be transmitted as the keys are being pressed. 4.4.2.2.2 Attach Decode No. "ON" format Attach Decode No. "ON" automatically encodes the users DTMF decode number after the encode number. This can be used for ANI purposes. Enter the required DTMF tones (up to sixteen tones except "B" tone) and then transmit the total tone sequence (including the users decode number) by pressing the [#] key. All tones will be transmitted in one continuous sequence after pressing the [#] key. Pressing the [ ] key will delete the last entered number. Always confirm that the LCD is clear before proceeding as it may take up to 5 seconds for the tones to be sent. e.g. Assume that your decode number is 12345, and that you wish to encode number 12346. You will input 12346, and then press the [#] key. The KG510 will encode 12346B12345. The called radio will display 12345 in their LCD indicating the calling party's number is 12345. NOTE: The "B" tone is used as the delimiter in this encoding format and therefore CANNOT be used as a DTMF tone. Pressing the [SHIFT] key and then the [#] will encode ONLY the encode number (and not the decode number). 134158 Page #12 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.4.2.3 Redialling with DTMF If during the programming of the KG510, the field has been set to "OFF", the redialling function operates as follows: Press [SHIFT], then press [#] and the KG510 will redial the last encoded DTMF number. If during the programming of the KG510, the field has been set to "ON", the redialling function operates as follows: Press [#] and the KG510 will redial the last encoded DTMF number with the KG510's programmed decode number. Press [SHIFT], and then press [#] and the KG510 will redial the last encoded DTMF number without the KG510's programmed decode number. 4.4.2.4 Restoring the last DTMF number to the LCD Display It is possible to restore the last encoded DTMF number to the LCD display, provided the field has been set to "ON" during the programming of the KG510 transceiver. Confirm that the LCD is NOT displaying any DTMF numbers, then press [✶] and the last encoded DTMF number will be displayed in the LCD display. It is possible to edit this number at this time by pressing the [✶] key (which will erase the last number) or by pressing the required keys to add additional numbers. 4.4.2.5 Encoding DTMF numbers with the 5-Tone system enabled It is possible to enter DTMF numbers even with the 5-Tone system enabled. This function must be enabled during the programming of the KG510 by setting the field in the <5Tone Encode Menu> to "ENABLE". To enter a DTMF number (with 5-Tone signalling enabled), the user must press the PTT lever while entering the first DTMF number. Second and subsequent numbers do NOT require the PTT lever to be pressed provided all numbers are entered within a few seconds (before the display reverts to 5-Tone mode and displays "5TON" in the LCD display). 4.4.3 Single Tone Encoding The KG510 has the ability to encode one of six single tone frequencies for 1, 2, 3, or 4 seconds. This function is enabled during programming of the KG510 by selecting the field in the and setting the encode period. Press the [SHIFT] and the [4] keys to put the KG510 into Single Tone Encoding mode. "S1" and the tone frequency ("xxxxHz") will be displayed in the tone area of the LCD display for about 4 seconds until the KG510 reverts back to the normal signalling mode. While the KG510 is in Single Tone Encoding mode, it is possible to advance to the next tone frequency by pressing the [A] key, or to return to the previous tone by pressing the [B] key. Pressing the [#] key will encode the displayed tone (for the programmed time period) and automatically exits the Single Tone Encoding mode and returns the KG510 to the normal signalling mode. 134158 Page #13 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.4.4 KILL Signalling The KG510 has the ability to transmit a specially coded signalling sequence that will disable ("KILL") another radio. This feature is particularly useful when transceivers become misplaced, are stolen, if they are used in an incorrect manner, or if they are used for the wrong purposes. To prevent accidental or mischievous "KILLING" of radios, several security features are in place. Firstly, the KG510 must have this function enabled during programming. Secondly, the user must know the required password and enter it correctly into the KG510, and, Thirdly, the user must know the required "KILL" number (of the radio to be "KILLED", and enter it correctly into the KG510. The "KILL" password has four numerical digits. [0] to [9]. With 5-Tone signalling systems, the "KILL" number for a particular radio comprises of the radio's decode number + D + the radio's KILL number. With DTMF signalling systems, the "KILL" number for a particular radio comprises of the radio's decode number + A + the radio's KILL number. In the case of DTMF signalling, both the decode number and the KILL number must have more than four digits. 4.4.4.1 Kill Signalling Operation Press [SHIFT] and the press [6] to place the KG510 into the KILL mode. The LCD display will indicate that the KG510 is in the KILL mode RX TX CH01 Kyodo-co Kill Pass -- Enter the required password by entering the correct four digit number. If the password has been correctly entered, the LCD display will show this message: RX TX CH01 Kyodo-co Kill Pass OK Then enter the "KILL" data from the keyboard that comprises of the decode number + D + the KILL number of the radio to be "KILLED". (In the case of DTMF signalling, it will be necessary to substitute the "A" tone instead of the "D" tone). Then press [#] to transmit the data. 134158 Page #14 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL If the incorrect password has been entered, the LCD display will show the following message: RX TX CH01 Kyodo-co Kill Pass NG If you enter the "KILL" data prior to entering the KILL password, and then press the [#] key, the LCD display will show the following message: RX TX CH01 Kyodo-co Input Password If the incorrect password has been entered more than the allowed number of tries, then the KG510 becomes disabled and the following message is displayed in the LCD display: Not Ready In such cases, it is necessary to return the KG510 to your radio supplier to have the KG510 repaired. 4.5 Scanning The KG510 is supplied with two scanning modes. These are All Channel Scan mode in which the KG510 will scan all channels that are programmed into the KG510, and the Program Channel Scan mode in which the KG510 will scan only the channels that have been designated during the programming of the KG510 transceiver. Furthermore, one HIGH priority, and one LOW priority scan channel can be set for each scan mode during the programming of the radio. 4.5.1 All Channel Scan Operation Pressing the [SCAN] key places the KG510 into All Channel Scan mode and the Scan mode symbol " " is displayed in the LCD display. Also the LCD will display "All Scan Mode-in" for two seconds as shown below: RX ====== TX CH01 Kyodo-co • All Scan Mode-in 134158 Page #15 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.5.2 Program Channel Scan Operation Pressing the [SHIFT] and then the [SCAN] key places the KG510 into Program Channel Scan mode and the Scan mode symbol " " is displayed in the LCD display. Also the LCD will display "PRG Scan Mode-in" for two seconds as shown below: RX ====== TX CH01 Kyodo-co • Prg Scan Mode-in 4.5.3 Exiting All Channel Scan and Program Channel Scan modes Pressing the [SCAN] key will take the KG510 out of either scanning mode and return the KG510 to normal mode. The scan symbol " " will be removed from the LCD display and the LCD will display "Scan Mode-out" for two seconds as shown below: RX ====== TX CH01 Kyodo-co Scan Mode-out 4.5.4 Priority Scanning The KG510 allows users to firstly enter the required scanning mode, and then they can enable Priority Scanning for the particular scanning mode chosen. Pressing the [SHIFT] key and then the [9] key places the KG510 into Priority Scanning mode as shown below: RX ====== TX CH01 Kyodo-co • Priority Scan Pressing the [SHIFT] and the [9] keys again will take the KG510 out of Priority Scan mode and return to the Normal Scan mode as shown below: RX ===== TX CH01 Kyodo-co • Normal Scan 134158 Page #16 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.5.5 Removing an Active Channel from the Scan List It is possible to temporarily delete an active channel from the scan list by pressing [SHIFT] and the [ ] key and holding the [SHIFT] and the [ ] keys depressed for more than one second. More than one channel can be deleted from the Scan list, provided that at least one channel remains in the Scan List. A "beep" sound from the radio confirms correct deletion of the channel from the scan list. This function CANNOT be used in the Priority Scan mode. The KG510 automatically restores all channels to their respective scanning list as soon as the KG510 exits from the scan mode. 4.5.6 Restoring Channels to the Scan List Channels can be restored to the scanning list without exiting from the scan mode by pressing the [SHIFT] key and pressing and holding the [A] key depressed for more than one second. This action will restore all channels to the scan list. This action CANNOT be used in the Priority Scan mode. 4.6 Locking the Keypad Pressing the [SHIFT] key and then the [8] key will lock all keys (except the [SHIFT] and [MON] keys) on the KG510's keypad to prevent accidental or inadvertent entry of data. After pressing the [SHIFT] and [8] keys the keypad becomes locked and the Key-Lock symbol is displayed in the LCD display. The display also shows "Key-Lock" for two seconds as shown below: RX ====== TX CH01 Kyodo-co • Key Lock Pressing [SHIFT] and [8] again will Unlock the keypad, remove the Key-Lock symbol from the LCD display, and display "Key-Unlock" in the LCD display for two seconds as shown below: RX ====== TX CH01 Kyodo-co Key Unlock 134158 Page #17 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.7 Changing Tone Signalling Systems It is possible to switch the KG510's tone signalling system among 5-Tone sequential signalling, DTMF signalling and Non(No-Tone system) (providing the field was set to "ENABLE" during the programming of the KG510). Press [SHIFT] and keep depressed the [0] key for more than one second to change among 5-Tone system, DTMF system and Non and indicate new signalling system in the LCD display as follows: RX ====== TX CH01 Kyodo-co System is DTMF Pressing [SHIFT] and pressing the [0] key for more than one second again will change next the signalling system and indicate new signalling system in the LCD display as shown below: RX ======= TX CH01 Kyodo-co System is Non 4.8 Displaying the Channel Information The KG510 can display information pertaining to the selected channel (provided that the field was set to "ENABLE" during the programming of the radio. This information is: The RX frequency of the selected channel. The TX frequency of the selected channel. The channel spacing for the selected channel (Wide or Narrow). The operating mode for the selected channel (Base, Repeater, simplex, duplex) The RX CTCSS/DCS tone for the selected channel (provided CTCSS/DCS has been programmed for use on the selected channel). The TX CTCSS/DCS tone for the selected channel (provided CTCSS/DCS has been programmed for use on the selected channel). The tone encoding format (providing 5-Tone signalling was selected during programming of the KG510). The tone set (providing 5-Tone signalling was selected during programming of the KG510). The ANI mode. The tone decoding set (provided 5-Tone or DTMF signalling was selected during programming of the KG510). The decode number (provided 5-Tone or DTMF signalling was selected during programming of the KG510). 134158 Page #18 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL To view this information in the LCD display, firstly select the required channel. Then press the [SHIFT] key and then the [7] key. You will need to keep the [7] key pressed until the KG510 has cycled through the information steps. This function is NOT available if the field has been set to "DISABLE" during the programming of the KG510. 4.9 Display of Received Tone Frequencies. It is possible to set the KG510 to display the received tone frequencies in the LCD display in the area normally used to display the strength of the received signals. Press [SHIFT] and then press [D] to enable this function. Once enabled, the LCD will show "RCV" in the area of the LCD display that normally shows the strength of the received signal, as well as "Tone Display on" for two seconds as shown below: RCV TX CH01 Kyodo-co Tone Display On Then, whenever a tone frequency is decoded, the frequency number will be displayed in the LCD display to the right of "RCV" as shown below: RCV 12345 TX CH01 Kyodo-co 5TON Pressing the [SHIFT] key and then the [D] key once again will disable this function and return the LCD display to normal as shown below: RX TX CH01 Kyodo-co Tone Display Off 134158 Page #19 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.10 Bar Graph Displays The KG510 will normally show the strength of the received signal to the right of "RX" in the LCD display, and the strength of the transmitted signal to the right of "TX" in the LCD display, both in the form of a bar graph. This function can be disabled by pressing the [SHIFT] key and then the [CH] key. The LCD display will indicate "RX Display Off" and "TX Display Off" as shown below: RX Display Off TX Display Off CH01 Kyodo-co Pressing the [SHIFT] key and then the [CH] key once again will return the KG510 to normal and the LCD display will show the normal bar graph display for both the RX signal strength and TX signal strength. 4.11 LCD Display Back Light The LCD Display has a Back-Light to illuminate the display. It normally switches "ON" whenever any key or the PTT lever is pressed, and will remain illuminated for five seconds after the most recent key press. Some users may prefer the Back-Light to remain illuminated to assist viewing the LCD display in poor viewing situations. Press the [SHIFT] key and then press the [1] key for more than one second and the LCD Back-light will remain illuminated. Once again, press the [SHIFT] key and then press the [1] key for more than one second and the LCD Back-light will revert to normal operation. 4.12 Transmit Power Change It is possible to change the KG510's transmit power from the high power setting to the low power setting from the keypad and vice versa (provided that this function has been enabled during the programming of the KG510). To enable this function, the field must be set to "ENABLE". Press the [SHIFT] key and the [2] key and the KG510 will change from the high transmit power setting to the low transmit power setting, and the " “symbol will be removed from the third line of the LCD display. Press the [SHIFT] key and the [2] key a second time, and the KG510 will change from the low transmit power setting to the high transmit power setting, and the " " symbol will be displayed in the third line of the LCD display. If this function is NOT required, the field must be set to "DISABLE". 134158 Page #20 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.13 Calling Party ID Display The KG510 has the capability to display a calling radio's ID (ANI) number after being called. When the KG510 is called, "CALL" will be displayed on the fourth line of the LCD display (and continue to flash) and the calling radio's ID number will be displayed to the right of "CALL" as shown below: RX TX CH01 Kyodo-co CALL 12346 If the KG510 user presses the [#] key (when "CALL" is flashing and the caller's ID number is displayed), the KG510 will automatically call the identified radio. In the case of 5-Tone signalling systems, this function is enabled in the <5Tone Encode Menu> field, by selecting one of the following parameters: "Encode + B + Decode" "Encode + A.Pause + Decode" "Decode + A.Pause + Encode" "Encode + ANI" In the case of DTMF signalling systems, this function is enabled by setting the field to "ON" during the programming of the KG510. 4.14 Displaying any Radio's ID Number The KG510 has the capability to display any calling radio's ID (ANI) number. When the KG510 receives an ANI number, "DISP" will be displayed on the fourth line of the LCD display (and continue to flash) and the radio's ID number will be displayed to the right of "DISP" as shown below: RX TX CH01 Kyodo-co DISP 1234 In the case of 5-Tone signalling systems, this function is enabled by setting the <5Tone Decode Menu> field to "ON" during the programming of the KG510. In the case of DTMF signalling systems, this function is enabled by setting the field to "ON" during the programming of the KG510. 134158 Page #21 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.15 Emergency Caller Display The KG510 has the ability to accept and display emergency calls from other radios within the radio system This function is enabled by setting the field to "ON" in the <5Tone Decode Menu> or during the programming of the radio. The calling (Emergency) radio must encode its emergency data in the following format: "000" + the calling radio's ID (decode number). This format applies to both 5 Tone and DTMF signalling systems. When the KG510 receives an emergency call, the KG510 will sound a warning tone from the speaker, display "EMG" (flashing) in the fourth line of the LCD display, and display the emergency radio's ID to the right of "EMG" as shown below: RX TX CH01 Kyodo-co EMG 12346 Upon receipt of an emergency call, the KG510 will automatically respond to the emergency radio by sending the emergency radio's ID number to it. If the KG510 user presses the [#] key, the KG510 will resend the emergency radio's ID number. While the KG510 is in the Emergency Mode, all keys (except the [#] key) on the keyboard become disabled. Pressing the [SHIFT] key and the [ ] key will return the KG510 to the normal operating mode. 4.16 Automatic Transmit in Repeater Mode The KG510 can be programmed to automatically repeat valid incoming messages. Firstly, the active channel of the KG510 must be programmed to operate as a repeater. It must then receive a carrier frequency on the designated channel. If the KG510 has been programmed for CTCSS or DCS operation, it must also receive a valid CTCSS or DCS tone. It will then automatically retransmit any received signals. When the KG510 ceases to receive a carrier frequency, or a valid CTCSS or DCS tone, it activates the timer. This will keep the KG510 repeating (for up to 9.9 seconds depending on the programming of the KG510), and allow other users with a valid CTCSS or DCS tone to access the repeater. 134158 Page #22 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.17 TX Test Mode The KG510 is provided with a TX (Transmit) Test Mode. When the KG510 is placed in the TX Test Mode, it will transmit a carrier frequency modulated with a 1KHz tone on the selected active channel. It is possible to change channels while in TX Test Mode. Pressing the [SHIFT] key and then the [B] key places the KG510 in TX Test Mode and displays the message in the LCD as shown below: RX TX CH01 Kyodo-co TXT TX Test Mode-in Pressing the [SHIFT] key and the [B] key a second time will return the KG510 to normal mode and displays the message in the LCD as shown below: RX TX CH01 Kyodo-co TXT TX Test Mode-out 4.18 Keypad Test Mode The KG510 is provided with a Keypad Test Mode that allows the user to electrically test all keypad keys as well as the PTT Key. Holding the [C] key pressed while switching the POWER SWITCH "ON" places the KG510 in Keypad Test Mode and displays the message in the LCD Display as shown below: KEY TEST Please Key-in Then press the keys to be tested one at a time. The respective key will be displayed in the LCD when the key is operating correctly. e.g. If you press the [CH] key, the LCD Display will indicate correct operation as shown below: KEY TEST CH Key Switch the KG510 "OFF" to exit this Keypad Test Mode. 134158 Page #23 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.19 Frequency Band Test Mode It is possible to display the KG510's operating Frequency Band in the LCD display when in Frequency Band Test Mode. Holding the [B] key pressed while switching the POWER SWITCH "ON" places the KG510 in Frequency Band Test Mode and displays the operating Frequency Band in the LCD Display as shown below: > 40D OK "40D" indicates the frequency band for a particular KG510 radio. Switch the KG510 "OFF" to exit the Frequency Band Test Mode. 4.20 Starting Message When the KG510 is Switched "ON", it will display a Starting Message in the LCD display for two seconds. The default Starting Message (using all dots) is shown below: ••••••••••• ••••••••••• • <51BS V095 510>• ••••••••••• A personalised message for your business may be shown as the Starting Message. If you require a personalised message, then it should be entered in the field during the programming of the radio. Such a message is shown below: Kyodo-co Japan <51BS V095 510> 134158 Page #24 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.21 Serial Number Display It is possible to display the KG510's Serial Number in the LCD Display. To do so, the Serial Number must be entered into the field during the programming of the radio. The serial number can be up to eight characters long and can comprise of any of these characters: "A - Z" & "0 - 9". Holding the [D] key pressed while switching the POWER SWITCH "ON" places the KG510 in Serial Number Display Mode and displays the KG510's Serial Number in the LCD Display as shown below: Serial KY000727 Switch the KG510 "OFF" to exit from the Serial Number Display Mode. 4.22 EEROM Data Check Mode As soon as the KG510 is switched "ON", it will automatically read and check all the data in the EEROM. If this check finds damaged or corrupted data, the KG510 will automatically enter the Programming Mode and display the following message in the LCD Display: EROM Data Error Should this happen, it is necessary to return the KG510 to your radio supplier or to a competent radio trades-person who has the facilities to reprogram the KG510. 134158 Page #25 of 26 Pages 26 January, 2001 KYODO KG510 OPERATORS MANUAL 4.23 Hardware Error Detection The KG510 automatically tests for certain hardware faults or failures, and when a fault is found, it will blink the "ALM" LED display above the LCD Display and indicate the nature of the fault in the LCD Display as shown below: RX TX CH01 Kyodo-co RX PLL Error This figure indicates an RX PLL error. RX TX CH01 Kyodo-co TX PLL Error This figure indicates a TX PLL error. RX TX CH01 Kyodo-co PA Error This figure indicates a PA error. Should the KG510 indicate any of these errors, then it is necessary to return the KG510 to your radio supplier or to a competent radio trades-person to have the fault remedied. 4.24 RS232C Communications Error If a fault is encountered during programming of the KG510, one of the following messages may be displayed in the LCD Display: ! Over Run Error ! Framing Error ! Parity Error ! Unknown Command ! Data Unmatch ! Send Error ! Answer Timeout ! Receive Timeout Please switch the KG510 "OFF", and then back "ON", and retry reprogramming the KG510 again, should any of the above error messages be displayed in the LCD Display. 134158 Page #26 of 26 Pages 26 January, 2001 Source Exif Data: File Type : PDF File Type Extension : pdf MIME Type : application/pdf PDF Version : 1.2 Linearized : Yes Create Date : 2001:01:26 15:09:47 Producer : Acrobat Distiller 4.0 for Windows Modify Date : 2001:01:26 15:09:48-05:00 Page Count : 26 EXIF Metadata provided by EXIF.tools FCC ID Filing: O6E710150B Contact Us DMCA
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(PDF) Cholinesterase Inhibitor Donepezil Dilates Cerebral Parenchymal Arterioles via the Activation of Neuronal Nitric Oxide Synthase PDF | An acetylcholinesterase inhibitor donepezil currently is used to treat patients with Alzheimer disease. However, its direct effect on cerebral... | Find, read and cite all the research you need on ResearchGate Article PDF Available Cholinesterase Inhibitor Donepezil Dilates Cerebral Parenchymal Arterioles via the Activation of Neuronal Nitric Oxide Synthase August 2008 Anesthesiology109(1):124-9 DOI: 10.1097/ALN.0b013e31817c0316 Source PubMed Authors: <here is a image 07e13d1066ed3d7a-daa425249d1ae565> Katsutoshi Nakahata Kansai Medical University <here is a image db51436938d2221c-88eba5e3e0c42c82> Hiroyuki Kinoshita Tokushima University Graduate School of Biomedical Sciences <here is a image f2f62089ad6ff61c-d19572ff1996375a> Keiko Hama-Tomioka Keiko Hama-Tomioka <here is a image 7793aab95be6312a-df5463c4b9ff5c88> Yuko Ishida Wakayama Medical University Abstract and Figures An acetylcholinesterase inhibitor donepezil currently is used to treat patients with Alzheimer disease. However, its direct effect on cerebral blood vessels has not been evaluated. The present study was designed to examine whether donepezil induces acute cerebral arteriolar dilation and whether neuronal nitric oxide synthase contributes to this vasodilator response. Brain slices were obtained from neuronal nitric oxide synthase knock-out or C57BL/6J strain (control) mice as well as Wistar rats. Parenchymal arterioles were monitored using videomicroscopy. During constriction to prostaglandin F2alpha (5 x 10 m), donepezil (10-10 m) or acetylcholine (10-10 m) was added. In some experiments, brain slices were treated with a nonselective or a selective nitric oxide synthase inhibitor (N-nitro-L-arginine methyl ester [10 m] and S-methyl-L-thiocitrulline [10 m], respectively). An immunohistochemical analysis was performed using antibodies for neuronal nitric oxide synthase and acetylcholinesterase. Acetylcholine concentration-dependently dilated rat parenchymal arterioles, while S-methyl-L-thiocitrulline as well as N-nitro-L-arginine methyl ester completely abolished this response. Donepezil produced arteriolar dilation, which was inhibited by S-methyl-L-thiocitrulline or N-nitro-L-arginine methyl ester. Donepezil failed to induce arteriolar dilation in the brain slice from the neuronal nitric oxide synthase knock-out mice. Immunohistochemical analysis revealed spatial relationship between neuronal nitric oxide synthase and acetylcholinesterase in the arteriolar wall. Donepezil produces acute vasodilation induced by a selective activation of neuronal nitric oxide synthase in the cerebral parenchymal arterioles. This agent may be capable of enhancing this enzymatic activity directly or via acetylcholinesterase existing on the arteriolar wall. <here is a image f1255259d7e992f4-b9a0a2cbcd4ae900> The representative examples of an arteriole and a venule in the rat brain parenchyma. The arteriole, but not the venule, has a smooth muscle layer. The longer and shorter arrow in each figure demonstrate the external and the internal diameters, respectively. … <here is a image cfc8e34fdb0ee455-77a3783a04315fe8> (A) Vasodilator responses to acetylcholine (10 6 –10 4 M) in the absence or in the presence of N G-nitro-L-arginine methyl ester (10 4 M) in the rat cerebral parenchymal arterioles. (B) Vasodilator responses to donepezil (10 9 –10 8 M) in the absence or in the presence of N Gnitro-L-arginine methyl ester (10 4 M) or S-methyl-L-thiocitrulline (10 5 M) in the rat cerebral parenchymal arterioles. Baseline internal diameter of arterioles were 7.0 1.4 and 6.7 1.5 m for control arterioles and arterioles treated with N G-nitro-L-arginine methyl ester for acetylcholine-induced vasodilation, and 6.2 0.7, 5.9 1.2, and 5.9 0.3 m for control arterioles, arterioles treated with N G-nitro-L-arginine methyl ester, and Smethyl-L-thiocitrulline for donepezil-induced vasodilation, respectively. Data are shown as mean SD. Difference between the control arterioles and the arterioles treated with N G-nitro-L-arginine methyl ester or S-methyl-L-thiocitrulline was statistically significant (* P < 0.05). … <here is a image 7edde0e364b5e1a5-8f33c2e8ad6fed83> Vasodilator responses to (A) donepezil (10 9 –10 8 M) and to (B) sodium nitroprusside (3 10 5 to 3 10 3 M) in the cerebral parenchymal arterioles of neuronal nitric oxide synthase knockout and control mice. Baseline internal diameters of arterioles were (A) 4.2 0.4 and 5.3 0.8 m and (B) 5.5 0.7 and 4.8 0.6 for control and neuronal nitric oxide synthase knock-out mice, respectively. Data are shown as mean SD. Difference between the arterioles of control and neuronal nitric oxide synthase knock-out mice was statistically significant (* P < 0.05). … <here is a image cd014f5662950cce-8b707f547e58918f> A double-color immunohistochemical analysis for the rat brain slice containing the neocortex was performed to determine the localization of neuronal nitric oxide synthase (nNOS, Cy3 stain, white arrows), acetylcholinesterase (AChE, fluorescein isothiocyanate stain, pink arrows), and both (Merged, yellow arrows) as described in Materials and Methods. Hematoxylin and eosin (HE)–stained brain sections (at the bottom) were adjacent to those upper panels. Figure shows representative results from among five different rats, with left and right panel from each pair being from different rats. A scale bar indicates 100 m in length in all pictures. … Figures - uploaded by Yuko Ishida CholinesteraseInhibitorDonepezilDilatesCerebral ParenchymalArterioles via theActivationofNeuronal NitricOxideSynthase KatsutoshiNakahata,M.D.,Ph.D., *HiroyukiKinoshita,M.D.,Ph.D., †KeikoHama-Tomioka,M.D., ‡YukoIshida,Ph.D., § NaoyukiMatsuda,M.D.,Ph.D., 㛳NoboruHatakeyama,M.D.,Ph.D., #MasanoriHaba,M.D., ‡ ToshikazuKondo,M.D.,Ph.D., **YoshioHatano,M.D.,Ph.D. †† Background: Anacetylcholinesteraseinhibitordonepezilcur- rentlyisusedtotreatpatientswithAlzheimerdisease.However, itsdirecteffectoncerebralbloodvesselshasnot beenevaluated. Thepresentstudywasdesignedtoexaminewhetherdonepezilin- ducesacutecerebralarteriolardilationandwhetherneuronalnitric oxidesynthasecontributestothisvasodilatorresponse. Methods: Brainsliceswereobtainedfromneuronalnitric oxidesynthaseknock-outorC57BL/6Jstrain(control)miceas wellasWistarrats.Parenchymalarteriolesweremonitored usingvideomicroscopy.Duringconstrictiontoprostaglandin F 2 ␣ (5 ⴛ10 ⴚ 7 M ),donepezil(10 ⴚ 9 –10 ⴚ 8 M )oracetylcholine (10 ⴚ 6 –10 ⴚ 4 M )wasadded.Insomeexperiments,brainslices weretreatedwithanonselectiveoraselectivenitricoxide synthaseinhibitor(N G -nitro-L-argininemethylester[10 ⴚ 4 M ] andS-methyl-L-thiocitrulline[10 ⴚ 5 M ],respectively).Animmu- nohistochemicalanalysiswasperformedusingantibodiesfor neuronalnitricoxidesynthaseandacetylcholinesterase. Results: Acetylcholineconcentration-dependentlydilatedratpa- renchymalarterioles,whileS-methyl-L-thiocitrullineaswellasN G - nitro-L-argininemethylestercompletelyabolishedthisresponse. Donepezilproducedarteriolardilation,whichwasinhibitedby S-methyl-L-thiocitrullineorN G -nitro-L-argininemethylester.Done- pezilfailedtoinducearteriolardilationinthebrainslicefromthe neuronalnitricoxidesynthaseknock-outmice.Immunohistochem- icalanalysisrevealedspatialrelationshipbetweenneuronalnitric oxidesynthaseandacetylcholinesteraseinthearteriolarwall. Conclusions: Donepezilproducesacutevasodilationinduced byaselectiveactivationofneuronalnitricoxidesynthaseinthe cerebralparenchymalarterioles.Thisagentmaybecapableof enhancingthisenzymaticactivitydirectlyor viaacetylcholines- teraseexistingonthearteriolarwall. ALZHEIMERdisease,whichisaleadingcauseofdemen- tiaintheelderlypopulation,iswellcharacterizedbythe impairmentofcentralcholinergicneurotransmission. 1 Indeed,previousstudiesdemonstratedthetightrelation- shipbetweenthecholinergicdysfunctionindiverse brainareasandtheseverityofcognitivedysfunction. 2,3 Cerebralbloodvesselsreportedlyareinnervatedwith cholinergicnervefibersinbothhumansandanimals, resultinginaugmentationofcerebralbloodflowand/or vasodilation via activationofneuronalnitricoxidesyn- thase. 4–8 Importantly,inpatientswithAlzheimerdis- ease,corticalcerebralbloodvesselsandnitricoxide synthase–containingneuronsaredeprivedofthecholin- ergiccontrol,indicatingsuchneurovasculardeficitsare majorpathogenicfactorsunderlyingthemalfunctionof cerebralbloodflowregulationinthisdiseasedstate. 9–12 Anacetylcholinesteraseinhibitor,donepezil,isclini- callyusedworldwideforpatientswithmildtosevere Alzheimerdisease. 1,13,14 Chronictreatmentwithdone- pezilisknowntopreserveregionalcerebralbloodflow inthesepatients. 15,16 However,thereisnodirectevi- denceshowingtheacutevasodilatoreffectofdonepezil via nitricoxidesynthaseoncerebralbloodvessels.In addition,recentstudieshavedemonstrated thatcholin- ergicactivationprovokedbyoraldonepezilreduces hypersensitivityofthespinalcordinananimalmodel ofneuropathicpain,indicatingthatthisagentmaybe ausefultoolinpainmedicine. 17,18 Theseresultsledus totheideathatstudiesevaluatingtheroleaswellas themechanismofthiscompoundinthemodulationof neurovascularfunctionwillallowustoobtaincrucial informationfordonepeziluseintheclinicalpractice. Therefore,theaimofthisstudywastoexamineinthe brainwhetherclinicallyrelevantconcentrationsofdone- pezilinduceacutearteriolardilation,andifso,whether thisvasodilatorresponseismediatedbytheselective activationofneuronalnitricoxidesynthase. MaterialsandMethods Theanimalexperimentwasapprovedandconducted inaccordancewithlocalinstitutionalguidelinesforthe careanduseoflaboratoryanimalsinWakayamaMedical University(Wakayama,Japan).MaleWistarrats(300– 400g),neuronalnitricoxideknock-outmiceor C57BL/6Jmiceasthecontrol(40–55g),wereobtained fromtheJacksonLaboratory(BarHarbor,ME) via CharlesRiverJapan(Yokohama,Japan).Ratsandmice werehousedingroupsofthreeincagesunderstandard conditionsforanimalstudies(20–21°C,12hofartificial lighting/day),werefed adlibitum,andhadfreeaccess * AssistantProfessor, † AssociateProfessor,‡ Staff, †† Professorand Chairman,DepartmentofAnesthesiology, § AssistantProfessor, **Professor andChairman,DepartmentofForensicMedicine,WakayamaMedicalUniver- sity,Wakayama,Japan. 㛳 AssociateProfessor,DepartmentsofPrimaryCareand EmergencyMedicine,GraduateSchoolofMedicine,KyotoUniversity,Kyoto, Japan. # AssociateProfessor,DepartmentofAnesthesiology,ToyamaUniversity SchoolofMedicine,Toyama,Japan. ReceivedfromtheDepartmentofAnesthesiology,WakayamaMedicalUniver- sity,Wakayama,Japan.SubmittedforpublicationJanuary18,2008.Acceptedfor publicationApril9,2008.ThisworkwassupportedinpartbyGrants-in-Aid 18689038(toDr.Nakahata),19390409and18659462(toDr.Kinoshita),and 17390432(toDr.Hatano)forScientificResearchfromtheMinistryofEducation, Culture,Sports,Science,andTechnologyofJapan,Tokyo,Japan.Presented,in part,attheannualmeetingoftheAmericanSocietyofAnesthesiologists,San Francisco,California,October13–17,2007. AddresscorrespondencetoDr.Kinoshita:DepartmentofAnesthesiology, WakayamaMedicalUniversity,811-1Kimiidera,Wakayama,Wakayama641-0012, Japan.hkinoshi@pd5.so-net.ne.jp.Informationonpurchasingreprintsmaybe foundatwww.anesthesiology.orgoronthemastheadpageatthebeginningof thisissue.A NESTHESIOLOGY ’sarticlesaremadefreelyaccessibletoallreaders,for personaluseonly,6monthsfromthecoverdateoftheissue. Anesthesiology,V109,No1,Jul2008 124 Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/109/1/124/655729/0000542-200807000-00020.pdf by guest on 29 July 2022 tofilteredtapwater.Animalswereanesthetizedbyin- halationof3%halothanein100%oxygen(3l/min)to performamidlinethoracotomy,and50mlofsalinewas infusedintracardiallyintotheleftventriclewhilearight atrialincisionsimultaneouslywasmadeforblooddrain- age.Theanimalswerethendecapitated,andthebrains wererapidlyremovedandrinsedwithartificialcerebro- spinalfluidofthefollowingcomposition(m M ):NaCl 119,KCl4.7,CaCl 2 2.5,MgSO 4 1.17,KH 2 PO 4 1.18, NaHCO 3 25,andglucose11. Brainswerecutfreehandintoblockscontainingthe neocortex,followedbyimmediatesectioningintoslices (125mmthick)withamechanicaltissueslicer(Vi- bratomes1000;TedPella,Redding,CA).Throughoutthe slicingprocedure,brainblockswerecontinuously bathedintheperfusionsolutionbubbledwith95%O 2 and5%CO 2 at4°C.Individually,sliceswerethentrans - ferredtoarecordingchamberfilledwiththeartificial cerebrospinalfluid,whichwasmountedonaninverted microscope(OlympusIX70;Shinjuku-ku,Tokyo,Japan). Therecordingsystemconsistedofarecordingchamber (3ml)andatubingcompartment(7ml)includingthe perfusionchamber.Thesliceswerecontinuouslysuper- fusedwithperfusionfluidattheflowrateof1.5ml/min, bubbledwithmixturegasofoxygenandcarbondioxide (P CO 2 ⫽ 40mmHg,pH⫽ 7.4,37°Cintherecording chamber).Anintraparenchymalarteriole(4.0–8.0 ␮ min internaldiameter , 11.0–16.5 ␮ minexternaldiameter) waslocatedwithintheneuronaltissue,andits internal diameterwascontinuouslymonitoredwiththelive computerizedvideomicroscopy. 19 Thevideomicros - copyequipmentconsistedofaninvertedmicroscope, a40 ⫻ objective(Olympus),anda2.25⫻ videopro- jectionlens(Olympus).Theimageofaparenchymal arteriolewastransmittedtoavideocamera(C6790-81, Olympus)anddisplayedonacomputer viaamedia converter(Physio-Tech;Chiyoda-ku,Tokyo,Japan). Thedifferentiationbetweenthearterioleandthe venuleinthebrainwasbasedonpreviousstudies documentingthat,inthebrain,alayerofsmooth musclecellsshouldbeidentifiedinthearterioleand thatthevenuleresemblesalargecapillarywithno moretoitswallsthanendothelialcellsrestingona basallamina. 20,21 Wecalculatedtheratioofinternaltoexternaldiam- eterofthevessel,andavesseldemonstratingaratio lessthan0.5wasusedasanarterioleforthefollowing experiments.Wedefinedtheinternaldiameterasthe lengthbetweentheinternalmarginsofarteriolar walls.Changesofinternaldiameterincerebralmi- crovesselswererecordedoncomputerimagefilesand thenanalyzedusingtheimageanalysissoftwarewith asensitivityto0.01 ␮ m(Physio-Tech). 19,22 Microves - seldiameterswerederivedasanaverageoffourmea- surementstakenalongapproximately20 ␮ mofvessel length. Eachslicewasequilibratedforatleast30minbefore thestartoftheexperimentalprotocols.Allexperiments wereperformedduringconstrictioninresponsetopros- taglandinF 2 ␣ (5 ⫻10 ⫺ 7 M ),aconcentrationthatpro - ducessubmaximalvasoconstrictionofapproximately 70%comparedwithmaximalcontractioninducedby prostaglandinF 2 ␣ (10 ⫺ 5 M )inthecerebralparenchymal arterioles. 19 Anonselectivenitricoxidesynthaseinhibi - torN G -nitro-L-argininemethylester(10 ⫺ 4 M )oraselec - tiveneuronalnitricoxidesynthaseinhibitorS-methyl-L- thiocitrulline(10 ⫺ 5 M )wasapplied15minbeforethe additionofprostaglandinF 2 ␣ (5 ⫻10 ⫺ 7 M ).Concentra - tion-responsestodonepezil(10 ⫺ 9 –10 ⫺ 8 M ),acetylcho - line(10 ⫺ 6 –10 ⫺ 4 M ),orsodiumnitroprusside(3 ⫻10 ⫺ 8 to3 ⫻ 10 ⫺ 6 M )wereobtainedinacumulativefashion. Onlyoneconcentration-responsewasmadeforeach slice.Theamountofdilationofthecerebralarteriole inducedbyvasodilatorswasnormalizedusingthecon- strictionproducedbyprostaglandinF 2 ␣ (5 ⫻10 ⫺ 7 M )in eacharteriole.Therefore,thepercentdilationwascal- culatedbythefollowingequation:%dilation ⫽ 100 ⫻ (thediameterafteradministrationofthevasodilatormi- nusthediameterafteradministrationofprostaglandin F 2 ␣ [5 ⫻10 ⫺ 7 M ])/(thediameterofcontrolcondition minusthediameterafteradministrationofprostaglandin F 2 ␣ [5 ⫻10 ⫺ 7 M ]).Percentageofconstrictiontoprosta - glandinF 2 ␣ ⫽ 100⫻ (thediameterafteradministration ofprostaglandinF 2 ␣ [5 ⫻10 ⫺ 7 M ]minusthediameterof controlcondition)/thediameterofcontrolcondition. ImmunofluorescenceAnalysis Insomeexperiments,thebrainsliceswerefixedwith 10%formalinbufferedwithphosphatebuffersolution (pH7.2)andembeddedinparaffin,followedbythe preparationof4-6– ␮ msections.Afterthedeparaffiniza- tion,sectionswereincubatedwithphosphatebuffer solutioncontaining1%normaldonkeyserumand1% bovineserumalbumintoreducenonspecificreactions. Thesectionswerefurtherincubatedwiththecombina- tionofrabbitantineuronalnitricoxidesynthaseandgoat antiacetylcholineesterasepolyclonalantibodiesatthe concentrationof1 ␮ g/mlat4°Covernight.Afterincu- bationwithCy3-conjugateddonkeyantirabbitimmuno- globulinGpolyclonalantibodiesandfluoresceinisothio- cyanate–conjugateddonkeyantigoatimmunoglobulinG polyclonalantibodies(10 ␮ g/ml)atroomtemperature for30min,thesectionswereobservedbyfluorescence microscopyandfluorescenceimagesweredigitally merged.Asnegativecontrols,specimenswereincubated withnormalrabbitandgoatimmunoglobulinGorinthe absenceoftheprimaryantibodies. Drugs Thefollowingpharmacologicagentswereused:acetyl- choline,dimethylsulfoxide,N G -nitro-L-argininemethyles - ter,S-methyl-L-thiocitrulline,sodiumnitroprusside,and 125 DONEPEZILANDNEURONALNITRICOXIDESYNTHASE Anesthesiology,V109,No1,Jul2008 Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/109/1/124/655729/0000542-200807000-00020.pdf by guest on 29 July 2022 prostaglandinF 2 ␣ (SigmaAldrich,St.Louis,MO).Therabbit antineuronalnitricoxidesynthaseandgoatantiacetylcho- lineesterasepolyclonalantibodieswereobtainedfrom SantaCruzBiotechnology(SantaCruz,CA).Donepezil wasagenerousgiftfromEizaiPharmaceutical(Tokyo, Japan).Drugsexceptdonepezilweredissolvedindis- tilledwatersuchthatvolumesoflessthan60 ␮ lwere addedtotheperfusionsystem.Thestocksolutionof donepezil(10 ⫺ 6 M )waspreparedindimethylsulfox - ide(3 ⫻10 ⫺ 4 M ).Drugsweredissolvedindistilled watersuchthatvolumesoflessthan60mlwereadded totheperfusionsystem.Theconcentrationsofdrugs areexpressedasfinalmolarconcentrations. StatisticalAnalysis Thedatawereexpressedasmeans ⫾ SD;nrefersto thenumberofratsormicefromwhichbrainsliceswere taken.Powercalculationsweredonewiththeinhibitory effectofS-methyl-L-thiocitrullineonthevasodilationin responsetodonepezilastheprimaryendpoint,andwe calculatedthatasamplesizeoffivegave80%powerto detectachangeof16.1%invasoconstrictionatasignif- icancelevelof0.05(SD ⫽8%).Statisticalanalysiswas performedbyStatView ® 5.0(SASInstitute,Cary,NC)or SamplePower ® 2.0(SSPSJapan,Tokyo,Japan).Data wereevaluatedusingrepeated-measuresofanalysisof varianceorafactorialanalysisofvarianceasappropriate, followedbyStudent-Newman-Keulstestasa posthoc analysis.Differenceswereconsideredtobestatistically significantwhen P ⬍0.05. Results Figure1showstherepresentativeexampleofthe arterioleandthevenulewithsimilarexternaldiameters (16.5or17.0 ␮ mforthearterioleandthevenule,re- spectively)inthebrainparenchyma.Thearteriole, whichhasasmoothmusclelayer,hasasmallerinternal diameter(5.5 ␮ m)comparedwiththatofthevenule (11.4 ␮ m). Duringsubmaximalconstrictioninresponsetopros- taglandinF 2 ␣ (5 ⫻10 ⫺ 7 M ),acetylcholinedilatedrat parenchymalarteriolesinaconcentration-dependent fashion,whileN G -nitro-L-argininemethylestercom - pletelyabolishedthisresponse(fig.2A).Donepezil(3 ⫻ 10 ⫺ 9 and10 ⫺ 8 M )producedarteriolardilation,which wascompletelyabolishedbyS-methyl-L-thiocitrullineas wellasN G -nitro-L-argininemethylester(fig.2B). Donepezil(3 ⫻10 ⫺ 9 and10 ⫺ 8 M )inducedcerebral arteriolardilationinthebrainslicefromcontrolmice (C57BL/6Jstrainmice),whileitdidnotinduceany dilatorresponsesinthatfromtheneuronalnitricoxide synthasegeneknock-outmice(fig.3A).Incontrast, sodiumnitroprussidesimilarlyproducedarteriolardila- tioninthebrainslicesfrombothstrains(fig.3B). Adouble-colorimmunofluorescenceanalysisrevealed thatinthebrainparenchyma,neuronalnitricoxide synthaseandacetylcholinesterasearesimilarlylocatedin thearteriolesaswellasneuronalcells(fig.4). Discussion Previousstudiesincludingourssuggestthatcholinergic stimuliaugmentcerebralbloodflowand/orvasodilation via activationof neuronalnitricoxidesynthase. 6–8 These resultsaresupportedbystudiesshowingthatcholine acetyltransferase–containingneuronsprojecttoneurons inwhichneuronalnitricoxidesynthaseisincluded, suggestingthataugmentationofcholinergicneurotrans- missioncontributestoincreasedcerebralbloodflow mediatedbyneuronalnitricoxidesynthase. 23 Histo - chemicalevaluationalsodocumentedtheexistenceof acetylcholinesteraseinnervefibersdistributingtocere- bralbloodvessels,indicatingthemodulationofcerebral vasomotorfunctionbythereductionofcholinergicneu- rotransmission. 4,5 Inthecurrentstudy,wehavefirst revealedthespatialrelationshipbetweenacetylcholines- teraseandneuronalnitricoxidesynthaseinthebrain structures,includingneuronalcellsandcerebralarte- rioles.Therefore,ourresultstogetherwithprevious studiesdrawtheconclusionthatthemodulationofcho- linergicneurotransmission via changesinacetylcholine Fig.1.Therepresentativeexamplesofanarterioleandavenule intheratbrainparenchyma.Thearteriole,butnotthevenule, hasasmoothmusclelayer.The longerand shorterarrowin eachfiguredemonstratetheexternalandtheinternaldiame- ters,respectively. 126 NAKAHATA ETAL. Anesthesiology,V109,No1,Jul2008 Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/109/1/124/655729/0000542-200807000-00020.pdf by guest on 29 July 2022 levelsplaysaroleintheregulationofcerebralblood flowand/orvasodilationmediatedbyenzymaticactivity ofneuronalnitricoxidesynthase. 24 Theimpairmentofcholinergicneurotransmissionin thebrainisreportedlyoneoftheleadingcausesof cognitivedysfunctioninpatientswithAlzheimerdis- ease. 3,25,26 Thisisareasonwhyacetylcholinesterase inhibitorshavebeenexpectedtoamelioratesymptoms inthesepatients.Importantly,inpatientswithAlzhei- merdisease,corticalcerebralbloodvesselsandnitric oxidesynthase–containingneuronsaredeprivedofcho- linergiccontrol,indicatingsuchneurovasculardeficits aremajorpathogenicfactorsunderlyingthemalfunction ofcerebralbloodflowregulationinthisdiseased state. 9–12 Therefore,itappearsreasonabletoadminister acetylcholinesteraseinhibitorstopatientswithAlzhei- merdiseasetorestoretheircerebralbloodflow.However, therehasbeennodirect evidenceshowingvasodilator responsesofcerebralarteriolestoanacetylcholinester- aseinhibitor,although invivostudiesusingsingle-pho- tonemissioncomputedtomographydocumentedthat, inthesepatients,ahighlyselectiveacetylcholinesterase inhibitordonepezilenhancesregionalcerebralblood flowincludingthatinthecerebralcortex. 1,27,28 Inthe currentstudy,wehaveusedbrainslicesfromthecere- bralcortextoevaluatetheeffectsofdonepezil,because thecortexreceivescholinergicneuronsanditisoneof themostaffectedbrainareasinAlzheimerdisease. 25 We havefoundthatdonepezilinducescerebralparenchymal arteriolardilation,whichwascompletelyabolishedbya selectiveaswellasanonselectiveinhibitorofneuronal nitricoxidesynthase. 29,30 Moreimportantly,wehave demonstratedthatvasodilatorresponsestodonepezil wereabsentintheparenchymalarterioleswithinthe cerebralcortexslicefromtheneuronalnitricoxide synthasegeneknock-outmice.Therefore,itismost likelythatdonepezilinducescerebralarteriolardilation via theselectiveactivationofneuronalnitricoxidesyn- thase.Inthecurrentstudy,vasodilationinresponsetoa nitricoxidedonorsodiumnitroprussidewasnotdiffer- entbetweenthegeneknock-outandcontrolmice,sug- gestingthatthevasodilatorresponsetowardnitricoxide ispreservedevenintheconditionwiththeneuronal nitricoxidesynthasegeneknockout. Thepeakplasmaconcentrationofdonepezilinhu- mansreportedlyreaches2–10ng/mlafterasingleoral doseandtheplasmaproteinbindingisabout89%,indi- catingtheplasma-freeconcentrationofdonepezilin Fig.2.( A)Vasodilatorresponsestoace- tylcholine(10 ⴚ 6 –10 ⴚ 4 M )intheabsence orinthepresenceofN G -nitro-L-arginine methylester(10 ⴚ 4 M )intheratcerebral parenchymalarterioles.( B)Vasodilator responsestodonepezil(10 ⴚ 9 –10 ⴚ 8 M )in theabsenceorinthepresenceofN G - nitro-L-argininemethylester(10 ⴚ 4 M )or S-methyl-L-thiocitrulline(10 ⴚ 5 M )inthe ratcerebralparenchymalarterioles. Baselineinternaldiameterofarterioles were7.0 ⴞ1.4and6.7 ⴞ1.5 ␮ mfor controlarteriolesandarteriolestreated withN G -nitro-L-argininemethylesterfor acetylcholine-inducedvasodilation,and 6.2 ⴞ0.7,5.9 ⴞ1.2,and5.9 ⴞ0.3 ␮ mfor controlarterioles,arteriolestreatedwith N G -nitro-L-argininemethylester,andS- methyl-L-thiocitrullinefordonepezil-in- ducedvasodilation,respectively.Data areshownasmean ⴞSD.Differencebe- tweenthecontrolarteriolesandthearteriolestreatedwithN G -nitro-L-argininemethylesterorS-methyl-L-thiocitrullinewas statisticallysignificant(* P <0.05). Fig.3.Vasodilatorresponsesto( A)done- pezil(10 ⴚ 9 –10 ⴚ 8 M )andto( B)sodium nitroprusside(3 ⴛ10 ⴚ 5 to3 ⴛ 10 ⴚ 3 M )in thecerebralparenchymalarteriolesof neuronalnitricoxidesynthaseknock- outandcontrolmice.Baselineinternal diametersofarterioleswere( A )4.2 ⴞ 0.4and5.3 ⴞ0.8 ␮ mand( B)5.5 ⴞ0.7 and4.8 ⴞ 0.6forcontrolandneuronal nitricoxidesynthaseknock-outmice, respectively.Dataareshownasmean ⴞ SD.Differencebetweenthearteriolesof controlandneuronalnitricoxidesyn- thaseknock-outmicewasstatistically significant(* P <0.05). 127 DONEPEZILANDNEURONALNITRICOXIDESYNTHASE Anesthesiology,V109,No1,Jul2008 Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/109/1/124/655729/0000542-200807000-00020.pdf by guest on 29 July 2022 clinicalpracticewouldbeupto3 ⫻10 ⫺ 9 M (drug informationsuppliedbyEizaiPharmaceutical,Tokyo, Japan).Therefore,concentrationsofthisagentusedin thecurrentstudyappeartobeclinicallyrelevant.We havedocumentedspatialrelationshipbetweenneuronal nitricoxidesynthaseandacetylcholinesteraseinthe cerebralparenchyma.Our resultssuggestthepossibil- itythatdonepezilincreasesthelocalconcentrationof acetylcholinearoundcerebralparenchymalarterioles, leadingtothedilation viatheincreasedenzymatic activityofneuronalnitricoxidesynthase.However,it isstillunclearwhetherthisagentiscapableofenhanc- ingtheenzymaticactivitydirectlyor viaacetylcho- linesterasedistributingtothecerebralarteriolarwall, andwhethertheenhancedneuronalactivityinduced bydonepezilactsontheincreaseincerebralblood flow. Itisimportanttonotethatinourexperimental system,brainslicesaremaintainedinartificialcondi- tionsinwhichvesselsarenotperfusedanddonot haveintraluminalflowandthatourconfocalmicro- scopicfindingscouldbedifferentfromthoseinpa- tientswithAlzheimerdisease.Therefore,itmaybe difficulttoextrapolatedirectlyourresultstothe in vivo diseasedcondition.However,asalreadypointed outbysomeresearchers,itisalsotruethatsuch preparations,inwhichneuronal–vascularinteractions arepreserved,offeranadditionalmeanstoisolated microvesselsandwholeanimalexperimentsforinves- tigatingthecerebralmicrocirculation. 31 Donepezilisaleadingproducttotreatpatientswith Alzheimerdisease,assupportedbyclinicalstudiesdem- onstratingthemarkedeffectivenessofthisagenton cognitivedysfunction. 1,32 Thedonepezil-inducedcere - bralarteriolardilationshowninthecurrentstudymayat leastpartlyaccountfortheclinicalsignificanceofthis agentinAlzheimerdisease.Donepezilreportedlypre- ventsapoptoticneuronaldeathinducedbyglutamate neurotoxicityintheanimalmodel,suggestingprotective effectsofthisagentagainstcerebraldamagesuchas ischemicbraininjury. 33 Inadditiontothebeneficial effectsonthebrainfunction,recentanimalstudieshave demonstratedthatcholinergicactivationprovokedby donepezilreduceshypersensitivityofthespinalcordin neuropathicpain,indicatingthatthisagentmaybeuse- fultocontrolsuchpaininhumans. 17,18 Moreimpor - tantly,thisacetylcholinesteraseinhibitorisundergoing clinicaltrialsinthetreatmentofdiabeticneuropathic pain.‡‡Therefore,therolesofdonepezilintheregula- tionofthecentralnervoussystemshouldbeincreasingly crucialintheclinicalpracticeincludingtheperiopera- tiveperiodandpainmedicine. Inconclusion,thisisthefirststudydemonstrating
https://www.researchgate.net/publication/5274398_Cholinesterase_Inhibitor_Donepezil_Dilates_Cerebral_Parenchymal_Arterioles_via_the_Activation_of_Neuronal_Nitric_Oxide_Synthase
SARS-CoV-2 IgG in Covid19 and SARS-CoV Infection and Transplantation Infection - Clinical Trials Registry - ICH GCP This project will provide novel data using a large cohort of more than 3000 transplanted patients. Risk and protective factors for SARS-CoV-2 infection and COVI... Prevalence and Outcome of SARS-CoV-2 Infection & COVID-19 in Transplant Recipients: The COVITRA Study (COVITRA) Prevalence and Outcome of SARS-CoV-2 Infection in Solid Organ and Hematopoietic Cell Transplant Recipients: The COVITRA Study This project will provide novel data using a large cohort of more than 3000 transplanted patients. Risk and protective factors for SARS-CoV-2 infection and COVID-19 disease severity will be identified. The proportion of patients who develop antibodies after infection will be revealed. In this way the presence of these antibodies can be evaluated as a test for prior infection. Our study additionally will demonstrate how long these antibodies remain present and whether they are protective against a new infection. Study Overview Status Unknown Conditions Covid19 SARS-CoV Infection Transplantation Infection Intervention / Treatment Diagnostic test: SARS-CoV-2 IgG Study Type Observational Enrollment (Anticipated) 2000 Contacts and Locations This section provides the contact details for those conducting the study, and information on where this study is being conducted. Study Contact Name: Jef Verbeek, MD, PhD Phone Number: + 32 16 34 42 25 Email: jef.verbeek@uzleuven.be Study Contact Backup Name: Natalie Van den Ende Phone Number: +32 16 340749 Email: natalie.vandenende@uzleuven.be Study Locations Belgium Vlaams Brabant Leuven, Vlaams Brabant, Belgium, 3000 Recruiting UZ Leuven Contact: Jef Verbeek, MD Phone Number: +32 16 345845 Email: jef.verbeek@uzleuven.be Contact: Natalie Vandenende Phone Number: +32 16 34 07 49 Email: natalie.vandenende@uzleuven.be Principal Investigator: Jef Verbeek, MD Participation Criteria Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments. Eligibility Criteria Ages Eligible for Study 18 years to 90 years (Adult, Older Adult) Accepts Healthy Volunteers No Genders Eligible for Study All Sampling Method Non-Probability Sample Study Population all patients who underwent solid organ or hematopoietic transplantation at UZ Leuven and who give informed consent Description Inclusion Criteria: all patients who underwent solid organ or hematopoietic cell transplantation at UZ Leuven and who give informed consent Exclusion Criteria: age under 18 years Study Plan This section provides details of the study plan, including how the study is designed and what the study is measuring. How is the study designed? Design Details Observational Models: Cohort Time Perspectives: Prospective 3 Cohorts and Interventions <table><tr><th> Group / Cohort</th><th> Intervention / Treatment</th></tr><tbody><tr><td> Transplanted patients All patients who underwent solid organ or hematopoietic cell transplantation at UZ Leuven</td><td> Diagnostic test: SARS-CoV-2 IgG Collection of clinical variables, assessment of IgG antibodies for SARS-CoV-2, plasma collection for translational immunology studies</td></tr><tr><td> Transplanted patients with past SARS-CoV-2 infection Transplanted patients with past SARS-CoV-2 infection will be followed for one year (at month 3, 6 and 12 after the initial study visit) to assess durability of IgG positivity</td><td> Diagnostic test: SARS-CoV-2 IgG Collection of clinical variables, assessment of IgG antibodies for SARS-CoV-2, plasma collection for translational immunology studies</td></tr><tr><td> Transplanted patients without past SARS-CoV-2 infection 100 transplanted patients without past SARS-CoV-2 infection will be followed for one year (at month 3, 6 and 12 after the initial study visit) to assess durability of IgG positivity and as control for the transplanted patients with WITH past SARS-CoV-2 infection</td><td> Diagnostic test: SARS-CoV-2 IgG Collection of clinical variables, assessment of IgG antibodies for SARS-CoV-2, plasma collection for translational immunology studies</td></tr></tbody></table> What is the study measuring? Primary Outcome Measures <table><tr><th> Outcome Measure</th><th> Measure Description</th><th> Time Frame</th></tr><tbody><tr><td> Prevalence and risk-factors for SARS-CoV-2 infection Time Frame: inclusion during 4 months</td><td> Prevalence and risk-factors for SARS-CoV-2 infection</td><td> inclusion during 4 months</td></tr><tr><td> Prevalence and risk-factors for COVID-19 Time Frame: inclusion during 4 months</td><td> Prevalence and risk-factors for COVID-19</td><td> inclusion during 4 months</td></tr></tbody></table> Secondary Outcome Measures <table><tr><th> Outcome Measure</th><th> Measure Description</th><th> Time Frame</th></tr><tbody><tr><td> Durability of IgG positivity Time Frame: 12 months</td><td> Durability of IgG positivity/immunity</td><td> 12 months</td></tr></tbody></table> Collaborators and Investigators This is where you will find people and organizations involved with this study. Sponsor Universitaire Ziekenhuizen KU Leuven Collaborators KU Leuven Hasselt University Jessa Hospital Ziekenhuis Oost-Limburg Investigators Principal Investigator: Jef Verbeek, MD, PhD, UZ Leuven Study record dates These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website. Study Major Dates Study Start (Actual) July 1, 2020 Primary Completion (Anticipated) December 31, 2021 Study Completion (Anticipated) December 31, 2021 Study Registration Dates First Submitted October 6, 2020 First Submitted That Met QC Criteria October 6, 2020 First Posted (Actual) October 8, 2020 Study Record Updates Last Update Posted (Actual) October 9, 2020 Last Update Submitted That Met QC Criteria October 8, 2020 Last Verified October 1, 2020 Other Study ID Numbers s64036 Plan for Individual participant data (IPD) Plan to Share Individual Participant Data (IPD)? Undecided Drug and device information, study documents Studies a U.S. FDA-regulated drug product No Studies a U.S. FDA-regulated device product No product manufactured in and exported from the U.S. No Clinical Trials on Covid19 NCT05930730 Not yet recruiting Immunogenicity and Safety of Comvigen (Bivalent) Vaccine Safety of a Single Dose of COMVIGEN Vaccine | Reactogenicity of a Single Dose of COMVIGEN Vaccine | Immunogenicity of a Single Dose of COMVIGEN Vaccine | Safety of a Single Dose of BIVALENT Pfizer/BNT Vaccine | Reactogenicity of a Single Dose of BIVALENT Pfizer/BNT Vaccine | Immunogenicity of a Single Dose of BIVALENT Pfizer/BNT Vaccine NCT05931497 Not yet recruiting NCT05926076 Not yet recruiting Safety and Efficacy of Anakinra Treatment for Patients With Post Acute Covid Syndrome (PRECISION) Post-Acute COVID-19 Syndrome NCT05925140 Recruiting LUSZ Treatment Efficacy in Hospitalized COVID-19 Patients (LUSZ_CTS_COVID) COVID-19 | Hospitalized COVID-19 Patients NCT05924685 Not yet recruiting PREPARE-iVAC Trial (PREPARE-iVAC) Vaccine Response | Immunosuppression | COVID-19 Vaccines | Varicella Zoster Vaccine Clinical Trials on SARS-CoV-2 IgG NCT05903456 Not yet recruiting Icaritin Soft Capsule Combined With Lenvatinib and TACE for the Treatment of Hepatocellular Carcinoma Hepatocellular Carcinoma NCT05218356 Recruiting Phase IIa Randomized Placebo Controlled Clinical Study of Codivir in Hospitalized Patients With Moderate COVID-19 COVID-19 NCT05172167 Recruiting Prospective Evaluation of SARS-CoV-2 Antibodies Levels in a Vaccinated Population of Valle de Aburra NCT05162456 NCT05094635 Not yet recruiting NCT05089565 Recruiting NCT04871165 NCT04808986 Not yet recruiting NCT04716179 Recruiting NCT04334876 Completed
https://ichgcp.net/clinical-trials-registry/NCT04579471
WSL: The Nicaraguan Revolution / TILC 1980 The Nicaraguan Revolution Trotskyist International Liaison Committee (April / May 1980) Written: April / May 1980. First Published: May 1980. Source: International Trotskyist Review No. 2, April / June 1985. Transcription/HTML Markup: Sean Robertson for the Encyclopaedia of Trotskyism On-Line (ETOL). Copyleft:Encyclopaedia of Trotskyism On-Line (marxists.org) 2012. Permission is granted to copy and/or distribute this document under the terms of the Creative Commons license . Please cite any editors, proofreaders and formatters noted above along with any other publishing information including the URL of this document. The Nicaraguan Revolution 1. The Beginning of the Nicaraguan Revolution The Trotskyist International Liaison Committee (for the Reconstruction of the Fourth International) hails the victory gained by the workers and peasants of Nicaragua with the revolutionary overthrow of the Somoza dictatorship. Their victory has dealt a blow against imperialism and strengthened the revolutionary forces of the international proletariat in its struggle for socialism. But the Nicaraguan revolution remains uncompleted: its vast potential has not yet been realized. The gains which have already been made are great but limited, and they have not been secured against the threats of attacks from imperialism and international reaction. The strongest defense of the Nicaraguan revolution is the fight to consolidate and develop these existing gains by a proletarian-internationalist struggle for a socialist revolution in Nicaragua. 2. The Challenge of the Nicaraguan Revolution The smashing of the Somoza tyranny struck a heavy blow against US imperialism, which had sustained the dictatorship as a vital force in its strategy of dominating the turbulent southern states of the Americas. Maimed by a succession of attacks, from their defeat in Southeast Asia to the Iranian revolution, the US imperialists now faced the certain prospect of renewed revolutionary mobilizations throughout the region, spurred on by the example of Nicaragua. This threat has already taken concrete form in El Salvador, Honduras, and Guatemala. Revolution in Nicaragua also brought fresh anxieties to world Stalinism, already grappling with the mounting problems of how to maintain a counterrevolutionary hold on the advancing struggles of the international proletariat. This new problem centered on the role to be adopted by the Castro regime in Cuba, the local agents of the Kremlin bureaucracy. But at the same time the world Trotskyist movement was confronted with vital questions of revolutionary strategy and the application of the revolutionary program. The Nicaraguan revolution brought once again to the fore issues which have underlain every stage of the postwar crisis of the Fourth International: the theory of permanent revolution and the essential political independence both of the proletariat as a class and of its revolutionary leadership. Faced with these issues, the United Secretariat of the Fourth International (USFI) split, and so a new phase was opened up in the struggle to reconstruct the Fourth International as the world party of socialist revolution. These developments make it all the more urgent for us to approach the necessary task of assessing the Nicaraguan revolution and answering the two key questions:1. What lessons are to be learned from the revolutionary struggles which overthrew Somoza’s dictatorship?2. What tasks are posed for Trotskyists to give a consistently revolutionary leadership to the struggles of the Nicaraguan proletariat and its potential allies in the peasantry and other oppressed social layers? 3. The Somoza Dictatorship The particular character of the Somoza dictatorship must first be understood. Installed and maintained in power by US imperialism, Somoza ensured the continued superexploitation of the Nicaraguan workers and peasants through the repressive apparatus of a brutal dictatorship – in particular through the US-trained National Guard. These conditions, with the total suppression of democratic rights, also drove the layers of the urban petty bourgeoisie into opposition. Yet Somoza’s tyranny also produced enemies among wide sections of the capitalist class itself, for its dictatorship was not merely political. The Somoza family owned 25 percent of all industry and 40 percent of all workable land. The economic dictatorship of this Somoza monopoly antagonized other capitalists, who were prevented by its stranglehold from developing the economy to satisfy their own drive for profits. Along with the reactionary power of the Roman Catholic church, this “anti-Somoza bourgeoisie” recognized the highly explosive state of the class struggle in Nicaragua. Seeking to avert the threat of revolution, these elements called for the “democratization” of the regime and turned for support to the Carter administration and, especially, to the European Social Democracy. which had begun (through the vehicle of the “Socialist International”) to pay particular attention to the hard tasks of counterrevolutionary activity in South and Central America. In this way they hoped to establish a bourgeois democracy which would either limit or eliminate the power of Somoza and leave them free to develop the exploitation of the workers and peasants for their own profits and not to stuff the private coffers of the Somoza family and its small surrounding clique. The Somoza dictatorship thus created the conditions for a “national revolution.” As in Tsarist Russia or as in Iran under the tyranny of the Shah, bourgeoisie, peasantry, and proletariat shared a common interest in the overthrow of the autocracy. The crucial question was which class would give the political leadership to that revolution and determine its class content. 4. The Sandinista National Liberation Front (FSLN) It was in these conditions that the Sandinista National Liberation Front (FSLN) came forward into increasing prominence as a force in the struggle against Somoza. Formed in July 1962, the FSLN was a petty-bourgeois nationalist movement which identified itself as “Marxist” and set itself the task of “national democratic revolution.” Different currents emerged within and split the FSLN over the course of the 1970’s. One developed a relatively fiercer anti-imperialist stance than the others (the Guerra Popular Prolongadatendency [GPP]). Another proclaimed itself “Leninist” and called for a primary orientation of building a party in the working class ( Tendencia Proletaria[TP]). But with “unification” early in 1979, hegemony over the FSLN was established by the Tercerista(“third-force”) tendency, which combined the traditional strategy of rural guerrilla warfare (based on an interpretation of the Cuban revolution) with a popular-frontist alliance with the anti-Somoza bourgeoisie, backed by the Latin American “social democracies” (Venezuela, Panama, Costa Rica). Despite its defeat, the rising of September 1978 revealed both the strength of the FSLN itself and the high degree of mass support which existed for a military victory of the FSLN over Somoza’s forces. But it is particularly important to stress the character of the mass strike action which gripped the cities in this period. Although there was undoubtedly mass enthusiasm among workers for this action, it was not independent class action by the proletariat – neither spontaneous nor led by a revolutionary proletarian leadership. On the contrary, these strikes were blessed by the Catholic hierarchy and in many cases directly organized by employers from the “anti-Somoza bourgeoisie,” who continued to pay wages throughout the stoppages. As in any other variety of popular-frontist alliance at whatever level between the proletariat and the bourgeoisie, it was the class interests of the proletariat which were inevitably subordinated to the political dominance of the bourgeoisie in this confusion of class interests. The “anti-Somoza bourgeoisie,” led by Las Doce[“The Twelve”], sought to gain political power by harnessing the revolutionary energies of the proletariat. It was clearly the essential task of Trotskyists to fight for the political independence of the working class from the bourgeoisie, in opposition to every section of the FSLN which opposed this strategy in the name of the “democratic” or “anti-imperialist” front. The direction of this strategy could be followed only by fighting to build soviets as organs of workers’ power independent of the “anti-Somoza bourgeoisie” and of the Sandinista leadership itself. After the September rising, the FSLN was clearly established as the leadership of the mass struggles against the tyranny. Over the next few months – and with their “unification” once accomplished – the FSLN leaders proceeded to consolidate their alliance with bourgeois forces in preparation for the final offensive against Somoza’s dictatorship. 5. The Government of National Reconstruction (GNR) As the last bloody days of the revolution of July 1979 were reached, the FSLN established a junta to replace the crumbling dictatorship. The Government of National Reconstruction (GNR) consisted of one leading Sandinista – and four bourgeois members: a millionaire sugar plantation owner, a large landowner, another major employer, and a technocrat formerly employed by the World Bank. The relationship between the FSLN leadership and the GNR was clearly spelled out by Daniel Ortega from the Joint National Directorate of the FSLN: Some people have asked whether the government is the FSLN or the Government of National Reconstruction . . . The truth is that the government Junta is in charge of all the high functions of the state. Then the FSLN, which at the beginning took charge of the country, is now in the process of handing over the administrative and government apparatus to the Junta. ( Barricada , 31 July 1979) Politically dominated by the bourgeoisie, the Government of National Reconstruction derived all its power from the authority of the FSLN forces and was clearly powerless to act in any direction without securing the agreement of – and indeed working through – the agency of the FSLN leadership. Once the Junta had appointed its ministers, it was actually the second tier of new state institutions, directly controlled by the FSLN, which put into practice the decrees of the GNR. But if the FSLN leadership was able to formalize rapidly the intimate bonds it sought with the bourgeoisie, its relationship with the proletariat and peasantry was a more complex affair. The final struggles to overthrow the Somoza dictatorship had taken place in conditions of tremendous mass mobilizations in both the urban and rural areas. The neighborhood “Sandinista Defense Committees,”[1]spontaneously organized on a local basis, were the characteristic form taken by this movement. As their name implies, these bodies were in no way set up in conscious opposition to the FSLN leadership. Nevertheless, they represented a serious potential threat to the popular-frontist strategy of the FSLN, both by their independent class nature and, in particular, by the class demands which they soon began to raise. The “Sandinista Defense Committees” could have developed into a genuine soviet movement of dual-power proportions, and it was therefore necessary for the FSLN leadership to curb their powers and control their evolution. This process was carried out alongside the first measures of the Government of National Reconstruction. 6. Capitalist Reconstruction Begins Protracted civil war and revolutionary struggles had brought the economy of Nicaragua to the brink of collapse. Agricultural production had been severely disrupted by the campaigns of the FSLN, while industrial production had been thrown into chaos by the mass strike action. The pro- Somoza bourgeoisie had fled, closing down businesses and removing capital, as the international agencies of finance capital (IMF, etc.) vacillated on granting desperately needed loans to a regime clearly on the point of destruction. Under these circumstances, the GNR set about its task of “reconstruction.” With the political dominance of the bourgeoisie and its class interests conceded by the FSLN, this could mean only one thing: the reconstruction of a capitalistNicaragua. But the scale of the mass mobilizations and the peculiar character of the Somoza dictatorship meant that the bourgeoisie was forced to act within specific constraints. The capitalists were unable to move directly to a redistribution of Somoza’s property among themselves. Pressure from the mobilized workers and peasants forced them to concede the nationalization of Somoza’s property, along with that of his family and the Somocistas(those elements most closely identified with the old regime). But the progressive aspect of these substantial nationalizations must be understood as inextricably bound up with the reality that they were carried through by a state committed to the defense of capital. As FSLN Commander Bayardo Ace declared: “Private property will not only be respected, but absolutely guaranteed” ( La Prensa, Buenos Aires, 1 August 1979). State control of the national banks and the state monopoly on exports of agricultural produce were measures whose dual nature was even more strongly dominated by the immediate economic needs of the bourgeoisie. It was in the field of international relations that the character of the new regime was most sharply revealed. The Government of National Reconstruction set about rescheduling the foreign debt with capitalist states and institutions and opened fresh negotiations for aid from the imperialist powers and the international bodies of finance capital. At first these approaches coincided with the new strategy imposed on US imperialism by the overthrow of Somoza. As Deputy Secretary of State Warren Christopher argued: With aid the chances will be enhanced [that the revolution] will move in the direction of a democratic regime . . . If we walk away we will almost certainly assure what we don’t want, a Communist or Cuban regime. But the US has vacillated and, a year later, is still refusing aid on any substantial scale. 7. The Government of National Reconstruction and the Workers’ Organizations While the Government of National Reconstruction pursued its aim of a deal with imperialism to stabilize capitalism on a new footing in Nicaragua, the mobilizations of workers and peasants had not subsided into passivity. The regime could afford no delay in tackling the problems posed to its political orientation by this class activity. But at the same time it was prevented from launching into direct confrontation with the workers and peasants by the precarious balance of class forces, where the weight of the bourgeoisie was maintained at all only by the firm hand of the FSLN leadership. The Government of National Reconstruction and the FSLN combined, therefore, specific attacks on individual actions taken by workers and peasants with a general drive to incorporate the independent political organs that had been formed into a reconstructed state apparatus. For example, peasants occupying land were ejected from the property of the “anti-Somoza bourgeoisie” by the FSLN-organized peasant union (the ATC) and the state agrarian reform agency (the INRA, headed by Jaime Wheelock, leader of the former Tendencia Proletaria). This dual offensive inevitably entailed an attack on those organizations which represented – in however distorted or inadequate a form – the independent interests of the proletariat. In particular, the regime has worked to suppress three organizations: 1) the Revolutionary Marxist League ( Liga Marxista Revolucionaria: LMR), formerly a sympathizing section of the USFI; 2) the Popular Action Movement ( Movimiento de Accion Popular: MAP), with its trade union face, the Workers Front ( Frente Obrero: FO), a grouping dominated by Maoism, but including self-styled Trotskyists along with other forces; and 3) the Simon Bolivar Brigade. 8. The Simon Bolivar Brigade Because its intervention has received massive international publicity as an example of Trotskyism in practice and because its expulsion from Nicaragua was the immediate cause of the splitting of the USFI, it is critically important that we make an assessment of this brigade. The Simon Bolivar Brigade was organized by the Morenist Bolshevik Faction of the USFI and recruited from 13 June 1979 by its Colombian section, the Socialist Workers Party ( Partido Socialista de Trabajadores: PST / Columbia). After an initial period of adaptation to petty-bourgeois nationalism and to the FSLN, the Bolshevik Faction had at length put forward its own program for Nicaragua, which called for a “workers’ and peasants’ government based on the FSLN” without giving any political support to the FSLN. The formal correctness of this demand – and of the rest of the program – was critically weakened by the failure to call for the building of soviet-type bodies to represent the independent interests of the proletariat. This was at the time – and remains – the key demand for Trotskyists to raise in Nicaragua. However, the Simon Bolivar Brigade was not recruited on the basis of this program. The Bolshevik Faction insisted that the Brigade should be open to all forces prepared to fight “under the military discipline of the FSLN” for what was actually the Brigade’s sole point of program: “to support the struggle of the Sandinista people” ( El Socialista[paper of the PST], 22 June 1979). This position was clearly agreed to by the FSLN, but at no stage does the formation of the Simon Bolivar Brigade seem to have been agreed to by the international leadership of the USFI. Much criticism of the Simon Bolivar Brigade has failed to distinguish two separate issues which were at stake: first, the urgent necessity for Trotskyists to intervene in the mass struggles against Somoza to fight for a revolutionary program, organized as a political force but preferably not trapped in isolation as a military unit; second, the proletarian internationalist duty of Trotskyists to organize material support in solidarity with the revolution against Somoza. (From its statements after the expulsion, the Bolshevik Faction seems, at least later, to have sometimes fallen into the same confusion as its critics.) The call to form the Simon Bolivar Brigade was a correct, principled action of proletarian internationalism, but such a limited united front was not – and never could have been – an adequate vehicle for Trotskyists to fight for their revolutionary program amid the mass struggles of the Nicaraguan workers and peasants. When Somoza fled to the USA on 17 July 1979 and the National Guard surrendered on 19 July, most of the Simon Bolivar Brigade was still in fact receiving military training in Costa Rica, and only a few dozen of its militants had been directly involved in the civil war for a couple of days. The main activities of the Brigade began with the overthrow of the tyranny, in districts of the capital Managua and in the Atlantic port of Bluefields. Here, whatever the program on which it had been recruited, the Simon Bolivar Brigade does seem to have worked strongly and consistently to develop the organizational and political independence of the proletariat. One particular sphere of activity was the building of independent trade unions, and militants of the Simon Bolivar Brigade were instrumental in forming some 100 factory-based unions. A pressing demand from many workers at this time was for the Government of National Reconstruction to guarantee the back-payment of wages lost since they followed the FSLN to come out on strike early in July. At the same time, the Simon Bolivar Brigade intervened in the Sandinista Defense Committees. In some areas these committees had begun to realize their potential of developing into soviet-type bodies by assuming administrative functions, and many organized the neighborhood armed militias. The Simon Bolivar Brigade attempted to defend these activities against the attacks of the Government of National Reconstruction. The regime did not have the ability to dismantle the Defense Committees. Rather, it followed the line of trying to control them and to exploit them to its own advantage by transforming them bureaucratically into an arm of the state. The clearest evidence of this process was the move to disarm and dissolve the militias, as explained by FSLN Commander Luis Carron: “The militias are being concentrated and trained to incorporate them into the army” ( Barricada, 27 July 1979). And this new army that was being forged was not designed as a weapon of the proletariat: The members of the National Army will not be allowed to engage in party political activities, but their political rights as citizens will be guaranteed. (Program of the Government of National Reconstruction, June 1979, paragraph 1.12) Alongside this fake promise of armed forces free of class interests was the reality that this army was being trained by the military of the bourgeois Panamanian state. The Simon Bolivar Brigade had already come into conflict with the FSLN over its attempts to agitate around democratic demands within the guerrilla forces and to carry out a propaganda campaign there for a revolutionary socialist perspective for the Nicaraguan revolution. As rumors spread that the Brigade was threatened with expulsion from Nicaragua, correctly a demonstration was organized to accompany the Simon Bolivar Brigade when it was summoned to the FSLN headquarters on 14 August. Three thousand workers marched on that day, their central demand the call for rights of citizenship to be granted to the non-Nicaraguan members of the Simon Bolivar Brigade. They also protested against the disarming of the militias and layoffs, demanded the back-payment of wages, and raised the slogans: “Long live the FSLN!”, “Long live the Simon Bolivar Brigade!”, and, apparently, “Power to the proletariat!” and “The revolution is in the hands of the bourgeoisie!” The FSLN took no action at this point, but within two days the non-Nicaraguan members of the Simon Bolivar Brigade had been deported, with the active and violent cooperation of Panamanian security forces, who beat up these militants and imprisoned them.[2] 9. The USFI Splits At the next meeting of the international secretariat of the USFI (early October 1979), the Bolshevik Faction – supported by the Leninist-Trotskyist Tendency – demanded that the USFI condemn this expulsion. In July the USFI majority leadership had issued a political statement on Nicaragua ( Intercontinental Press, 16 July 1979) which did not differ in essentials from the formal correctness and crucial weaknesses of the Bolshevik Faction’s own program. But, in the meantime, the USFI’s official delegation to Nicaragua had developed (under the leadership of the American Socialist Workers Party) a quite new and sharply contrasting assessment of the revolution, based on their vivid but superficial impressions of the character of the mass mobilizations. This dramatic revision of position led the delegation to its supportfor the expulsion of the Simon Bolivar Brigade in a public letter to the FSLN leadership: To defend this revolution means to support the struggle whose vanguard is the FSLN. All activities which seek today to create divisions between the mobilized masses and the FSLN are contrary to the interests of the revolution. This was the case, specifically, with the activities of the Simon Bolivar Brigade. This group actually had a dual policy: to capitalize on the prestige of the FSLN, it cloaked itself with the Sandinista banner; but, at the same time, in the mass organizations its sectarian policy tried to separate the workers from their vanguard. According to certain assertions that have appeared in the press, the activities of this group represented the attitude of our organization toward the revolution and its leadership. This is totally false. This group acted on its own. In a political and economic situation that required the greatest possible unity in struggle, the FSLN was right to demand that the non-Nicaraguan members of this group – which defined itself above all as a military organization – leave the country. (“Statement by United Secretariat Delegation”, 3 September 1979; Intercontinental Press, 24 September 1979) The logic of this scandalous position was argued through at the October meeting of the USFI international secretariat by Jack Barnes, leader of the American Socialist Workers Party (SWP/US). Barnes called for the USFI to give full support to the Government of National Reconstruction (a government dedicated to the capitalistreconstruction of Nicaragua), arguing that the GNR was not to be characterized as a class-collaborationist, counterrevolutionary popular front but as an alliance between the forces of the bourgeoisie and a revolutionaryparty (that is, the FSLN) in which the politics of the revolutionary party predominates. Thus the Government of National Reconstruction was, he claimed, “a revolutionary government,” and the USFI should give it support against those “sectarian” forces which sought to drive a wedge between it and the masses. Barnes also argued that the USFI should campaign for a defensive front of the Latin American bourgeois democracies to support the Nicaraguan revolution against the threat of imperialist intervention and that the USFI should make the major thrust of its solidarity campaign the demand on bourgeois and imperialist governments that they give aid to the Government of National Reconstruction – this at a time when the US imperialists were seeking precisely to exploit aid as a method of controlling the development of the Nicaraguan revolution. Since then, the pages of the USFI’s SWP / US-produced Intercontinental Presshave been opened to totally uncritical reproduction of FSLN propaganda – the same treatment already given to the speeches and declarations of Castro’s “revolutionary” Stalinist regime in Havana. The USFI majority agreed to the fundamental line of these positions in a less blatantly revisionist form and went on to take organizational steps to ensure that they were implemented: The United Secretariat resolves that in Nicaragua, in El Salvador, in Guatemala, and in Honduras, all the political activity of the members of the Fourth International [that is, the USFI] or those who accept the leadership of the Fourth International, should be undertaken under the direct control of the leadership of the United Secretariat on the basis of the political line adopted by it [in practice, the direct control of the USFI delegation in Nicaragua and so, in practical reality, of the American SWP]. The OST of Costa Rica and the Bolshevik Faction in particular are instructed to cease all activity in Nicaragua – including the construction of organizations – and to limit themselves to activities undertaken in collaboration with the United Secretariat and on the basis of the line of the International [that is, the USFI]. As the resolution on the Nicaraguan revolution adopted by the United Secretariat of 1st October 1979 outlined, all Nicaraguans who are members or sympathizers of the Fourth International [the USFI] should act “as loyal militants in the framework of the organization which led the overthrow of Somoza and leads this revolution . . . to defend the fundamental ideas of revolutionary Marxism.” The Bolshevik Faction and the Leninist-Trotskyist Tendency withdrew from the United Secretariat and issued the call for an open conference against liquidationism in Nicaragua. This call was immediately supported by the Lambertist OCRFI, and these three groupings set up the present Parity Commission. For this action the Bolshevik Faction and the Leninist-Trotskyist Tendency were both expelled from the USFI shortly before its “eleventh” World Congress (held 17-25 November). We have declared our assessment of these developments in other documents. What must be stressed here is the depth of the questions involved, which reach right back through the postwar crisis of the Fourth International to the origins of Pabloism. As Pablo had done before them, today’s leaders of the USFI denied the independent Trotskyist party its leading role as the conscious vanguard of the proletariat in the struggle to realize the perspective of permanent revolution. Indeed, they went further than Pablo had done in 1953 and followed the example of his later liquidationist exploits in Algeria. They did not only fail to fight for the building of an independent Trotskyist party in Nicaragua and fail to raise demands to develop the political independence of the proletariat; as if this were not enough, they also ordered the liquidation of the Trotskyist forces already there in Nicaragua, ordered them to undertake no factional work within the FSLN, and supported FSLN repression of forces actually fighting for the independent interests of the proletariat. Beside this foul record of sordid opportunism and gross betrayals, the positions of the Morenist Bolshevik Faction could scarcely fail to appear in a more favorable light. Yet when we recognize the important strengths of their positions, we cannot overlook their failings and weaknesses. We must attempt to understand how they have been able to develop. For all the formally correct demands of its program – and even despite the apparently principled work of its cadres inside Nicaragua under very difficult conditions – the Bolshevik Faction never raised the critically important demand for the building of soviet-type bodies in Nicaragua. We do not suggest that the application of this demand would somehow have prevented the expulsion of the Simon Bolivar Brigade. But we do recognize that the adoption of a similarly inadequate program paved the way for the revisionist capitulation of the USFI majority to the forces of petty-bourgeois nationalism. If the comrades of the Bolshevik Faction are to grasp fully the lessons which the Nicaraguan revolution holds for Trotskyists and so be able to play a positive role in the struggle to reconstruct the Fourth International as the democratic-centralist world party of socialist revolution, it is essential that they too understand the way in which the poison of Pabloism, lingering undetected, infected their own political positions. The sole point of program for recruitment to the Simon Bolivar Brigade represented in its way a parallel capitulation to the ideology of petty-bourgeois nationalism. The Bolshevik Faction did not call for political support to the FSLN, but it did demand support for the “struggle of the Sandinista people” [emphasis added] – one small phrase, yet a formulation which conceded the cross-class, “anti-imperialist,” “national-democratic” character of the revolution, failed utterly to focus on the independent leading role that must be played by the proletariat, and so strengthened the ultimate counterrevolutionary trajectory of the FSLN leadership, which could lead to only one immediate point: the placing of power in the hands of the bourgeoisie. But any assessment of the Simon Bolivar Brigade must recognize that the initiative of the Bolshevik Faction has posed to all Trotskyists questions of the practice of proletarian internationalism that have been ignored for decades. Their intervention into the Nicaraguan revolution opened up a vital discussion on the methods of work which Trotskyists can use to develop material forms of international solidarity and extend their fight for the revolutionary program into previously inaccessible areas of crisis in the class struggle. The lessons of this practical experience in struggle will not be won by erecting a defensive barricade of “principled” criticism of the Bolshevik Faction’s activities around the Simon Bolivar Brigade. Abstention, with splendid ritual denunciations of “opportunism”, offers no way forward to resolving the historic crisis of proletarian leadership. These lessons will be grasped only through a full discussion of the opportunities which the concrete situation opened to Trotskyists, of the way in which the Bolshevik Faction sought to exploit those opportunities to fight for the revolutionary program in Nicaragua, and of the implications which that experience in struggle holds for Trotskyists fighting to reconstruct the Fourth International as the world party of socialist revolution. That discussion can be in no way separated from discussion of the postwar crisis of the Fourth International; on the contrary, the response of Trotskyists to the Nicaraguan revolution reveals in an undeniably living form all the major elements which have compounded that disastrous crisis. Such discussion must take place on the widest possible basis, and above all it must involve the comrades of the Bolshevik Faction themselves, as they provide their own account and assessment of the Simon Bolivar Brigade. 10. The FSLN and the Post-revolutionary Crisis What direction has the Nicaraguan revolution taken since the overthrow of Somoza? As the barely disputed leadership of the mass struggles against Somoza’s dictatorship, the FSLN came to power at the head of a politicalrevolution whose particular character posed sharply, in a concrete form, the necessity of moving forward with the tasks of social revolution. Political and economic conditions combined to determine the nationalization of the Somoza holdings, and other measures of state centralization. Cripplingly deformed by the burden of Somoza’s private plundering and maimed by the struggles of civil war, capitalism offered no solution to the crisis of the economy. Such a situation demanded the repudiation of the foreign debt to imperialism; expropriation of all the major capitalist holdings in land, industry, finance, and other sectors; and the development of a socialist plan for the reconstruction and development of the economy. A massive program of public works was needed urgently to provide for the needs of the workers and peasants (housing; hospitals and clinics; nurseries, schools, and colleges; irrigation and roads; etc.) and to reduce the huge mass of unemployed workers. Beyond the redistribution of land, a cheap credit scheme for small peasants was essential, along with incentives to encourage cooperative methods and collective farming. These methods offered the only alternative to a capitalist reconstruction of Nicaragua, and they were all rejected by the FSLN. When a delegation from COSEP (the bosses’ federation) visited New York in December, they argued vehemently that the Government of National Reconstruction and the FSLN were not heading a “communist” regime and declared their firm intention of continuing their business of profitable exploitation in Nicaragua. It was not reprisals they were seeking from the imperialists but economic aid for the “national reconstruction.” Unemployment shows every sign of rising rather than falling from November’s level of 45 percent. In December Jaime Wheelock (former leader of the Tendencia Proletaria) announced that “Nicaragua” could no longer afford to pay the Christmas bonus – the payment of a month’s wages, won from the Somoza regime by workers in struggle. After the eviction of peasants occupying land owned by the “anti-Somoza bourgeoisie”, the Government of National Reconstruction proceeded at the end of November to annul the decree of expropriation of the Somocistas, with the argument that this authority was being abused by some local Sandinista leaders. Three birds were killed with this stone: the process of nationalization was halted; a gesture was made to still the rising protests against the arrogance, greed, and various abuses of authority of some local FSLN representatives who were preparing themselves for a future as a corrupt and parasitic bureaucratic caste; and, at the same time, the investigations which were promised to follow would undoubtedly be used as a weapon in the internal power struggles of the FSLN. Since establishing the Government of National Reconstruction, the FSLN leadership has followed a consistent strategy of bureaucratizingthe revolution. The economic measures it has taken in the ultimate defense of capitalist property relations and profitability have been accompanied by counterrevolutionary initiatives to weld the independent bodies of trade unions, peasant unions, and Sandinista Defense Committees into rigid national institutions, subservient to the political authority of the FSLN leadership and intended to function as an arm of the state reaching into the very heart of the labor movement. These initiatives required the expulsion of the Simon Bolivar Brigade and the repression directed against the LMR and MAP / FO (their publications have been suppressed and many of their militants imprisoned – though later to be released after pressure from sections of workers, only to be imprisoned again more recently). And all the while the FSLN leadership has continued to work for the disarming of the workers and the building of some classless, apolitical army, dedicated to serving “Nicaragua” and the “Sandinista people.” This bureaucratization has been particularly evident with regard to the trade union movement. It was their role in building independent unions which partly prompted the victimization of the members of the Simon Bolivar Brigade. And the suppression of El Pueblo, the paper of the Frente Obrero, followed its attempts to mobilize the workers and its accusations that the FSLN “had sold out to the local bourgeoisie”. More recently, even the trade union body established by the Communist Party, the Centro de Accion y Unidad Sindical(CAUS), has been the object of repression. But, despite the energy of the FSLN in suppressing any symptoms of the independent mobilization of the masses, it continues to be under pressure from its supporters whom it has failed to bring fully under control. By May 1980 this pressure was being reflected in growing strains between the FSLN and the representatives of the bourgeoisie in the Junta. First conservative figurehead Violetta Chamorro left the government (on 19 April) to live in Panama. She was followed out (on 22 April) by millionaire capitalist Alfonso Robelo, who remains in Nicaragua at the head of the right-wing Nicaraguan Democratic Movement (MDN). The break coincided with the “coming into being” (announced on 21 April) of the new forty-seven-seat unelected Council of State. The MDN was allocated one seat in this fake legislature. The FSLN only took six seats for itself but packed it with nominees from the Sandinista Defense Committees. While one of the effects of the retirement of important bourgeois elements from the Junta is to permit the FSLN to refurbish its radical image, the break shows that, regardless of the FSLN’s intentions, the direction in which it will be forced to move is by no means yet finally and definitively decided. 11. Nicaragua, Imperialism, and Stalinism The process of bureaucratization has brought a measure of relief to both the imperialist powers and to the ruling Stalinist bureaucracies. Each had seen most to fear in the independent class mobilization of the proletariat, with the attendant specter of communism. It has been precisely through the Government of National Reconstruction’s international relations with the imperialists and the Stalinist bureaucracies (specifically, Castro’s regime) that the FSLN has exposed most clearly its own political essence and revealed the pressures bearing down upon it. Through reaching an agreement with the “anti-Somoza” wing of the bourgeoisie, the FSLN leadership secured the backing of the “social democracies” of Costa Rica, Panama, and Venezuela. Deepening its alliance with the bourgeoisie once in power, the FSLN leadership then sought aid from the imperialist powers, including above all the USA – the only force which had sustained Somoza in his dictatorship! It was the military of capitalist Panama which was brought in to train the re-formed armed forces. The imperialists have not been slow to take advantage of the FSLN’s evident desire for accommodation and have made the most of the leverage this gives them. Broad promises and partial negotiations have not yet resulted in a flow of funds, as the imperialists (acting especially through the World Bank) have held back both to ensure that the FSLN is capable of controlling the mass movement of workers and peasants and to increase the pressure on the FSLN to make further guarantees of capitalist stability in Nicaragua. This tactical position of the imperialists has been reinforced by developments beyond Nicaragua. On the one hand has come the new aggressive stance adopted by the US imperialists towards the Kremlin bureaucracy – an aggression already primed, but actually triggered by the Soviet invasion of Afghanistan. This latest posture has involved a shift back to the central position of US foreign policy since the second world war: the maintenance of military dictatorships and other fiercely repressive regimes as bastions of imperialist might against the “threat of communism” – in the shape of independent action by workers and peasants within these states at least as much as against the forces controlled by the Soviet bureaucracy and its underlings. The implications of this have been evident in Central America, where the rising tide of revolutionary struggles threatens to sweep away the pro-imperialist regimes in El Salvador, Honduras, and now Guatemala. The mass mobilizations in these states have been spurred on to new heights by the example of the Nicaraguan revolution, yet they have received absolutely no direct political or material assistance from the leadership of that revolution. On the contrary, when the military dictatorship of Honduras resorted to the desperate expedient of fueling a chauvinist campaign directed against the Nicaraguan revolution in order to divert support from the growing revolutionary struggles in Honduras itself, then the FSLN leadership responded by seeking closer ties with the “progressive” military dictatorship of El Salvador, which had been installed with the connivance of US imperialism as a last-ditch stand against the increasing power of the leftist guerrilla movement and its mass support. This betrayal of the workers and peasants of El Salvador typifies the foreign policy of the FSLN leadership. Far frozen following a policy of proletarian internationalism, it has remained very firmly within the bounds of petty-bourgeois nationalism. Its foreign policy is the Siamese twin of its domestic policy. Rather than build the surest defense of the Nicaraguan revolution against imperialist intervention – by winning the support of the revolutionary proletariat beyond the borders of Nicaragua through aid and leadership for its other struggles against agents of imperialism in Central America – the FSLN rejected the road towards a Socialist United States of Central America and turned instead to the imperialist powers themselves for their “aid.” This project has received the enthusiastic backing of Castro. The Cuban Stalinists especially feared the emergence of an independent proletarian opposition to the petty-bourgeois nationalism of the FSLN leadership – a force which could have acted as a revolutionary pole of attraction counterposed to the political hegemony which the Havana bureaucracy seeks to impose on all the anti-imperialist struggles throughout the continent. Such a development would also have produced dangerous repercussions for the bureaucracy within Cuba itself, where Castro is clearly facing an upsurge of pressure from the proletariat and even from within the ranks of the Cuban Communist Party. Relieved by the firm action which the FSLN leadership has taken to repress the independent strength of the working class, Castro has warmly welcomed its overtures to imperialism. But the tactics of the imperialists themselves are posing fresh problems for the Stalinists. The imperialists have not yet resigned themselves to a Sandinista regime in Nicaragua, however conciliatory it may be. With the renewal of “cold war” aggression and the real possibility of further revolutionary overthrows in Central America, it has even become more rather than less likely that US imperialism will attempt a military intervention in the region – with one of its aims being to isolate or even crush the FSLN regime. Such considerations have played their part in the delay by the imperialists in “giving” aid to the Government of National Reconstruction. This, in turn, has increased the difficulties of the GNR itself, which inevitably faces a resurgence of militant pressure from the working class if the colossal economic crisis shows no sign of alleviation. So the imperialists are reviving the very specter of communism which they most want to crush, and in this dilemma it is Castro who comes to their rescue. The Cuban bureaucracy played no positive role in the overthrow of Somoza; yet it has no desire whatsoever to see imperialism regain all its lost authority and more by a military intervention in the region. And it is as fearful as the imperialists of the consequences of starving the Government of National Reconstruction of the materials with which to reconstruct capitalism in Nicaragua. For these reasons, the Cuban bureaucracy has been forced to step up its offers of assistance to the GNR. The FSLN leadership has responded cautiously to these initiatives, recognizing the very slippery rope it has chosen to step out on. When Havana offered 4,000 teachers, Managua accepted only 100, emphasizing how ready it was to accept similar offers from other Latin American states. Yet, at the same time, the Panamanian authorities have responded indignantly to what they claim is the swelling influx of Cuban officers and military experts by pulling out many of their military advisers. The December 1979 cabinet reshuffle was part of this shift in the relations of the FSLN leadership to the imperialists on the one hand and to the Cuban Stalinists on the other. After the collective resignation of 4 December, the new Government of National Reconstruction emerged at the end of the month with fewer bourgeois members and now more evidently dominated numerically by the FSLN. This move reflected the pressure from workers on the FSLN leadership to break its ties with the bourgeoisie, but the capitalist members still expressed the bourgeois political character of the government, which so far has shown no evidence of changing its established policies inside Nicaragua. The most recent resignations from the government – by Violetta Chamorro and Alfonso Robelo – along with the hardening of relations with the US, take this process one step further – though they still do not mark a definitive qualitative change in the relations of the FSLN with the Nicaraguan bourgeoisie or with imperialism. Externally, the FSLN leadership is now making a futile attempt to use the threat of Cuban involvement as a gun to hold at the heads of the imperialists when it demands the speeding up of financial aid. In August, FSLN leader Tomas Borge publicly rebuked his deputy for talk of buying arms from the Soviet Union and the deformed workers’ states, declaring that approaches would be made to Belgium and the USA. But on 17 November the same Borge defiantly cried that, “Nicaragua did not stand alone; it had excellent friends, such as Cuba” ( Latin American Newsletter). These threats can mean little to the imperialists. The FSLN leadership is already begging them to take on the mortgage of the Nicaraguan revolution lock, stock, and barrel. If the imperialists continue to hold back, then the Stalinists will have little option but to move towards giving Nicaragua a new status as the Angola of Latin America: a zone whose wealth imperialism may plunder and whose labor imperialism may exploit within limits that can guarantee the economic interests of the Stalinist bureaucracies, yet where imperialism has no direct political or military power but depends for access on the Stalinists and their continued repression of the proletariats symbol of counterrevolutionary Stalinism and its policies of “detente” with imperialism. But imperialists, Stalinists, and FSLN leaders alike are treading a very dangerous path in unpredictable conditions. Further developments in the “new cold war” and within Latin America could close the “Angola” option for good and all. They could even create conditions that would force the Kremlin and Havana bureaucracies to move for a complete social overturn in Nicaragua, with the transformation of sections of the FSLN leadership into a new Stalinist leadership and so to effect by bureaucratic – and perhaps even military – means the structural assimilation of Nicaragua into a deformed workers’ state. While such a possibility seems remote at present, the rapid tempo of international developments could bring it swiftly to the fore. What is clear at present, despite the distortions of the American SWP, is that – through the Government of National Reconstruction, the reconstruction of the state apparatus, and the bureaucratization of the revolution – the FSLN leadership has been attempting to lay a firm basis for developing friendly relations with either imperialism or the ruling Stalinist bureaucracies – or indeed both – and that this activity has been undertaken at the expense of the independent class interests of the proletariat in Nicaragua. 12. For the Independent Program of the Revolutionary Proletariat The task of Trotskyists is to give an independent leadership to the proletariat by the fight for a revolutionary program that can unite the peasantry behind the vanguard of the working class in the struggle for socialistrevolution in Nicaragua. That program must direct itself centrally and at all times to the independent class interests, independent class organization, and independent class strength of the proletariat. It is not impossible that even now elements in the FSLN leadership may break from the Government of National Reconstruction and rally to the call for the dictatorship of the proletariat; but no strategy can be based in any way on such possibilities. Any compromise or collaboration with the proven petty-bourgeois nationalism of the FSLN leadership can only betray the workers and peasants of Nicaragua and all Central America. Without the building of an independent Trotskyist party, committed to the reconstruction of the Fourth International and fighting consistently among the workers and peasants for a revolutionary program, the gains made in the great struggles against Somoza will be rolled back by imperialist reaction or chained in bureaucratization by the FSLN leaders and their Stalinist accomplices. Such a party, which does not yet exist in Nicaragua, would now have vast potential to lead Nicaraguan workers towards an extension of the revolutionary gains which are now threatened by the policy of the FSLN. As workers and peasants so recently mobilized in mass struggles against the imperialist-backed dictator, come in practice into conflict with their new rulers, they will be disposed to align themselves with a party which offers an independent solution to the material and political problems they face. The program which must be put forward by Trotskyists is one which is directed towards completing the revolution which began with the successful struggle against Somoza and which, therefore, expresses the strategy of permanent revolution. It should include a set of demands placed upon the FSLN, the bureaucratized workers’ states, and the labor movement in the imperialist countries, to defend against imperialist attack – by military means if necessary – all the gains so far made. It must embody the existing political need of the oppressed masses for the right to have their voices heard and for the building of organs through which this could be achieved. As long as the bourgeois-democratic aspects of the FSLN’s own program remain unfulfilled and the FSLN itself increasingly violates democratic rights, it is incumbent upon the Trotskyists to bring democratic demands to the forefront of the struggle. They must demand the end of all censorship against workers’ publications, the release of all imprisoned worker and peasant militants, an end to bureaucratic measures against independent trade unions, and no disarming of the masses. In addition to these demands against FSLN repression, the demand for a sovereign constituent assembly elected by universal franchise remains valid and can be sharply counterposed to the bureaucratic Council of State established by the FSLN. But it is fundamental that, alongside these demands for bourgeois forms of democracy and democratic rights, the Trotskyists fight simultaneously for the building of independent political organs of workers’ power – popular assemblies (soviets) in which workers’ and peasants’ organizations will be represented and which can become the political basis of the establishment of a workers’ state. Revolutionaries will also fight for the establishment of armed workers’ militias responsible to the popular assemblies – as opposed to the FSLN’s attempt to rebuild a standing army. But before such organs are built, the Trotskyists must at all times advance a governmental slogan which is appropriate to the moment. Today the most important element of this continues to be the call for the expulsion of the bourgeois ministers from the government. Such a call is not a formal one: in fact, it may take place formally by the voluntary departure of the bourgeois ministers. As a political slogan the call for expulsion must be accompanied by demands on the FSLN, which still dominates the mass movement and gains ever more control of the government, to implement a program designed to meet the material needs of the masses. These demands would focus on the need to expropriate all capitalist property under workers’ management and without compensation – in contrast to the FSLN’s policy of restricting nationalizations to punitive ones against Somocistas; the need for a program of useful public works to resolve the massive unemployment problem; the need for adequate wages protected against inflation and the rationing of essential goods; the need for the expropriation of the remaining large landholdings and their redistribution to democratically elected peasant cooperatives and collectives; the need to disavow all the international debts entered into by the Somoza regime; the need for the nationalized banking system to be placed under workers’ management; the need for the banks to initiate cheap credit schemes for the peasant cooperatives. Viewed in isolation, of course, such a program, in a country which is as backward and beset with economic crisis as Nicaragua, can easily be laughed out of court as idealistic. Trotskyists, however, see such a program to meet the basic economic needs of the masses as inseparably tied to the political conditions for its fulfillment. The economic program, therefore, must be linked to demands on the bureaucratized workers’ states to supply unconditional economic assistance to a government carrying out such a program – especially assistance which neutralizes any economic sanctions imposed by the imperialists. Demands on the workers’ movement in imperialist countries to mobilize in concrete solidarity against any economic and other sanctions are also important. In addition, the economic development of Nicaragua in the long run is tied to the rest of the area and to the development of an international socialist planned economy. It is also necessary, therefore, to raise in this context the slogan of the United Socialist States of Central America and the Caribbean. This again is today not an abstract slogan, since political developments with revolutionary potential are taking place throughout the region. In concrete terms, the implementation of the slogan requires maximum possible political and material support to the struggles in neighboring countries – in sharp contrast to the FSLN’s treacherous diplomatic neutrality towards the mass struggle in other countries. The revolutionary program is not a sectarian method of merely denouncing the FSLN. In the course of a struggle for this program, tens of thousands of supporters of the FSLN and even some of its existing leadership can be won to a revolutionary perspective – and the enemies of the masses within its ranks can be finally exposed and the road to socialism opened. Notes 1. The militant neighborhood organizations spontaneously set up before the July revolution were generally known as ‘Civil Defense Committees’ (CDCs). The network of neighborhood organizations set up after the July revolution by the Sandinista regime, which bureaucratically incorporated the CDCs, was called the ‘Sandinista Defense Committees’ (CDSs). The TILC resolution describes correctly the two phases in the development of neighborhood organizations but uses the later name for both phases. [International Trotskyist Review]. 2. That is, these Brigade members were deported to Panama and detained and beaten by Panamanian security forces in Panama. [International Trotskyist Review]. Workers Socialist League Index|Encyclopedia of Trotskyism|Marxists’ Internet Archive
https://www.marxists.org/history/etol/document/wsl/Nicaragua80-TILC.htm
Buster Simpson's commission to create public art for Seattle's massive waterfront redevelopment is announced on January 9, 2013. - HistoryLink.org Buster Simpson's commission to create public art for Seattle's massive waterfront redevelopment is announced on January 9, 2013. HistoryLink.org Essay 10996 Secured Embrace(Buster Simpson, 2001-2013), Seattle, August 28, 2013 Photo by Colleen E. O'Connor On January 9, 2013, Buster Simpson (b. 1942) is named as the first of five artists commissioned to create permanent public artworks on Seattle's central waterfront, which is undergoing a major years-long redevelopment. An internationally known public artist who has been documenting environmental and economic change in Seattle for four decades, Simpson is chosen to work with the designers of a new seawall that the Seattle Department of Transportation is building to replace the aging, deteriorated wall that holds back the waters of Elliott Bay from the downtown waterfront. Following the selection he begins planning a series of works to be installed at a new beach to be constructed near Pioneer Square as part of the seawall project. The seawall commission is not Simpson's first attempt to engage with the design of Seattle's waterfront. In 1974, not long after arriving in Seattle, he suggested designing what became Myrtle Edwards Park by "re-orchestrating the rubble," largely freeway-construction debris, that then lined the shoreline, rather than covering or removing it, but his idea was not adopted. Doomed Locations Lewis Cole "Buster" Simpson moved to Seattle in 1973 and shortly thereafter created his first "eco-art installation" (Graves, "Buster Simpson Arrives ..."). Hired to clear out the junk that had accumulated over the years in two long-vacant floors of an old warehouse above a Pioneer Square gallery, he and fellow artist Chris Jonic (b. 1950) made the project into an art exhibition titled Selective Disposal Project, selecting, adapting, and rearranging objects in the rooms, documenting everything in photos and film, and finally giving away all the usable materials they had found. In Belltown, "where he was based from 1974 to 1987, moving from doomed location to doomed location and using the conditions of real estate as the basis for his work" (Graves, "The Outside Artist"), Simpson continued documenting and making art out of what was left behind in a rapidly changing city. He photographed and filmed historic old buildings slated to be replaced by new construction and collected discarded lumber and other materials from the doomed buildings, using the recovered objects to create works displayed in the buildings, on the streets, and in gallery shows. Learning Lessons In 1974, Simpson set his sights on a far larger pile of discarded rubble than any single building could provide. At the time the city was planning to create a park -- then known as Elliott Bay Park, but later named Myrtle Edwards Park -- extending north from Pier 70, the northernmost of the downtown piers, to the Pier 86 Grain Terminal. Most of that stretch of shoreline then consisted of piles of debris from demolished buildings and existing streets dumped there two decades earlier during construction of Interstate 5. As Seattle Timescolumnist Alf Collins described it following a 1975 visit to the area with Simpson: "The banks and coves are covered with an avalanche of chunks of concrete. The top of the bank is mounded with other construction debris covered with natural growth...."There is a wondrous assortment of building fragments in the short stretch of land including huge chunks of granite and sandstone, conglomerations of bricks, scraps of ornate tile work and whole flights of stairs" ("Elliott Bay Park ..."). Not surprisingly, the city parks department planned to remove or cover up the debris, hauling it to the shoreline to control erosion or covering it with grass, trees, and plantings to create a typical park green space. Simpson saw that as a wasted opportunity to learn from and about the city's past. Rather than paying to hide or get rid of the rubble, Simpson proposed using the money "to hire artists to rearrange the sculptural elements and the heavy equipment to move it around" ("Elliott Bay Park ..."). He called this "Creative use of Seattle's architectural rubble: As much of Seattle's history is torn down, its material, instead of rubble, could become a resource for the park" (Simpson to Chapman). As described four decades later (in a major exhibition of Simpson's work at Seattle's Frye Art Museum), with his 1974 proposal for "re-orchestrating the rubble," called Learning Lessons, Simpson "wanted the park design to be 'honest' about its source material and for the site to reflect and document the city's own history of progress and renewal" ("Myrtle Edwards Park Proposal"). Simpson also advocated "Park development as a learning experience" -- having much of the work done by the Neighborhood Youth Corp guided by "skilled craftsmen, engineers, architects, and artists all working together" (Simpson to Chapman). In July 1974 Simpson presented his ideas for learning lessons in the design and construction of the park at a meeting of the parks department. That September he wrote to Seattle City Council member Bruce Chapman: "Though the presentation was received well, I felt that the Parks Department was apprehensive about the feasibility of my ideas. I believe that my ideas are feasible and could be implemented at a savings to the taxpayer and as a social service to the community" (Simpson to Chapman). Simpson was still promoting his ideas when he toured the future park area with Alf Collins in the summer of 1975, but he did not convince the parks department or the city council. The rubble in which Simpson saw beauty and potential was removed or covered, and Myrtle Edwards Park developed like most parks with grass, trees, and landscaping. Although Simpson's ideas for Myrtle Edwards Park were not adopted, he went on to work frequently on public-art projects with various City of Seattle departments and agencies as he built an international reputation for his public art over the next 40 years, with permanent work on display not just in Seattle but across the United States and Canada. In 2013, the same year that the Frye Art Museum mounted the first full retrospective of his career, Simpson got another chance to play a role in designing Seattle's waterfront, for which city officials and planners were envisioning a total makeover. A New Waterfront Myrtle Edwards Park was by no means the only part of Seattle's waterfront built over buried fill and rubble. In fact, the entire central waterfront extending south from the park all the way to Washington Street below Pioneer Square was built on fill dumped into the tidelands over the years. That central-waterfront fill was protected from the waters of Elliott Bay by a seawall built early in the twentieth century, and traversed by an elevated roadway, the Alaskan Way Viaduct, built in the middle of that century. Both aging structures were deteriorating, and after years of study, debate, discussion, and controversy following the 2001 Nisqually earthquake, city and state officials decided to build a new seawall and to replace the viaduct with a bored tunnel. Even before work got underway (seawall construction and tunneling both began in 2013, although the tunnel-boring machine ground to an unplanned stop later that year, with timing of a re-start uncertain as of late 2014), officials began planning for the new central waterfront that would result from the two massive projects. The city hired James Corner Field Operations, a New York City firm known for its work on that city's High Line, a former elevated railroad converted into a hugely popular park, to come up with an overall design plan for a new viaduct-free waterfront. In addition, the Seattle Office of Arts & Culture set out to commission artists to create permanent public artworks on that newly designed waterfront. Five were selected, with the last and largest commission going to Ann Hamilton (b. 1956). Multidisciplinary visual artist Norie Sato (b. 1949), sound artist Stephen Vitiello (b. 1964), and sculptor Oscar Tuazon (b. 1975) also received commissions. The first waterfront-art commission, announced in a January 9, 2013, post on the Office of Arts & Culture's Art Beatblog, went to Buster Simpson. He was chosen to work with designers of the reconstructed Elliott Bay Seawall being built by the Seattle Department of Transportation "to develop ... artwork that will that contribute to the overall project goals of both habitat restoration and the development of public open space along the seawall" ("Buster Simpson to Create ..."). Funding for the commission came from the city's 1 Percent for Arts program, in which a small portion of construction-project costs is reserved for public art. Anthropocene Beach By January 2014, Simpson was designing a series of artworks to be installed at a new beach that seawall designers planned to construct on the waterfront near Pioneer Square, between Yesler Way and Washington Street. He called the piece Anthropocene Beach, a reference to the "Anthropocene Epoch," a name some scientists had recently proposed using to identify the current geological epoch as one influenced by human activity. The name, and the materials Simpson hoped to use, reflected the same commitment to honesty about the landscape's human origins that his Elliott Bay Park proposal had years earlier. He proposed using "Anthropomorphic Pods ... as both a metaphor of human intervention and, as intended, an engineered solution to shoreline armor and anchor" ("Anthropocene Beach"). The pods would consist of "reinforced-concrete tetrapods that embrace bunches of reclaimed tree root wads and driftwood" (Graves, "The First Artists ..."). Root-wads held in place by hidden concrete tetrapods had become a common feature in habitat-restoration projects, but Simpson saw hiding the concrete as "not honest about the fact that this is a man-made intervention to correct earlier man-made environmental damage" (Graves, "Simpson, Buster"). When he exhibited a root-wad-and-tetrapod sculpture called Secured Embraceat the Frye exhibition the concrete was in plain sight, and he hoped to leave his concrete pods visible on the seawall beach -- if federal requirements to use "natural" materials in beach-habitat restoration allowed. If not, he said, "I'm hoping they will let us use sculptural stone anchors" (Graves, "The First Artists ..."). Simpson's proposals also reflected his career-long commitment to conveying the city's environmental and human history through artwork that recycled and re-used materials others might see as rubble to clear away. Stone anchors "would ... either be carved to suggest or be actual architectural artifacts," part of a "promenade where city meets beach ... would consist of inert architectural and cultural rubble reconstituted in blocks to be sliced ... into paver threshold units," and a "sitting sea wall" would be built of blocks of Wilkeson sandstone (a stone mined in Pierce County and used in the Washington State Capitol and many other historic buildings) shaped to resemble sandbags or products unloaded from ships by stevedores ("Anthropocene Beach"). Simpson even called for preserving portions of the elevated roadway whose removal from the waterfront was a primary goal of city planners. One proposed element of his beach artwork was "Alaskan Way Viaduct Totems," created by "saving ... two and possibly four or more columns as artifact relics of the Alaskan Way Viaduct," and he went beyond the confines of his own project to argue "that the vestige of a combination of footprints and columns [of the viaduct] along the entire waterfront (where possible) would provide an additional layer of meaning and complexity [in] the streetscape design and create another unifying vector" ("Anthropocene Beach"). This essay made possible by: Seattle Office of Arts & CultureKing County Future site of Elliott Bay (later Myrtle Edwards) Park, Seattle, ca. 1970 Courtesy Seattle Municipal Archives (77721) Construction of new seawall near Yesler Way, viewed from Pier 50, Seattle, October 2014 HistoryLink.org Photo by Kit Oldham Sources: Visual Arts
https://historylink.org/File/10996
The effect of physical activity on mortality and cardiovascular disease in 130 000 people from 17 high-income, middle-income, and low-income countries: the PURE study - The Lancet Articles | Volume 390, ISSUE 10113 , P2643-2654, December 16, 2017 The effect of physical activity on mortality and cardiovascular disease in 130 000 people from 17 high-income, middle-income, and low-income countries: the PURE study Correspondence Correspondence to: Dr Scott A Lear, Healthy Heart Program, St Paul's Hospital, Vancouver, BC, Canada, V6Z 1Y6 Contact Affiliations Faculty of Health Sciences, Simon Fraser University, Burnaby and Division of Cardiology, Providence Health Care, Vancouver, BC, Canada Weihong Hu, MSc Weihong Hu Affiliations Population Health Research Institute, Hamilton Health Sciences & McMaster University, Hamilton, ON, Canada Sumathy Rangarajan, MSc Sumathy Rangarajan Affiliations Population Health Research Institute, Hamilton Health Sciences & McMaster University, Hamilton, ON, Canada Danijela Gasevic, PhD Danijela Gasevic Affiliations Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK Darryl Leong Affiliations Population Health Research Institute, Hamilton Health Sciences & McMaster University, Hamilton, ON, Canada Romaina Iqbal, PhD Romaina Iqbal Affiliations Department of Community Health Sciences and Medicine, Aga Khan University, Karachi, Pakistan et al. Amparo Casanova, PhD Amparo Casanova Affiliations Population Health Research Institute, Hamilton Health Sciences & McMaster University, Hamilton, ON, Canada Sumathi Swaminathan, PhD Sumathi Swaminathan Affiliations St John's Research Institute, St John's National Academy of Health Sciences, Bangalore, India R M Anjana, PhD R M Anjana Madras Diabetes Research Foundation, Chennai, India Rajesh Kumar, MD Rajesh Kumar Affiliations School of Public Health, Postgraduate Institute of Medical Education & Research, Chandigarh, India Annika Rosengren, MD Annika Rosengren Affiliations Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Li Wei, PhD Li Wei Affiliations Medical Research & Biometrics Center, National Center for Cardiovascular Diseases, Fu Wai Hospital, Beijing, China Wang Yang, MSc Wang Yang Affiliations Medical Research & Biometrics Center, National Center for Cardiovascular Diseases, Fu Wai Hospital, Beijing, China Wang Chuangshi Affiliations Medical Research & Biometrics Center, National Center for Cardiovascular Diseases, Fu Wai Hospital, Beijing, China Liu Huaxing Liu Huaxing Affiliations Center for Disease Control & Prevention, Mengla County, Xishuangbanna Prefecture, Yunnan Province, China Sanjeev Nair, MD Sanjeev Nair Affiliations Government Medical College, Trivandrum, India Rafael Diaz, MD Rafael Diaz Affiliations Estudios Clinicos Latinoamerica ECLA, Rosario, Santa Fe, Argentina Hany Swidon, MD Hany Swidon Affiliations Rajeev Gupta, MD Rajeev Gupta Affiliations Eternal Heart Care Centre & Research Institute, Mount Sinai New York Affiliate, Jaipur, India Noushin Mohammadifard, PhD Noushin Mohammadifard Affiliations Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran Patricio Lopez-Jaramillo, MD Patricio Lopez-Jaramillo Affiliations FOSCAL, Medical School Universidad de Santander, Bucaramanga, Colombia Aytekin Oguz, MD Aytekin Oguz Affiliations Department of Internal Medicine, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey Katarzyna Zatonska, PhD Affiliations Department of Social Medicine, Medical University of Wroclaw, Wroclaw, Poland Pamela Seron, PhD Pamela Seron Affiliations Universidad de La Frontera, Temuco, Chile Alvaro Avezum, MD Alvaro Avezum Affiliations Dante Pazzanese Institute of Cardiology, São Paulo, Brazil Paul Poirier, MD Paul Poirier Affiliations Institut universitaire de cardiologie et de pneumologie de Québec, Québec City, QC, Canada Koon Teo, MB Koon Teo Affiliations Population Health Research Institute, Hamilton Health Sciences & McMaster University, Hamilton, ON, Canada Salim Yusuf, DPhil Salim Yusuf Affiliations Population Health Research Institute, Hamilton Health Sciences & McMaster University, Hamilton, ON, Canada Published: September 21, 2017 DOI: https://doi.org/10.1016/S0140-6736(17)31634-3 Summary Summary Background Physical activity has a protective effect against cardiovascular disease (CVD) in high-income countries, where physical activity is mainly recreational, but it is not known if this is also observed in lower-income countries, where physical activity is mainly non-recreational. We examined whether different amounts and types of physical activity are associated with lower mortality and CVD in countries at different economic levels. Methods In this prospective cohort study, we recruited participants from 17 countries (Canada, Sweden, United Arab Emirates, Argentina, Brazil, Chile, Poland, Turkey, Malaysia, South Africa, China, Colombia, Iran, Bangladesh, India, Pakistan, and Zimbabwe). Within each country, urban and rural areas in and around selected cities and towns were identified to reflect the geographical diversity. Within these communities, we invited individuals aged between 35 and 70 years who intended to live at their current address for at least another 4 years. Total physical activity was assessed using the International Physical Activity Questionnaire (IPQA). Participants with pre-existing CVD were excluded from the analyses. Mortality and CVD were recorded during a mean of 6·9 years of follow-up. Primary clinical outcomes during follow-up were mortality plus major CVD (CVD mortality, incident myocardial infarction, stroke, or heart failure), either as a composite or separately. The effects of physical activity on mortality and CVD were adjusted for sociodemographic factors and other risk factors taking into account household, community, and country clustering. Findings Between Jan 1, 2003, and Dec 31, 2010, 168 916 participants were enrolled, of whom 141 945 completed the IPAQ. Analyses were limited to the 130 843 participants without pre-existing CVD. Compared with low physical activity (<600 metabolic equivalents [MET] × minutes per week or <150 minutes per week of moderate intensity physical activity), moderate (600–3000 MET × minutes or 150–750 minutes per week) and high physical activity (>3000 MET × minutes or >750 minutes per week) were associated with graded reduction in mortality (hazard ratio 0·80, 95% CI 0·74–0·87 and 0·65, 0·60–0·71; p<0·0001 for trend), and major CVD (0·86, 0·78–0·93; p<0·001 for trend). Higher physical activity was associated with lower risk of CVD and mortality in high-income, middle-income, and low-income countries. The adjusted population attributable fraction for not meeting the physical activity guidelines was 8·0% for mortality and 4·6% for major CVD, and for not meeting high physical activity was 13·0% for mortality and 9·5% for major CVD. Both recreational and non-recreational physical activity were associated with benefits. Interpretation Higher recreational and non-recreational physical activity was associated with a lower risk of mortality and CVD events in individuals from low-income, middle-income, and high-income countries. Increasing physical activity is a simple, widely applicable, low cost global strategy that could reduce deaths and CVD in middle age. Funding Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Ontario SPOR Support Unit, Ontario Ministry of Health and Long-Term Care, AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, GSK, Novartis, King Pharma, and national and local organisations in participating countries that are listed at the end of the Article. References 1. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015; 385 : 117-171 2. Bloom DE Cafiero ET Jané-Llopis E et al. The global economic burden of noncommunicable diseases. World Economic Forum , Geneva 2011 3. Roth GA Forouzanfar MH Moran AE et al. Demographic and epidemiologic drivers of global cardiovascular mortality. N Engl J Med. 2015; 372 4. Benziger CP Roth GA Moran AE The Global Burden of Disease Study and the preventable burden of NCD. Glob Heart. 2016; 11 : 393-397 5. Beaglehole R Bonita R Global public health: a scorecard. : 1988-1996 6. Sallis JF Bull F Guthold R et al. Progress in physical activity over the Olympic quadrennium. Lancet. 2016; 388 : 1325-1336 7. Sixty-sixth World Health Assembly. Follow-up to the political declaration of the high-level meeting of the General Assembly on the Prevention and Control of Non-communicable Diseases: United Nations, 2013. 8. 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Influence of exercise, walking, cycling, and overall nonexercise physical activity on mortality in Chinese women. : 1343-1350 34. Yu R Leung J Woo J Housework reduces all-cause and cancer mortality in Chinese men. PLoS One. 2013; 8 : e61529 35. Besson H Brage S et al. Relationship between subdomains of total physical activity and mortality. Med Sci Sports Exerc. 2008; 40 : 1909-1915 36. Autenrieth CS Baumert J Baumeister SE et al. Association between domains of physical activity and all-cause, cardiovascular and cancer mortality. Eur J Epidemiol. 2011; 26 : 91-99 37. Sabia S Dugravot A Kivimaki M Brunner E Shipley MJ Singh-Manoux A Effect of intensity and type of physical activity on mortality: results from the Whitehall II cohort study. Am J Public Health. 2012; 102 : 698-704 38. Hu G Jousilahti P Antikainen R Tuomilehto J Occupational, commuting, and leisure-time physical activity in relation to cardiovascular mortality among Finnish subjects with hypertension. Am J Hypertens. 2007; 20 : 1242-1250 39. Wu CY Hu HY Chou YC Huang N Chou YJ Li CP The association of physical activity with all-cause, cardiovascular, and cancer mortalities among older adults. Prev Med. 2015; 72 : 23-29 40. Vaes AW Garcia-Aymerich J Marott JL et al. Changes in physical activity and all-cause mortality in COPD. Eur Respir J. 2014; 44 : 1199-1209 41. Bauman A Bull F Chey T et al. The International Prevalence Study on Physical Activity: results from 20 countries. Int J Behav Nutr Phys Act. 2009; 6 21 42. Wanner M Probst-Hensch N Kriemler S Meier F Autenrieth C Martin BW Validation of the long international physical activity questionnaire: influence of age and language region. Prevent Med Rep. 2016; 3 : 250-256 Article info Publication history Published: September 21, 2017 Identification DOI:https://doi.org/10.1016/S0140-6736(17)31634-3 Copyright © 2017 Elsevier Ltd. All rights reserved.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31634-3/fulltext
Electrospinning through the prism of time | Request PDF Request PDF | Electrospinning through the prism of time | Electrospinning is a versatile and flexible technique for the preparation of ultrafine fibers. The present study aims to provide a comprehensive... | Find, read and cite all the research you need on ResearchGate Electrospinning through the prism of time DOI: 10.1016/j.mtchem.2021.100543 Abstract Electrospinning is a versatile and flexible technique for the preparation of ultrafine fibers. The present study aims to provide a comprehensive overview of electrospinning, as a complex technique, its evolution toward the high-throughput techniques, including the basic principles, parameters influencing the fibers production process, methods applied to solve the alignment difficulties, commonly used polymers and solvents, and the applications of the electrospun materials. We begin with an insight into the history of electrospinning, followed by its theoretical background and typical apparatus. Then, its renaissance over the past two decades as a powerful technology for the production of nanofibers suitable for industrial scale is presented. Afterward, we briefly discuss the applications of electrospun fibers, including use in different fields of industry, energy harvesting/conversion/storage, photonic and electronic devices, as well as biomedical applications. In the end, we also offer perspectives on the challenges and new directions for developments in electrospinning. ... Electrospinning technology, as an excellent method for producing nano-to-microscale fibers, has attracted much attention due to its versatility, rapidness, controllability, low cost, and large surface area to volume ratio micro/nanofibers with uniform or special microscopic morphology [1] [2] [3]. Electrospinning has had a century-long development [2,4,5]. In 1745, Bose determined that a large electric potential is necessary to generate aerosols from fluid drops [6]. ... ... Electrospinning technology, as an excellent method for producing nano-to-microscale fibers, has attracted much attention due to its versatility, rapidness, controllability, low cost, and large surface area to volume ratio micro/nanofibers with uniform or special microscopic morphology [1][2][3]. Electrospinning has had a century-long development [2, 4,5]. In 1745, Bose determined that a large electric potential is necessary to generate aerosols from fluid drops [6]. ... [2, 13]. With the increasing popularity of nanofibers, electrospinning technology has been employed extensively. ... Electrospun Nanofibers for Dura Mater Regeneration: A Mini Review on Current Progress Dural defects are a common problem in neurosurgical procedures and should be repaired to avoid complications such as cerebrospinal fluid leakage, brain swelling, epilepsy, intracranial infection, and so on. Various types of dural substitutes have been prepared and used for the treatment of dural defects. In recent years, electrospun nanofibers have been applied for various biomedical applications, including dural regeneration, due to their interesting properties such as a large surface area to volume ratio, porosity, superior mechanical properties, ease of surface modification, and, most importantly, similarity with the extracellular matrix (ECM). Despite continuous efforts, the development of suitable dura mater substrates has had limited success. This review summarizes the investigation and development of electrospun nanofibers with particular emphasis on dura mater regeneration. The objective of this mini-review article is to give readers a quick overview of the recent advances in electrospinning for dura mater repair. ... The concept of electrospinning was proposed as early as 400 years ago, evolved from the original electrospray technology, and has developed to the present. It is classified from its fluid strands: single-fluid electrospinning (blended electrospinning and emulsion electrospinning), double-fluids electrospinning (coaxial electrospinning and side-by-side electrospinning) and multi-fluids electrospinning (tri-fluid tri-layer coaxial electrospinning and other multi-fluid electrospinning) ( Figure 6) [71] . medical device for hospital surgery to treat wounds, surgical sutures can effectively improve the healing rates of wounds and reduce the pain of patients. ... ... The concept of electrospinning was proposed as early as 400 years ago, evolved from the original electrospray technology, and has developed to the present. It is classified from its fluid strands: single-fluid electrospinning (blended electrospinning and emulsion electrospinning), double-fluids electrospinning (coaxial electrospinning and side-by-side electrospinning) and multi-fluids electrospinning (tri-fluid tri-layer coaxial electrospinning and other multi-fluid electrospinning) ( Figure 6) [71] . ... Electrospun Medical Sutures for Wound Healing: A Review With the increasing demand for wound healing around the world, the level of medical equipment is also increasing, but sutures are still the preferred medical equipment for medical personnel to solve wound closures. Compared with the traditional sutures, the nanofiber sutures produced by combining the preparation technology of drug-eluting sutures have greatly improved both mechanical properties and biological properties. Electrospinning technology has attracted more attention as one of the most convenient and simple methods for preparing functional nanofibers and the related sutures. This review firstly discusses the structural classification of sutures and the performance analysis affecting the manufacture and use of sutures, followed by the discussion and classification of electrospinning technology, and then summarizes the relevant research on absorbable and non-absorbable sutures. Finally, several common polymers and biologically active substances used in creating sutures are concluded, the related applications of sutures are discussed, and the future prospects of electrospinning sutures are suggested. ... Electrostatic fiber fabrication, also known as "electrospinning", has emerged as the most preferred choice for producing continuous fibers with diameters below 1 μm. [1][2] [3] Both synthetic, natural polymers and co-polymers are successfully electrospun. Natural polymers such as collagen, cellulose, silk fibroin, keratin, gelatin and polysaccharides (chitosan, alginate) are used to prepare the corresponding electrospun nanofibers by electrospinning. ... Electrospun Cellulose Nanofiber Composites in Catalysis: A Review ... The application of nanotechnology such as electrospinning to design and construct biomaterial scaffolds is a promising trend in the fields of tissue engineering and regenerative medicine [22]. Currently, the conventional electrospinning device commonly employs a metal plain plate or low-speed roller to collect electrospun nanofibers, and in this context, the electrospun nanofibers are harvested in a totally chaotic and randomly deposited manner [23][24] [25] . It is well known that the morphology and structure of tissue-engineered scaffolds play important roles in physical and biological performance [26,27]. ... Designing an Innovative Electrospinning Strategy to Generate PHBV Nanofiber Scaffolds with a Radially Oriented Fibrous Pattern Qiuyu Wang Jianwei Ma Shaojuan Chen Shaohua Wu Electrospinning has contributed substantially to the construction of nanofibrous scaffolds for potential tissue engineering and regenerative medicine applications. However, conventional electrospinning only has the ability to generate and collect nanofiber scaffolds with a randomly oriented fibrous pattern, which lack the necessary cell alignment guidance function. In this study, a novel electrospinning fiber-collecting device was designed and developed by setting a series of small pin-ring-structured collectors on a large plain plate. Specifically, we demonstrated that the pin-ring-structured collectors, which were constructed by inserting a metal pin into the center of a metal ring, could collect the as-electrospun nanofibers with radially oriented structures in an innovative manner. We first investigated the suitable polymeric concentration for electrospinning poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and the optimum electrospinning concentration of PHBV was found to be 12% (w/v) PHBV dissolved in hexafluoroisopropyl alcohol (HFIP). Then, 12% (w/v) PHBV solution was electrospun into radially oriented nanofiber scaffolds using our novel electrospinning strategy, and their various performances were further compared with conventionally randomly oriented nanofiber scaffolds that were also produced from 12% (w/v) PHBV solution. The results showed that the radially oriented PHBV nanofiber scaffolds exhibited obviously enhanced mechanical properties and decreased hydrophobicity compared with the randomly oriented PHBV nanofiber scaffold controls. Importantly, the biological properties of radially oriented PHBV nanofiber scaffolds were also demonstrated to be enhanced, compared with randomly oriented PHBV nanofiber scaffolds, by effectively inducing cell alignment and significantly promoting cell proliferation. In sum, the present study indicates that our as-prepared nanofiber scaffolds with a radially oriented pattern are of great interest for advanced applications, such as wound dressings and tissue-engineered scaffolds. ... As a consequence, it is obvious that the nanofibers will provide a greater surface area in a certain volume than a commonly used natural/synthetic macrofibers (50,51). The surface-area-to-volume ratio of a nanofiber can be as large as 10 3 times of a macrofibers (52, 53) . Eventually, the surface area of a nanofibers mat ranges from 10 to 20 m 2 /g, which is much higher than that of the commonly used macrofibers based woven-fabric/nonwoven-mat (2,7,8). ... Polymer Nanofibers Chapter Full-text available Sumit Mandal Guowen Song Hongbo Zeng Lynn Boorady ... [ 65, 72] According to the literature, pristine polymeric ENMs cannot reach the required process performance and efficacy, thus limiting their practicability [18,73,74]. Various approaches have been used to enhance the hydrophobicity, permeate flux, and mechanical strength of the ENMs for the MD process [75]. ... Modified Electrospun Membranes Using Different Nanomaterials for Membrane Distillation Muzamil Khatri Lijo Francis Nidal Hilal Obtaining fresh drinking water is a challenge directly related to the change in agricultural, industrial, and societal demands and pressure. Therefore, the sustainable treatment of saline water to get clean water is a major requirement for human survival. In this review, we have detailed the use of electrospun nanofiber-based membranes (ENMs) for water reclamation improvements with respect to physical and chemical modifications. Although membrane distillation (MD) has been considered a low-cost water reclamation process, especially with the availability of low-grade waste heat sources, significant improvements are still required in terms of preparing efficient membranes with enhanced water flux, anti-fouling, and anti-scaling characteristics. In particular, different types of nanomaterials have been explored as guest molecules for electrospinning with different polymers. Nanomaterials such as metallic organic frameworks (MOFs), zeolites, dioxides, carbon nanotubes (CNTs), etc., have opened unprecedented perspectives for the implementation of the MD process. The integration of nanofillers gives appropriate characteristics to the MD membranes by changing their chemical and physical properties, which significantly enhances energy efficiency without impacting the economic costs. Here, we provide a comprehensive overview of the state-of-the-art status, the opportunities, open challenges, and pitfalls of the emerging field of modified ENMs using different nanomaterials for desalination applications. ... Functional electrospun mats can be used to develop nanocomposite material from a diverse range of performance-enhanced plastics for packaging applications. In addition, they can be used to reinforce the physical properties of both plastics and bioplastics as transparent gas barrier layers or even as new technologies for designing bioactive packaging with antimicrobial protection and delivering nutraceuticals to food products [97] . Numerous electrospinning stimuli-responsive materials have recently been synthesized, which can achieve the controlled release of active substances, thus producing a long-term biological effect [98,99]. ... Innovations in the Packaging of Meat and Meat Products—A Review Marian Gil Mariusz Rudy This study aims to systematize the knowledge about innovative solutions to understand the composition of packaging materials and bioactive substances used in the packaging processes of meat and meat products, given the contemporary trends and consumer expectations. In edible packaging, the application of natural and renewable biopolymers is gaining popularity as, unlike petroleum-based plastic packaging materials, they do not cause environmental problems. Packaging using active compounds further extends the shelf life of food products compared with traditional packaging by reducing the adverse effects during storage, such as oxidation, microbial growth, and moisture loss. On the other hand, the inclusion of natural bioactive substances in packaging provides an opportunity to increase the shelf life of food products and/or decrease the use of preservatives. This direction offers a wide field for research due to the multitude of substances, their impact, and the properties of the packaged product. ... It is also worthy to note that at low concentrations, an increase in charge favours the bead population (Shepa et al. 2021; Xue et al. 2017). The polymer solution will aggregate around the electrode when an electric field is applied. ... Effect of Polymer Concentrations on Pores Mechanism in Electrospun Fibre Samson Oluwagbemiga Alayande Oluseyi Afolabi Adeyemi Oyesolape Akinsipo Titus Alfred Makudali Msagati Advanced material science has resulted in materials with atomic-scale dimensions whose tremendous application includes filtration, drug delivery, membrane, sensor, and encapsulation. Nanoporous fibre has been formed using temperature-induced phase separation (TIPS) and vapour-induced phase separation (VIPS) mechanism, but polymer concentration has been underestimated in the electrospinning parameter. This work aims at showcasing the effect of electrospinning parameters including polymer concentration and resultant phases on pore formation on fibre. Pore formation in electrospun fibre was carried out by electrospinning expanded polystyrene (EPS). The surface morphology of the resulting nanoporous fibre was characterized with Scanning Electron Microscope (SEM) while the pore distribution was analyzed with a BET (Brunauer, Emmet, Teller) micromeritics analyzer. From the result, an increased concentration of polymer from 10 % decreased bead population to zero, meanwhile, bombardment with high electrostatic power resulted in beaded fibres at 10% and 15% w/v. Further increase in EPS concentration resulted in beadless fibres and electrospun 20% EPS fibre at 8.5 kV resulted in porous fibre with meso, micro and macropores. At 11.5 kV, pore dimension in fibre reduced with predominant pore width less than 100 nm. An increased voltage to 13.5 kV resulted in morphologies showing brittled fibre probably due to excess pores formed. Conclusively, polymer concentration moderates variables interaction that resulted in phase separation which controls fibre orientation. Therefore, pore formation does not solely depend on TIPS, VIPS, and breath figures but also polymer concentration. ... In particular, nanofibers have the sizeable 1D morphology, highly aligned nanoparticles and a large pore structure, which could provide rich charge-transfer channels for effective photocatalytic reactions. Electrospinning has been proposed to construct various 1D nanofibers materials for photocatalytic hydrogen evolution and dye degradation [36] [37] [38][39][40]. ... Constructing the Sulfur-Doped CdO@In2O3 Nanofibers Ternary Heterojunction for Efficient Photocatalytic Hydrogen Production Haiyan Zhang Zi Zhu Min Yang Dai-Bin Kuang An S-doped CdO@In2O3 nanofiber was successfully designed by in-situ electrospinning along and subsequent calcination treatment. Under artificial sunlight illumination, the S/CdO@In2O3-25 displayed a superior photocatalytic hydrogen evolution rate of 4564.58 μmol·g−1·h−1, with approximately 22.0 and 1261.0-fold of those shown by the S/CdO and S/In2O3 samples, respectively. The experimental and theoretical analyses illustrate that the unique one-dimensional (1D) nanofiber morphology and rich oxygen vacancies optimized the electronic structure of the nanofibers and adsorption/desorption behaviors of reaction intermediates, contributing to the realization of the remarkable solar-to-H2 conversion efficiencies. Moreover, the staggered band structure and intimate contact heterointerfaces facilitate the formation of a type-II double charge-transfer pathway, promoting the spatial separation of photoexcited charge carriers. These results could inform the design of other advanced catalyst materials for photocatalytic reactions. ... The solution behavior of polymers affects the ability to use certain methods of the preparation of polymer films and scaffolds. Among other approaches, ES molding has been successfully used in obtaining fibrous materials for different applications [152, 153] . However, this method remains practically unused for sidechain PCPAs, despite their polyelectrolyte nature. ... Design, Synthesis and Actual Applications of the Polymers Containing Acidic P–OH Fragments: Part 2—Sidechain Phosphorus-Containing Polyacids INT J MOL SCI Ilya E. Nifant’ev Macromolecules containing acidic fragments in side-groups—polyacids—occupy a special place among synthetic polymers. Properties and applications of polyacids are directly related to the chemical structure of macromolecules: the nature of the acidic groups, polymer backbone, and spacers between the main chain and acidic groups. The chemical nature of the phosphorus results in the diversity of acidic >P(O)OH fragments in sidechain phosphorus-containing polyacids (PCPAs) that can be derivatives of phosphoric or phosphinic acids. Sidechain PCPAs have many similarities with other polyacids. However, due to the relatively high acidity of –P(O)(OH)2 fragment, bone and mineral affinity, and biocompatibility, sidechain PCPAs have immense potential for diverse applications. Synthetic approaches to sidechain PCPAs also have their own specifics. All these issues are discussed in the present review. ... Electrospinning is a simple and effective technology for preparing nanofibers, which can control the morphology and structure of nanofibers by adjusting spinning solution components, spinning process parameters, ambient conditions, and post-processing parameters. An electrospinning device is mainly composed of a spinning solution supply device, a spinneret, a high-voltage power supply, and a collector [16] . On applying a high voltage, a Taylor cone is formed at the spinning nozzle. ... Preparation and Characterization of Simvastatin-Loaded PCL/PEG Nanofiber Membranes for Drug Sustained Release Full-text available Oct 2022 MOLECULES Lu Pan Jiahao Yang Lan Xu Simvastatin (SIM) particles are liposoluble drugs with large particle sizes, resulting in poor compatibility with electrospun polycaprolactone (PCL)/polyethylene glycol (PEG) nanofibers, so that part of them will be exposed to the electrospun nanofiber surface, which is easy to cause the burst release of drugs. Therefore, in this paper, stearic acid (SA) with good biocompatibility was innovatively added to increase the dispersion uniformity of SIM in the spinning solution, thus improving the performances of SIM-loaded PCL/PEG nanofiber membranes (NFMs). Accordingly, the effects of SA addition on the morphologies, mechanical properties, wettability, and drug release properties of the SIM-loaded NFMs were studied. The results showed that after SIM was dissolved in SA solution, the particle size of SIM was significantly reduced and could be evenly dispersed in the polymer spinning solution, thus obtaining the SIM-loaded composite NFMs with the best morphology and performance. ... When drug nanocarriers are prepared by electrospinning, the morphology of the nanofibers is often a combination of different elements [60]. The crucial elements are the feedstock properties, the process parameters of the spinning machine, and environmental conditions [56, 61, 62]. In Table 1, the effect of process parameters, solution parameters, ambient parameters on fiber morphology were summarized. ... Electrospinning and Nanofibers: Building drug delivery systems and potential in pesticide delivery Article Sep 2022 Wenjie Shangguan Shuqi Li Lidong Cao Hongliang Xu Flexible and efficient electrospinning technology is favored in pharmaceutical processing. Nanocarriers obtained in this way have high drug loading capacity, encapsulation, and excellent mechanical properties, thus enriching the equipment library of drug delivery systems. It is also noteworthy that the superior performance of nanofiber carriers has attracted the attention of the pesticide nanoformulation field, this technology is gradually promoting pesticide delivery systems moving to the nanoscale, which will increase the application scenarios and safety of traditional pesticides. It is a mainstream trend to obtain multi-structured fiber carriers at the microscopic level through needle modification of electrospinning equipment. In this paper, electrospinning technology and electrospun nanofiber are introduced in detail, included drug nanocarriers and multiple electrospinning methods, these are necessary and comprehensive for the expansion and translation of nanotechnology applications. More importantly, the development and challenges of electrospinning in pesticide micro/nano formulation are reviewed, and prospects were also prospected from the perspective of nanoscale pesticide formulation processing and application, all to improve the combination of electrospinning nanotechnology and plant protection. ... To fabricate the PCL nanofibers, highly toxic volatile organic solvents and/ or solvent systems such as chloroform, dimethylformamide (DMF), tetrahydrofuran (THF), dichloromethane (DCM), chloroform/ methanol, DMF/THF as well as DMF/chloroform have been traditionally used [18,19]. These organic solvents are not only a source of danger to the operator and environment but also to end-users in the form of residual solvent [20] . Removal of residual solvents from the electrospun nanofiber is usually tricky. ... AC electrospinning: impact of high voltage and solvent on the electrospinnability and productivity of polycaprolactone electrospun nanofibrous scaffolds Article Jul 2022 Manikandan Sivan Divyabharathi Madheswaran Šárka Hauzerová David Lukas Electrospinning technology employs direct current high voltage to produce electrospun fibers from the polymeric liquid or melt. However, until now, the impact of alternating current (AC) high voltage on the spinnability of polymers remains inadequately explored. This work studies the effects of various less toxic solvents and AC high voltage (25 and 32 kV_RMS) on the spinnability, morphology, and productivity of polycaprolactone (PCL) electrospun nanofibrous scaffolds (ENS). Besides this, cellular activity on various PCL ENS is also evaluated. Herein, formic acid (F), formic acid/acetic acid (FA), and formic acid/acetic acid/acetone (FAA) solvent systems are used to prepare various concentrations of PCL solutions. Preliminary polymer–solvent interaction studies confirm that FAA is the better solvent choice for PCL than FA and F. FAA-PCL exhibits higher viscosity than FA-PCL and F-PCL due to better polymer–solvent interactions and PCL stability. Consequently, FAA-PCL shows higher electrospun nanofiber productivity at 32 kVRMS (12.4 ± 0.3 g/h), followed by FA-PCL (6.9 ± 0.1 g/h) and F-PCL (2.2 ± 0.2 g/h). Finally, the cytotoxicity and in vitro experiments indicate that the fabricated ENS are noncytotoxic and biocompatible with 3T3-L1 mouse fibroblast cells. This study will inspire the academic and industrial communities to fabricate various polymeric nanofibers on a large scale using AC electrospinning technique. ... One of the approaches to producing nanofibers comprises the use of high-voltage polymeric solutions [16, 17] . This electrohydrodynamic phenomenon results in the creation of so-called Tylor cones on the deformed surface of the solution. ... The Potential for the Direct and Alternating Current-Driven Electrospinning of Polyamides Article Full-text available Feb 2022 Pavel Holec Radek Jirkovec Tomáš Kalous Jiri Chvojka The paper provides a description of the potential for the direct current- and alternating current-driven electrospinning of various linear aliphatic polyamides (PA). Sets with increasing concentrations of selected PAs were dissolved in a mixture of formic acid and dichloromethane at a weight ratio of 1:1 and spun using a bar electrode applying direct and alternating high voltage. The solubility and spinnability of the polyamides were investigated and scanning electron microscopy (SEM) images were acquired of the resulting nanofiber layers. The various defects of the spun fibers and their diameters were detected and subsequently measured. Moreover, the dynamic viscosity and conductivity were also subjected to detailed investigation. The most suitable concentrations for each of the PAs were determined according to previous findings, and the solutions were spun using a NanospiderTM device at the larger scale. The fiber diameters of these samples were also measured. Finally, the surface energy of the fiber layers produced by the NanospiderTM device was measured aimed at selecting a suitable PA for a particular application. View ... The pristine PHB fibers demonstrate the large concentration of ellipsoid structures as the anomalous bead-like fragments existing in the fibrous mats along with conventional cylindrical form being typical for electrospun fibers, see Figure 2A. As it was stated in the literature and a series of our works [39][40] [41] [42], the reason for the ellipsoids' formation is low electrical conductivity (<1 µS/cm) and low surface tension of ES polymer solutions. The size of the ellipsoid beads in the transverse direction is 7.5 ± 2.5 µm, and in the longitudinal direction is~17 ± 7 µm. ... Evaluation and Characterization of Ultrathin Poly(3-hydroxibutirate) Fibers Loaded with Tetraphenylporphyrin and Its Complexes with Fe(III) and Sn(IV) Article Full-text available Feb 2022 S.G. Karpova N. A. Chumakova A. V. Lobanov A. L. Iordanskii The effect of small additions (1–5 wt.%) of tetraphenylporphyrin (TPP) and its complexes with Fe (III) and Sn (IV) on the structure and properties of ultrathin fibers based on poly (3-hydroxybutyrate) (PHB) has been studied. A comprehensive study of biopolymer compositions included X-ray diffraction (XRD), differential scanning calorimetry (DSC), spin probe electron paramagnetic resonance method (EPR), and scanning electron microscopy (SEM). It was demonstrated that the addition of these dopants to the PHB fibers modifies their morphology, crystallinity and segmental dynamics in the amorphous regions. The annealing at 140 °C affects crystallinity and molecular mobility in the amorphous regions of the fibers, however the observed changes exhibit multidirectional behavior, depending on the type of porphyrin and its concentration in the fiber. Fibers exposure to an aqueous medium at 70 °C causes a nonlinear change in the enthalpy of melting and challenging nature of a change of the molecular dynamics. ... Electrospinning is a relatively new fabrication technique in biomedical engineering. While the electrospinning process appeared in literature as early as the late 1800s [20] , biomedical applications of the technique first appeared in the early 2000s [21]. In electrospinning, a thermoplastic polymer is either melted or dissolved in a solvent and then pumped through a needle to which a high voltage is applied. ... Mechanical and Shape Memory Properties of Electrospun Polyurethane with Thiol-Ene Crosslinking Article Full-text available Jan 2022 Sam T Briggs Scott M. Herting Grace K. Fletcher Duncan John Maitland The ability to treat complex medical issues often requires dynamic and versatile materials. Electrospinning is a fabrication technique which produces nano-/microfibers that can mimic the extracellular matrix of many biological tissues while shape memory polymers allow for geometric changes in devices upon implantation. Here, we present the fabrication of electrospun polyurethane which exhibits the shape memory effect. To improve the mechanical and shape memory properties of this system, we incorporate vinyl side chains in the polymer backbone which enable crosslinking via thiol-ene click chemistry post fabrication. We also discuss a novel technique to improve photoinitiated crosslinking for electrospun materials. A material with these properties is potentially beneficial for various medical applications, such as vascular anastomosis, and the characterization of this material will be valuable in directing those applications. Rapid quantitative detection of luteolin using electrochemical sensor based on electrospinning of carbon nanofibers doped with single-walled carbon nanoangles Article Jun 2023 Liwen Zhang Danfeng Qin Jun Feng Hao Cheng In this study, single-walled carbon nanoangles/carbon nanofibers (SWCNHs/CNFs) were synthesized by electrospinning, followed by annealing in a N2 atmosphere. The synthesized composite was structurally characterized by scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. The electrochemical sensor was fabricated by modifying a glassy carbon electrode (GCE) for luteolin detection, and its electrochemical characteristics were investigated using differential pulse voltammetry, cyclic voltammetry, and chronocoulometry. Under optimized conditions, the response range of the electrochemical sensor to luteolin was 0.01-50 μM, and the detection limit was 3.714 nM (S/N = 3). The SWCNHs/CNFs/GCE sensor showed excellent selectivity, repeatability, and reproducibility, thus enabling the development of an economical and practical electrochemical method for the detection of luteolin. Electrospun nanofibers for medical face mask with protection capabilities against viruses: State of the art and perspective for industrial scale-up Article May 2023 A Cimini Enrico Imperi A Picano M Rossi
https://www.researchgate.net/publication/354123567_Electrospinning_through_the_prism_of_time
Nanostructural engineering of metal-organic frameworks: Construction strategies and catalytic applications | Request PDF Request PDF | Nanostructural engineering of metal-organic frameworks: Construction strategies and catalytic applications | Famous as emerging inorganic-organic hybrid materials, metal-organic frameworks (MOFs) and MOF-based composites have been displaying bright... | Find, read and cite all the research you need on ResearchGate Article Nanostructural engineering of metal-organic frameworks: Construction strategies and catalytic applications October 2022 Matter5(10):3260-3310 DOI: 10.1016/j.matt.2022.07.014 Authors: <here is a image f2f62089ad6ff61c-d19572ff1996375a> Yutian Qin Yutian Qin <here is a image f2f62089ad6ff61c-d19572ff1996375a> Zhixi Li Zhixi Li <here is a image f2f62089ad6ff61c-d19572ff1996375a> Yulong Duan Yulong Duan <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Guo Jun Tiangong University Abstract Famous as emerging inorganic-organic hybrid materials, metal-organic frameworks (MOFs) and MOF-based composites have been displaying bright prospects in catalysis fields. It is desirable to develop highly efficient MOF-based catalysts with excellent activity, selectivity, and stability. The nanostructure of MOFs can bring dramatic effects on their inherent physical/chemical properties and the interaction with reaction substrates/intermediates. Therefore, it is applicable to promote the performance of MOF-based catalysts via nanostructure engineering. In this review, we focus on four classes of nanostructures, i.e., ultrathin nanostructure, hierarchically porous nanostructure, defective nanostructure, and MOF-shelled nanostructure (composite with MOF shell). Strategies for nanostructure engineering of MOF-based catalysts are summarized, their applications in thermo-catalysis, electrocatalysis, and photocatalysis are overviewed, and the effects of nanostructure engineering on catalytic performance are discussed. We hope this review will be instructive for researchers in the rational and controllable construction of MOF nanostructures for catalytic performance promotions. <here is a image 175d1bd4b7439d95-754927124da715c1> ... The research and development of materials play vital roles in the development of modern society [1][2][3][4]. As a new type of functional material, complexes' structures are modifiable and thus have easy to modify functions [5] [6][7]. In the field of materials chemistry, the complex has been a hot topic [8][9][10]. ... ... In view of this, the semirigid 3,3 -(2,3,5,6-tetramethyl-1,4-phenylene)dipropionic acid (H 2 X), 2,2 -(2,3,5,6-tetramethyl-1,4-phenylene)bis(methylene)dimalonic acid (H 4 Y), rigid 1,3-benzenedicarboxylic acid (m-H 2 bdc), and 5-(tert-butyl)isophthalic acid) (5-H 2 tbia) are selected as the primary ligand in this paper (Scheme 1). When 4,4 -bipyridine (4,4 - (5) , and [Cd(5-tbia 2− )(bebiyh)] n (6). We discuss the crystal structures of 1-6 and investigate the fluorescence properties of 1 and 4. ... Cd(II)/Mn(II)/Co(II)/Ni(II)/Zn(II) Coordination Polymers Built from Dicarboxylic Acid/Tetracarboxylic Acid Ligands: Their Structural Diversity and Fluorescence Properties Article Full-text available Apr 2023 Lu Liu Jian-Min Li Meng-Di Zhang Cheng-Xing Cui Six Cd(II)/Mn(II)/Co(II)/Ni(II)/Zn(II) coordination complexes are formulated as [Cd2(X2−)2(μ3-O)2/3]n (1), [Mn2(X2−)2(μ3-O)2/3]n (2), {[Co1.5(Y4−)0.5(4,4′-bpy)1.5(OH−)]·2H2O}n (3), {[Ni(X2−)(4,4′-bpy)(H2O)2]·4H2O}n (4), [Zn(m-bdc2−)(bebiyh)]n (5), and [Cd(5-tbia2−)(bebiyh)]n (6) (H2X = 3,3′-(2,3,5,6-tetramethyl-1,4-phenylene) dipropionic acid. H4Y = 2,2′-(2,3,5,6-tetramethyl-1,4-phenylene)bis(methylene) dimalonic acid, bebiyh = 1,6-bis(2-ethyl-1H-benzo[d]imidazol-1-yl)hexane, m-H2bdc = 1,3-benzenedicarboxylic acid, and 5-H2tbia = 5-(tert-butyl)isophthalic acid) were obtained by hydrothermal reactions and structurally characterized. Complexes 1 and 2 have a 6-connected 3D architecture and with several point symbols of (36·46·53). Complex 3 features a 5-connected 3D net structure with a point symbol of (5·69). Complex 4 possesses a 4-connected 2D net with a vertex symbol of (44·62). Complex 5 is a 3-connected 2D network with a point symbol of (63). Complex 6 is a (3,3)-connected 2D network with a point symbol of (63)2. In addition, complexes 1 and 4 present good photoluminescence behaviors. The electronic structures of 1 and 4 were investigated with the density functional theory (DFT) method to understand the photoluminescence behaviors. ... Catalytic materials have become prominent in many high-tech fields in recent years [1]. These materials are not categorized according to their nature, bonding form, or processing methods, but rather according to their functions [2, 3]. The emergence of catalytic materials in energy (energy storage, conversion, and utilization) [4][5][6][7][8][9][10][11][12] and environmental (detection, protection, and rehabilitation) applications has received increased attention from both academic and industry scientists [13][14][15][16][17][18][19][20]. ... Synthesis and Application of Catalytic Materials in Energy and Environment Article Full-text available Jan 2023 <here is a image b99b64f39715a11a-d6886b8e1fbc8158> Dezhi Han <here is a image cb4a7e0be2389a8c-cdcf63567cd37d8a> Wentai Wang <here is a image 7985b5f12a01df3e-bab81c8fe67b732f> Ning Han Catalytic materials have become prominent in many high-tech fields in recent years [...] Scalable Fabrication of Cu2S@NiS@Ni/NiMo Hybrid Cathode for High‐Performance Seawater Electrolysis Article Full-text available May 2023 ADV FUNCT MATER <here is a image 2a3bb6ffc42c1445-8994b5fe0c4f949d> Wenwen Xu Tengfei Ma Haocheng Chen Zhiyi Lu Electrochemical hydrogen evolution reaction (HER) with cost‐effectiveness, high performance, and repeatable scale‐up production hold promises for large‐scale green hydrogen generation technology. Herein, a convenient method for scaling up Cu2S@NiS@Ni/NiMo electrocatalysts on Cu foam with high geometric area over 100 cm² is presented. The hybrid electrode exhibits high hydrogen evolution activity with 190 and 250 mV overpotential at 1000 mA cm⁻² and superior stability with negligible overpotential loss after over 2000 h at 500 mA cm⁻² under steady‐state conditions in both artificial seawater and real seawater. Detailed characterizations and simulations demonstrate that high intrinsic activity resulting from the unique boundary interface, enhance mass transport resulting from superaerophobic nanoarray architecture, and corrosion resistance resulting from polyanion‐rich passivating layers together lead to the outstanding performance. The practicability is also demonstrated in an alkaline seawater electrolyzer coupling with the hybrid electrode and stable commercial anode. Dynamically modulated synthesis of hollow metal-organic frameworks for selective hydrogenation reactions Liyun Xiao Chuanqi Cheng Zhixi Li <here is a image d3447ad8c443059a-d0ee140f98444886> Meiting Zhao Hollow metal-organic frameworks (MOFs) have attracted increasing attention in the field of catalysis in recent years due to their unique cavity structure with fast mass-diffusion rates and easily accessible active sites. Here, we report the use of dynamic modulators, which are formed by the in-situ imine condensation reaction of 4-aminobenzoic acid and 4-formylbenzoic acid, to regulate the growth of MOFs to synthesize well-defined hollow thioether functionalized UiO-67 (denoted as H-UiO-67-S) single crystals. After supporting Pd nanoparticles, the designed catalysts Pd@H-UiO-67-S show excellent conversion (> 99.9%), selectivity (> 99.9%), and stability (10 cycles) in the selective hydrogenation of nitrobenzenes with other reducible groups. Density functional theory calculations and the experimental results reveal that Pd nanoparticles not only selectively adsorb the nitro-groups on nitrobenzene, but also restrict the adsorption of the aniline product, due to the interaction of thioether with Pd in the confined pores of H-UiO-67-S, finally result in a significant increase in selectivity of nitro-hydrogenation. Recent progress of two-dimensional metal-organic-frameworks: From synthesis to electrocatalytic oxygen evolution Huakai Xu Xiaofei Wei Hui Zeng Fangna Dai High-performance electrocatalysts for oxygen evolution reaction (OER) are crucial for water splitting and metal-air batteries. Two-dimensional (2D) metal-organic framework (MOF) has become a new class of efficient OER electrocatalysts due to the rich coordination unsaturated metal nodes, large specific surface area, and adjustable structures. In addition, because inheriting the original microstructure of MOFs and having stronger chemical and mechanical stability, metal/alloy/oxide, metal sulfide/selenide/phosphide, and other compounds derived from 2D MOFs have also shown their unique OER catalytic ability. Here, we briefly introduced the existing reaction mechanism and evaluation parameters of catalyst performance of OER, introduced the synthesis methods and corresponding characterization techniques of 2D MOFs and their derivatives, and summarized the latest progress of 2D MOFs and their derivatives as OER catalysts. Finally, we put forward some views and suggestions on the existing problems hindering the development of 2D MOFs as OER for advancing the field. Electronic Modulation of Metal-Organic Frameworks Caused by Atomically Dispersed Ru for Efficient Hydrogen Evolution SMALL Xinyue Li Dian Luo Fan Jiang Yonghong Ni Designing excellent electrocatalysts for the hydrogen evolution reaction (HER) is extremely significant in producing clean and sustainable hydrogen fuel. Herein, a rational strategy is developed to fabricate a promising electrocatalyst by introducing atomically dispersed Ru into a cobalt-based metal-organic framework (MOF), Co-BPDC (Co(bpdc)(H2 O)2 , BPDC: 4,4'-Biphenyldicarboxylic acid). The obtained CoRu-BPDC nanosheet arrays exhibit remarkable HER performance with an overpotential of 37 mV at a current density of 10 mA cm-2 in alkaline media, which is superior to most of the MOF-based electrocatalysts and comparable to the commercial Pt/C. Synchrotron radiation-based X-ray absorption fine structure (XAFS) spectroscopy studies verify that the isolated Ru atoms are dispersed in Co-BPDC nanosheets with the formation of five-coordinated Ru-O5 species. XAFS spectroscopy combined with density functional theory (DFT) calculations unravels that atomically dispersed Ru can modulate the electronic structure of the as-obtained Co-BPDC, contributing to the optimization of binding strength for H* and the enhancement of HER performance. This work opens a new avenue to rationally design highly-active single-atom modified MOF-based HER electrocatalysts via modulating electronic structures of MOF. Mesoporous Silica-Guided Synthesis of Metal-Organic Framework with Enhanced Water Adsorption Capacity for Smart Indoor Humidity Regulation Full-text available <here is a image 2e562945c60ed82c-f7fd1b72a4d26fe7> Lurong Ge <here is a image 51ab939533ae2f94-9e96cb7d983f5f00> Yaohui Feng Yanan Xue Tianshu Ge Metal–organic frameworks (MOFs) are promising for indoor humidity regulation due to steep stepwise water uptake and moderate regeneration temperature. Current approaches for performance improvement of MOFs such as impregnating hygroscopic salts and grafting functional groups face the challenge of corrosion and instability. Herein, a template‐guided tuning strategy is proposed to synthesize binary nanocomposite. Highly ordered mesoporous channels of MCM‐41 provide uniform nucleation sites for MOF growth, enabling a 21.5% promotion of specific surface area (3188.14 m² g⁻¹) and 23.4% improvement of water uptake (1.53 g g⁻¹ at 20°C/90% relative humidity) for the nanocomposite compared with parent MIL‐101(Cr). The fast kinetics and superior stability together guarantee its practical application. Further, a paradigm of continuous indoor humidity regulation driven by sunlight is demonstrated, which realizes smart regulation of the indoor humidity to the human comfort zone (40–60%) with near‐zero energy input. Metal-organic frameworks for fast electrochemical energy storage: Mechanisms and opportunities <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Chulgi Nathan Hong Audrey Crom Jeremy I. Feldblyum <here is a image 9c10caa773a9bb22-73e92e068d6fd1f1> Maria Lukatskaya Regulating interlayer spacing of aminated graphene oxide membranes for efficient flow reactions Shuai Pang Daoling Peng <here is a image 4c2ef2272c47ecf4-fd3c2a83d4ea920a> Yuwei Hao Lei Jiang Using Defect Control To Break the Stability–Activity Trade-Off in Enzyme Immobilization via Competitive Coordination Jianghua Yang <here is a image d263532866f8da5f-0737d22b182c803d> Huang Wenguang <here is a image 8cd9bf11ffbd266e-f3a7374deb54d0e0> Wentao Zhang <here is a image e6b1dae828009f05-71b9c6cdc0399641> Shujuan Zhang Immobilization of enzymes within metal-organic frameworks is a powerful strategy to enhance the long-term usability of labile enzymes. However, the thus-confined enzymes suffer from the trade-off between enhanced stability and reduced activity because of the contradiction between the high crystallinity and the low accessibility. Here, by taking laccase and zeolitic imidazolate framework-8 (ZIF-8) as prototypes, we disclosed an observation that the stability-activity trade-off could be solved by controlling the defects via competitive coordination. Owing to the presence of competitive coordination between laccase and the ligand precursor of ZIF-8, there existed a three-stage process in the de novo encapsulation: nucleation-crystallization-recrystallization. Our results show that the biocomposites collected before the occurrence of recrystallization possessed both increased activity and enhanced stability. The findings here shed new light on the control of defects through the subtle use of competitive coordination, which is of great significance for the engineering application of biomacromolecules. Piezoelectric Metal‐Organic Frameworks Mediated Mechanoredox Borylation and Arylation Reactions by Ball Milling Rundong Ding <here is a image a2af049c6496b663-84709aed3e72b463> Qing Liu Lifei Zheng Herein, metal organic frameworks UiO‐66 and UiO‐66‐NH2 were synthesized and their piezoelectric properties were characterized by piezoresponse force microscopy. Under mechanical agitation, the highly polarized UiO‐66 and UiO‐66‐NH2 can act as electron donors to reduce aryl diazonium salts, forming the aryl radical species which further react with bis(pinacolato)diborane or heteroarenes to generate the desired products with broad substrate scope. For all substrates, it was found that the reactions mediated by UiO‐66‐NH2 which exhibited better piezoelectric property were more efficient than those promoted by UiO‐66. Moreover, we have shown the convenient regeneration of spent catalysts which can be reused for promoting mechanoredox reactions without loss of activities by taking advantage of the unmatched repairability of metal organic frameworks. Mechanistic studies revealed that a radical pathway was involved in these transformations. MOF Derived Oxygen vacancy‐rich Co/CoO@NC‐CNTs hybrid Electrocatalyst for Oxygen Reduction Reaction Xinjie Guo Xingyu Gan Yun Wang Shan Peng Low‐cost and high‐efficiency oxygen reduction reaction (ORR) electrocatalysts are the basis for large‐scale applications of electrochemical energy storage and conversion technologies such as fuel cells and metal‐air batteries. Herein, cobalt and oxygen vacancy‐rich cobalt oxide encapsulated in nitrogen‐doped carbon and carbon nanotubes (Co/CoO@NC‐CNT) have been prepared by direct solid‐state pyrolysis of Co‐MOF. The carbon morphology, oxygen vacancy content and type of nitrogen can be finely tuned by mixing Co‐MOF with proper amounts of melamine. The optimized material has an interwoven CNT structure with abundant micro‐ and mesopores, suitable nitrogen type and certain number of oxygen vacancies and exhibiting outstanding ORR electrocatalytic performance in alkaline media with an onset potential of 0.96 V and a half‐wave potential of 0.88 V vs RHE, which is higher than 20 wt% Pt/C, as well as being highly stable and well resistant to methanol. Pristine Metal–Organic Frameworks and their Composites for Renewable Hydrogen Energy Applications Full-text available ADV FUNCT MATER <here is a image 8594c196b3ab5c9f-ddffaebcbef14860> Rajendra Prasad Paitandi Yinji Wan <here is a image 363eb72337d36fef-4c9a5a1edf64fced> Waseem Aftab Ruqiang Zou Metal–organic frameworks (MOFs) have emerged as ideal multifunctional platforms for renewable hydrogen (H2) energy applications owing to their tunable chemical compositions and structures and high porosity. Their advanced component species and porous structure contribute greatly to the enhanced activity, electrical conductivity, photo response, charge‐hole separation efficiency, and structural stability of MOF materials, which are promising for practical H2 economy. In this review, we mainly introduce design strategies for the enhancement of electro‐/photochemical behaviors or adsorption performance of porous MOF materials for H2 production, storage, and utilization from compositional perspective. Following these engineering strategies, the correlation between composition and property‐structure‐performance of pristine MOFs and their composite with advanced components is illustrated. Finally, challenges and directions of future development of related MOFs and MOF composites for H2 economy are provided. Nanoemulsion-directed growth of MOFs with versatile architectures for the heterogeneous regeneration of coenzymes Article As one of the most appealing strategies for the synthesis of nanomaterials with various architectures, emulsion-directed methods have been rarely used to control the structure of metal-organic frameworks (MOFs). Herein, we report a versatile salt-assisted nanoemulsion-guided assembly to achieve continuous architecture transition of hierarchical Zr-based MOFs. The morphology of nanoemulsion can be facilely regulated by tuning the feed ratio of a dual-surfactant and the introduced amount of compatible hydrophobic compounds, which directs the assembly of MOFs with various architectures such as bowl-like mesoporous particle, dendritic nanospheres, walnut-shaped particles, crumpled nanosheets and nanodisks. The developed dendritic nanospheres with highly open and large mesochannels is successfully used as matrix for the co-immobilization of coenzymes and corresponding enzymes to realize the in situ heterogeneous regeneration of NAD+. This strategy is expected to pave a way for exploring sophisticated hierarchical MOFs which can be competent for practical applications with bulk molecules involved. Controlling the structure of hierarchical metal-organic frameworks via soft template remains a challenge. Here, the authors report a salt-assisted nanoemulsion-guided strategy to achieve continuous structure transition of hierarchical Zr-based MOFs. Low‐dimensional material supported single‐atom catalysts for electrochemical CO2 reduction Article Full-text available Converting CO2 emissions to valuable carbonaceous chemicals/fuels under mild conditions provides a sustainable way to maintain carbon balance and alleviate the energy shortage. Low‐dimensional material (LDM) supported single‐atom catalysts (SACs) have been attracted significant attention for electrochemical CO2 reduction reaction (ECR) in recent years. This is mainly because integrating the single‐atoms and LDMs can inherit the advantages of themselves and the synergy effects between them are potential to enhance the ECR performance. In this review, we summarized the strategies for synthesizing LDM supported SACs for ECR, and different LDM supported SACs for ECR have been briefly introduced. Moreover, some optimization strategies for LDM supported SACs towards CO2 electroreduction are highlighted. At the end of this review, the perspectives and challenges of LDM supported SACs for ECR are provided. In this review, we have systematically summarized the low‐dimensional material (LDM) supported single‐atom catalysts (SACs) for ECR, and the perspectives and challenges of LDM supported SACs for ECR are also provided. 2D π‐conjugated metal–organic frameworks for CO2 electroreduction Article Full-text available Electrochemically converting CO2 molecules into valuable chemicals and fuels opens up a promising route to utilize CO2 source. To overcome the low efficiency and durability that hinder its practical applications, tremendous research efforts have been devoted to nano‐level or atomic‐level catalyst design. The advent of metal–organic frameworks (MOFs) provides novel opportunities for CO2 reduction catalysts, which may integrate the respective advantages of traditional catalysts and single‐atom catalysts. In this review, we summarize the recent advances in two‐dimensional (2D) π‐conjugated MOF catalysts and discuss their practical applications in CO2 reduction reaction (CO2RR). First, we systematically introduce the development of electrocatalysts for CO2RR applications. Meanwhile, various types of 2D porphyrin/phthalocyanine‐based MOFs and corresponding electrocatalytic performances arising from active‐site engineering, surface reconstruction, and thickness control are briefly overviewed. Finally, we highlight their major challenges and opportunities facing CO2RR, and hope that this review can offer new insight into MOF catalyst design. Two‐dimensional (2D) π‐conjugated metal–organic frameworks (MOFs), including 2D porphyrin‐based and phthalocyanine‐based MOFs, integrate the advantages of traditional catalysts and single‐atom catalysts. The ultrathin thickness, fully exposed active center, structural homogeneity, and light‐coupling capacity endow 2D π‐conjugated MOFs with great potential in CO2 reduction reaction (CO2RR). In this review, their development and practical application in CO2RR and photo‐coupled CO2RR are summarized. Lattice Matching Growth of Conductive Hierarchical Porous MOF/LDH Heteronanotube Arrays for Highly Efficient Water Oxidation Article Full-text available Adv. Mater. 2021, 33, 2006351 DOI: 10.1002/adma.202006351 According to new synchrotron X-ray powder diffraction data,[¹] the chemical composition and crystal structure of Co-LDH (JCPDS Card 48-0083[²]) needs to be corrected in the published article. Its composition, thought to be Co(CO3)0.5(OH)·0.11H2O, should be corrected to Co6(CO3)2(OH)·8H2O. Further, the space group should be corrected to hexagonal P-62m with unit cell parameters of a = b = 10.3236(4) Å, and c = 3.12244(15) Å; and the related crystal planes (100), (110), (021), (002), (300) and (311) should be corrected to (010), ((Formula presented.)), ((Formula presented.)), (001), (011) and ((Formula presented.)). The reflections observed for the crystalline components of the reported material, as shown in Figure 2a (and in Figure S2–S4, Supporting Information) of the published article, may correspond to Co-LDH and consequently also to isostructural CoNiFe-LDH and cMOF/LDH-48. Selective ligand removal to improve accessibility of active sites in hierarchical MOFs for heterogeneous photocatalysis Article Full-text available Metal-organic frameworks (MOFs) are commended as photocatalysts for H2 evolution and CO2 reduction as they combine light-harvesting and catalytic functions with excellent reactant adsorption capabilities. For dynamic processes in liquid phase, the accessibility of active sites becomes a critical parameter as reactant diffusion is limited by the inherently small micropores. Our strategy is to introduce additional mesopores by selectively removing one ligand in mixed-ligand MOFs via thermolysis. Here we report photoactive MOFs of the MIL-125-Ti family with two distinct mesopore architectures resembling either large cavities or branching fractures. The ligand removal is highly selective and follows a 2-step process tunable by temperature and time. The introduction of mesopores and the associated formation of new active sites have improved the HER rates of the MOFs by up to 500%. We envision that this strategy will allow the purposeful engineering of hierarchical MOFs and advance their applicability in environmental and energy technologies. Light‐Assisted CO2 Hydrogenation over Pd3Cu@UiO‐66 Promoted by Active Sites in Close Proximity Article Full-text available CO 2 hydrogenation to methanol has attracted great interest while suffering from low conversion and high energy input. Herein, tiny Pd 3 Cu nanoparticles are confined into a metal-organic framework (MOF), UiO-66, to afford Pd 3 Cu@UiO-66 for CO 2 hydrogenation. Remarkably, it achieves a methanol production rate of 340 µmol g -1 h -1 at 200 °C and 1.25 MPa under light irradiation, far surpassing that in the dark. The photo-generated electron transfer from the MOF to antibonding orbitals of CO 2 * promotes CO 2 activation and HCOO* formation. In addition, the Pd 3 Cu microenvironment plays a critical role in CO 2 hydrogenation. In contrast to the MOF-supported Pd 3 Cu (Pd 3 Cu/UiO-66), the Pd 3 Cu@UiO-66 exhibits a much higher methanol production rate due to the close proximity between CO 2 and H 2 activation sites, which greatly facilitates their interaction and conversion. This work provides a new avenue to the integration of solar and thermal energy for efficient CO 2 hydrogenation under moderate conditions. Large-Scale Production of Hierarchically Porous Metal-Organic Frameworks by a Reflux-Assisted Post-Synthetic Ligand Substitution Strategy Article Full-text available The mass production of hierarchically porous metal–organic frameworks (HP-MOFs) with adjustable morphology and size as well as retained crystallinity is highly desirable yet challenging. Herein, we have developed a versatile post-synthetic ligand substitution (PSLS) strategy to convert typical microporous MOFs and even their composites to HP-MOFs and their composites at a 10 g level and beyond in a simple reflux system. The resulting HP-MOFs feature intrinsic micropores and abundant defective mesopores, which greatly facilitate the transport and activation of large substrates for stable and efficient heterogeneous catalysis. Furthermore, the presence of defective mesopores in the HP-MOF composites improves activity and selectivity for large molecule-involved one-pot tandem catalysis. This strategy opens a new door to fast, facile, general, and scale-up production of HP-MOFs and related composites for expanding applications of conventional microporous MOF-based materials. Recent advances on electrochemical methods in fabricating two‐dimensional organic‐ligand‐containing frameworks Article Full-text available Organic-ligand-containing frameworks have drawn considerable attention due to their multifunctional properties as well as tunable structures for broad applications. Among numerous synthesis methods developed in the past two decades, electrochemical processing has been demonstrated as one of the most efficient, safe, and facile ways to realize the large-scale and highly controllable production of organic-ligand-containing frameworks. In this review, the progress of electrochemically induced crystallization and thin film fabrication of organic-ligand-containing frameworks is summarized in a well-rounded way. Besides, the mechanism and processing parameters are also discussed. Moreover, the main challenges are also expounded for providing some guidance on the future development of organic-ligand-containing frameworks, especially for covalent-organic frameworks and hydrogen-bonded organic frameworks. Integration of metal-organic frameworks and covalent organic frameworks: Design, synthesis, and applications Article Full-text available Metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), featuring porous crystalline materials, have attracted tremendous attention for various applications due to their periodic and well-defined structures, high surface area, and tunable pore architectures. In particular, the facile modification of MOFs and COFs enables their intermesh into MOF/COF hybrids to enhance performance and/or extend scope toward diverse applications. In this review, we provide an overview of significant progress in the design and synthesis of MOF/COF hybrids, including [email protected], [email protected], MOF + COF, C-MOF, and COF-in-MOF, and their various applications in catalysis, gas adsorption, sensing, energy storage, and photodynamic therapy. The challenges and prospects of the construction of MOF/COF hybrids for various applications are also briefly discussed. Metal–Organic Framework-Based Solid Acid Materials for Biomass Upgrade Article Full-text available Biomass is a green and producible source of energy and chemicals. Hence, developing high-efficiency catalysts for biomass utilization and transformation is urgently demanded. Metal–organic framework (MOF)-based solid acid materials have been considered as promising catalysts in biomass transformation. In this review, we first introduce the genre of Lewis acid and Brønsted acid sites commonly generated in MOFs or MOF-based composites. Then, the methods for the generation and adjustment of corresponding acid sites are overviewed. Next, the catalytic applications of MOF-based solid acid materials in various biomass transformation reactions are summarized and discussed. Furthermore, based on our personal insights, the challenges and outlook on the future development of MOF-based solid acid catalysts are provided. We hope that this review will provide an instructive roadmap for future research on MOFs and MOF-based composites for biomass transformation. Programmable Logic in Metal–Organic Frameworks for Catalysis Article Full-text available Metal–organic frameworks (MOFs) have emerged as one of the most widely investigated materials in catalysis mainly due to their excellent component tunability, high surface area, adjustable pore size, and uniform active sites. However, the overwhelming number of MOF materials and complex structures has brought difficulties for researchers to select and construct suitable MOF‐based catalysts. Herein, a programmable design strategy is presented based on metal ions/clusters, organic ligands, modifiers, functional materials, and post‐treatment modules, which can be used to design the components, structures, and morphologies of MOF catalysts for different reactions. By establishing the corresponding relationship between these modules and functions, researchers can accurately and efficiently construct heterometallic MOFs, chiral MOFs, conductive MOFs, hierarchically porous MOFs, defective MOFs, MOF composites, and MOF‐derivative catalysts. Further, this programmable design approach can also be used to regulate the physical/chemical microenvironments of pristine MOFs, MOF composites, and MOF‐derivative materials for heterogeneous catalysis, electrocatalysis, and photocatalysis. Finally, the challenging issues and opportunities for the future research of MOF‐based catalysts are discussed. Overall, the modular design concept of this review can be applied as a potent tool for exploring the structure–activity relationships and accelerating the on‐demand design of multicomponent catalysts. Recent key progress achieved in designing metal–organic framework (MOF)‐based catalysts, the active sites, and associated regulation strategies is summarized. Besides, the effects of metal ions, organic ligands, modifiers, functional materials, and post‐treatment modules on the compositions, structures, and morphologies are also highlighted. Modular design may inspire researchers who attempt to develop MOF‐based catalysts with desired functional properties. Interfacial Microenvironment Modulation Boosting Electron Transfer between Metal Nanoparticles and MOFs for Enhanced Photocatalysis Article Interfacial electron transfer between cocatalyst and photosensitizer plays a key role in heterogeneous photocatalysis, yet the underlying mechanism remains subtle and unclear. Particularly, the surfactant coated on the metal cocatalysts, greatly modulating the microenvironment of catalytic sites, is largely ignored. Herein, a series of Pt co‐catalysts with modulated microenvironments, including polyvinylpyrrolidone (PVP) capped Pt nanoparticles (denoted as Pt PVP ), Pt with partially removed PVP (Pt rPVP ), and clean Pt without PVP (Pt), have been encapsulated into a representative metal‐organic framework (MOF), UiO‐66‐NH 2 , to afford Pt PVP @UiO‐66‐NH 2 , Pt rPVP @UiO‐66‐NH 2 , and Pt@UiO‐66‐NH 2 , respectively, for photocatalytic hydrogen production. Systemic investigations suggest that the PVP presents a negative influence on the interfacial electron transfer between Pt and the MOF. Compared with Pt PVP @UiO‐66‐NH 2 , the removal of interfacial PVP effectively improves the sluggish kinetics of electron transfer, accordingly boosting the photocatalytic hydrogen production. Rational incorporation of defects within metal-organic frameworks generates highly active electrocatalytic sites Article The allure of metal-organic frameworks (MOFs) in heterogeneous electrocatalysis is that catalytically active sites may be designeda prioriwith an unparalleled degree of control. An emerging strategy to generate coordinatively-unsaturated active sites is through the use of organic linkers that lack a functional group that would usually bind with the metal nodes. To execute this strategy, we synthesize a model MOF, Ni-MOF-74 and incorporate a fraction of 2-hydroxyterephthalic acid in place of 2,5-dihydroxyterephthalic acid. The defective MOF, Ni-MOF-74D, is evaluatedvs.the nominally defect-free Ni-MOF-74 with a host ofex situandin situspectroscopic and electroanalytical techniques, using the oxidation of hydroxymethylfurtural (HMF) as a model reaction. The data indicates that Ni-MOF-74D features a set of 4-coordinate Ni-O4sites that exhibit unique vibrational signatures, redox potentials, binding motifs to HMF, and consequently superior electrocatalytic activity relative to the original Ni-MOF-74 MOF, being able to convert HMF to the desired 2,5-furandicarboxylic acid at 95% yield and 80% faradaic efficiency. Furthermore, having such rationally well-defined catalytic sites coupled within situRaman and infrared spectroelectrochemical measurements enabled the deduction of the reaction mechanism in which co-adsorbed *OH functions as a proton acceptor in the alcohol oxidation step and carries implications for catalyst design for heterogeneous electrosynthetic reactions en route to the electrification of the chemical industry. Micro/Nano‐Scaled Metal‐Organic Frameworks and Their Derivatives for Energy Applications Article Metal‐organic frameworks (MOFs), as a distinctive class of crystalline porous materials, are constructed by organic linkers and metal ions/clusters. By virtue of their high surface area, structural diversity, and functional adjustability, MOFs and their derivatives, especially with tunable morphologies and sizes, have been well exploited for versatile applications, becoming a rapidly developing interdisciplinary research area. This review focusses on the design and synthesis of 1D, 2D, and 3D MOF nanostructures and their derivatives at micro/nanoscale, with promising catalytic applications including electrocatalysis and photocatalysis, as well as, energy storage like batteries and supercapacitors. The results are discussed and the critical insights gained from the works in this review are summarized, and the challenges and future prospects for this emerging field are outlined. Micro/nano‐scaled metal‐organic frameworks and their derivatives have been widely considered to be promising materials for catalysis and energy applications. This review presents recent progress and advances in their synthesis, characterizations, as well as, applications of catalysis (e.g., electrocatalysis and photocatalysis) and energy (e.g., batteries and supercapacitors). Systematic Modification of UiO‐66 Metal‐Organic Frameworks for Glucose Conversion into 5‐Hydroxymethyl Furfural in Water Metal organic framework UiO‐66 is studied as an adaptable heterogeneous catalyst for glucose conversion. UiO‐66 was modified by; i) partial linker substitution, ii) particle size modulation and iii) linker defects. We studied the effect of crystallinity and functional groups on the glucose conversion and product yields. The main products are: i) fructose from the isomerisation of glucose, ii) mannose from the epimerisation of glucose and iii) 5‐hydroxymethyl furfural from the dehydration of fructose. We found that defective and nano crystalline UiO‐66 catalyst performs best for isomerisation. When 50 % of the linkers of UiO‐66 are replaced by a sulfonate‐containing linker, the catalyst shows higher isomerisation activity than other UiO‐66 catalysts. Naphthalene‐dicarboxylate linkers were introduced to induce hydrophobicity and this catalyst further increased isomerisation activity showing 31 % fructose selectivity. Finally, the promising catalysts were tested in a flow reactor and a bifunctional mixed linker catalyst possessing both hydrophobic and acidic functional groups is shown to be stable in a time‐on‐stream study. The Role of Defects in Metal-Organic Frameworks for Nitrogen Reduction Reaction: When Defects Switch to Features Full-text available The electrochemical nitrogen reduction reaction (NRR), a contributor for producing ammonia under mild conditions sustainably, has recently attracted global research attention. Thus far, the design of highly efficient electrocatalysts to enhance NRR efficiency is a specific focus of the research. Among them, defect engineering of electrocatalysts is considered a significant way to improve electrocatalytic efficiency by regulating the electronic state and providing more active sites that can give electrocatalysts better physicochemical properties. Recently, metal–organic frameworks (MOFs), along with their derivatives, have captured immense interest in electrocatalytic reactions owing to not only their large surface area and high porosity but also the ability to create rich defects in their structures. Hence, they can provide plenty of exposed active sites for electron transfer, NN cleavage, and N2 adsorption to enhance NRR performance. Herein, the concept, the in situ characterizations techniques for defects, and the most common ways to create defects into MOFs have been summarized. Furthermore, the recent advances of MOF‐based electrocatalysts towards NRR have been recapitulated. Ultimately, the major challenges and outlook of defects in MOFs for NRR are proposed. This paper is anticipated to provide critical guidelines for optimizing NRR electrocatalysts. Nitrogen reduction reaction (NRR) is one of the most attractive topics for achieving clean and sustainable ammonia. This review discusses the recent progress of defect engineering of metal–organic frameworks (MOFs) for NRR. There are different types of MOF‐derived materials that enhance NRR performance. These outputs render MOFs to be the centerpiece for various applications especially energy conversion applications. Encapsulating Copper Nanocrystals into Metal–Organic Frameworks for Cascade Reactions by Photothermal Catalysis Article
https://www.researchgate.net/publication/364189333_Nanostructural_engineering_of_metal-organic_frameworks_Construction_strategies_and_catalytic_applications
Abstract Pre-Service Teachers’ Understanding of the Nature of Science in a Reformed, Standards-Driven Science Content Course April Dean Adams, Northeastern State University Monica Macklin, Northeastern State University Pamela G. Christol, Northeastern State University Skyleen Willingham, Mounds Public Schools Vicky Hurst, Beggs Public Schools Melissa Underwood, Glenpool Public Schools Abstract This paper documents the changes in pre-service teachers’ understanding of the nature of science after taking a reformed, standards-based science content course. The SUSSI, an instrument with both Likert items and open-ended responses was given at the beginning and again at the end of the course. Over three-quarters of the participants were white (76.1%) with the remaining participants primarily American Indian (18.7%). The pretest was used to determine initial views of the participants. The paper presents the pretest-posttest subscale differences, both Likert and open-ended responses, for which there was a significant difference in scores. The open-ended responses were used to clarify the changes in pre-service teachers’ thinking after taking the course. How this innovative course might have resulted in significant student improvement concerning some aspects of the nature of science and what changes might be necessary to additionally improve pre-service teachers’ understanding is also discussed. Introduction In science education, there exists the expectation of producing ‘scientifically literate’ individuals, defined as all citizens having an understanding and ability in science in order to be fully functioning citizens (American Association for the Advancement of Science (AAAS), 1989; 1993; National Research Council (NRC), 2000). One component of being scientifically literate is an understanding of the nature of science (NOS). Certain aspects of the NOS have been debated, but agreement has been reached among science educators that a set of general characteristics separates science from other disciplines. The NOS has been described as the values and assumptions inherent to the development of scientific knowledge (Lederman & Zeidler, 1987). Teaching the NOS to improve scientific literacy has had widespread support (Hand et al., 1999)and researchers have given much consideration to assessing student understanding of the nature of science ( Cleminson, 1990; Craven, et al., 2003; Lederman, 1992, 1998; Alters, 1997; Norris, 1997; Matthews, 1998).Although scientific inquiry and the NOS have been identified as essential components of scientific literacy, multiple studies of students and teachers conclude that neither group reliably demonstrates a clear understanding about the process of how science operates or the development of scientific knowledge (Aikenhead 1987; Cooley & Klopfer, 1961; Lederman, 1992; Rubba & Anderson, 1978; Abd-El-Khalick & Lederman, 2000a, 2000b). Alters (1997) and Lederman (1999) report unsuccessful attempts to address the NOS with students. Studies have further found that implicit instructional approaches that attempt to teach student understanding of the NOS through activities and project work fall short of achieving the goal at the college level (Ryder & Leach, 1999). Matthews (1994) states that when teachers understand the NOS, they tend to make decisions that promote a deeper sense of scientific literacy.More recently, Khishfe and Lederman (2006) have shown that explicit NOS instruction can improve high school students understanding of the NOS.According to Siebert and McIntosh (2001, p. xviii), “The pre-service courses and the future teachers they serve will, in large part, determine the nation’s comfort with, knowledge about, and interest in science.” Therefore, an understanding of the development of pre-service teachers’ knowledge of the NOS is critical to teacher education programs. Context of Study The course investigated in this study is a science content requirement for all elementary education, early childhood education, and special education majors at a regional university in Oklahoma. The total enrollment on the university’s three campuses is approximately 9,500 students. The original campus primarily serves students from rural Oklahoma. The other campuses serve students from more urban areas. The university is a comprehensive, primarily undergraduate institution that focuses on teacher preparation. The College of Education is the largest college, and teacher preparation is an important mission of the university. Methods courses for specific content areas are taught in the content area college, not the College of Education. This practice facilitates the hiring of science education and math education faculty by the College Science and Health Professions. Description of the Course Entitled, Science in the Elementary School , the course is a general science content course that teaches science through inquiry. One of the major goals of the course is to help students integrate knowledge of science, learning, pedagogy and students. The course utilizes integrated hands-on inquiry, discussion, demonstration, and lecture format in which students and instructors are able to move seamlessly from one instructional format to another as needed. Whenever feasible, concepts are taught through guided inquiry using hands-on materials. Discussions and interactions with groups and individual students are used to draw attention to important aspects of the inquiry including the nature of science. Short lectures provide explanations that are not directly available through hands-on inquiry and focus on fundamental concepts. Students are given time to explore for themselves before class discussion and explanations. The course also attempts to help pre-service teachers integrate knowledge concerning science, learning, pedagogy, and students by providing contexts in which integration may occur and providing tasks that require integration of knowledge bases. Students write a science unit plan for their choice of grades kindergarten through 8 th-grade. The unit plan is aligned with state science standards and must include both science content and science process skills from the Oklahoma Priority for Academic Student Skills (PASS) (Oklahoma State Department of Education, 2002) for the appropriate grade level. These standards are in alignment with the National Science Education Standards (NSES) (NRC, 1996). The PASS standards emphasize inquiry as an appropriate means of teaching content. The common misconceptions of K-8 thgrade students and how to address them are also discussed in the course. The course is guided by the following NSES professional development standards: Professional Development Standard A: Professional development for teachers of science requires learning essential science content through the perspectives and methods of inquiry. (p. 59) Professional Development Standard B: Professional development for teachers of science requires integrating knowledge of science, learning, pedagogy, and students; it also requires applying that knowledge to science teaching. (p. 62) The instructor for the rural campus (First Author) taught two sections of the course in fall 2005. She holds a B.S. in Physics, an M.S. in Biology, and an Ed.D. in Curriculum and Instruction, Science Education. The instructor for one of the more urban campuses (Third Author) taught five sections of the course in fall 2005. She holds a B.S. in Elementary Education, an M.S. in Curriculum and Instruction, and a Ph.D. in Environmental Science. Both of the instructors are College of Science and Health Professions fulltime faculty. Naturally there were some differences in instruction due to the fact that there were two different instructors for the sections. However, the instructors have worked carefully to achieve course goals, and the inquiries incorporated into the course were done in all sections. Data from all seven sections were combined into one data set because it is the framework and goals of the course that we are attempting to evaluate. The Science Teaching Efficacy Beliefs Instrument Form B (STEBI-B) (Riggs & Enochs, 1990) was administered as a pretest and posttest to 51 pre-service teachers who were enrolled in this course during the spring of 2005. The STEBI-B consists of two subscales: a Personal Science Teaching Efficacy (PSTE) Belief Scale and the Science Teaching Outcome Expectancy (STOE) Scale. An independent, two-tailed t-test was applied to the STEBI-B PSTE subscale scores and to the STEBI-B STOE subscale scores separately to determine if there was a significant difference between the means of the pre-tests and the post-tests. The comparison indicated a statistically significant improvement was found in self-efficacy, but no statistically significant change was found in outcome expectancy (Christol & Adams, 2006). Participant Demographic Information The participants in this study were 134 pre-service teachers enrolled in the course, Science in the Elementary School. The total enrollment in the seven sections was approximately 180. However, some students chose not to participate, and some students did not complete the pretest or posttest survey. Those students were deleted from the analysis. Table 1 summarizes the demographic information for the 134 participants. The participants were primarily women (91.8%). Over half of the students were 18-24 years of age (53.7%) and over one-third of the students were 25-40 years of age (35.1%). Over three-quarters of the students were white (76.1%) with the remaining students primarily American Indian (18.7%). The majority of the students were Elementary Education majors (67.2%) with 23.1% of the students Early Childhood majors and 5.2% Special Education majors. The Elementary Education program prepares 1 st-8 thgrade teachers and the Early Childhood degree prepares PK-3 rd-grade teachers. Most of the students (94.7%) were in their third or fourth year of college study. Table 1 Participant Demographic Information CharacteristicNumber of Participants (Percentage)GenderWomenMenNo Response123 (91.8%)10 (7.5%)1 (0.7%)Age18-24 years of age25-40 years of ageOver 40 years of ageNo Response72 (53.7%)47 (35.1%)14 (10.4%)1 (0.7%)Ethnicity (Self Identified)WhiteAmerican IndianAsian/Pacific IslanderAfrican AmericanLatino/HispanicOtherNo Response102 (76.1%)25 (18.7%)2 (1.5%)2 (1.5%)1 (0.7%)1 (0.7%)1 (0.7%)MajorElementary EducationEarly Childhood EducationSpecial EducationNatural ScienceSecondary ScienceOtherNo Response90 (67.2%)31 (23.1%)7 (5.2%)2 (1.5%)1 (0.7%)2 (1.5%)1 (0.7%)Current Level of StudyFirst year of collegeSecond year of collegeThird year of collegeFourth year of collegeGraduate studentOtherNo Response0 (0.0%)0 (0.0%)46 (34.3%)81 (60.4%)2 (1.5%)4 (3.0%)1 (0.7%) N = 134 Methodology Research Questions The following research questions were investigated in this study: What do pre-service elementary, early childhood, and special education teachers enrolled in the course initially understand about the nature of science? How did the pre-service teachers’ understanding of the nature of science change after taking the course? How can the SUSSI which includes Likert and open-response items be used to assess changes in pre-service teachers’ understanding of the nature of science? Development and Validation of the Instrument The Student Understanding of Science and Scientific Inquiry (SUSSI) questionnaire was developed over a period of three years in collaboration with an international research team that included researchers from the United States, China, and Turkey. (Liang, et al., 2005; Liang, et al., 2006). The instrument was translated into Chinese and Turkish and administered to pre-service teachers in each country. Previous students enrolled in Science in the Elementary School were participants in this project and were part of the U.S. sample. The instrument was designed to be used with large samples. It utilizes both quantitative data which can be analyzed statistically and qualitative data for each subscale. There are six subscales: Observations and Inferences, Nature of Scientific Theories, Scientific Laws vs. Theories, Social and Cultural Influence on Science, Imagination and Creativity in Scientific Investigations, and Scientific Investigation. Within each subscale, there is an open-ended prompt that relates to the four Likert items in the subscale. The purpose of the open-ended item is to provide qualitative data that can be utilized to clarify student Likert responses and to provide additional details concerning student thinking. The Likert responses can be used to select students from a large sample based on their responses. The qualitative responses of these selected students can then be analyzed for patterns. Procedure The SUSSI was administered as a pretest and posttest during the first week and last week of class respectively. Of the students enrolled in the course on two of the three campuses, 134 students responded to all Likert items on both the pretest and posttest and were included in the study. The means on the pretest and posttest were compared with a two-tailed, paired t-test. In addition, subscale means were compared using the same method. Participants with open-ended pretest and posttest responses who also scored at least four points higher on the posttest than they did on the pretest for Subscale 3: Laws vs. Theories (N = 9) and Subscale 5: Imagination and Creativity in Scientific Investigations (N = 14) were selected for further analysis. For each of these participants’ surveys, unchanged and changed responses for each Likert item in the subscale were summarized, and unchanged and changed aspects of the associated open-ended responses were compared to the Likert analysis. Results Summary of Pretest Understanding of the Nature of Science An analysis of the frequencies of pretest responses on the Likert items of the SUSSI was conducted in order to determine the initial views of this particular sample of students. Table 2 summarizes these frequencies. 1. Observations and Inferences Subscale Most of the participants seem to have an informed view concerning the formation and interpretation of observations. Ninety-one percent of the sample agreed that prior knowledge may affect observations. Only 12.7% agreed that observations of the same event will be the same because scientists are objective, while 75.4% disagreed with the statement that observations of the same event will be the same because observations are facts and 71.6% disagreed with the statement that observations of the same event will be the same because scientists are objective. A large portion of the sample (97.8%) agreed that scientists may make different interpretations based on the same observations. 2. Nature of Scientific Theories Subscale The participants also seem to have informed views concerning the tentativeness of theories. A large portion agreed that theories are subject to ongoing testing and revisions (94.8%), that theories may be completely replaced by new theories in the light of new evidence (89.6%), and that theories may be changed because scientists reinterpret existing observations (75.4%). However, only 66.4% disagreed with the statement thattheories based on accurate experimentation will not be changed. 3. Scientific Laws vs. Theories Subscale The results from the Likert items indicate that, like many others, these pre-service teachers agreed that scientific laws are theories that have been proven (82.8%) and thatunlike theories, scientific laws are not subject to change (61.9%). In addition, many agreed that scientific theories exist in the natural world and are uncovered through scientific investigations (72.4%), while only 47.8% agreed that scientific theories explain scientific laws. 4. Social and Cultural Influence on Science Subscale The majority of participants seemed to hold informed views on social and cultural influences on science. Most participants agreed that cultural values and expectations determine what science is conducted and accepted (56.0%) and how science is conducted and accepted (61.9%). In addition, most participants disagreed with the statements that scientific research is not influenced by society and culture (68.7%) and that all cultures conduct scientific research the same way because science is universal and independent of society and culture (78.4%). 5. Imagination and Creativity in Scientific Investigations Subscale Many of the participants held uninformed views concerning the role of imagination and creativity in science. Less than half of the respondents agreed that scientists use their imagination and creativity when they collect data (43.3%) and when they analyze and interpret data (29.9%).In addition, less than half of the respondents disagreed with the statements that scientists do notuse their imagination and creativity because these conflict with logical reasoning (36.6%) or because these conflict with objectivity (35.1%). 6. Scientific Investigation Subscale This subscale had mixed results. Ninety percent of the respondents agreed that scientists use a variety of methods to produce fruitful results and 83.6% agreed that experiments are not the only means used in the development of scientific knowledge. However, many respondents also seemed to believe in a correct method of doing science. Only 36.6% disagreed with the statement that scientists follow the same step-by-step scientific method, and only 40.3% disagreed with the statement that when scientists use the scientific method correctly, their results are true and accurate. In summary, according to the Likert pretest items, ·Most participants held informed views concerning observations and inferences (71.6% - 97.8%), the tentativeness of theories (66.4% - 94.8%), and the influence society and culture has on science (56.0% - 78.4%). ·Less than half of the participants had informed views on the differences between laws and theories (6.0% - 47.8%) and the importance of imagination and creativity in science (29.9% - 43.3%). ·Most participants had mixed views concerning the methods of science. Most thought that there are many ways to do science (83.6% - 90.0%), but less than half disagreed with the statements concerning a correct method in science (36.6% - 40.3%). Table 2: Frequencies of the Pretest Likert Responses on the SUSSI ItemFrequency of Strongly Agree and Agree(Percentage)Frequency of Unsure Response(Percentage)Frequency of Strongly Disagree and Disagree(Percentage)1. Observations and Inferences Subscale1A. Scientists’ observations of the same event may be different because scientists’ prior knowledge may affect their observations.122*(91.0%)2(1.5%)10(7.5%)1B. Scientists’ observations of the same event will be the same because scientists are objective.17(12.7%)21(15.7%)96*(71.6%)1C. Scientists’ observation of the same event will be the same because observations are facts.21(15.7%)12(9.0%)101*(75.4%)1D.Scientists may make different interpretations based on the same observations.131*(97.8%)2(1.5%)1(0.75%)2. Nature of Scientific Theories Subscale2A. Scientific theories are subject to on-going testing and revision.127*(94.8%)6(4.5%)1(0.75%)2B. Scientific theories may be completely replaced by new theories in light of new evidence.120*(89.6%)5(3.7%)9(6.7%)2C. Scientific theories may be changed because scientists reinterpret existing observations.101*(75.4%)20(14.9%)13(9.7%)2D. Scientific theories based on accurate experimentation will not be changed.25(18.7%)20(14.9%)89*(66.4%)3. Scientific Laws vs. Theories Subscale3A.Scientific theories exist in the natural world and are uncovered through scientific investigations.97(72.4%)27(20.1%)10*(7.5%)3B. Unlike theories, scientific laws are not subject to change.83(61.9%)30(22.4%)21*(15.7%)3C. Scientific laws are theories that have been proven.111(82.8%)15(11.2%)8*(6.0%)3D. Scientific theories explain scientific laws.64*(47.8%)40(29.9%)30(22.4%)4. Social and Cultural Influence on Science Subscale4A. Scientific research is not influenced by society and culture because scientists are trained to conduct “pure”, unbiased studies.20(14.9%)22(16.4%)92*(68.7%)4B. Cultural values and expectations determine whatscience is conducted and accepted.75*(56.0%)34(25.4%)25(18.7%)4C. Cultural values and expectations determine howscience is conducted and accepted.83*(61.9%)25(18.7%)26(19.4%)4D. All cultures conduct scientific research the same way because science is universal and independent of society and culture.10(7.5%)19(14.2%)105*(78.4%)5. Imagination and Creativity in Scientific Investigations Subscale5A. Scientists use their imagination and creativity when they collect data.58*(43.3%)20(14.9%)56(41.8%)5B. Scientists use their imagination and creativity when they analyze and interpret data.40*(29.9%)27(20.1%)67(50.0%)5C. Scientists do notuse their imagination and creativity because these conflict with logical reasoning.61(45.5%)24(17.9%)49*(36.6%)5D. Scientists do notuse their imaginations and creativity because these interfere with objectivity.63(47.0%)24(17.9%)47*(35.1%)6. Scientific Investigation Subscale6A. Scientists use a variety of methods to produce fruitful results.120*(90.0%)7(5.2%)7(5.2%)6B. Scientists follow the same step-by step scientific method.58(43.3%)27(20.1%)49*(36.6%)6C. When scientists use the scientific method correctly, their results are true and accurate.50(37.3%)30(22.4%)54*(40.3%)6D. Experiments are not he only means used in the development of scientific knowledge.112*(83.6%)20(14.9%)2(1.5%) N=134 *Indicates informed response Statistical Analysis of Pre-Test/Post-Test SUSSI Responses Table 3 summarizes the results of the two-tailed, paired t-tests conducted on pretest-posttest total SUSSI scores and on the six SUSSI subscales. The pretest mean 81.87 (SD=7.30) and posttest mean 82.77 (SD=9.07) were not found to be statistically significantly different. Two subscales were found to have statistically significant increases in pretest and posttest means. The Scientific Laws vs. Theories Subscale pre-test mean was 9.70 (SD = 2.16) and the post-test mean was 10.17 (SD = 2.24) at p< 0.05 ( t= 1.98). The Imagination and Creativity in Scientific Investigations Subscale pretest mean was 11.49 (SD = 3.67) and the posttest mean was 12.62 (SD = 4.17) at p< 0.003 ( t= 3.10). Table 3: Results of Two-Tailed, Paired t- Tests SUSSI SubscalesPretest Mean(SD)Posttest Mean(SD) tStatisticSignificance1. Observations and Inferences Subscale16.16(2.39)16.22(2.442)0.2.46NS2. Nature of Scientific Theories Subscale15.95(2.32)15.66(2.58)-1.02NS3. Scientific Laws vs. Theories Subscale9.70(2.16)10.17(2.24)1.98 p < 0.054. Social and Cultural Influence on Science Subscale14.65(2.64)14.20(3.06)-1.85NS5. Imagination and Creativity in Scientific Investigations Subscale11.49(3.67)12.62(4.17)3.10 p < 0.0036. Scientific Investigation Subscale13.91(2.04)13.89(2.29)0.099NSTotal Score81.87(7.30)82.77(9.07)1.17NS N = 134 Note: The higher the mean score, the more informed the response. Comparisons of Likert Items and Open-Ended Responses for Statistically Significant Subscale Pretest-Posttest Means Scientific Laws vs. Theories Subscale Analysis The prompt for the open-ended response stated, “With examples, explain the difference between scientific theories and scientific laws.” Of the twenty respondents who increased their score on this section by at least four points, nine of them responded to the open-ended prompt for this subscale on both the pretest and the posttest. The open-ended responses of these students were analyzed in conjunction with their pretest and posttest Likert responses. This analysis resulted in nine individual descriptions of how students’ concepts did, or did not change after taking the course. The results are summarized in Table 4. Table 4: Summary of Patterns and Supporting Data for Subscale 3: Scientific Laws vs. Scientific Theories for High-Gain Students with Pretest and Posttest Open-Ended Responses
https://theaste.org/pubs/proceedings/2007proceedings/2007proceedings/adams.htm
Rotavirus exploits SREBP pathway for hyper lipid biogenesis during replication | Microbiology Society Species A rotavirus (RVA) is one of the pathogens causing severe acute gastroenteritis in young children and animals worldwide. RVA replicates and assembles its immature particle within electron dense compartments known as viroplasm. Despite the importance of lipid droplet (LD) formation in the RVA viroplasm, the upstream molecules modulating LD formation have remained elusive. Here, we demonstrate that RVA infection reprogrammes sterol regulatory element binding proteins (SREBPs)-dependent lipogenic pathways in virus-infected cells. Interestingly, silencing of SREBPs significantly reduced RVA protein synthesis, genome replication and progeny virus production. Moreover, knockout of SREBP-1c gene conferred resistance to RVA-induced diarrhoea, reduction of RVA replication, and mitigation of small intestinal pathology in mice. This study identifies SREBPs-mediated lipogenic reprogramming in RVA-infected host cells for facilitating virus replication and SREBPs as a potential target for developing therapeutics against RVA infection. Rotavirus exploits SREBP pathway for hyper lipid biogenesis during replication Ahsan Naveed 1​ , Muhammad Ammar Naveed 2​ , Lubna Akram 2​ , Muhammad Sharif 1​ , Mun-Il Kang 1​ , Sang-Ik Park 1​ Affiliations: 1​ Laboratory of Veterinary Pathology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea 2​ District Headquarter Hospital, Pakpattan Sharif 57400, Pakistan *Correspondence: Ahsan Naveed, ahsannaveed.uaf@gmail.com Abstract Species A rotavirus (RVA) is one of the pathogens causing severe acute gastroenteritis in young children and animals worldwide. RVA replicates and assembles its immature particle within electron dense compartments known as viroplasm. Despite the importance of lipid droplet (LD) formation in the RVA viroplasm, the upstream molecules modulating LD formation have remained elusive. Here, we demonstrate that RVA infection reprogrammes sterol regulatory element binding proteins (SREBPs)-dependent lipogenic pathways in virus-infected cells. Interestingly, silencing of SREBPs significantly reduced RVA protein synthesis, genome replication and progeny virus production. Moreover, knockout of SREBP-1c gene conferred resistance to RVA-induced diarrhoea, reduction of RVA replication, and mitigation of small intestinal pathology in mice. This study identifies SREBPs-mediated lipogenic reprogramming in RVA-infected host cells for facilitating virus replication and SREBPs as a potential target for developing therapeutics against RVA infection. Received: 03/02/2022 Accepted: 05/04/2022 Published Online: 20/05/2022 Keyword(s): knockout , mice , rotavirus , SREBPs and viroplasm Chukkapalli V , Heaton NS , Randall G . 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https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001757
9.2 Distribution Types and Operations 9.2 Distribution Types and Operations syntax ( PDF In ) The type of probability density functions, or pdfs , defined as ( case-> ( In -> Flonum ) ( In Any -> Flonum ) ) For any function of this type, the second argument should default to #f . When not #f , the function should return a log density. syntax ( Sample Out ) The type of a distribution’s sampling procedure, defined as ( case-> ( -> Out ) ( Integer -> ( Listof Out ) ) ) When given a nonnegative integer n as an argument, a sampling procedure should return a length- n list of independent, random samples. syntax ( CDF In ) The type of cumulative distribution functions, or cdfs , defined as ( case-> ( In -> Flonum ) ( In Any -> Flonum ) ( In Any Any -> Flonum ) ) For any function of this type, both optional arguments should default to #f , and be interpreted as specified in the description of cdf . syntax ( Inverse-CDF Out ) The type of inverse cumulative distribution functions, or inverse cdfs , defined as ( case-> ( Real -> Out ) ( Real Any -> Out ) ( Real Any Any -> Out ) ) For any function of this type, both optional arguments should default to #f , and be interpreted as specified in the description of inv-cdf . struct ( struct distribution ( pdf sample ) ) pdf : ( PDF In ) sample : ( Sample Out ) The parent type of distribution objects . The In type parameter is the data type a distribution accepts as arguments to its pdf . The Out type parameter is the data type a distribution returns as random samples. Examples: > ( distribution? ( discrete-dist ' ( a b c ) ) ) #t > ( distribution? ( normal-dist ) ) #t > ( ( distribution-pdf ( normal-dist ) ) 0 ) 0.39894228040143265 > ( ( distribution-sample ( normal-dist ) ) ) 0.4967005325279395 See pdf and sample for uncurried forms of distribution-pdf and distribution-sample . struct ( struct ordered-dist distribution ( cdf inv-cdf min max median ) ) cdf : ( CDF In ) inv-cdf : ( Inverse-CDF Out ) min : Out max : Out median : ( Promise Out ) The parent type of ordered distribution objects . Similarly to distribution , the In type parameter is the data type an ordered distribution accepts as arguments to its pdf , and the Out type parameter is the data type an ordered distribution returns as random samples. Additionally, its cdf accepts values of type In , and its inverse cdf returns values of type Out . Examples: > ( ordered-dist? ( discrete-dist ' ( a b c ) ) ) #f > ( ordered-dist? ( normal-dist ) ) #t The median is stored in an ordered-dist to allow interval probabilities to be computed accurately. For example, for d = ( normal-dist ) , whose median is 0.0 , ( real-dist-prob d -2 .0 -1 .0 ) is computed using lower-tail probabilities, and ( real-dist-prob d 1.0 2.0 ) is computed using upper-tail probabilities. syntax Real-Dist The parent type of real-valued distributions, such as any distribution returned by normal-dist . Equivalent to the type ( ordered-dist Real Flonum ) . procedure ( pdf d v[ log?] )→ Flonum d : ( dist In Out ) v : In log? : Any = #f An uncurried form of distribution-pdf . When log? is not #f , returns a log density. Examples: > ( pdf ( discrete-dist ' ( a b c ) ' ( 1 2 3 ) ) ' a ) 0.16666666666666666 > ( pdf ( discrete-dist ' ( a b c ) ' ( 1 2 3 ) ) ' a #t ) -1.791759469228055 procedure ( sample d )→ Out d : ( dist In Out ) ( sample d n ) → ( Listof Out ) d : ( dist In Out ) n : Integer An uncurried form of distribution-sample . Examples: > ( sample ( exponential-dist ) ) 2.3456060483451924 > ( sample ( exponential-dist ) 3 ) '(0.7604211636317459 2.2200646486810895 0.011030713033138451) procedure ( cdf d v[ log? 1-p?] )→ Flonum d : ( ordered-dist In Out ) v : In log? : Any = #f 1-p? : Any = #f An uncurried form of ordered-dist-cdf . When log? is #f , cdf returns a probability; otherwise, it returns a log probability. When 1-p? is #f , cdf returns a lower-tail probability or log probability (depending on log? ); otherwise, it returns an upper-tail probability or log-probability. procedure ( inv-cdf d p[ log? 1-p?] )→ Out d : ( ordered-dist In Out ) p : Real log? : Any = #f 1-p? : Any = #f An uncurried form of ordered-dist-inv-cdf . When log? is #f , inv-cdf interprets p as a probability; otherwise, it interprets p as a log probability. When 1-p? is #f , inv-cdf interprets p as a lower-tail probability or log probability (depending on log? ); otherwise, it interprets p as an upper-tail probability or log probability. procedure ( real-dist-prob d a b[ log? 1-p?] )→ Flonum d : Real-Dist a : Real b : Real log? : Any = #f 1-p? : Any = #f Computes the probability of the half-open interval ( a , b ]. (If b < a , the two endpoints are swapped first.) The log? and 1-p? arguments determine the meaning of the return value in the same way as the corresponding arguments to cdf . procedure ( real-dist-hpd-interval d p )→ ( Values Flonum Flonum ) d : Real-Dist p : Real Finds the smallest interval for which d assigns probability p , if one exists. Examples: > ( define d ( beta-dist 3 2 ) ) > ( define-values ( x0 x1 ) ( real-dist-hpd-interval d 0.8 ) ) > ( plot ( list ( function-interval ( λ ( x ) 0 ) ( distribution-pdf d ) x0 x1 #:line1-style ' transparent #:line2-style ' transparent #:label "80% HPD region" ) ( function ( distribution-pdf d ) 0 1 #:label "Beta(3,2)" ) ) )
https://download.racket-lang.org/releases/6.1.1/doc/math/Distribution_Types_and_Operations.html
Scanning probe microscopy from the perspective of the sensor — the University of Bath's research portal Scanning probe microscopy from the perspective of the sensor Julian Stirling Department of Physics Research output : Thesis › Doctoral Thesis Abstract The class of instruments considered in this thesis, scanning probe microscopes (SPM), raster scan a sensory probe over a surface to form both high resolution images and quantitative interaction measurements. Understanding and extracting information from SPM data has been considered extensively in the three decades since the first SPM. Major developments tend to be greeted with their own theory and data analysis techniques. The more gradual evolution of equipment has not, however, attracted the same level of theoretical consideration. In this thesis we consider the SPM from an instrumentation perspective, concentrating on two specific types of microscope: the scanning tunnelling microscope (STM) and the atomic force microscope (AFM). Both of these microscopes rely on a sensory probe or sensor to induce and measure the desired interaction. We have carefully considered a range of experiments from a ‘sensor-eye-view’, both theoretically and experimentally. We first consider the effect of the geometry of AFM sensors on quantitative force measurements, identifying that the length of tips that the length of tips can induce an unwanted coupling of lateral and normal forces. We go further by developing methods to experimentally correct these force measurements along with designing a sensor which exploits symmetry to separate lateral and normal forces. We also consider the ways to automatically optimise the apex of the sensory probe of an STM to give the desired imaging resolution using a combination of prescribed routines and genetic algorithms. Image analysis techniques developed for this work have been developed into an open source toolbox to automatically process and analyse SPM images. Finally, we use control theory to analyse the feedback controlling the SPM probe. We find that the methods used in the literature do not fully consider the method with which the control loop is implemented in SPM. We employ a modified approach which results in more realistic simulated SPM operation. Original language English Qualification Ph.D. Awarding Institution University of Nottingham Publication status Published - Mar 2014 Access to Document http://eprints.nottingham.ac.uk/14000/1/Thesis.pdf Fingerprint Dive into the research topics of 'Scanning probe microscopy from the perspective of the sensor'. Together they form a unique fingerprint. Scanning probe microscopy Engineering & Materials Science 100% Microscopes Engineering & Materials Science 59% Scanning Engineering & Materials Science 34% Sensors Engineering & Materials Science 31% Force measurement Engineering & Materials Science 10% Image resolution Engineering & Materials Science 4% Control theory Engineering & Materials Science 4% Image analysis Engineering & Materials Science 4% Cite this APA Standard Harvard Vancouver Author BIBTEX RIS Stirling, J. (2014). Scanning probe microscopy from the perspective of the sensor . [Doctoral Thesis, University of Nottingham]. Scanning probe microscopy from the perspective of the sensor./ Stirling, Julian. 2014. 215 p. Research output : Thesis › Doctoral Thesis Stirling, J 2014, ' Scanning probe microscopy from the perspective of the sensor ', Ph.D., University of Nottingham. < http://eprints.nottingham.ac.uk/14000/1/Thesis.pdf > Stirling J. Scanning probe microscopy from the perspective of the sensor . 2014. 215 p. Stirling, Julian. / Scanning probe microscopy from the perspective of the sensor . 2014. 215 p. @phdthesis{9b10a0006991488eab933d028442f32f, title = "Scanning probe microscopy from the perspective of the sensor", abstract = "The class of instruments considered in this thesis, scanning probe microscopes (SPM), raster scan a sensory probe over a surface to form both high resolution images and quantitative interaction measurements. Understanding and extracting information from SPM data has been considered extensively in the three decades since the first SPM. Major developments tend to be greeted with their own theory and data analysis techniques. The more gradual evolution of equipment has not, however, attracted the same level of theoretical consideration. In this thesis we consider the SPM from an instrumentation perspective, concentrating on two specific types of microscope: the scanning tunnelling microscope (STM) and the atomic force microscope (AFM). Both of these microscopes rely on a sensory probe or sensor to induce and measure the desired interaction. We have carefully considered a range of experiments from a {\textquoteleft}sensor-eye-view{\textquoteright}, both theoretically and experimentally. We first consider the effect of the geometry of AFM sensors on quantitative force measurements, identifying that the length of tips that the length of tips can induce an unwanted coupling of lateral and normal forces. We go further by developing methods to experimentally correct these force measurements along with designing a sensor which exploits symmetry to separate lateral and normal forces. We also consider the ways to automatically optimise the apex of the sensory probe of an STM to give the desired imaging resolution using a combination ofprescribed routines and genetic algorithms. Image analysis techniques developed for this work have been developed into an open source toolbox to automatically process and analyse SPM images. Finally, we use control theory to analyse the feedback controlling the SPM probe. We find that the methods used in the literature do not fully consider the method with which the control loop is implemented in SPM. We employ a modified approach which results in more realistic simulated SPM operation.", author = "Julian Stirling", year = "2014", month = mar, language = "English", school = "University of Nottingham", } TY - THES T1 - Scanning probe microscopy from the perspective of the sensor AU - Stirling, Julian PY - 2014/3 Y1 - 2014/3 N2 - The class of instruments considered in this thesis, scanning probe microscopes (SPM), raster scan a sensory probe over a surface to form both high resolution images and quantitative interaction measurements. Understanding and extracting information from SPM data has been considered extensively in the three decades since the first SPM. Major developments tend to be greeted with their own theory and data analysis techniques. The more gradual evolution of equipment has not, however, attracted the same level of theoretical consideration. In this thesis we consider the SPM from an instrumentation perspective, concentrating on two specific types of microscope: the scanning tunnelling microscope (STM) and the atomic force microscope (AFM). Both of these microscopes rely on a sensory probe or sensor to induce and measure the desired interaction. We have carefully considered a range of experiments from a ‘sensor-eye-view’, both theoretically and experimentally. We first consider the effect of the geometry of AFM sensors on quantitative force measurements, identifying that the length of tips that the length of tips can induce an unwanted coupling of lateral and normal forces. We go further by developing methods to experimentally correct these force measurements along with designing a sensor which exploits symmetry to separate lateral and normal forces. We also consider the ways to automatically optimise the apex of the sensory probe of an STM to give the desired imaging resolution using a combination ofprescribed routines and genetic algorithms. Image analysis techniques developed for this work have been developed into an open source toolbox to automatically process and analyse SPM images. Finally, we use control theory to analyse the feedback controlling the SPM probe. We find that the methods used in the literature do not fully consider the method with which the control loop is implemented in SPM. We employ a modified approach which results in more realistic simulated SPM operation. AB - The class of instruments considered in this thesis, scanning probe microscopes (SPM), raster scan a sensory probe over a surface to form both high resolution images and quantitative interaction measurements. Understanding and extracting information from SPM data has been considered extensively in the three decades since the first SPM. Major developments tend to be greeted with their own theory and data analysis techniques. The more gradual evolution of equipment has not, however, attracted the same level of theoretical consideration. In this thesis we consider the SPM from an instrumentation perspective, concentrating on two specific types of microscope: the scanning tunnelling microscope (STM) and the atomic force microscope (AFM). Both of these microscopes rely on a sensory probe or sensor to induce and measure the desired interaction. We have carefully considered a range of experiments from a ‘sensor-eye-view’, both theoretically and experimentally. We first consider the effect of the geometry of AFM sensors on quantitative force measurements, identifying that the length of tips that the length of tips can induce an unwanted coupling of lateral and normal forces. We go further by developing methods to experimentally correct these force measurements along with designing a sensor which exploits symmetry to separate lateral and normal forces. We also consider the ways to automatically optimise the apex of the sensory probe of an STM to give the desired imaging resolution using a combination ofprescribed routines and genetic algorithms. Image analysis techniques developed for this work have been developed into an open source toolbox to automatically process and analyse SPM images. Finally, we use control theory to analyse the feedback controlling the SPM probe. We find that the methods used in the literature do not fully consider the method with which the control loop is implemented in SPM. We employ a modified approach which results in more realistic simulated SPM operation. M3 - Doctoral Thesis ER -
https://researchportal.bath.ac.uk/en/publications/scanning-probe-microscopy-from-the-perspective-of-the-sensor/
Bank of Hawaii v. Davis Radio Sales & Service, Inc., No. 11039 - Hawaii - Case Law - VLEX 886212282 0: [object Object]. 1: [object Object]. 2: [object Object]. 3: [object Object]. 4: [object Object]. 5: [object Object] Bank of Hawaii v. Davis Radio Sales & Service, Inc., No. 11039 <table><tbody><tr><td> Court</td><td> Court of Appeals of Hawai'i</td></tr><tr><td> Writing for the Court</td><td> Before HEEN, Acting C.J., TANAKA; HEEN</td></tr><tr><td> Citation</td><td> 6 Haw.App. 469,727 P.2d 419</td></tr><tr><td> Parties</td><td> , 2 UCC Rep.Serv.2d 1459 BANK OF HAWAII, a Hawaii corporation, and United States of America, Plaintiffs- Appellees, v. DAVIS RADIO SALES &amp; SERVICE, INC., a Hawaii corporation; Davis Radio Corporation, a Hawaii corporation; Ross Alan Davis and Noriko Davis, Defendants-Appellants, and Radio Specialists, Inc., a Hawaii corporation; Hugh J. Campbell; Nancy I. Campbell; Philip W. Bridges; Akiko K. Bridges; Wallace S. Tao; Miwako Tao; Gibralter Savings and Loan Association, a California corporation; Jason A. McCree; First Federal Bank of Connecticut, fka First Federal Savings and Loan Association of New Haven, a Connecticut corporation; and Association of Apartment Owners of Ridgecrest-Melemanu Woodlands by its Board of Directors, Defendants-Appellees, and John Does 2-10, and Doe Partnerships, Corporations and Other Entities 4-10, Defendants.</td></tr><tr><td> Decision Date</td><td> 30 October 1986</td></tr><tr><td> Docket Number</td><td> No. 11039</td></tr></tbody></table> Page 419 727 P.2d 419 6 Haw.App. 469, 2 UCC Rep.Serv.2d 1459 BANK OF HAWAII, a Hawaii corporation, and United States of America, Plaintiffs- Appellees, v. DAVIS RADIO SALES & SERVICE, INC., a Hawaii corporation; Davis Radio Corporation, a Hawaii corporation; Ross Alan Davis and Noriko Davis, Defendants-Appellants, and Radio Specialists, Inc., a Hawaii corporation; Hugh J. Campbell; Nancy I. Campbell; Philip W. Bridges; Akiko K. Bridges; Wallace S. Tao; Miwako Tao; Gibralter Savings and Loan Association, a California corporation; Jason A. McCree; First Federal Bank of Connecticut, fka First Federal Savings and Loan Association of New Haven, a Connecticut corporation; and Association of Apartment Owners of Ridgecrest-Melemanu Woodlands by its Board of Directors, Defendants-Appellees, and John Does 2-10, and Doe Partnerships, Corporations and Other Entities 4-10, Defendants. No. 11039. Intermediate Court of Appeals of Hawai'i. Oct. 30, 1986. Page 420 Syllabus by the Court 1. A motion for summary judgment is properly granted under Rule 56(c), Hawaii Rules of Civil Procedure (1980), if the record shows that there is no genuine issue as to any material fact and that the moving party is entitled to judgment as a matter of law. 2. Where a secured creditor has disposed of personal property pledged as security without complying with the notice to debtor requirement of Hawaii Revised Statutes [6 Haw.App. 470] (HRS) § 490:9-504(3) (Supp.1984), the fair market value of the collateral at the time of disposition and any damages that the debtor may have suffered from the lack of notice are issues of material fact, and where they have not been determined summary judgment is not proper. 3. When there is a change in the law by court decision between the time of the trial court ruling and the time of appeal, the appellate court applies the law prevailing at the time of the appellate disposition. 4. Where a secured creditor fails to comply with the notice to debtor requirement of HRS § 490:9-504(3) and disposes of collateral pledged as security for the underlying obligation, the secured creditor has the burden of rebutting the presumption that the fair market value of the collateral equals the unpaid balance of the outstanding debt. In proving fair market value, the secured creditor may not rely solely on the value received at the disposition sale, but must prove the fair market value by other evidence. 5. Where the secured creditor has failed to rebut the presumption applicable upon his violation of HRS § 490:9-504(3), the debtor is entitled to have the debt extinguished or where the secured creditor shows that the fair market value is higher Page 421 than the sale price of the collateral but lower than the debt due, the debtor is entitled to have the debt reduced by the difference between the fair market value and the sale price. 6. Where the debtor is harmed by the secured creditor's failure to comply with the notification requirement of HRS § 490:9-504(3), the debtor will be entitled under HRS § 490:9-507(1) (1976) to have the amount of damages set-off against any deficiency the secured creditor would otherwise recover. 7. The provisions of article 9 of HRS chapter 490 (1976 and Supp.1984) governing the rights of secured creditors to proceed against the collateral pledged by a debtor as security, do not apply to security interests in real estate. 8. Under HRS § 490:9-501(1) and (4) (1976), where a security agreement covers both real and personal property, the secured party may, upon breach of the underlying agreement by the obligor, proceed against the real property separately from the personalty or against both the real property and the personal property. Where the secured creditor proceeds against both the real property and the personal property, the provisions of article 9 of HRS chapter 490 do not apply and the creditor's rights are determined by the law relating to real property. 9. Although the provisions of article 9 of HRS chapter 490 are not applicable in a mortgage foreclosure proceeding, they are relevant in determining whether foreclosure should be granted. 10. Where the secured creditor who has not complied with the notice requirements of HRS § 490:9-504(3) is unable to rebut the presumption that the fair market value of the personal property sold in enforcement of his security interest equals the balance of the [6 Haw.App. 471] outstanding debt, foreclosure of a mortgage pledged as additional security for the underlying obligation should be denied. 11. Where in a proceeding for a deficiency judgment under article 9 of HRS chapter 490 the action is amended to include a proceeding for foreclosure of a mortgage of real property, the entire proceeding becomes equitable in nature and thereafter is governed by the rules of equity. 12. A complaint in equity is an appeal to the exercise of the equity court's sound discretion. Equity jurisprudence is not bound by strict rules of law but can mold its decree "to do justice," and a court of equity, once having acquired jurisdiction may retain the case to afford complete relief. 13. Where, in an action for foreclosure of a mortgage by a secured creditor who, in violation of the HRS § 490:9-504(3) notice provision had previously disposed of personal property given as security for the same underlying obligation secured by the mortgage, the fair market value of the personal property had not been determined, the equity court should have denied the interlocutory decree of foreclosure until the fair market value had been determined and the debtor credited with the difference between the fair market value and the sale price, and any damages suffered by reason of the notice violation. 14. Where a mortgagee assigns his interest in a mortgage, the assignee stands in the shoes of the mortgagee and is subject to any rights of setoff by the debtor at the time of the assignment. [6 Haw.App. 484] Jeffrey M. Taylor, Honolulu, for defendants-appellants. Roy T. Chikamoto, Sp. Asst. U.S. Atty., U.S. Atty.'s Office, Honolulu, for plaintiff-appellee United States of America, on behalf of SBA. Emma S. Matsunaga (Vernon Y.T. Woo and Foster Thorbjornsen, with her on the brief; Woo, Kessner & Duca, of counsel), Honolulu, for plaintiff-appellee BOH. [6 Haw.App. 469] Before HEEN, Acting C.J., TANAKA, J., and Circuit Judge DANIEL HEELY in place of Chief Judge BURNS, Recused. Page 422 HEEN, Acting Chief Judge. Defendants-appellants Davis Radio Sales and Service, Inc. (DRSS), Davis Radio Corporation (DRC), Ross Alan Davis (Davis), and Noriko Davis (hereinafter, where appropriate, Ross Alan Davis and Noriko Davis will be collectively referred to as the Davises, and all defendants-appellants will be collectively referred to as Defendants) appeal (1) the trial court's June 17, 1981 order (June 17, 1981 order) authorizing plaintiff-appellee Bank of Hawaii (BOH) to proceed with the foreclosure of a second mortgage (mortgage) executed by the Davises; and (2) an interlocutory decree of foreclosure (interlocutory decree) of that mortgage in favor of plaintiff-appellee the United States [6 Haw.App. 472] of America on behalf of the Small Business Administration (SBA). 1We vacate the order and the interlocutory decree, and remand for further proceedings. FACTS In 1973, Davis was the sole stockholder of DRSS and DRC, two Hawaii corporations. In August of 1973, DRSS obtained a $100,000 line of credit (line of credit) from BOH in order to purchase car radios and stereos to sell in its business. The loan was secured by security interests in DRSS' and DRC's inventory, accounts receivable, and after-acquired property, and guaranties from DRC and the Davises personally. Between December 6, 1974, and June 30, 1975, BOH made nine loans to DRSS under the line of credit, totalling approximately $60,455. On September 17, 1974, DRSS obtained from BOH a further $100,000 loan guaranteed by SBA (SBA guaranteed loan). The proceeds of the SBA guaranteed loan were to be used to pay $50,000 to First Hawaiian Bank 2on a previous debt and $50,000 for working capital. DRSS again secured the loan with its business inventory, accounts receivable, and after-acquired property. As additional security, the Davises executed another personal guaranty and the mortgage on their personal residence in favor of BOH. 3 On September 1, 1976, Davis sold DRSS and all of its inventory to Radio Specialists, Inc. (RSI), a Hawaii corporation formed by three former DRSS employees, Hugh J. Campbell (Campbell), Phillip W. Bridges (Bridges) and Wallace Tao (Tao). RSI assumed all of the debts and obligations owed by DRSS and gave BOH security interests in RSI's inventory and accounts receivable. BOH retained all the security it had obtained from DRSS, DRC, and the Davises, including the [6 Haw.App.473] mortgage. In May, 1977, RSI ceased making payments on the loans. PROCEDURAL HISTORY On October 20, 1977, BOH filed suit against Defendants, RSI, and Campbell, Bridges, Tao, and their wives, 4alleging that defendants owed BOH $44,454.61 on the line of credit and $84,177.41 in principal and $3,824.72 in interest on the SBA guaranteed loan. 5The complaint sought possession of RSI's business inventory, which BOH alleged to be valued at $47,000, and Page 423 judgment against all the defendants individually. BOH seized the business inventory pursuant to an ex parte order of the lower court, and on February 25, 1978, sold it at auction for $11,839.26. The net proceeds of $8,879.44 were applied to the repayment of the line of credit debt. Defendants were not given notice of the sale as required by Hawaii Revised Statutes (HRS) § 490:9-504(3) (Supp.1984). 6 [6 Haw.App. 474] On May 11, 1979, Defendants filed a motion for summary judgment on the ground that BOH's failure to give them notice of the sale of the business inventory discharged them from all liability for the balance due on the loans. On May 25, 1979, BOH filed a... 12 practice notes Burke v. Countrywide Mortg. Ventures, LLC, CIVIL NO. 17-00220 DKW-RLP United States U.S. District Court — District of Hawaii December 19, 2017 ...the UCC "does not apply to mortgages and other interests in real property") (citing Bank of Hawaii v. Davis Radio Sales & Service, Inc., 6 Haw. App. 469, 479 (1986)); In re Endresen, 548 B.R. 258, 269 (B.A.P. 9th Cir. 2016), appeal dismissed (July 1, 2016) ("Article 9 of the UCC does not ap...... Beneficial Hawaii, Inc. v. Kida, No. 22420. United States Supreme Court of Hawai'i August 31, 2001 ...such suits to be brought in equity") (some brackets added and some in original); Bank of Hawaii v. Davis Radio Sales and Service, Inc., 6 Haw. App. 469, 480-81, 727 P.2d 419, 427 A complaint in equity is an appeal to the exercise of the equity court's sound discretion, Fleming v. Napili Kai...... Ching v. Case, SCAP-18-0000432 United States Supreme Court of Hawai'i August 23, 2019 ...bound by strict rules of law, but can mold its decree ‘to do justice[.]’ " (quoting Bank of Hawaii v. Davis Radio Sales & Serv., Inc., 6 Haw. App. 469, 481, 727 P.2d 419, 427 (1986) )). We therefore hold that the portions of the court’s order directing the State to undertake specific action...... HAWAI'I NAT. BANK v. Cook, No. 22225. United States Court of Appeals of Hawai'i May 16, 2000 ...Fleming v. Napili Kai, Ltd., 50 Haw. 66, 70, 430 P.2d 316, 319 (1967). See also Bank of Hawaii v. Davis Radio Sales & Service, 6 Haw.App. 469, 480-81, 727 P.2d 419, 427 (1986) ("Equity jurisprudence is not bound by strict rules of law, but can mold its decree `to do justice[.]'") (quoting F...... 12 cases Burke v. Countrywide Mortg. Ventures, LLC, CIVIL NO. 17-00220 DKW-RLP United States U.S. District Court — District of Hawaii December 19, 2017 ...the UCC "does not apply to mortgages and other interests in real property") (citing Bank of Hawaii v. Davis Radio Sales & Service, Inc., 6 Haw. App. 469, 479 (1986)); In re Endresen, 548 B.R. 258, 269 (B.A.P. 9th Cir. 2016), appeal dismissed (July 1, 2016) ("Article 9 of the UCC does not ap...... Beneficial Hawaii, Inc. v. Kida, No. 22420. United States Supreme Court of Hawai'i August 31, 2001 ...such suits to be brought in equity") (some brackets added and some in original); Bank of Hawaii v. Davis Radio Sales and Service, Inc., 6 Haw. App. 469, 480-81, 727 P.2d 419, 427 A complaint in equity is an appeal to the exercise of the equity court's sound discretion, Fleming v. Napili Kai...... Ching v. Case, SCAP-18-0000432 United States Supreme Court of Hawai'i August 23, 2019 ...bound by strict rules of law, but can mold its decree ‘to do justice[.]’ " (quoting Bank of Hawaii v. Davis Radio Sales & Serv., Inc., 6 Haw. App. 469, 481, 727 P.2d 419, 427 (1986) )). We therefore hold that the portions of the court’s order directing the State to undertake specific action...... HAWAI'I NAT. BANK v. Cook, No. 22225. United States Court of Appeals of Hawai'i May 16, 2000 ...Fleming v. Napili Kai, Ltd., 50 Haw. 66, 70, 430 P.2d 316, 319 (1967). See also Bank of Hawaii v. Davis Radio Sales & Service, 6 Haw.App. 469, 480-81, 727 P.2d 419, 427 (1986) ("Equity jurisprudence is not bound by strict rules of law, but can mold its decree `to do justice[.]'") (quoting F......
https://case-law.vlex.com/vid/bank-of-hawaii-v-886212282
% poorest households (with IWI value under 35) - Area Database - Region Ranking - Global Data Lab Area Database (v4.2.1) % poorest households (with IWI value under 35) First decile Country / Region Albania / Berat Albania / Diber Albania / Durres Albania / Elbasan Albania / Gjirokaster Albania / Korce Albania / Kukes Albania / Shkoder Albania / Vlore Algeria / Hauts Plateaux Est (Setif, Batna, Khenchela, Bordj Bou Arreridj, Oum El Bouaghi, Tebessa) Algeria / Nord Est (Annaba, Constantine, Skikda, Jijel, Mila, Souk Ahras, El Tarf, Guelma) Argentina urban / Cuyo Argentina urban / NOA Argentina urban / Pampeana Argentina urban / Patagonia Armenia / Aragatsotn Armenia / Armavir Armenia / Gegharkunik Armenia / Kotayk Armenia / Lori Armenia / Shirak Armenia / Syunik Armenia / Tavush Armenia / Vayots Dzor Armenia / Yerevan Azerbaijan / Baku Belarus / Grodno region Belarus / Vitebsk region Bosnia and Herzegovina / Northern Bosnia Bosnia and Herzegovina / Western Bosnia Bosnia and Herzegovina / Western herzegovina Brazil / Distrito Federal Brazil / Rio de Janeiro Brazil / Sao Paulo Colombia / Bogota D.C. Colombia / Quindio Costa Rica / Cartago Costa Rica / Heredia Costa Rica / San Jose Cuba / C. Habana Cuba / Isla Egypt / Alexandria Egypt / Aswan Egypt / Behera Egypt / Cairo Egypt / Dakahlia Egypt / Gharbia Egypt / Giza Country / Region Egypt / Kalyubia Egypt / Menoufia Egypt / Port Said Egypt / Suez Georgia / Tbilisi India / Lakshadweep Iraq / Baghdad Iraq / Basra Iraq / Diala Iraq / Dohouk Iraq / Erbil Iraq / Nenava Iraq / Qadisiya Iraq / Ta-amem-Karkuk Iraq / Thi-Qar Jordan / Aljoun Jordan / Amman Jordan / Irbid Jordan / Jarash Jordan / Karak Jordan / Ma'an Jordan / Tafiela Kazakhstan / Almaty city Kazakhstan / Central region (Karagandinskaya) Kazakhstan / South region (Almatinskaya, Zhambylskaya, Kyzylordinskaya, South-Kazakhstanskaya) Kosovo / Ferizaj Kosovo / Gjakova Kosovo / Mitrovica Kosovo / Peja Kosovo / Pristina Kosovo / Prizren Kyrgyzstan / Bishkek Kyrgyzstan / Chuy Kyrgyzstan / Issyk-Kul Kyrgyzstan / Jalal-Abad Kyrgyzstan / Talas Malaysia / Central (Perak, Selangor, Wilayah Persekutuan) Malaysia / East (Kelantan, Terengganu, Pahang) Malaysia / North (Perlis, Kedah, Penang) Malaysia / South (Negeri Sembilan, Melaka, Johor) Maldives / Central Maldives / Male Maldives / South Maldives / South Central Mauritius / South (Grand Port, Savanne, Plaines Wilhems, Black River) Monte Negro / Centre Morocco / Eastern Morocco / South Country / Region Morocco / Tensift North Macedonia / East North Macedonia / North East North Macedonia / Pelagoniski North Macedonia / Poloski North Macedonia / Skopski North Macedonia / South East North Macedonia / South West North Macedonia / Vardarski Palestine / Deir El-Balah, Khan Yunis, Rafah Palestine / Jenin, Tubas, Tulkarm, Nablus, Qalqiliya Palestine / Jerusalem Saudi Arabia / North (Northern Borders, Al Jawf, Hail) Serbia / Belgrade Serbia / South and East Serbia Syria / Al Latakia Syria / Al Qunitara - Quneitra Syria / Damascus Tajikistan / Duchanbe Thailand / Bangkok Thailand / Central Thailand / Northeast Tonga / Ongo Niua Tunisia / Grand Tunis (Tunis, Ariana, Ben Arous, Manouba) Turkey / Central Anatolia (Kayseri, Kirsehir, Nevsehir, Nigde, Sivas, Yozgat, Aksaray, Kirikkale) Turkey / Istanbul Turkey / West Anatolia (Ankara, Konya, Karaman) Turkey / West Black Sea (Amasya, Cankiri, Corum, Kastamonu, Samsun, Sinop, Tokat, Zonguldak, Bartin, Karabuk) Turkey / West Marmara (Balikesir, Canakkale, Edirne, Kirklareli, Tekirdag) Turkmenistan / Akhal Turkmenistan / Ashgabat City Turkmenistan / Balkan Turkmenistan / Dashoguz Turkmenistan / Lebap Turkmenistan / Mary Turks & Caicos Islands / Providenciales Uruguay / Centro (Durazno and Tacuarembo) Uruguay / Centro Sur (Flores, Florida and Lavalleja) Uruguay / Costa Este (Canelones, Maldonado and Rocha) Uruguay / Litoral Norte (Paysandu, Salto and Rio Negro) Uruguay / Litoral Sur (Soriano, Colonia and San Jose) Uruguay / Montevideo and Metropolitan area Uruguay / Norte (Artigas, Rivera, Cerro Largo and Trienta y Tres) Uzbekistan / Tashkent Venezuela / Region Capital Venezuela / Region Central Venezuela / Region Los Andes Venezuela / Region Los Llanos Second decile Country / Region Albania / Fier Albania / Lezhe Albania / Tirana Algeria / Hauts Plateaux Ouest (Tiaret, Saida, Tissemsilt, Naama, El Bayadh) Algeria / Nord Centre (Alger, Blida, Boumerdes, Tipaza, Bouira, Medea, Tizi-Ouzou, Bejaia, Chlef, Ain Defla) Algeria / Nord Ouest (Oran, Tlemcen, Mostaganem, Ain Temouchent, Relizane, Sidi Bel Abbes, Mascara) Algeria / Sud (Bechar, Tindouf, Adrar, Ghardaia, Biskra, El Oued, Ouargla, Tamanrasset,Illizi) Argentina urban / Gran Buenos Aires Argentina urban / NEA Armenia / Ararat Barbados / Christ Church and St. Philip Barbados / St. James, St. George, and St. Thomas Belarus / Brest region Belarus / Gomel region Belarus / Minsk region Belarus / Mogilev region Bhutan / Thimphu Bosnia and Herzegovina / Central Bosnia Bosnia and Herzegovina / Republica Srpska Brazil / Espirito Santo Brazil / Goias Brazil / Parana Brazil / Rio Grande do Sul Brazil / Santa Catarina Cape Verde / Fogo Chili / Region Metropolitana China / Beijing, Tianjin, Hebei, Shandong China / Beijing China / Jilin China / Shanghai China / Tianjin Colombia / Atlantico (incl Barranquilla) Colombia / Caldas Colombia / Risaralda Colombia / San Andres Colombia / Valle (incl Cali) Colombia / Vichada Costa Rica / Alajuela Costa Rica / Guanacaste Costa Rica / Limon Dominican Republic / Region 0 (Distrito Nacional, Santo Domingo, Monte Plata) Egypt / Assuit Egypt / Beni Suef Egypt / Damietta Egypt / Fayoum Egypt / Ismailia Egypt / Kafr El-Sheikh Egypt / Menya Country / Region Egypt / Qena Egypt / Sharkia Egypt / Souhag Fiji / Naitasiri Georgia / Ajaria Georgia / Imereti Racha-Lochkhumi Kvemo Svaneti Georgia / Kvemo Kartli Georgia / Samtskhe-Javakheti India / New Delhi Indonesia / DKI Jakarta Iran / Bushehr Iran / Esfahan Iran / Mazandaran Iran / Qazvin Iran / Qom Iran / Semnan Iran / Tehran and Alborz Iraq / Anbar Iraq / Babylon Iraq / Kerbela Iraq / Maysan Iraq / Muthanna Iraq / Najaf Iraq / Salaheldeen Iraq / Suleimaniya Iraq / Wasit Jordan / Aqaba Jordan / Madaba Jordan / Mafraq Jordan / Zarqa Kazakhstan / East region (East-Kazakhstanskaya) Kazakhstan / North region (Akmolinskaya (incl Astana city), Kostnaiskaya, Pavlodarskaya, North-Kazakhstanskaya) Kazakhstan / West region (Aktyubinskaya, Atyrauskaya, Mangistauskaya, West-Kazakhstanskaya) Kosovo / Gjilan Kyrgyzstan / Batken Kyrgyzstan / Naryn Kyrgyzstan / Osh Lao / Vientiane Municipality Malaysia / Kuala Lumpur Federal Territory Maldives / North Maldives / North Central Mauritius / North (Port Louis, Pamplemousses, Riviere du Rempart, Flacq, Moka) Mexico / CDMX-Edo Mexico Ciudad de Mexico (Estado de Mexico) Mexico / Centro (Guerrero, Morelos, Puebla, Tlaxcala, Hidalgo, Michoacan y Colima) Mexico / Noreste (Aguascalientes, Coahuila, Guanajuato, Nuevo Leon, Queretaro, San Luis Potosi, Tamaulipas, Mexico / Noroeste (Baja California, Baja California Sur, Chihuahua, Durango, Jalisco, Nayarit, Sinaloa y Son Mexico / Aguascalientes Mexico / Distrito Federal Country / Region Mexico / Nuevo Leon Moldova / Chisinau Mongolia / Ulaanbaatar Monte Negro / North Monte Negro / South Morocco / Centre Morocco / Centre north Morocco / North west Palestine / Bethlehem, Hebron Palestine / North Gaza, Gaza Palestine / Salfit, Ramallah, Al-Bireh, Jericho, Al Aghwar Philippines / National Capital Region Samoa / Apia Urban Area Senegal / Dakar Serbia / Sumadija and West Serbia Serbia / Vojvodina Suriname / Paramaribo Suriname / Wanica and Para Syria / Halab - Aleppo Syria / Hamaa Syria / Homs Syria / Rural Damascus Syria / Tartous Thailand / North Thailand / South Tonga / Eua Tonga / Tongatapu Tonga / Vava-u Tunisia / Centre Est (Sousse, Monastir, Mahdia, Sfax) Tunisia / Centre Ouest (Kairouan, Kasserine, Sidi Bouzid) Tunisia / Nord Est (Nabeul, Zaghouan, Bizerte) Tunisia / Sud Est (Gabes, Medinine, Tataouine) Tunisia / Sud Ouest (Gafsa, Tozeur, Kebili) Turkey / Aegean (Afyon, Aydin, Denizli, Izmir, Kutahya, Manisa, Mugla, Usak) Turkey / Central East Anatolia (Bingol, Bitlis, Elazig, Hakkari, Malatya, Mus, Tunceli, Van) Turkey / East Black Sea (Artvin, Giresun, Gumushane, Ordu, Rize, Trabzon) Turkey / East Marmara (Bilecik, Bolu, Bursa, Duzce, Eskisehir, Kocaeli, Sakarya, Yalova) Turkey / Mediterranean (Adana, Antalya, Burdur, Hatay, Isparta, Icel, K Maras, Osmaniye) Turkey / South East Anatolia (Adiyaman, Diyarbakir, Gaziantep, Mardin, Siirt, Sanliurfa, Batman, Sirnak, Kili Turks & Caicos Islands / Turks islands Ukraine / Central Ukraine / East Ukraine / South Venezuela / Region Oriental Venezuela / Region Zuliana Venezuela / Federal District Vietnam / Red River Delta Vietnam / South East Third decile Country / Region Algeria / Hauts Plateaux Centre (Djelfa, Laghouat, MSila) Azerbaijan / Absheron Bangladesh / Dhaka Barbados / St Michael Barbados / St. Lucy, St. Peter, St. Andrew, St. Joseph, and St. John Belize / Belize Brazil / Mato Grosso Brazil / Mato Grosso do Sul Brazil / Minas Gerais Brazil / Paraiba Brazil / Pernambuco Brazil / Rio Grande do Norte Brazil / Sergipe Cambodia / Phnom Penh Cape Verde / S.Vicente Cape Verde / Santiago- Praia Chili / Antofagasta Chili / Magallanes and La Antartica Chilena Chili / Valparaiso (former Aconcagua) China / Fujian, Guangdong, Hainan China / Gansu, Qinghai, Ningxia, Xinjiang China / Henan, Shanxi, Shaanxi, Inner Mongolia China / Liaoning, Jilin, Heilongjiang China / Shanghai, Jiangsu, Zhejiang, Anhui China / Fujian China / Gansu China / Guangdong China / Hainan China / Hebei China / Heilongjiang China / Hubei China / Jiangsu China / Liaoning China / Ningxia China / Qinghai China / Shaanxi China / Shandong Colombia / Arauca Colombia / Cundinamarca Colombia / Guaviare Colombia / Santander Costa Rica / Puntarenas Cuba / Matanzas Cuba / Pinar del Rio Cuba / Prov. Habana Dominican Republic / Region II (Espaillat, Puerto Plata, Santiago) Dominican Republic / Region VIII (La Vega, Monsenor Nouel, Sanchez Ramirez) Egypt / Frontier governorates (Red Sea, New Valley, Matroh, North Sainai, South Sainai) Country / Region Fiji / Ba Fiji / Kadavu, Lau, Lomaiviti, Rotuma Fiji / Macuata Fiji / Rewa Fiji / Serua, Namosi Gabon / Libreville-Port Gentil Gambia / Banjul Georgia / Guria Georgia / Kakheti Georgia / Mtskheta-Mtianeti Georgia / Samegrelo-Zemo Svateni Georgia / Shida Kartli Guatemala / Metropolitan Guinea / Conakry Guyana / Essequibo Islands-West Demerara Guyana / Upper Demerara-Berbice Honduras / Cortes Honduras / Islas de la Bahia India / Chandigarth India / Daman and Diu India / Goa India / Kerala India / Puducherry India / Punjab India / Sikkim Indonesia / DI Yogyakarta Indonesia / East Kalimantan Indonesia / Riau (incl. Riau islands) Iran / Ardebil Iran / EastAzarbayejan Iran / Fars Iran / Golestan Iran / Hamedan Iran / Khorasan-e-Razavi Iran / Khuzestan Iran / Kordestan Iran / Markazi Iran / WestAzarbayejan Iran / Yazd Jamaica / Kingston, St Andrew Jordan / Balqa Malaysia / Johor Malaysia / Melaka Malaysia / Pulau Pinang Malaysia / Selangor Mauritius / Rodrigues Mexico / Baja California Mexico / Coahuila Fourth decile Country / Region Azerbaijan / Guba Khachmaz Belize / Stann Creek, Toledo Bhutan / Paro Botswana / South-East Brazil / Alagoas Brazil / Amapa Brazil / Bahia Brazil / Ceara Brazil / Rondonia Brazil / Tocantins Cameroon / Sud Ouest Cape Verde / Santiago-Interior Chili / Centro V - VII Chili / Norte I - IV Chili / Atacama Chili / Bio Bio Chili / Coquimbo Chili / Maule Chili / OHiggins Chili / Tarapaca (incl Arica and Parinacota) China / Chongqing, Sichuan, Guizhou, Yunnan, Tibet China / Hubei, Jiangxi, Hunan, Guangxi China / Anhui China / Chongqing China / Guangxi Zhuang China / Guizhou China / Henan China / Hunan China / Inner Mongolia China / Jiangxi China / Shanxi China / Sichuan China / Yunnan China / Zhejiang Colombia / Antioquia (incl Medellin) Colombia / Boyaca Colombia / Casanare Colombia / Huila Colombia / Meta Colombia / Norte de Santander Colombia / Putumayo Colombia / Tolima Cuba / Ciego de Avila Cuba / Cienfuegos Cuba / Guantanamo Cuba / S.Spiritus Cuba / Villa Clara Dominican Republic / Region I (Peravia, San Cristobal, San Jose de Ocoa, Azua) Country / Region Dominican Republic / Region III (Duarte, Maria Trinidad Sanchez, Salcedo, Samana) Dominican Republic / Region V (El Seibo, La Altagracia, La Romana, San Pedro de Macoris, Hato Mayor) Dominican Republic / Region VII (Dajabon, Monte Cristi, Santiago Rodriguez, Valverde) El Salvador / Central I Ethiopia / Addis Fiji / Cakaudrove, Bua Fiji / Nadroga or Navosa Fiji / Tailevu Gambia / Kanifing Guyana / Demerara-Mahaica Guyana / East Berbice-Corentyne Guyana / Mahaica-Berbice Honduras / Atlantida Honduras / Francisco Morazan India / Andaman and Nicobar Islands India / Arunachal Pradesh India / Haryana India / Himachal Pradesh India / Karnataka India / Mizoram India / Uttaranchal Indonesia / Bali Indonesia / Bangka Belitung Indonesia / Banten Indonesia / Bengkulu Indonesia / Central Java Indonesia / Jambi Indonesia / Lampung Indonesia / North Sulawesi Indonesia / West Java Indonesia / West Sumatra Iran / Chaharmahal and Bakhtiyari Iran / Gilan Iran / Hormozgan Iran / Ilam Iran / Kermanshah Iran / Lorestan Iran / North Khorasan Iran / Zanjan Jamaica / St Ann, St Catherine Lao / Borikhamxay Lao / Champasack Lao / Vientiane Province Malaysia / East Malaysia (Saba, Sarawak) Malaysia / Kedah Malaysia / Negeri Sembilan Malaysia / Perak Malaysia / Perlis Country / Region Mauritania / Nouadhibou Mauritania / Tiris-Zemmour Mexico / Sur (Campeche, Chiapas, Oaxaca, Quintana Roo, Tabasco, Veracruz y Yucatan) Mexico / Baja California Sur Mexico / Campeche Mexico / Chihuahua Mexico / Durango Mexico / Hidalgo Mexico / Michoacan de Ocampo Mexico / Nayarit Mexico / Puebla Mexico / Quintana Roo Mexico / Sinaloa Mexico / Sonora Mexico / Tabasco Mexico / Yucatan Moldova / South Mongolia / Central (Dornogovi, Dundgovi, Umnugovi, Selenge, Tuv, Darkhan-Uul, Govisumber) Mongolia / Eastern (Dornod, Sukhbaatar, Khentii) Nepal / Mid-western Pakistan / Gilgit Baltistan Panama / Colon Panama / Los Santos Paraguay / South-East (Guaira, Misiones, Paraguari, Neembucu) Peru / West (Ancash, Lima, Callao) Philippines / I-Ilocos Philippines / III-Central Luzon Philippines / IVA-CALABARZON Saint Lucia / St Lucia rural Saint Lucia / St Lucia urban Saudi Arabia / Center (Riadh, Qassim) Saudi Arabia / South (Bahah, Jizan, Asir, Najran) South Africa / Free State South Africa / Northern Province Syria / Al Hasaka Syria / Al Raka-Raqqa Tajikistan / GBAO Trinidad & Tobago / East Tuvalu / Vaitupu, Nui, Nukufetau Uzbekistan / Central (Navoi, Bukhara, Samarkand) Venezuela / Aragua Venezuela / Carabobo Venezuela / Miranda Venezuela / Tachira Venezuela / Vargas Vietnam / Central Highlands Vietnam / North East, North West Fifth decile Country / Region Afghanistan / Central (Kabul Wardak Kapisa Logar Parwan Panjsher) Afghanistan / North (Samangan Sar-e-Pul Balkh Jawzjan Faryab) Angola / Luanda Azerbaijan / Lankaran Azerbaijan / Shaki Zaqatala Belize / Corozal, Orange Walk Bhutan / Bumthang Botswana / Kgatleng Brazil / Acre Brazil / Amazonas Brazil / Maranhao Brazil / Para Brazil / Piaui Brazil / Roraima Cameroon / Littoral (incl Douala) Cape Verde / S.Antao Chili / Sur VIII - XII Chili / Aisen Chili / Arbucania Chili / Los Lagos (incl Los Rios) Colombia / Amazonas Colombia / Bolivar (Sur and Norte) Colombia / Caqueta Colombia / Cauca Colombia / Cordoba Colombia / Magdalena Colombia / Narino Colombia / Sucre Congo Brazzaville / Brazzaville Cuba / Camaguey Cuba / Holguin Cuba / Las Tunas Cuba / Santiago de Cuba Dominican Republic / Region IV (Independencia, Bahoruco, Barahona, Pedernales) Dominican Republic / Region VI (San Juan, Elias Pina) Ecuador / Coste Ecuador / Sierra El Salvador / Central II Fiji / Ra Gambia / Brikama Ghana / Greater Accra Guatemala / Central Guyana / Cuyuni-Mazaruni Guyana / Pomeroon-Supenaam Honduras / Colon Honduras / Comayagua Honduras / Copan Honduras / La Paz Country / Region Honduras / Ocotepeque Honduras / Santa Barbara Honduras / Valle Honduras / Yoro India / Andhra Pradesh India / Dadra and Nagar Haveli India / Gujarat India / Jammu and Kashmir India / Maharashtra India / Nagaland India / Rajasthan India / Tamil Nadu India / Telangana Indonesia / Central Kalimantan Indonesia / Central Sulawesi Indonesia / DI Aceh Indonesia / East Java Indonesia / Gorontalo Indonesia / North Sumatra Indonesia / South Kalimantan Indonesia / South Sulawesi (incl Sulawesi Barat) Indonesia / South Sumatra Indonesia / Southeast Sulawesi Indonesia / West Kalimantan Indonesia / West Nusa Tenggara Iran / Kerman Iran / Kohgiluyeh and Boyerahmad Iran / South Khorasan Jamaica / Manchester, Clarendon Jamaica / St James, Hanover, Westmoreland Jamaica / St Thomas, Portland, St Mary Jamaica / Trelawny, St Elizabeth Kenya / Nairobi Lao / Khammuane Lao / Sayabury Lao / Xiengkhuang Malaysia / Kelantan Malaysia / Pahang Malaysia / Terengganu Mali / Bamako Mauritania / Trarza incl Nouakchott Mexico / San Luis Potosi Mexico / Veracruz Moldova / Center Moldova / North Mongolia / Khangai (Arkhangai, Bayankhongor, Bulgan, Uvurkhangai, Khuvsgul, Orkhon) Myanmar / Kachin Myanmar / Yangon Country / Region Nepal / Western Nigeria / Abia Nigeria / Imo Nigeria / Lagos Pakistan / AJK Pakistan / Punjab Panama / Area Oriental Panama / Chiriqui Panama / Cocle Panama / Herrera Papua New Guinea / National Capital District Paraguay / North-East (Caaguazu, Alto Parana, Canideyu) Paraguay / South-West (Caazapa, Itapua) Philippines / Cordillera Admin Region Philippines / II-Cagayan Valley Philippines / VII-Central Visayas Philippines / XI-Davao Philippines / XIII-Caraga Saudi Arabia / West (Makka, Madinah, Tabuk) Senegal / Thies Sierra Leone / Western Urban South Africa / Gauteng South Africa / KwaZulu Natal South Africa / North West South Africa / Northern Cape Sudan / Northern Tanzania / Zanzibar West Timor Leste / Dili Togo / Lome Uganda / Kampala Uzbekistan / South (Kashkadarya, Surkhandarya) Vanuatu / Port Vila Venezuela / Amazonas Federal Territory Venezuela / Anzoategui Venezuela / Bolivar Venezuela / Cojedes Venezuela / Falcon Venezuela / Lara Venezuela / Merida Venezuela / Monagas Venezuela / Trujillo Venezuela / Yaracuy Venezuela / Zulia Yemen / Jawf, Hadramet, Shabda (Shabwah), Marib, Mohra (Al Mahrah) Yemen / Sana a (capital; Al Amana), Sana a (governorate) Zimbabwe / Bulawayo Zimbabwe / Harare Sixth decile Country / Region Afghanistan / South (Uruzgan Helmand Zabul Nimroz Kandahar) Afghanistan / South East (Ghazni Paktya Paktika Khost) Azerbaijan / Aran Azerbaijan / Dakhlik Shirvan Azerbaijan / Ganja Gazakh Azerbaijan / Yukhari Karabakh Bangladesh / Brahmanbaria, Chandpur, Comilla Bangladesh / Chittagong Bangladesh / Chuadanga, Jhenaidah, Kushtia, Meherpur Bangladesh / Gazipur, Narayanganj, Narsingdi Bangladesh / Gopalganj, Madaripur, Munshiganj, Shariatpur Bangladesh / Jessore, Magura, Narail Bhutan / Chukha Bhutan / Haa Bhutan / Punakha Bhutan / Sarpang Bhutan / Trashigang Bhutan / Trashiyangtse Bolivia / Santa Cruz Bolivia / Tarija Botswana / Chobe Botswana / Kgalagadi Botswana / Kweneng Botswana / North-East Botswana / Southern Cambodia / Banteay Mean Chey Cambodia / Bat Dambang-Krong Pailin Cambodia / Kandal Cambodia / Prey Veaeng Cambodia / Svay Rieng Cambodia / Takaev Cameroon / Centre (incl Yaounde) Colombia / Cesar Colombia / Choco Congo Brazzaville / Pointe Noire Congo Democratic Republic / Kinshasa Cote d'Ivoire / Sud, Abidjan Cuba / Granma Ecuador / Oriente El Salvador / Occidental El Salvador / Oriental Eswatini / Hhohho Eswatini / Manzini Gabon / Estuaire Gabon / Haut Ogooue Gabon / Ogooue Maritime Gambia / Kerewan Ghana / Ashanti Country / Region Ghana / Eastern Ghana / Western Guatemala / North-Occidental Guatemala / North-Oriental Guatemala / South-Occidental Guatemala / South-Oriental Guyana / Barima-Waini Honduras / Choluteca Honduras / El Paraiso Honduras / Intibuca Honduras / Lempira Honduras / Olancho India / Chhattisgarh India / Madhya Pradesh India / Manipur India / Meghalaya India / Orissa India / Tripura India / Uttar Pradesh India / West Bengal Indonesia / Irian Jaya (Papua and Papua Barat) Indonesia / Maluku Iran / Sistanand Baluchestan Kiribati / Souyth Tarawa Lao / Attapeu Lao / Bokeo Lao / Huaphanh Lao / Luangnamtha Lao / Luangprabang Lao / Oudomxay Lao / Phongsaly Lao / Savannakhet Lao / Sekong Lesotho / Maseru Malaysia / Labuan Federal Territory Malaysia / Sarawak Mexico / Chiapas Mexico / Guerrero Mexico / Oaxaca Mongolia / Western (Bayan-Ulgii, Govi-Altai, Zavkhan, Uvs, Khovd) Myanmar / Kayah Namibia / Erongo Namibia / Hardap Namibia / Karas Namibia / Khomas Namibia / Otjozondjupa Nepal / Central Nepal / Eastern Country / Region Nepal / Far-western Nepal / Sudoorpaschim Province Nicaragua / Pacifico (Chinandega, Leon, Managua, Masaya, Granada, Carazo, Rivas) Nigeria / Abuja FCT Nigeria / Akwa Ibom Nigeria / Anambra Nigeria / Delta Nigeria / Edo Nigeria / Ogun Nigeria / Rivers Pakistan / Balochistan Pakistan / Khyber Pakhtunkhwa (NWFrontier) Panama / Area Central Panama / Area Occidental Panama / Bocas del Toro Paraguay / North-West (Boqueron, Alto Paraguay, Presidente Hayes, Conception, Amambay, San pedro, Cordillera) Peru / North (Tumbes, Piura, Lambayeque, Cajamarca, La Libertad) Peru / South (Tacna, Moquegua, Arequipa, Ica, Ayacucho) Philippines / IVB-MIMAROPA Philippines / IX-Zamboanga Peninsula Philippines / V-Bicol Philippines / VI-Western Visayas Philippines / VIII-Eastern Visayas Philippines / X-Northern Mindanao Philippines / XII-SOCCSKSARGEN Rwanda / City of Kigali Sao Tome & Principe / Regiao Centro Sao Tome & Principe / Regiao do Principe Sao Tome & Principe / Regiao Norte Sao Tome & Principe / Regiao Sul Senegal / Diourbel Senegal / Ziguinchor South Africa / Eastern Cape South Africa / Mpumalanga Sudan / Khartoum Sudan / Nahr El Nil Suriname / Brokopondo and Sipaliwini Tanzania / Dar Es Salam Vanuatu / Luganville Venezuela / Amacuros Delta Federal Territory Venezuela / Barinas Venezuela / Guarico Venezuela / Portuguesa Venezuela / Sucre Yemen / Abyan, Aden (town and countryside), Lahej, Ad Dali (Al Dhalih) Yemen / Ibb Zambia / Lusaka Seventh decile Country / Region Afghanistan / Central Highlands (Bamyan Daikundi) Afghanistan / East (Nangarhar Kunar Laghman Nooristan) Afghanistan / North East (Baghlan Takhar Badakhshan Kunduz) Afghanistan / West (Ghor Herat Badghis Farah) Angola / Cabinda Bangladesh / Bagerhat, Khulna, Satkhira Bangladesh / Barisal, Jhalokati, Pirojpur Bangladesh / Bogra, Gaibandha, Jaypurhat Bangladesh / Dinajpur, Nilphamari, Panchagarh, Thakurgaon Bangladesh / Faridpur, Manikganj, Rajbari Bangladesh / Feni, Lakshmipur, Noakhali Bangladesh / Jamalpur, Sherpur, Tangail Bangladesh / Maulvibazar, Sylhet Bangladesh / Naogaon, Nawabganj, Rajshahi Bangladesh / Natore, Pabna, Sirajganj Belize / Cayo Benin / Atlantique (incl Littoral (Cotonou)) Bhutan / Lhuntse Bhutan / Mongar Bhutan / Pemagatshel Bhutan / Samdrup jongkhar Bhutan / Samtse Bhutan / Trongsa Bhutan / Tsirang Bhutan / Wangdi Bolivia / Beni Bolivia / Chuquisaca Bolivia / Cochabamba Bolivia / La Paz Bolivia / Oruro Bolivia / Pando Bolivia / Potosi Botswana / Central Botswana / Ghanzi Botswana / North-West, Ngamiland Burkina Faso / Centre (incl Ouagadougou) Cambodia / Kampong Cham (incl Tboung Khmum) Cambodia / Kampong Chhnang Cambodia / Kampong Spueu Cambodia / Kampong Thum Cambodia / Kampot-Krong Kaeb-Krong Preah Sihanouk Cambodia / Kaoh Kong Cambodia / Mondol Kiri-Rotanak Kiri Cambodia / Pousat Cambodia / Siem Reab-Otdar Mean Chey Cameroon / Ouest Cameroon / Sud Chad / Zone 1 (N'Djamena) Country / Region China / Xinjiang Colombia / Guainja Colombia / Guajira Comoros / Anjouan (Ndzouani) Comoros / Grande Comore (Ngazidja) Comoros / Moheli Cote d'Ivoire / Centre Cote d'Ivoire / Centre Est Cote d'Ivoire / Centre Nord Djibouti / Djibouti Equatorial Guinea / Annobon, Bioko Eritrea / Maekel Eswatini / Lubombo Eswatini / Shiselweni Ethiopia / Dire Dawa Ethiopia / Harari Gabon / Moyen Ogooue Gabon / Ngounie Gabon / Nyanga Gabon / Ogooue Lolo Gabon / Woleu Ntem Gambia / Basse Gambia / Mansakonko Ghana / Brong Ahafo Ghana / Central Ghana / Northern Ghana / Volta Guatemala / Peten Guinea Bissau / Bissau Guyana / Potaro-Siparuni Guyana / Upper Takutu-Upper Essequibo Haiti / West (incl Metropolitain area) India / Assam India / Bihar India / Jharkhand Indonesia / East Nusa Tenggara Kenya / Central Lao / Saravane Lesotho / Berea Lesotho / Leribe Liberia / Monrovia Liberia / Montserrado Madagascar / Analamanga Malaysia / Sabah Mauritania / Adrar Mauritania / Inchiri Mozambique / Maputo Cidade Myanmar / Bago Country / Region Myanmar / Chin Myanmar / Kayin Myanmar / Magway Myanmar / Mandalay, NayPyitaw Myanmar / Mon Myanmar / Sagaing Myanmar / Shan Myanmar / Taninthayi Namibia / South Nepal / Karnali Province Nigeria / Cross River Nigeria / Ekiti Nigeria / Enugu Nigeria / Kaduna Nigeria / Kogi Nigeria / Kwara Nigeria / Nassarawa Nigeria / Ondo Nigeria / Osun Nigeria / Oyo Pakistan / FATA Pakistan / Sindh Panama / Darien Panama / Veraguas Peru / Central (Huancavelica, Huanuco, Junin, Pasco) Peru / East (Madre de Dios, Cusco, Puno, Apurimac) Peru / North East (Amazonas, Loreto, San Martin, Ucayali) Philippines / ARMM Senegal / Fatick Senegal / Kaolack Senegal / Louga Senegal / Saint Louis Somalia / Banadir Sudan / Al Gezira Tanzania / Zanzibar South Timor Leste / Aileu Timor Leste / Baucau Timor Leste / Bobonaro Timor Leste / Lautem Timor Leste / Liquica Timor Leste / Manatuto Timor Leste / Manufahi Vanuatu / Shefa Venezuela / Apure Yemen / Beida (Al Bayda), Dhamar, Raimah Yemen / Taiz Zambia / Copperbelt Eight decile Country / Region Angola / Bengo Angola / Benguela Angola / Lunda Sul Angola / Malange Angola / Namibe Angola / Zaire Bangladesh / Bandarban, Cox s Bazar Bangladesh / Barguna, Bhola, Patuakhali Bangladesh / Habiganj, Sunamganj Bangladesh / Khagrachhari, Rangamati (Chattagram) Bangladesh / Kishoreganj, Mymensingh, Netrakona Bangladesh / Kurigram, Lalmonirhat, Rangpur Benin / Atacora (incl Donga) Benin / Queme (incl Plateau) Benin / Zou (incl Collines) Bhutan / Dagana Bhutan / Gasa Bhutan / Zhemgang Burkina Faso / Cascades Burkina Faso / Hauts Bassins Cambodia / Preah Vihear-Stueng Traeng-Kracheh Cameroon / Adamaoua Cameroon / Est Cameroon / Nord Ouest Central African Republic CAR / Bangui Colombia / Vaupis Congo Brazzaville / Bouenza Congo Brazzaville / Cuvette Congo Brazzaville / Niari Congo Brazzaville / Sangha Cote d'Ivoire / Centre Ouest Cote d'Ivoire / Nord Cote d'Ivoire / Nord Est Cote d'Ivoire / Nord Ouest Cote d'Ivoire / Ouest Cote d'Ivoire / Sud Ouest Djibouti / Other Districts Equatorial Guinea / Litoral Eritrea / Debubawi Keih Bahri Gabon / Ogooue Ivindo Gambia / Janjabureh Gambia / Kuntaur Ghana / Upper East Ghana / Upper West Guatemala / North Guinea / Boke Guinea / Kankan Guinea / Kindia Country / Region Guinea / Mamou Guinea Bissau / Bafata Haiti / Artibonite Haiti / North Haiti / North-East Haiti / South Honduras / Gracias a Dios Kenya / Coast Kenya / Eastern Kenya / Rift Valley Kiribati / Line and Phoenix Group Kiribati / Northern Gilbert Lesotho / Butha-Buthe Lesotho / Mafeteng Lesotho / Mohale s Hoek Lesotho / Qasha s Nek Lesotho / Quthing Liberia / Margibi Madagascar / Antananarivo Madagascar / Antsiranana Madagascar / Toamasina Madagascar / Analanjirofo Madagascar / Atsinanana Madagascar / Diana Madagascar / Sava Malawi / Blantyre Mali / Kayes Mali / Koulikoro Mali / Segou Mali / Sikasso Mauritania / Assaba Mauritania / Brakna Mauritania / Hodh Gharbi Mauritania / Tagant Mozambique / Maputo Provincia Myanmar / Ayeyarwaddy Myanmar / Rakhine Namibia / Central Namibia / Kunene Namibia / Omaheke Namibia / Oshana Namibia / Oshikoto Nicaragua / Atlantico (Rio San Juan, Atlantico Norte (Raan), Atlantico Sur (Raas)) Nicaragua / Central-Norte (Boaco, Chontales, Jinotega, Matagalpa, Esteli, Madriz, Nueva Segovia) Niger / Agadez Nigeria / Adamawa Nigeria / Bauchi Nigeria / Bayelsa Country / Region Nigeria / Benue Nigeria / Borno Nigeria / Ebonyi Nigeria / Gombe Nigeria / Kano Nigeria / Katsina Nigeria / Niger Nigeria / Plateau Panama / Embera Wounaan Papua New Guinea / West New Britain Senegal / Kolda Senegal / Tambacounda Sierra Leone / Western Rural Somalia / Bari Somalia / Mudug Somalia / Nugal Somalia / W Galbeed Sudan / Blue Nile Sudan / Red Sea Sudan / Sinnar Sudan / White Nile Tanzania / Kilimanjaro Tanzania / Pemba North Tanzania / Pemba South Tanzania / Tanga Tanzania / Zanzibar North Timor Leste / Ainaro Timor Leste / Cova Lima Timor Leste / Ermera Timor Leste / Oecussi Timor Leste / Viqueque Togo / Centrale Togo / Kara Togo / Maritime Togo / Plateaux Uganda / Central 1 (Central South) Uganda / Central 2 (Central North) Yemen / Hajja, Sada, Amran (Omran) Yemen / Hodeida (Al Hudaydah), Mahweit (Al Mahwit) Zambia / Southern Zimbabwe / Manicaland Zimbabwe / Mashonaland Central Zimbabwe / Mashonaland East Zimbabwe / Mashonaland West Zimbabwe / Masvingo Zimbabwe / Matebeleland South Zimbabwe / Midlands Ninth decile
https://globaldatalab.org/areadata/rankings/iwipov35/?highlight=CAFr106
Deceptively real - Medizin Aspekte Deceptively real For many patients with heart failure, an artificial heart pump is a lifesaver – but one that often causes side effects. There is a risk of blood clots or a rejection of the foreign material, which can lead to severe immune responses. Researchers at Zurich University Hospital, together with col-leagues from the University of Zurich and ETH Zurich, therefore launched the „Zurich Heart“ project back in 2011. The project involves physicians, engineers, biologists and materials scientists with the aim of developing common heart pumps further and at the same time coming up with new solutions to eradicate existing risks. Researchers from various universities and research institutes – including Empa – are working on new approaches in around ten subprojects. Empa involved in several projects Several Empa teams are part of Zurich Heart and are working on a new generation of heart pumps that will be „camouflaged“ in such a way that human immune cells cannot distinguish them from a real heart. Natural blood vessels – including the heart – are lined on the inside with endothelial cells that regulate the exchange between blood and the body’s tissues. An artificial heart pump must thus have a surface, on which the body’s own endothelial cells can settle. This tissue surface fools the blood into believing that it is not an artificial organ but a real heart. Researchers led by Eduardo Mazza, head of Empa’s Experimental Continuum Mechanics lab, professor at ETH Zurich and co-project leader of Zurich Heart, have succeeded in developing a membrane that offers optimal conditions for the colonization of endothelial cells. This membrane not only provides a suitable basis for the necessary cells, but also dampens the natural pumping movement – if the contractions are too strong, cells can hardly hold on to even the most temptingly prepared surface and are washed away by the blood. Hexagon solution Aldo Ferrari, a researcher at ETH Zurich and Empa, has developed a substrate with a special structure that makes endothelial cells feel comfortable on the membrane so that they can hold on to it. Like a honeycomb, individual hexagons line up in a row and offer the cells an optimal space to nest in them and not be washed away. The method has proven successful; the researchers were able to confirm in both in vitro and in vivo experiments that the cells adhere to the membrane even after several pumping movements and thus provide a potential solution for the development of more biocompatible heart pumps. Despite these successful initial trials further challenges remain, however. The aim is to not only coat the membrane but also the entire inner surface of the pump with the hexagonal structure. Next steps already initiated Zurich Heart is now entering its second phase. „We want to translate some of the solutions devel-oped within Zurich Heart into clinically relevant products,“ says Mazza. This could take several years, though, so Zurich Heart has no time limit. The first generation of PhD students involved in Zurich Heart have now completed their theses and produced numerous publications and patents with positive feedback. „With our hybrid membrane project, we have come much further than we had originally expected,“ says Mazza. With his team he is already planning the next steps: The longterm behavior of such an „endothelialized“ heart pump has not yet been investigated, and Mazza now wants to address this issue. After all, such a heart pump has to withstand several mil-lion beats. „Our motivation has increased even further in recent years“, Mazza concludes. He is confident that the upcoming projects will yield important knowledge as well as practical solutions for and around the human heart.
https://medizin-aspekte.de/deceptively-real-110666/
Evolution of Life-Threatening COVID-19 as the SARS-CoV-2 Pandemic Has Progressed | medRxiv medRxiv - The Preprint Server for Health Sciences Evolution of Life-Threatening COVID-19 as the SARS-CoV-2 Pandemic Has Progressed Sudish C. Murthy , Ashley M. Lowry , Steven M. Gordon , Eugene H. Blackstone doi: https://doi.org/10.1101/2023.02.15.23285759 Abstract Full Text Info/History Metrics ABSTRACT RationaleAs the SARS-CoV-2 pandemic progressed, hospital mortality among patients admitted with COVID-19 decreased; however, its mechanism remains unclear. ObjectiveTo determine underlying factors that might explain the declining observed mortality of hospitalized patients with COVID-19. MethodsThis observational study used a prospective COVID-19 clinical database compiled by a 15-hospital health system. Participants were persons testing positive for SARS-CoV-2 (n=185,636), among whom 26,872 were hospitalized for COVID-19 from 3/1/2020 to 6/1/2022. MeasurementsEndpoints were hospital and 60-day mortality assessed by randomForests-for-survival machine learning using patient demographics, medical history, symptoms, and admission laboratory test results. Main ResultsMortality of patients hospitalized with COVID-19 fell from 11% in 3/2020 to 3.7% in 3/2022; 60-day mortality was 17% in 5/2020 and 4.7% in 5/2022. Advanced age was the most important predictor of mortality, followed by admission laboratory test results. Risk-adjusted 60-day mortality was 15% had all patients been admitted in 3/2020, minimally unchanged at 12% had they been admitted in 5/2022. Dissociation between observed and predicted mortality was largely explained by change in admission patient profile, particularly admission laboratory test results. Transition to intensive care occurred rapidly for those predicted to do poorly. ConclusionMortality from COVID-19 requiring hospitalization has declined as the pandemic has evolved, but surprisingly, persists for 60 days following admission. Demographics, medical history, and at-admission laboratory results continue to accurately predict mortality despite reduction of observed mortality and in spite of therapeutic advances. Importantly, rapid escalation of care can be predicted at admission using standardly obtained information. There has been a subtle but perceptible change in the at-risk population that explains these findings. INTRODUCTION Few anticipated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 1and its associated illness coronavirus disease 2019 (COVID-19) 2would still be a major public health problem 3 years after its clinical detection in December 2019. 3Identifying its genetic sequence synchronous with its clinical emergence, 4coupled with past experience with members of this viral family, 5led many to believe that the disease would soon pass. Unfortunately, despite rapid dissemination of information regarding the unique clinical characteristics and modes of transmission, early adoption of public health measures, 6and fairly rapid understanding of pathogenesis of severe disease, 7a pandemic emerged, only partially abated by rapid manufacture of vaccines. 8 Nearly 100 million persons have contracted SARS-CoV-2 in the United States, with more than 1 million related deaths, 9thus it is important to understand changes in clinical profiles and outcomes as the pandemic has evolved given the emerging variants, widespread but incomplete population vaccination, and availability of antiviral therapy during the early stage of infection. 10Specifically, because of the observed reduction in hospital mortality from COVID-19, we questioned the effect of SARS-CoV-2 variant evolution, dissemination of vaccines, and development of advanced therapeutics as important inflection points in the pandemic. Finally, as patients were followed after hospital discharge, we were surprised by the number who had died soon after discharge, leading us to wonder if we knew the true magnitude of the illness in terms of associated mortality beyond hospitalization needed to help us prepare for what lies ahead in these still uncertain times. Therefore, our aim with this study was to understand the risk of mortality of patients admitted to our health system hospitals with COVID-19 as the pandemic progressed by answering the following questions: 1) How did patients hospitalized with COVID-19 differ from non-hospitalized persons testing positive for SARS-CoV-2? 2) What was the mortality of patients in-hospital and early after hospital discharge? 3) What were the predictors of mortality? 4) Could the observed decrease in hospital mortality within our hospital system from COVID-19 over time be explained by the factors we studied and methodology we employed? We limited our investigation to what was known about these patients at hospital admission – their initial encounter – ignoring events and therapies in their subsequent hospital course, to help clinicians marshal appropriate resources at first contact with ill patients. PATIENTS AND METHODS Patients and Data From 3/1/2020 to 6/1/2022, 185,636 people tested positive for SARS-CoV-2 in the Cleveland Clinic Health System. Of these, 26,872 (15%) were admitted with COVID-19 to 1 of 14 of its 15 Northeast Ohio and Florida hospitals (Table 1andFigure 1). Early in the pandemic, our System established a COVID-19 Registry, capturing data from our electronic health records via automated feeds 11using standardized templates and manually by a study team. The Institutional Review Board (IRB) approved data collection with informed consent waived (IRB Record 136 under IRB 20-283, 4/27/2020). Table 1. Characteristics and physiologic response to SARS-CoV-2 of persons testing positive and those admitted to Cleveland Clinic Health System hospitals with COVID-19 Figure 1: Trends inA)number of persons testing positive for SARS-CoV-2 from March 2020 to June 2022 (blue line and symbols) and number hospitalized for severe and life-threatening COVID-19 (red line and symbols), andB)percentage of persons testing positive for SARS-CoV-2 who were hospitalized. Each symbol represents a 1-week average. Vertical lines represent epochs of dominant SARS-CoV-2 variants: Pre-4/1/21: Alpha B.1.1.7 4/1/2021 to 7/1/21: Alpha Q 7/1/21 to 12/1/21: Delta B.1.617.2 and AY 12/1/21 to 2/1/22: Omicron BA.1 2/1/22 to 3/21/22: BA.1.1 3/21/22 to 5/21/22: Omicron BA.2 5/21/22 to 6/1/22: BA2.12.1 Endpoints The primary endpoint was all-cause mortality from date of hospital admission to 60 days or last date of follow-up if less than that for patients with incomplete follow-up. A secondary endpoint was admission to the intensive care unit (ICU). Discharged patients were followed at 2 weeks by a COVID home-monitoring program and subsequently by periodic telephone calls, use of MyChart (Epic Systems), and encounters recorded in the electronic medical record until January 1, 2022. Thereafter, Ohio patients were systematically followed for vital status using the state death registry, while Florida patients were less systematically followed. Yet 81% of patients discharged alive were followed at least 60 days after hospital admission (Figure E1). In-hospital events and discharge location are presented in Table E1. Data Analysis SAS v9.4 (SAS Institute, Cary, NC) and R v4.0.0 (R Foundation for Statistical Computing, Vienna, Austria) were used for data analysis. Profile of SARS-CoV-2– positive persons and of COVID-19 patients at hospital admission are depicted by temporal trends across the pandemic. Time-related mortality after hospital admission was estimated parametrically by a temporal decomposition method to derive the instantaneous risk of death (hazard function). 12 Two machine-learning analyses of time-related mortality were performed. The first, a “pre–COVID-19” model, incorporated demographics, medical history, medications, and vaccination status before SARS-CoV-2 infection (34 variables, Appendices 1 and 2); the second, an “at-admission” model, incorporated all the pre– COVID-19 variables plus symptoms, results of routine laboratory tests at hospital admission for COVID-19, and “variant-dominant” periods according to our Infectious Disease department (28 additional variables;Table 1, Appendices 1 and 2). For modeling, the R program randomForest-SRC was used, with missing data imputed on-the-fly. 13One thousand trees were grown with bootstrap samples of patients, and branch splits using a log-rank rule were based on a random subset of 6 or 8 variables, respectively, with a terminal node size of 15. Predictive importance of variables was assessed by variable importance (VIMP), which hierarchically orders variables by magnitude of reduction of prediction error. 14Partial dependency plots were generated to visualize the relation of variables to outcome. 15 To determine whether mortality of a patient admitted early in the pandemic differed from that had the same patient been admitted late in the series (virtual-twin analysis 16), we incorporated date of hospital admission into random forest models. Sixty-day predicted mortality for each patient was then calculated as if that patient had been admitted on 3/1/2020 by substituting for actual date of admission this counterfactual date. This was repeated day-by-day to 6/1/2022 for the entire group of patients. To investigate the difference between observed and predicted mortality, we performed a secondary analysis using all variables except date of admission. Then, probabilities of 60-day survival were predicted for each patient’s risk profile. These were aggregated into 7 risk categories to investigate change in risk profile across the pandemic and to characterize patients in each of these risk categories. RESULTS SARS-CoV-2–Positive and Hospitalized Individuals Across the Pandemic People tested positive for SARS-CoV-2 in our Health System in waves, similar to the country as a whole, with multiple peaks and valleys and multiple viral variants (Figure 1A). The fraction of those hospitalized was 16% over the pandemic, but was higher early in the experience and again in the spring of 2021 and winter of 2022 (Figure 1B). Average age of SARS-CoV-2–positive individuals decreased, then increased: from 65 years in 3/2020 to 55 in 5/2021 and 63 in 5/2022; average age of those hospitalized was 10 to 20 years older (Table 1andFigure 2A). Early in the pandemic, more males than females were admitted, but this quickly approached 50:50 (Figure 2B), with slightly more females. Trends in race presented a complex pattern (Figures 2Cand2D), but with a higher proportion of Blacks hospitalized than non-hospitalized. More hospitalized patients than non-hospitalized ones were on medications for chronic diseases, commensurate with an older hospitalized population. Figure 2: Trends in demographics. Symbols are 1-week averages. In panels Aand B, blue symbols refer to persons testing positive for SARS-CoV-2 (SARS-CoV-2 +), and red symbols refer to patients admitted with COVID-19.A)Mean age.B)Proportion female.C)Race of persons testing positive for SARS-CoV-2. Key: White (Blue); Black (Black); Asian (Red); Multiracial/Other (Green).D)Race of persons hospitalized with COVID-19 (color key as in panel C). Symptoms among both SARS-CoV-2–positive and hospitalized patients changed substantially across the pandemic, with self-reported fever and cough progressively declining (Figures 3Aand3B). Hospitalized patients were more symptomatic than non-hospitalized individuals, particularly with dyspnea and gastrointestinal symptoms (Figures 3Cand3D). Figure 3: Trends in symptoms of persons testing positive for SARS-CoV-2 (SARS-CoV-2 +, blue symbols) and of patients hospitalized for severe or life-threatening COVID-19 (red symbols). Symbols are 1-week averages.A)Fever.B)Cough.C)Dyspnea.D)Gastrointestinal symptoms. Format as inFigure 2, panels Aand B. Results of routine laboratory tests at hospital admission also fluctuated across the pandemic, somewhat synchronous with disease surges (Figure 4). In particular, C-reactive protein declined early in the experience and more so in patients admitted in 2022 (Figure 4D), as did hepatic function enzymes (Figure 4E). Figure 4: Temporal trends in physiologic response to SARS-CoV-2 at hospital admission for COVID-19. Symbols are 1-week averages.A)Blood urea nitrogen.B)Creatinine.C)Red cell distribution width.D)C-reactive protein.E)Aspartate aminotransferase.F)Albumin. Mortality Across the Pandemic Observed hospital mortality fell from 11% in 3/2020 to 7.2% in 9/2020, 4.8% in 3/2021, 4.9% in 9/2021, and 3.7% in 3/2022 (Figure 5). However, mortality continued after hospital discharge: 9.9% at 30 days, 12% at 60 days, 13% at 90 days, 15% at 180 days, and 17% at 360 days (Figure 6). Instantaneous (unadjusted) risk of death peaked at 0.45%/day 9 days after hospital admission (Figure 6, inset), falling thereafter to reach 0.037%/day at 60 days, 4.0 times greater than an age-sex-race–matched U.S. population reference of 0.0093%/day. Actuarial mortality was highest for alpha variant B.1.1.7, lower for delta B.1 and omicron BA.1, and lowest for alpha-Q B.1.1 and omicron BA.2 (Figure 7A), although after risk adjustment, these differences were small (Figure 7B). Figure 5: Weekly hospital mortality of patients admitted with COVID-19. Symbols depict actual mortality, and solid line is a loess (locally weighted scatterplot) smoother. Open in new tab Figure 6: Time-related mortality of patients hospitalized with COVID-19. Each circle represents a death; vertical bars are 68% confidence limits (equivalent to ±1 standard error), and solid line enclosed within a 68% confidence band represents parametric estimates from which the instantaneous risk of mortality (inset) was derived. Number of patients remaining at risk at various intervals is shown beneath horizontal axis. Dash-dot-dash line represents mortality of an age-sex-race–matched U.S. population. Note that the early hazard extends out to at least 60 days. Figure 7 Mortality after hospital admission for COVID-19 according to SARS-CoV-2 variant.A)Unadjusted Kaplan-Meier estimates with 68% confidence limits (bars) equivalent to ±1 standard error, representing each variant (see key).B)Partial dependency plot of mortality according to SARS-CoV-2 variant from at-admission model. Key: Black: Pre-4/1/21: Alpha B.1.1.7; n = 11,483 (43%) Red: 4/1/2021 to 7/1/21: Alpha Q; n = 1,560 (5.8%) Orange: 7/1/21 to 12/1/21: Delta B.1.617.2 and AY; n = 5,280 (20%) Blue: 12/1/21 to 2/1/22: Omicron BA.1; n = 6,601 (25%) Green: 2/1/22 to 3/21/22: BA.1.1; n = 785 (2.9%) Purple: 3/21/22 to 5/21/22: Omicron BA.2; n = 878 (3.3%) Brown: 5/21/22-6/1/22: BA2.12.1; n = 285 (1.1%) Predictors of 60-Day Mortality Pre–COVID-19 Model Older age was the most important predictor of mortality (Figures 8Aand8B), with an upward inflection beginning about age 50 years, followed by a rapid increase with each year of age (Figure E2). It eclipsed the importance of body size, race, and heart and chronic pulmonary diseases. Neither SARS-CoV-2 vaccination nor SARS-CoV-2 variant was importantly associated with mortality (Figures 8A,8C, and9, the latter showing the small fraction of hospitalized patients who had been vaccinated at least 2 weeks prior to hospital admission). Figure 8: Variable importance (VIMP) for models of mortality.A)VIMP for pre–COVID-19 model of mortality (error=0.25). Key to variable names along vertical axis is provided in Appendices 1 and 2.B)Partial dependence plot of predicted 60-day mortality with respect to both age and date of hospital admission, based on pre–COVID-19 random forest analysis shown in panel A. “Days” refers to hospital admission date expressed as number of days since March 1, 2020.C)VIMP for at-admission model of mortality (error=0.18). Notice that after age, the most important variables are admission laboratory values reflecting physiologic response to SARS-CoV-2.D)Partial dependence plot of predicted 60-day mortality with respect to both age and date of hospital admission, based on at-admission random forest analysis shown in panel C. Figure 9: Percent of hospitalized patients vaccinated against SARS-CoV-2. Note that persons vaccinated within 2 weeks of hospital admission with COVID-19 were not considered fully vaccinated for this analysis. At-Admission Model When the presenting symptoms and results of routine-admission laboratory tests were added to the pre–COVID-19 model (Figures 8Cand8D), older age remained the most important predictor of mortality (Figure E2), but its importance was somewhat blunted (Figures 2B,2D, and E2). Rather, several laboratory values at hospital admission emerged as important risk factors. Higher values of renal and liver dysfunction, greater systemic inflammatory response, abnormal hematologic values, and low albumin levels were associated with higher mortality (Figure 10). Figure 10: Partial dependency plots of predicted 60-day mortality according to routine laboratory findings at hospital admission for COVID-19.A)Blood urea nitrogen.B)Aspartate transaminase.C)C-reactive protein.D)Red blood cell distribution width.E)Albumin. Unchanging Risk Factors, But Changing Patient Profile, Lead to Changes in Mortality Based on the at-admission model, 60-day predicted mortality from date of admission had all 26,872 patients been admitted in 3/2020 was 15%, in 5/2020 14%, in 11/2020 13%, in 5/2021 12%, in 11/2021 12%, and in 5/2022 12%, essentially unchanged over the pandemic (Figure 11). These small changes were far less than the observed actuarial trajectory of mortality: 17% in 5/2020, 14% in 11/2020, 5.2% in 5/2021, 12% in 11/2021, and 4.7% in 5/2022. Divergence of observed and risk-adjusted predicted mortality—a Simpson’s Paradox 17—was attributable both to changes across the pandemic in the profile of demographics and pre–COVID-19 conditions, but in particular to changes in the profile of patients’ physiologic response to the disease as assessed by laboratory values at hospital admission (Figure 12A). Specifically, when coalesced into 7 predicted risk groups, progressively fewer highest risk patients were admitted over time, which contributed to the decline in observed mortality. Simultaneously, there was a mild reduction of the lowest risk patients, but expansion of patients with intermediate risk profiles, narrowing the risk profile of admitted patients across the pandemic. Figure 11 Actuarial and simulated 60-day mortality of patients hospitalized with COVID-19 across the pandemic. Black symbols represent observed 60-day unadjusted actuarial mortality for patients admitted each month, and black line is a loess (locally weighted scatterplot) smoother. Red and blue curves represent simulated 60-day mortality if all hospitalized patients across the pandemic were admitted on the same date from 3/1/2020 to 6/1/2022, according to pre–COVID-19 (red curve) and at-admission (blue curve) mortality models. Vertical lines denote approximate epochs of SARS-CoV-2 variants. Pre-4/1/21: Alpha B.1.1.7 4/1/2021 to 7/1/21: Alpha Q 7/1/21 to 12/1/21: Delta B.1.617.2 and AY 12/1/21 to 2/1/22: Omicron BA.1 2/1/22 to 3/21/22: BA.1.1 3/21/22 to 5/21/22: Omicron BA.2 5/21/22 to 6/1/22: BA2.12.1 Figure 12: Distribution of 7 risk profiles of patients with COVID-19 across date of hospital admission and observed survival for each profile.A, Predicted 60-day survival using the at-admission model for mortality for profiles 1-7 are as follows: (1) ≥95%, (2) 90% to <95%, (3) 85% to <90%, (4) 80% to <85%, (5) 70% to <80%, (6) 60% to <70%, (7) <60%. Note particularly the gradual reduction in percentage of hospital admissions of the highest risk patients (pink and purple) and increase in number of patients in lower risk categories.B,Observed mortality stratified by predicted risk profile.C,Observed escalation of care to intensive care unit (ICU). In panels Band C, each symbol represents an event estimated by the Kaplan-Meier method, and vertical bars are 68% confidence intervals equivalent to ±1 standard error. Actuarial survival of patients in these 7 risk groups demonstrated a large separation, particularly among the 3 highest risk groups (predicted survival less than 80%) (Figure 12B). The highest risk groups were elderly patients, more often White, with many comorbidities being treated medically, higher C-reactive protein, and elevated neutrophil counts but lower lymphocyte counts (Table 2). These same patients had the highest likelihood of being escalated to intensive care within 24 hours of admission (Figure 12C). In contrast, the lowest risk group (34% of hospitalized patients) had a median age 48, had few comorbidities and were taking few medications, and had few derangements of their at-admission laboratory profile. Table 2. Profile of hospitalized patients according to 7 predicted 60-day survival categories by at-admission model: (1) ≥95%, (2) 90% to <95%, (3) 85% to <90%, (4) 80% to <85%, (5) 70% to <80%, (6) 60% to <70%, and (7) <60% (seeFigure 11, A). Blue and salmon shaded columns highlight contrasting patient characteristics between lowest and highest risk groups. DISCUSSION Undoubtedly, mortality among patients hospitalized with COVD-19 is trending downward. Our longitudinal assessment of these patients, both singularly and as a population, has allowed us to gain unique perspectives as this pandemic has evolved. We have been able to predict rapid deterioration of certain hospitalized patients based on a single assessment performed at hospital admission and to discover a continued post-hospitalization mortality from the disease. In addition, we have gained some clarity on the effectiveness of public health efforts and how hospital-requiring COVID-19 has changed as vaccination, preadmission therapeutics, and variants have permeated the landscape. Moreover, we now have insight into what to expect in the future as this pandemic morphs into an endemic disease. Principal Findings There is decreasing observed 60-day mortality among patients hospitalized with COVID-19. Despite this, mortality for every risk profile based on routine admission assessment has decreased minimally. Thus, likelihood of mortality remains eminently predictable at hospital admission. Prediction accuracy is substantially refined by early physiologic response, as measured by routine admission laboratory tests, in addition to patients’ demographics and preexisting medical conditions, despite continued evolution of SARS-CoV-2 variants and an increasingly vaccinated population. Appearance of new SARS-CoV-2 variants, advancements in care, and introduction of therapeutics have had surprisingly minimal effects on 60-day mortality prediction for hospitalized patients. Those predicted on hospital admission to do poorly demonstrate a rapid progression of illness, with transition to the ICU within the first 24 hours. Finally, although hospital mortality is the commonly quoted outcome metric for hospitalized patients, it underestimates the lethality of COVID-19, which continues to at least 60 days after hospital admission. Findings in Context Crude mortality of hospitalized patients decreased throughout the pandemic, but once simple characteristics of patients being admitted were taken into account, predicted mortality was unchanged from the beginning of the pandemic to this time, suggesting that it is the profile of hospitalized patients that has changed and created a Simpson’s Paradox. 17We clearly demonstrate the continuous change of the at-risk population and have defined 7 risk groups that remained evident throughout the pandemic, although their constituents have fluctuated in number across the pandemic. These categories predict not only mortality but the escalation of care once patients are hospitalized. It is becoming clear that despite emergence of SARS-CoV-2 variants and declining effectiveness of the initial vaccine platforms to generate vaccine-induced immunity, protection against hospital admission, and consequently COVID-related death, has remained surprisingly robust during evolution of the illness. 18Prevention of severe illness requiring hospitalization in the vaccinated cohort, as well as presumed slowly developing herd immunity in the general population and early treatment and mitigation of infection, 19are presumably censoring many otherwise high-risk patients from the cohort we are studying and contributing to the Simpson’s Paradox that is observed. Unfortunately, it is these same high-risk individuals with the greatest observed waning protection afforded by vaccination 20who still serve as the substrate for our study and continue to be identified by our model. The at-admission risk model we generated uses simple, standard demographic data, medical history, vaccination status, symptoms, and routine admission laboratory data, yet impressively predicts outcome of hospitalized patients. Severity of subsequent disease can be fairly crudely estimated by symptom-complex (such as respiratory rate, oxygen saturation, blood pressure, heart rate, temperature, alertness), limited laboratory analysis (blood urea nitrogen, C-reactive protein), and demographics (age, sex), as several other models have demonstrated. 21 – 23 Some of these models require a 24-hour period of assessment to become informed, which compromises their utility. Of these variables, routine hematologic and serum chemistry data are critical. During the “incubation” period, and perhaps in the early phase of the disease, hematologic constituents seem relatively unperturbed. 24In patients whose disease progresses to hospitalization, there is a profound derangement of serum chemistries and increase of inflammatory mediators and cytokines that give rise to a severe inflammatory response syndrome. 25 , 26 The genesis of life-threatening illness seems to be the induction of multiple interleukins, macrophage proinflammatory proteins and tumor necrosis factor-alpha, thrombosis and endothelial dysfunction, and platelet activation among innumerable other identified homeostatic derangements. 27At some transition point, which we suspect is just prior to hospital admission, individuals begin to declare their fate, as predicted by at-admission demographics, comorbidity, and laboratory values. Lymphopenia and neutrophilia are important predictors of severe disease, with decreased lymphocyte count at admission being associated with ICU destination, and higher neutrophil count identified as a risk factor for death. 28 – 30Moreover, increased levels of inflammatory markers at admission, such as C-reactive protein, procalcitonin, lactate dehydrogenase, and ferritin, seem to portend a more ominous prognosis. 24 , 28 , 31 , 32Many of these variables have been similarly shown to predict poor outcome in our study and serve as reliable biomarkers of mortality to be used in risk calculators. Although it is comforting that fewer patients are progressing to life-threatening illness, it remains concerning that mortality of a patient admitted in 3/2020 and predicted to be at high risk is essentially no different from that predicted for the same patient tomorrow. We are surprised by what we have found, given the types of resources we can marshal and the clinical strength of our hospital system. We can only speculate that we are starting late in the race to combat this disease. We are seeing many patients coming to the hospital already in extremis—dyspneic, lethargic, or dehydrated—and receiving rapidly escalating care soon after their arrival, suggesting severe disease at admission. It has been suggested that although viremia peaks within the first week of infection, peak host primary immunologic response may not be evident for perhaps as long as a week later. 33 Appreciating that most patients will seek emergency room care only when the intensity of disease has progressed to severe illness, it could be anticipated that interventions targeting reducing viral load may not be effective if the viremia is no longer driving the disease process. 34 , 35Recommendations for convalescent plasma administration for COVID-19 focus on early use 36and are consistent with early intervention being more favorable than later for similar therapeutics. Consequently, it is not surprising that anti-inflammatories such as corticosteroids, targeted toward the disease component presumably driving hospital outcome, have become a central and critically important intervention for hospitalized patients. 27 , 28 We postulate that the late risk of mortality after discharge is related to the initial COVID-19 disease and represents persisting disease and debility post-discharge or transfer as opposed to post-acute COVID-19 sequelae. 37This elevated risk above that expected in the U.S. population even beyond 60 days 38suggests the chronic and insidious nature of late COVID-19 mortality and may be part of post–COVID-19 conditions. 39 , 40 Finally, it is interesting that vaccination status did not protect patients from mortality once hospitalized. We are confident that vaccination has reduced hospital readmissions for COVID-19 and favorably contributes to the decreasing trend of severely ill patients. It has been speculated that host immune evasion in vaccinated patients is promoted by viral mutations occurring outside the spike coding region and that this is one mechanism of the apparent dissociation of vaccination status and outcome in those culled by hospital admission who populate this study. 41Unfortunately, vaccination as a variable is extraordinarily confounded by its timing, number of boosters received, and vaccine platform. None of this information was captured in our data set. This limits the appreciation of the contribution of vaccinations as the pandemic evolved. Limitations This is a study of the COVID-19 experience in a single hospital system and is not necessarily generalizable nationwide. It focuses on patients hospitalized with severe or life-threatening COVID-19. Granular information, however, about the decision to admit a given patient is not available. Data elements recorded in the COVID-19 Registry reflect health-system decisions made at the beginning of the pandemic and were not modified to include potentially important variables such as certain presentation variables and laboratory tests such as ferritin, lactate dehydrogenase, coagulation factors, and patient-specific SARS-CoV-2 variant information. Because of lags in data entry into the COVID-19 Registry, risk factors currently identified as important in this study are not available in real time for clinical decision-making. We restricted our analyses to the earliest available clinical information to enable generation of useful models that could predict mortality and direct allocation of resources. Thus, we did not consider additional hospital events, such as mechanical ventilation or extracorporeal membrane oxygenation. The study was conducted in real time during the pandemic, amid changing variants, 42changing thoughts about respiratory support, experimentation with therapeutics, and a variety of clinical trials. Consequently, care of patients across the pandemic has been difficult to standardize. Conclusions and Relevance The evolution of the pandemic as addressed by us and others 23strongly suggests that COVID-19 remains lethal, albeit for a declining at-risk group of the general population. Observed mortality of patients hospitalized with COVID-19 appears to be decreasing over time, corroborating this. That there appear to be fewer patients who manifest severe disease in response to exposure and infection suggests that something has changed to favorably affect disease outcome. Clearly, dissemination of vaccination programs and herd immunity are at play, and there may be a change in viral virulence with development of variants that has led to a smaller fraction of the general population presenting with advanced disease. Early use of antiviral agents may sufficiently blunt the disease, and fewer people now need to seek advanced medical attention. It is unlikely that we are done with COVID-19. Unfortunately, there is likely an underreporting of COVID-19–related mortality when only in-hospital outcomes are examined, as we find that risk of death persists well after hospital discharge. With continued emergence of variants having possibly different virulence, interval outcomes assessment is critical. The surprisingly nimble adaptability of the virus, and seemingly unchanging fate of those who develop severe hospital-requiring COVID-19, mandate that continued individual and public health efforts remain in place. Data Availability Data used for this study include human research participant data that are sensitive and cannot be publicly shared due to legal and ethical restrictions by the Cleveland Clinic regulatory bodies, including the Institutional Review Board and legal counsel. In particular, variables such as date of testing or dates of hospitalization are HIPAA-protected health information and legally cannot be publicly shared. We will make our data sets available on request, under appropriate data use agreements with the specific parties interested in academic collaboration. Requests for data access can be made to Dr. Sudish C. Murthy. ACKNOWLEDGMENTS The authors thank Alex Milinovich and Greg Strnad for management of the COVID-19 Registry, Ben Kramer for data verification, Beth Lieber for statistical programming, Leslie Jelinski for reference management, Brian Kohlbacher for graphic design expertise, and Tess Parry for editorial assistance. Appendix 1 Variables considered in analyses, with short names in parentheses, as seen on variable importance graphs (Figures 8A and 8C) Pre-COVID-19 Patient Characteristics Demographics Age (y) (age), sex (female), race (Black, White, Asian, mixed/other) (race_grp), Hispanic ethnicity (ethnicity), body mass index (kgom -2) (bmi) Comorbidities Smoking history (hx_smoke), pack-years of smoking (packyrs), chronic obstructive pulmonary disease, emphysema (copd_emp), chronic asthma (asthma), heart failure (hrtfail), coronary artery disease (cad), hypertension (htn), diabetes (diabetes), cancer (cancer), musculoskeletal disease (msclero), prior transplant (tx_hx), connective tissue disease (contxdz), inflammatory bowel disease (ibd), epilepsy (epilepsy), immune compromised (immu_dz), pregnant (pregnant) Treatments and Medications Has had a seasonal influenza vaccination (flu_shot), has had a pneumococcal pneumonia immunization (pneushot), pre-COVID-19 medications (nonsteroidal anti-inflammatory drug (nsaids), steroid (steroids), beta-blocker for hypertension (carvedil), angiotension-converting enzyme inhibitor (aceinhib), angiotensin receptor blocker (arb), selective serotonin reuptake inhibitor (paroxeti), melatonin (melatoni), colchicine (colchici) Hospital Admission Variables Date of hospital admission (as count of days since 3/1/2020) (iv_daysa) SARS-CoV-2 Variant Pre-4/1/21: Alpha B.1.1.7; 4/1/2021 to 7/1/21: Alpha Q; 7/1/21 to 12/1/21: Delta B.1.617.2 and AY; 1/1/21 to 2/1/22: Omicron BA.1; 2/1/22 to 3/21/22: BA.1.1; 3/21/22 to 5/21/22: Omicron BA.2; 5/21/22 to 6/15/22: BA2.12.1 Symptoms and Laboratory Values at Hospital Admission Symptoms (cough (cough), fatigue (fatigue), dyspnea (sob), diarrhea (diarrhea), loss of appetite (lossappt), vomiting (vomit), fever (fever01), sputum production (sputprod), flu-like symptoms (flu_symp), C-reactive protein (mgoL -1) (ad_crp), white blood cell count (10 9•L -1) (ad_wbc), neutrophil count (10 9•L -1) (ad_neutr), lymphocyte count (10 9•L -1) (ad_lymoh), red blood cell count (10 12•L -1) (ad_rbc), red blood cell distribution width (%) (ad_rdw), platelet count (10 9•L -1) (ad_plate), hemoglobin (godL -1) (ad_hemog), hematocrit (%) (ad_hct), creatinine (mgodL -1) (ad_creat), blood urea nitrogen (mgodL -1) (ad_bun), albumin (godL -1) (ad_album), bilirubin (mgodL -1) (ad_bilir), alanine aminotransferase (IU•L -1) (ad_alt), aspartate aminotransferase (IU•L -1) (ad_ast), alkaline phosphatase (IU•L -1) (ad_alkph), potassium (mmol•L -1) (ad_potas), chloride (mEq•L -1) (ad_chlor), d-dimer (ngomL -1) (ad_ddime) Appendix 2 Alphabetic list of short names of variables considered in multivariable analyses and plots of variable importance Footnotes Funding:Cleveland Clinic Health System and Heart, Vascular & Thoracic Institute, Department of Thoracic and Cardiovascular Surgery Conflict of Interest:None Ethics:Cleveland Clinic Institutional Review Board approved data collection, with informed consent waived (IRB Record 136 under IRB 20-283, 4/27/2020). 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Bear Head Energy (BHE) to create ammonia/hydrogen plant Canada’s Atlantic sector is blessed with a plethora of renewable energy resources: onshore wind power, offshore wind power, and even tidal power are all viable options. News Hydrogen Canada’s Atlantic sector is blessed with a plethora of renewable energy resources: onshore wind power, offshore wind power, and even tidal power are all viable options. Not surprisingly two Canadian energy companies chose to take advantage of everything the area offers, with two simultaneous operations for producing ammonia and green hydrogen about to commence. The first company is Bear Head Energy. The company originally had approval for a LGN site in the Point Tupper Industrial Park on the strait of Canso. That project has since been shelved in favour of a dramatic new plan to produce ammonia and hydrogen while taking advantage of the region’s robust green power resources. The project will involve 2 gigawatts of hydrogen electrolysers. Running at peak capacity, the plant is expected to generate 350,000 tonnes of hydrogen and two million tonnes of ammonia annually. The project will be constructed in phases. It is expected that the first deliveries of ammonia and hydrogen will take place in 2028. Thanks to support from the Canadian government, the availability of low cost, abundant renewable energy from onshore and offshore wind, the area’s deep-water ports, and a location that allows unrestricted access to world markets, it is anticipated that the prices will rank among the most competitive in the world. Because of the advantageous location, it’s not surprising that Bear Head Energy will have company at the Point Tupper Industrial Park. EverWind Fuels, developer of green hydrogen and ammonia production, is also a resident of the park. Recently, EverWind Fuels received environmental approval for the initial phase of a $6 billion, 1 million tonnes per annum green hydrogen and green ammonia project in the same location. According to EverWind, receiving environmental approval was a significant milestone for the company and its First Nations equity partners, Membertou, Paqtnkek (Bayside Development Corporation), and Potlotek, and it paves the way for construction to commence in the first half of 2023. True to its name, EverWind is now applying for leases on 137,000 acres of land to develop a 2 GW onshore wind farm expected to power the second phase of its green hydrogen production facility by 2026. EverWind has plans to deliver green ammonia to German off-takers, E.ON and Uniper, by 2025, achieving the goals outlined in the Canada-Germany Hydrogen Alliance signed in August of 2022. EverWind acquired the Point Tupper terminal in early 2022, which the company asserts has the capacity to produce more than 10 million tonnes per year of green ammonia. With around $1 billion of existing storage and logistics assets, the terminal makes for an ideal hydrogen hub. In addition to its port facility, it is also connected with critical infrastructure including rail, road, and pipelines. Once up and running, EverWind expects to produce 1 million tonnes per annum (mtpa) of green hydrogen and ammonia. With two major projects funded, approved, and under-way, it seems that Canada’s Atlantic coast is set to become a major player in the world’s green fuel markets, with plenty of room and scope for additional expansion in the years to come. He boasts extensive experience of living and working in North America, spending time developing various trade journals, and was most recently in the role of managing editor with Perendale Publishers back in the UK in Cheltenham. This involved production and editorship of two particular B2B titles – International Aquafeed (covering the world of aquaculture) and Milling and Grain (covering grain production from harvest through to final milling into feed/flour and packaging).
https://www.gasworld.com/story/canadian-company-bear-head-energy-bhe-to-create-ammonia-hydrogen-plant/#/close
State v. Philip Morris, Inc., 41679. - Idaho - Case Law - VLEX 898567243 0: [object Object]. 1: [object Object]. 2: [object Object]. 3: [object Object]. 4: [object Object]. 5: [object Object] Idaho State v. Philip Morris, Inc., 41679. <table><tbody><tr><td> Court</td><td> United States State Supreme Court of Idaho</td></tr><tr><td> Writing for the Court</td><td> HORTON, Justice.</td></tr><tr><td> Citation</td><td> 158 Idaho 874,354 P.3d 187</td></tr><tr><td> Parties</td><td> STATE of Idaho, Plaintiff–Appellant, v. PHILIP MORRIS, INC., R.J. Reynolds Tobacco Company, Lorillard Tobacco Company, Inc., Commonwealth Brands, Inc., Compania Industrial de Tabacos Monte Paz, S.A., Daughters & Ryan, Inc., House of Prince A/S, Japan Tobacco International U.S.A., Inc., King Maker Marketing, Inc., Kretek International, Inc., Liggett Group LLC, Peter Stokkebye Tobaksfabrik A/S, P.T. Djarum, Santa Fe Natural Tobacco Company, Inc., Scandinavian Tobacco Group Lane Ltd., Sherman 1400 Broadway N.Y.C., Inc., Top Tobacco, L.P., and Von Eicken Group, foreign corporations, Defendants–Respondents, and RJR Nabisco Holdings Corp., RJR Nabisco, Inc., American Tobacco Co., Inc., Brown & Williamson Tobacco Corp., Liggett & Myers, Inc., United States Tobacco Co., B.A.T. Industries, PLC, British American Tobacco Co., Ltd., The Council for Tobacco Research—U.S.A., Inc., and Tobacco Institute, Inc., foreign corporations, Defendants.</td></tr><tr><td> Docket Number</td><td> No. 41679.,41679.</td></tr><tr><td> Decision Date</td><td> 23 July 2015</td></tr></tbody></table> 158 Idaho 874 354 P.3d 187 STATE of Idaho, Plaintiff–Appellant, v. PHILIP MORRIS, INC., R.J. Reynolds Tobacco Company, Lorillard Tobacco Company, Inc., Commonwealth Brands, Inc., Compania Industrial de Tabacos Monte Paz, S.A., Daughters & Ryan, Inc., House of Prince A/S, Japan Tobacco International U.S.A., Inc., King Maker Marketing, Inc., Kretek International, Inc., Liggett Group LLC, Peter Stokkebye Tobaksfabrik A/S, P.T. Djarum, Santa Fe Natural Tobacco Company, Inc., Scandinavian Tobacco Group Lane Ltd., Sherman 1400 Broadway N.Y.C., Inc., Top Tobacco, L.P., and Von Eicken Group, foreign corporations, Defendants–Respondents, and RJR Nabisco Holdings Corp., RJR Nabisco, Inc., American Tobacco Co., Inc., Brown & Williamson Tobacco Corp., Liggett & Myers, Inc., United States Tobacco Co., B.A.T. Industries, PLC, British American Tobacco Co., Ltd., The Council for Tobacco Research—U.S.A., Inc., and Tobacco Institute, Inc., foreign corporations, Defendants. No. 41679. Supreme Court of Idaho, Boise, January 2015 Term. July 23, 2015. 354 P.3d 188 Hon. Lawrence G. Wasden, Attorney General, Boise, for appellant. Michael Gilmore argued. Brassey Crawford & Howell, PLLC, Boise and Jones Day, Washington, D.C., for respondent R.J. Reynolds Tobacco Company. Peter J. Biersteker argued. Evans Keane LLP, Boise, for respondent Philip Morris USA, Inc. Andersen Banducci, PLLC, for respondent Lorillard Tobacco Company. Varin Wardwell Thomas & Kunkel, LLC, Boise and Baker & Hostetler, LLP, Washington D.C., for respondents Commonwealth Brands, Inc., Compania Industrial de Tobacos Monte Paz, S.A., Daughters & Ryan, Inc., House of Prince A/S, Japan Tobacco International U.S.A., Inc., King Maker Marketing, Inc., Kretek International, Inc., Liggett Group LLC, Peter Stokkebye Tobaksfabrik A/S, P.T. Djarum, Santa Fe Natural Tobacco Company, Inc., Scandinavian Tobacco Group Lane Ltd., Sherman 1400 Broadway N.Y.C., Inc., Top Tobacco, L.P., Von Eicken Group. Robert J. Brookhiser argued. SUBSTITUTE OPINION THE COURT'S PRIOR OPINION DATED JUNE 22, 2015 IS HEREBY WITHDRAWN. HORTON, Justice. 158 Idaho 875 The State of Idaho appeals the judgment entered by the district court denying the State's motion to vacate portions of a Stipulated Partial Settlement and Award entered by an arbitration panel. This case arises out of the 1998 Tobacco Master Settlement Agreement, wherein certain cigarette manufacturers entered into an agreement with the State to pay damages for the cost of treating smoking-related illnesses. A dispute arose between the parties as to the amount owed in 2003 and the district court entered an order compelling arbitration. The arbitration panel entered a Stipulated Partial Settlement and Award in March of 2013. In June of 2013, the State moved the district court to vacate, modify, or correct the award. The district court concluded the State did not have standing to move to vacate or modify the award.The State appealed. We affirm. I. FACTUAL AND PROCEDURAL BACKGROUND In the 1990s, litigation arose between the states and tobacco companies regarding responsibility for the costs of treating tobacco-related illness. On November 23, 1998, Idaho 158 Idaho 876 354 P.3d 189 and fifty-one other states and territories (MSA States) entered into the Master Settlement Agreement (MSA) with various tobacco companies in the United States (the Participating Manufacturers). Under the MSA, the MSA States released their claims against these major domestic cigarette manufacturers. In return, the Participating Manufacturers agreed to make annual payments to the MSA States and to abide by cigarette marketing and advertising restrictions. Since the signing of the MSA, additional cigarette manufacturers, known as Subsequent Participating Manufacturers, have signed onto the MSA. For purposes of this appeal, the Participating Manufacturers and Subsequent Participating Manufacturers will be collectively referred to as the PMs. Under the MSA, on April 15 of each year, in perpetuity, each PM is required to pay its relative market share of an agreed upon amount into an escrow account (MSA Annual Payments). Payments are not made directly to the states; instead, the PMs make payments to an Independent Auditor in an amount determined by the Independent Auditor based on the PMs' relative market share. The Independent Auditor then allocates the payments among the MSA States based on each state's allocable share percentage (Allocable Share); Idaho's Allocable Share is .36%. In 2002, Idaho received approximately $25.2 million as its MSA Annual Payment. If a PM or a MSA State disputes the final calculation made by the Independent Auditor, the disputed portion of the amount owed by the PMs is placed into the Disputed Payments Account (DPA). Money placed in the DPA is not subject to interest. Funds placed in the DPA are distributed to the appropriate payee once the dispute is finally resolved. Once the dispute is resolved, the Independent Auditor instructs the escrow agent to credit the funds to the appropriate party. Each MSA Annual Payment is subject to annual adjustments, including an adjustment for inflation and an adjustment for the volume of cigarettes sold. This appeal relates to one annual adjustment, the Non–Participating Manufacturer Adjustment (NPM Adjustment). The NPM Adjustment is intended to account for any gain in market share obtained by those cigarette manufacturers which do not participate in the MSA, referred to as Non–Participating Manufacturers (NPMs). The NPM Adjustment is calculated by the Independent Auditor. The intent of the NPM adjustment is to correct for the market advantage gained by NPMs resulting from the MSA. SeeFrank Sloan & Lindsey Chepke, Litigation, Settlement, and the Public Welfare: Lessons from the Master Settlement Agreement,17 Widener L. Rev. 159, 199 (2011) ; Commw.ex rel. Kane v. Philip Morris USA, Inc.,114 A.3d 37(Pa.Cmwlth.2015). As a result of their responsibility to make the MSA Annual Payments to the states, the PMs have been required to increase the price of their cigarettes. As the NPMs have no such obligation, the PMs are placed at a competitive disadvantage. In order to compensate for this competitive disparity, the MSA requires that MSA States enact statutes mandating NPMs to make payments into escrow accounts in an amount comparable to that which they would have paid if they had entered into the MSA (Qualifying Statute). Idaho's Qualifying Statute is found at Idaho Code section 39–7803, and requires NPMs to place money into an escrow account based upon the number of "units sold" 1in Idaho each year. The MSA was structured to provide the MSA States with an incentive to enforce their Qualifying Statutes.This incentive is 158 Idaho 877 354 P.3d 190 the NPM Adjustment, which reduces the PMs' MSA Annual Payment under certain circumstances. First, the market share of the PMs must decline by 2% or more, nationally, as compared to the PMs' market share in 1997. Second, if there is such a decline, an independent economic consultant must determine whether the MSA was a significant contributing factor in the PMs' loss of the market share. If the PMs experience a market share loss, and it is determined that this loss is due to the disadvantages experienced as a result of the MSA, then the NPM Adjustment is available to the PMs for that year. However, an individual state may avoid the NPM Adjustment, thus receiving the entirety of its MSA Annual Payment, if that state has a Qualifying Statute and diligently enforced the provisions of such statute. As all MSA States have enacted a Qualifying Statute, the only question to be resolved regarding the NPM Adjustment is that of diligent enforcement. Although the MSA Annual Payment of a diligent state is not reduced by the NPM Adjustment, the MSA Annual Payment of a non-diligent state is reduced by the NPM Adjustment in an amount equal to its allocable share of the aggregate NPM Adjustment amount. As increased incentive for enforcement of the Qualifying Statutes, the NPM Adjustment attributable to those states that have diligently enforced their Qualifying Statutes is reallocated among the non-diligent states. In short, the national burden of the NPM Adjustment is borne by the non-diligent states on a pro rata basis in proportion to their respective Allocable Shares. This creates a two-step reduction in the MSA Annual Payment for non-diligent states: first, a reduction for the non-diligent state's share of the NPM Adjustment; and second, a pro rata share of the reallocated NPM Adjustment. Despite every MSA State enacting a Qualifying Statute, the PMs experienced a market share loss following the MSA. The NPM Adjustments for the years 1999 through 2002 were resolved by settlement. However, no such agreement was reached by the PMs with the MSA States for 2003. The Independent Auditor determined that the PMs experienced a market share loss for the year 2003 and an independent economic consultant...
https://case-law.vlex.com/vid/state-v-philip-morris-898567243
Documents Library | Global Forum on Migration and Development Documents Library What can be found in the documents library? The documents library consists of substantive documents and documents that relate to the GFMD process. Among the substantive documents, you can find background papers, research works and other documents that have been used as references in the preparation of the Roundtables or thematic meetings. It is noteworthy that most of these GFMD-related documents were prepared by government-led teams. This approach has helped promote confidence-building and a sense of partnerships between and among governments and key partners in the GFMD process. The process-related documentsinclude the Roundtable concept themes for each annual meeting, the list of GFMD participants, and Reports of Proceedings of the meetings of the GFMD Steering Group and Friends of the Forum. In addition, information on the engagement of the civil society and the business sector can be found. The documents library does not contain the migration and development policies and practices that are stored in the GFMD Database in thePlatform for Partnerships. For whom is the documents library? The GFMD documents library is generally open to the public. The wealth of information that is showcased in the library could be useful for all migration and development enthusiasts - government policy-makers and practitioners, international organizations, civil society, business, researchers and students, and migrants themselves. How should I use the documents library? The search engine below allows you to search by any key word(s) you choose. Alternatively, you may filter the documents by (annual) GFMD meetings, and/or by thematic area or tag (on the right). If the themes and tags do not appear, try clicking the ‘reset’ button next to the search bar. National Labour Migration Policy for Sri Lanka. Padmini Ratnayake, Ministry of Labour & Labour Relations, Sri Lanka Thematic Meeting on Facilitating South-South Labour Migration (16-18 Oct 2011, Abuja) L'intermédiation privée à l‘étranger et la régulation des établissements prives de Placement à l’étranger (les EPPE): Cas de la Thematic Meeting on M&D Policy Assessment (13-15 Jun 2011, Marseille) Addressing the Challenges and Opportunities of Migration as Part of Sectoral Strategies - Employment. Anna Farkas, Subregional P Thematic Meeting on Mainstreaming Migration into Strategic Policy Development (12-13 Oct 2011, Chisinau) Addressing the Challenges and Opportunities of Migration as Part of Sectoral Strategies - Employment: Experience of the Republic Thematic Meeting on Mainstreaming Migration into Strategic Policy Development (12-13 Oct 2011, Chisinau) Vocational Skills, Non-Formal and Informal Learning, Migration: The Case of the Republic of Moldova. Siria Taurelli, European Tr Thematic Meeting on Mainstreaming Migration into Strategic Policy Development (12-13 Oct 2011, Chisinau) "Impact de l’éducation sur la migration en Tunisie Walid Blel, Direction de la migration et de la main d’oeuvre étrangère, Minis Thematic Meeting on Mainstreaming Migration into Strategic Policy Development (12-13 Oct 2011, Chisinau) Guide on Ratification: International Convention on the Protection of the Rights of All Migrant Workers and Members of their Fami Thematic Meeting on Mainstreaming Migration into Strategic Policy Development (12-13 Oct 2011, Chisinau) Integrating Migration in National Development Agendas of Bangladesh: Experiences and Fundamental Principles. Mohammad Iftekhar H Thematic Meeting on Mainstreaming Migration into Strategic Policy Development (12-13 Oct 2011, Chisinau) Moldovan Diaspora Organizations: an Asset for the Country’s European Integration. Dorin Duşciac Thematic Meeting on Mainstreaming Migration into Strategic Policy Development (12-13 Oct 2011, Chisinau) Optimizing Development Gains: Non-Governmental Actors. Manuel G. Imson, Labor Attaché, Permanent Mission of the Philippines, Gen Thematic Meeting on Mainstreaming Migration into Strategic Policy Development (12-13 Oct 2011, Chisinau) Migration and Economic Development: Mainstreaming migration into the Moldova 2020 Strategy Thematic Meeting on Mainstreaming Migration into Strategic Policy Development (12-13 Oct 2011, Chisinau) Addressing the Challenges and Opportunities of Migration as Part of Sectoral Strategies - Employment: Experience of the Republic Thematic Meeting on Mainstreaming Migration into Strategic Policy Development (12-13 Oct 2011, Chisinau) Ways of Asking About the Impact of Overseas Work on Filipino Families. Michael Clemens, Center for Global Development Thematic Meeting on M&D Policy Assessment (13-15 Jun 2011, Marseille) Experience de l’aneti en matiere de l’emploi a l’international. Mohamed Mani, Directeur, Analyse des données du marché de l’empl Thematic Meeting on M&D Policy Assessment (13-15 Jun 2011, Marseille) Migration, Employment and Protection of Migrants. María Luisa Casado López, Directorate General for Immigration, Ministry of Lab Thematic Meeting on M&D Policy Assessment (13-15 Jun 2011, Marseille) Regulating Private Recruitment: Policy Options and Key Challenges. Dovelyn Rannveig Agunias, Regional Research Officer, Internat Thematic Meeting on M&D Policy Assessment (13-15 Jun 2011, Marseille) Reflections on New Zealand's Recognised Seasonal Employer (RSE) Policy. Sankar Ramasamy, New Zealand Thematic Meeting on M&D Policy Assessment (13-15 Jun 2011, Marseille) Migration as Development. Manjula Luthria, Senior Economist, World Bank Thematic Meeting on M&D Policy Assessment (13-15 Jun 2011, Marseille) Accord entre le gouvernement de la République Française et le gouvernement de la République de Maurice relatif au séjour et à la Thematic Meeting on M&D Policy Assessment (13-15 Jun 2011, Marseille) Circular Migration as a Development Tool –The Mauritian Approach. Anil K. Kokil, Ministry of Finance and Economic Development, M Thematic Meeting on M&D Policy Assessment (13-15 Jun 2011, Marseille) Towards a National Policy on International Migration and Development for Jamaica. Toni-Shae Freckleton, Planning Institute of Ja Thematic Meeting on M&D Policy Assessment (13-15 Jun 2011, Marseille) Synergies between Migration and Development. Policies and programs: Moldova. Diana Hincu, Ministry of Foreign Affairs and Europe Thematic Meeting on M&D Policy Assessment (13-15 Jun 2011, Marseille) Managing Migration for Development and Employment. Roberta Gatti, World Bank Thematic Meeting on M&D Policy Assessment (13-15 Jun 2011, Marseille) Briefing Note No. 3 International Labor Intermediation Thematic Meeting on M&D Policy Assessment (13-15 Jun 2011, Marseille) Briefing Note No. 2 Temporary Labor Migration Programs Thematic Meeting on M&D Policy Assessment (13-15 Jun 2011, Marseille)
https://www.gfmd.org/docs?f%5B0%5D=field_thematic_areas%3A3&f%5B1%5D=field_gfmd_meeting%3A56&f%5B2%5D=field_catergory%3A392&f%5B3%5D=field_thematic_areas%3A6
Oneida, WI 1910 Federal Census ftp://ftp.us-census.org/pub/usgenweb/census/wi/oneida/1910/ (File 2 of 3 for ED:122) This Census was transcribed by Susan Swanson and proofread by Myron and Phyllis Lammert for the USGenWeb Census Project http://www.us-census.org/ Copyright (c) 2002 by Susan Swanson ========================================================================= USGENWEB NOTICE: These electronic pages may NOT be reproduced in any format for profit or presentation by any other organization or persons. Persons or organizations desiring to use this material must obtain the written consent of the transcriber or the legal representative of the transcriber and contact the USGenWeb Census Project File Manager via the email address <Transcriber@US-Census.Org> with proof of this consent. ========================================================================= Formatted by USGenWeb Census Project File Manager, Connie Burkett All of the above information must remain when copied or downloaded. ========================================================================= Census Year 1910 Microfilm Roll #T624-1730 State WISCONSIN County Oneida ---------------------Begin Actual Transcription---------------------------------- INDIAN POPULATION SCHEDULE ==================================================================================================================================================================================================================================================================================================================================================================================================================================== CENSUS YEAR: 1910 STATE: WI COUNTY: Oneida TOWNSHIP: Sugar Camp - Chippewa Indian Settlement MICROFILM#: T624-1730 SUPV/DISTR: 9 ENUM/DISTR: 122 ENUMERATOR: Wm. J. Neis ENUM/DATE-RANGE: April 19 - May 7, 1910 ==================================================================================================================================================================================================================================================================================================================================================================================================================================== Stamped AGE S-M #YRS # #CHILD BIRTH FATHER MOTHER YEAR NATUR- SPEAK TRADE OR GENERAL EMPL OUT OF #WKS CAN CAN ATTD OWN FREE FARM #FARM SURV DEAF TRIBE FATHER'S MOTHER'S Full/Mixed Times Poly- Wives GRADUATED YEAR OWN CIV/ TRANSCRIBER'S PG# LN# ED SH# STR HS# DW# FM# LAST NAME FIRST NAME RELATION SEX RACE LAST W-D MAR CHILD LIVING PLACE BIRTHPL BIRTHPL IMMI ALIZED ENG? PROFESSION INDUSTRY ACCT WORK UNEMPL READ WRITE SCH RENT MORT HOME SCH WAR BLIND DUMB NAME TRIBE TRIBE BLOOD Mar'd gamy Sister EDUC INST TAX? ALLT LAND ABOR REMARKS (1) (2) (3) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22) (23) (24) (25) (26) (27) (28) (29) (30) (31) (32) (33) (34) (35) (36) (37) (38) (39) (40) (41) (42) (43) (44) (45) (46) ==================================================================================================================================================================================================================================================================================================================================================================================================================================== 60A 1 122 8A . . 1 1 White, John Head M In 42 M1 14 . . Wisconsin Wisconsin Wisconsin . . English Farmer General Farm OA . . No No . O F F 1 . . . Chippewa Chippewa Chippewa 1/2 1/2 No 1 No No None Yes About 1890 Yes Civilized Chippewa Indian Settlement 60A 2 122 8A . . 1 1 White, Anna Wife F In 38 M1 14 7 3 Wisconsin Wisconsin Wisconsin . . Chippewa None . . . . No No . . . . . . . . Chippewa Chippewa Chippewa full . No 1 No No None . About 1897 . Civilized Handwritten page 9566 60A 3 122 8A . . 1 1 White, Fred Son M In 10 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes Yes . . . . . . . Chippewa Chippewa Chippewa 3/4 1/4 No . . . None . . . Civilized Contains more information on tribe. 60A 4 122 8A . . 1 1 White, Jessie Daughter F In 7 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes Yes . . . . . . . Chippewa Chippewa Chippewa 3/4 1/4 No . . . None . . . Civilized . 60A 5 122 8A . . 1 1 White, Minnie Daughter F In 5 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes No . . . . . . . Chippewa Chippewa Chippewa 3/4 1/4 No . . . None . . . Civilized . 60A 6 122 8A . . 1 1 Big, Clarlie Father In Law M In 78 M1 30 . . Wisconsin Wisconsin Wisconsin . . Chippewa Farmer General Farm OA . . No No . . . . . . . . Chippewa Chippewa Chippewa full . . 1 No . None Yes About 1897 . Civilized . 60A 7 122 8A . . 1 1 Big, Minclamvie* Mother In Law F In 60 M1 30 12 2 Wisconsin Wisconsin Wisconsin . . Chippewa None . . . . No No . . . . . . . . Chippewa Chippewa Chippewa full . . 1 No . None . About 1897 . Civilized . 60A 8 122 8A . . 3 3 St. Germaine, Fred Head M In 60 M1 38 . . Wisconsin Wisconsin Wisconsin . . English Farmer General Farm OA . . No No . O F F 3 . . . Chippewa Chippewa Chippewa full . . 1 No . None Yes About 1897 . Civilized . 60A 9 122 8A . . 3 3 St. Germaine, Biddie Wife F In 55 M1 38 12 5 Wisconsin Wisconsin Wisconsin . . English None . . . . No No . . . . . . . . Chippewa Chippewa Chippewa full . . 1 No . None . About 1897 . Civilized . 60A 10 122 8A . . 3 3 St. Germaine, Ferris* Son M In 35 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes . . . . . . . . Chippewa Chippewa Chippewa full . . 0 No . None . . . Civilized . 60A 11 122 8A . . 3 3 St. Germaine, Martin Son M In 32 M1 20 . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes . . . . . . . . Chippewa Chippewa Chippewa full . . M1 No . None . About 1897 . Civilized . 60A 12 122 8A . . 3 3 St. Germaine, Agnus Daughter F In 30 M1 8 6 2 Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes . . . . . . . . Chippewa Chippewa Chippewa full . . M1 No . None . About 1897 . Civilized . 60A 13 122 8A . . 3 3 St. Germaine, Alice Daughter F In 28 M1 10 5 4 Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes . . . . . . . . Chippewa Chippewa Chippewa full . . M1 No . None . About 1897 . Civilized . 60A 14 122 8A . . 3 3 St. Germaine, Mary Daughter F In 26 M1 15 6 2 Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes . . . . . . . . Chippewa Chippewa Chippewa full . . M1 No . None . About 1897 . Civilized . 60A 15 122 8A . . 3 3 St. Germaine, Frances Daughter In law F In 30 M1 20 0 0 Wisconsin Wisconsin Wisconsin . . Chippewa None . . . . No No . . . . . . . . Chippewa Chippewa Chippewa full . . M1 No . None . About 1897 . Civilized . 60A 16 122 8A . . 3 3 Weunn* Walter Son In Law M In 28 M1 8 . . Wisconsin Wisconsin Wisconsin . . English None . . . . No No . . . . . . . . Chippewa Chippewa Chippewa full . . M1 No . None . About 1897 . Civilized Surname unreadable 60A 17 122 8A . . 3 3 Pine*, Eddie Son In Law M In 28 M1 10 . . Wisconsin Wisconsin Wisconsin . . English None . . . . No No . . . . . . . . Chippewa Chippewa Chippewa full . . M1 No . None . About 1897 . Civilized Surname unreadable 60A 18 122 8A . . 3 3 Patterson, John Son In Law M In 28 M1 15 . . Wisconsin Wisconsin Wisconsin . . English None . . . . No No . . . . . . . . Chippewa Chippewa Chippewa full . . M1 No . None . About 1897 . Civilized . 60A 19 122 8A . . 3 3 Weunn* Brissett Daughter F In 10 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . No No Yes . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . 60A 20 122 8A . . 3 3 Weunn* Sussie Daughter F In 8 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . No No yes . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . ==================================================================================================================================================================================================================================================================================================================================================================================================================================== CENSUS YEAR: 1910 STATE: WI COUNTY: Oneida TOWNSHIP: Sugar Camp - Chippewa Indian Settlement MICROFILM#: T624-1730 SUPV/DISTR: 9 ENUM/DISTR: 122 ENUMERATOR: Wm. J. Neis ENUM/DATE-RANGE: April 19 - May 7, 1910 ==================================================================================================================================================================================================================================================================================================================================================================================================================================== Stamped AGE S-M #YRS # #CHILD BIRTH FATHER MOTHER YEAR NATUR- SPEAK TRADE OR GENERAL EMPL OUT OF #WKS CAN CAN ATTD OWN FREE FARM #FARM SURV DEAF TRIBE FATHER'S MOTHER'S Full/Mixed Times Poly- Wives GRADUATED YEAR OWN CIV/ TRANSCRIBER'S PG# LN# ED SH# STR HS# DW# FM# LAST NAME FIRST NAME RELATION SEX RACE LAST W-D MAR CHILD LIVING PLACE BIRTHPL BIRTHPL IMMI ALIZED ENG? PROFESSION INDUSTRY ACCT WORK UNEMPL READ WRITE SCH RENT MORT HOME SCH WAR BLIND DUMB NAME TRIBE TRIBE BLOOD Mar'd gamy Sister EDUC INST TAX? ALLT LAND ABOR REMARKS (1) (2) (3) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22) (23) (24) (25) (26) (27) (28) (29) (30) (31) (32) (33) (34) (35) (36) (37) (38) (39) (40) (41) (42) (43) (44) (45) (46) ==================================================================================================================================================================================================================================================================================================================================================================================================================================== 60B 21 122 8B . . 3 3 Pine*, Katie Daughter F In 10 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . No No No . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized Handwritten page 9586 60B 22 122 8B . . 3 3 Pine*, George Son M In 8 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . No No No . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . 60B 23 122 8B . . 3 3 Pine*, Albert Son M In 6 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . No No No . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . 60B 24 122 8B . . 3 3 Patterson, Jim Son M In 8 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes Yes . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . 60B 25 122 8B . . 3 3 Patterson, John Son M In 6 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . No No No . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . 60B 26 122 8B . . 4 4 Wauams,* John Head M In 52 M1 32 . . Wisconsin Wisconsin Wisconsin . . English None . . . . No No . O F F 4 . . . Chippewa Chippewa Chippewa full . . M1 No . None ? About 1897 Yes Civilized Surname Unreadable 60B 27 122 8B . . 4 4 Wauams,* Emily Wife F In 46 M1 32 9 8 Wisconsin Wisconsin Wisconsin . . Chippewa None . . . . No No . . . . . . . . Chippewa Chippewa Chippewa full . . M1 No . None . . . Civilized . 60B 28 122 8B . . 4 4 Wauams,* Helen Daughter F In 30 M1 5 1 1 Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes . . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . 60B 29 122 8B . . 4 4 Wauams,* John Son M In 28 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes . . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . 60B 30 122 8B . . 4 4 Wauams,* Annie Daughter F In 26 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes Yes . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . 60B 31 122 8B . . 4 4 Wauams,* Nellie Daughter F In 24 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes Yes . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . 60B 32 122 8B . . 4 4 Wauams,* Elsie Daughter F In 22 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes Yes . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . 60B 33 122 8B . . 4 4 Wauams,* Celia Daughter F In 20 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes Yes . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . 60B 34 122 8B . . 4 4 Wauams,* Gurtrude Daughter F In 18 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes Yes . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . 60B 35 122 8B . . 4 4 Wauams,* Francis* Daughter F In 16 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes Yes . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized Name Unreadable 60B 36 122 8B . . 4 4 Edwards, Jonas Son In Law M In 35 M1 5 . . Wisconsin Wisconsin Wisconsin . . English None . . . . No No . . . . . . . . Chippewa Chippewa Chippewa full . . M1 No . None . . . Civilized . 60B 37 122 8B . . 4 4 Edwards, Lulibelle Grand child F In 2 S . . . Wisconsin Wisconsin Wisconsin . . . None . . . . . . . . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . 60B 38 122 8B . . 5 5 Pat, Little Head M In 36 M1 18 . . Wisconsin Wisconsin Wisconsin . . English Farmer General Farm OA . . No No . O F F 5 . . . Chippewa Chippewa Chippewa full . . M1 No . None . About 1897 . Civilized . 60B 39 122 8B . . 5 5 Pat, Annie Wife F In 33 M1 18 9 2 Wisconsin Wisconsin Wisconsin . . Chippewa None . . . . No No . . . . . . . . Chippewa Chippewa Chippewa full . . M1 No . None . About 1897 . Civilized . 60B 40 122 8B . . 5 5 Pat, Celia . F In 8 S . . . Wisconsin Wisconsin Wisconsin . . Chippewa None . . . . No No No . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized . ==================================================================================================================================================================================================================================================================================================================================================================================================================================== CENSUS YEAR: 1910 STATE: WI COUNTY: Oneida TOWNSHIP: Sugar Camp - Chippewa Indian Settlement MICROFILM#: T624-1730 SUPV/DISTR: 9 ENUM/DISTR: 122 ENUMERATOR: Wm. J. Neis ENUM/DATE-RANGE: April 19 - May 7, 1910 ==================================================================================================================================================================================================================================================================================================================================================================================================================================== Stamped AGE S-M #YRS # #CHILD BIRTH FATHER MOTHER YEAR NATUR- SPEAK TRADE OR GENERAL EMPL OUT OF #WKS CAN CAN ATTD OWN FREE FARM #FARM SURV DEAF TRIBE FATHER'S MOTHER'S Full/Mixed Times Poly- Wives GRADUATED YEAR OWN CIV/ TRANSCRIBER'S PG# LN# ED SH# STR HS# DW# FM# LAST NAME FIRST NAME RELATION SEX RACE LAST W-D MAR CHILD LIVING PLACE BIRTHPL BIRTHPL IMMI ALIZED ENG? PROFESSION INDUSTRY ACCT WORK UNEMPL READ WRITE SCH RENT MORT HOME SCH WAR BLIND DUMB NAME TRIBE TRIBE BLOOD Mar'd gamy Sister EDUC INST TAX? ALLT LAND ABOR REMARKS (1) (2) (3) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22) (23) (24) (25) (26) (27) (28) (29) (30) (31) (32) (33) (34) (35) (36) (37) (38) (39) (40) (41) (42) (43) (44) (45) (46) ==================================================================================================================================================================================================================================================================================================================================================================================================================================== 60b* 1 122 9A . . 5 5 Pat, George Son M In 4 S . . . Wisconsin Wisconsin Wisconsin . . Chippewa None . . . . No No No . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized No Page Number on this page 60b* 2 122 9A . . 6 6 John, Big Head M In 70 M1 35 . . Wisconsin Wisconsin Wisconsin . . Chippewa None . . . . No No . O F F 6 . . . Chippewa Chippewa Chippewa full . . M1 No . None Yes About 1897 . Civilized No Page Number on this page 60b* 3 122 9A . . 6 6 John, Helen Wife F In 65 M1 35 7 2 Wisconsin Wisconsin Wisconsin . . English None . . . . No No . . . . . . . . Chippewa Chippewa Chippewa full . . M1 No . None . . . Civilized No Page Number on this page 60b* 4 122 9A . . 6 6 John, Johnnie Son M In 28 M1 4 . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes . . . . . . . . Chippewa Chippewa Chippewa full . . M1 No . None . About 1897 . Civilized No Page Number on this page 60b* 5 122 9A . . 6 6 John, Tommy Son M In 14 S . . . Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes Yes . . . . . . . Chippewa Chippewa Chippewa full . . . . . None . . . Civilized No Page Number on this page 60b* 6 122 9A . . 6 6 John, Mary Daughter In law F In 26 M1 4 0 0 Wisconsin Wisconsin Wisconsin . . English None . . . . Yes Yes . . . . . . . . Chippewa Chippewa Chippewa full . . M1 No . None . . . Civilized No Page Number on this page
http://us-census.org/pub/usgenweb/census/wi/oneida/1910/ed122-sh08a.txt
The effectiveness of strategies to change organisational culture to improve healthcare performance - Parmelli, E - 2011 | Cochrane Library The effectiveness of strategies to change organisational culture to improve healthcare performance - Parmelli, E - 2011 | Cochrane Library The effectiveness of strategies to change organisational culture to improve healthcare performance Elena Parmelli Gerd Flodgren Mary Ellen Schaafsma Nick Baillie Fiona R Beyer Martin P Eccles Authors' declarations of interest Version published: 19 January 2011Version history https://doi.org/10.1002/14651858.CD008315.pub2 Abstract available in Background Organisational culture is an anthropological metaphor used to inform research and consultancy and to explain organisational environments. Great emphasis has been placed during the last years on the need to change organisational culture in order to pursue effective improvement of healthcare performance. However, the precise nature of organisational culture in healthcare policy often remains underspecified and the desirability and feasibility of strategies to be adopted has been called into question. Objectives To determine the effectiveness of strategies to change organisational culture in order to improve healthcare performance. To examine the effectiveness of these strategies according to different patterns of organisational culture. Search methods We searched the following electronic databases for primary studies: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Sociological Abstracts, Web of Knowledge, PsycINFO, Business and Management, EThOS, Index to Theses, Intute, HMIC, SIGLE, and Scopus until October 2009. The Database of Abstracts of Reviews of Effectiveness (DARE) was searched for related reviews. We also searched the reference lists of all papers and relevant reviews identified, and we contacted experts in the field for advice on further potential studies. Selection criteria We considered randomised controlled trials (RCTs) or well designed quasi‐experimental studies, controlled clinical trials (CCTs), controlled before and after studies (CBAs) and interrupted time series analyses (ITS) meeting the quality criteria used by the Cochrane Effective Practice and Organisation of Care Group (EPOC). Studies should be set in any type of healthcare organisation in which strategies to change organisational culture in order to improve healthcare performance were applied. Our main outcomes were objective measures of professional performance and patient outcome. Data collection and analysis At least two review authors independently applied the criteria for inclusion and exclusion criteria to scan titles and abstracts and then to screen the full reports of selected citations. At each stage results were compared and discrepancies solved through discussion. Main results The search strategy yielded 4239 records. After the full text assessment, no studies met the quality criteria used by the EPOC Group and evaluated the effectiveness of strategies to change organisational culture to improve healthcare performance. Authors' conclusions It is not possible to draw any conclusions about the effectiveness of strategies to change organisational culture because we found no studies that fulfilled the methodological criteria for this review. Research efforts should focus on strengthening the evidence about the effectiveness of methods to change organisational culture to improve health care performance. Plain language summary available in Strategies to change organisational culture to improve healthcare performance 'Organisational culture' refers to the shared characteristics among people within the same organisation. These characteristics may include: beliefs, values, norms of behaviour, routines, traditions, and sense‐making. In the last several years, great emphasis has been placed on changing both organisational culture and organisational structure to improve healthcare performance. While the management of organisational culture is increasingly viewed as a necessary part of health system reform, evidence from the research literature on the link between organisational culture and health performance is weak. Therefore, It is important for policymakers to review the effectiveness of strategies aiming to change organisational culture on healthcare performance. This Cochrane review did not find any rigorous evidence to demonstrate the effect of strategies to change organisational culture on healthcare performance. There are examples (within the excluded studies) of researchers attempting to do this, but well designed studies are lacking. Visual summary
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD008315.pub2/full/zh_HANT
An possible ancestor of Homo floresiensis from the Middle Pleistocene of Flores Gerrit van den Bergh and coworkers describe dental remains and a jaw from Mata Menge, 700,000 years ago. An possible ancestor of Homo floresiensis from the Middle Pleistocene of Flores Gerrit van den Bergh and coworkers describe dental remains and a jaw from Mata Menge, 700,000 years ago. Dental evidence from Mata Menge. Image: S. Hayes in The Conversation CC-BY I was really excited yesterday to read about the work of Gerrit van den Bergh and colleagues at Mata Menge, where they have uncovered hominin fossil remains attributable to an ancient population on Flores. The six teeth and one partial jaw were recovered from a “high-volume” excavation covering more than 200 square meters. They document the existence of a small-toothed and small-jawed human population on Flores approximately 700,000 years ago. Mata Menge MM4 mandible, from figure 1 of van den Bergh et al. 2016. Phylogenetic position of the Flores hominins Earlier this spring, I reviewed the work by Sutikna and colleagues that revised the timeline of the Liang Bua hominin sample (“What the revised Liang Bua chronology leaves unanswered”). All of the remains of small-bodied hominins from Liang Bua now predate 60,000 years ago, making them earlier than the first known occurrence of modern humans anywhere in Indonesia. Paleoanthropologists have generated rival explanations for the phylogenetic relationships of the Liang Bua skeleton. Some propose that it represents evolutionary dwarfing from a larger-boded Homo erectusancestor; others hypothesize that a previously unknown population of australopiths or smaller-bodied Homomay have existed in Asia and given rise to the Flores population. LB1 preserves most of a skeleton, providing the potential for Homo floresiensisto be one of the most well-represented species in any phylogenetic analysis of the hominins. Most other hominin species are represented only by jaws and teeth, and maybe parts of the face and cranial vault. Yet despite the richness of evidence from LB1, its phylogenetic position remains uncertain. The biggest problem is not the LB1 skeleton, it is the lack of evidence from other species. To understand the scope of the problem, we can look at the two most recent attempts to place the LB1 specimen into the hominin phylogenetic tree. Both considered only the morphology of the skull, mandible and teeth. Valéry Zeitoun and colleagues (2016) concluded that LB1 lies within the variation of early H. erectusspecimens from Java, including the Sangiran 2 and 17 specimens, the Trinil 2 specimen, added to the KNM-WT 15000 skull. They concluded that later “H. erectus”specimens from Java belong to a different clade, closer to Middle Pleistocene humans elsewhere and modern humans. Most parsimonious phylogeny from Zeitoun and colleagues (2016), figure 3. The LB1 specimen is nested within a group of specimens including Sangiran, Trinil and KNM-WT 15000 crania. Meanwhile, Mana Dembo and colleagues (2015) concluded that H. floresiensisis an outgroup to a clade including H. rudolfensis, H. erectusand later species of Homo(but not H. habilis). However, the Bayes factor comparisons in this study could not reject the hypothesis that the closest sister group for H. floresiensiswas H. erectus. Highest probability phylogeny from Dembo and colleagues (2015), figure 1. In this tree, the Homo floresiensis branch is a sister to a branch including Homo rudolfensis and other species of Homo except for H. habilis . Note that the H. floresiensis branch is inferred to have originated just after 3 million years ago. Those are two very different conclusions. The analyses included different groups of fossils, grouped them in different ways (species versus individual specimens), and looked at different sets of characters, with a different pattern of missing data. In the end, although the Bayes factor analysis by Dembo and colleagues (2015) did not look at the precise scenario favored by Zeitoun and colleagues (2016), it did show that a similar scenario cannot be rejected by the data. In the end, the data just aren’t good enough to tell between these. It gets worse. Looking at whole-body evidence from hominin populations, it is evident that the few features of skulls and teeth that determine the outcomes of phylogenetic analyses are not necessarily typical of the skeleton as a whole. When we look at basal lineages within Homo, like populations of Homo erectus, Homo habilis, Homo rudolfensis, and Homo floresiensis, we are looking at a series of branches that diverged very close to each other, probably within a million years and potentially within a few hundred thousand years, which means that there may be few shared derived features linking the species within a clade. Yet some of those branches may be very long, particularly Homo floresiensis, meaning that there is a strong chance that the signal of phylogenetic relationship will be lost within the noise of long, independent evolutionary history. I will add that there is a very real possibility of population mixing and introgression during the initial evolution of Homo, that would tend to obscure any simple tree of relationships among these species. Homo floresiensisis not a uniquely confusing case. We face similar issues with the very complete skeletal evidence from Homo naledi. More evidence does not make this species easier to place on the phylogeny of Homo. In many ways, better evidence just directs our attention to how poor our efforts using partial jaws and teeth must be. In that context, it is probably hopeless to expect that a partial fragment of jaw and six teeth are going to add useful data to better understand the phylogenetic context of the Flores hominins. Some people have commented that the Mata Menge teeth are “ erectus-like”, or more similar to H. erectusthan to H. habilis. I find the data unpersuasive. The jaw is unquestionably smaller than any adult mandible assigned to H. erectus, H. habilis, or H. naledi, as is the lower molar (whether it is a first or second) and the premolar. The small sizes of all these elements would be derived relative to any primitive species within Homo, so being closer in size to H. erectusis not useful information—after all, they are even closerin size to H. sapiens! The deciduous canines and the central upper incisor stand out as unusually small and not morphologically typical of modern humans or fossil Homo erectus, but they are approximately the same sizes as the deciduous canines of Homo naledi. If no one else has suggested that H. naledigave rise to the Flores hominins, I’ll be happy to be the first. The mandibular corpus preserves no diagnostic morphology other than its small size, and it is within the range of sizes of modern humans. There are only a few non-metric traits of the teeth that can be assessed, which are shared with specimens of H. erectusand H. habilis, and the shape of the molar is more erectus-like than habilis-like. That’s weak evidence, since the small size of the molar probably confounds its shape (it’s like modern humans in shape as well). If these specimens had been recovered from the surface instead of from an excavation, they would have been difficult or impossible to authenticate as representing an ancient population. There’s just too little evidence there. Flores reinvasion? The authors of the research have done well by not over-emphasizing the quality of the morphological evidence in their research paper. The remains do not share any of the traits used to diagnose Homo floresiensis, which justifies the caution of van den Bergh and colleagues in not assigning them to that species. The remains also do not settle whether small body size had appeared in the Mata Menge hominins. Some commentators seem to be assuming that these teeth do belong to the same population as the later Liang Bua remains, and are inferring a small body size on the basis of a slightly smaller size than the Liang Bua mandibular and dental sample. But nowhere else in the hominin fossil record would we be safe in assuming that jaw and tooth size are good indicators of body size, and I think the assumption is unwarranted here. It is certainly possible that the small Mata Menge teeth and jaw represent a similarly small-bodied population, and I would not be surprised if the next bone to be discovered was a tiny tibia along the lines of LB6. But the next most comparable species for the sizes of the teeth are modern humans and Homo naledi, neither of which are nearly so small in body size as LB1 or LB6 from Liang Bua. More broadly, body size and tooth and jaw size are not well correlated among hominin species. There are notably big-toothed and small-bodied Homo erectusspecimens, and smaller-toothed and big-bodied Homo erectusspecimens. These teeth and this jaw are within the size range of modern human jaws and teeth; their bodies may have been as well. Realistically, the morphology can give little indication that the Mata Menge hominin sample represents an ancestral population for the later Liang Bua sample. As some have pointed out, Flores may have been invaded more than once by hominin populations, and such populations may independently have evolved small mandible and tooth sizes, or even small body sizes. To know that reinvasion is a plausible scenario, we need look no further than the local proboscideans. Flores wasinvaded at least twice by successive Stegodonspecies that apparently did evolve smaller body size independently. These creatures are abundant in the fossil record of Mata Menge and Liang Bua, and they likely existed at higher population densities than the hominins—even though elephants in general live at fairly low densities when compared to other smaller terrestrial herbivores. The idea that Flores could not have been reinvaded by hominins seems to be based on the assumption that the ancestral population arrived by accident and constituted a “lost world” phenomenon. I wouldn’t make that assumption. Moreover, there’s a problem with the “lost world” hypothesis. If hominins on Flores had the same low population densities as we think characterized continental hominin populations during the Pleistocene, there couldn’t have been many of them. Such a population would have been more or less constantly at risk of extinction or mutational meltdown. It may not have been viable over evolutionary time. Flores may have even undergone periods of complete abandonment followed by the introduction of new founder populations. Or new immigrants from a larger population may have had a genetic advantage within the strongly inbred Flores population. In either case, strong genetic and population turnovers may have occurred repeatedly, even if (maybe especially if) migration to the island was rare. I would even speculate that repeated entry of new populations onto Flores was accompanied by some introgression from the earlier population, if it was not extinct. Maybe small body size really did evolve a single time, and was retained over time due to adaptive introgression. The founders of Flores populations may have come from the same source population or from different sources. As Chris Stringer pointed out inhis public comment, the source population for Flores may well have inhabited Sulawesi, in which case the source population may itself have been a dwarf population of hominins, although larger in numbers than would be sustainable on Flores. For that matter, the body sizes of Javan and Chinese H. erectuspopulations were not as large as those reported for East African Early Pleistocene H. erectus. This is all unfounded speculation, but it is consistent with what we know (and don’t know) about the hominin fossil record and our knowledge of evolutionary processes. I remain excited about the recovery of evidence from Mata Menge, but that excitement is tempered by the inability of the evidence to test many interesting hypotheses. Fast evolution of small body size? Last, I’m very surprised to see paleoanthropologists in the press commenting that the dwarfing of Homo floresiensiswas very rapid. The data are completely silent about the rate of evolutionary change in this case. To assess evolutionary rate, we need to know both the magnitude of change and the time available for change to have occurred. In this case, we know neither. First, we simply do not know the body size of the Mata Menge hominins. Second, even if we assume they were small-bodied, we do not know the body size of their ancestral population. If they evolved from something like Dmanisi, we are talking about a rather minor amount of size reduction. If they evolved from an australopith-like ancestor, we may be looking at stasis in body and brain size. Third, we have absolutely no reason to think that 300,000 years is the total time available for the evolutionary change. The first occurrence of archaeology on the island must be later thanthe first appearance of hominins. The artifacts from Wolo Sege show hominin activity prior to 1 million years ago, and Brumm and colleagues (2010) concluded that the existing sedimentary record of the Soa Basin “may not be old enough to register the initial arrival of hominins on the island.” We have no reason to assume that the date of the Wolo Sege artifacts was close to the arrival time. Indeed, if Dembo and colleagues were correct about the evolutionary relationships of H. floresiensis, their estimate for the origin of the branch leading to the species is nearly 3 million years ago. Is it possible that hominins were on Flores more than a million years before the Wolo Sege artifacts? Maybe so. We cannot test the hypothesis at present. This goes to a broader problem in paleoanthropology: Too many of our professional colleagues assume that the origin of a species can be equated with its first occurrence in the fossil record. It would be worse than foolish to assume that the record is good enough to document the earliest occupation of Flores by hominins. The literature on the subject tells us directly that the record is notgood enough to test when hominins arrived on the island. So we do not know the rate of evolutionary change in this case. I will add just say one more thing: Three hundred thousand years is a lotof time. It is more time that we used to imagine for the initial expansion of body and brain size in Homo erectus. It is plenty of time for selection to transform body and brain size in a hominin population. References van den Bergh, Gerrit D., Yousuke Kaifu, Iwan Kurniawan, Reiko T. Kono, Adam Brumm, Erick Setiyabudi, Fachroel Aziz and Michael J. Morwood. Homo floresiensis-like fossils from the early Middle Pleistocene of Flores. Nature534, 245–248.doi:10.1038/nature17999 Brumm, Adam, Gerrit D. van den Bergh, Michael Storey, Iwan Kurniawan, Brent V. Alloway, Ruly Setiawan, Erick Setiyabudi, Rainer Grün, Mark W. Moore, Dida Yurnaldi, Mika R. Puspaningrum, Unggul P. Wibowo, Halmi Insani, Indra Sutisna, John A. Westgate, Nick J. G. Pearce, Mathieu Duval, Hanneke J. M. Meijer, Fachroel Aziz, Thomas Sutikna, Sander van der Kaars, Stephanie Flude and Michael J. Morwood. Age and context of the oldest known hominin fossils from Flores. Nature 534, 249–253.doi:10.1038/nature17663 Brumm, Adam, Gitte M. Jensen, Gert D. van den Bergh, Michael J. Morwood, Iwan Kurniawan, Fachroel Aziz, and Michael Storey. 2010. Hominins on Flores, Indonesia, by one million years ago. Nature464, 748-752.doi:10.1038/nature08844 Sutikna, T., Tocheri, M. W., Morwood, M. J., Saptomo, E. W., Awe, R. D., Wasisto, S., ... & Storey, M. (2016). Revised stratigraphy and chronology for Homo floresiensis at Liang Bua in Indonesia. Nature.doi:10.1038/nature17179 Zeitoun, Valéry, Véronique Barriel, and Harry Widianto. 2016 Phylogenetic analysis of the calvaria of Homo floresiensis. Comptes Rendus Palevol15, 555-568.doi:10.1016/j.crpv.2015.12.002 Dembo, Mana, Nicholas J. Matzke, Arne Ø. Mooers, and Mark Collard. 2015. Bayesian analysis of a morphological supermatrix sheds light on controversial fossil hominin relationships. Proc. R. Soc. B, 282, 20150943.doi:10.1098/rspb.2015.0943 Homo floresiensis Flores Middle Pleistocene phylogeny body size
https://johnhawks.net/weblog/an-possible-ancestor-of-homo-floresiensis-from-the-middle-pleistocene-of-flores/#/portal/signup
The Voter's Self Defense System - Vote Smart Vote Smart provides free, unbiased, in-depth information about current officials, candidates, issues, legislation, and voting. Non-partisan and nonprofit since 1988. Hearing of the Finance Subcommittee, of the United States Senate Committee on Finance Location: Washington, DC Issues: Trade Agriculture and Food Today during a Finance Subcommittee hearing, U.S. Senator Maria Cantwell (D-WA) pressed the nation's top negotiator for agricultural trade issues to continue working to gain full access to Mexico's markets for American potatoes. Currently, American potatoes can only be exported to a region within 16 miles of the U.S.-Mexico border. Full access would expand the U.S. potato export market to Mexico by at least fourfold, from $24 million to $100 million in the next five years, according to U.S. potato industry estimates. "It is important to continue to focus on what we're doing to gain market access for products," Cantwell said today to United States Trade Representative's Chief Agricultural Negotiator Islam Siddiqui at today's hearing. "So I wanted to ask first Ambassador Isi Siddiqui about the potato market in Mexico. We've been very aggressive about trying to get Northwest product into that country and so what are we doing to make sure we're fully opening access and resolving the issues there?" Ambassador Siddiqui responded: "Senator, the potato issue with Mexico is a very high priority issue for both the USTR and USDA. …We have made it very clear to Mexico that we expect them to resolve this issue sooner than later. This 26 kilometer boundary that has been set was not based on science and there's adequate science to support our contention. … So we are hoping that Mexico can resolve this issue in the near future." Watch a video of Cantwell remarks at today's hearing.In December 2010, Cantwell sent a letter to Department of Agriculture Secretary Tom Vilsack urging an agreement with Mexico to allow American potato growers full access to Mexico's markets. Since Vilsack's trip to Mexico in December 2010, Mexico has agreed to move forward on opening up full access for American potato growers but progress has stalled. Today, Cantwell urged the USTR's top agriculture negotiator to keep pressure on Mexico to get this done. In 2003, Cantwell traveled to Mexico with the Washington Potato Commission to support expanded fresh potato trade with Mexico. Shortly thereafter, Mexico agreed to allow fresh potato exports into the 16-mile zone, with the expectation that all of Mexico would soon be open to American potato exports. Prior to the 2003 U.S.-Mexican agreement, Mexico allowed no fresh potato exports from the United States. Since the agreement, Mexico has become the second largest buyer of U.S. fresh potatoes, importing over $24 million worth in 2009.During today's hearing,Cantwell also pressed Ambassador Siddiqui and a U.S. Department of Agriculture (USDA) official to aggressively pursue resolving phytosanitary issues with South Korea to allow for U.S. apple exports to the South Korean market. "We're very excited obviously that the free trade agreement got signed and obviously we think it represents an opportunity for a lot of Washington products," Cantwell said to Ambassador Siddiqui. "Wine, probably all Northwest wine. But obviously there's lots of other products that we want to gain access. Apples being an important Northwest product and so just want to see what steps we need to take to make sure that they are going to get that access." "It appears that Korea has indicated that they will begin that pest risk assessment process to assess the risk for fire blight which is the first step in, unfortunately, a lengthy process in order to gain access," replied Darci Vetter, Deputy Under Secretary, Farm and Foreign Agriculture Services, USDA. "But at least that is now underway and they are beginning in concert with our regulatory officials to go through that process. So we have pushed for them to begin and they have indicated their willingness to do so. And we'll make sure they'll continue along in that process."Cantwell responded: "I hope that we're going to be aggressive about pursuing this in a timely fashion."Vetter: "We absolutely will."With the implementation of the U.S.-Korea Free Trade Agreement last month came the immediate elimination of dozens of tariffs on various agricultural products important to Washington state's economy. The deal is expected to provide a boost in exports for Washington state cherries, wine, beef, potatoes, hay, and wheat as soon as this year. However, apples are currently not allowed into South Korea for phytosanitary reasons. Washington state has a lot to gain from access to South Korea's market for apples. South Korea is an important export market for Washington state. The country is the fourth largest export market for Washington state goods, taking in $1.4 billion worth of agriculture exports from the state last year. Today, Cantwell questioned top agriculture officials on the United States' progress in gaining access to the Korean apple market.Opening up the Chinese market to American pears and apples and the South Korean market to apples would not only help Washington farmers, it would also provide more business for the state's ports and cargo transporters. Washington's ports and waterways are the closest to Asia and Alaska of all U.S. ports. Nearly $13 billion in food and agricultural products were exported through Washington ports in 2010, the third largest total in the United States. During today's hearing, Cantwell also questioned the vice president of the Northwest Horticultural Council, Mark Powers of Yakima, on the importance to local growers of expanding market access in China for pears and apples.China currently does not allow imports of American pears but the United States allows imports of Chinese Ya and fragrant pears. Washington state produces more pears than any other state in the nation, with a total crop value of $189 million in 2010. Currently China only accepts two varieties of U.S. apples -- red and golden delicious -- and South Korea accepts none due to phytosanitary reasons. In the Yakima Valley, the top apple producing area in the state, nearly two-thirds of the total apple growing acreage is devoted to apple varieties not currently sold at grocery stores in China. "Obviously they [China] do allow access to two varieties and yet if you look at the Yakima Valley and our production in general, two-thirds of that production, you know, we're looking at a variety of varietals that are not allowed in China," Cantwell said to Powers. "So what do we need to do to make sure that we get more than two varieties and get past these issues that are not, we don't need pest assessments; that's not what the problem is. So how do we get past this?"Powers responded: "It takes more than what we've been able to do so far. …I think there has to be something of value to China in order to move forward. And at this point what we know is that they have basically said that until we allow them to have access into U.S. for their apples we're not going to move forward on our apple access issue.""And where do you think we are with pears?" Cantwell asked Powers."On pears I'm much more optimistic," Powers said. "There is a clear recognition that China needs to allow us in the Northwest and California to have access for our pears going into China. They are working on a work plan. Agencies are involved on that so we're hopeful that perhaps by this next harvest season or if not then the next one that the technical issues will be resolved and exports will be allowed to move forward." The United States and China have had discussions about opening the pear market for nearly two decades to allow the import of fresh sand pears from China and the export of U.S. pears to China. However, since last November, talks between the two countries to open the pear market have gained momentum. Chinese and American officials are still discussing the details of mitigation measures for pests and disease. On February 15, during a meeting with Chinese Vice President Xi Jingping in Washington, D.C., Cantwell urged China to further open its market to American pears. Xi, who is likely to be the next leader of China, was meeting with U.S. Senators and Congressmen on Capitol Hill. Cantwell encouraged him to move forward on a deal that would enable Washington pears to be sold in China.Currently China only accepts two varieties of U.S. apples -- red and golden delicious. Washington state produces more than 20 different apple varieties. In the Yakima Valley, the top apple producing area in the state, nearly two-thirds of the total apple growing acreage is devoted to apple varieties not currently sold at grocery stores in China. The potential for apple export growth in China is huge. China has 1.3 billion people -- or one-fifth of the world's population -- and is already Washington state's tenth largest export market for apples.A complete transcript of Cantwell's remarks made at today's hearing follows:First Panel Senator Cantwell: Thank you Mr. Chairman and thanks for holding this important hearing. It is important to continue to focus on what we're doing to gain market access for products. And yes there's a lot that goes on between Portland and Seattle and we're very proud of our large export markets there. So I wanted to ask first Ambassador Isi Siddiqui about the potato market in Mexico. We've been very aggressive about trying to get Northwest product into that country and so what are we doing to make sure we're fully opening access and resolving the issues there? Ambassador Isi Siddiqui: Senator the potato issue with Mexico is a very high priority issue for both the USTR and USDA. Both Ambassador Kirk and Secretary Vilsack at USDA have raised the issue there after meeting with their counterparts in Mexico. We have made it very clear to Mexico that we expect them to resolve this issue sooner than later. This twenty-six kilometer boundary that has been set was not based on science and there's adequate science and justification to support our contention. So we'd like to have that issue resolved. As you know there was a panel, a scientific panel put together at the request of USDA which actually agreed in principal by and large with our contention on this issue. So we are hoping that Mexico can resolve this issue in the near future. Senator Cantwell: Do you think the panel of experts on…?Ambassador Isi Siddiqui: This was on potatoes; it's called North American Plant Protection Organization. The panel was assembled after Secretary Vilsack met with his counterpart, Secretary Mayorga, about I believe a year and a half ago. And so we are waiting for Mexico to make a move.Senator Cantwell: And when do you expect the finality of that report?Ambassador Isi Siddiqui: That is, Senator, hard for me to predict but it continues to be one of the highest priorities in terms of the issues we have with Mexico in agriculture, we will expect them to resolve.Senator Cantwell: Okay. And what are we doing with South Korea and phyto-sanitary issues as is it relates to getting apples into South Korea? What are the next steps? Ambassador Isi Siddiqui: Senator I don't have the information on….if you're talking about the pesticide MRL issue…but I don't have…Senator Cantwell: Well we're very excited obviously that the free trade agreement got signed and obviously we think it represents an opportunity for a lot of Washington products. Wine, probably all Northwest wine. But obviously there's lots of other products that we want to see gain access. Apples being an important Northwest product and so just want to see what steps we need to take to make sure that they are going to gain that access. Ambassador Isi Siddiqui: I was just given a note so I think this issue has to do, I suspect it's not pesticide, its fire blight. It's a disease of apples where many of the countries put these restrictions against apples but we'll continue to work with our counterparts in Korea to again, lift those restrictions based on science and international standards. This is not the first time we've faced if you remember we had similar issues with Japan before Japan allowed our market access for US apples. So this is an old issue which comes up in many countries which either do not have fire blight or if they have it they don't want to admit it. Ms. Darci Vetter: Senator if I might, it appears that Korea has indicated that they will begin that pest risk assessment process to assess the risk for fire blight which is the first step in, unfortunately, a lengthy process in order to gain access. But at least that is now underway and they will be working in concert with our regulatory officials to go through that process. So we have pushed for them to begin and they have indicated their willingness to do so. And we'll make sure that they continue along in that process.Senator Cantwell: I hope that we're going to be aggressive about pursuing this in a timely fashion. Ms. Darci Vetter: We absolutely will.Senator Cantwell: Thank you. Thank you Mr. Chairman. I know we're going to have a second panel so I have questions for them as well.Second Panel Senator Cantwell: Thank you Mr. Chairman, thank you for that courtesy. I greatly appreciate it and panelists thank you so much for your testimony. Mr. Crider I think you actually have a facility in Skagit County as well.Mr. Steve Crider: That's wine based yes. Senator Cantwell: Great. Well glad you're here and Amy's is good product so thank you for having facilities in our state as well. And Mr. Thompson I'm sending a letter to the agricultural committee this week in support of the MAP program, it's vitally important and hopefully this proposed legislation will include that.Mr. Steve Thomson: Thank you. I'd also like to point out that King Estate winery has a winery project in the Columbia Valley, Walla Walla, and we produce Washington wines as well. Senator Cantwell: All I have to say is there is good wine in the Northwest and that's good by us. So, Mr. Powers I wanted to talk about apples if we could. Thank you for representing the Northwest horticultural industry and all that you do. One of the issues I wanted to talk about was China. Obviously they do allow access to two varieties and yet if you look at the Yakima Valley and our production in general, two-thirds of that production, you know, we're looking at a variety of varietals that are not allowed in China. And we've had, you know, these issues in discussions you've heard what my questions were to our trade representatives trying to push forward on getting access to markets. So what do we need to do to make sure that we get more than two varieties and get passed these issues that are not, we don't need pest assessments that's not what the problem is so how do we get past this? Mr. Mark Powers: (off mic) seeking access for apples to China since the early 90s. And we do have access for two varieties. Really varietal issues are not at the heart of SPS questions, really. I mean if we have access for apples we should have access for all varieties of apples. However, China doesn't necessarily see it that way. And while the two technical agencies have been involved in dialogues for years. At a certain point, and this happened a few years ago, there was a recognition that this wasn't about a technical dialogue. This was basically a political matter. And I think that's at the heart of it. What we're facing. And we're not just facing it in China. We're facing it in many countries where the technical discussions can go on and on and on and often times do and what is needed is a political solution. Or a political trade-off at the end of the day that needs to occur. With China I think that's the same situation and it's a dicey one. Because as you may know the Chinese want access into the US for their apples. And so the US is working through the Animal Plant Health Inspection Service, is working through that pest assessment on Chinese apples and that process is unfolding. And we have legitimate concerns about the threat of invasive pests that might be present on apples coming from China. And so until that process works through, and we want to make sure that it is thorough, we're unlikely to see much in the way of advances on our other apple varieties into China. Simply because things aren't necessarily resolved on the basis of their technical merits. And I don't have a solution, quite frankly. I think that we will have to continue to be part of the dialogue between the two governments and hopefully the resolution will appear. But there is no real technical reason at this point related to fire blight that wouldn't allow our apples… Senator Cantwell: And so what do you think the solution is from a political perspective. How do you get the issue above you know the discussions that is on the technical points and up to the political level. What do you think that takes?Mr. Mark Powers: It takes more than what we've been able to do so far. I mean I don't have a great solution to that. I think there has to be something of value to China in order to move forward. And at this point what we know is that they have basically said that until we allow them to have access into US for their apples we're not going to move forward on our apple access issue. Senator Cantwell: And where do you think we are with pears?Mr. Mark Powers: On pears I'm much more optimistic. Again it's a long-standing issue, China has access to the US for two varieties of its pears and it's now, APHIS is now working on a third variety. That process is in rule-making at this point and appears to be moving forward. And there is a clear recognition that China needs to allow us in the Northwest and California to have access for our pears going into China. They are working on a work plan. Agencies are involved on that so we're hopeful that perhaps by this next harvest season or if not then the next one that the technical issues will be resolved and exports will be allowed to move forward.Senator Cantwell: Well I certainly hope so. And I thank you for your work in this area. Having visited Chinese supermarkets and seeing these products there you want to make sure we get access, that we get access and compensation for the products that are there. So I would hope that we could continue to make movement on these issues and find a solution that would give this wide variety of products from our state access to that market. So thank you Mr. Chairman I appreciate it.
https://justfacts.votesmart.org/public-statement/685874/hearing-of-the-finance-subcommittee-of-the-united-states-senate-committee-on-finance
PFAS: Medtech Restrictions and Impacts Article-PFAS: Medtech Restrictions and Impacts Image: Serdarbayraktar / iStock via Getty Images. Graphic courtesy of MD+DI <here is a image 7a1452f25bef8c21-4c6c34af3628a3ba> For medical device manufacturers that use PTFE or PFAS-containing chemicals in their processes, additional justification, including superiority to alternatives, may soon be a necessity. Per- and polyfluoroalkyl substances (PFAS) are a large, complex group of synthetic chemicals that have been used in consumer products around the world since about the 1950s. 1 PFAS are widely used, for example, on food packaging or cookware to produce a highly non-stick surface coating. We all have enjoyed making pancakes or eggs for breakfast that do not lose their aesthetic appearance due to their unwillingness to detach from the surface of the pan when needed. The inner surface of many microwave popcorn bags is also coated with PFAS to hinder sticking. 2 Similarly, many medical devices are coated with PTFE comprised of PFAS to make the surface of the device more hydrophobic and prevent adherence of cells, fluids, or blood components to the device. The PFAS family consists of thousands of known and developed compounds, but in general they all include a carbon chain of varying length, studded with fluorine atoms. This chemical structure makes them inherently inert substances, as the bond between carbon and fluorine is so strong it is not easily degradable and therefore can bioaccumulate. Exposure to PFAS can occur in many ways. Daily use of PFAS-coated consumer products, and the use of PFAS-containing medical devices, can lead to PFAS exposures that may bring about toxicological concern. In addition to this, due to their wide use and strong chemical bonds that make them stable over a long time, they are prone to accumulate in the environment when discarded. There, PFAS can leak into the soil, air, and ground water or accumulate in aquatic organisms. It can then be for consumed through, for instance, drinking water. But why are we so worried about PFAS? It has been shown that these chemicals have a relatively long half-life (ranging from 3.8 to 8.5 years), 3 which means that the PFAS can bioaccumulate in the human body, and therefore begin to impact the health of the population. To understand the full extent of exposure to PFAS, in the US alone, over 95% of adolescents and adults have measurable serum levels of various PFAS chemicals. 4 Over the past several years, there has been numerous publications on the potential impact of exposure to PFAS and the implications to adverse health effects, including altered metabolism, fertility, reduced fetal growth, increased risk of being overweight or obese, increased risk of some cancers, and reduced ability of the immune system to fight infections. 1 In 2017, the Swedish Chemicals Agency (KEMI) and the German Environment Agency (UBA) proposed a restriction of six PFAS variants under REACH 5 due to their link to a variety of health concerns, their very slow degradation profile, and bioaccumulation potential. This initiated the movement toward regulating their use and led to the final decision by the EU in February 2023 to ban, in phases, 200 PFAS. To note, although the actual ban only covers six long-chained PFAS chemicals — where the molecules consist of between 9 and 14 fluorinated carbon atoms — the number of PFAS being restricted is 200, since they can all be broken down into one of the banned six substances. 5 Furthermore, in March 2023, the US Environmental Protection Agency (EPA) announced a proposed PFAS drinking water regulation where the legally enforceable Maximum Contaminant Level (MCL) for the six PFAS variants is set at 1.0 up to 4.0 parts per trillion (or 4.0 ng/L). 6 Table courtesy of Nelson Labs <here is a image aec7db14ed21288b-f370eec3cd6eb64b> What do these restrictions and proposed MCLs mean for medical devices? When devices are evaluated for their safety during use, they are tested for their biocompatibility, and oftentimes due to short contact duration a detailed chemical analysis is not performed; as risks for any chemical, including PFAS, to leach out of a device and be exposed to the patient depends on the duration of contact. Knowing that there is a specified limit to a subgroup of PFAS, it might be easy to say that we need to start regulating their exposure for medical devices as well; as the standard approach to evaluating toxicological risks is based on known, standardized limits set forth by guidance document or governmental institutions. However, for example, understanding that the allowable limit of perfluorooctanoic acid (PFOA) (one of the six PFAS under regulation) is set at 4 ng/L in drinking water, should it and, most of all, can it be applied to a medical device with PFAS coating? Moreover, if we are mostly worried about environmental impact, where do we draw the line on allowable PFAS levels for the medical devices in general? For medical device manufacturers that do not use PTFE or other PFAS-containing chemicals in their processes, this movement may only mean an additional so-called “pen-and-paper” approach that clarifies that these substances are not used in their devices. However, if PFAS are present, additional justification for their necessity, including superiority to alternative chemicals may be on the horizon. This, along with the actual testing for the restricted PFAS substances may need to be figured out. Which sounds easier said than done, as the MCL set forth by the US EPA for drinking water seems so low that reaching those analytical thresholds for medical devices may prove to be potentially impossible. References: 1.https://www.niehs.nih.gov/health/topics/agents/pfc/index.cfm 2.https://ipen.org/documents/toxic-hazards-microwave-popcorn 3. Olsen GW, Burris JM, Ehresman DJ, Froehlich JW, Seacat AM, Butenhoff JL, Zobel LR. Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ Health Perspect. 2007 Sep;115(9):1298-305. doi: 10.1289/ehp.10009. PMID: 17805419; PMCID: PMC1964923.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1964923/ 4. Kato K., Wong L.Y., Jia L.T., Kuklenyik Z., Calafat A.M. Trends in exposure to polyfluoroalkyl chemicals in the U.S. Population: 1999–2008. Environ. Sci. Technol. 2011;45:8037–8045. doi: 10.1021/es1043613 5.https://chemsec.org/proposed-restriction-of-200-pfas-intended-to-prevent-regrettable-substitution/ 6.https://www.epa.gov/sdwa/and-polyfluoroalkyl-substances-pfas 7.https://echa.europa.eu/hot-topics/perfluoroalkyl-chemicals-pfas 8.https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32019R1021&from=EN 9.https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32020R0784&from=EN 10.https://www.ncsl.org/environment-and-natural-resources/per-and-polyfluoroalkyl-substances# 11.https://19january2017snapshot.epa.gov/assessing-and-managing-chemicals-under-tsca/and-polyfluoroalkyl-substances-pfass-under-tsca_.html 12.https://www.oecd.org/chemicalsafety/portal-perfluorinated-chemicals/countryinformation/european-union.htm 13.https://www.hbm4eu.eu/wp-content/uploads/2019/03/HBM4EU_D4.9_Scoping_Documents_HBM4EU_priority_substances_v1.0-PFAS.pdf TAGS: Manufacturing Processes
https://www.mddionline.com/manufacturing/pfas-medtech-restrictions-and-impacts?infscr=1&parent=14138
Nanoporous Hybrid Electrolytes for High-Energy Batteries Based on Reactive Metal Anodes (Journal Article) | DOE PAGES The U.S. Department of Energy's Office of Scientific and Technical Information Title: Nanoporous Hybrid Electrolytes for High-Energy Batteries Based on Reactive Metal Anodes Abstract Successful strategies for stabilizing electrodeposition of reactive metals, including lithium, sodium, and aluminum are a requirement for safe, high-energy electrochemical storage technologies that utilize these metals as anodes. Unstable deposition produces high-surface area dendritic structures at the anode/electrolyte interface, which causes premature cell failure by complex physical and chemical processes that have presented formidable barriers to progress. In this work, it is reported that hybrid electrolytes created by infusing conventional liquid electrolytes into nanoporous membranes provide exceptional ability to stabilize Li. Electrochemical cells based on γ-Al 2O 3ceramics with pore diameters below a cut-off value above 200 nm exhibit long-term stability even at a current density of 3 mA cm -2. The effect is not limited to ceramics; similar large enhancements in stability are observed for polypropylene membranes with less monodisperse pores below 450 nm. These results are critically assessed using theories for ion rectification and electrodeposition reactions in porous solids and show that the source of stable electrodeposition in nanoporous electrolytes is fundamental. Authors: Tu, Zhengyuan [1]; Zachman, Michael J. [1]; Choudhury, Snehashis [1]; Wei, Shuya [1]; Ma, Lin [1]; Yang, Yuan [2]; Kourkoutis, Lena F. [1]; Archer, Lynden A. [1] Cornell Univ., Ithaca, NY (United States) Colorado School of Mines, Golden, CO (United States) Publication Date: 2017-01-06 Research Org.: Cornell Univ., Ithaca, NY (United States). Energy Frontier Research Center (EFRC) Energy Materials Center at Cornell (EMC2) Sponsoring Org.: USDOE Advanced Research Projects Agency - Energy (ARPA-E); USDOE Office of Science (SC), Basic Energy Sciences (BES); National Science Foundation (NSF) OSTI Identifier: 1397227 Alternate Identifier(s): OSTI ID: 1401040 Grant/Contract Number: SC0001086; AR‐0000750; FOA‐001002 Resource Type: Accepted Manuscript Journal Name: Advanced Energy Materials Additional Journal Information: Journal Volume: 7; Journal Issue: 8; Related Information: Emc2 partners with Cornell University (lead); Lawrence Berkeley National Laboratory; Journal ID: ISSN 1614-6832 Publisher: Wiley Country of Publication: United States Language: English Subject: 36 MATERIALS SCIENCE; 25 ENERGY STORAGE; dendrite; ion rectification; lithium metal batteries; lithium transference number; nanoporous electrolyte Journal Article: Free Publicly Available Full Text Accepted Manuscript (Publisher) Accepted Manuscript (DOE) Publisher's Version of Record https://doi.org/10.1002/aenm.201602367 <here is a image 8eb7e35c676233ec-f6aaeb694846a0b0> Search WorldCat to find libraries that may hold this journal Citation Metrics: Cited by: 105 works Citation information provided by Web of Science Works referenced in this record: The Variation of Transference Numbers with Concentration journal, April 1954 Stokes, R. H. Journal of the American Chemical Society, Vol. 76, Issue 7 DOI: 10.1021/ja01636a086 Nanostructured Electrolytes for Stable Lithium Electrodeposition in Secondary Batteries journal, October 2015 Tu, Zhengyuan; Nath, Pooja; Lu, Yingying Accounts of Chemical Research, Vol. 48, Issue 11 DOI: 10.1021/acs.accounts.5b00427 Nanoporous Polymer-Ceramic Composite Electrolytes for Lithium Metal Batteries journal, September 2013 Tu, Zhengyuan; Kambe, Yu; Lu, Yingying Advanced Energy Materials, Vol. 4, Issue 2, Article No. 1300654 DOI: 10.1002/aenm.201300654 Ionic-Liquid-Nanoparticle Hybrid Electrolytes: Applications in Lithium Metal Batteries journal, November 2013 Lu, Yingying; Korf, Kevin; Kambe, Yu Angewandte Chemie International Edition, Vol. 53, Issue 2 DOI: 10.1002/anie.201307137 Issues and challenges facing rechargeable lithium batteries journal, November 2001 Tarascon, J.-M.; Armand, M. Nature, Vol. 414, Issue 6861, p. 359-367 DOI: 10.1038/35104644 “Direct” Detection and Separation of DNA Using Nanoporous Alumina Filters journal, November 2004 Vlassiouk, Ivan; Krasnoslobodtsev, Alexey; Smirnov, Sergei Langmuir, Vol. 20, Issue 23 DOI: 10.1021/la047959a A Dendrite-Free Lithium Metal Battery Model Based on Nanoporous Polymer/Ceramic Composite Electrolytes and High-Energy Electrodes journal, February 2015 Tu, Zhengyuan; Lu, Yingying; Archer, Lynden Small, Vol. 11, Issue 22 DOI: 10.1002/smll.201403568 Transference Number Approaching Unity in Nanocomposite Electrolytes journal, December 2006 Jorne, Jacob Nano Letters, Vol. 6, Issue 12 DOI: 10.1021/nl062182m The Li–CO2 battery: a novel method for CO2 capture and utilization journal, January 2013 Xu, Shaomao; Das, Shyamal K.; Archer, Lynden A. RSC Advances, Vol. 3, Issue 18 DOI: 10.1039/c3ra40394g Electrochemical aspects of the generation of ramified metallic electrodeposits journal, December 1990 Chazalviel, J. -N. Physical Review A, Vol. 42, Issue 12 DOI: 10.1103/PhysRevA.42.7355 Works referencing / citing this record: 3D-Printed Graphene Oxide Framework with Thermal Shock Synthesized Nanoparticles for Li-CO 2 Batteries journal, October 2018 Qiao, Yun; Liu, Yang; Chen, Chaoji Advanced Functional Materials, Vol. 28, Issue 51 DOI: 10.1002/adfm.201805899 Reviving Lithium-Metal Anodes for Next-Generation High-Energy Batteries journal, June 2017 Guo, Yanpeng; Li, Huiqiao; Zhai, Tianyou Advanced Materials, Vol. 29, Issue 29 Lin, Dingchang; Yuen, Pak Yan; Liu, Yayuan Advanced Materials, Vol. 30, Issue 32 Salvatierra, Rodrigo V.; López‐Silva, Gladys A.; Jalilov, Almaz S. Advanced Materials, Vol. 30, Issue 50 Li, Rui; Liu, Xiongjun; Wu, Ruoyu Advanced Materials, Vol. 31, Issue 49 Pu, Kaichao; Qu, Xiaolei; Zhang, Xin Advanced Science, Vol. 6, Issue 24 Luo, Jing; Fang, Chia-Chen; Wu, Nae-Lih Advanced Energy Materials, Vol. 8, Issue 2 Ionogel Electrolytes for High-Performance Lithium Batteries: A Review journal, January 2018 Chen, Nan; Zhang, Haiqin; Li, Li Advanced Energy Materials, Vol. 8, Issue 12 DOI: 10.1002/aenm.201702675 Vertically Aligned Lithiophilic CuO Nanosheets on a Cu Collector to Stabilize Lithium Deposition for Lithium Metal Batteries journal, April 2018 Zhang, Chen; Lv, Wei; Zhou, Guangmin Advanced Energy Materials, Vol. 8, Issue 21 DOI: 10.1002/aenm.201703404 Improved Rechargeability of Lithium Metal Anode via Controlling Lithium-Ion Flux journal, October 2018 Xiang, Jingwei; Yuan, Lixia; Shen, Yue Advanced Energy Materials, Vol. 8, Issue 36 DOI: 10.1002/aenm.201802352 Nanostructured Electrolytes for Stable Lithium Electrodeposition in Secondary Batteries Journal Article Tu, Zhengyuan; Nath, Pooja; Lu, Yingying; ... - Accounts of Chemical Research Secondary batteries based on lithium are the most significant energy storage technology for contemporary portable devices. The lithium ion battery (LIB) in widespread commercial use today is a compromise technology. It compromises high energy, high power, and design flexibility for long cell operating lifetimes and safety. Materials science, transport phenomena, and electrochemistry in the electrodes and electrolyte that constitute such batteries are areas of active study worldwide because significant improvements in storage capacity and cell lifetime are required to meet new demands, including the electrification of transportation and for powering emerging autonomous aircraft and robotics technologies. By replacing the carbonaceous more » host material used as the anode in an LIB with metallic lithium, rechargeable lithium metal batteries (LMBs) with higher storage capacity and compatibility with low-cost, high-energy, unlithiated cathodes such as sulfur, manganese dioxide, carbon dioxide, and oxygen become possible. Large-scale, commercial deployment of LMBs are today limited by safety concerns associated with unstable electrodeposition and lithium dendrite formation during cell recharge. LMBs are also limited by low cell operating lifetimes due to parasitic chemical reactions between the electrode and electrolyte. These concerns are greater in rechargeable batteries that utilize other, more earth abundant metals such as sodium and to some extent even aluminum. Inspired by early theoretical works, various strategies have been proposed for alleviating dendrite proliferation in LMBs. A commonly held view among these early studies is that a high modulus, solid-state electrolyte that facilitates fast ion transport, is nonflammable, and presents a strong-enough physical barrier to dendrite growth is a requirement for any commercial LMB. Unfortunately, poor room-temperature ionic conductivity, challenging processing, and the high cost of ceramic electrolytes that meet the modulus and stability requirements have to date proven to be insurmountable obstacles to progress. In this Account, we first review recent advances in continuum theory for dendrite growth and proliferation during metal electrodeposition. We show that the range of options for designing electrolytes and separators that stabilize electrodeposition is now substantially broader than one might imagine from previous literature accounts. In particular, separators designed at the nanoscale to constrain ion transport on length scales below a theory-defined cutoff, and structured electrolytes in which a fraction of anions are permanently immobilized to nanoparticles, to a polymer network or ceramic membrane are considered particularly promising for their ability to stabilize electrodeposition of lithium metal without compromising ionic conductivity or room temperature battery operation. Furthermore, we review recent progress in designing surface passivation films for metallic lithium that facilitate fast deposition of lithium at the electrolyte/electrode interface and at the same time protect the lithium from parasitic side reactions with liquid electrolytes. An enticing finding from both theory and experiment is that simple film-forming halide salt additives in a conventional liquid electrolyte can substantially extend the lifetime and safety of LMBs. « less Nanoporous separators for supercapacitor using activated carbon monolith electrode from oil palm empty fruit bunches Journal Article Nor, N. S. M.,; Deraman, M., E-mail: madra@ukm.my; Omar, R., E-mail: madra@ukm.my; ... - AIP Conference Proceedings Activated porous carbon electrode prepared from fibres of oil palm empty fruit bunches was used for preparing the carbon based supercapacitor cells. The symmetrical supercapacitor cells were fabricated using carbon electrodes, stainless steel current collector, H{sub 2}SO{sub 4} electrolyte, and three types of nanoporous separators. Cells A, B and C were fabricated using polypropylene, eggshell membrane, and filter paper, respectively. Electrochemical characterizations data from Electrochemical Impedance Spectroscopy, Cyclic Voltammetry, and Galvanic Charge Discharge techniques showed that specific capacitance, specific power and specific energy for cell A were 122 F g{sup −1}, 177 W kg{sup −1}, 3.42 Wh kg{sup −1}, cell more » B; 125 F g{sup −1}, 179 W kg{sup −1}, and 3.64 Wh kg{sup −1}, and cell C; 180 F g{sup −1}, 178 W kg{sup −1}, 4.27 Wh kg{sup −1}. All the micrographs from Field Emission Scanning Electron Microscope showed that the different in nanoporous structure of the separators lead to a significant different in influencing the values of specific capacitance, power and energy of supercapacitors, which is associated with the mobility of ion into the pore network. These results indicated that the filter paper was superior than the eggshell membrane and polypropylene nanoporous separators. However, we found that in terms of acidic resistance, polypropylene was the best nanoporous separator for acidic medium. « less Design principles for electrolytes and interfaces for stable lithium-metal batteries Journal Article Tikekar, Mukul D.; Choudhury, Snehashis; Tu, Zhengyuan; ... - Nature Energy The future of electrochemical energy storage hinges on the advancement of science and technology that enables rechargeable batteries that utilize reactive metals as anodes. With specific capacity more than ten times that of the LiC6 anode used in present-day lithium-ion batteries, cells based on Li-metal anodes are of particular interest. Effective strategies for stabilizing the anode in such cells are now understood to be a requirement for progress on exceptional storage technologies, including Li–S and Li–O2 batteries. Multiple challenges—parasitic reactions of Li-metal with liquid electrolytes, unstable and dendritic electrodeposition, and dendrite-induced short circuits—derailed early efforts to commercialize such lithium-metal batteries. more » Here we consider approaches for rationally designing electrolytes and Li-metal/electrolyte interfaces for stable, dendrite-free operation of lithium-metal batteries. On the basis of fundamental understanding of the failure modes of reactive metal anodes, we discuss the key variables that govern the stability of electrodeposition at the Li anode and propose a universal framework for designing stable electrolytes and interfaces for lithium-metal batteries. « less Using X-ray Microscopy To Understand How Nanoporous Materials Can Be Used To Reduce the Large Volume Change in Alloy Anodes Journal Article Cook, John B.; Lin, Terri C.; Detsi, Eric; ... - Nano Letters Tin metal is an attractive negative electrode material to replace graphite in Li-ion batteries due to its high energy density. However, tin undergoes a large volume change upon alloying with Li, which pulverizes the particles, and ultimately leads to short cycling lifetimes. Nevertheless, nanoporous materials have been shown to extend battery life well past what is observed in nonporous material. Despite the exciting potential of porous alloying anodes to significantly increase the energy density in Li-ion batteries, the fundamental physics of how nanoscale architectures accommodate the electrochemically induced volume changes are poorly understood. Here, operando transmission X-ray microscopy has been more » used to develop an understanding of the mechanisms that govern the enhanced cycling stability in nanoporous tin. We found that in comparison to dense tin, nanoporous tin undergoes a 6-fold smaller areal expansion after lithiation, as a result of the internal porosity and unique nanoscale architecture. The expansion is also more gradual in nanoporous tin compared to the dense material. The nanoscale resolution of the microscope used in this study is ~30 nm, which allowed us to directly observe the pore structure during lithiation and delithiation. We found that nanoporous tin remains porous during the first insertion and desinsertion cycle. This observation is key, as fully closed pores could lead to mechanical instability, electrolyte inaccessibility, and short lifetimes. Here, while tin was chosen for this study because of its high X-ray contrast, the results of this work should be general to other alloy-type systems, such as Si, that also suffer from volume change based cycling degradation. « less Fabrication of ultra-high aspect ratio silicon nanopores by electrochemical etching Journal Article Schmidt, Torsten; Zhang, Miao; Linnros, Jan; ... - Applied Physics Letters We report on the formation of ultra-high aspect ratio nanopores in silicon bulk material using photo-assisted electrochemical etching. Here, n-type silicon is used as anode in contact with hydrofluoric acid. Based on the local dissolution of surface atoms in pre-defined etching pits, pore growth and pore diameter are, respectively, driven and controlled by the supply of minority charge carriers generated by backside illumination. Thus, arrays with sub-100 nm wide pores were fabricated. Similar to macropore etching, it was found that the pore diameter is proportional to the etching current, i.e., smaller etching currents result in smaller pore diameters. To find the more » limits under which nanopores with controllable diameter still can be obtained, etching was performed at very low current densities (several μA cm{sup −2}). By local etching, straight nanopores with aspect ratios above 1000 (∼19 μm deep and ∼15 nm pore tip diameter) were achieved. However, inherent to the formation of such narrow pores is a radius of curvature of a few nanometers at the pore tip, which favors electrical breakdown resulting in rough pore wall morphologies. Lowering the applied bias is adequate to reduce spiking pores but in most cases also causes etch stop. Our findings on bulk silicon provide a realistic chance towards sub-10 nm pore arrays on silicon membranes, which are of great interest for molecular filtering and possibly DNA sequencing. « less
https://www.osti.gov/pages/biblio/1397227
IJMS | Free Full-Text | Role of Dehydrodiferulates in Maize Resistance to Pests and Diseases Phenolic esters have attracted considerable interest due to the potential they offer for peroxidase catalysed cross-linking of cell wall polysaccharides. Particularly, feruloyl residues undergo radical coupling reactions that result in cross-linking (intra-/intermolecular) between polysaccharides, between polysaccharides and lignin and, between polysaccharides and proteins. This review addresses for the first time different studies in which it is established that cross-linking by dehydrodiferulates contributes to maize’s defences to pests and diseases. Dehydrodiferulate cross-links are involved in maize defence mechanisms against insects such as the European, Mediterranean, and tropical corn borers and, storage pest as the maize weevil. In addition, cross-links are also discussed to be involved in genetic resistance of maize to fungus diseases as Gibberella ear and stalk rot. Resistance against insects and fungus attending dehydrodiferulates could go hand in hand. Quantitative trait loci mapping for these cell wall components could be a useful tool for enhancing resistance to pest and diseases in future breeding programs. Role of Dehydrodiferulates in Maize Resistance to Pests and Diseases by Rogelio Santiago * and Rosa A. Malvar Author to whom correspondence should be addressed. Int. J. Mol. Sci. 2010 , 11 (2), 691-703; https://doi.org/10.3390/ijms11020691 Received: 15 January 2010 / Accepted: 4 February 2010 / Published: 9 February 2010 Abstract Phenolic esters have attracted considerable interest due to the potential they offer for peroxidase catalysed cross-linking of cell wall polysaccharides. Particularly, feruloyl residues undergo radical coupling reactions that result in cross-linking (intra-/intermolecular) between polysaccharides, between polysaccharides and lignin and, between polysaccharides and proteins. This review addresses for the first time different studies in which it is established that cross-linking by dehydrodiferulates contributes to maize’s defences to pests and diseases. Dehydrodiferulate cross-links are involved in maize defence mechanisms against insects such as the European, Mediterranean, and tropical corn borers and, storage pest as the maize weevil. In addition, cross-links are also discussed to be involved in genetic resistance of maize to fungus diseases as Gibberella ear and stalk rot. Resistance against insects and fungus attending dehydrodiferulates could go hand in hand. Quantitative trait loci mapping for these cell wall components could be a useful tool for enhancing resistance to pest and diseases in future breeding programs. Keywords: plant cell walls ; ferulic acid ; dehydrodimers ; ; corn borer ; maize weevil ; Gibberella ear ; stalk rot 1. Introduction In the Poaceae family (grasses and cereals) the primary cell wall is built of a skeleton of cellulosic microfibrils embedded in a matrix composed mainly of hemicelluloses (arabinoxylans, xyloglucan and, in some tissues, mixed-linked glucans) and smaller amounts of pectins and glycoproteins [ 1 ]. In addition, grasses have unusually high concentrations of ferulic and p -coumaric acids ester-linked to cell wall polymers ( Figure 1 ) [ 2 ]. Depending on the tissue and its stage of development, cell walls in C4 grasses tend to have higher levels of hydroxycinnamic acids than C3 grasses; as C4, maize and sorghum cell walls can contain up to 4% ferulates (monomers plus dimers) and up to 3% p -coumarate [ 3 , 4 ]. p -Coumarate is mainly esterified to the γ–position of phenylpropanoid sidechains of S units in lignin [ 5 – 7 ]. Although very small quantities of p -coumarate are esterified to arabinoxylans in immature tissues, most p -coumarate accretion occurs in tandem with lignification [ 8 , 9 ], making p -coumarate accumulation a convenient indicator of lignin deposition. Ferulates are intracellularly esterified to the C5-hydroxyl of α- l -arabinose sidechains of xylans and deposited into primary and secondary walls of a variety of grass tissues [ 10 – 12 ]. During cell wall deposition and lignification, xylans are cross-linked by peroxidase-mediated coupling of ferulate monomers into a complex array of dimers and trimers and by extensive copolymerization of these ferulates into lignin ( Figure 1 ) [ 13 ]. Figure 1. Chemical structures of cell wall phenylpropanoids identified in diverse maize tissues (modified from Santiago et al. [ 56 ]). 2. Cell Wall Cross-Linking by Dehydrodiferulates The structural and functional roles of plant cell walls are controlled by the composition and organization of individual wall components. Cross-linking of cell wall components is expected to have a marked influence on numerous wall properties such as accessibility, extensibility, plasticity, digestibility, and adherence. Phenolic esters have attracted considerable interest due to the potential they provide for peroxidase catalysed cross-linking of cell wall polysaccharides [ 14 , 15 ]. Dimers of ferulic and p -coumaric acids can be generated enzymatically by peroxidase (5,5’-diferulic acid) or through photochemical reactions (truxillic and trucinic acids) [ 16 ]. In particular, feruloyl residues undergo radical coupling reactions that result in cross-linking between polysaccharides (intra-/intermolecularly) ( Figure 2 ) [ 4 , 17 ], between polysaccharides and lignin [ 18 , 19 ] and, between polysaccharides and proteins [ 20 ]. Figure 2. Cell wall cross-linking between two arabinoxylans chains mediated by dehydrodiferulates (DFAs) (from Santiago et al. [ 57 ]). Formation of oxidatively coupled ferulate dimers was first described in 1971 [ 21 ]. Since then, a diverse range of dehydrodiferulates have been detected in various plant materials and were characterized as 8-5′, 5-5′, 8-O-4′, 8-8′, and 4-O-5′ coupled dehydrodimers [ 22 – 30 ]. In addition, certain specific isomers of triferulic acid [ 31 – 35 ] and tetraferulic acid [ 33 ] have been isolated and structurally elucidated from primary cell walls in grass and cereal species, particularly from maize bran. Cross-linking of wall polysaccharides is of considerable interest in food chemistry, food technology and nutritional sciences, but also in neighbouring disciplines like agricultural chemistry and plant physiology [ 36 ]. Ferulate dimers have been considered responsible for phenomena such as terminating the expansion of cell wall growth [ 24 ], cell stiffening [ 37 ], cell wall adhesion influencing the cripness and softening fruits and vegetables [ 38 – 41 ], gelling properties of pectins and arabinoxylans [ 39 , 42 , 43 ], insolubility of cereal dietary fibers [ 30 ], and limited cell wall degradability by ruminants [ 3 , 13 , 44 , 45 ]. Cross-linking by dehydrodiferulates also contributes to plants’ defences to pest and diseases as revised in detail in the current review. 3. Role of Dehydrodiferulates Compounds in Maize Resistance to Pests 3.1. Corn Borer Resistance Lepidopteran stalk boring larvae cause significant economic losses to maize ( Zea mays L.) production throughout the world. One of the major corn borer pests is the European corn borer (ECB) [ Ostrinia nubilalis (Hübner)] [ 46 ]. This pest reduces maize yield not only damaging kernels by direct feeding, but also tunneling stalks which cause plant lodging at harvest. ECB also acts as a vector for several Fusarium stalk-rot fungi which lead to a further destruction of the stalk. Infestation begins at an early phenological stage of the maize plant. First generation larvae fed on the whorl leaf tissues of juvenile plants, while subsequent generations attack maize at its reproductive stage. The main importance is on later generations larvae that feed on the stalk. In studies of borer resistance, the content of isomers of dehydrodiferulic acids (DFAs) in corn leaves was highly and negatively correlated across genotypes of maize with field leaf damage caused by ECB [ 47 ]. In a later study, those authors suggest that early cell wall fortification through phenolic cross-linking of hemicellulose by diferulic acid increases leaf tissue toughness, and therefore, decreases neonate larvae penetration into leaf tissues [ 48 ]. Additional confirmation was provided by the observation that DFA content of maize increased in different tissues over cycles of selection for borer resistance in the Iowa stiff stalk synthetic BS9 [ 49 ]. High fibre content alone may increase the bulk density of the tissue, but in presence of phenolic-carbohydrate complexes, fibre strength may increase, providing a tougher physical barrier to restrict insect penetration and render nutrients within the tissues less accessible [ 49 ]. Besides, in the same study, both DFA and p -coumaric acids were negatively related with damage parameters for rind, node and pith tissue [ 49 ]. Ramputh [ 50 ] extended previous research with the observation that resistance to important tropical and subtropical stem borers could be sensitive to early cell wall fortification by phenolic cross-linking. Host plant resistance in maize to the southwestern corn borer ( Diatraea grandiosella Dyar) and the sugarcane borer [ Diatraea saccharalis (Fabricius)] was investigated in relation to bound phenolics in the leaf cell wall. In that study, dehydrodiferulic acids were found to be significantly correlated to tissue toughness and significant negative correlations were found between DFA and leaf feeding damage by both insects. The oxidative potential of H 2 O 2 to contribute to cell wall strengthening could retard insect feeding through the oxidative cross linking of specific cell wall structural proteins [ 51 ], polymerization of coniferyl alcohol affecting lignin formation [ 52 ] and cell wall peroxidase mediated cross linking of hemicellulose microfibrils with diferulic acid DFA [ 53 ]. A molecular transformation of maize was employed to increase cell wall hydrogen peroxide in order to enhance DFA formation and European corn borer resistance [ 54 ]. Corn transformed with a wheat oxalate oxidase gene (germin) under the control of the rice promoter elements (pActOXO) expressed the enzyme activity constitutively. Field testing showed that the transgenic maize exhibited more resistance to ECB than the non-transgenic counterpart. However, the transformation did not increase DFA formation as predicted, and resistance was associated with the direct effects of H 2 O 2 on insect physiology. In a subsequent study was found that transgenic oxalate oxidase elicits defence responses by generation of H 2 O 2 , increasing soluble phenolics contents, and activating jasmonic acid signaling [ 55 ]. Recent studies evaluated the putative role of dehydrodiferulate contents in maize pith and leaf-sheaths in the resistance against the Mediterranean corn borer (MCB) ( Sesamia nonagrioides Lef.) [ 56 – 58 ]. Three hydroxycinnamates, p -coumaric, trans -ferulic, and cis -ferulic acids, and three dehydrodiferulates, 8-5′, 8-O-4′, and 8-5′ b (benzofuran form), were identified [ 56 ]. The amount of all these compounds in the pith was correlated with the resistance level in the genotypes, with the resistant inbreds having the highest concentrations [ 56 ]. In addition, significant negative correlations were found between larvae weight reared on leaf-sheaths and diferulic acid content for six genotypes of the seven evaluated [ 57 ]. The genotypes used in those studies were a limited number of inbred lines with diverse background and perhaps exhibiting different mechanisms of defence. Therefore, the real relationship between DFA content and resistance was not established because it could be biased by background differences among genotypes. In order to remove this bias, several cycles of selection for MCB resistance derived from the synthetic population EPS12 were evaluated for cell-wall phenolic concentrations in the pith tissues [ 58 ]. In this sense, higher concentrations of total DFAs were associated with less tunnel length and number of larvae per stem [ 58 ]. Santiago and co-workers [ 58 ] showed new and concrete evidence that the cell-wall bound phenolics could have a significant role in the resistance to the MCB, although current development of divergent recurrent selection cycles maximizing differences for DFA concentrations will definitively clarify the role of DFAs in the resistance to the Mediterranean corn borer larvae. In 2007, the divergent selection for total DFAs content in the pith was initiated from the F 2 derived from the cross of two inbred lines, CO125 (high DFA content) and PB130 (low DFA content). 3.2. Maize Weevil Resistance The maize weevil (MW) ( Sitophilus zeamais Motsch.) is a destructive insect feeding on stored maize throughout the world [ 59 ]. Subsistence farmers in tropical and subtropical agroecosystems often experience grain damage exceeding 30% during on-farm storage [ 60 ]. Various biochemical and physical characteristics have been identified as mechanisms of kernel resistance to MW [ 61 – 65 ]. Phenolic acids have been studied extensively as biochemical components correlated with resistance and found to act in two ways: through mechanical resistance (cell wall bound hydroxycinnamic acids) and antibiosis (phenolic acid amides) in the pericarp and aleurone layer, respectively [ 65 ]. Arnason and coworkers [ 64 ] has demonstrated that MW resistant genotypes have higher concentrations of total DFAs in the whole kernel. These dimers probably contribute to the observed correlations between phenolic acid content and grain hardness [ 65 , 66 ]. To understand the importance of dehydrodiferulates in MW resistance, a detailed analysis of DFAs in the pericarp was conducted by García-Lara and co-workers [ 67 ]. The analysis revealed the presence of three major simple phenolic acids ( p -coumaric acid, cis -ferulic acid and trans -ferulic acid) and four isomers of DFAs (8-5′ DFA, 5-5′ DFA, 8-O-4′ DFA, 8-5′b DFA). In that study, DFA accounted for 8% of the total phenolic acid content, with resistant genotypes having a three-fold higher level than susceptible genotypes. On the basis of step-wise regression models, 5-5′ DFA, 8-O-4′ DFA, p -coumaric acid, and trans -ferulic acid were the most important phenolic acids in explaining phenotypic variance for MW resistance. Besides, weevil susceptibility was negatively correlated with total DFAs. In conclusion, maize genotypes with elevated levels of cell wall cross-linking components in the pericarp were more resistant to MW [ 67 ]. 4. Role of Dehydrodiferulates Compounds in Maize Resistance to Fungal Diseases 4.1. Gibberella Ear Rot Resistance Fusarium graminearum Schwabe, [teleomorph Gibberella zeae (Schwein.) Petch], is responsible for one of the major fungal diseases occurring sporadically in cool and temperate maize cultivation areas [ 68 ]. This disease known as Gibberella ear rot, is a cause of great concern because of the ability of this mold to produce mycotoxins, such as trichothecenes and zearalenone that affect grain quality and also represent a potential risk for livestock and human health [ 69 – 71 ]. Previous studies on maize indicate that phenolic compounds such as inducible flavones in silks [ 72 ] and structural phenolics in kernels [ 73 , 74 ] may be involved in maize resistance to ear rot. Attending to these results, Bily and co-workers [ 75 ] determined the concentrations of dehydrodimers of ferulic acid in the pericarp and aleurone tissues of some maize genotypes of varying susceptibility. Significant negative correlations were found between disease severity and total DFAs content, and even stronger negative correlations were observed between total DFA and ergosterol, a fungal component of the cell membrane which is an indicator of fungal biomass in infected plant tissues [ 75 ]. DFAs are known to stabilize the wall at the early stage of plant development [ 76 ]. It is also known that DFAs impede in vitro cell-wall degradation by fungal hydrolases, such as Aspergillus esterases [ 77 ]. In Bily’s study [ 75 ], initial penetration in the ears was mechanically facilitated, but mycelial progression on intact neighboring grains was reduced in maize genotypes with high levels of DFAs. Besides, F. graminearum , as many other pathogenic fungi, has a large spectrum of extracellular enzymatic activities [ 78 , 79 ], and the activity of fungal esterases can release free forms of ferulic ester from maize tissues. Once released, free ferulate may inhibit the ability of Fusarium to produce mycotoxins [ 80 ]. 4.2. Gibberella Stalk Rot Resistance Fusarium graminearum is only one of many species responsible for stalk rot, but is considered to possess the highest pathogenicity (the ability to cause disease) and aggressiveness (the amount of disease caused) [ 81 , 82 ]. These fungal organisms decay pith tissue in the lower stalk internodes, which can often result in premature plant death, poor kernel filling and/or lodging. Besides, trichothecenes such as deoxynivalenol (DON) is water soluble, and translocation in the phloem as a bulk flow of solution is assumed to occur [ 81 , 83 ]. DON produced in the stalk or ear of maize can be found in tissues not invaded by F. graminearum [ 84 , 85 ]. Phenolic compounds have been shown to inhibit in vitro growth of several fungal genera [ 86 , 87 ]; significant inhibitory effects were reported for Fusarium species [ 73 , 88 , 89 ]. In addition, evidence strongly suggests that esterification of phenols to cell-wall materials is a common theme in the expression of resistance [ 73 – 75 , 90 ]. Therefore, Santiago and co-workers [ 91 ] tried to determine if a relationship exists between phenolic compounds and resistance to stalk infection by F. graminearum monitoring field-grown inbred lines of maize after artificial inoculation. Reinforcing the possible role of DFAs in fungal resistance, significant negative correlations between DFAs contents and disease severity ratings four days after inoculation were found. The abundance of DFAs in cell walls makes polysaccharides less sensitive to the cell wall-degrading enzymes of pathogens [ 92 , 93 ]. In this case, the DFAs could function in the pith tissues as preformed resistance barriers prior to infection. Low contents of DFAs at early stages of infection would leave time for the pathogen to develop abundantly and to produce toxins, breaking a possible resistance response and leading to typical symptoms of disease. 5. Conclusions In summary, cross-linking of plant cell wall polymers by dehydrodiferulates contributes consistently to the maize’s defence mechanisms against pests and diseases. Dehydrodiferulate cross-links are involved in the defence mechanisms against insects such as the European and Mediterranean corn borer, the southwestern corn borer, the sugarcane borer, and the maize weevil. In addition, DFA cross-links are also discussed to be involved in genetic resistance of maize to Gibberella ear rot and stalk rot. These compounds have been related with resistance in a wide range of maize tissues as leaf, kernel, rind, or pith. The role of dehydrodiferulates in the cell wall fortification has been noted in the literature, and this structural resistance could be more difficult to overcome than an antibiotic defence. Resistance against insects and fungi due to dehydrodiferulates content could go hand in hand. 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Role of Dehydrodiferulates in Maize Resistance to Pests and Diseases. Int. J. Mol. Sci. 2010, 11, 691-703. https://doi.org/10.3390/ijms11020691 AMA Style Santiago R, Malvar RA. Role of Dehydrodiferulates in Maize Resistance to Pests and Diseases. International Journal of Molecular Sciences. 2010; 11(2):691-703. https://doi.org/10.3390/ijms11020691 Chicago/Turabian Style Santiago, Rogelio, and Rosa A. Malvar. 2010. "Role of Dehydrodiferulates in Maize Resistance to Pests and Diseases" International Journal of Molecular Sciences11, no. 2: 691-703. https://doi.org/10.3390/ijms11020691
https://www.mdpi.com/1422-0067/11/2/691/htm
Cloud Computing Reduces Uncertainties in Quality-of-Service-Matching! | Request PDF Request PDF | Cloud Computing Reduces Uncertainties in Quality-of-Service-Matching! | Cloud computing resulted in a continuously growing number of provided software services to be used by consumers. Brokers discover services that... | Find, read and cite all the research you need on ResearchGate Cloud Computing Conference Paper Cloud Computing Reduces Uncertainties in Quality-of-Service-Matching! September 2014 Communications in Computer and Information Science 508 DOI: 10.1007/978-3-319-14886-1_15 Conference: Proceedings of the 2nd International Workshop on cloud Service Brokerage (CSB 2014) At: Manchester, United Kingdom Authors: ABB, Deutschland Steffen Becker Universität Stuttgart Abstract Cloud computing resulted in a continuously growing number of provided software services to be used by consumers. Brokers discover services that fit best to consumers’ requirements by matching Qualityof- Service (QoS) properties. In order to negotiate Service-Level Agreements (SLAs), a provider has to determine the provided QoS based on QoS analyses. However, the risk for the provider to violate the SLA is high as the service’s actual quality can deviate from the specified QoS due to uncertainties that occur during the provider’s quality analysis. In this paper, we discuss current software engineering paradigms like cloud computing and service-oriented computing with respect to the amount of uncertainty they induce into service matching and SLA negotiations. As a result, we explain, why cloud computing reduces such uncertainties. ResearchGate has not been able to resolve any citations for this publication. The Internet of Services and USDL Article Full-text available Feb 2012 Orestis Terzidis Daniel Oberle Andreas Friesen Alistair P. Barros A prominent research focus, especially in the context of EU public funding, has been the systematic use of the Internet for new ways of value creation in the services sector. This idea of service networks in the Internet, frequently dubbed the Internet of Services orWeb service ecosystems, wants to make services tradable in digital media. In order to enable communication and trade between providers and consumers of services, the Internet of Services requires a standard that creates a “commercial envelope” around a service. This is where the Unified Service Description Language (USDL) comes into play as a normative and balanced unification of service information. The unified description established by USDL is machineprocessable, considers technical and business aspects of a service as well as functional and non-functional attributes. Conference Paper Full-text available Jun 2013 Matthias Becker Markus Luckey Steffen Becker Self-adaptation allows continuously running software systems to operate in changing and uncertain contexts while meeting their requirements in a broad range of contexts, e.g., from low to high load situations. As a consequence, requirements for self-adaptive systems are more complex than requirements for static systems as they have to explicitly address properties of the self-adaptation layer. While approaches exist in the literature to capture this new type of requirements formally, their achievement cannot be analyzed in early design phases yet. In this paper, we apply RELAX to formally specify non-functional requirements for self-adaptive systems. We then apply our model-based SimuLizar approach for a semi-automatic analysis to test whether the self-adaptation layer ensures that these non-functional requirements are met. We evaluate our approach on the design of a proof-of-concept load balancer system. As this evaluation demonstrates, we can iteratively improve our system design by improving unsatisfactory self-adaption rules. A Survey of Fuzzy Service Matching Approaches in the Context of On-The-Fly Computing Conference Paper Full-text available Jun 2013 Marie Platenius-Mohr Markus von Detten Steffen Becker Gregor Engels In the last decades, development turned from monolithic software products towards more flexible software components that can be provided on world-wide markets in form of services. Customers request such services or compositions of several services. However, in many cases, discovering the best services to address a given request is a tough challenge and requires expressive, gradual matching results, considering different aspects of a service description, e.g., inputs/ouputs, protocols, or quality properties. Furthermore, in situations in which no service exactly satisfies the request, approximate matching which can deal with a certain amount of fuzziness becomes necessary. There is a wealth of service matching approaches, but it is not clear whether there is a comprehensive, fuzzy matching approach which addresses all these challenges. Although there are a few service matching surveys, none of them is able to answer this question. In this paper, we perform a systematic literature survey of 35 (out of 504) service matching approaches which consider fuzzy matching. Based on this survey, we propose a classification, discuss how different matching approaches can be combined into a comprehensive matching method, and identify future research challenges. Article Full-text available Jan 2009 J SYST SOFTWARE Steffen Becker Heiko Koziolek Ralf H. Reussner One aim of component-based software engineering (CBSE) is to enable the prediction of extra-functional properties, such as performance and reliability, utilising a well-defined composition theory. Nowadays, such theories and their accompanying prediction methods are still in a maturation stage. Several factors influencing extra-functional properties need additional research to be understood. A special problem in CBSE stems from its specific development process: Software components should be specified and implemented independently from their later context to enable reuse. Thus, extra-functional properties of components need to be specified in a parametric way to take different influencing factors like the hardware platform or the usage profile into account. Our approach uses the Palladio component model (PCM) to specify component-based software architectures in a parametric way. This model offers direct support of the CBSE development process by dividing the model creation among the developer roles. This paper presents our model and a simulation tool based on it, which is capable of making performance predictions. Within a case study, we show that the resulting prediction accuracy is sufficient to support the evaluation of architectural design decisions. Classifying Software Component Interoperability Errors to Support Component Adaption Conference Paper Full-text available May 2004 Steffen Becker Sven Overhage Ralf H. Reussner This paper discusses various classifications of component interoper- ability errors. These classifications aim at supporting the automation of component adaptation. The use of software components will only demonstrate beneficial, if the costs for component deployment (i.e., acquisition and composition) are con- siderably lower than those for custom component development. One of the main reasons for the moderate progress in component-based software engineering are the high costs for component deployment. These costs are mainly caused by adapt- ing components to bridge interoperability errors between unfitting components. One way to lower the costs of component deployment is to support component adaptation by tools, i.e., for interoperability checks of (semi-)automated adaptor generation. This automation of component adaptation requires a deep understand- ing of component interoperability errors. In particular, one has to differentiate between different classes of interoperability errors, as different errors require dif- ferent adaptors for resolving. Therefore, the presented classification of component interoperability errors supports the automation of component adaptation by aiding automated interoperability problem detection and semi-automated adaptor gener- ation. The experience gained from already implemented solutions for a specific class of interoperability errors provides hints for the solution of similar problems of the same class. Three Performance Models at Work: A Software Designer Perspective Article Full-text available Jul 2004 Electron Notes Theor Comput Sci Vittorio Cortellessa Antinisca Di Marco Paola Inverardi This chapter focuses on the transformational approaches from software system specifications to performance models. These transformations aim at filling the gap between the software development process and the performance analysis by generating performance model ready to be validated from the software models. Three approaches are discussed in detail presenting their foundations and their application to an e-commerce case study. Moreover, the chapter briefly reviews representatives of other transformational approaches present in the literature. All the presented approaches are discussed with respect to a set of relevant dimensions such as software specification, performance model, evaluation methods and level of automated support for performance prediction. Towards SLA-Supported Resource Management Conference Paper Full-text available Sep 2006 Lect Notes Comput Sci Peer Hasselmeyer Bastian Koller Lutz Schubert Philipp Wieder Achievements and experiences in projects with focus on resource management have shown that the goals and needs of High Performance Computing service providers have not or only inadequately been taken into account in Grid research and development. Mapping real-life business behaviour and workflows within the service provider domain to the electronic level implies focusing on the business rules of the provider as well as on the complexity of the jobs and the current state of the HPC system. This paper describes an architectural approach towards a business-oriented and Service Level Agreement-supported resource management, valuable for High Performance Computing providers to offer and sell their services. With the introduction of a Conversion Factory the authors present a component that is able to combine the Service Level Agreement, the system status, and all business objectives of the provider in order to address the business needs of service providers in the Grid. Making components contract aware Article Full-text available Aug 1999 COMPUTER Antoine Beugnard Jean-Marc Jézéquel Noël Plouzeau Damien Watkins Components have long promised to encapsulate data and programs into a box that operates predictably without requiring that users know the specifics of how it does so. Many advocates have predicted that components will bring about widespread software reuse, spawning a market for components usable with such mainstream software buses as the Common Object Request Broker Architecture (CORBA) and the Distributed Component Object Model (DCOM). In the Windows world, at least, this prediction is becoming a reality. Yet recent reports indicate mixed results when using and reusing components in mission-critical settings. Such results raise disturbing questions. How can you trust a component? What if the component behaves unexpectedly, either because it is faulty or simply because you misused it? Before we can trust a component in mission-critical applications, we must be able to determine, reliably and in advance, how it will behave. In this article the authors define a general model of sofware contracts and show how existing mechanisms could be used to turn traditional components into contract-aware ones Managing Imprecise Criteria in Cloud Service Ranking with a Fuzzy Multi-Criteria Decision Making Method. Conference Paper Sep 2013 Ioannis Patiniotakis Stamatia Rizou Yiannis Verginadis Gregoris Mentzas The increase of cloud technology solutions has made the evaluation and selection of desired cloud services, a cumbersome task for the user. In particular, the lack of standard mechanisms that allow the comparison of cloud service specifications against user requirements taking into account the implicit uncertainty and vagueness is a major hindrance during the cloud service evaluation and selection. In this paper, we discuss an alternative classification of metrics used for ranking cloud services based on their level of fuzziness and present an approach that allows cloud service evaluation based on a heterogeneous model of service characteristics. Our approach allows the multi-objective assessment of cloud services in a unified way, taking into account precise and imprecise metrics. We use fuzzy numbers to model the imprecise service characteristics and vague user preferences and we validate a fuzzy AHP approach that solves the problem of service ranking. Uncertainties in the modeling of self-adaptive systems: A taxonomy and an example of availability evaluation Conference Paper Mar 2014 Diego Perez-Palacin Raffaela Mirandola The complexity of modern software systems has grown enormously in the past years with users always demanding for new features and better quality of service. Besides, software is often embedded in dynamic contexts, where requirements, environment assumptions, and usage profiles continuously change. As an answer to this need, it has been proposed the usage of self-adaptive systems. Self-adaptation endows a system with the capability to accommodate its execution to different contexts in order to achieve continuous satisfaction of requirements. Often, self-adaptation process also makes use of runtime model evaluations to decide the changes in the system. However, even at runtime, context information that can be managed by the system is not complete or accurate; i.e, it is still subject to some uncertainties. This work motivates the need for the consideration of the concept of uncertainty in the model-based evaluation as a primary actor, classifies the avowed uncertainties of self-adaptive systems, and illustrates examples of how different types of uncertainties are present in the modeling of system characteristics for availability requirement satisfaction. Component Software : Beyond Object-Oriented Programming Book Jan 2002 Clemens Alden Szyperski Component Software: Beyond Object-Oriented Programming explains the technical foundations of this evolving technology and its importance in the software market place. It provides in-depth discussion of both the technical and the business issues to be considered, then moves on to suggest approaches for implementing component-oriented software production and the organizational requirements for success. The author draws on his own experience to offer tried-and-tested solutions to common problems and novel approaches to potential pitfalls. Anyone responsible for developing software strategy, evaluating new technologies, buying or building software will find Clemens Szyperski's objective and market-aware perspective of this new area invaluable. View Show abstract Fuzzy Service Matching in On-The-Fly Computing Article Aug 2013 Marie Platenius-Mohr In the future vision of software engineering, services from world-wide markets are composed automated in order to build custom-made systems. Supporting such scenarios requires an adequate service matching approach. Many existing approaches do not fulfill two key requirements of emerging concepts like On-The-Fly-Computing, namely (1) comprehensiveness, i.e., the consideration of different service views that cover not only functional properties, but also non-functional properties and (2) fuzzy matching, i.e., the ability to deliver gradual results in order to cope with a certain extent of uncertainty, incompleteness, and tolerance ranges. In this paper, I present a fuzzy matching process that distinguishes between different fuzziness sources and leverages fuzziness in different matching steps which consider several service views, e.g., behavior and quality properties. Model Transformations in Non-Functional Analysis Conference Paper Jun 2012 Steffen Becker The quality assessment of software design models in early development phases can prevent wrong design decisions on the architectural level. As such wrong decisions are usually very cost-intensive to revert in late testing phases, model-driven quality predictions offer early quality estimates to prevent such erroneous decisions. By model-driven quality predictions we refer to analyses which run fully automated based on model-driven methods and tools. In this paper, we give an overview on the process of model-driven quality analyses used today with a special focus on issues that arise in fully automated approaches. From software models to performance models V Cortellessa Di Marco A Inverardi Conference Paper A Context-Based Strategy for SLA Negotiation in the IoT Environment March 2019
https://www.researchgate.net/publication/265607152_Cloud_Computing_Reduces_Uncertainties_in_Quality-of-Service-Matching
Mississippi Land Company Articles of Agreement, 3 June 1763 Mississippi Land Company Articles of Agreement, 3 June 1763 Mississippi Land Company Articles of Agreement, 3 June 1763 Mississippi Land Company Articles of Agreement We whose names are underwritten do agree to form a Body of Adventurers by the name of the Mississipi Company, with aview to explore and settle some Tracts of Land upon the Mississipi and its Waters; and the better to succeed in this design have determined on the following Rules and Regulation’s. First. it is proposed that the Company shall consist of Fifty Members and no more,1who are to contribute equally toward the expence of sending an Agent to England to obtain from the Crown a Grant of Lands on the Mississipi aforesaid and its Waters to the amount and upon the terms hereafter mentiond.2 1st Every single Adventurer to have 50,000 Acres of Land for a share— 2. The Lands to lye on the Mississipi and its Waters 3. The Settlement to be protected from the Insults of the Savages, by the assistance of His Majestys Forces disposed of in such manner as the Ministry shall think proper 4. The Lands to be obtained if possible clear of all Composition Money, Expences and Quit Rents for the space of Twelve Years or longer upon Condition that we settle the same in that time if not interrupted by the Savages 3 That the Subscribers begin to sollicit the Grant without further delay before the number to be admitted is made up; and the Adventurers who join to be liable for an equal share of all expences incurred— That the Lands obtained by such Grant be not held in Jointenancy but that every adventurer hold his respective share to himself and his Heirs in Fee simple, any thing in the said Grant to the Contrary notwithstanding. That a General Meeting of the Company be annually had on the [ ]day of [ ]at [ ]4and to consist of a Majority of the Members residing in Virginia and Maryland who shall have power and Authority to determine by a Majority of the Members so met all matters relative to the purposes for which the Company is instituted And to make such Rules and Regulations as they shall from time to time think expedient, and for the Interest of the common cause Provided that if any Member of the Company residing in Great Britain or any other part of the World shall at any General Meeting of the Company happen to be present it shall be lawful for such Member to vote at such meeting. Whereas it will be highly necessary to preserve Order and Decency at the General Meetings of the said Company; It isagreed that the Majority of the Company shall choose a President who is to preside for that Meeting only and to have the casting Vote in case of a Division And the President so chosen shall collect the Votes of the Members present whose Orders and Resolutions shall be entered in a Book to be kept for that purpose, and shall be absolutely conclusive on the said Company. That it shall be in the power of the said Company from time to time at a general Meeting as aforesaid to direct and appoint any Sum and Sums of money that they shall judge necessary for the purposes for which this Company is instituted to be paid into the hands of the Treasurer for the time being by every particular Member; which Sum and Sums of money the Subscribers do bind themselves, their Heirs, Executors and Administrator⟨s⟩ to pay into the hands of such Treasurer at the times to be appointed for the payment of the same Provided that if any Member or Members shall neglect or refuse to pay into the hands of the said Treasurer upon demand or shall fail to pay down to him at the next general Meeting of the Company the full Sum with legal Interest thereon from the time of the demand so made the said delinquent shall forfeit all Right Title and interest in the said Company and be no longer deemed a Member thereof. The said Company at the first general meeting to be had shall appoint a Treasurer out of their Number5who shall immediately on his appointment and before he is admitted to Act in that Office enter into Bond with two or More good and sufficient Securities to the said Company by the name of the Mississipi Company for the just and faithful performance of his Office of Treasurer and shall also make Oath that he will execute the same with justice and punctuality; which said Treasurer shall also act to the said Company as Clerk or Secretary and shall act in the Capacity of Clerk and Treasurer one Year and from thence to the next meeting of the Company and no longer And shall be allowed by the said Company for his Services five per Centum for all Moneys that shall pass through his hands. A Committee of Ten Members to be chosen by the Compa. five of which shall be a sufficient number to do business who shall meet twice a year (to wit) on the [ ]day of [ ]and on the [ ]day of [ ]or oftener as the exigencies of theCompany shall require6upon notice of such extraordinary meeting being published in the Virginia and Maryland Gazette by one or more of the members of the Committee And it shall be lawful for any member of the said Company that shall happen to be present at such Committee tho’ not nominated as one of the Committee to vote at such meeting Provided nevertheless that the Treasurer for the time being shall have no Right to vote at the meeting of such Committee. Such Committee shall have power to put in Execution suc[h] Plans as shall be laid down by a General meeting of the Company and apply the moneys raised by the said Company for the effecting such Plans. The Treasurer and Secretary of the Company aforesd shall act as Clerk or Secretary to the Committee and shall enter all the Orders of the said Committee in a Book to be kept for that purpose. That no Member shall have a Right to dispose of his share without first acquainting the Company at a General meeting and giving the Company the preference of purchasing. If any of the Members of the said Company shall hereafter sell and dispose of his whole share to divers Persons he shall loose his Right of voting in the said Company and it shall be in the power of the said Company to choose which of the said Purchasers they shall most approve to be a member of the said Company; no more than one Vote being to be allowed for one share But if any member shall dispose of only part of his share he shall not loose his Right of Voting at any meeting of the said Company, any thing to the contrary of this and the foregoing clause seeming to the contrary thereof notwithstanding. It shall not be lawful for any Member of the said Company purchasing the share or Shares of any other Member or Member’s therof to have more than one Vote. In testimony whereof we have hereunto set our hands this 3d day of June 1763. Francis Lightfoot Lee Richard Henry Lee Jno. Auge Washington Thos Lud. Lee Anthony Stewart Adam Stephen Richd Parker William Lee Robert Woddrop Presley Thornton Wm Flood William Booth Robert Brent Thos Bullitt _link_ William Beale Junr William Brockenbrough Henry Fitzhugh William Fitzhugh Go: Washington 7 D(copy), in GW’s hand, DLC:GW; D(copy), P.R.O., 30/8, Chatham Papers, ff. 124–25. The prospect of the French withdrawal from continental North America at the end of the French and Indian War precipitated in the early 1760s in America and Britain the formation of a number of companies for taking up and colonizing the vast lands that came under British protection. The Mississippi Land Company (or, as GW called it, the Mississippi Adventure) was one of these. Formed by the efforts largely of four Lee brothers, it was composed mostly of Virginians living in the Potomac River valley. At the time that GW attended the meeting on 3 June to organize the Mississippi Land Company, he was on his way home to Mount Vernon from a trip to Williamsburg and the Dismal Swamp (seeDismal Swamp Land Company: Articles of Agreement, 3 Nov. 1763, source note). On 2 June he was at Leedstown (then in King George County), and on 3 June he crossed the Potomac at Hooe’s ferry in Stafford County (seeCash Accounts, June 1763). It is likely that the organizational meeting of 3 June was at one of the sites of subsequent meetings, at Stafford County Court House, then on Potomac Creek, or at nearby Belleview (Bellview), the house of Thomas Ludwell Lee. The first regular meeting of the company held under the Articles of Agreement was at Belleview on 9 Sept. 1763, when GW was present; and the Mississippi Land Company was active at least as late as 1768 (seethe source note in the Mississippi Land Company’s Memorial to the King, 9 Sept. 1763). The minutes of the first regular meeting of the Mississippi Land Company on 9 Sept. 1763 are in Carter, Illinois Country description begins Clarence Edwin Carter. Great Britain and the Illinois Country: 1763–1774 . Washington, D.C., 1910. description ends, 165–71; the minutes of the meeting of the executive committee of the Mississippi Company, 26 Sept. 1763, are in Carter, “Mississippi Land Company,” description begins Clarence E. Carter, “Documents Relating to the Mississippi Land Company, 1763–1769.” American Historical Review 16 (1910–11): 311–19. description ends311–15. 1 .At the initial meeting of the Mississippi Land Company on 9 Sept., there were five men listed as members who were not among the nineteen who signed the Articles of Agreement on 3 June. Eighteen of the nineteen who signed the Articles on 3 June were living in Virginia, and four of the five new men who attended the September meeting also were from Virginia. Nine of the fifty places were reserved for men in London (seenote 2). “Resolved that the Treasurer pay into the hands of Mr. Chas. Digges One hundred Guineas to be by him delivered to Mr. Cumming agreeable to the resolves of the Company” ( Carter, “Mississippi Land Company,” description begins Clarence E. Carter, “Documents Relating to the Mississippi Land Company, 1763–1769.” American Historical Review 16 (1910–11): 311–19. description ends315). 3 .For amplification of these terms, seethe Mississippi Land Company’s Memorial to the King, 9 Sept. 1763, and the letter of 26 Sept. to Thomas Cumming printed innote 2of that document. 4 .The company voted to hold “the annual general meeting” at Stafford Court House on 1 Oct. ( Carter, Illinois Country description begins Clarence Edwin Carter. Great Britain and the Illinois Country: 1763–1774 . Washington, D.C., 1910. description ends, 169). 5 .William Lee was appointed treasurer on 9 Sept. (ibid.). 6 .The following were named on 9 Sept. to be members of this committee to meet twice a year at Westmoreland Court House: Presley Thornton, Thomas Ludwell Lee, Richard Henry Lee, Francis Lightfoot Lee, Henry Fitzhugh, John Augustine Washington, William Booth, William Brockenbrough, Richard Parker, and Dr. William Flood (ibid., 169–70). 7 .The four Lees signing the Articles of Agreement—Thomas Ludwell Lee (1730–1778), Richard Henry Lee (1732–1794), Francis Lightfoot Lee (1734–1797), and William Lee (1739–1795)—were sons of Thomas Lee of Stratford Hall in Westmoreland County. A fifth brother, Arthur Lee (1740–1792), at this time studying medicine in Scotland, was to become a member of the Mississippi Land Company and represent it in England. GW and his brother John Augustine Washington (1736–1787) were later joined as members by their two brothers Samuel and Charles. Dr. William Flood (d. 1775) and Richard Parker (1729–1813), a lawyer, were from Westmoreland County. Col. William Brockenbrough (1715–1778) and William Beale, Jr. (d. 1778), were Richmond County planters. Col. Presley Thornton, a planter and member of the Virginia council, and the merchant Robert Woddrop (d. 1767), lived in Northumberland County. Robert Brent (c.1730–1780) of Woodstock, Col. Henry Fitzhugh (1723–1783) of Bedford (probably the Henry Fitzhugh who signed), and William Fitzhugh (probably William Fitzhugh, Sr. [1725–1791], of Marmion but possibly Capt. William Fitzhugh [1729–1785] or William Fitzhugh, Jr. [1741–1809], of Somerset [later of Chatham]), were all planters in Stafford County except for Captain Fitzhugh. Anthony Stewart (died c.1791), the lone Marylander involved in the initial organization of theMississippi Land Company, was a merchant in Annapolis. Adam Stephen and Thomas Bullitt were GW’s former companions in arms. Only GW and two or three other signers were not living in one of the counties of the Northern Neck between the Potomac and Rappahannock rivers: Stafford, King George, Westmoreland, Northumberland, and Richmond. The five men who appeared at the meeting on 9 Sept. and were not signers of the Articles of Agreement were Charles Digges, a merchant in Upper Marlboro, Prince George’s County, Md., and Alexandria; James Douglas, a merchant in Dumfries, Prince William County, on the Potomac, who was married to a sister of Robert Brent (see above); Francis Thornton (d. 1784) of Society Hill, then in Stafford County, now in King George County, a brother of Presley Thornton (see above); William Brent (1733–1782) of Richland in Stafford County; and George Simpson, who may be the man by that name who lived in Fairfax County and died in 1782. The identifications of William Fitzhugh, Sr., Francis Thornton, and William Brent are all tentative. https://founders.archives.gov/documents/Washington/02-07-02-0134 Reference Cite as
https://founders.archives.gov/documents/Washington/02-07-02-0134
- Supreme Court E-Library 464 Phil. 173 EN BANC [ G.R. No. 159139. January 13, 2004 ] INFORMATION TECHNOLOGY FOUNDATION OF THE PHILIPPINES, MA. CORAZON M. AKOL, MIGUEL UY, EDUARDO H. LOPEZ, AUGUSTO C. LAGMAN, REX C. DRILON, MIGUEL HILADO, LEY SALCEDO, AND MANUEL ALCUAZ JR., PETITIONERS, VS. COMMISSION ON ELECTIONS; COMELEC CHAIRMAN BENJAMIN ABALOS SR.; COMELEC BIDDING AND AWARD COMMITTEE CHAIRMAN EDUARDO D. MEJOS AND MEMBERS GIDEON DE GUZMAN, JOSE F. BALBUENA, LAMBERTO P. LLAMAS, AND BARTOLOME SINOCRUZ JR.; MEGA PACIFIC ESOLUTIONS, INC.; AND MEGA PACIFIC CONSORTIUM, RESPONDENTS. D E C I S I O N PANGANIBAN, J.: There is grave abuse of discretion (1) when an act is done contrary to the Constitution, the law or jurisprudence; [1] or (2) when it is executed whimsically, capriciously or arbitrarily out of malice, ill will or personal bias. [2] In the present case, the Commission on Elections approved the assailed Resolution and awarded the subject Contract not only in clear violation of law and jurisprudence, but also in reckless disregard of its own bidding rules and procedure. For the automation of the counting and canvassing of the ballots in the 2004 elections, Comelec awarded the Contract to “Mega Pacific Consortium” an entity that had not participated in the bidding. Despite this grant, the poll body signed the actual automation Contract with “Mega Pacific eSolutions, Inc.,” a company that joined the bidding but had not met the eligibility requirements. Comelec awarded this billion—peso undertaking with inexplicable haste, without adequately checking and observing mandatory financial, technical and legal requirements. It also accepted the proferred computer hardware and software even if, at the time of the award, they had undeniably failed to pass eight critical requirements designed to safeguard the integrity of elections, especially the following three items: They failed to achieve the accuracy rating criteria of 99.9995 percent set—up by the Comelec itself They were not able to detect previously downloaded results at various canvassing or consolidation levels and to prevent these from being inputted again They were unable to print the statutorily required audit trails of the count/canvass at different levels without any loss of data Because of the foregoing violations of law and the glaring grave abuse of discretion committed by Comelec, the Court has no choice but to exercise its solemn “constitutional duty” [3]to void the assailed Resolution and the subject Contract. The illegal, imprudent and hasty actions of the Commission have not only desecrated legal and jurisprudential norms, but have also cast serious doubts upon the poll body’s ability and capacity to conduct automated elections. Truly, the pith and soul of democracy — credible, orderly, and peaceful elections — has been put in jeopardy by the illegal and gravely abusive acts of Comelec. The Case Before us is a Petition [4]under Rule 65 of the Rules of Court, seeking (1) to declare null and void Resolution No. 6074 of the Commission on Elections (Comelec), which awarded “Phase II of the Modernization Project of the Commission to Mega Pacific Consortium (MPC);” (2) to enjoin the implementation of any further contract that may have been entered into by Comelec “either with Mega Pacific Consortium and/or Mega Pacific eSolutions, Inc. (MPEI);” and (3) to compel Comelec to conduct a re—bidding of the project. The Facts The following facts are not disputed. They were culled from official documents, the parties’ pleadings, as well as from admissions during the Oral Argument on October 7, 2003. On June 7, 1995, Congress passed Republic Act 8046, [5]which authorized Comelec to conduct a nationwide demonstration of a computerized election system and allowed the poll body to pilot—test the system in the March 1996 elections in the Autonomous Region in Muslim Mindanao (ARMM). On December 22, 1997, Congress enacted Republic Act 8436 [6]authorizing Comelec to use an automated election system (AES) for the process of voting, counting votes and canvassing/consolidating the results of the national and local elections. It also mandated the poll body to acquire automated counting machines (ACMs), computer equipment, devices and materials; and to adopt new electoral forms and printing materials. Initially intending to implement the automation during the May 11, 1998 presidential elections, Comelec — in its Resolution No. 2985 dated February 9, 1998 [7]— eventually decided against full national implementation and limited the automation to the Autonomous Region in Muslim Mindanao (ARMM). However, due to the failure of the machines to read correctly some automated ballots in one town, the poll body later ordered their manual count for the entire Province of Sulu. [8] In the May 2001 elections, the counting and canvassing of votes for both national and local positions were also done manually, as no additional ACMs had been acquired for that electoral exercise allegedly because of time constraints. On October 29, 2002, Comelec adopted in its Resolution 02—0170 a modernization program for the 2004 elections. It resolved to conduct biddings for the three (3) phases of its Automated Election System; namely, Phase I — Voter Registration and Validation System; Phase II — Automated Counting and Canvassing System; and Phase III — Electronic Transmission. On January 24, 2003, President Gloria Macapagal—Arroyo issued Executive Order No. 172, which allocated the sum of P2.5 billion to fund the AES for the May 10, 2004 elections. Upon the request of Comelec, she authorized the release of an additional P500 million. On January 28, 2003, the Commission issued an “Invitation to Apply for Eligibility and to Bid,” which we quote as follows: “INVITATION TO APPLY FOR ELIGIBILITY AND TO BID The Commission on Elections (COMELEC), pursuant to the mandate of Republic Act Nos. 8189 and 8436, invites interested offerors, vendors, suppliers or lessors to apply for eligibility and to bid for the procurement by purchase, lease, lease with option to purchase, or otherwise, supplies, equipment, materials and services needed for a comprehensive Automated Election System, consisting of three (3) phases: (a) registration/verification of voters, (b) automated counting and consolidation of votes, and (c) electronic transmission of election results, with an approved budget of TWO BILLION FIVE HUNDRED MILLION (Php2,500,000,000) Pesos. Only bids from the following entities shall be entertained: Duly licensed Filipino citizens/proprietorships; Partnerships duly organized under the laws of the Philippines and of which at least sixty percent (60%) of the interest belongs to citizens of the Philippines; Corporations duly organized under the laws of the Philippines, and of which at least sixty percent (60%) of the outstanding capital stock belongs to citizens of the Philippines; Manufacturers, suppliers and/or distributors forming themselves into a joint venture, i.e., a group of two (2) or more manufacturers, suppliers and/or distributors that intend to be jointly and severally responsible or liable for a particular contract, provided that Filipino ownership thereof shall be at least sixty percent (60%); and Cooperatives duly registered with the Cooperatives Development Authority. Bid documents for the three (3) phases may be obtained starting 10 February 2003, during office hours from the Bids and Awards Committee (BAC) Secretariat/Office of Commissioner Resurreccion Z. Borra, 7 thFloor, Palacio del Governador, Intramuros, Manila, upon payment at the Cash Division, Commission on Elections, in cash or cashier’s check, payable to the Commission on Elections, of a non—refundable amount of FIFTEEN THOUSAND PESOS (Php15,000.00) for each phase. For this purpose, interested offerors, vendors, suppliers or lessors have the option to participate in any or all of the three (3) phases of the comprehensive Automated Election System. A Pre—Bid Conference is scheduled on 13 February 2003, at 9:00 a.m. at the Session Hall, Commission on Elections, Postigo Street, Intramuros, Manila. Should there be questions on the bid documents, bidders are required to submit their queries in writing to the BAC Secretariat prior to the scheduled Pre—Bid Conference. Deadline for submission to the BAC of applications for eligibility and bid envelopes for the supply of the comprehensive Automated Election System shall be at the Session Hall, Commission on Elections, Postigo Street, Intramuros, Manila on 28 February 2003 at 9:00 a.m. The COMELEC reserves the right to review the qualifications of the bidders after the bidding and before the contract is executed. Should such review uncover any misrepresentation made in the eligibility statements, or any changes in the situation of the bidder to materially downgrade the substance of such statements, the COMELEC shall disqualify the bidder upon due notice without any obligation whatsoever for any expenses or losses that may be incurred by it in the preparation of its bid.” [9] On February 11, 2003, Comelec issued Resolution No. 5929 clarifying certain eligibility criteria for bidders and the schedule of activities for the project bidding, as follows: “1.) Open to Filipino and foreign corporation duly registered and licensed to do business and is actually doing business in the Philippines, subject to Sec. 43 of RA 9184 (An Act providing In the Modernization Standardization and Regulation of the Procurement Activities of the Government and for other purposes etc.) 2.) Track Record: a) For counting machines — should have been used in at least one (1) political exercise with no less than Twenty Million Voters; b) For verification of voters — the reference site of an existing data base installation using Automated Fingerprint Identification System (AFIS) with at least Twenty Million. 3.) Ten percent (10%) equity requirement shall be based on the total project cost; and 4.) Performance bond shall be twenty percent (20%) of the bid offer. RESOLVED moreover, that: 1) A. Due to the decision that the eligibility requirements and the rest of the Bid documents shall be released at the same time, and the memorandum of Comm. Resurreccion Z. Borra dated February 7, 2003, the documents to be released on Friday, February 14, 2003 at 2:00 o’clock p.m. shall be the eligibility criteria, Terms of Reference (TOR) and other pertinent documents; B. Pre—Bid conference shall be on February 18, 2003; and C. Deadline for the submission and receipt of the Bids shall be on March 5, 2003. 2) The aforementioned documents will be available at the following offices: a) Voters Validation: Office of Comm. Javier b) Automated Counting Machines: Office of Comm. Borra c) Electronic Transmission: Office of Comm. Tancangco” [10] On February 17, 2003, the poll body released the Request for Proposal (RFP) to procure the election automation machines. The Bids and Awards Committee (BAC) of Comelec convened a pre—bid conference on February 18, 2003 and gave prospective bidders until March 10, 2003 to submit their respective bids. Among others, the RFP provided that bids from manufacturers, suppliers and/or distributors forming themselves into a joint venture may be entertained, provided that the Philippine ownership thereof shall be at least 60 percent. Joint ventureis defined in the RFP as “a group of two or more manufacturers, suppliers and/or distributors that intend to be jointly and severally responsible or liable for a particular contract.” [11] Basically, the public bidding was to be conducted under a two—envelope/two stage system.The bidder’s first envelope or the Eligibility Envelope should establish the bidder’s eligibility to bid and its qualifications to perform the acts if accepted. On the other hand, the second envelope would be the Bid Envelope itself. The RFP outlines the bidding procedures as follows: “25. Determination of Eligibility of Prospective Bidders “25.1 The eligibility envelopes of prospective Bidders shall be opened first to determine their eligibility. In case any of the requirements specified in Clause 20 is missing from the first bid envelope, the BAC shall declare said prospective Bidder as ineligible to bid. Bid envelopes of ineligible Bidders shall be immediately returned unopened. “25.2 The eligibility of prospective Bidders shall be determined using simple ‘pass/fail’ criteria and shall be determined as either eligible or ineligible. If the prospective Bidder is rated ‘passed’ for all the legal, technical and financial requirements, he shall be considered eligible. If the prospective Bidder is rated ‘failed’ in any of the requirements, he shall be considered ineligible. “26. Bid Examination/Evaluation “26.1 The BAC will examine the Bids to determine whether they are complete, whether any computational errors have been made, whether required securities have been furnished, whether the documents have been properly signed, and whether the Bids are generally in order. “26.2 The BAC shall check the submitted documents of each Bidder against the required documents enumerated under Clause 20, to ascertain if they are all present in the Second bid envelope (Technical Envelope). In case one (1) or more of the required documents is missing, the BAC shall rate the Bid concerned as ‘failed’ and immediately return to the Bidder its Third bid envelope (Financial Envelope) unopened. Otherwise, the BAC shall rate the first bid envelope as ‘passed’. “26.3 The BAC shall immediately open the Financial Envelopes of the Bidders whose Technical Envelopes were passed or rated on or above the passing score. Only Bids that are determined to contain all the bid requirements for both components shall be rated ‘passed’ and shall immediately be considered for evaluation and comparison. “26.4 In the opening and examination of the Financial Envelope, the BAC shall announce and tabulate the Total Bid Price as calculated. Arithmetical errors will be rectified on the following basis: If there is a discrepancy between words and figures, the amount in words will prevail. If there is a discrepancy between the unit price and the total price that is obtained by multiplying the unit price and the quantity, the unit price shall prevail and the total price shall be corrected accordingly. If there is a discrepancy between the Total Bid Price and the sum of the total prices, the sum of the total prices prevail and the Total Bid Price shall be corrected accordingly. “26.5 Financial Proposals which do not clearly state the Total Bid Price shall be rejected. Also, Total Bid Price as calculated that exceeds the approved budget for the contract shall also be rejected. 27. Comparison of Bids 27.1 The bid price shall be deemed to embrace all costs, charges and fees associated with carrying out all the elements of the proposed Contract, including but not limited to, license fees, freight charges and taxes. 27.2 The BAC shall establish the calculated prices of all Bids rated ‘passed’ and rank the same in ascending order. <table><tbody><tr><td> x x x</td><td></td><td> x x x</td><td></td><td> x x x</td></tr></tbody></table> “29. Postqualification “29.1 The BAC will determine to its satisfaction whether the Bidder selected as having submitted the lowest calculated bid is qualified to satisfactorily perform the Contract. “29.2 The determination will take into account the Bidder’s financial, technical and production capabilities/resources. It will be based upon an examination of the documentary evidence of the Bidder’s qualification submitted by the Bidder as well as such other information as the BAC deems necessary and appropriate. “29.3 A bid determined as not substantially responsive will be rejected by the BAC and may not subsequently be made responsive by the Bidder by correction of the non—conformity. “29.4 The BAC may waive any informality or non—conformity or irregularity in a bid which does not constitute a material deviation, provided such waiver does not prejudice or affect the relative ranking of any Bidder. “29.5 Should the BAC find that the Bidder complies with the legal, financial and technical requirements, it shall make an affirmative determination which shall be a prerequisite for award of the Contract to the Bidder. Otherwise, it will make a negative determination which will result in rejection of the Bidder’s bid, in which event the BAC will proceed to the next lowest calculated bid to make a similar determination of that Bidder’s capabilities to perform satisfactorily.” [12] Out of the 57 bidders, [13]the BAC found MPC and the Total Information Management Corporation (TIMC) eligible. For technical evaluation, they were referred to the BAC’s Technical Working Group (TWG) and the Department of Science and Technology (DOST). In its Report on the Evaluation of the Technical Proposals on Phase II, DOST said that both MPC and TIMC had obtained a number of failed marks in the technical evaluation. Notwithstanding these failures, Comelec en banc, on April 15, 2003, promulgated Resolution No. 6074 awarding the project to MPC. The Commission publicized this Resolution and the award of the project to MPC on May 16, 2003. On May 29, 2003, five individuals and entities (including the herein Petitioners Information Technology Foundation of the Philippines, represented by its president, Alfredo M. Torres; and Ma. Corazon Akol) wrote a letter [14]to Comelec Chairman Benjamin Abalos Sr. They protested the award of the Contract to Respondent MPC “due to glaring irregularities in the manner in which the bidding process had been conducted.” Citing therein the noncompliance with eligibility as well as technical and procedural requirements (many of which have been discussed at length in the Petition), they sought a re—bidding. In a letter—reply dated June 6, 2003, [15]the Comelec chairman — speaking through Atty. Jaime Paz, his head executive assistant — rejected the protest and declared that the award “would stand up to the strictest scrutiny.” Hence, the present Petition. [16] The Issues In their Memorandum, petitioners raise the following issues for our consideration: “1. The COMELEC awarded and contracted with a non—eligible entity; x x x “2. Private respondents failed to pass the Technical Test as required in the RFP. Notwithstanding, such failure was ignored. In effect, the COMELEC changed the rules after the bidding in effect changing the nature of the contract bidded upon. “3. Petitioners have locus standi. “4. Instant Petition is not premature. Direct resort to the Supreme Court is justified.” [17] In the main, the substantiveissue is whether the Commission on Elections, the agency vested with the exclusive constitutional mandate to oversee elections, gravely abused its discretion when, in the exercise of its administrative functions, it awarded to MPC the contract for the second phase of the comprehensive Automated Election System. Before discussing the validity of the award to MPC, however, we deem it proper to first pass upon the proceduralissues: the legal standing of petitioners and the alleged prematurity of the Petition. This Court’s Ruling The Petition is meritorious. First Procedural Issue: Locus Standi of Petitioners Respondents chorus that petitioners do not possess locus standi, inasmuch as they are not challenging the validity or constitutionality of RA 8436. Moreover, petitioners supposedly admitted during the Oral Argument that no law had been violated by the award of the Contract. Furthermore, they allegedly have no actual and material interest in the Contract and, hence, do not stand to be injured or prejudiced on account of the award. On the other hand, petitioners — suing in their capacities as taxpayers, registered voters and concerned citizens — respond that the issues central to this case are “of transcendental importance and of national interest.” Allegedly, Comelec’s flawed bidding and questionable award of the Contract to an unqualified entity would impact directly on the success or the failure of the electoral process. Thus, any taint on the sanctity of the ballot as the expression of the will of the people would inevitably affect their faith in the democratic system of government. Petitioners further argue that the award of any contract for automation involves disbursement of public funds in gargantuan amounts; therefore, public interest requires that the laws governing the transaction must be followed strictly. We agree with petitioners. Our nation’s political and economic future virtually hangs in the balance, pending the outcome of the 2004 elections. Hence, there can be no serious doubt that the subject matter of this case is “a matter of public concern and imbued with public interest”; [18]in other words, it is of “paramount public interest” [19]and “transcendental importance.” [20]This fact alone would justify relaxing the rule on legal standing, following the liberal policy of this Court whenever a case involves “an issue of overarching significance to our society.” [21]Petitioners’ legal standing should therefore be recognized and upheld. Moreover, this Court has held that taxpayers are allowed to sue when there is a claim of “illegal disbursement of public funds,” [22]or if public money is being “deflected to any improper purpose”; [23]or when petitioners seek to restrain respondent from “wasting public funds through the enforcement of an invalid or unconstitutional law.” [24]In the instant case, individual petitioners, suing as taxpayers, assert a material interest in seeing to it that public funds are properly and lawfully used. In the Petition, they claim that the bidding was defective, the winning bidder not a qualified entity, and the award of the Contract contrary to law and regulation. Accordingly, they seek to restrain respondents from implementing the Contract and, necessarily, from making any unwarranted expenditure of public funds pursuant thereto. Thus, we hold that petitioners possess locus standi. Second Procedural Issue: Alleged Prematurity Due to Non—Exhaustion of Administrative Remedies Respondents claim that petitioners acted prematurely, since they had not first utilized the protest mechanism available to them under RA 9184, the Government Procurement Reform Act, for the settlement of disputes pertaining to procurement contracts. Section 55 of RA 9184 states that protests against decisions of the Bidding and Awards Committee in all stages of procurement may be lodged with the head of the procuring entity by filing a verified position paper and paying a protest fee. Section 57 of the same law mandates that in no case shall any such protest stay or delay the bidding process, but it must first be resolved before any award is made. On the other hand, Section 58 provides that court action may be resorted to only after the protests contemplated by the statute shall have been completed. Cases filed in violation of this process are to be dismissed for lack of jurisdiction. Regional trial courts shall have jurisdiction over final decisions of the head of the procuring entity, and court actions shall be instituted pursuant to Rule 65 of the 1997 Rules of Civil Procedure. Respondents assert that throughout the bidding process, petitioners never questioned the BAC Report finding MPC eligible to bid and recommending the award of the Contract to it (MPC). According to respondents, the Report should have been appealed to the Comelec en banc, pursuant to the aforementioned sections of RA 9184. In the absence of such appeal, the determination and recommendation of the BAC had become final. The Court is not persuaded. Respondent Comelec came out with its en banc Resolution No. 6074 dated April 15, 2003, awarding the project to Respondent MPC even before the BAC managed to issue its written report and recommendation on April 21, 2003. Thus, how could petitioners have appealed the BAC’s recommendation or report to the head of the procuring entity (the chairman of Comelec), when the Comelec en banchad already approved the award of the contract to MPC even before petitioners learned of the BAC recommendation? It is claimed [25]by Comelec that during its April 15, 2003 session, it received and approved the verbalreport and recommendation of the BAC for the award of the Contract to MPC, and that the BAC subsequently re—affirmed its verbal report and recommendation by submitting it in writing on April 21, 2003. Respondents insist that the law does not require that the BAC Report be in writing before Comelec can act thereon; therefore, there is allegedly nothing irregular about the Report as well as the en bancResolution. However, it is obvious that petitioners could have appealed the BAC’s report and recommendation to the head of the procuring entity (the Comelec chair) only upon their discoverythereof, which at the very earliest would have been on April 21, 2003, when the BAC actually put its report in writing and finally released it. Even then, what would have been the use of protesting/appealing the report to the Comelec chair, when by that time the Commission en banc ( including the chairman himself) had already approved the BAC Report and awarded the Contract to MPC? And even assuming arguendothat petitioners had somehow gotten wind of the verbal BAC report on April 15, 2003 (immediately after the en bancsession), at that point the Commission en banchad already given its approval to the BAC Report along with the award to MPC. To put it bluntly, the Comelec en banc itself made it legally impossible for petitioners to avail themselves of the administrative remedy that the Commission is so impiously harping on. There is no doubt that they had not been accorded the opportunity to avail themselves of the process provided under Section 55 of RA 9184, according to which a protest against a decision of the BAC may be filed with the head of the procuring entity. Nemo tenetur ad impossible, [26]to borrow private respondents’ favorite Latin excuse. [27] Some Observations on theBAC Report to the Comelec We shall return to this issue of alleged prematurity shortly, but at this interstice, we would just want to put forward a few observations regarding the BAC Report and the Comelec en banc’sapproval thereof. First, Comelec contends that there was nothing unusual about the fact that the Report submitted by the BAC came only after the former had already awarded the Contract, because the latter had been asked to render its report and recommendation orally during the Commission’s en bancsession on April 15, 2003. Accordingly, Comelec supposedly acted upon such oral recommendation and approved the award to MPC on the same day, following which the recommendation was subsequently reduced into writing on April 21, 2003. While not entirely outside the realm of the possible, this interesting and unique spiel does not speak well of the process that Comelec supposedly went through in making a critical decision with respect to a multi—billion—peso contract. We can imagine that anyone else standing in the shoes of the Honorable Commissioners would have been extremely conscious of the overarching need for utter transparency. They would have scrupulously avoided the slightest hint of impropriety, preferring to maintain an exacting regularity in the performance of their duties, instead of trying to break a speed record in the award of multi—billion—peso contracts. After all, between April 15 and April 21 were a mere six (6) days. Could Comelec not have waited out six more days for the written report of the BAC, instead of rushing pell—mell into the arms of MPC? Certainly, respondents never cared to explain the nature of the Commission’s dire need to act immediately without awaiting the formal, written BAC Report. In short, the Court finds it difficult to reconcile the uncommon dispatch with which Comelec acted to approve the multi—billion—peso deal, with its claim of having been impelled by only the purest and most noble of motives. At any rate, as will be discussed later on, several other factors combine to lend negativecredence to Comelec’s tale. Second, without necessarily ascribing any premature malice or premeditation on the part of the Comelec officials involved, it should nevertheless be conceded that this cart—before—the—horse maneuver (awarding of the Contract ahead of the BAC’s written report) would definitely serve as a clever and effective way of averting and frustrating any impending protest under Section 55. Having made the foregoing observations, we now go back to the question of exhausting administrative remedies. Respondents may not have realized it, but the letter addressed to Chairman Benjamin Abalos Sr. dated May 29, 2003 [28]serves to eliminate the prematurity issue as it was an actual written protest against the decision of the poll body to award the Contract. The letter was signed by/for, inter alia, two of herein petitioners: the Information Technology Foundation of the Philippines, represented by its president, Alfredo M. Torres; and Ma. Corazon Akol. Such letter—protest is sufficient compliancewith the requirement to exhaust administrative remedies particularly because it hews closely to the procedure outlined in Section 55 of RA 9184. And even without that May 29, 2003 letter—protest, the Court still holds that petitioners need not exhaust administrative remedies in the light of Paat v. Court of Appeals. [29]Paat enumerates the instances when the rule on exhaustion of administrative remedies may be disregarded, as follows: “(1) when there is a violation of due process, (2) when the issue involved is purely a legal question, (3) when the administrative action is patently illegal amounting to lack or excess of jurisdiction, (4) when there is estoppel on the part of the administrative agency concerned, (5) when there is irreparable injury, (6) when the respondent is a department secretary whose acts as an alter egoof the President bears the implied and assumed approval of the latter, (7) when to require exhaustion of administrative remedies would be unreasonable, (8) when it would amount to a nullification of a claim, (9) when the subject matter is a private land in land case proceedings, (10) when the rule does not provide a plain, speedy and adequate remedy, and (11) when there are circumstances indicating the urgency of judicial intervention.” [30] The present controversy precisely fallswithin the exceptions listed as Nos. 7, 10 and 11: “ (7) when to require exhaustion of administrative remedies would be unreasonable; (10) when the rule does not provide a plain, speedy and adequate remedy, and (11) when there are circumstances indicating the urgency of judicial intervention.” As already stated, Comelec itself made the exhaustion of administrative remedies legally impossible or, at the very least, “unreasonable.” In any event, the peculiar circumstances surrounding the unconventional rendition of the BAC Report and the precipitate awarding of the Contract by the Comelec en banc— plus the fact that it was racing to have its Contract with MPC implemented in time for the elections in May 2004 (barely four months away) — have combined to bring about the urgent need for judicial intervention, thus prompting this Court to dispense with the procedural exhaustion of administrative remedies in this case. Main Substantive Issue: Validity of the Award to MPC We come now to the meat of the controversy. Petitioners contend that the award is invalid, since Comelec gravely abused its discretion when it did the following: Awarded the Contract to MPC though it did not even participate in the bidding Allowed MPEI to participate in the bidding despite its failure to meet the mandatory eligibility requirements Issued its Resolution of April 15, 2003 awarding the Contract to MPC despite the issuance by the BAC of its Report, which formed the basis of the assailed Resolution, only on April 21, 2003 [31] Awarded the Contract, notwithstanding the fact that during the bidding process, there were violations of the mandatory requirements of RA 8436 as well as those set forth in Comelec’s own Request for Proposal on the automated election system Refused to declare a failed bidding and to conduct a re—bidding despite the failure of the bidders to pass the technical tests conducted by the Department of Science and Technology Failed to follow strictly the provisions of RA 8436 in the conduct of the bidding for the automated counting machines After reviewing the slew of pleadings as well as the matters raised during the Oral Argument, the Court deems it sufficient to focus discussion on the following major areas of concernthat impinge on the issue of grave abuse of discretion: A. Matters pertaining to the identity, existence and eligibility of MPC as a bidder B. Failure of the automated counting machines (ACMs) to pass the DOST technical tests C. Remedial measures and re—testings undertaken by Comelec and DOST after the award, and their effect on the present controversy A. Failure to Establish the Identity, Existence and Eligibility of the Alleged Consortium as a Bidder On the question of the identity and the existence of the real bidder, respondents insist that, contrary to petitioners’ allegations, the bidder was not Mega Pacific eSolutions, Inc. (MPEI), which was incorporated only on February 27, 2003, or 11 days prior to the bidding itself. Rather, the bidder was Mega Pacific Consortium (MPC), of which MPEI was but a part. As proof thereof, they point to the March 7, 2003 letter of intent to bid, signed by the president of MPEI allegedly for and on behalf of MPC. They also call attention to the official receipt issued to MPC, acknowledging payment for the bidding documents, as proof that it was the “consortium” that participated in the bidding process. We do not agree. The March 7, 2003 letter, signed by only one signatory — “Willy U. Yu, President, Mega Pacific eSolutions, Inc., (Lead Company/ Proponent) For: Mega Pacific Consortium” — and without any further proof, does not by itself prove the existence of the consortium. It does not show that MPEI or its president have been duly pre—authorized by the other members of the putative consortium to represent them, to bid on their collective behalf and, more important, to commit them jointly and severally to the bid undertakings. The letter is purely self—serving and uncorroborated. Neither does an official receipt issued to MPC, acknowledging payment for the bidding documents, constitute proof that it was the purported consortium that participated in the bidding. Such receipts are issued by cashiers without any legally sufficient inquiry as to the real identity or existence of the supposed payor. To assure itself properly of the due existence (as well as eligibility and qualification) of the putative consortium, Comelec’s BAC should have examined the bidding documents submitted on behalf of MPC. They would have easily discovered the following fatal flaws. Two—Envelope, Two—Stage System As stated earlier in our factual presentation, the public bidding system designed by Comelec under its RFP (Request for Proposal for the Automation of the 2004 Election) mandated the use of a two—envelope, two—stage system. A bidder’s first envelope(Eligibility Envelope) was meant to establish its eligibility to bid and its qualifications and capacity to perform the contract if its bid was accepted, while the second envelopewould be the Bid Envelope itself. The Eligibility Envelope was to contain legal documentssuch as articles of incorporation, business registrations, licenses and permits, mayor’s permit, VAT certification, and so forth; technical documentscontaining documentary evidence to establish the track record of the bidder and its technical and production capabilities to perform the contract; and financial documents, including audited financial statements for the last three years, to establish the bidder’s financial capacity. In the case of a consortium or joint venture desirous of participating in the bidding, it goes without saying that the Eligibility Envelope would necessarily have to include a copy of the joint venture agreement, the consortium agreement or memorandum of agreement — or a business plan or some other instrument of similar import — establishing the due existence, composition and scope of such aggrupation. Otherwise, how would Comelec know who it was dealing with, and whether these parties are qualified and capable of delivering the products and services being offered for bidding? [32] In the instant case, no such instrument was submitted to Comelec during the bidding process. This fact can be conclusively ascertained by scrutinizing the two—inch thick “Eligibility Requirements” file submitted by Comelec last October 9, 2003, in partial compliance with this Court’s instructions given during the Oral Argument. This file purports to replicate the eligibility documents originally submitted to Comelec by MPEI allegedly on behalf of MPC, in connection with the bidding conducted in March 2003. Included in the file are the incorporation papers and financial statements of the members of the supposed consortium and certain certificates, licenses and permits issued to them. However, there is no sign whatsoever of any joint venture agreement, consortium agreement, memorandum of agreement, or business plan executed among the members of the purported consortium. The only logical conclusion is that no such agreement was ever submitted to the Comelec for its consideration, as part of the bidding process. It thus follows that, prior the award of the Contract, there was no documentary or other basis for Comelec to conclude that a consortium had actually been formed amongst MPEI, SK C&C and WeSolv, along with Election.com and ePLDT. [33]Neither was there anything to indicate the exact relationships between and among these firms; their diverse roles, undertakings and prestations, if any, relative to the prosecution of the project, the extent of their respective investments (if any) in the supposed consortium or in the project; and the precise nature and extent of their respective liabilities with respect to the contract being offered for bidding. And apart from the self—serving letter of March 7, 2003, there was not even any indication that MPEI was the lead company duly authorized to act on behalf of the others. So, it necessarily follows that, during the bidding process, Comelec had no basis at all for determining that the alleged consortium really existed and was eligible and qualified; and that the arrangements among the members were satisfactory and sufficient to ensure delivery on the Contract and to protect the government’s interest. Notwithstanding such deficiencies, Comelec still deemed the “consortium” eligible to participate in the bidding, proceeded to open its Second Envelope, and eventually awarded the bid to it, even though — per the Comelec’s own RFP — the BAC should have declared the MPC ineligible to bid and returned the Second (Bid) Envelope unopened. Inasmuch as Comelec should not have considered MPEI et al.as comprising a consortium or joint venture, it should not have allowed them to avail themselves of the provision in Section 5.4 (b) (i) of the IRR for RA 6957 (the Build—Operate—Transfer Law), as amended by RA 7718. This provision states in part that a joint venture/consortium proponent shall be evaluated based on the individual or collective experience of the member—firmsof the joint venture or consortium and of the contractor(s) that it has engaged for the project. Parenthetically, respondents have uniformly argued that the said IRR of RA 6957, as amended, have suppletory application to the instant case. Hence, had the proponent MPEI been evaluated based solely on its own experience, financial and operational track record or lack thereof, it would surely not have qualified and would have been immediately considered ineligible to bid, as respondents readily admit. At any rate, it is clear that Comelec gravely abused its discretionin arbitrarily failing to observe its own rules, policies and guidelines with respect to the bidding process, thereby negating a fair, honest and competitive bidding. Commissioners NotAware of Consortium In this regard, the Court is beguiled by the statements of Commissioner Florentino Tuason Jr., given in open court during the Oral Argument last October 7, 2003. The good commissioner affirmed that he was aware, of his own personal knowledge, that there had indeed been a written agreement among the “consortium” members, [34]although it was an internal matter among them, [35]and of the fact that it would be presented by counsel for private respondent. [36] However, under questioning by Chief Justice Hilario G. Davide Jr. and Justice Jose C. Vitug, Commissioner Tuason in effect admitted that, while he was the commissioner—in—charge of Comelec’s Legal Department, he had never seen, even up to that late date, the agreement he spoke of. [37]Under further questioning, he was likewise unable to provide any information regarding the amounts invested into the project by several members of the claimed consortium. [38]A short while later, he admitted that the Commission had not taken a look at the agreement(if any). [39] He tried to justify his position by claiming that he was not a member of the BAC. Neither was he the commissioner—in—charge of the Phase II Modernization project (the automated election system); but that, in any case, the BAC and the Phase II Modernization Project Team did look into the aspect of the composition of the consortium. It seems to the Court, though, that even if the BAC or the Phase II Team had taken charge of evaluating the eligibility, qualifications and credentials of the consortium—bidder, still, in all probability, the former would have referred the task to Commissioner Tuason, head of Comelec’s Legal Department. That task was the appreciation and evaluation of the legal effects and consequences of the terms, conditions, stipulations and covenants contained in any joint venture agreement, consortium agreement or a similar document — assuming of course that any of these was available at the time. The fact that Commissioner Tuason was barely aware of the situation bespeaks the complete absence of such document, or the utter failure or neglect of the Comelec to examine it — assuming it was available at all — at the time the award was made on April 15, 2003. In any event, the Court notes for the record that Commissioner Tuason basically contradicted his statements in open court about there being one written agreement among all the consortium members, when he subsequently referred [40]to the four (4) Memoranda of Agreement (MOAs) executed by them. [41] At this juncture, one might ask: What, then, if there are four MOAs instead of one or none at all? Isn’t it enough that there are these corporations coming together to carry out the automation project? Isn’t it true, as respondent aver, that nowhere in the RFP issued by Comelec is it required that the members of the joint venture execute a single written agreement to prove the existence of a joint venture. Indeed, the intention to be jointly and severally liable may be evidenced not only by a single joint venture agreement, but also by supplementary documents executed by the parties signifying such intention. What then is the big deal? The problem is not that there are four agreements instead of only one. The problem is that Comelec never bothered to check. It never based its decision on documents or other proof that would concretely establish the existence of the claimed consortium or joint venture or agglomeration. It relied merely on the self—serving representation in an uncorroborated letter signed by only one individual, claiming that his company represented a “consortium” of several different corporations. It concluded forthwith that a consortium indeed existed, composed of such and such members, and thereafter declared that the entity was eligible to bid. True, copies of financial statements and incorporation papers of the alleged “consortium” members were submitted. But these papers did not establish the existence of a consortium, as they could have been provided by the companies concerned for purposes other than to prove that they were part of a consortium or joint venture. For instance, the papers may have been intended to show that those companies were each qualified to be a sub—contractor (and nothing more) in a major project. Those documents did not by themselves support the assumption that a consortium or joint venture existed among the companies. In brief, despite the absenceof competent proof as to the existence and eligibility of the alleged consortium (MPC), its capacity to deliver on the Contract, and the members’ joint and several liability therefor, Comelec nevertheless assumedthat such consortium existed and was eligible. It then went ahead and considered the bid of MPC, to which the Contract was eventually awarded, in gross violation of the former’s own bidding rules and procedures contained in its RFP. Therein lies Comelec’s grave abuse of discretion. Sufficiency of theFour Agreements Instead of one multilateral agreement executed by, and effective and binding on, all the five “consortium members” — as earlier claimed by Commissioner Tuason in open court — it turns out that what was actually executed were four (4) separate and distinct bilateral Agreements. [42]Obviously, Comelec was furnished copies of these Agreements only afterthe bidding process had been terminated, as these were not included in the Eligibility Documents. These Agreements are as follows: A Memorandum of Agreement between MPEI and SK C&C A Memorandum of Agreement between MPEI and WeSolv A “Teaming Agreement” between MPEI and Election.com Ltd. A “Teaming Agreement” between MPEI and ePLDT. In sum, each of the four different and separate bilateral Agreements is valid and binding only between MPEI and the other contracting party, leaving the other “consortium” members total strangers thereto. Under this setup, MPEI dealt separatelywith each of the “members,” and the latter (WeSolv, SK C&C, Election.com, and ePLDT) in turn had nothing to do with one another, each dealing only with MPEI. Respondents assert that these four Agreements were sufficient for the purpose of enabling the corporations to still qualify (even at that late stage) as a consortium or joint venture, since the first two Agreements had allegedly set forth the joint and several undertakings among the parties, whereas the latter two clarified the parties’ respective roles with regard to the Project, with MPEI being the independent contractor and Election.com and ePLDT the subcontractors. Additionally, the use of the phrase “particular contract” in the Comelec’s Request for Proposal (RFP), in connection with the joint and several liabilities of companies in a joint venture, is taken by them to mean that all the members of the joint venture need not be solidarily liable for the entire project or joint venture, because it is sufficient that the lead company and the member in charge of a particular contract or aspect of the joint venture agree to be solidarily liable. At this point, it must be stressed most vigorously that the submission of the four bilateral Agreements to Comelec after the end of the bidding processdid nothing to eliminate the grave abuse of discretion it had alreadycommitted on April 15, 2003. Deficiencies HaveNot Been “Cured” In any event, it is also claimed that the automation Contract awarded by Comelec incorporates all documents executed by the “consortium” members, even if these documents are not referred to therein. The basis of this assertion appears to be the passages from Section 1.4 of the Contract, which is reproduced as follows: “All Contract Documents shall form part of the Contract even if they or any one of them is not referred to or mentioned in the Contract as forming a part thereof. Each of the Contract Documents shall be mutually complementary and explanatory of each other such that what is noted in one although not shown in the other shall be considered contained in all, and what is required by any one shall be as binding as if required by all, unless one item is a correction of the other. “The intent of the Contract Documents is the proper, satisfactory and timely execution and completion of the Project, in accordance with the Contract Documents. Consequently, all items necessary for the proper and timely execution and completion of the Project shall be deemed included in the Contract.” Thus, it is argued that whatever perceived deficiencies there were in the supplementary contracts — those entered into by MPEI and the other members of the “consortium” as regards their joint and several undertakings — have been cured. Better still, such deficiencies have supposedly been prevented from arising as a result of the above—quoted provisions, from which it can be immediately established that each of the members of MPC assumes the same joint and several liability as the other members. The foregoing argument is unpersuasive. First, the contract being referred to, entitled “The Automated Counting and Canvassing Project Contract,” is between Comelec and MPEI, not the alleged consortium, MPC. To repeat, it is MPEI — not MPC — that is a party to the Contract. Nowhere in that Contract is there any mention of a consortium or joint venture, of members thereof, much less of joint and several liability. Supposedly executed sometime in May 2003, [43]the Contract bears a notarization date of June 30, 2003, and contains the signature of Willy U. Yu signing as president of MPEI (not for and on behalf of MPC), along with that of the Comelec chair. It provides in Section 3.2 that MPEI (not MPC) is to supply the Equipment and perform the Services under the Contract, in accordance with the appendices thereof; nothing whatsoever is said about any consortium or joint venture or partnership. Second, the portions of Section 1.4 of the Contract reproduced above do nothave the effect of curing (much less preventing) deficiencies in the bilateral agreements entered into by MPEI with the other members of the “consortium,” with respect to their joint and several liabilities. The term “Contract Documents,” as used in the quoted passages of Section 1.4, has a well—defined meaning and actually refers only to the following documents: The Contract itself along with its appendices The Request for Proposal (also known as “Terms of Reference”) issued by the Comelec, including the Tender Inquiries and Bid Bulletins The Tender Proposal submitted by MPEI In other words, the term “Contract Documents” cannot be understood as referring to or including the MOAs and the Teaming Agreements entered into by MPEI with SK C&C, WeSolv, Election.com and ePLDT. This much is very clear and admits of no debate. The attempt to use the provisions of Section 1.4 to shore up the MOAs and the Teaming Agreements is simply unwarranted. Thirdand last, we fail to see how respondents can arrive at the conclusion that, from the above—quoted provisions, it can be immediately established that each of the members of MPC assumes the same joint and several liability as the other members. Earlier, respondents claimed exactly the opposite — that the two MOAs (between MPEI and SK C&C, and between MPEI and WeSolv) had set forth the joint and several undertakings among the parties; whereas the two Teaming Agreements clarified the parties’ respective roles with regard to the Project, with MPEI being the independent contractor and Election.com and ePLDT the subcontractors. Obviously, given the differences in their relationships, their respective liabilities cannot be the same. Precisely, the very clear terms and stipulations contained in the MOAs and the Teaming Agreements — entered into by MPEI with SK C&C, WeSolv, Election.com and ePLDT — negate the idea that these “members” are on a par with one another and are, as such, assuming the same joint and several liability. Moreover, respondents have earlier seized upon the use of the term “particular contract” in the Comelec’s Request for Proposal (RFP), in order to argue that all the members of the joint venture did not need to be solidarily liable for the entire projector joint venture. It was sufficient that the lead company and the member in charge of a particular contract or aspect of the joint venture would agree to be solidarily liable. The glaring lack of consistency leaves us at a loss. Are respondents trying to establish the same joint and solidary liability among all the “members” or not? Enforcement of Liabilities Problematic Next, it is also maintained that the automation Contract between Comelec and the MPEI confirms the solidary undertaking of the lead company and the consortium member concernedfor each particular Contract, inasmuch as the position of MPEI and anyone else performing the services contemplated under the Contract is described therein as that of an independent contractor. The Court does not see, however, how this conclusion was arrived at. In the first place, the contractual provision being relied upon by respondents is Article 14, “Independent Contractors,” which states: “ Nothing contained herein shall be construed as establishing or creating between the COMELEC and MEGA the relationship of employee and employer or principal and agent, it being understood that the position of MEGA and of anyone performing the Services contemplated under this Contract, is that of an independent contractor.” Obviously, the intent behind the provision was simply to avoid the creation of an employer—employee or a principal—agent relationship and the complications that it would produce. Hence, the Article states that the role or position of MPEI, or anyone else performing on its behalf, is that of an independent contractor. It is obvious to the Court that respondents are stretching matters too farwhen they claim that, because of this provision, the Contract in effect confirms the solidary undertakingof the lead company and the consortium member concerned for the particular phase of the project. This assertion is an absolute non sequitur. Enforcement of LiabilitiesUnder the Civil Code Not Possible In any event, it is claimed that Comelec may still enforce the liability of the “consortium” members under the Civil Code provisions on partnership, reasoning that MPEI et al. represented themselves as partners and members of MPC for purposes of bidding for the Project. They are, therefore, liable to the Comelec to the extent that the latter relied upon such representation. Their liability as partners is solidary with respect to everything chargeable to the partnership under certain conditions. The Court has two points to make with respect to this argument. First, it must be recalled that SK C&C, WeSolv, Election.com and ePLDT never represented themselves as partners and members of MPC, whether for purposes of bidding or for something else. It was MPEI alonethat represented them to be members of a “consortium” it supposedly headed. Thus, its acts may not necessarily be held against the other “members.” Second, this argument of the OSG in its Memorandum [44]might possibly apply in the absence of a joint venture agreement or some other writingthat discloses the relationship of the “members” with one another. But precisely, this case does not deal with a situation in which there is nothing in writing to serve as reference, leaving Comelec to rely on mere representations and therefore justifying a falling back on the rules on partnership. For, again, the terms and stipulations of the MOAs entered into by MPEI with SK C&C and WeSolv, as well as the Teaming Agreements of MPEI with Election.com and ePLDT (copies of which have been furnished the Comelec) are very clear with respect to the extent and the limitations of the firms’ respective liabilities. In the case of WeSolv and SK C&C, their MOAs state that their liabilities, while joint and several with MPEI, are limited only to the particular areas of work wherein their services are engaged or their products utilized. As for Election.com and ePLDT, their separate “Teaming Agreements” specifically ascribe to them the role of subcontractor vis—à—visMPEI as contractor and, based on the terms of their particular agreements, neither Election.com nor ePLDT is, with MPEI, jointly and severally liable to Comelec. [45]It follows then that in the instant case, there is no justification for anyone, much less Comelec, to resort to the rules on partnership and partners’ liabilities. Eligibility of a Consortium Based on the Collective Qualifications of Its Members Respondents declare that, for purposes of assessing the eligibility of the bidder, the members of MPC should be evaluated on a collective basis. Therefore, they contend, the failure of MPEI to submit financial statements (on account of its recent incorporation) should not by itself disqualify MPC, since the other members of the “consortium” could meet the criteria set out in the RFP. Thus, according to respondents, the collective nature of the undertaking of the members of MPC, their contribution of assets and sharing of risks, and the community of their interest in the performance of the Contract lead to these reasonable conclusions: (1) that their collective qualificationsshould be the basis for evaluating their eligibility; (2) that the sheer enormity of the project renders it improbable to expect any single entity to be able to comply with all the eligibility requirements and undertake the project by itself; and (3) that, as argued by the OSG, the RFP allows bids from manufacturers, suppliers and/or distributors that have formed themselves into a joint venture, in recognition of the virtual impossibility of a single entity’s ability to respond to the Invitation to Bid. Additionally, argues the Comelec, the Implementing Rules and Regulations of RA 6957 (the Build—Operate—Transfer Law) as amended by RA 7718 would be applicable, as proponents of BOT projects usually form joint ventures or consortiums. Under the IRR, a joint venture/consortium proponent shall be evaluated based on the individual or the collective experience of the member—firms of the joint venture/consortium and of the contractors the proponent has engaged for the project. Unfortunately, this argument seems to assume that the “collective” nature of the undertaking of the members of MPC, their contribution of assets and sharing of risks, and the “community” of their interest in the performance of the Contract entitle MPC to be treated as a joint venture or consortium; and to be evaluated accordingly on the basis of the members’ collective qualifications when, in fact, the evidence before the Court suggest otherwise. This Court in Kilosbayan v. Guingona [46]defined joint ventureas “an association of persons or companies jointly undertaking some commercial enterprise; generally, all contribute assets and share risks. It requires a community of interest in the performance of the subject matter, a right to direct and govern the policy in connection therewith, and [a] duty, which may be altered by agreement to share both in profit and losses.” Going back to the instant case, it should be recalled that the automation Contract with Comelec was not executed by the “consortium” MPC — or by MPEI for and on behalf of MPC — but by MPEI, period. The said Contract contains no mention whatsoeverof any consortium or members thereof. This fact alone seems to contradict all the suppositions about a joint undertaking that would normally apply to a joint venture or consortium: that it is a commercial enterprise involving a community of interest, a sharing of risks, profits and losses, and so on. Now let us consider the four bilateral Agreements, starting with the Memorandum of Agreement between MPEI and WeSolv Open Computing, Inc., dated March 5, 2003. The body of the MOA consists of just seven (7) short paragraphs that would easily fit in one page. It reads as follows: “1. The parties agree to cooperate in successfully implementing the Project in the substance and form as may be most beneficial to both parties and other subcontractors involved in the Project. “2. Mega Pacific shall be responsible for any contract negotiations and signing with the COMELEC and, subject to the latter’s approval, agrees to give WeSolv an opportunity to be present at meetings with the COMELEC concerning WeSolv’s portion of the Project. “3. WeSolv shall be jointly and severally liable with Mega Pacific only for the particular products and/or services supplied by the former for the Project. “4. Each party shall bear its own costs and expenses relative to this agreement unless otherwise agreed upon by the parties. “5. The parties undertake to do all acts and such other things incidental to, necessary or desirable or the attainment of the objectives and purposes of this Agreement. “6. In the event that the parties fail to agree on the terms and conditions of the supply of the products and services including but not limited to the scope of the products and services to be supplied and payment terms, WeSolv shall cease to be bound by its obligations stated in the aforementioned paragraphs. “7. Any dispute arising from this Agreement shall be settled amicably by the parties whenever possible. Should the parties be unable to do so, the parties hereby agree to settle their dispute through arbitration in accordance with the existing laws of the Republic of the Philippines.” (Underscoring supplied.) Even shorter is the Memorandum of Agreement between MPEI and SK C&C Co. Ltd., dated March 9, 2003, the body of which consists of only six (6) paragraphs, which we quote: “1. All parties agree to cooperate in achieving the Consortium’s objective of successfully implementing the Project in the substance and form as may be most beneficial to the Consortium members and in accordance w/ the demand of the RFP. “2. Mega Pacific shall have full powers and authority to represent the Consortium with the Comelec, and to enter and sign, for and in behalf of its members any and all agreement/s which maybe required in the implementation of the Project. “3. Each of the individual members of the Consortium shall be jointly and severally liable with the Lead Firm for the particular products and/or services supplied by such individual member for the project, in accordance with their respective undertaking or sphere of responsibility. “4. Each party shall bear its own costs and expenses relative to this agreement unless otherwise agreed upon by the parties. “5. The parties undertake to do all acts and such other things incidental to, necessary or desirable for the attainment of the objectives and purposes of this Agreement. “6. Any dispute arising from this Agreement shall be settled amicably by the parties whenever possible. Should the parties be unable to do so, the parties hereby agree to settle their dispute through arbitration in accordance with the existing laws of the Republic of the Philippines.” (Underscoring supplied.) It will be noted that the two Agreements quoted above are very similar in wording. Neither of them contains any specifics or details as to the exact nature and scope of the parties’ respective undertakings, performances and deliverables under the Agreement with respect to the automation project. Likewise, the two Agreements are quite bereft of pesos—and—centavos data as to the amount of investments each party contributes, its respective share in the revenues and/or profit from the Contract with Comelec, and so forth — all of which are normal for agreements of this nature. Yet, according to public and private respondents, the participation of MPEI, WeSolv and SK C&C comprises fully 90 percent of the entire undertaking with respect to the election automation project, which is worth about P1.3 billion. As for Election.com and ePLDT, the separate “Teaming Agreements” they entered into with MPEI for the remaining 10 percent of the entire project undertaking are ironically much longer and more detailed than the MOAs discussed earlier. Although specifically ascribing to them the role of subcontractor vis—à—visMPEI as contractor, these Agreements are, however, completely devoid of any pricing data or payment terms. Even the appended Schedules supposedly containing prices of goods and services are shorn of any price data. Again, as mentioned earlier, based on the terms of their particular Agreements, neither Election.com nor ePLDT — with MPEI — is jointly and severally liable to Comelec. It is difficult to imagine how these bare Agreements — especially the first two — could be implemented in practice; and how a dispute between the parties or a claim by Comelec against them, for instance, could be resolved without lengthy and debilitating litigations. Absent any clear—cut statement as to the exact nature and scope of the parties’ respective undertakings, commitments, deliverables and covenants, one party or another can easily dodge its obligation and deny or contest its liability under the Agreement; or claim that it is the other party that should have delivered but failed to. Likewise, in the absence of definite indicators as to the amount of investments to be contributed by each party, disbursements for expenses, the parties’ respective shares in the profits and the like, it seems to the Court that this situation could readily give rise to all kinds of misunderstandings and disagreements over money matters. Under such a scenario, it will be extremely difficult for Comelec to enforce the supposed joint and several liabilities of the members of the “consortium.” The Court is not even mentioning the possibility of a situation arising from a failure of WeSolv and MPEI to agree on the scope, the terms and the conditions for the supply of the products and services under the Agreement. In that situation, by virtue of paragraph 6 of its MOA, WeSolv would perforce cease to be bound by its obligations — including its joint and solidary liability with MPEI under the MOA — and could forthwith disengage from the project. Effectively, WeSolv could at any time unilaterally exit from its MOA with MPEI by simply failing to agree. Where would that outcome leave MPEI and Comelec? To the Court, this strange and beguiling arrangement of MPEI with the other companies does not qualify them to be treated as a consortium or joint venture, at least of the type that government agencies like the Comelec should be dealing with. With more reason is it unable to agree to the proposal to evaluate the members of MPC on a collective basis. In any event, the MPC members claim to be a joint venture/consortium; and respondents have consistently been arguing that the IRR for RA 6957, as amended, should be applied to the instant case in order to allow a collective evaluation of consortium members. Surprisingly, considering these facts, respondents have not deemed it necessary for MPC members to comply with Section 5.4 (a) (iii) of the IRR for RA 6957 as amended. According to the aforementioned provision, if the project proponent is a joint venture or consortium, the members or participants thereof are required to submit a sworn statement that, if awarded the contract, they shall bind themselves to be jointly, severally and solidarily liable for the project proponent’s obligations thereunder. This provision was supposed to mirror Section 5 of RA 6957, as amended, which states: “In all cases, a consortium that participates in a bid must present proof that the members of the consortium have bound themselves jointly and severally to assume responsibility for any project. The withdrawal of any member of the consortium prior to the implementation of the project could be a ground for the cancellation of the contract.” The Court has certainly not seen any joint and several undertaking by the MPC members that even approximates the tenor of that which is described above. We fail to see why respondents should invoke the IRR if it is for their benefit, but refuse to comply with it otherwise. B. DOST Technical Tests Flunked by the Automated Counting Machines Let us now move to the second subtopic, which deals with the substantive issue: the ACM’s failure to pass the tests of the Department of Science and Technology (DOST). After respondent “consortium” and the other bidder, TIM, had submitted their respective bids on March 10, 2003, the Comelec’s BAC — through its Technical Working Group (TWG) and the DOST — evaluated their technical proposals. Requirements that were highly technical in nature and that required the use of certain equipment in the evaluation process were referred to the DOST for testing. The Department reported thus: TEST RESULTS MATRIX [47][Technical Evaluation of Automated Counting Machine] <table><tbody><tr><td></td><td> KEY REQUIREMENTS[QUESTIONS]</td><td colspan=2> MEGA—PACIFICCONSORTIUM</td><td colspan=2> TOTAL INFORMATION MANAGEMENT</td></tr><tr><td></td><td> </td><td> YES</td><td> NO</td><td> YES</td><td> NO</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 1.</td><td> Does the machine have</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> an accuracy rating of at</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> least 99.995 percent</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> At COLD</td><td> x</td><td></td><td> x</td><td></td></tr><tr><td></td><td> environmental</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> condition</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> At NORMAL</td><td></td><td> x</td><td></td><td> x</td></tr><tr><td></td><td> environmental</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> conditions</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> At HARSH</td><td></td><td> x</td><td> x</td><td></td></tr><tr><td></td><td> environmental</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> conditions</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 2.</td><td> Accurately records and</td><td> x</td><td></td><td> x</td><td></td></tr><tr><td></td><td> reports the date and time</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> of the start and end of</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> counting of ballots per</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> precinct?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>3.</td><td> Prints election returns</td><td> x</td><td></td><td> x</td><td></td></tr><tr><td></td><td> without any loss of date</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> during generation of</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> such reports?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>4.</td><td> Uninterruptible back—up</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> power system, that will</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> engage immediately to</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> allow operation of at</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> least 10 minutes after</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> outage, power surge or</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> abnormal electrical</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> occurrences?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 5.</td><td> Machine reads two—</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> sided ballots in one</td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td> pass?</td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>6.</td><td> Machine can detect</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> previously counted</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> ballots and prevent</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> previously counted</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> ballots from being</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> counted more than</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> once?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 7.</td><td> Stores results of counted</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> votes by precinct in</td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td> external (removable)</td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td> storage device?</td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 8.</td><td> Data stored in external</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> media is encrypted?</td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 9.</td><td> Physical key or similar</td><td> x</td><td></td><td> x</td><td></td></tr><tr><td></td><td> device allows, limits, or</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> restricts operation of the</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> machine?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 10.</td><td> CPU speed is at least</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> 400mHz?</td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 11.</td><td> Port to allow use of</td><td> x</td><td></td><td> x</td><td></td></tr><tr><td></td><td> dot—matrix printers?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 12.</td><td> Generates printouts of</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> the election returns in a</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> format specified by the</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> COMELEC?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> Generates printouts</td><td> x</td><td></td><td> x</td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> In format specified by</td><td></td><td> x</td><td></td><td> x</td></tr><tr><td></td><td> COMELEC</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 13.</td><td> Prints election returns</td><td> x</td><td></td><td> x</td><td></td></tr><tr><td></td><td> without any loss of data</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> during generation of</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> such report?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 14.</td><td> Generates an audit trail</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> of the counting</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> machine, both hard copy</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> and soft copy?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td>Hard copy</td><td> x</td><td></td><td> x</td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td>Soft copy</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 15.</td><td> Does the</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> City/Municipal</td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td> Canvassing System</td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td> consolidate results from</td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td> all precincts within it</td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td> using the encrypted soft</td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td> copy of the data</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> generated by the</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> counting machine and</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> stored on the removable</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> data storage device?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 16.</td><td> Does the</td><td></td><td> x</td><td></td><td> x</td></tr><tr><td></td><td> City/Municipal</td><td></td><td> Note: This</td><td></td><td> Note: This</td></tr><tr><td></td><td> Canvassing System</td><td></td><td> particular</td><td></td><td> particular</td></tr><tr><td></td><td> consolidate results from</td><td></td><td> requirement</td><td></td><td> requirement</td></tr><tr><td></td><td> all precincts within it</td><td></td><td> needs further</td><td></td><td> needs further</td></tr><tr><td></td><td> using the encrypted soft</td><td></td><td> verification</td><td></td><td> verification</td></tr><tr><td></td><td> copy of the data</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> generated by the</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> counting machine and</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> transmitted through an</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> electronic transmission</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> media?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 17.</td><td> Does the system output</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> a Zero City/Municipal</td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td> Canvass Report, which</td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td> is printed on election</td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td> day prior to the conduct</td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td> of the actual canvass</td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td> operation, that shows</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> that all totals for all the</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> votes for all the</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> candidates and other</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> information, are indeed</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> zero or null?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 18.</td><td> Does the system</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> consolidate results from</td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td> all precincts in the</td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td> city/municipality using</td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td> the data storage device</td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td> coming from the</td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td> counting machine?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 19.</td><td> Is the machine 100%</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> accurate?</td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 20.</td><td> Is the Program able to</td><td></td><td> x</td><td></td><td> x</td></tr><tr><td></td><td> detect previously</td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td> downloaded precinct</td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td> results and prevent these</td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td> from being inputted</td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td> again into the System?</td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 21.</td><td> The System is able to</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> print the specified</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> reports and the audit</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> trail without any loss of</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> data during generation</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> of the above—mentioned</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> reports?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> Prints specified reports</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> Audit Trail</td><td></td><td> x</td><td></td><td> x</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 22.</td><td> Can the result of the</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> city/municipal</td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td> consolidation be stored</td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td> in a data storage device?</td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 23.</td><td> Does the system</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> consolidate results from</td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td> all precincts in the</td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td> provincial/district/</td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td> national using the data</td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td> storage device from</td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td> different levels of</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> consolidation?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 24.</td><td> Is the system 100%</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> accurate?</td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 25.</td><td> Is the Program able to</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> detect previously</td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td> downloaded precinct</td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td> results and prevent these</td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td> from being inputted</td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td> again into the System?</td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> 26.</td><td> The System is able to</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> print the specified</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> reports and the audit</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> trail without any loss of</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> data during generation</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> of the abovementioned</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> reports?</td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> Prints specified reports</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td> Audit Trail</td><td></td><td> x</td><td></td><td> x</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> verification</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>27.</td><td> Can the results of the</td><td> x</td><td></td><td></td><td> x</td></tr><tr><td></td><td> provincial/district/</td><td></td><td></td><td></td><td> Note: This</td></tr><tr><td></td><td> national consolidation</td><td></td><td></td><td></td><td> particular</td></tr><tr><td></td><td> be stored in a data</td><td></td><td></td><td></td><td> requirement</td></tr><tr><td></td><td> storage device?</td><td></td><td></td><td></td><td> needs further</td></tr><tr><td></td><td></td><td></td><td></td><td></td><td> verification</td></tr></tbody></table> According to respondents, it was only after the TWG and the DOST had conducted their separate tests and submitted their respective reports that the BAC, on the basis of these reports formulated its comments/recommendations on the bids of the consortium and TIM. The BAC, in its Report dated April 21, 2003, recommended that the Phase II project involving the acquisition of automated counting machines be awarded to MPEI. It said: “After incisive analysis of the technical reports of the DOST and the Technical Working Group for Phase II — Automated Counting Machine, the BAC considers adaptability to advances in modern technology to ensure an effective and efficient method, as well as the security and integrity of the system. “The results of the evaluation conducted by the TWG and that of the DOST (14 April 2003 report), would show the apparent advantage of Mega—Pacific over the other competitor, TIM. “The BAC further noted that both Mega—Pacific and TIM obtained some ‘failed marks’ in the technical evaluation. In general, the ‘failed marks’ of Total Information Management as enumerated above affect the counting machine itself which are material in nature, constituting non—compliance to the RFP. On the other hand, the ‘failed marks’ of Mega—Pacific are mere formalities on certain documentary requirements which the BAC may waive as clearly indicated in the Invitation to Bid. “In the DOST test, TIM obtained 12 failed marks and mostly attributed to the counting machine itself as stated earlier. These are requirements of the RFP and therefore the BAC cannot disregard the same. “Mega—Pacific failed in 8 items however these are mostly on the software which can be corrected by reprogramming the software and therefore can be readily corrected. “The BAC verbally inquired from DOST on the status of the retest of the counting machines of the TIM and was informed that the report will be forthcoming after the holy week. The BAC was informed that the retest is on a different parameters they’re being two different machines being tested. One purposely to test if previously read ballots will be read again and the other for the other features such as two sided ballots. “The said machine and the software therefore may not be considered the same machine and program as submitted in the Technical proposal and therefore may be considered an enhancement of the original proposal. “Advance information relayed to the BAC as of 1:40 PM of 15 April 2003 by Executive Director Ronaldo T. Viloria of DOST is that the result of the test in the two counting machines of TIM contains substantial errors that may lead to the failure of these machines based on the specific items of the RFP that DOST has to certify. OPENING OF FINANCIAL BIDS “The BAC on 15 April 2003, after notifying the concerned bidders opened the financial bids in their presence and the results were as follows: Mega—Pacific: Option 1 — Outright purchase: Bid Price of Php1,248,949,088.00 Option 2 — Lease option: 70% Down payment of cost of hardware or Php642,755,757.07 Remainder payable over 50 months or a total of Php642,755,757.07 Discount rate of 15% p.a. or 1.2532% per month. Total Number of Automated Counting Machine — 1,769 ACMs (Nationwide) TIM: Total Bid Price — Php1,297,860,560.00 Total Number of Automated Counting Machine — 2,272 ACMs (Mindanao and NCR only) “Premises considered, it appears that the bid of Mega Pacific is the lowest calculated responsive bid, and therefore, the Bids and Awards Committee (BAC) recommends that the Phase II project re Automated Counting Machine be awarded to Mega Pacific eSolutions, Inc.” [48] The BAC, however, also stated on page 4 of its Report: “ Based on the 14 April 2003 report (Table 6) of the DOST, it appears that both Mega—Pacific and TIM (Total Information Management Corporation) failed to meet some of the requirements. Below is a comparative presentation of the requirements wherein Mega—Pacific or TIM or both of them failed : . . ..” What followed was a list of “key requirements,” referring to technical requirements, and an indication of which of the two bidders had failed to meet them. Failure to Meet theRequired Accuracy Rating The first of the key requirements was that the counting machines were to have an accuracy rating of at least 99.9995 percent. The BAC Report indicates that both Mega Pacific and TIM failed to meet this standard. The key requirement of accuracy rating happens to be part and parcel of the Comelec’s Request for Proposal (RFP). The RFP, on page 26, even states that the ballot counting machines and ballot counting software “ must have an accuracy rating of 99.9995% (not merely 99.995%) or better as certified by a reliable independent testing agency.” When questioned on this matter during the Oral Argument, Commissioner Borra tried to wash his hands by claiming that the required accuracy rating of 99.9995 percent had been set by a private sector group in tandem with Comelec. He added that the Commission had merely adopted the accuracy rating as part of the group’s recommended bid requirements, which it had not bothered to amend even after being advised by DOST that such standard was unachievable. This excuse, however, does not in any way lessen Comelec’s responsibility to adhere to its own published bidding rules, as well as to see to it that the consortium indeed meets the accuracy standard. Whichever accuracy rating is the right standard — whether 99.995 or 99.9995 percent — the fact remains that the machines of the so—called “consortium” failed to even reach the lesser of the two. On this basis alone, it ought to have been disqualified and its bid rejected outright. At this point, the Court stresses that the essence of public bidding is violated by the practice of requiring very high standards or unrealistic specifications that cannot be met — like the 99.9995 percent accuracy rating in this case — only to water them down afterthe bid has been award. Such scheme, which discourages the entry of prospective bona fidebidders, is in fact a sure indication of fraud in the bidding, designed to eliminate fair competition. Certainly, if no bidder meets the mandatory requirements, standards or specifications, then no award should be made and a failed bidding declared. Failure of Software to DetectPreviously Downloaded Data Furthermore, on page 6 of the BAC Report, it appears that the “consortium” as well as TIM failed to meet another key requirement — for the counting machine’s software program to be able to detect previously downloaded precinct results and to prevent these from being entered again into the counting machine.This same deficiency on the part of both bidders reappears on page 7 of the BAC Report, as a result of the recurrence of their failure to meet the said key requirement. That the ability to detect previously downloaded data at different canvassing or consolidation levels is deemed of utmost importance can be seen from the fact that it is repeated three times in the RFP. On page 30 thereof, we find the requirement that the city/municipalcanvassing system software must be able to detect previously downloaded precinct results and prevent these from being “inputted” again into the system. Again, on page 32 of the RFP, we read that the provincial/districtcanvassing system software must be able to detect previously downloaded city/municipal results and prevent these from being “inputted” again into the system. And once more, on page 35 of the RFP, we find the requirement that the nationalcanvassing system software must be able to detect previously downloaded provincial/district results and prevent these from being “inputted” again into the system. Once again, though, Comelec chose to ignore this crucial deficiency, which should have been a cause for the gravest concern. Come May 2004, unscrupulous persons may take advantage of and exploit such deficiency by repeatedly downloading and feeding into the computers results favorable to a particular candidate or candidates. We are thus confronted with the grim prospect of election fraud on a massive scale by means of just a few key strokes. The marvels and woes of the electronic age! Inability to Printthe Audit Trail But that grim prospect is not all. The BAC Report, on pages 6 and 7, indicate that the ACMs of both bidders were unable to print the audit trailwithout any loss of data. In the case of MPC, the audit trail system was “not yet incorporated” into its ACMs. This particular deficiency is significant, not only to this bidding but to the cause of free and credible elections. The purpose of requiring audit trails is to enable Comelec to trace and verify the identities of the ACM operators responsible for data entry and downloading, as well as the times when the various data were downloaded into the canvassing system, in order to forestall fraud and to identify the perpetrators. Thus, the RFP on page 27 states that the ballot counting machines and ballot counting softwaremust print an audit trail of all machine operations for documentation and verification purposes. Furthermore, the audit trail must be stored on the internal storage device and be available on demand for future printing and verifying. On pages 30—31, the RFP also requires that the city/municipalcanvassing system softwarebe able to print an audit trail of the canvassing operations, including therein such data as the date and time the canvassing program was started, the log—in of the authorized users (the identity of the machine operators), the date and time the canvass data were downloaded into the canvassing system, and so on and so forth. On page 33 of the RFP, we find the same audit trail requirement with respect to the provincial/districtcanvassing system software; and again on pages 35—36 thereof, the same audit trail requirement with respect to the nationalcanvassing system software. That this requirement for printing audit trails is not to be lightly brushed aside by the BAC or Comelec itself as a mere formality or technicality can be readily gleaned from the provisions of Section 7 of RA 8436, which authorizes the Commission to use an automated system for elections. The said provision which respondents have quoted several times, provides that ACMs are to possess certain features divided into two classes: those that the statute itself considers mandatoryand other features or capabilities that the law deems optional. Among those considered mandatory are “provisions for audit trails”! Section 7 reads as follows: “ The Systemshall contain the following features: (a) use of appropriate ballots; (b) stand—alone machine which can count votes and an automated system which can consolidate the results immediately; (c)with provisions for audit trails; (d) minimum human intervention; and (e) adequate safeguard/security measures.”(Italics and emphases supplied.) In brief, respondents cannot deny that the provision requiring audit trails is indeed mandatory, considering the wording of Section 7 of RA 8436. Neither can Respondent Comelec deny that it has relied on the BAC Report, which indicates that the machines or the software was deficient in that respect. And yet, the Commission simply disregarded this shortcoming and awarded the Contract to private respondent, thereby violating the very law it was supposed to implement. C. Inadequacy of Post FactoRemedial Measures Respondents argue that the deficiencies relating to the detection of previously downloaded data, as well as provisions for audit trails, are mere shortcomings or minor deficiencies in software or programming, which can be rectified. Perhaps Comelec simply relied upon the BAC Report, which states on page 8 thereof that “ Mega Pacific failed in 8 items[;] however these are mostly on the software which can be corrected by re—programming . . . and therefore can be readily corrected.” The undersigned ponente’s questions, some of which were addressed to Commissioner Borra during the Oral Argument, remain unanswered to this day. First of all, who made the determination that the eight “fail” marks of Mega Pacific were on account of the software — was it DOST or TWG? How can we be sure these failures were not the results of machine defects? How was it determined that the software could actually be re—programmed and thereby rectified? Did a qualified technical expert read and analyze the source code [49]for the programs and conclude that these could be saved and remedied? (Such determination cannot be done by any other means save by the examination and analysis of the source code.) Who was this qualified technical expert? When did he carry out the study? Did he prepare a written report on his findings? Or did the Comelec just make a wild guess? It does not follow that all defects in software programs can be rectified, and the programs saved. In the information technology sector, it is common knowledge that there are many badly written programs, with significant programming errors written into them; hence it does not make economic sense to try to correct the programs; instead, programmers simply abandon them and just start from scratch. There’s no telling if any of these programs is unrectifiable, unless a qualified programmer reads the source code. And if indeed a qualified expert reviewed the source code, did he also determine how much work would be needed to rectify the programs? And how much time and money would be spent for that effort? Who would carry out the work? After the rectification process, who would ascertain and how would it be ascertained that the programs have indeed been properly rectified, and that they would work properly thereafter? And of course, the most important question to ask: could the rectification be done in time for the elections in 2004? Clearly, none of the respondents bothered to think the matter through. Comelec simply took the word of the BAC as gospel truth, without even bothering to inquire from DOST whether it was true that the deficiencies noted could possibly be remedied by re—programming the software. Apparently, Comelec did not care about the software, but focused only on purchasing the machines. What really adds to the Court’s dismay is the admission made by Commissioner Borra during the Oral Argument that the software currently being used by Comelec was merely the “demo” version, inasmuch as the final version that would actually be used in the elections was still being developed and had not yet been finalized. It is not clear when the final version of the software would be ready for testing and deployment. It seems to the Court that Comelec is just keeping its fingers crossed and hoping the final product would work. Is there a “Plan B” in case it does not? Who knows? But all these software programs are part and parcel of the bidding and the Contract awarded to the Consortium. Why is it that the machines are already being brought in and paid for, when there is as yet no way of knowing if the final version of the software would be able to run them properly, as well as canvass and consolidate the results in the manner required? The counting machines, as well as the canvassing system, will never work properly without the correct software programs. There is an old adage that is still valid to this day: “Garbage in, garbage out.” No matter how powerful, advanced and sophisticated the computers and the servers are, if the software being utilized is defective or has been compromised, the results will be no better than garbage. And to think that what is at stake here is the 2004 national elections — the very basis of our democratic life. Correction of Defects? To their Memorandum, public respondents proudly appended 19 Certifications issued by DOST declaring that some 285 counting machines had been tested and had passed the acceptance testing conducted by the Department on October 8—18, 2003. Among those tested were some machines that had failed previous tests, but had undergone adjustments and thus passed re—testing. Unfortunately, the Certifications from DOST fail to divulge in what manner and by what standards or criteria the condition, performance and/or readiness of the machines were re—evaluated and re—appraised and thereafter given the passing mark. Apart from that fact, the remedial efforts of respondents were, not surprisingly, apparently focused again on the machines — the hardware. Nothing was said or done about the software— the deficiencies as to detection and prevention of downloading and entering previously downloaded data, as well as the capability to print an audit trail. No matter how many times the machines were tested and re—tested, if nothing was done about the programming defects and deficiencies, the same danger of massive electoral fraud remains. As anyone who has a modicum of knowledge of computers would say, “That’s elementary!” And only last December 5, 2003, an Inq7.net news report quoted the Comelec chair as saying that the new automated poll system would be used nationwide in May 2004, even as the software for the system remained unfinished. It also reported that a certain Titus Manuel of the Philippine Computer Society, which was helping Comelec test the hardware and software, said that the software for the counting still had to be submitted on December 15, while the software for the canvassing was due in early January. Even as Comelec continues making payments for the ACMs, we keep asking ourselves: who is going to ensure that the software would be tested and would work properly? At any rate, the re—testing of the machines and/or the 100 percent testing of all machines (testing of every single unit) would not serve to eradicate the grave abuse of discretion already committed by Comelec when it awarded the Contract on April 15, 2003, despite the obvious and admitted flaws in the bidding process, the failure of the “winning bidder” to qualify, and the inability of the ACMs and the intended software to meet the bid requirements and rules. Comelesuasive c’s Latest “Assurances” Are Unper Even the latest pleadings filed by Comelec do not serve to allay our apprehensions. They merely affirm and compound the serious violations of law and gravely abusive acts it has committed. Let us examine them. The Resolution issued by this Court on December 9, 2003 required respondents to inform it as to the number of ACMs delivered and paid for, as well as the total payment made to date for the purchase thereof. They were likewise instructed to submit a certification from the DOST attesting to the number of ACMs tested, the number found to be defective; and “ whether the reprogrammed software has been tested and found to have complied with the requirements under Republic Act No. 8436.” [50] In its “Partial Compliance and Manifestation” dated December 29, 2003, Comelec informed the Court that 1,991 ACMs had already been delivered to the Commission as of that date. It further certified that it had already paid the supplier the sum of P849,167,697.41, which corresponded to 1,973 ACM units that had passed the acceptance testing procedures conducted by the MIRDC—DOST [51]and which had therefore been accepted by the poll body. In the same submission, for the very first time, Comelec also disclosed to the Court the following: “The Automated Counting and Canvassing Project involves not only the manufacturing of the ACM hardware but also the development of three (3) types of software, which are intended for use in the following: Evaluation of Technical Bids Testing and Acceptance Procedures Election Day Use.” Purchase of the First Type ofSoftware Without Evaluation In other words, the first type of software was to be developed solely for the purpose of enabling the evaluation of the bidder’s technical bid. Comelec explained thus: “ In addition to the presentation of the ACM hardware, the bidders were required to develop a ‘base’ software program that will enable the ACM to function properly. Since the software program utilized during the evaluation of bids is not the actual software program to be employed on election day, there being two (2) other types of software program that will still have to be developed and thoroughly tested prior to actual election day use, defects in the ‘base’ software that can be readily corrected by reprogramming are considered minor in nature, and may therefore be waived.” In short, Comelec claims that it evaluated the bids and made the decision to award the Contract to the “winning” bidder partly on the basis of the operation of the ACMs running a “base” software. That software was therefore nothing but a sample or “demo” software, which would not be the actual one that would be used on election day. Keeping in mind that the Contract involves the acquisition of not just the ACMs or the hardware, but also the software that would run them, it is now even clearer that the Contract was awarded without Comelec having seen, much less evaluated, the finalproduct — the software that would finally be utilized come election day. (Not even the “near—final” product, for that matter). What then was the point of conducting the bidding, when the software that was the subject of the Contract was still to be createdand could conceivably undergo innumerable changes before being considered as being in final form? And that is not all! No Explanation for Lapsesin the Second Type of Software The second phase, allegedly involving the second type of software, is simply denominated “Testing and Acceptance Procedures.” As best as we can construe, Comelec is claiming that this second type of software is also to be developedand delivered by the supplier in connection with the “testing and acceptance” phase of the acquisition process. The previous pleadings, though — including the DOST reports submitted to this Court — have not heretofore mentioned any statement, allegation or representation to the effect that a particular set of software was to be developed and/or delivered by the supplier in connection with the testing and acceptance of delivered ACMs. What the records do show is that the imported ACMs were subjected to the testing and acceptance process conducted by the DOST. Since the initial batch delivered included a high percentage of machines that had failed the tests, Comelec asked the DOST to conduct a 100 percent testing; that is, to test every single one of the ACMs delivered. Among the machines tested on October 8 to 18, 2003, were some units that had failed previous tests but had subsequently been re—tested and had passed. To repeat, however, until now, there has never been any mention of a second set or type of software pertaining to the testing and acceptance process. In any event, apart from making that misplaced and uncorroborated claim, Comelec in the same submission also professes (in response to the concerns expressed by this Court) that the reprogrammed software has been tested and found to have complied with the requirements of RA 8436. It reasoned thus: “Since the software program is an inherent element in the automated counting system, the certification issued by the MIRDC—DOST that one thousand nine hundred seventy—three (1,973) units passed the acceptance test procedures is an official recognition by the MIRDC—DOST that the software component of the automated election system, which has been reprogrammed to comply with the provisions of Republic Act No. 8436 as prescribed in the Ad Hoc Technical Evaluation Committee’s ACM Testing and Acceptance Manual, has passed the MIRDC—DOST tests.” The facts do not support this sweeping statement of Comelec. A scrutiny of the MIRDC—DOST letter dated December 15, 2003, [52]which it relied upon, does not justify its grand conclusion. For clarity’s sake, we quote in full the letter—certification, as follows: “15 December 2003 “HON. RESURRECCION Z. BORRACommissioner—in—ChargePhase II, Modernization ProjectCommission on ElectionsIntramuros, Manila <table><tbody><tr><td colspan=2> Attention: Atty. Jose M. Tolentino, Jr.</td></tr><tr><td></td><td> Project Director</td></tr></tbody></table> “Dear Commissioner Borra: “We are pleased to submit 11 DOST Test Certifications representing 11 lots and covering 158 units of automated counting machines (ACMs) that we have tested from 02—12 December 2003. “To date, we have tested all the 1,991 units of ACMs, broken down as follow: ( sic) <table><tbody><tr><td> 1 stbatch — 30 units</td><td> 4 thbatch — 438 units</td></tr><tr><td> 2 ndbatch — 288 units</td><td> 5 thbatch — 438 units</td></tr><tr><td> 3 rdbatch — 414</td><td> units 6 thbatch — 383 units</td></tr></tbody></table> “It should be noted that a total of 18 units have failed the test. Out of these 18 units, only one (1) unit has failed the retest. “Thank you and we hope you will find everything in order. “Very truly yours, “ROLANDO T. VILORIA, CESO IIIExecutive Director cumChairman, DOST—Technical Evaluation Committee” Even a cursory glance at the foregoing letter shows that it is completely bereft of anything that would remotely support Comelec’s contention that the “software component of the automated election system x x x has been reprogrammed to comply with” RA 8436, and “has passed the MIRDC—DOST tests.” There is no mention at all of any software reprogramming. If the MIRDC—DOST had indeed undertaken the supposed reprogramming and the process turned out to be successful, that agency would have proudly trumpeted its singular achievement. How Comelec came to believe that such reprogramming had been undertaken is unclear. In any event, the Commission is not forthright and candid with the factual details. If reprogramming has been done, who performed it and when? What exactly did the process involve? How can we be assured that it was properly performed? Since the facts attendant to the alleged reprogramming are still shrouded in mystery, the Court cannot give any weight to Comelec’s bare allegations. The fact that a total of 1,973 of the machines has ultimately passed the MIRDC—DOST tests does not by itself serve as an endorsement of the soundness of the software program, much less as a proof that it has been reprogrammed. In the first place, nothing on record shows that the tests and re—tests conducted on the machines were intended to address the serious deficiencies noted earlier. As a matter of fact, the MIRDC—DOST letter does not even indicate what kinds of tests or re—tests were conducted, their exact nature and scope, and the specific objectives thereof. [53]The absence of relevant supporting documents, combined with the utter vagueness of the letter, certainly fails to inspire belief or to justify the expansive confidence displayed by Comelec. In any event, it goes without saying that remedial measures such as the alleged reprogramming cannot in any way mitigate the grave abuse of discretion already committed as early as April 15, 2003. Rationale of Public Bidding Negatedby the Third Type of Software Respondent Comelec tries to assuage this Court’s anxiety in these words: “ The reprogrammed software that has already passed the requirements of Republic Act No. 8436 during the MIRDC—DOST testing and acceptance procedures will require further customization since the following additional elements, among other things, will have to be considered before the final software can be used on election day: 1. Final Certified List of Candidates x x x 2. Project of Precincts x x x 3. Official Ballot Design and Security Features x x x 4. Encryption, digital certificates and digital signatures . . . The certified list of candidates for national elective positions will be finalized on or before 23 January 2004 while the final list of projects of precincts will be prepared also on the same date. Once all the above elements are incorporated in the software program, the Test Certification Group created by the Ad Hoc Technical Evaluation Committee will conduct meticulous testing of the final software before the same can be used on election day. In addition to the testing to be conducted by said Test Certification Group, the Comelec will conduct mock elections in selected areas nationwide not only for purposes of public information but also to further test the final election day program. Public respondent Comelec, therefore, requests that it be given up to 16 February 2004 to comply with this requirement.” The foregoing passage shows the imprudent approach adopted by Comelec in the bidding and acquisition process. The Commission says that before the software can be utilized on election day, it will require “customization” through addition of data — like the list of candidates, project of precincts, and so on. And inasmuch as such data will become available only in January 2004 anyway, there is therefore no perceived need on Comelec’s part to rush the supplier into producing the final (or near—final) version of the software before that time. In any case, Comelec argues that the software needed for the electoral exercise can be continuously developed, tested, adjusted and perfected, practically all the way up to election day, at the same time that the Commission is undertaking all the other distinct and diverse activities pertinent to the elections. Given such a frame of mind, it is no wonder that Comelec paid little attention to the counting and canvassing software during the entire bidding process, which took place in February—March 2003. Granted that the software was defective, could not detect and prevent the re—use of previously downloaded data or produce the audit trail — aside from its other shortcomings — nevertheless, all those deficiencies could still be corrected down the road. At any rate, the software used for bidding purposes would not be the same one that will be used on election day, so why pay any attention to its defects? Or to the Comelec’s own bidding rules for that matter? Clearly, such jumbled ratiocinations completely negate the rationale underlying the bidding process mandated by law. At the very outset, the Court has explained that Comelec flagrantly violated the public policy on public biddings (1) by allowing MPC/MPEI to participate in the bidding even though it was not qualified to do so; and (2) by eventually awarding the Contract to MPC/MPEI. Now, with the latest explanation given by Comelec, it is clear that the Commission further desecrated the law on public bidding by permitting the winning bidder to change and alter the subject of the Contract (the software), in effect allowing a substantive amendment without public bidding. This stance is contrary to settled jurisprudence requiring the strict application of pertinent rules, regulations and guidelines for public bidding for the purpose of placing each bidder, actual or potential, on the same footing. The essence of public bidding is, after all, an opportunity for fair competition, and a fair basis for the precise comparison of bids. In common parlance, public bidding aims to “level the playing field.” That means each bidder must bid under the same conditions; and be subject to the same guidelines, requirements and limitations, so that the best offer or lowest bid may be determined, all other things being equal. Thus, it is contrary to the very concept of public bidding to permit a variance between the conditions under which bids are invited and those under which proposals are submitted and approved; or, as in this case, the conditions under which the bid is won and those under which the awarded Contract will be complied with. The substantive amendment of the contract bidded out, without any public bidding — afterthe bidding process had been concluded — is violative of the public policy on public biddings, as well as the spirit and intent of RA 8436. The whole point in going through the public bidding exercise was completely lost. The very rationale of public bidding was totally subverted by the Commission. From another perspective, the Comelec approach also fails to make sense. Granted that, before election day, the software would still have to be customized to each precinct, municipality, city, district, and so on, there still was nothing at all to prevent Comelec from requiring prospective suppliers/bidders to produce, at the very start of the bidding process, the “next—to—final” versions of the software (the best software the suppliers had) — pre—tested and ready to be customized to the final list of candidates and project of precincts, among others, and ready to be deployed thereafter. The satisfaction of such requirement would probably have provided far better bases for evaluation and selection, as between suppliers, than the so—called demo software. Respondents contend that the bidding suppliers’ counting machines were previously used in at least one political exercise with no less than 20 million voters. If so, it stands to reason that the software used in that past electoral exercise would probably still be available and, in all likelihood, could have been adopted for use in this instance. Paying for machines and software of that category (already tried and proven in actual elections and ready to be adopted for use) would definitely make more sense than paying the same hundreds of millions of pesos for demo software and empty promises of usable programs in the future. But there is still another gut—level reason why the approach taken by Comelec is reprehensible. It rides on the perilous assumption that nothing would go wrong; and that, come election day, the Commission and the supplier would have developed, adjusted and “re—programmed” the software to the point where the automated system could function as envisioned. But what if such optimistic projection does not materialize? What if, despite all their herculean efforts, the software now being hurriedly developed and tested for the automated system performs dismally and inaccurately or, worse, is hacked and/or manipulated? [54]What then will we do with all the machines and defective software already paid forin the amount of P849 million of our tax money? Even more important, what will happen to our country in case of failure of the automation? The Court cannot grant the plea of Comelec that it be given until February 16, 2004 to be able to submit a “certification relative to the additional elements of the software that will be customized,” because for us to do so would unnecessarily delay the resolution of this case and would just give the poll body an unwarranted excuse to postpone the 2004 elections. On the other hand, because such certification will not cure the gravely abusive actions complained of by petitioners, it will be utterly useless. Is this Court being overly pessimistic and perhaps even engaging in speculation? Hardly. Rather, the Court holds that Comelec should not have gambled on the unrealistic optimism that the supplier’s software development efforts would turn out well. The Commission should have adopted a much more prudent and judicious approach to ensure the delivery of tried and tested software, and readied alternative courses of action in case of failure. Considering that the nation’s future is at stake here, it should have done no less. Epilogue Once again, the Court finds itself at the crossroads of our nation’s history. At stake in this controversy is not just the business of a computer supplier, or a questionable proclamation by Comelec of one or more public officials. Neither is it about whether this country should switch from the manual to the automated system of counting and canvassing votes. At its core is the ability and capacity of the Commission on Elections to perform properly, legally and prudently its legal mandate to implement the transition from manual to automated elections. Unfortunately, Comelec has failed to measure up to this historic task. As stated at the start of this Decision, Comelec has not merely gravely abused its discretion in awarding the Contract for the automation of the counting and canvassing of the ballots. It has also put at grave risk the holding of credible and peaceful elections by shoddily accepting electronic hardware and software that admittedly failed to pass legally mandated technical requirements. Inadequate as they are, the remedies it proffers post factodo not cure the grave abuse of discretion it already committed (1) on April 15, 2003, when it illegally made the award; and (2) “sometime” in May 2003 when it executed the Contract for the purchase of defective machines and non—existent software from a non—eligible bidder. For these reasons, the Court finds it totally unacceptable and unconscionable to place its imprimatur on this void and illegal transaction that seriously endangers the breakdown of our electoral system. For this Court to cop—out and to close its eyes to these illegal transactions, while convenient, would be to abandon its constitutional duty of safeguarding public interest. As a necessary consequence of such nullity and illegality, the purchase of the machines and all appurtenances thereto including the still—to—be—produced (or in Comelec’s words, to be “reprogrammed”) software, as well as all the payments made therefor, have no basis whatsoever in law. The public funds expended pursuant to the void Resolution and Contract must therefore be recovered from the payees and/or from the persons who made possible the illegal disbursements, without prejudice to possible criminal prosecutions against them. Furthermore, Comelec and its officials concerned must bear full responsibility for the failed bidding and award, and held accountable for the electoral mess wrought by their grave abuse of discretion in the performance of their functions. The State, of course, is not bound by the mistakes and illegalities of its agents and servants. True, our country needs to transcend our slow, manual and archaic electoral process. But before it can do so, it must first have a diligent and competent electoral agency that can properly and prudently implement a well—conceived automated election system. At bottom, before the country can hope to have a speedy and fraud—free automated election, it must first be able to procure the proper computerized hardware and software legally, based on a transparent and valid system of public bidding. As in any democratic system, the ultimate goalof automating elections must be achieved by a legal, valid and above—board process of acquiring the necessary tools and skills therefor. Though the Philippines needs an automated electoral process, it cannot accept just any system shoved into its bosom through improper and illegal methods. As the saying goes, the end never justifies the means. Penumbral contracting will not produce enlightened results. WHEREFORE, the Petition is GRANTED. The Court hereby declares NULLand VOIDComelec Resolution No. 6074 awarding the contract for Phase II of the CAES to Mega Pacific Consortium (MPC). Also declared null and void is the subject Contract executed between Comelec and Mega Pacific eSolutions (MPEI). [55]Comelec is further ORDEREDto refrain from implementing any other contract or agreement entered into with regard to this project. Let a copy of this Decision be furnished the Office of the Ombudsman which shall determine the criminal liability, if any, of the public officials (and conspiring private individuals, if any) involved in the subject Resolution and Contract. Let the Office of the Solicitor General also take measures to protect the government and vindicate public interest from the ill effects of the illegal disbursements of public funds made by reason of the void Resolution and Contract. SO ORDERED. Carpio, Austria—Martinez, Carpio—Morales,and Callejo, Sr., JJ.,concur. Davide, Jr., C.J., Vitug,and Ynares—Santiago, JJ.,see separate opinion. Puno, J.,concur, and also joins the opinion of J.Ynares—Santiago. Quisumbing, J.,in the result. Sandoval—Gutierrez, J.,see concurring opinion. Corona,and Azcuna, JJ.,joins the dissent of J.Tinga. Tinga, J.,pls. see dissenting opinion. [1] Republic v. Cocofed , 372 SCRA 462, 493, December 14, 2001. [2] Tañada v. Angara, 272 SCRA 18, 79, May 2, 1997. [3] Francisco v. House of Representatives, GR No. 160261 and consolidated cases, November 10, 2003, per Morales, J. [4] Rollo, Vol. I, pp. 3—48. While petitioners labeled their pleading as one for prohibition and mandamus, its allegations qualify it also as one for certiorari. [5]An act authorizing the Commission on Elections to conduct a nationwide demonstration of a computerized election system and pilot—test it in the March 1996 elections in the Autonomous Region in Muslim Mindanao (ARMM) and for other purposes. [6]An act authorizing the Commission on Elections to use an automated election system in the May 11, 1998 national or local elections and in subsequent national and local electoral exercises, providing funds therefor and for other purposes. [7]Section 6 of RA 8436 provides “[i]f in spite of its diligent efforts to implement this mandate in the exercise of this authority, it becomes evident by February 9, 1998 that the Commission cannot fully implement the automated election system for national positions in the May 11, 1998 elections, the elections for both national and local positions shall be done manually except in the Autonomous Region in Muslim Mindanao (ARMM) where the automated election system shall be used for all positions.” [8] Loong v. Comelec, 365 Phil. 386, April 14, 1999; see also Panganiban, Leadership by Example, 1999 ed., pp. 201—249. [9]Annex “7” of the Comment of Private Respondents MPC and MPEI, Rollo, Vol. II, p. 638. [10]Annex “8” of the Comment of Private Respondents MPC and MPEI, Rollo, Vol. II, pp. 641—642. [11]Annex “G” of the Petition, Request for Proposal, p. 12; Rollo, Vol. I, p. 71. [12] Id., pp. 21—23 & 80—82. [13]According to Public Respondent Comelec’s Memorandum prepared by the OSG, p. 8; Rollo, Vol. IV, p. 2413. [14]Photocopy appended as Annex “B” of the Petition; Rollo, Vol. I, pp. 52—53. [15]Photocopy appended as Annex “C” of the Petition; Rollo, Vol. I, pp. 54—55. [16]The case was deemed submitted for decision on November 5, 2003, upon this Court’s receipt of Private Respondent MPC/MPEI’s Memorandum, which was signed by Attys. Alfredo V. Lazaro Jr., Juanito I. Velasco Jr. and Ma. Concepcion V. Murillo of the Lazaro Law Firm. On October 27, 2003, the Court received petitioners’ Memorandum, which was signed by Atty. Alvin Jose B. Felizardo of Pastelero Law Office, and Public Respondent Comelec’s Memorandum, signed by Comelec Comm. Florentino A. Tuason Jr. Apart from these, the Office of the Solicitor General (OSG) filed another Memorandum on behalf of Comelec, also on October 27, 2003, signed by Asst. Sol. Gen. Carlos N. Ortega, Asst. Sol. Gen. Renan E. Ramos, Sol. Jane E. Yu and Asso. Sol. Catherine Joy R. Mallari, with a note that Sol. Gen. Alfredo L. Benipayo “inhibited himself.” The writing of the Decision in this case was initially raffled to Justice Dante O. Tinga. However, during the Court’s deliberations, the present ponente’s then “Dissenting Opinion” to the draft report of Justice Tinga was upheld by the majority. Hence, the erstwhile Dissent was rewritten into this full ponencia. [17]Page 11; Rollo, Vol. IV, p. 2390. During the Oral Argument on October 7, 2003, the Court limited the issues to the following: (1) locus standi of petitioners; (2) prematurity of the Petition because of non—exhaustion of administrative remedies for failure to avail of protest mechanisms; and (3) validity of the award and the Contract being challenged in the Petition. [18] Chavez v. Presidential Commission on Good Government, 360 Phil. 133, December 9, 1998, perPanganiban, J. [19] Kilosbayan, Inc. v. Morato, 320 Phil. 171, November 16, 1995, perMendoza, J. [20] Tatad v. Secretary of the Department of Energy, 346 Phil. 321, November 5, 1997, perPuno, J. [21] Del Mar v. Philippine Amusement and Gaming Corporation, 346 SCRA 485, November 29, 2000, perPuno, J. [22] Kilosbayan, Inc. v. Morato, supra. [23] Dumlao v. Comelec, 95 SCRA 392, January 22, 1980, per Melencio—Herrera, J. [24] Philconsa v. Mathay, 124 Phil. 890, October 4, 1966, perReyes J.B.L., J. [25]Respondent Comelec’s Memorandum, pp. 50—51. [26]The law obliges no one to perform the impossible. [27]See private respondents’ Memorandum, p. 60. [28]Photocopy appended as Annex “B” of the petition. [29]334 Phil. 146, January 10, 1997. [30] Id., p. 153, perTorres Jr., J. [31]Although by its Resolution 6074, Comelec awarded the bid to MPC, the actual Contract was entered into by Comelec with MPEI. The Contract did not indicate an exact date of execution (except that it was allegedly done on the “____ day of May,”) but it was apparently notarized on June 30, 2003. [32]In connection with this, public respondents, in their Memorandum made reference to the Implementing Rules and Regulations of RA 6957 as amended by RA 7718 (the Build—Operate—Transfer Law), and considered said IRR as being applicable to the instant case on a suppletory basis, pending the promulgation of implementing rules for RA 9184 (the Government Procurement Act). For our purposes, it is well worth noting that Sec. 5.4 of the IRR for RA 6957 as amended, speaks of prequalification requirements for project proponents, and in sub—section (b)(i), it provides that, for purposes of evaluating a joint venture or consortium, it shall submit as part of its prequalification statement a business plan which shall among others identify its members and its contractor(s), and the description of the respective roles said members and contractors shall play or undertake in the project. If undecided on a specific contractor, the proponent may submit a short list of contractors from among which it will select the final contractor. Short listed contractors are required to submit a statement indicating willingness to participate in the project and capacity to undertake the requirements of the project. The business plan shall disclose which of the members of the joint venture/consortium shall be the lead member, the financing arm, and/or facility operator(s), and the contractor(s). In other words, since public respondents argue that the IRR of RA 6957 as amended would be suppletorily applicable to this bidding, they could not have been unaware of the requirement under Sec. 5.4 (b)(i) thereof, in respect of submission of the requisite business plan by a joint venture or consortium participating in a bidding. [33]Now, what would prevent an enterprising individual from obtaining copies of the Articles of Incorporation and financial statements of, let us say, San Miguel Corporation and Ayala Corporation from the SEC, and using these to support one’s claim that these two giant conglomerates have formed a consortium with one’s own penny—ante company for the purpose of bidding for a multi—billion peso contract? As far as Comelec is concerned, the answer seems to be: Nothing. [34]TSN, October 7, 2003, p. 104. [35] Ibid. [36] Id., pp. 104—105. [37] Id., pp. 103—108. [38] Id., pp. 108—114. [39] Id., pp. 142—145. [40]On pp. 42—43 of the Memorandum of public respondents, filed with this Court on October 27, 2003, Comm. Tuason himself signed this pleading in his capacity as counsel of all the public respondents. [41]Copies of these four agreements were belatedly submitted to this Court by MPEI through a Manifestation with Profuse Apologies filed on October 9, 2003. [42]Copies of the four separate bilateral agreements were submitted to the Court last October 9, 2003. [43]The date was carelessly stated as “____ May, 2003.” [44]At p. 38. [45]During the Oral Argument, counsel for public respondents admitted that Comelec was aware that not all the members of the “consortium” had agreed to be jointly and solidarily liable with MPEI. [46]232 SCRA 110, 144, May 5, 1994, perDavide Jr., J.(now CJ). [47]Culled from table 6, DOST Report; Rollo, Vol. II, pp. 1059—1072. [48]Annex “I” of the Petition, Vol. I, pp. 116—118. [49]Source code is the program instructions in their original form. Initially, a programmer writes a computer program in a particular programming language. This form of the program is called the source program, or more generically, source code. To execute the program, however, the programmer must translate it into machine language, the language that the computer understands. Source code is the only format that is readable by humans. When you purchase programs, you usually receive them in their machine—language format. This means that you can execute them directly, but you cannot read or modify them. Some software manufacturers provide source code, but this is useful only if you are an experienced programmer. [50]The key passages of the Court’s Resolution of December 9, 2003 were cited and reproduced verbatim in the Comelec’s Partial Compliance and Manifestation. [51]Metals Industry Research and Development Center (MIRDC) of the Department of Science & Technology (DOST). [52]Photocopy of the MIRDC—DOST letter of Dec. 15, 2003 is attached as Annex “A” to Respondent Comelec’s Partial Compliance and Manifestation. However, the 11 Test Certifications of the DOST (covering 11 lots or 158 ACMs) which were purportedly attached to this letter, have not been reproduced and submitted to the Court, for reasons known only to respondents. [53]For example, one can conduct tests to see if certain machines will tip over and fall on their sides when accidentally bumped, or if they have a tendency to collapse under their own weight. A less frivolous example might be that of conducting the same tests, but lowering the bar or passing mark. [54]In the December 15, 2003 issue of the Philippine Daily Inquireris an item titled “Digital ‘dagdag—bawas’: a nonpartisan issue” by Dean Jorge Bocobo, from which the following passages appear: “The Commission on Elections will use automated counting machines to tally paper ballots in the May elections, and a telecommunications network to transmit the results to headquarters, along with CDs of the data. Yet, with only five months to go, the application software packages for that crucial democratic exercise—several hundred thousand lines of obscure and opaque code—has not yet even been delivered in its final form, Comelec Chairman Benjamin Abalos admitted last week. “My jaw dropped in amazement. Having built software for General Electric Co.'s medical systems business and military aircraft engines division (in another lifetime), I have learned the hard and painful way that 90 percent of unintended fatal problems with complex software lies in the last 10 percent of the code produced. From experience, I can assure you now with metaphysical certainty that not even the people furiously writing that software know whether it will actually work as intended on May 10, much less guarantee it. Simply put, the proposed software—hardware combination has neither been tested completely nor verified to comply with specifications.” [55]Dated “ ____ May, 2003” but notarized on June 30, 2003. SEPARATE OPINION DAVIDE, JR., C. J.: I join Mr. Justice Jose C. Vitug in his separate opinion and strongly recommend, for the reasons therein stated, that this case be DISMISSED. Let me further add other compelling reasons which strengthen my view that this case should be dismissed. The Court did not issue a Temporary Restraining Order in this case. This showed an initial finding that on its face the allegations in the petition were insufficient to justify or warrant the grant of a temporary restraining order. In the meantime then the parties were not barred from performing their respective obligations under the contract. As of today, the COMELEC has already paid a large portion of its contracted obligation and the private respondent has delivered the contracted equipment for automation. It is to be reasonably presumed that during the same period the COMELEC focused its attention, time and resources toward the full and successful implementation of the comprehensive Automated Election System for the May 2004 elections. Setting aside the contract in question at this late hour may have unsettling, disturbing and even destabilizing effect. For one, it will leave the COMELEC insufficient time to prepare for a non-automated electoral process, i.e., the manual process, which would necessarily include the acquisition of the security paper and the purchase of a “dandy roll” to watermark the ballot paper, printing of other election forms, as well as the bidding and acquisition of the ballot boxes. For another, the law on Automated Election System (R.A. 8436) and Executive Order No. 172 (24 January 2003) which allocated the sum of P2.5 Billion, and Executive Order No. 175 (10 February 2003) which allocated the additional sum of P500 Million for the implementation in the May 2004 elections of the Automated Election System would be put to naught as there is absolutely no more time to conduct a re-bidding. Finally, there is no suggestion that graft and corruption attended the bidding process, or that the contract price is excessive or unreasonable. All that the petitioners claim is that “the bidding and the award process was fatally flawed. The public respondents acted without or excess of its jurisdiction or with grave abuse of discretion amounting to lack or excess of jurisdiction when it [sic] awarded the project.” It may be precipitate for this Court to declare void the contract in question. SEPARATE OPINION VITUG, J.: While the Supreme Court exercises original jurisdiction over petitions for certiorariand prohibition (along with petitions for prohibition, mandamus, quo warranto, habeas corpusand injunction), that jurisdiction, however, is not exclusive. [1]A direct recourse to the Supreme Court, for the issuance of these writs, in disregard of the rule on hierarchy, should be appropriate only when, besides the attendance of clearly exceptional and compelling reasons clearly set out in the petition, [2]there are no contentious factual assertions of the parties that need to be threshed out before any objective and definitive conclusion can be reached. What appears to be a significant issue in the instant petition is the legality of respondent COMELEC’s award of the contract relative to the procurement of automated counting machines to respondent Mega Pacific under alleged questionable circumstances. The Supreme Court is not a trier of facts; indeed, a review of the evidence is not the proper office of a petition for certiorari, prohibition or mandamus. [3]These proceedings are availed of only when there can be no other plain, adequate and speedy remedy in the ordinary course of law. In certiorarior prohibition, issues affecting the jurisdiction of the tribunal, board and officers involved may be resolved solely on the basis of undisputed facts. [4]The enormity of the factual disputes in the instant petition, among which include the eligibility of Mega Pacific to participate in the bidding process, the veracity and effectivity of the testing, and the technical evaluation conducted by the Department of Science and Technology (DOST) on the automated counting machine of the bidders, would essentially require an extensive inquiry into the facts. An insistence that it be resolved despite unsettled factual points would be inadequate to allow an intrusion by the Court. [5] The Supreme Court is not expected, whenever one is simply minded to pass judgment on an action of a government agency upon which authority, as well as corresponding duty, devolves. The Court neither controls nor supervises the exercise of authority and the discharge of function by another government office. If it were otherwise, the act of governance and the responsibility that thereto attaches are then effectively shifted from where they belong over to where they should not be. The Court is bound merely to construe and to apply the law, regardless of its wisdom and salutariness, and to strike it down only when constitutional proscriptions are disregarded. It is what the fundamental law mandates, and it is what the Court must do. The electoral process, it is true, should be of paramount and immediate concern to every Filipino. It is also probably true that the computerization/automation of our electoral process, as well as the progress that it brings, is just as important. Nevertheless, it could also be unwise for the Court, for that sake alone, to precipitately take on the case; after all, we have been without it for decades. The opinions expressed by my colleagues, collectively and individually, should indeed give compelling reasons for the Commission on Elections to perhaps take notice and, on its own, to forthwith reexamine the assailed bidding process. Accordingly, at this stage, I am constrained to vote against the Court’s taking cognizance of the case. [1] People v. Cuaresma , 172 SCRA 415. [2] Santiago v. Vasquez, 217 SCRA 633. [3] People v. Chavez, 358 SCRA 810. [4] Matuguina Integrated Wood Products, Inc. vs. Court of Appeals, 263 SCRA 490; Mafinco Trading Corp. vs. Ople, et al., 70 SCRA 139. [5]See Article VIII, Section 17 of the 1987 Constitution. CONCURRING OPINION YNARES-SANTIAGO, J.: I am mindful of our ruling, expressed only recently in Makalintal v. COMELEC, [1]that the Commission on Elections (“COMELEC”), being an independent constitutional body, ought to be given considerable latitude in the discharge of its functions. The key point to be remembered is the fundamental objective which all of the COMELEC’s actuations should be destined to achieve, i.e.the accomplishment of free, orderly and honest elections. If the means adopted by the COMELEC run clearly contrary to its fundamental objective, it is our right — more, our duty — to nullify the COMELEC’s actuations. Our experience during the May 11, 1998 regular elections held in the Autonomous Region in Muslim Mindanao (ARMM) [2]should have taught us that the Philippines may be unprepared for the use of automated counting machines. Whereas it is successfully adopted in many countries around the world, this sophisticated technological advancement seems beyond the reach of the Philippines at this stage in our country’s development. If we persist in attempting the use thereof, even if — as in this case — such machines do not meet the standards of accuracy that our own laws demand, we would be tampering with the conduct of free, orderly and honest elections, and thus we would be distorting the will of the electorate. As pointed out by the Honorable Justice Jose C. Vitug in his Separate Opinion, this Court is not a trier of facts, and a review of the technical evidence is not the proper office of a petition for certiorari, prohibition and mandamus. [3]The questions of law, however, and the questions of the COMELEC’s grave abuse of discretion, are squarely within the purview of this Court in this case. In my opinion, there are three main grounds which warrant granting the instant petition. First, I believe that the special circumstances availing in this case warrant the relaxation of the rule on exhaustion of administrative remedies. Second, the COMELEC gravely abused its discretion when it clearly contracted with a non-eligible entity, and therefore the contract for the second phase of the automated counting system is null and void. Finally, even assuming the eligibility of the other contracting party, the COMELEC gravely abused its discretion when it changed the technical requirements for accuracy of the automated machines and software, which warrants the nullification of the contract. I. On Non-Exhaustion of Administrative Remedies A long line of cases establishes the basic rule that regular courts of justice should not interfere in matters which are addressed to the sound discretion of government agencies entrusted with the regulation of activities coming under the special technical knowledge and training of such agencies. [4]The underlying principle of the rule on exhaustion of administrative remedies rests on the presumption that when the administrative body, or grievance machinery, is afforded a chance to pass upon the matter, it will decide the same correctly. [5] The principle of exhaustion of administrative remedies is not an ironclad rule. This doctrine is relative, and its flexibility is called upon by the peculiarity and uniqueness of the factual and circumstantial settings of a case. [6] In the past, the principle has been disregarded when (1) there is a violation of due process; [7](2) the issue involved is purely a legal question; [8](3) the administrative action is patently illegal amounting to lack or excess of jurisdiction; [9](4) there is estoppelon the part of the administrative agency concerned; [10](5) there is irreparable injury; [11](6) the respondent is a department secretary whose acts, as an alter ego of the President, bear the implied and assumed approval of the latter; [12](7) to require exhaustion of administrative remedies would be unreasonable; [13](8) it would amount to a nullification of a claim; [14](9) the subject matter is a private land in land case proceedings; [15](10) the rule does not provide a plain, speedy and adequate remedy; and (11) there are circumstances indicating the urgency of judicial intervention, [16]as when public interest is involved. [17] There is no plainer example of a case in which the issues are of transcendental importance. The preservation of an honest, upright system of electing our nation’s public officers bears urgent public interest considerations. More, as I will discuss below, the administrative action involved here is patently illegal, amounting to lack or excess of jurisdiction. These two reasons warrant the relaxation of the rule of exhaustion of administrative remedies. II. On the Non-Eligibility of Private Respondents. I am not persuaded by the argument that the individual members of the so-called “Consortium” bound themselves to perform particular obligations under individual agreements executed with MPEI, and that these separate agreements suffice to constitute an eligible “joint venture” under the Request For Proposal (“RFP”) promulgated by the COMELEC. The fact that WeSolve, SK C & C, Election.Com and ePLDT bound themselves to MPEI does not mean that a joint venture was executed. These individual entities are merely the sub-contractors of MPEI, and their liability for any breach is onlyto MPEI. Under the RFP, a “joint venture” has been given a very strict definition. To be eligible to submit a bid, the following criteria must be met: Manufacturers, suppliers and/or distributors forming themselves into a joint venture, that intend to be jointly and severally liable for a particular contract, provided Filipino ownership thereof shall be 60%. [18](underscoring supplied) There are therefore three qualifications for eligibility under the RFP. First, the manufacturers, suppliers and/or distributors must expressly form themselves into a joint venture. Second, this joint venture must demonstrate an intent that the individual members be jointly and severally liable for a particular contract. Finally, the Filipino ownership of the joint venture must be 60%. Whereas the RFP does not require the members of the joint venture to execute a single document to constitute the joint venture, there must be sufficient evidence that such a joint venture was indeed formed, whether this evidence is a single document, or a multiplicity of documents. It is plain that the “joint venture” must be formed as a single entity,responsible for the entirety of the contract, even if separate agreements among the individual members of the joint venture would lay out the specific tenor of their obligations to each other; otherwise, it would be impossible to evaluate the nationality of this joint venture, which nationality is the third requirement for eligibility. Conspicuously absent from the records of this case are documents that demonstrate that the individual members of the so-called “Consortium” actually formed or constituted themselves into a joint venture. Jurisprudence discussing a joint venture lays out the rule that such an entity “presupposes generally a parity of standing between the joint co-ventures or partners, in which each party has an equal proprietary interest in the capital or property contributed, and where each party exercises equal rights in the conduct of the business.” [19] In Aurbach, et. al. v. Sanitary Wares Manufacturing Corporation, et. al., [20]we expressed the view that a joint venture may be likened to a partnership, thus: The legal concept of a joint venture is of common law origin. It has no precise legal definition, but it has been generally understood to mean an organization formed for some temporary purpose. It is hardly distinguishable from the partnership, since their elements are similar—community of interest in the business, sharing of profits and losses, and a mutual right of control. The main distinction cited by most opinions in common law jurisdiction is that the partnership contemplates a general business with some degree of continuity, while the joint venture is formed for the execution of a single transaction, and is thus of a temporary nature. This observation is not entirely accurate in this jurisdiction, since under the Civil Code, a partnership may be particular or universal, and a particular partnership may have for its object a specific undertaking. It would seem therefore that under Philippine law, a joint venture is a form of partnership and should thus be governed by the law of partnerships. The Supreme Court has however recognized a distinction between these two business forms, and has held that although a corporation cannot enter into a partnership contract, it may however engage in a joint venture with others. (citations omitted) In other words, the legal concept of a “joint venture”, since akin to a partnership, involves a common agreement — in which all individuals and entities party to the joint venture bind themselves, jointly, to perform a common undertaking or undertakings. The definition of a “joint venture” under the RFP is in line with this legal definition. There is nothing in the records that would indicate that any such entity was created by the individual members of the so-called “Consortium”. In the absence of any evidence, we must conclude that no such agreement exists. Since we are unable to conclude that the “joint venture” has any legal existence, it is impossible to evaluate whether or not the third criterion — setting out the nationality requirement for an eligible joint venture — has been met by the so-called “Consortium”. The so-called “Consortium”, therefore, has failed to meet the first and third criteria. There is also a gross failure on the part of the private respondents to meet the second criterion. There is a marked absence of intent that the individual members of the so-called “Consortium” be jointly and severally liable for the contract. The records contain particular individual agreements that MPEI entered into with other entities. A perusal of the individual agreements that MPEI entered into with the other entities readily demonstrates that it was always the intent of MPEI to have direct and primary liability for any breach of the Contact with COMELEC. Part of the records are so-called “Teaming Agreements” which MPEI entered into with Election.Com Ltd. [21] and ePLDT Inc., [22] both dated March 3, 2003. An examination of the language of these “Teaming Agreements” would once more demonstrate that it was MPEI, and MPEI alone, which intended to bid for the Contract with the COMELEC, and intended to be bound thereby . First, both these “Teaming Agreements” contain stipulations designating MPEI as the “Contractor” and the other party as merely the “Subcontractor”. [23] Each of these “Teaming Agreements” acknowledges that the agreements were entered into in the expectation that COMELEC would award the Contract to the Contractor , MPEI. [24] Absent from either of these “Teaming Agreements” is any reference to the possibility that COMELEC would contract with the so-called “Consortium”. Moreover, both of these agreements state that the obligation of the Subcontractor was the delivery of equipment or provision of services to the Contractor, MPEI, [25]and indeed expressly limit the Subcontractor’s role in the entire project to be merely that of a provider of the equipment and services. [26]Liability for failure to perform these obligations is expressly limited. The Subcontractors would be liable only to MPEI, and not to the COMELEC. Also part of the records is the “Memorandum of Agreement” entered into between MPEI and WeSolv Open Computing, Inc. [27]The very first preambulatory clause thereof reads: WHEREAS, pursuant to an open competitive bidding to be conducted by the Commission on Elections (“COMELEC”) of the Philippine Government, Mega Pacificintends to submit a bid for Phase II: Automated Counting and Canvassing System(the “Project”) of the Modernization Program of the Philippine Electoral System; [28](underscoring supplied) “Mega Pacific”, the entity referred to, is defined as “Mega Pacific eSolutions, Inc.” [29]and not the so-called “Consortium”. In other words, MPEI and WeSolv understood that MPEIwould be bidding for the Contract, and MPEI alone would be contracting with COMELEC. The expression of “joint and several liability” of “WeSolv” does not transform the agreement into a joint venture. There is a clear limit to the extent of this liability. As plainly stated in the Memorandum of Agreement: WeSolv shall be jointly and severally liable with Mega Pacific only for the particular products and/or services supplied by the former for the Project. [30] The very first reference to any so-called “Consortium” is in the “Memorandum of Agreement” dated March 9, 2003, between MPEI and SK C & C, “a corporation organized and existing under and by virtue of the laws of the Republic of Korea”. [31]The initial preambulatory clause reads: WHEREAS, pursuant to an open competitive bidding to be conducted by the Commission on Elections (“COMELEC”) of the Philippine Government, the Mega Pacific Consortium shall bid for Phase II: Automated Counting and Canvassing System(the “Project”) of the Modernization Program of the Philippine Electoral System; . . . [32] That Memorandum of Agreement also contains the following clause: Each of the individual members of the Consortium shall be jointly and severally liable with the Lead Firm for the particular products and/or services supplied by such individual member for the project, in accordance with their respective undertaking or sphere of responsibility. [33] Three things are significant about this Memorandum of Agreement. First, whereas there is reference to a “Consortium”, the specific composition of the “Consortium” is not specified. Thus, the records are bereft of any evidence that would demonstrate which entities, if any, would be parties to this “Consortium”. It is therefore impossible to make a factual determination as regards whether the “Consortium” would meet the strict requirements for a qualified bidder outlined in the RFP. Second, the Memorandum of Agreement specifically limits the liability of each member of this “Consortium” only in accordance with their respective undertaking or sphere of responsibility. Thus, the “joint and several” liability of each member of the Consortium would again be only within a very limited application, i.e., only to the extent of its individual undertaking. Third, and most significant, the Memorandum of Agreement is only between MPEI and SK C & C. There is no evidence of any similar Memorandum of Agreement, referring to a Consortium, entered into between MPEI and any other entity. The joint and several liability referred to in the quoted paragraph, therefore, would pertain only to MPEI and SK C & C, since these are the only two parties to this particular contract, and not to any other member of the Consortium, if any. In the absence of evidence, it is impossible to conclude that there are other members of the Consortium, and equally impossible to determine the extent of their liability, if any. In sum, therefore, there is a conspicuous dearth of evidence to demonstrate that there was, indeed, a Consortium; if there was a Consortium, the specific composition thereof; and, if there was a Consortium, the liability of its individual members, for breach of the contract to COMELEC. All this demonstrates that, even if the other contracting party were the so-called “Consortium”, this “Consortium” would be ineligible to enter into the contract with the COMELEC. However, it is plain that the COMELEC entered into a contract notwith this “Consortium”, but rather with MPEI — an entity which, it is acknowledged, would per sebe ineligible to bid. A plain reading of the contract denominates the parties to be: COMMISSION ON ELECTIONS, the government institution charged with the enforcement and administration of laws relative to the conduct of elections, with principal office address at Postigo Street, Intramuros, Manila, Philippines, represented in this act by its Chairman, Hon. Benjamin S. Abalos, hereinafter referred to as the “COMELEC”. — and — MEGA PACIFIC eSOLUTIONS, INC., a corporation duly organized and existing under and by virtue of the laws of the Republic of the Philippines, with principal office address at Suite 707, Tower One & Exchange Plaza, Ayala Triangle, Ayala Avenue, Makati City, Philippines, represented in this act by its President, Willy U. Yu, hereinafter referred to as “MEGA”. [34] The “Contract Documents” referred to are the following: 1.4. Contract Documents The following documents, referred to collectively as the Contract Documents, are hereby incorporated and made integral parts of the Contract: (1) this Contract together with its Appendices; (2) the Request for Proposal (also known as “Terms of Reference”) issued by the Comelec including Tender Inquiries and Bid Bulletins; (3) Tender Proposal as submitted by Mega. All Contract Documents shall form part of the Contract even if they or any one of them is not referred to or mentioned in the Contract as forming a part thereof. Each of the Contract Documents shall be mutually complementary and explanatory of each other such that what is noted in one although not shown in the other shall be as binding as if required by all, unless one item is a correction of the other. The Intent of the Contract Documents is the proper, satisfactory, and timely execution and completion of the Project in accordance with the Contract Documents. Consequently, all items necessary for the proper and timely execution and completion of the Project shall be deemed included in the Contract. Again, conspicuously absentfrom this contractual definition of a “Contract Document” is any mentionof any subsidiary agreement between a purported “Consortium” and the COMELEC. Indeed, a plain reading of the definition of the “Contract Document” would indicate that, insofar as the parties to the contract were concerned, the bid itselfwas submitted by MPEI and not the “Consortium”. Moreover, the definition of “Contract Document” could easily have integrated the subsidiary agreements, incorporating them by reference, in the same way that the “Request for Proposal” and “Tender Proposal” were incorporated by reference. These contracts were not even appended as annexes to the main contract. The appendices to the main contract are: “Products and Services to be Acquired from, and Provided by, Mega Pacific Solutions, Inc., and Technical Specifications”; [35]“Ballot Counting System”; [36]“Canvassing of Votes System/Software”; [37]“Project Management Approach”; [38]“Implementation and Roll-Out Plan”; [39]“Timelines”; [40]“List of Goods”; [41]“List of Documentation”; [42]“Training Summary”; [43]“List of Services”; [44]“Schedule of Communication/Information Dissemination Materials”; [45]and “Global Price Summary”. [46] Moreover, an examination of the various obligations in the contract readily demonstrates that all those obligations pertain only to either COMELEC or MPEI. None of the other entities under the so-called “Consortium” has any obligations to COMELEC under the Contract. It is apparent that only COMELEC and MPEI are bound thereunder. The argument that the “Consortium”, as an entity, bound itself to perform particular obligations under the contract is easily debunked by an examination of the contract itself. Various other documents also support the fact that only MPEI, not any so-called “Consortium”, contracted with COMELEC. For instance, there is the Secretary’s Certificate, dated March 5, 2003, executed by Enrique T. Tansipek, the Corporate Secretary of MPEI, which attests to the corporate authority given by the M [47]There are various “Affidavits of Undertaking” dated March 7, 2003, executed by Willy U. Yu, President of MPEI, which attest that (1) MPEI(not any so-called “Consortium”) will be participating in the bid for the contract; and (2) the other entities, such as WeSolv, Oracle, and Election.com Ltd., are referred to merely as the “foreign suppliers”, [48]and not as joint venture partners, or as individual members of a so-called “Consortium”. III. On the Failure of Private Respondents to Meet the Requirements for Eligible Bids. Finally, even if we were to concede that the COMELEC contracted with an eligible entity, it appears that the counting machines and ballot-counting software submitted by the so-called “Consortium” simply failed to meet the accuracy rating required by the RFP. In the RFP, the COMELEC required that both the counting machines and ballot-counting software should have an accuracy rating of 99.9995 or better. After the bids were submitted, the accuracy criteria were suddenly changed to 99.995 percent. Only very recently, in the Piatco [49]case, we held: An essential element of a publicly bidded contract is that all bidders must be on equal footing. Not simply in terms of application of the procedural rules and regulations imposed by the relevant government agency, but more importantly, on the contract bidded upon. Each bidder must be able to bid on the same thing. The rationale is obvious. If the winning bidder is allowed to later include or modify certain provisions in the contract awarded such that the contract is altered in any material respect, then the essence of fair competition in the public bidding is destroyed. A public bidding would indeed be a farce if after the contract is awarded, the winning bidder may modify the contract and include provisions which are favorable to it that were not previously made available to the other bidders. It is inherent in public biddings that there shall be a fair competition among the bidders. The specifications in such biddings provide the common ground or basis for the bidders. The specifications should, accordingly, operate equally or indiscriminately upon all bidders. [50] To change the eligibility requirements mid-stream, and afterbids had already been submitted, completely subverts the integrity of the bidding process and warrants the nullification of the award of the contract, whether the other contracting party was MPEI or the so-called “Consortium”. In sum, the serious defects in the bidding process indicate a grave abuse of discretion on the part of public respondent COMELEC, which seemed to display a marked bias in favor of awarding the contract to the private respondent MPEI or the so-called “Consortium”. Whereas automated counting might greatly speed up our election process, we should take great pains to make certain that the machines used are not flawed. To my mind, the subversion of the bidding process already makes the automation of the 2004 elections inherently suspect, which will have a potential negative effect on the integrity of the results. At this stage in our nation’s history, we should all strive toward restoring the public’s faith in the stability of our government institutions, and the use of suspect machines in counting votes cannot but subvert that faith. IN VIEW WHEREOF, I CONCURwith the majority opinion and vote to GRANT the petition, specifically, to: (1) declare NULL and VOID Resolution No. 6074 of the COMELEC awarding the contract for the second phase of the automated counting and canvassing system of the Modernization Program of the Philippine Electoral System to either Mega Pacific eSolutions, Inc. or the Mega Pacific Consortium; (2) PROHIBIT the COMELEC from implementing any contract entered into with either Mega Pacific eSolutions, Inc. or the Mega Pacific Consortium for the second phase of the automated counting and canvassing system of the Modernization Program of the Philippine Electoral System; and (3) COMPEL the COMELEC to conduct a re-bidding of the second phase of the automated counting and canvassing system of the Modernization Program of the Philippine Electoral System. [1] G.R. No. 157013, 10 July 2003. [2]See Loong v. Commission on Elections, 365 Phil. 386 (1999). [3]Separate Opinion, Vitug, J., at p. 2. [4] Sta. Ines Melale Forest Products Corporation v. Macaraig, 359 Phil. 831 (1998); Felipe Ysmael, Jr. and Co. v. Deputy Executive Secretary, G.R. No. 79538, 18 October 1990, 190 SCRA 673; Concerned Officials of MWSS v. Vasquez, 310 Phil. 549 (1995). See SEVERIANO S. TABIOS, Annotation on Failure to Exhaust Administrative Remedies as a Ground for Motion To Dismiss, 165 SCRA 352, 357-362 (1988). [5] Union Bank of the Philippines v. Court of Appeals, 352 Phil. 808 (1998); University of the Philippines v. Catungal, Jr., 338 Phil. 808 (1997). [6] Paat v. Court of Appeals, 334 Phil. 146 (1997). [7] Quisumbing v. Judge Gumban, G.R. No. 85156, 5 February 1991, 193 SCRA 520; Salinas v. NLRC, G.R. No. 114671, 24 November 1999, 319 SCRA 54; Samson v. NLRC, 32 Phil. 135 (1996). See SEVERIANO S. TABIOS, Annotation on Failure to Exhaust Administrative Remedies as a Ground for Motion to Dismiss, 165 SCRA 352, 357-362 (1988). [8]Eastern Shipping Lines v. POEA, G.R. No. L-76633, 18 October 1988, 166 SCRA 533; Paat v. Court of Appeals, 334 Phil. 146 (1997). [9] Industrial Power Sales, Inc. v. Sinsuat, G.R. No. L-29171, 15 April 1988, 160 SCRA 19. [10] Vda. De Tan v. Veterans Backpay Commission, 105 Phil. 377 (1959). [11] De Lara v. Cloribel, 121 Phil. 1062 (1965). [12] Demaisip v. Court of Appeals, 106 Phil. 237 (1959). [13] Cipriano v. Marcelino, 150 Phil. 336 (1972). [14] Alzate v. Aldana, 107 Phil. 298 (1960). [15] Soto v. Jareno, G.R. No. L-38962, 15 September 1986, 144 SCRA 116. [16] Quisumbing v. Judge Gumban, G.R. No. 85156, 5 February 1991, 193 SCRA 520; Indiana Aerospace University v. Commission on Higher Education (CHED), G.R. No. 139371, 4 April 2001, 356 SCRA 367. [17] Indiana Aerospace University v. Commission on Higher Education (CHED), G.R. No. 139371, 4 April 2001, 356 SCRA 367, citing Liberty Insurance Corp. v. Court of Appeals, 222 SCRA 37, 47 (1993); Alindao v. Joson, 264 SCRA 211, 220 (1996); Tan v. Court of Appeals, 275 SCRA 568, 574-575 (1997); and Tan Jr. v. Sandiganbayan, 292 SCRA 452, 457-458 (1998). [18]RFP, at p. 12. [19] Sevilla v. Court of Appeals, G.R. Nos. L-41182-83, 15 April 1988, 160 SCRA 171. [20]G.R. No. 75875, 15 December 1989, 180 SCRA 130. [21] Rollo, p. 2355. [22] Id., p. 2364. [23] Id., pp. 2355 and 2364. [24] Id., pp. 2358 and 2367. [25] Id., pp. 2355 and 2364. [26] Id. [27] Id., p. 2348. [28] Id. [29] Id. [30] Id., p. 2349. [31] Id., p. 2352. [32] Id. [33] Id., p. 2353. [34]“Automated Counting and Canvassing Project Contract”, Rollo, at p. 2198. [35] Id., Appendix A, Rollo, at p. 2218. [36] Id., Appendix B, Rollo, at p. 2238. [37] Id., Appendix C, Rollo, at p. 2259. [38] Id., Appendix D, Rollo, at p. 2275. [39] Id., Appendix E, Rollo, at p. 2292. [40]Id., Appendix F, Rollo, at p. 2310. [41] Id., Appendix H, Rollo, at p. 2314. Appendix G, if any, is not part of the records. [42]Id., Appendix I, Rollo, at p. 2322. [43] Id., Appendix J, Rollo, at p. 2326. [44] Id., Appendix K, Rollo, at p. 2335. [45] Id., Appendix L, Rollo, at p. 2341. [46] Id., Appendix M, Rollo, at p. 2344. [47] Rollo, p. 1408. [48] Id., pp. 1870; 1954; 2052. [49] Lopez v. Piatco, G.R. No. 155661, 5 May 2003. [50]A. Cobacha & D. Lucenario, LAW ON PUBLIC BIDDING AND GOVERNMENT CONTRACTS 13 (1960). CONCURRING OPINION SANDOVAL-GUTIERREZ, J.: “Hasty and adventurous schemes are at first viewflattering, in execution difficult, and in the issuedisastrous.” [1] Election is indeed the bedrock of every democratic institution. Thus, when it comes to automating the election system, the standards must be as high as the stakes. The government and the suppliers of the voting machines carry the burden of proof that the machines are working correctly and that the election results will be accurate. All of democracy is founded on the idea that the loser of an election understands that he lost fair and square and that the election represents the will of the electorate. If we get into elections with outcomes that people do not believe in, where the candidates challenge the integrity of the machine, people are going to feel less and less confident in the results of elections run on these machines. [2] The petition before us raises a number of serious concerns about the viability of the automated voting machines intended for the May 2004 Elections. The matter strikes at the heart of our democratic system. If the system fails, there again looms a threat to our country’s stability. More than any other time, what we need today is a system that will bolster the legitimacy of our government. With the foregoing premise, I vote to grant the petition and declare Comelec Resolution No. 6074 null and void. The facts are undisputed. On December 22, 1997, Congress enacted Republic Act No. 8436 [3]authorizing the Commission on Election (COMELEC) to use an automated election system for the process of voting, counting of votes and consolidating results of the national and local elections. It mandated the COMELEC to acquire automated counting machines (ACM), computer equipment, devices and materials. [4] Accordingly, the COMELEC issued an Invitation to Bid on January 28, 2003, inviting interested bidders to apply for eligibility and to bid for the supply and delivery of the ACM with an estimated budget of P2,500,000,000.00. [5] On February 17, 2003, the COMELEC released to the public the “Request for Proposal” providing that bids from manufacturers, suppliers and/or distributors forming themselves into a joint venture may be entertained as long as the Filipino ownership thereof shall be at least 60%. For this purpose, a joint venture was defined as “a group of two (2) or more manufacturers, suppliers and/or distributors that intend to be jointly and severally responsible or liable for the contract.” [6] The next day, February 18, 2003, the Bids and Awards Committee (BAC) convened a pre-bid conference and gave prospective bidders until March 10, 2003 to submit their bid proposals. On March 10, 2003, Mega Pacific Consortium (MP CONSORTIUM) submitted its bid. Enclosed in it bidding documents was a letter dated March 7, 2003 expressing that Mega Pacific eSolutions, Inc. (MPEI), Election. Com, Ltd. (Election.Com), We Solv Open Computing, Inc. (We Solv), SK CeC, ePLDT and Oracle System (Philippines), Inc. (Oracle) have agreed to form a consortium to bid for the Project. In the same letter, MPEI, through its President, made known its role as the lead company and proponent of MP CONSORTIUM. Of more than 57 bidders, the BAC found MP CONSORTIUM and Total Information Management Corporation (TIMC) eligible to bid. Their bid proposals were thereafter referred to the BAC’s Technical Working Group (TWG) and the Department of Science and Technology (DOST) for technical evaluation. Thereafter, the TWG prepared a Technical Evaluation Form listing the minimum requirements for the Project with columns to indicate whether the bidder “passed” or “failed” to meet certain requirements. Requirements that were highly technical in nature and called for technical equipment for evaluation were referred to the DOST. Based on the findings of the TWG and the DOST, the BAC submitted a Report [7]noting that both MP CONSORTIUM and TIMC obtained some failed marks in the technical evaluation. Regardless thereof, the COMELEC en banc, in Resolution No. 6074 awarded the Project to MP CONSORTIUM on April 15, 2003. It publicized this Resolution on May 16, 2003. Unsatisfied with the COMELEC’s bidding process, five individuals and entities (including petitioner Information Technology Foundation of the Philippines) wrote a letter dated May 29, 2003 to COMELEC Chairman Benjamin Abalos, Sr. protesting the award of the contract to MP CONSORTIUM. They cited MP CONSORTIUM’s non-compliance with eligibility as well as technical requirements. On June 6,2003, COMELEC Chairman Abalos rejected the protest and declared that the award “would stand up to strictest scrutiny.” Undaunted, Information Technology Foundation of the Philippines (ITFP), Ma Corazon M. Akol, Miguel Uy, Eduardo H. Lopez, Augusto C. Lagman, Rex C. Drilon, Miguel Hilado, Ley Salcedo and Manuel Alcuaz, Jr., petitioners herein, filed the present petition for prohibition and mandamusseeking (1) to declare null and void COMELEC’s Resolution No. 6074; (2) to enjoin the implementation of the contract that may have been entered into by COMELEC either with MP CONSORTIUM or MPEI; and (3) to compel COMELEC to conduct a re-bidding of the Project. After carefully reviewing the records of this case, I find the exhaustive ponenciaof Mr. Justice Artemio V. Panganiban worthy of my fullest concurrence. First, I must deal with the procedural roadblocks. Petitioners come to us viaa petition for prohibition and mandamus, thus, it is argued that the recourse taken is improper. It is a well established rule, particularly in public biddings, that courts cannot compel an agency to do a particular act or to enjoin such act within its prerogative or discretion. This is not an iron-clad rule. One noted exception is when in the exercise of its authority it gravely abuses or exceeds its jurisdiction. [8] Judicial review may be justified on the grounds of grave abuse of discretion, arbitrary rejection of bids, and lack of freedom of competition among bidders. [9]In the case at bar, petitioners alleged in their petition that public respondents “acted without or in excess of its jurisdiction or with grave abuse of discretion” [10]when they awarded the Project to MPEI. Thus, the following pronouncement of this Court in JG Summit Holdings, Inc. vs. Court of Appeals [11]deserves reiteration: Be that as it may, the Court of Appeals erred when it dismissed the petition on the sole ground of the impropriety of the special civil action of mandamus. It must be stressed that the petition was also one for certiorari, seeking to nullify the award of the sale to private respondent of the PHILSECO shares. Verily, the petition alleges that ‘respondents COP and APT have committed such a grave abuse of discretion tantamount to lack or excess of their jurisdiction in insisting on awarding the bid to Philyards, for the various reasons stated herein, particularly since the right of first refusal and the right to top the bid are unconstitutional, contrary to law and public policy.’ Petitioner's failure to include certiorari in its caption should not negate the fact that the petition charged public respondent with grave abuse of discretion in awarding the sale to private respondent. Well-settled is the rule that it is not the caption of the pleading but the allegations therein that determine the nature of the action and the Court shall grant relief warranted by the allegations and the proof even if no such relief is prayed for. Neither can I subscribe to respondents’ view that petitioners have no legal standing to file the present case and that the petition should be dismissed for their failure to exhaust administrative remedies. Section 7 of R.A. No. 8436 provides that the COMELEC, in the procurement of an automated election system, shall create an “Advisory Council to be composed of technical experts from the Department of Science and Technology (DOST), the Information Technology Foundation of the Philippines (ITFP),the University of the Philippines (UP) and two (2) representatives form the private sector recommended by the Philippine Computer Society (PCS).” Obviously, petitioner ITFP is a member of the Advisory Council mandated to aid the COMELEC in the procurement of the ACM. As such, it has “actual and material interest” to ensure that in the procurement of the ACM, the bidding procedures are followed and the technical requirements are complied with. The same interest redounds to petitioners who are members of the ITFP and who, in addition, are suing as “taxpayers, registered voters and concerned citizens of the Philippines.” In Del Mar vs. Philippine Amusement and Gaming Corporation, [12]we ruled that taxpayers are allowed to sue (1) where there is a claim of illegal disbursement of public funds, (2) or that public money is being deflected to any improper purpose, (3) or where petitioners seek to restrain respondent from wasting public funds through the enforcement of an invalid or unconstitutional law. Considering that the assailed award involves the disbursement of billions of pesos from the public treasury, I must say that petitioners possess the required locus standi. Anent petitioners’ failure to exhaust administrative remedies, suffice it to say that their letter dated May 29, 2003 to COMELEC Chairman Abalos objecting to the process which led to the award of the contract to MPEI satisfies the above procedural condition. Certainly, petitioners could not be expected to follow the protest mechanisms outlined in Section 55, [13]Rule XVII of Republic Act No. 9184 [14]considering that the assailed award was made known to the public only on May 16, 2003 or more than one (1) month from the time Resolution No. 6074 was promulgated. Respondents would argue that under the subsequent provision, Section 58 [15]of the same Rule, the court which has jurisdiction over final decisions of the head of the procuring entity is the Regional Trial Court. This is not really a legal obstacle. In Commission on Elections vs. Quijano-Padilla, [16]we ruled that: “[T]he doctrine of hierarchy of courts is not an iron-clad dictum. On several instances where this Court was confronted with cases of national interest and of serious implications, it never hesitated to set aside the rule and proceed with the judicial determination of the case. [17]The case at bar is of similar import. It is in the interest of the State that questions relating to government contracts be settled without delay. This is more so when the alleged contract involves the disbursement of public funds and the modernization of our country’s election process.” The substantive issues in this case may be reduced into two queries: first, Did the Comelec abuse its discretion when it allowed MPEI to actively participate in the bidding despite its failure to meet the mandatory eligibility requirement?; and second, Did the COMELEC abuse its discretion when it awarded the contract to MPEI? At this juncture, it bears stressing that MPEI was incorporated only on February 27, 2003as evidenced by its Certificate of Incorporation. [18]This goes to show that from the time the COMELEC issued its Invitation to Bid ( January 28, 2003) and Request for Proposal ( February 17, 2003) up to the time it convened the Pre-bid Conference (February 18, 2003), MPEI was literally a non-existent entity. It came into being only on February 27, 2003 or eleven (11) days prior to the submission of its bid, i.e. March 10, 2003. This poses a legal obstacle to its eligibility as a bidder. The Request for Proposal requires the bidder to submit financial documents that will establish to the BAC’s satisfaction its financial capability which include: “(1) audited financial statements of the Bidder’s firm for the last three (3) calendar years, stamped “RECEIVED” by the appropriate government agency, to show its capacity to finance the manufacture and supply of Goods called for and a statement or record of volumes of sales; (2) Balance Sheet; (3) Income Statement; and (4) Statement of Cash Flow.” As correctly pointed out by petitioners, how could MPEI comply with the above requirement of audited financial statements for the last three (3) calendar yearsif it came into existence only eleven (11) days prior to the bidding? To do away with such complication, MPEI asserts that it was MP CONSORTIUM who submitted the bid on March 10, 2003. It pretends compliance with the requirements by invoking the financial capabilities and long time existence of the alleged members of the MP CONSORTIUM, namely, Election.Com, We Solv, SK CeC, ePLDT and Oracle. It wants this Court to believe that it is MP CONSORTIUM who was actually dealing with the COMELEC and that its (MPEI) participation is merely that of a “lead company and proponent” of the joint venture. This is hardly convincing. For one, the contract for the supply and delivery of ACM was between COMELEC and MPEI, not MP CONSORTIUM. [19] As a matter of fact, there cannot be found in the contract any reference to the MP CONSORTIUM or any member thereof for that matter. [20]For another, the agreements among the alleged members of MP CONSORTIUM do not show the existence of a joint-venture agreement. Worse, MPEI cannot produce the agreement as to the “joint and several liability” of the alleged members of the MP CONSORTIUM as required by this Court in its Resolution dated October 7, 2003. What is apparent from the four (4) agreements I gathered is the existence of either a “contractor-subcontractor” or “buyer-supplier” relationship between MPEI on the one hand and the alleged members of the MP CONSORTIUM. There was no assumption of a “joint and several liability” over the entire Project of the COMELEC nor an intention to enter directly into a contract with COMELEC. In the “ Memorandum of Agreement” between MPEI and WeSolv, the latter only agreed to be one of its suppliers. Contrary to MPEI’s asseveration that it was MP CONSORTIUM which bid for the project, the Memorandum clearly states that MPEI “will undertake negotiations with the COMELEC for the purpose of finalizing the contract for the said Project in the event that it [MPEI] is declared as the winning bidder and the Project is awarded in its [MPEI] favor.” As if to emphasize the absence of “joint and several liability” to the entire Project, the Memorandum expressly provides that WeSolv shall be jointly and severally liable with MPEI “ only for the particular products and/or services supplied by the former for the Project” and that “in the event that they failed to agree on the terms and conditions of the supply of the products and services including but not limited to the scope of the products and services to be supplied and payment terms, WeSolv shall cease to be bound by its obligations.” The same provisions are to be found in the “Memorandum of Agreement” between MPEI and SK C & C. [21] The “ Teaming Agreement” between MPEI and Election.Com [22]also negates MPEI’s assertion that it was MP CONSORTIUM that bid for the Project. Here, MPEI is singled out as the one who intended to submit a proposal to the COMELEC. Under the “Teaming Agreement,” MPEI “has identified the subcontractor [Election.Com] as one of its suppliers.” It was stipulated therein that “ the parties shall each be individually liable for any penalties or liabilities incurred by them in connection with the Project, if it can be shown that the said penalties or liabilities are a direct result of errors in data or, non-performance of products and/or services supplied.” The same limitation on liability is present in the “Teaming Agreement” between MPEI and ePLDT. [23] A joint venture is an association of persons or companies jointly undertaking some commercial enterprise with all of them generally contributing assets and sharing risks. It requires a community of interest in the performance of the subject matter, a right to direct and govern the policy in connection therewith, and duty, which may be altered by agreement to share both in profit and losses. [24]In the Philippines, the prevailing school of thought is that a joint venture is a species of partnerships. [25]Since joint venture is a species or a special type of partnership, it is said to have the following characteristics of partnership: “(a) It would have a juridical personality separate and distinct from that of each of the joint-venturers; (b) Each of the co-venturers would be liable with their private property to the creditors of the joint venture beyond their contributions to the joint venture; (c) Even if a co-venturer transfers his interest to another, the transferee does not become a co-venturer to the others in the joint venture unless all the other co-venturers consent. This is in consonance with the delectus personarumprinciple applicable to partnerships; (d) Generally, the co-venturers acting on behalf of the joint venture are agents thereof as to bind the joint venture; and (e) Death, retirement, insolvency, civil interdiction or dissolution of a co-venturer dissolves the joint venture.” [26] The agreements cited above do not show that each of the alleged members of the MP CONSORTIUM recognizes the latter as an entity with a separate and distinct juridical personality. What is more, its member limits its liability only to the extent of their participation. Surely, it is grave abuse of discretion on the part of the COMELEC to award a billion worth of contract to an entity whose existence and eligibility is highly questionable. It risks the accomplishment of a great undertaking such as the automation of our country’s election system. From a brief survey of the four (4) agreements, I am convinced that the COMELEC, and ultimately the people, stand on the losing end should the Project fail because of the obvious difficulty in determining where the culpability lies. It bears reiterating for the consumption of our public officers that in the exercise of their contracting prerogative, they should be the first judges of the legality, propriety and wisdom of the contract they entered into. They must exercise a high degree of caution so that the Government may not be the victim of ill-advised or improvident action. [27]Prudence should be their primordial virtue. Thus, even though they have broad discretion to determine the qualifications of the bidders, it may not act arbitrarily and they must conform to statutory requirements governing the awarding of public contracts. [28] Reason must govern the acts of such officials, and courts will not hesitate to interfere when it is clearly made to appear that they have acted arbitrarily, dishonestly or beyond the reasonable limits of the discretion conferred upon them. Another arbitrary act of the COMELEC is its awarding of the contract to MPEI despite the fact that it failed in some of the technical requirements. “Below is a comparative presentation of the requirements wherein Mega-Pacific or TIM or both of them failed. <table><tbody><tr><td> KEY REQUIREMENTS</td><td colspan=3> BIDDER/S THAT FAILED</td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Does the machine have an</td><td></td><td></td><td></td></tr><tr><td> accuracy rating of at least</td><td></td><td></td><td></td></tr><tr><td> 99.995 percent? (Item No. 1,</td><td></td><td></td><td></td></tr><tr><td> Table 6, DOST Report)</td><td></td><td></td><td></td></tr><tr><td> At normal environment</td><td> Mega</td><td></td><td>TIM</td></tr><tr><td> At harsh environment</td><td></td><td> Mega</td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Uninterruptible back-up power</td><td></td><td></td><td></td></tr><tr><td> system, that will engage</td><td></td><td></td><td></td></tr><tr><td> immediately to allow operation of</td><td></td><td></td><td></td></tr><tr><td> at least 10 minutes after outrage,</td><td></td><td></td><td></td></tr><tr><td> power surge or abnormal</td><td></td><td></td><td></td></tr><tr><td> electrical occurrences? (Item No.</td><td></td><td></td><td> TIM</td></tr><tr><td> 4, Table 6, DOST Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td>Machines read two sided ballots</td><td></td><td></td><td> TIM*</td></tr><tr><td> in one pass? (Item No. 5,</td><td></td><td></td><td></td></tr><tr><td> Table 6, DOST Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td>Machine can detect previously</td><td></td><td></td><td></td></tr><tr><td> counted ballots and prevent</td><td></td><td></td><td></td></tr><tr><td> previously counted ballots from</td><td></td><td></td><td>TIM</td></tr><tr><td> being counted more than once?</td><td></td><td></td><td></td></tr><tr><td> (Item No. 6, Table 6, DOST</td><td></td><td></td><td></td></tr><tr><td> Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td>Store results of counted votes by</td><td></td><td></td><td></td></tr><tr><td> precinct in external (removable)</td><td></td><td></td><td> TIM</td></tr><tr><td> storage device? (Item No. 7,</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Table 6, DOST Report)</td><td></td><td></td><td></td></tr><tr><td> Data stored in external media is</td><td></td><td></td><td> TIM</td></tr><tr><td> encrypted? (Item No. 8, Table 6,</td><td></td><td></td><td></td></tr><tr><td> DOST Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> KEY REQUIREMENTS</td><td colspan=3> BIDDER/S THAT FAILED</td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> CPU speed is at least 400 mHz?</td><td></td><td></td><td> TIM</td></tr><tr><td> (Item No. 10, Table 6, DOST</td><td></td><td></td><td></td></tr><tr><td> Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Generates printouts of the</td><td></td><td></td><td></td></tr><tr><td> election returns in a format</td><td></td><td></td><td></td></tr><tr><td> specified by the Comelec?</td><td></td><td></td><td></td></tr><tr><td> (Item No. 12, Table 6, DOST</td><td>Mega</td><td></td><td>TIM</td></tr><tr><td> Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Generates an audit trail of the</td><td></td><td></td><td></td></tr><tr><td> counting machine, both hard and</td><td></td><td></td><td></td></tr><tr><td> soft copy? (Item No. 14, Table 6,</td><td></td><td></td><td>TIM*</td></tr><tr><td> DOST Report)</td><td></td><td></td><td></td></tr><tr><td>Soft copy</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Does the city/municipal</td><td></td><td></td><td></td></tr><tr><td> canvassing system consolidates</td><td></td><td></td><td></td></tr><tr><td> results from all precincts within it</td><td></td><td></td><td></td></tr><tr><td> using the encrypted soft copy of</td><td></td><td></td><td></td></tr><tr><td> the data generated by the</td><td></td><td></td><td></td></tr><tr><td> counting machine and stored on</td><td></td><td></td><td></td></tr><tr><td> the removable data storage</td><td></td><td></td><td></td></tr><tr><td> device? (Item No. 15, Table 6,</td><td></td><td></td><td> TIM*</td></tr><tr><td> DOST Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Does the city/municipality</td><td></td><td></td><td></td></tr><tr><td> canvassing system consolidate</td><td></td><td></td><td> TIM*</td></tr><tr><td> results from all precincts within</td><td></td><td></td><td></td></tr><tr><td> it using the encrypted soft copy</td><td></td><td></td><td></td></tr><tr><td> of the data generated by</td><td></td><td></td><td></td></tr><tr><td> counting machine and</td><td></td><td></td><td></td></tr><tr><td> transmitted through an</td><td></td><td></td><td></td></tr><tr><td> electronic transmission media?</td><td></td><td></td><td>Mega</td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> (Item No. 16, Table 6, DOST</td><td></td><td></td><td></td></tr><tr><td> Report)</td><td></td><td></td><td></td></tr><tr><td> Note: No facilities/resources</td><td></td><td></td><td></td></tr><tr><td> available to test the transmission</td><td></td><td></td><td></td></tr><tr><td> of data through electronic means.</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> KEY REQUIREMENTS</td><td colspan=3> BIDDER/S THAT FAILED</td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Does the system output a Zero</td><td></td><td></td><td></td></tr><tr><td> City/ Municipal Canvass Report,</td><td></td><td></td><td>TIM*</td></tr><tr><td> which is printed on election day</td><td></td><td></td><td></td></tr><tr><td> prior to the conduct of the actual</td><td></td><td></td><td></td></tr><tr><td> canvass operation, that shows</td><td></td><td></td><td></td></tr><tr><td> that all totals for all the votes for</td><td></td><td></td><td></td></tr><tr><td> all the candidates and other</td><td></td><td></td><td></td></tr><tr><td> information are indeed zero or</td><td></td><td></td><td></td></tr><tr><td> null? (Item No. 17, Table 6, DOST</td><td></td><td></td><td></td></tr><tr><td> Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Does the system consolidate</td><td></td><td></td><td></td></tr><tr><td> results from all precincts in the</td><td></td><td></td><td></td></tr><tr><td> city/municipality using the data</td><td></td><td></td><td>TIM*</td></tr><tr><td> storage device coming from the</td><td></td><td></td><td></td></tr><tr><td> counting machine? (Item No. 18,</td><td></td><td></td><td></td></tr><tr><td> Table 6, DOST Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Is the machine 100% accurate?</td><td></td><td></td><td></td></tr><tr><td>(Item No. 19, Table 6, DOST</td><td></td><td></td><td> TIM*</td></tr><tr><td> Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Is the Program able to detect</td><td></td><td></td><td></td></tr><tr><td> previously downloaded</td><td></td><td></td><td></td></tr><tr><td> precinct results and prevent</td><td></td><td></td><td></td></tr><tr><td> these from being inputted again</td><td>Mega</td><td></td><td>Mega</td></tr><tr><td> into the System? (Item No. 20,</td><td></td><td></td><td></td></tr><tr><td> Table 6, DOST Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> The System is able to print the</td><td></td><td></td><td></td></tr><tr><td> specified reports and the audit</td><td></td><td></td><td></td></tr><tr><td> trail without any loss of data</td><td></td><td></td><td></td></tr><tr><td> during generation of the</td><td></td><td></td><td></td></tr><tr><td> abovementioned reports? (Item</td><td></td><td></td><td></td></tr><tr><td> No. 21, Table 6, DOST Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td>Print specified reports</td><td></td><td>Mega</td><td> TIM*</td></tr><tr><td>Audit trail</td><td></td><td> (Note: Audit</td><td> TIM*</td></tr><tr><td></td><td></td><td> trail not yet</td><td></td></tr><tr><td></td><td></td><td> incorporated)</td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> KEY REQUIREMENTS</td><td colspan=3> BIDDER/S THAT FAILED</td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Can the result of the</td><td></td><td></td><td></td></tr><tr><td> city/municipal consolidation be</td><td></td><td></td><td></td></tr><tr><td> stored in a data storage device?</td><td></td><td></td><td> TIM*</td></tr><tr><td> (Item No. 22, Table 6, DOST</td><td></td><td></td><td></td></tr><tr><td> Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Does the System consolidate</td><td></td><td></td><td></td></tr><tr><td> results from all precincts in the</td><td></td><td></td><td></td></tr><tr><td> provincial/district/national using</td><td></td><td></td><td></td></tr><tr><td> the data storage device from</td><td></td><td></td><td></td></tr><tr><td> different levels of consolidation?</td><td></td><td></td><td></td></tr><tr><td> (Item No. 23, Table 6, DOST</td><td></td><td></td><td></td></tr><tr><td> Report)</td><td></td><td></td><td>TIM*</td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Is the System 100% accurate?</td><td></td><td></td><td></td></tr><tr><td> (Item No. 24, Table 6, DOST</td><td></td><td></td><td></td></tr><tr><td> Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> Is the Program able to detect</td><td></td><td></td><td></td></tr><tr><td> previously downloaded precinct</td><td></td><td></td><td></td></tr><tr><td> results and prevent these from</td><td></td><td></td><td></td></tr><tr><td> being imported again into the</td><td></td><td></td><td></td></tr><tr><td> System? (Item No. 25, Table 6,</td><td></td><td></td><td></td></tr><tr><td> DOST Report)</td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td> The System is able to print the</td><td></td><td></td><td></td></tr><tr><td> specified reports and the audit</td><td></td><td></td><td></td></tr><tr><td> trail without any loss of data</td><td></td><td></td><td></td></tr><tr><td> during generation of the</td><td></td><td></td><td></td></tr><tr><td> abovementioned reports? (Item</td><td></td><td></td><td></td></tr><tr><td> No. 26, Table 6, DOST Report)</td><td></td><td></td><td> TIM*</td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td>Print specified reports?</td><td> Mega</td><td></td><td> TIM*</td></tr><tr><td>Audit trail?</td><td rowspan=2 colspan=2> (Audit trail notyet incorporated)</td><td></td></tr><tr><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td>Can the results of the provincial/</td><td></td><td></td><td></td></tr><tr><td> district/ national consolidation be</td><td></td><td></td><td></td></tr><tr><td> stored in a data storage device?</td><td></td><td></td><td>TIM*</td></tr><tr><td> (Item No. 27, Table 6, DOST</td><td></td><td></td><td></td></tr><tr><td> Report)</td><td></td><td></td><td></td></tr></tbody></table> Notwithstanding the above failed marks the COMELEC still awarded the contract to MPEI. This is highly irregular. The above requirements where MPEI failed cannot be considered as insubstantial. They have a bearing on the required features of the automated election system under Section 7 of R.A. No. 8436, such as (1) use of appropriate ballots, (2) stand-alone machine which can count votes and an automated system which can consolidate the results immediately, (c) with provisions for audit trails, (d) minimum human intervention, and (e) adequate safeguard/security measures. COMELEC’s stance that it can waive certain requirements is misplaced in the present case because what it waives are those which concerns the integrity and accuracy of the ACM and thus, affect the substance and the validity of the bids. Statutory or regulatory mandatory requirements with respect to bidding on public contracts cannot be waived. Presidential Decree No. 1594, [29]for one, expressly states that the Government, in the evaluation of bid received, "reserves the right to waive the consideration of minor deviations in the bids received which do not affect the substance and validity of the bids." Thus, while a reservation in the advertisement of the right to reject any bid generally vests in the authorities a wide discretion as to who is the best and most advantageous bidder, however, it may not be used as a shield to a fraudulent award. [30] Should this be the case, judicial interference would be justified. One final note. There is a long history of election irregularities that suggest that vote fraud using voting machines has been occurring. As a matter of fact, many voting security experts agree that voting machines represent a pandora’s box for the election process. If the computer science community remains mute and allow unreliable voting systems to be procured, then it abdicates what may be its only opportunity to ensure the democratic process in elections. Government officials need help in understanding the serious risks inherent in computer-related elections system. Like petitioners, everyone must do his share. WHEREFORE, I vote to GRANT the Petition. COMELEC Resolution No. 6074 is declared NULL and VOID. [1] LIVY, History . Bk. XXXV, ch. 32. [2] Electronic Voting: What You Need To Know, William Rivers Pitt, Interview of David L. Dill, a Professor of Computer Science at Stanford University. Monday, 20 October 2003. [3]An act authorizing the Commission on Elections to use an automated election system in the May 11, 1998 national or local elections and in subsequent national and local electoral exercises, providing funds therefore and for other purposes. [4]Section 7. [5]President Gloria Macapagal-Arroyo had earlier issued Executive Order (EO) No. 172 on January 24, 2003, allocating P2,500,000,000.00 to fund the AES. To augment this amount, the President issued EO No. 175 on February 10, 2003, allocating an additional P500,000,000.00 for the Project. The COMELEC reconfigured the modernization program into the three (3) phases mentioned above and reallocated the budget as follows: (a) P1 Billion for Phase I; (2) P1.7 Billion for Phase II; and (3) P300 Million for Phase III. [6] Rolloat 124. [7]Report on the Evaluation of the Technical Proposal on Phase II. [8] Republic of the Philippines vs. Silerio, G.R. No. 108869, May 6, 1997, 272 SCRA 280, citing Provident Tree Farms, Inc. vs. Batario, Jr., 231 SCRA 471 (1994); Lim, Sr. v. Secretary of Agriculture and Natural Resources, 34 SCRA 751 (1970). [9]50 SCRA 498-499 (1973). [10]Petition at 39. [11]G.R. No. 124293, November 20, 2000, 345 SCRA 143. [12]G.R. No. 138298, November 29, 2000, 346 SCRA 485. [13]Section 55. Protests on Decisions of the BAC 55.1 Decisions of the BAC with respect to the conduct of bidding may be protested in writing to the head of the procuring entity; Provided, however, That a prior motion for reconsideration should have been filed by the party concerned within the reglementary periods specified in this IRR-A and the same has been resolved. The protest must be resolved filed within seven (7) calendar days from receipt by the party concerned of the resolution of the BAC denying its motion for reconsideration. A protest may be made by filing a verified position paper with the head of the procuring agency concerned, accompanied by the payment of a non-refundable protest fee. The non-refundable protest fee shall be in an amount equivalent to no less than one percent (1%) of the ABC. [14]An Act Providing for the Modernization, Standardization, and Regulation of the Procurement Activities of the Government and for Other Purposes. [15]Section 58. Resort to Regular Courts: Certiorari. 58.1 Court action may be resorted to only after the protests contemplated in this Rule shall have been completed, i.e., resolved by the head of the procuring entity with finality. The regional trial court shall have jurisdiction over final decisions of the head of the procuring entity. Court actions shall be governed by Rule 65 of the 1997 Rules of Civil Procedure. [16]G.R. No. 151992, September 18, 2002, 389 SCRA 353. [17]See Buklod ng Kawaning EIIB vs. Zamora, G.R. Nos. 142801-802, July 10, 2001; Dario vs. Mison, G.R. No. 81954, August 8, 1989, 176 SCRA 84; Fortich vs. Corona, G.R. No. 131457, April 24, 1998, 289 SCRA 624. [18] Rollo, Vol. IV at 1784. [19]In open court, Atty. Lazaro, counsel for private respondent Mega Pacific eSolutions, Inc. was directed by this Court to submit the following documents: (a) contract executed between consortium represented by Mega Pacific eSolutions, Inc. and COMELEC; (b) agreement among the consortium members; (c) financial statements of the members of the consortium; (d) agreement as to the joint and several liability of the members of the consortium; status report of the Department of Science and Technology (DOST) as to whether the machines are already free of the eight (8) defects or failing marks. (Resolution dated October 7, 2003, Rollo, Vol. II at 1221-1222.) [20] Rollo, Vol. IV at 2198. [21]The MOA between MPEI and SK C & C was entered only on March 9, 2003. [22] Rollo, Vol. IV at 2355-2363. [23] Id.at 2364-2371. [24] JG Summit Holdings, Inc., vs. Court of Appeals, supra. [25]Villanueva, Philippine Corporate Law, 2002 at 917 [26] Id.at 918-919. [27] Rivera vs. Maclang, G.R. No. L-15948, January 31, 1963, 7 SCRA 57. [28]64 Am Jur 2d 64§ 64. [29]Prescribing Policies, Guidelines, Rules and Regulations for Government Infrastructure Contracts; Promulgated June 11, 1978. [30]Fernandez, Jr., A Treatise on Government Contracts Under Philippine Law, 2001 at 30-31, citing Borromeo vs. City of Manila, 62 Phil. 512 (1960); Jalandoni vs. NARRA, 108 Phil. 486 (1935); Filipinas Engineering vs. Ferrer, G.R. No. L-31455, February 28, 1985, 135 SCRA 25. DISSENTING OPINION TINGA, J.: Prologue Once again, the Court availing of its extraordinary powers or so-called “ certiorari” jurisdiction has struck down a government contract, sealed no less by the respondent Commission on Elections (COMELEC) in the exercise of its administrative powers granted by the Constitution in relation to the conduct of elections. Apparently, the Court has opted to trudge the trail it blazed recently in the Amari [1]and PIATCO [2]cases. Amarivoided the Manila Bay reclamation project on constitutional grounds [3]and PIATCOstruck down the NAIA Terminal III contract for violations of the Constitution [4]and some other laws [5]to boot. But in this case, no constitutional provision or letter of a statute was alleged to have been violated. The Court nullified the contract for an automated election system (“AES”) simply on the ground that in making the award the COMELEC has allegedly violated its bidding rules and an unfounded apprehension that the counting machines would not work on election day. On the other hand, not one of the losing bidders has joined the petition, as neither they nor the petitioners questioned the fairness of the price tag for the machines. The year 2004 could have well been marked in the annals of the Philippines by the maiden use of the automated election. But the country was deprived of the golden chance to join the growing roster of states with modern election systems which include developing countries such as Kenya, Mali, Zambia, Romania, Albania, Mexico and Argentina because of the Decisionof the Court. In the process, the Court has disregarded the fundamental postulates by which this case should have been decided. They are the following: First. The instant original petition is one for prohibition and mandamus under Rule 65 of the 1997 Rules of Civil Procedure. Prohibition is an extraordinary writ directed against any tribunal, corporation, board, officer or person, whether exercising judicial, quasi-judicial or ministerial functions, commanding the respondent to desist from further proceedings when said proceedings are without or in excess of the respondent’s jurisdiction or are attended with grave abuse of discretion amounting to lack or excess of jurisdiction and there is no appeal or any other plain, speedy, and adequate remedy in the ordinary course of law. [6] Mandamus, on the other hand, is an extraordinary writ commanding a tribunal, corporation, board, officer or person, immediately or at some other specified time, to do the act required to be done, when the respondent unlawfully neglects the performance of an act which the law specifically enjoins as a duty resulting from an office, trust, or station, or when the respondent excludes another from the use and enjoyment of a right or office to which such other is entitled, and there is no other plain, speedy and adequate remedy in the ordinary course of law. [7] Second. In deciding the instant case, the Court shall consider only the undisputed or admitted facts and resolve only the specific questions raised by the parties. [8]The Court is not a repository of remedies or a “super-legal-aid bureau.” [9]We cannot grant relief for every perceived violation of the law or worse, on the basis of prophetic wisdom. Paraphrasing an old decision, Mr. Justice Felix Frankfurter wrote: “Judicial power, however large, has an orbit more or less strictly defined by well-recognized presuppositions regarding the kind of business that properly belongs to courts. Their business is adjudication, not speculation. They are concerned with actual, living controversies, and not abstract disputation.” [10] Third. The Court does not, as indeed it cannot, guarantee the success of the automation or the integrity of the coming elections. It is not the Court’s function to activelyensure that the automation is successfully implemented or that the elections are made free of fraud, violence, terrorism and other threats to the sanctity of the ballot. This duty lies primarily with the COMELEC. [11] Fourth. The Court has constantly underscored the importance of giving the COMELEC considerable latitude in adopting means and methods that will insure the accomplishment of the objective for which it was created — to promote free, orderly, honest, peaceful and credible elections. Thus, in the past we have prudently declined to interfere with the COMELEC’s exercise of its administrative functions absent any showing of grave abuse of discretion. [12]As luminously stated in Sumulong v. COMELEC, [13]“[I]n the matter of the administration of the laws relative to the conduct of elections, as well as in the appointment of election inspectors, we must not by any excessive zeal take away from the Commission on Elections the initiative which by constitutional and legal mandates properly belongs to it. Due regard to the independent character of the Commission, as ordained in the Constitution, requires that the power of this court to review the acts of that body should, as a general proposition, be used sparingly, but firmly in appropriate cases.” [14] For the reasons I shall discuss hereunder, I find myself unable to subscribe to the ponenciaand join the ranks of my colleagues in the majority. Let me first mention that at the opening part of the Decision, the Court opined that there is grave abuse of discretion when the assailed act is contrary to “jurisprudence.” Yet, the 99-page Decision failed to mention a single Court decision which the respondents have defied. Petitioners failed to exhaustadministrative remedies I agree with the respondents that the petitioners failed to exhaust, or better still avail of, the administrative remedies outlined in R.A. 9184, as follows: “SEC. 55. Protests on Decisions of the BAC. — Decisions of the BAC in all stages of procurement may be protested to the head of the procuring entity and shall be in writing. Decisions of the BAC may be protested by filing a verified position paper and paying a non-refundable protest fee. The amount of the protest fee and the periods during which the protests may be filed and resolved shall be specified in the IRR. SEC. 56. Resolution of Protests. — The protests shall be resolved strictly on the basis of the records of the BAC. Up to a certain amount to be specified in the IRR, the decisions of the Head of the Procuring Entity shall be final. SEC. 57. Non-interruption of the Bidding Process. — In no case shall any protest taken from any decision treated in this Article stay or delay the bidding process. Protests must first be resolved before any award is made. SEC. 58. Resort to Regular Courts; Certiorari. — Court action may be resorted to only after the protests contemplated in this Article shall be have been completed. Cases that are filed in violation of the process specified in this Article shall be dismissed for lack of jurisdiction. The regional trial court shall have jurisdiction over final decisions of the head of the procuring entity. Court actions shall be governed by Rule 65 of the 1997 Rules of Civil Procedure. This provision is without prejudice to any law conferring on the Supreme Court the sole jurisdiction to issue temporary restraining orders and injunctions relating to Infrastructure Projects of Government.” [Emphasis supplied] As correctly pointed out by the respondents, at no time during the entire bidding process did the petitioners question the determination of the COMELEC Bids and Awards Committee (BAC) finding Mega Pacific Consortium ( MPC) eligible to bid. Under R.A. 9184, decisions of the BAC should be appealed to the COMELEC en banc. Consequently, the determination of the BAC that MPCwas eligible to bid, adopted subsequently by the COMELEC, became final. The doctrine of exhaustion of administrative remedies requires that when an administrative remedy is provided by law, relief must be sought by exhausting this remedy before the courts will act. No recourse can be had until all such remedies have been exhausted and special civil actions against administrative officers should not be entertained if superior administrative officers could grant relief. [15]In Hon. Carale v. Hon. Abarintos, [16]the Court enunciated the reasons for the doctrine, thus: Observance of the mandate regarding exhaustion of administrative remedies is a sound practice and policy. It ensures an orderly procedure which favors a preliminary sifting process, particularly with respect to matters peculiarly within the competence of the administrative agency, avoidance of interference with functions of the administrative agency by withholding judicial action until the administrative process had run its course, and prevention of attempts to swamp the courts by a resort to them in the first instance. The underlying principle of the rule rests on the presumption that the administrative agency, if afforded a complete chance to pass upon the matter, will decide the same correctly. There are both legal and practical reasons for this principle. The administrative process is intended to provide less expensive and more speedy solutions to disputes. Where the enabling statute indicates a procedure for administrative review, and provides a system of administrative appeal, or reconsideration, the courts, for reasons of law, comity and convenience, will not entertain the case unless the available administrative remedies have been resorted to and the appropriate authorities have been given an opportunity to act and correct the errors committed in the administrative forum. Accordingly, the party with an administrative remedy must not merely initiate the prescribed administrative procedure to obtain relief, but also pursue it to its appropriate conclusion before seeking judicial intervention in order to give the administrative agency an opportunity to decide the matter by itself correctly and prevent unnecessary and premature resort to the court. [17][Emphasis supplied] Moreover, under the Rules of Court, judicial review of administrative decisions may be availed of only through special civil actions. Such proceedings cannot lie if there is an appeal, or any other plain, speedy, and adequate remedy in the ordinary course of law. [18] In Paat vs. Court of Appeals, [19]the Court enumerated the instances when the rule on exhaustion of administrative remedies may be disregarded: …(1) when there is a violation of due process, (2) when the issue involved is purely a legal question, (3) when the administrative action is patently illegal amounting to lack or excess of jurisdiction, (4) when there is estoppel on the part of the administrative agency concerned, (5) when there is irreparable injury, (6) when the respondent is a department secretary whose acts as an alter egoof the President bear the implied and assumed approval of the latter, (7) when to require exhaustion of administrative remedies would be unreasonable, (8) when it would amount to a nullification of a claim, (9) when the subject matter is a private land in land case proceedings, (10) when the rule does not provide a plain, speedy and adequate remedy, and (11) when there are circumstances indicating the urgency of judicial intervention. [20] The petitioners’ allegations do not bring their case within the jurisprudentially recognized exceptions to the rule on exhaustion of administrative remedies. It is noteworthy that the protest mechanism outlined in R.A. 9184, in allowing protests of decisions of the BAC “in all stages of procurement,” [21]reinforces and even institutionalizes the exhaustion doctrine insofar as public bidding is concerned. Hence, had petitioners intended to pursue the available administrative remedies, they could have easily asked for a reconsideration the moment the BAC determined MPCeligible to bid, failing which, they could have filed a protest with the COMELEC en bancitself. Petitioners did neither. Instead they sat in waiting until the final hour and now insist that the Court disregard the rule on exhaustion of administrative remedies on the puerile reason that there was no opportunity for the protest mechanism instituted in R.A. 9184 to apply because the BAC rendered its report and recommendation in open session on April 15, 2003, the same day and on the same occasion that the COMELEC issued the assailed Resolution No. 6074awarding the Contract to MPC. The majority opinion posits that it would have been futile for petitioners to protest/appeal the BAC report to the COMELEC chair since by the time they could have made the move the COMELEC had already approved the report. Not necessarily so. The petitioners could have, or better still, should have appealed directly to the COMELEC en banc. After all, matters of this nature have to be decided by the COMELEC as a collegial body. To state that the poll body would not act on the appeal is to uncharitably state that it would disregard its duty to respond as required by the Code of Ethical Conduct. [22]Thus, the Court’s statement that the COMELEC en bancmade it impossible for petitioners to make use of the administrative remedy is simply baseless. Be it noted that the petitioners wasted nearly five (5) months from the time the BAC Report was released on April 21, 2003 before they filed the instant Petitionon August 6, 2003. The significant time gap precludes the availability of the exceptions to the exhaustion doctrine. Specifically, the petitioners cannot successfully claim that to require exhaustion of administrative remedies would be unreasonable, or that the rule does not provide a plain, speedy and adequate remedy, or that judicial intervention has become urgent because of the circumstances. Considering the circumstances, it is my view that the premature invocation of this Court’s judicial power is fatal to the petitioners’ cause of action. MPC, the consortium,participated in the bidding According to the Court, the first major concern which bears on the issue of grave abuse of discretion relates to the identity and existence of the MPCas a bidder. Petitioners claim that the real bidder was Mega Pacific eSolutions, Inc. (MPEI). On the other hand, the respondents insist that the bidder was MPCof which MPEIwas the lead member. On record are the following documents: Letter of MPEI’sPresident, Willy Yu, dated March 7, 2003, which states <table><tbody><tr><td></td><td></td><td></td><td></td><td> March 7, 2003</td></tr></tbody></table> BIDS AND AWARDS COMMITTEE Commission On ElectionIntramuros, Manila Sir: In response to your Invitation to Bid for the COMELEC Modernization Project corresponding to the various phases which are as follows: <table><tbody><tr><td> Phase I :</td><td> Voters Registration – Voters Validation System</td></tr><tr><td></td><td></td></tr><tr><td> Phase II :</td><td> Vote Counting and Canvassing – Automated</td></tr><tr><td></td><td> Counting/Canvassing</td></tr><tr><td></td><td></td></tr><tr><td> Phase III :</td><td> Transmission & Dissemination of Results –</td></tr><tr><td></td><td> Electronic Transmission/Consolidation &</td></tr><tr><td></td><td> Dissemination of Result</td></tr></tbody></table> The following companies listed below have agreed to form a consortium to bid for the said project; Mega Pacific eSolutions, Inc. Election.Com Ltd EPLDT SK C & C We Solv Open Computing, Inc. (Subsidiary of Fujitsu Phils. Inc.) Oracle System (Philippines) Inc. Very truly yours, (Sgd.) WILLY U. YUPresidentMEGA PACIFIC eSOLUTIONS, INC.(Lead Company/Proponent)For: MEGA PACIFIC CONSORTIUM Agreements among the members of the consortium, namely:
https://elibrary.judiciary.gov.ph/thebookshelf/showdocs/14/58622
Cellular F-Actin Levels as a Marker for Cellular Transformation: Relationship to Cell Division and Differentiation1 | Cancer Research | American Association for Cancer Research Cellular F-Actin Levels as a Marker for Cellular Transformation: Relationship to Cell Division and Differentiation 1 Departments of Urology [J.Y.R., R.E.H., P.L.J., R.A.B., G.P.H.], Pathology [G.P.H.], Biochemistry [R.E.H.], and Environmental Health [R.E.H., G.P.H.], University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73190 ; Flow Cytometry Laboratory, Department of Pathology, Veterans Administration Medical Center , Oklahoma City, Oklahoma 73104 [W. D. B., L. T. A.] ; and Norman, Oklahoma 73019 [P. B. B.] Abstract Transformation is associated with profound structural and quantitative changes in the cytoskeleton. Herein we report studies using F-actin, a major cytoskeletal protein, as a quantitative marker for transformation cells, focusing on separating the effects of the cell cycle, cell differentiation, and transformation. The model system for these studies consisted of three lymphoblastic cell lines, one untransformed line (RPMI) and two transformed lines, one (HL-60) of which can be induced to differentiate and the other (Daudi) which cannot. The relation of F-actin levels to cell cycle was studied by flow cytometry with the use of fluorescein-phalloidin to label F-actin and propidium iodide to label DNA. F-Actin levels in transformed Daudi and HL-60 lines were only two-thirds that of the untransformed RPMI cells. Histograms of the distribution of F-actin showed that the transformed lines consisted of two cell populations, one having an F-actin content near that of untransformed cells and the other having much less. Cell cycle analysis showed that F-actin in untransformed cells increased 10–15% as cells entered the S compartment, remaining approximately constant through G 2+ M phases of the cell cycle, but in transformed cells the major increase in F-actin occurred during G 2+ M phase. Double-label studies with rhodamine-phalloidin for F-actin and KI-67 monoclonal antibody for dividing cells (cells at late G 1,S,G 2, and M) measured with quantitative fluorescence image analysis showed that the mean F-actin content of dividing cells was twice that of nondividing cells. These results suggested that most of the cell division-related F-actin increase occurred during late G 1phase in untransformed cells. Differentiation of HL-60 cells with dimethyl sulfoxide or retinoic acid normalized the F-actin content of the nondividing cell population, but dimethyl sulfoxide and retinoic acid produced no detectable change in F-actin in the undifferentiable Daudi cells. A tumor promoter (12- O-tetradecanoylphorphol-13-acetate) inhibits differentiation of hematopoietic cells, resulted in a 32% decrease in the mean F-actin content of RPMI cells due to the appearance of a new subpopulation of low F-actin content. The 12- O-tetradecanoylphorbol-13-acetate-induced changes reversed slowly after removal of 12- O-tetradecanoylphorbol-13-acetate but more rapidly in the presence of retinoic acid. These results indicate that F-actin quantification can serve as a marker for cellular transformation and provides a tool for studying the mechanisms of cellular differentiation that may lead to a better understanding of the oncogenic process. 1 This work was supported, in part, by a subcontract from the Cancer Institute of the Chinese Academy of Medical Sciences, Beijing, People's Republic of China, for “Quantitative Fluorescence Image Analysis (QFIA) of Esophageal Samples to Detect Abnormal Levels of Nuclear Nucleic Acid,” as a part of a National Cancer Institute-sponsored “Study of the Effect of Nutritional Intervention on Intermediate Endpoints of Esophageal Cancer in Linxian, China”; by a Postdoctoral Research Fellowship awarded to J.Y.R. by the Graduate College of the University of Oklahoma Health Sciences Center; and in part by the Veterans Administration and CDC/National Institute of Occupation Safety and Health Grant R01-OH02647.
https://aacrjournals.org/cancerres/article/50/8/2215/496359/Cellular-F-Actin-Levels-as-a-Marker-for-Cellular?searchresult=1
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https://lasp.colorado.edu/maven/sdc/public/data/sites/site-20190411T185526/anc/eng/usm4/sci_anc_usm414_106_109.drf
ORS 480.341 - Customer operation of gasoline dispensing device in low-population county of eastern Oregon ORS Title 38, Protection from Fire; Chapter 480, Explosives; Flammable Materials; Pressure Vessels; Section 480.341, Customer operation of gasoline dispensing device in low-population county of eastern Oregon. Refreshed: 2023-06-16 Explosives ORS 480.341 Customer operation of gasoline dispensing device in low-population county of eastern Oregon TextAnnotations (1) As used in this section: (a) “Eastern Oregon” means that portion of the State of Oregon lying east of a line beginning at the intersection of the northern boundary of this state and the western boundary of Hood River County, and from there proceeding southerly along the western boundaries of Hood River, Wasco, Jefferson, Deschutes and Klamath Counties to the southern boundary of this state. (b) “Low-population county” means a county that, based on a certificate of population prepared under ORS 190.510 (Definitions for ORS 190) to 190.610 (State census program) , has a population of not more than 40,000. (2) Notwithstanding ORS 480.320 (Use of coin-operated pumps and dispensing of gasoline by self-service declared hazardous) , 480.330 (Operation of gasoline dispensing device by public prohibited) and 480.340 (Coin-operated or self-service gasoline pumps prohibited) , and subject to subsection (3) of this section, if a filling station, service station, garage or other dispensary where Class 1 flammable liquids are dispensed at retail is located in a low-population county of eastern Oregon, the owner or operator may: (a) Permit a person other than an owner, operator or employee to use or manipulate a device for dispensing liquids into the fuel tank of a motor vehicle or other retail container; (b) Permit the use of an installed coin-operated or self-service dispensing device for the liquids; and (c) Allow the use of an automatic nozzle to dispense the liquids without an owner, operator or employee being in the immediate vicinity of the tank or container being filled. (3) If the site of a dispensary described in subsection (2) of this section includes retail space providing goods or services, other than goods or services for maintaining, repairing or cleaning a motor vehicle, the dispensary shall make an owner, operator or employee available for dispensing Class 1 flammable liquids after 6 a.m. and before 6 p.m. (4) Notwithstanding ORS 480.320 (Use of coin-operated pumps and dispensing of gasoline by self-service declared hazardous) , 480.330 (Operation of gasoline dispensing device by public prohibited) , 480.340 (Coin-operated or self-service gasoline pumps prohibited) and 480.345 (Conditions for operation of dispensing device by certain nonretail customers) , if a nonretail facility is located in a low-population county of eastern Oregon, the owner or operator may: (a) Permit the dispensing of Class 1 flammable liquids at retail; (b) Permit a person other than an owner, operator, employee or nonretail customer to use or manipulate a device for dispensing liquids into the fuel tank of a motor vehicle or other retail container; (c) Permit the use of an installed coin-operated or self-service dispensing device for the liquids; and (d) Allow the use of an automatic nozzle to dispense the liquids without an owner, operator or employee being in the immediate vicinity of the tank or container being filled. (5)(a) Sales under subsection (2) of this section do not make a filling station, service station, garage or other dispensary where Class 1 flammable liquids are dispensed at retail subject to any provisions of ORS 480.315 (Policy) to 480.385 (Civil penalty for gasoline dispensing law violations) regulating nonretail facilities. (b) Sales under subsection (4) of this section do not require that a nonretail facility possess a license to dispense Class 1 flammable liquids at retail. (c) Sales under subsection (4) of this section do not require that a nonretail facility possess a conditional use license issued under ORS 480.355 (Conditional use license) . However, sales under subsection (4) of this section do not prevent a nonretail facility that qualifies under ORS 480.355 (Conditional use license) from also possessing a conditional use license. (d) Purchasing Class 1 flammable liquids under subsection (4) of this section does not make a retail customer subject to any gallonage requirement set forth in ORS 480.345 (Conditions for operation of dispensing device by certain nonretail customers) . (e) Purchasing Class 1 flammable liquids under subsection (4) of this section does not make a retail customer subject to rules of the State Fire Marshal establishing safety training requirements. (6) This section does not prohibit, limit or condition any dispensing of Class 1 flammable liquids or diesel fuel otherwise authorized under ORS 480.315 (Policy) to 480.385 (Civil penalty for gasoline dispensing law violations) . (7) No later than 90 days prior to commencing sales under subsection (4) of this section, a nonretail facility shall notify the State Fire Marshal that the facility plans to dispense Class 1 flammable liquids at retail under this section. (8) If a county where sales are authorized under this section ceases to be a low-population county, dispensaries and nonretail facilities located within the county may operate as described in this section notwithstanding the change in county population. [2015 c.525 §2; 2017 c.207 §1]
https://oregon.public.law/statutes/ors_480.341
THOMAS vs. MENA, MISC 18-000589 AKIMA THOMAS, f/k/a Akima Corbin v. SHARON MENA, MASSACHUSETTS HOUSING PARTNERSHIP FUND, and SANTANDER BANK, N.A., f/k/a Sovereign Bank MISC 18-000589 November 8, 2019 Essex, ss. VHAY, J. FINDINGS OF FACT, CONCLUSIONS OF LAW AND ORDER This case concerns a single-family property at 26 Union Court in Lynn, Massachusetts. According to the latest recorded deed for 26 Union Court, its owners are plaintiff Akima Corbin (now known by her married name, Akima Thomas) and her mother, defendant Sharon Mena, as joint tenants with rights of survivorship. But land records don't always tell the full story. In this case, Ms. Mena claims she owns all of 26 Union Court, and that Ms. Thomas holds her half for Mena, under the doctrines of resulting trust and constructive trust. Mena also contends that Thomas should be estopped from claiming any interest in 26 Union Court. If Mena prevails on any of her claims, Thomas won't have the right under M.G.L. c. 241, §1 et seq., as a normal joint tenant would, to a court-supervised partition of 26 Union Court. Ms. Thomas has petitioned this Court for precisely that relief. The parties appeared for trial on October 7, 2019, solely on Ms. Mena's claims. Having heard the parties' witnesses, having reviewed the exhibits admitted into evidence, having accepted the parties' stipulations of fact, and having considered the arguments of counsel, this Court finds the facts set forth above as well as these: 1. Ms. Mena is 64 years old. She was born in Trinidad and Tobago. While there, she married and gave birth to two daughters, one of whom is Ms. Thomas. Mena later divorced her husband. 2. In 1990, Ms. Mena placed Ms. Thomas (who was then five years old) with relatives, and came alone to Massachusetts. She worked first as a live-in babysitter, and later as a certified nursing assistant. She also did other work, performing as many as three jobs at a time. 3. Ms. Thomas turned eighteen in 2003. She graduated from high school in Trinidad and moved to Massachusetts to live with Ms. Mena. At the time, Mena was renting an apartment in Salem, Massachusetts. In 2004, Thomas moved out of Mena's apartment and started living with her boyfriend. Thomas subsequently broke up with her boyfriend, but was pregnant by that time. She returned to reside again in Mena's apartment. 4. Upon Ms. Thomas's return, Ms. Mena started thinking of buying a larger place to live. She started saving more purposefully for a down payment and took a first-time homebuyer course. Taking that course qualified Mena for a home-purchase subsidy. But after completing the course, Mena's credit union told her that she didn't qualify for a suitably sized loan. 5. Ms. Mena thus discussed with Ms. Thomas her becoming a co-borrower on a future residential loan. Thomas agreed, and she joined in Mena's efforts to locate a suitable new home. Mena eventually attended an open house for 26 Union Court in the spring of 2005. On the same day as the open house, Mena made an offer and paid a $500 deposit towards the purchase. That deposit came entirely from Mena's savings. 6. Ms. Mena and Ms. Thomas hired an attorney to help them review a purchase and sale agreement for 26 Union Court. That agreement named Mena and Thomas (then Corbin) as the property's "Buyer." Mena gave two explanations as to how that occurred. She first believed, and reportedly told Thomas, that having them both listed as "Buyer" would facilitate passing the property to Thomas upon Mena's death, without the property having to go through probate. The eventual deed to Mena and Thomas, reflecting the parties' rights of survivorship, is consistent with that understanding. Mena's second explanation for why she understood that Thomas had to be listed as a "Buyer" is that Mena understood that a lender would insist on that, given that Mena and Thomas were to be co-borrowers on a loan to buy the property. 7. While I believe Ms. Mena's explanations for why she was willing to have Ms. Thomas listed as a "Buyer" on the purchase and sale agreement, and have her name appear on the property's deed, I further find that at no time prior to the purchase of 26 Union Court did Mena and Thomas discuss their relative interests in 26 Union Court or other tenancy issues. In particular, at no time did Thomas ever promise that she would hold for Mena whatever interest Thomas got in the property, nor did Thomas promise not to assert ownership while Mena was still alive. 8. Both Ms. Mena and Ms. Thomas signed the purchase and sale agreement identifying both of them as "Buyer," and both of them initialed each of the agreement's pages. At the time they executed the agreement, Mena paid an additional $4,500 deposit on the property, entirely out of her own funds. 9. Ms. Mena and Ms. Thomas thereafter began applying for financing. The one loan application submitted into evidence, Trial Exhibit 4, shows the parties' liquid assets as approximately $27,700, not including Mena's deposits towards the house. The disclosed liquid assets were entirely Mena's. Thomas reported nothing in the way of liquid assets on Exhibit 4, but she did list her monthly income (as did Mena). Both Mena and Thomas signed the loan application. 10. The parties did not place in evidence a HUD-1 or other summary of the final costs paid at the closing of the purchase of 26 Union Court, which occurred on August 4, 2019. The Court nevertheless can find the following: a. The price of the property was $240,000, exclusive of closing costs. b. Ms. Mena had paid by closing $5,000 in deposits. c. Ms. Mena and Ms. Thomas signed first- and second-mortgage notes, in favor of Sovereign Bank, totaling $230,000. (They signed a third note, called a "subsidy note," that provided funds directly to the holder of the second mortgage so as to reduce Mena and Thomas's monthly payments on their second-mortgage note. The proceeds of the third note weren't applied to the purchase price or closing costs.) 11. While the parties stipulated that "[a]t the closing, there was approximately $5,000 due and owing from the Buyer's side in order to consummate the purchase," that $5,000 difference covers only the difference between the property's price, Ms. Mena's deposits, and the first- and second-mortgage notes. Both Mena and Ms. Thomas testified that more than $5,000 was paid at closing, as there were closing costs. They agree that Mena paid $7,000 at the closing. But Thomas claimed to have paid an additional $3,000 towards the closing costs, for a total payment from Mena and Thomas at the closing of $10,000. I find that Thomas's recollection is mistaken, and that consistent with what had happened up to the point of closing, Ms. Mena paid all of the costs and deposits in advance of closing. 13. Sometime after the closing, Ms. Mena and Ms. Thomas agreed that Thomas would pay the household's monthly utility, cable television/wifi, and telephone bills, and Mena would pay the mortgages, real estate taxes, and insurance. The parties largely abided by this arrangement until January 2013, when Mena left for Trinidad. At that point, Thomas started paying all of the mortgage expenses, real estate taxes, and insurance, in addition to the utility, cable television/wifi, and telephone bills, even though Mena returned to 26 Union Court for occasional visits. 14. Ms. Mena returned to 26 Union Court more permanently in May 2015. In August 2015, Ms. Thomas married and moved out of 26 Union Court. Since that time, Ms. Mena has been paying all of the property's expenses, plus all utilities. 15. In October 2015, Ms. Thomas asked Ms. Mena to get Thomas's name "off the mortgages" for 26 Union Court. Mena explored refinancing the mortgages and was told that her credit wouldn't allow her to refinance solely in her name. The parties' dispute over what to do with the mortgages and 26 Union Court resulted in Thomas petitioning this Court in November 2018 for partition of 26 Union Court. 16. From the time Ms. Thomas first moved to Salem through the purchase of 26 Union Court, Ms. Mena controlled her own financial and personal affairs, and did not rely on Thomas in making financial or other personal decisions. The sole issue tried is whether Ms. Thomas is holding her share of 26 Union Court in a "resulting trust" for her mother. "A resulting trust in real estate arises where one party furnishes the consideration to purchase property, not intending a gift or advancement, yet title is taken in the name of another." Fortin v. Roman Catholic Bishop of Worcester,416 Mass. 781, 789 (1994). The doctrine rests on the assumption that, "in the absence of anything to show the contrary, he who supplies the purchase price intends that the property bought shall inure to his own benefit and not that of another, and that the conveyance is taken in the name of another for some incidental reason." Quinn v. Quinn,260 Mass. 494, 501 (1927). See also McPherson v. McPherson,337 Mass. 611, 613-614 (1958) (discussing Quinn assumption). It's the burden of the party who claims a resulting trust to "prove that he furnished himself the entire consideration or a specific and definite part thereof, for which it was intended he should receive a determinate and fixed fraction of the whole estate conveyed," and that "it was not intended at the time of the conveyance that [the other party holding title] should take a beneficial interest in the property by way of gift, settlement or advancement." Pollock v. Pollock,223 Mass. 382, 384 (1916). Ms. Mena easily passes the second of these tests: it's undisputed that she and Ms. Thomas never discussed the issue of who would own what percentages of 26 Union Court, and Mena had no intent to gift Thomas a present interest in the property (as opposed to a future interest, via survivorship). Ms. Mena has a harder time with the first prong of the test. It's true that she furnished the down payment for 26 Union Court and paid all closing costs. But that amount ($12,000) wasn't the entire consideration for 26 Union Court: $242,000 was due at closing, and $230,000 of that came from Sovereign Bank, as the proceeds of two notes Mena and Ms. Thomas willingly agreed to co-sign. In the absence of a further agreement by Mena, at the time of closing, to pay Thomas's share of the two mortgages with nothing in return, or to indemnify Thomas in the event of any loss under the mortgages, Massachusetts law deems Thomas (by having co-signed the two notes and mortgages) to have provided some of the consideration for 26 Union Court. See Carroll v. Markey,321 Mass. 87, 89 (1947); see also Gerace v. Gerace,301 Mass. 14(1938) (father and other relatives who co-signed mortgage on property that son wished to purchase held not to have furnished consideration for the property, and to hold property in resulting trust, where parties had agreed that father and relatives would take title in their names, but where son provided down payment and agreed to make everyone else's mortgage payments). Where does that leave Ms. Mena? The Supreme Judicial Court has looked to the Restatement (Third) of Trusts (2003) and the Restatement (Second) of Trusts (1959) for guidance on resulting-trust issues. See, for example, Cavadi v. DeYeso,458 Mass. 615, 631-632 (2011). Under both Restatements, it's presumed that parties own property that's subject to a resulting trust in proportion to each owner's contribution towards acquiring it. See Restatement (Third) at §9, comment (d); Restatement (Second) at §454 ("Where a transfer of property is made to one person and a part of the purchase price is paid by another, a resulting trust arises in favor of the person by whom such payment is made in such proportion as the part paid by him bears to the total purchase price . . . . "); id. at §454, comments (b) and (f). That means that Ms. Mena owns a share of 26 Union Court that acknowledges her cash contribution to the purchase ($12,000) plus her assuming one half of the parties' mortgage obligation ($115,000). That totals $127,000. Dividing that number by 26 Union Court's purchase price and closing costs ($242,000) gives Ms. Mena, under Massachusetts law, a 52.5% share of the property. Ms. Thomas owns the remaining 47.5%. Ms. Mena contends that she should be given the entirety of Ms. Thomas's interest under a second doctrine, that of "constructive trust." Under Massachusetts law, a court may declare that one person holds property for another via a constructive trust so as to prevent unjust enrichment resulting from fraud, a violation of a fiduciary duty, mistake, or "other circumstances." Fortin, 416 Mass. at 789; see also Nessralla v. Peck,403 Mass. 757, 762-63 (1989). The facts of this case don't support a conclusion that Thomas holds her 47.5% interest in 26 Union Court in constructive trust for Mena. Mena has provided no evidence that Thomas engaged in a fraud aimed at depriving Mena of her rightful share of 26 Union Court. Mena also hasn't proven that Thomas was her fiduciary at the time of the 26 Union Court purchase. "It is settled in this Commonwealth that a fiduciary relationship does not arise merely because the parties to a conveyance are members of the same family, even if the transferee promised to hold the land in trust." Kelly v. Kelly,358 Mass. 154, 156 (1920). Ms. Mena also hasn't proven any of the other facts that produce constructive trusts. Mena hasn't established that the deed to her and Ms. Thomas - prepared in a transaction in which both had counsel - mistakenly stated the parties' agreement as to 26 Union Court's ownership: the Court finds that the parties hadn't discussed ownership at all. Mena also hasn't proven other circumstances that would allow this Court to conclude that, given the parties' relative positions at the time of the closing on 26 Union Court, Thomas would be unjustly enriched in the absence of a declaration that she holds her 47.5% share in a constructive trust for Mena: after all, by co-signing the three notes and mortgages, Thomas permitted Mena to buy 26 Union Court, something Mena couldn't do on her own. Thomas's smaller ownership share fully adjusts for her not contributing to the down payment or closing costs for 26 Union Court. Ms. Mena last claims that Ms. Thomas should be estopped, under the doctrine of promissory estoppel, from claiming any share in 26 Union Court. That doctrine "permits recovery if (1) a promisor makes a promise which he should reasonably expect to induce action or forbearance of a define and substantial character on the part of the promisee, (2) the promise does induce such action or forbearance, and (3) injustice can be avoided only by enforcement of the promise." Loranger Construction Corp. v. E.F. Hauserman Co.,6 Mass. App. Ct. 152, 154 (1978). But Mena rests her promissory-estoppel argument on a fact she didn't prove at trial: that Thomas agreed to have her name put on the deed for 26 Union Court but not claim any ownership of the property until Mena passed away. The Court finds that Thomas made no such promise. What does today's ruling mean for Ms. Thomas's request for partition? It means that she and Ms. Mena are joint tenants, and thus Thomas is entitled to a partition of 26 Union Court. It means that in addressing the issues that might arise in connection with partition, the Court will be treating Mena as owning 52.5% of the property and Thomas as owning 47.5%. The Court hasn't ruled as to any issues concerning compensable improvements or other accounting or reimbursement issues. And most importantly, the Court hasn't determined how 26 Union Court shall be partitioned. The Court thus ORDERS the parties to appear for a telephonic status conference on November 20, 2019 at 10:30 a.m. to discuss how this case should proceed from here.
http://masscases.com/cases/land/2019/2019-18-000589-FINDINGS.html
State v. Montplaisir, No. 20140459 - North Dakota - Case Law - VLEX 889022944 0: [object Object]. 1: [object Object]. 2: [object Object]. 3: [object Object]. 4: [object Object]. 5: [object Object] North Dakota State v. Montplaisir, No. 20140459 Court United States State Supreme Court of North Dakota Writing for the Court McEvers Citation 2015 ND 237 Parties State of North Dakota, Plaintiff and Appellee v. Steven James Montplaisir, Defendant and Appellant Decision Date 17 September 2015 Docket Number No. 20140459 2015 ND 237 State of North Dakota, Plaintiff and Appellee v. Steven James Montplaisir, Defendant and Appellant No. 20140459 SUPREME COURT STATE OF NORTH DAKOTA September 17, 2015 Appeal from the District Court of Cass County, East Central Judicial District, the Honorable John C. Irby, Judge. AFFIRMED. Opinion of the Court by McEvers, Justice. Renata June Olafson Selzer, Assistant State's Attorney, Cass County Courthouse, P.O. Box 2806, Fargo, N.D. 58108-2806, for plaintiff and appellee. Jonathan T. Garaas, DeMores Office Park, 1314 23rd Street South, Fargo, N.D. 58103-3796, for defendant and appellant. McEvers, Justice. [¶1] Steven J. Montplaisir appeals from a criminal judgment entered after a jury found him guilty of criminal vehicular injury. Montplaisir argues the criminal information was deficient, the criminal vehicular injury statute is unconstitutionally vague, the jury instructions were improper, and the evidence was insufficient to find him guilty. We affirm, concluding Montplaisir had proper notice of the charges against him, the criminal vehicular injury statute is not vague, the jury was properly instructed, there was sufficient evidence to find him guilty, and the district court did not abuse its discretion in imposing the statutory mandatory minimum sentence. I [¶2] On September 20, 2013, a motorcycle stopped at an intersection in Fargo was struck from behind by a pickup driven by Montplaisir. A Fargo police officer was also stopped at the intersection and observed the victim jumping around and screaming. The officer noticed Montplaisir had the strong odor of alcohol and slurred speech. Another officer arrived at the scene to investigate Montplaisir for driving under the influence. Montplaisir failed field sobriety tests and laboratory results indicated he had a blood alcohol concentration of 0.217 percent. Montplaisir was arrested and charged with criminal vehicular injury, a class C felony. The criminal information alleged Montplaisir drove a vehicle while under the influence of alcohol and, as a result, he caused substantial bodily or serious bodily injury to another individual. [¶3] The victim was initially treated at Essentia Hospital for pain to his leg and ankles, and a cut to his leg requiring stitches. Following the accident, the victim made additional visits to the emergency room reporting continued severe pain in his leg. One of his leg wounds became infected and he also complained of having neck and back discomfort. [¶4] Before the preliminary hearing, Montplaisir submitted a brief arguing the criminal information was deficient. Specifically, he argued he did not cause a substantial or serious bodily injury to the victim, one of the essential elements of criminal vehicular injury. The State responded with a brief providing a more detailed factual background of the accident. The State's brief also described some of the victim's injuries to his leg and stated it would provide more details at the preliminary hearing. After hearing testimony at the preliminary hearing from the victim and one of the police officers responding to the accident, the district court found probable cause existed to bind Montplaisir over for trial on the charge of criminal vehicular injury. [¶5] After the preliminary hearing, Montplaisir moved to dismiss the information arguing, as a matter of law, the victim's injury was not serious or substantial, and the criminal vehicular injury statute is unconstitutionally vague and overbroad. The court denied his motions, concluding the statute was not unconstitutionally vague or overbroad, and whether the victim's injury was serious or substantial was a question for the jury. [¶6] At trial in November 2014, the State's witnesses included the victim and two doctors who treated him following the accident. The victim's medical records were also admitted into evidence. Montplaisir moved for a judgment of acquittal under N.D.R.Crim.P. 29 at the conclusion of the State's case, arguing there was no evidence the victim suffered a substantial or serious bodily injury. The court denied the motion. After the conclusion of Montplaisir's case, he requested a jury instruction on culpability and an instruction on the legal definitions of "serious bodily injury" and "substantial bodily injury." The district court denied Montplaisir's requests, and a jury found him guilty. The court sentenced Montplaisir to one year in prison and 18 months of supervised probation following his release from prison. II [¶7] Montplaisir argues the district court made numerous errors in the pretrial and trial stages of the proceedings. Much of Montplaisir's argument centers around the phrase "substantial bodily or serious bodily injury" as it is used in N.D.C.C. § 39-08-01.2(2). Montplaisir first argues the court erred in not dismissing a deficient information, and the State presented insufficient evidence at the preliminary hearing. A [¶8] Montplaisir argues the district court erred in failing to dismiss the criminal information because the information did not describe the nature of the victim's injuries; it only states the victim suffered substantial or serious bodily injury. He argues the information asserts only legal conclusions of substantial or serious bodily injury to the victim, without describing the nature of any injury. [¶9] Under N.D.R.Crim.P. 7(c)(1), an information must contain "a plain, concise, and definite written statement of the essential facts constituting the elements of the offense charged." An information is adequate if it is "sufficiently specific to provide the defendant with notice of the pending charges to enable the defendant to prepare a defense." State v. Bertram , 2006 ND 10 , ¶ 23, 708 N.W.2d 913 . Generally, an information is sufficient if it sets forth the offense in the words of the statute. Hamling v. United States , 418 U.S. 87 , 117 (1974). [¶10] Nearly 40 years ago, this Court addressed an argument regarding an insufficient information: In these days of broadening pretrial discovery in criminal cases, open or almost completely open prosecutorial files, and availability of omnibus hearings and pretrial conferences, it would be almost anachronistic to reverse a conviction because the language of the information or indictment is insufficiently detailed. When the prosecutor's files are generally open to the defense, when motions for discovery and for bills of particulars may be made, it would be most surprising if the defendant and his attorney were unaware prior to trial of the claims of the prosecution . . . and the facts upon which the prosecution relies. State v. Motsko , 261 N.W.2d 860 , 864 (N.D. 1977) (internal citations omitted). [¶11] Here, the information charging Montplaisir with criminal vehicular injury under N.D.C.C. § 39-08-01.2(2) stated: [On] September 20, 2013: [t]he Defendant operated a vehicle while under the influence of alcohol and as a result he caused substantial bodily or serious bodily injury to another individual to-wit: that on or about the above-stated date, the defendant . . . drove a vehicle in Fargo, . . . when at the time the defendant was under the influence of intoxicating liquor or had an alcohol concentration of at least .08% by weight at the time of the performance of a chemical test within two hours after driving and as a result caused substantial or serious bodily injury to [the victim]. [¶12] The criminal vehicular injury statute, N.D.C.C. § 39-08-01.2(2), provides in relevant part: An individual is guilty of criminal vehicular injury if the individual violates section 39-08-01 or equivalent ordinance and as a result that individual causes substantial bodily or serious bodily injury to another individual. [¶13] The information tracked the language of N.D.C.C. § 39-08-01.2(2) by alleging Montplaisir drove under the influence of alcohol, a violation of N.D.C.C. § 39-08-01, and caused substantial or serious bodily injury to another individual. Additionally, as mentioned above, the State filed a brief responding to Montplaisir's brief filed before the preliminary hearing, which described the nature of the accident and the victim's injuries. The State also provided Montplaisir with the victim's relevant medical records before the preliminary hearing. We conclude Montplaisir had proper notice of the pending charges against him allowing him to prepare a defense. The district court did not err by failing to dismiss the information. B [¶14] Montplaisir argues the district court erred in finding probable cause to bind him over for trial because the State presented insufficient evidence of "serious bodily injury" or "substantial bodily injury" at the preliminary hearing. It is unnecessary to decide whether the district court erred when it found probable cause existed to bind Montplaisir over for trial, because that issue became moot when Montplaisir was found guilty at trial. [¶15] In Kartes v. Kartes , 2013 ND 106 , ¶ 18, 831 N.W.2d 731 , we held that any issue regarding the evidentiary basis for a district court's decision that a prima facie case has been established under N.D.C.C. § 14-09-06.6(4) justifying a modification of primary residential responsibility is rendered moot once the evidentiary hearing is held. We also discussed how the prima facie case requirement in N.D.C.C. § 14-09-06.6(4) is similar to a preliminary hearing in a criminal case and a motion for summary judgment dismissal in a civil case. Id. at ¶ 13. Regarding those preliminary matters, we stated "it is generally held that the question of the adequacy of the preliminary showing is rendered moot when the case proceeds to trial and is resolved upon the merits." Id. [¶16] Although we discussed and noted that "courts in other jurisdictions have held that any question whether probable cause was established at the preliminary hearing is rendered moot if the defendant is convicted after a trial," our holding in Kartes has not been specifically applied... 14 practice notes City of Fargo v. Nikle, 20180292 United States United States State Supreme Court of North Dakota March 13, 2019 ...determined N.D.C.C. § 39-08-01 is a strict liability offense, meaning there is no culpability requirement. See State v. Montplaisir , 2015 ND 237 , ¶ 33, 869 N.W.2d 435 ; State v. Glass , 2000 ND 212, ¶ 21, 620 N.W.2d 146. Although we have not previously addressed strict liability and actual...... State v. Pemberton, 20180414 United States United States State Supreme Court of North Dakota June 27, 2019 ...hearing that probable cause existed to bind a defendant over for trial is rendered moot once the trial is held." State v. Montplaisir, 2015 ND 237 , ¶ 16, 869 N.W.2d 435. Pemberton was found guilty at trial, and the district court's determination on probable cause made at the preliminary hea...... State v. Houkom, 20210058 United States United States State Supreme Court of North Dakota December 9, 2021 ...specific to provide the defendant with notice of the pending charges to enable the defendant to prepare a defense." State v. Montplaisir , 2015 ND 237 , ¶ 9, 869 N.W.2d 435. An information does not require exact specificity but only "enough specificity so that the defendant can prepare a mea...... McIntee v. Knoke (In re Knoke), 20210081 United States United States State Supreme Court of North Dakota December 23, 2021 ...has held the court's preliminary determination is rendered moot once the trial or evidentiary hearing is held. See State v. Montplaisir , 2015 ND 237 , ¶ 16, 869 N.W.2d 435 (holding a district court's decision at a preliminary hearing in a criminal case that probable cause exists to hold the...... 13 cases City of Fargo v. Nikle, No. 20180292 United States United States State Supreme Court of North Dakota March 13, 2019 ...determined N.D.C.C. § 39-08-01 is a strict liability offense, meaning there is no culpability requirement. See State v. Montplaisir , 2015 ND 237 , ¶ 33, 869 N.W.2d 435 ; State v. Glass , 2000 ND 212, ¶ 21, 620 N.W.2d 146. Although we have not previously addressed strict liability and actual...... State v. Pemberton, No. 20180414 United States United States State Supreme Court of North Dakota June 27, 2019 ...hearing that probable cause existed to bind a defendant over for trial is rendered moot once the trial is held." State v. Montplaisir, 2015 ND 237 , ¶ 16, 869 N.W.2d 435. Pemberton was found guilty at trial, and the district court's determination on probable cause made at the preliminary hea...... State v. Houkom, 20210058 United States United States State Supreme Court of North Dakota December 9, 2021 ...specific to provide the defendant with notice of the pending charges to enable the defendant to prepare a defense." State v. Montplaisir , 2015 ND 237 , ¶ 9, 869 N.W.2d 435. An information does not require exact specificity but only "enough specificity so that the defendant can prepare a mea...... McIntee v. Knoke (In re Knoke), 20210081 United States United States State Supreme Court of North Dakota December 23, 2021 ...has held the court's preliminary determination is rendered moot once the trial or evidentiary hearing is held. See State v. Montplaisir , 2015 ND 237 , ¶ 16, 869 N.W.2d 435 (holding a district court's decision at a preliminary hearing in a criminal case that probable cause exists to hold the......
https://case-law.vlex.com/vid/state-v-montplaisir-no-889022944
Topic Detection and Tracking Evaluation Overview | Request PDF Request PDF | Topic Detection and Tracking Evaluation Overview | The objective of the Topic Detection and Tracking (TDT) program is to develop technologies that search, organize and structure multilingual, news... | Find, read and cite all the research you need on ResearchGate Topic Detection and Tracking Evaluation Overview January 2002 DOI: 10.1007/978-1-4615-0933-2_2 George R. Doddington Abstract The objective of the Topic Detection and Tracking (TDT) program is to develop technologies that search, organize and structure multilingual, news oriented textual materials from a variety of broadcast news media. This research program uses controlled laboratory simulations of hypothetical systems to test the efficacy of potential technologies, to gauge research progress, and to provide a forum for the exchange of research information. This chapter introduces TDT's evaluation methodology including: the Linguistic Data Consortium's TDT corpora, evaluation metrics used in TDT and the five TDT research tasks: Topic Tracking, Link Detection, Topic Detection, First Story Detection, and Story Segmentation. ... Topic Detection and Tracking (TDT) [12] aims to capture the appearances of new topics in continuously generated text data in real-time; a topic is defined as "a seminal event or activity along with all directly related events and activities" [12]. First story detection (FSD) is one of the parts of TDT research tasks. ... ... Topic Detection and Tracking (TDT) [12] aims to capture the appearances of new topics in continuously generated text data in real-time; a topic is defined as "a seminal event or activity along with all directly related events and activities" [12] . First story detection (FSD) is one of the parts of TDT research tasks. ... Analyzing the generalizability of the network-based topic emergence identification method Article Full-text available <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Sukhwan Jung <here is a image a41338178631c6d3-a6110155ecccf4b7> Aviv Segev Topic evolution helps the understanding of current research topics and their histories by automatically modeling and detecting the set of shared research fields in academic publications as topics. This paper provides a generalized analysis of the topic evolution method for predicting the emergence of new topics, which can operate on any dataset where the topics are defined as the relationships of their neighborhoods in the past by extrapolating to the future topics. Twenty sample topic networks were built with various fields-of-study keywords as seeds, covering domains such as business, materials, diseases, and computer science from the Microsoft Academic Graph dataset. The binary classifier was trained for each topic network using 15 structural features of emerging and existing topics and consistently resulted in accuracy and F1 over 0.91 for all twenty datasets over the periods of 2000 to 2019. Feature selection showed that the models retained most of the performance with only one-third of the tested features. Incremental learning was tested within the same topic over time and between different topics, which resulted in slight performance improvements in both cases. This indicates there is an underlying pattern to the neighbors of new topics common to research domains, likely beyond the sample topics used in the experiment. The result showed that network-based new topic prediction can be applied to various research domains with different research patterns. ... With the progressive prevalence of mobile devices in recent decades, massive sequential texts are continuously generated in various forms, e.g., news and tweets. For these sequential documents, we focus on modeling a topic evolution, i.e., various and frequent emergences, growths and fades of topics, which is commonly applied to emerging topic detection tasks, such as emerging topic clustering 1 and novel topic detection 2 Fiscus and Doddington 2002) . For these tasks, the critical issue in modeling is to capture fades and emergences of each topic and discriminate outliers from each emerging topics. ... ... Firstly, to investigate the sensitivity of the baseline models for novel topics, we calculated novelties for our model and other topic modeling based methods in real data. Novelty (Yan et al. 2015) is used to measure the freshness of a word or a topic, which is widely applied in the tasks of emerging topic clustering and novel topic detection (Fiscus and Doddington 2002) . We adopt it to evaluate how sensitive a topic model is in detecting an emerging topic. ... Topic modeling for sequential documents based on hybrid inter-document topic dependency Article Full-text available <here is a image bcf4dd8e221b2f38-53c492ec62f2acf0> Li Wenbo Hiroto Saigo Bin Tong <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Einoshin Suzuki We propose two new topic modeling methods for sequential documents based on hybrid inter-document topic dependency. Topic modeling for sequential documents is the basis of many attractive applications such as emerging topic clustering and novel topic detection. For these tasks, most of the existing models introduce inter-document dependencies between topic distributions. However, in a real situation, adjacent emerging topics are often intertwined and mixed with outliers. These single-dependency based models have difficulties in handling the topic evolution in such multi-topic and outlier mixed sequential documents. To solve this problem, our first method considers three kinds of topic dependencies for each document to handle its probabilities of belonging to a fading topic, an emerging topic, or an independent topic. Secondly, we extend our first method by considering fine-grained dependencies in a given context for more complex topic evolution sequences. Our experiments conducted on six standard datasets on topic modeling show that our proposals outperform state-of-the-art models in terms of the accuracy of topic modeling, the quality of topic clustering, and the effectiveness of outlier detection. ... On the Internet, a sequence of web media content on a specific subject forms a topic. A topic can be defined fromally as "a seminal event or activity, along with all directly related events and activities" [2] . Most research on new topic detection mainly focuses on the method based on topic models (also include its variants) and text clustering [3] [4] [5] [6] [7]. ... ... 1: For the topic T P , the corresponding event scenario model is queried from the event ontology according to the topic name. 2 ... Topic Detection and Tracking Based on Event Ontology Article Full-text available In recent years, Topic Detection and Tracking (TDT) has served as a core technology for searching, organizing and structuring news oriented textual materials from a variety of internet news and social media. The biggest challenges of TDT are the sparsity and complexity of data, organization of topic granularity, unexpectedness of emergency topics, and the unpredictability of topics evolution. This paper proposes a new TDT method based on event ontology for hierarchical topic detection and tracking topic evolution, named TDTEO. As domain-oriented event knowledge base, the event ontology provides event classes hierarchy based on domain common sense, as well a set of scenario models that describe the occurrence and evolution of different types of emergency events. The proposed method solves the problem that new emerging events are easy to be missed in the process of topic detection, and solves the problem that the topic model is easy to result in semantics drift due to the dynamic evolution of topic, and it can effectively improve the accuracy of topic detection and tracking. Experiments show our models achieve satisfactory performance of topic detection with a maximum macro-F1 value of 85.25%, and the (CDet)Norm of topic tracking in the datasets is as low as 0.1028. Experimental results show that hierachical topic model can effectively detect the topics and tracking model based on event scenario can reflect the trend of topic evolution. ... TDT [41] proposed several evaluation metrics for topic detection, including Precision P, Recall R and F1 score. In addition, the Miss Rate ( ) and False Alarm Rate ( ) are also important evaluation metrics of system performance. ... ... In this paper, the detection cost function is used to evaluate the system performance [41] , which is a metric that combines the miss rate and the false alarm rate proposed in TDT2004 [42] and is calculated by Formula (10): ... Food Safety Event Detection Based on Multi-Feature Fusion Article Full-text available <here is a image b4fd0ec78039317b-382be268a1fa5ed0> Wenjiao Xiao <here is a image 0086a26316ac9f8f-d862ad9d4689914c> Cheng Wang <here is a image 56ed007fdf5f9c66-3fe1957144f8df3f> Yiyi Zhang <here is a image 4ac40697e8654ef4-f3f0b163d10f1e51> Yuehui Qian Food safety event detection is a technique used to discover food safety events by monitoring online news. In general, a set of keywords are extracted as features to represent news, and then the news is clustered to generate events. The most popular method for news feature extraction is Term Frequency-Inverse Document Frequency (TF-IDF), however, it has some defects such as being prone to the “dimension disaster”, low computational efficiency, and a lack of semantic information. In addition, Latent Dirichlet Allocation (LDA) is also widely used in news representation. Despite its low dimension, it still suffers from some drawbacks such as the need to set a predefined number of clusters and has difficulty recognizing new events. In this paper, a method based on multi-feature fusion is proposed, which combines the TF-IDF features, the named entity features, and the headline features to represent the news. Based on the representations, the incremental clustering method is used to cluster the news documents and to detect food safety events. Compared with the traditional methods, the proposed method achieved higher Precision, Recall, and F1 scores. The proposed method can help regulatory authorities to make decisions and improve the reputation of the government, whilst reducing social anxiety and economic losses. ... Novelty detection based on vector space model: Cosine similarity is proven to be effective in TDT task [53] and it is frequently used as a baseline in novelty detection. In tweet summarization, cosine similarity was widely used to estimate the similarity between tweets [63,61,123]. ... ... The performance of a novelty detection method is evaluated in terms of missed detection and false alarm error probabilities (P Miss and P Fa ) as defined by [53] . P Miss is the probability of missing a tweet that conveys a novel information whereasP Fa is the probability of pushing a redundant tweet (false alarm). ... Event summarization on social media stream : retrospective and prospective tweet summarization Thesis Abdelhamid Chellal User-generated content on social media, such as Twitter, provides in many cases, the latest news before traditional media, which allows having a retrospective summary of events and being updated in a timely fashion whenever a new development occurs. However, social media, while being a valuable source of information, can be also overwhelming given the volume and the velocity of published information. To shield users from being overwhelmed by irrelevant and redundant posts, retrospective summarization and prospective notification (real-time summarization) were introduced as two complementary tasks of information seeking on document streams. The former aims to select a list of relevant and non-redundant tweets that capture "what happened". In the latter, systems monitor the live posts stream and push relevant and novel notifications as soon as possible. Our work falls within these frameworks and focuses on developing a tweet summarization approaches for the two aforementioned scenarios. It aims at providing summaries that capture the key aspects of the event of interest to help users to efficiently acquire information and follow the development of long ongoing events from social media. Nevertheless, tweet summarization task faces many challenges that stem from, on one hand, the high volume, the velocity and the variety of the published information and, on the other hand, the quality of tweets, which can vary significantly. In the prospective notification, the core task is the relevancy and the novelty detection in real-time. For timeliness, a system may choose to push new updates in real-time or may choose to trade timeliness for higher notification quality. Our contributions address these levels: First, we introduce Word Similarity Extended Boolean Model (WSEBM), a relevance model that does not rely on stream statistics and takes advantage of word embedding model. We used word similarity instead of the traditional weighting techniques. By doing this, we overcome the shortness and word mismatch issues in tweets. The intuition behind our proposition is that context-aware similarity measure in word2vec is able to consider different words with the same semantic meaning and hence allows offsetting the word mismatch issue when calculating the similarity between a tweet and a topic. Second, we propose to compute the novelty score of the incoming tweet regarding all words of tweets already pushed to the user instead of using the pairwise comparison. The proposed novelty detection method scales better and reduces the execution time, which fits real-time tweet filtering. Third, we propose an adaptive Learning to Filter approach that leverages social signals as well as query-dependent features. To overcome the issue of relevance threshold setting, we use a binary classifier that predicts the relevance of the incoming tweet. In addition, we show the gain that can be achieved by taking advantage of ongoing relevance feedback. Finally, we adopt a real-time push strategy and we show that the proposed approach achieves a promising performance in terms of quality (relevance and novelty) with low cost of latency whereas the state-of-the-art approaches tend to trade latency for higher quality. This thesis also explores a novel approach to generate a retrospective summary that follows a different paradigm than the majority of state-of-the-art methods. We consider the summary generation as an optimization problem that takes into account the topical and the temporal diversity. Tweets are filtered and are incrementally clustered in two cluster types, namely topical clusters based on content similarity and temporal clusters that depends on publication time. Summary generation is formulated as integer linear problem in which unknowns variables are binaries, the objective function is to be maximized and constraints ensure that at most one post per cluster is selected with respect to the defined summary length limit. ... Social Sensing, on the other hand, is the process of clustering together text sources such as news items and social media posts that pertain to the same real-world event. This process is called event detection [1], [6] . In this way, GeoSensor is able to provide insights into the changes extracted from satellite images by associating them with relevant news and social media content for the same location. ... ... The Event Detector 5 component receives the latest news and social media items stored in Cassandra and groups them into events, using a modified version of the NewSum[7] algorithm 6 . ... GeoSensor: On-line Scalable Change and Event Detection over Big Data Conference Paper Full-text available <here is a image 0e68d6e22c83545a-2a26242acd75cbba> Giorgos Argyriou Anca Popescu <here is a image 79bdfb3eb7fce12f-4c3e6a49d4b2bead> Argyros Argyridis <here is a image 3522bc158b735bee-d746b471007644c7> E. Angiuli GeoSensor is a novel system that enriches change detection over satellite images with event detection over news items and social media content. GeoSensor faces the major challenges of Big Data: volume (a single satellite image may be a few GBs), variety (its data sources include two different types of satellite images and various types of user-generated content) and veracity, as the accuracy of the end result is crucial for the usefulness of our system. To overcome these three challenges, while offering on-line functionality, GeoSensor comprises a complex architecture that is based on the open-source platform developed in the H2020 project Big Data Europe. Through the presented demonstration, both the effectiveness and the efficiency of GeoSensor's functionalities are highlighted. ... Segmentation helps to break down a sequential bulletin into logical groups which subsequently allows high level applications like news classification, summarization, content analysis, sentiment analysis, opinion mining and many others [6]. Automatic story segmentation of news broadcast is a challenging task due to the wide variety of topics covered, the fluidity with which one story flows into another, and the variable length of individual stories [12] . As a function of the modality, techniques for story segmentation can be based on visual, audio or textual content. ... LSTM-based Siamese neural network for Urdu news story segmentation Article Full-text available INT J DOC ANAL RECOG Muhammad Nauman Ahmed Bhatti <here is a image 5eadfd829170dd35-1e24ff4804425b5c> Imran Siddiqi <here is a image d5d9853e86f1103b-2ca819892db59cba> Momina Moetesum News story segmentation is a challenging task mainly due to the dynamic range of topics, smooth story transitions, and varied duration of each story. This paper presents a technique to segment stories from Urdu news bulletins. The technique relies on a Long Short-Term Memory-based Siamese neural network that is trained on positive (belonging to the same story) and negative (belonging to different stories) pairs of sentences. The model, once trained, identifies the transition between stories by detecting the dissimilarity between the adjacent sentences of a given text. For algorithmic development and experimental study, we employ two datasets, a dataset of Urdu news as well as transcriptions of news bulletins from multiple news channels. Experiments report promising results in identifying story boundaries validating the ideas put forward in this study. ... The TDT can be subdivided into the subject areas Story Segmentation, Topic Detection, Topic Tracking, First Story Detection and Link Detection (Fiscus and Doddington, 2002) . The aim of story segmentation is to divide the texts into individual stories. ... Multidimensional Knowledge Representation through Integrative Text Mining - A knowledge base framework for extracted information from text Thesis Oct 2022 <here is a image fbf57b8e95c4b10e-8ca8ff5ad90cafd6> Johannes Zenkert Natural language processing and text mining methods can be used to identify and extract valuable information from unstructured texts. Methodically extracted data provide helpful results but can be difficult to interpret in their individuality and cannot be used directly as knowledge. Cognitively, we as humans are able to process unstructured data, such as natural language in text form, filter out extracted information, classify it semantically, or interpret it. Computer systems cannot do this without help because it requires meaningful processing and combination of the data and information. Knowledge-based approaches attempt to solve this problem by providing appropriate representations for data and information and, by implementing them as expert systems, offer the possibility of reaching conclusions through inference using the knowledge base. A methodology for structuring and representing acquired information, which can lead to the transformation of data and information from text to knowledge, is conceptualized, implemented, and evaluated in case studies in this dissertation. The developed approach is called Multidimensional Knowledge Representation (MKR), since the results of different analysis dimensions are combined into a common representation structure by applying individual single text mining approaches, so-called pipelines. The results of text analysis and facets of knowledge acquisition are stored multi-dimensional in a document-oriented database, which can serve as the basis for a knowledge base in knowledge-based applications. Current systems and tools for text mining are mostly one-dimensional in their application and focus on a specific evaluation in the analysis. They usually provide insights for a previously defined question, which is methodically investigated within the text data as a linear process. In this context, the various perspectives and interpretations of the pipelines can be described as individual analysis dimensions. From the text information can be extracted, for example, after the pre-processing of the text, the named entities, the present topic, contained semantic relations or the sentiment. The methods of knowledge extraction, such as named entity recognition, topic detection or sentiment analysis are mostly applied individualized by trained methods and deliver a result that is finally interpreted. If the respective analysis question changes, the modified pipeline is often executed again in current state-of-the-art approaches. The core idea of MKR in contrast to current approaches is the support of multi-perspective questions by providing dimensional analysis results in the knowledge base. For example, complex questions such as the sentiment over time about a selected entity in a topic area can be answered efficiently by providing and accessing relevant data in the knowledge base. In addition to the theoretical foundations of the dissertation project, which lead to the conceptualization and modeling of MKR, the implementation as KB:mkr Knowledge Base Maker is presented. Using specially created text corpora in German and English language, the representation structure is evaluated in an exploratory and case-based manner in various application and project examples in academic and industrial contexts. ... Dans ce domaine, nombreux sont les travaux qui depuis plus de vingt ans, c'est-àdire depuis que le projet Topic Detection and Tracking a fondé la discipline, analysent l'évolution des événements -ici parfois nommés sujets -tant à la fois sur la presse [GD02] . ... Détection et suivi d’événements dans des documents de presse historique Thesis Reconstruire le fil des événements dans la presse, retracer le parcours de fausses informations ou identifier le point d’origine d’une publication, véridique ou non, sont des enjeux de ce début de siècle. La numérisation croissante des contenus numériques favorise des analyses massives de la presse. La miseà disposition depuis le début des années 2010 de fonds documentaires de presse par les bibliothèques du monde entier ouvre de nouvelles opportunités. Il devient possible d’adopter un autre regard sur des événements du passé, en découdre le fil et en connaître à la fois les chronologies et les diffusionsgéographiques.L’analyse des documents historiques relève de processus singuliers. En apparences similaires à des articles issus de la presse numérique, ils diffèrent pourtant en tout point : sur la forme (type de document, format des données) et sur le fond (style journalistique, thèmes abordés, personnagesmentionnés). Ce travail de thèse est adossé au projet NewsEye dédié à l’analyse de la presse historique pour les humanités numériques. Au sein de ce projet a émergé le besoin d’analyser les événements et la manière dont on en parle : connaissons-nous vraiment tout des événements du passé. Pouvons-nous identifier des relais et réseaux propices à l’introduction de fausses informations ? Ce sont des questions auxquelles les travaux engagés dans cette thèse permettront de répondre.Cette recherche ne se limite pas à exploiter des mécanismes déjà connus et éprouvés de détection et de suivi d’événements rapportés par la presse historique. Au-delà de ces contraintes évidentes, l’accent est mis sur deux éléments essentiels. Nous évaluons l’impact des documents historiques sur desalgorithmes et processus adoptés pour la presse nativement numérique. Nous fournissons des procédés sobres en ressources informatiques. Ce travail produit une première ébauche de système adapté au contexte écologique dans lequel nous vivons.Cette thèse s’associe aux travaux de recherche liés à la numérisation des fonds de presse historique. Elle a pour objectif de proposer différentes architectures répondant aux enjeux de suivi de mentions d’événements dans la presse. Nous proposons un cadre d’étude intégral comprenant d’abord la synthétisation de documents. Nous créons artificiellement des articles pour qu’ils présentent des spécificités communes aux documents historiques numérisés. Nous décrivons les processus d’analyse de ces derniers et une évaluation qui tient compte de différentes contraintes et des effets de ces dégradations. Nous cherchons à formuler par ce travail de premières recommandations pour orienter la recherche dédiée à l’analyse d’événements dans la presse ancienne. Nous proposons deux méthodes différentes, chacune adaptée pour répondre au même besoin. En tant qu’utilisateur ou utilisatrice d’archives numériques de presse, comme spécialiste ou simple particulier, comment puis-je découvrir tous les articles qui mentionnent ce même événement historique. Ces méthodes, ajustées à des contextes différents, sont plutôt classiques, par génération d’un modèle d’apprentissage ou plus orthodoxes, fonctionnant à la façon d’un moteur de recherche dédié aux événements du passé.Toutes les données que nous avons générées, tous les algorithmes implémentés, les différents modèles et résultats sont librement partagés conjointement à cette thèse afin de s’intégrer dans les mouvements de science ouverte. Nous publions les codes sources sur l’archive publique Software Heritage et les autres données et documents sur la plate-forme Zenodo. ... There are several studies dedicated to identifying new topics with varying definitions of topics, from simple words, through end users' interests, to consolidated keywords from publication venues. First story detection (FSD) is one of the research tasks of Topic Detection and Tracking ( Fiscus & Doddington, 2002 ) , capturing emergent topics in continuously generated text data in real-time. The goal of FSD is to search and organize new topics from multilingual news articles or identify the first article introducing the new story ( Allan, Carbonell, Doddington, Yamron & Yang, 1998 ;Zhang, Ghahramani & Yang, 2004 ). ... DAC: Descendant-aware clustering algorithm for network-based topic emergence prediction Article J INFORMETR <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Sukhwan Jung <here is a image a41338178631c6d3-a6110155ecccf4b7> Aviv Segev Topic emergence detection aids in pinpointing prominent topics within a given domain, providing practical insights into all interested parties on where to focus the limited resources. This paper employs the network-based topic evolution approach to overcome limitations in text-based topic evolution, providing prospective topic emergence prediction capabilities by representing emergent topics by their ancestors. A descendant-aware clustering algorithm is proposed to generate non-exhaustive and overlapping clusters, utilizing the pace of collaborations and structural similarities between topics with iterative edge removal and addition processes. Over 100 datasets specific to a research topic were extracted from the Microsoft Academic Graph dataset for the experiments, where the proposed algorithm consistently outperformed existing clustering algorithms in generating clusters with a higher likelihood of being ancestors to an emergent topic up to three years in the future. Regression-based cluster filtering using five structural cluster features and topic cluster qualities showed that the prediction performance can be enhanced by automatically classifying undesirable clusters from previously known data. The results showed that the proposed algorithm can enhance topic emergence predictions on a wide range of research domains regardless of their maturities, popularities, and magnitudes without having access to the data in the predicted year, paving a road to prospective predictions on emergent topics. ... We evaluate the effectiveness of migration detection in terms of two metrics, probability of missed detection ( ) and probability of false alarm ( ) over two datasets. These two metrics are widely used to evaluate the effectiveness of event detection and topic tracking tasks [14, 38], and fits the application of emergency applications 2 . A target is defined as a ground truth tweet that should be assigned to an event, while a non-target is the opposite. ... Migrating Social Event Recommendation Over Microblogs Conference Paper Full-text available Sep 2022 <here is a image deaf5986c2e82af9-9ec59338b6d6c0d4> Xiangmin Zhou <here is a image 9bf92971440ff3e4-2faf72f5675b1aab> Lei Chen Real applications like crisis management require the real time awareness of critical situations. However, the services using traditional methods like phone calls can be easily delayed due to busy lines, transfer delays or limited communication ability in disaster areas. Existing social event analysis solutions enhanced the situation awareness of systems. Unfortunately, they cannot recognize the complex migrating social events that are first observed in social media at a specific time, place and state, but have further moved in space and time, which may affect the system comprehension. While the discussion on events appears in microblogs, their movement over different contexts is unavoidable. So far, the problem of migrating social event analysis from big media is not well investigated yet. To address this issue, we propose a novel framework to monitor and deliver the migrating events in big social media data, which fully exploits the social media information over multiple attributes and their inherent interactions among events. Specifically, we first propose a Concept TF/IDF model to capture the content that is constrained by the time and location of media without costly learning process. Then, we construct a novel Maximal User Influence Graph (MUIG) to extract the social interactions. With MUIG, the event migrations over space and time are well identified. Finally, we design efficient query strategies over Apache Spark for recommending events in real time. Extensive tests over big media are conducted to prove the high effectiveness and efficiency of our approach. ... (2) Normalized detection cost (.C det / norm /. .C det / norm [27] is also widely used to evaluate topic detection performance. The smaller the .C det / norm , the better the performance of the model. ... News Topic Detection Based on Capsule Semantic Graph Article Full-text available Jun 2022 Shuang Yang Yan Tang Most news topic detection methods use word-based methods, which easily ignore the relationship among words and have semantic sparsity, resulting in low topic detection accuracy. In addition, the current mainstream probability methods and graph analysis methods for topic detection have high time complexity. For these reasons, we present a news topic detection model on the basis of capsule semantic graph (CSG). The keywords that appear in each text at the same time are modeled as a keyword graph, which is divided into multiple subgraphs through community detection. Each subgraph contains a group of closely related keywords. The graph is used as the vertex of CSG. The semantic relationship among the vertices is obtained by calculating the similarity of the average word vector of each vertex. At the same time, the news text is clustered using the incremental clustering method, where each text uses CSG; that is, the similarity among texts is calculated by the graph kernel. The relationship between vertices and edges is also considered when calculating the similarity. Experimental results on three standard datasets show that CSG can obtain higher precision, recall, and F1 values than several latest methods. Experimental results on large-scale news datasets reveal that the time complexity of CSG is lower than that of probabilistic methods and other graph analysis methods. ... Vlerësimi i prototipit të ndërtuar ishte i pamundur të realizohej sipas rekomandimeve në literaturë dhe punëve të ngjashme të autorëve të tjerë [17, 23] . Qasja e zakonshme është krahasimi i rezultateve të algoritmeve me bashkësi të dhënash testuese të etiketuara manualisht. ... Aplikimi i Teknikave të Gjetjes së Informacionit mbi Koleksione Dokumentesh në Gjuhën Shqipe Thesis Full-text available Dec 2021 <here is a image 5ce5aef2c4e18daf-893e3edbb6ee9d1c> Klesti Hoxha In the recent years the number of documents in Albanian published in internet has increased considerably. They range from news articles to legal documents, scientific publishings, multimedia (photo, video, audio) ones, etc. This considerable amount of information has made available numerous possibilities for analysts, researchers, legal workers, and any other interested parties. However, even though the available information has increased considerably, it is still not easy to quickly identify relevant documents written in Albanian due to the lack of availability of appropriate tools that facilitate this. In this disertation are reported various applications of information retrieval tech- niques in collections of documents written in Albanian. The experimental work makes use of articles of a scientific journal written in Albanian and news articles published online by various media. The implemented protototypes serve as proof-of-concept for further implementations of similar systems in industry. Since information retrieval is strongly connected with natural language process- ing, this work includes results in this regard related to training / testing datasets. Firstly, we have provided a high performant custom trained model for machine learn- ing identification of Albanian language. Secondly, we have created an automatically generated corpus of annotated news articles that may be used for training machine learning models for named entity recognition. It contains about 25.000 annotated sentences for each focus entity class (person, organization, location). Lastly, we have provided a set of 388.325 news articles clustered by topic and named-entity annotated. ... Early work in topic detection and segmentation (Hirschberg and Litman, 1993;Passonneau and Litman, 1997) focused on identifying cue phrases (such as on a different note) or examining lexical cohesion to segment topical chunks. Other work (Fiscus and Doddington, 2002) investigated topic detection and tracking (TDT) in a stream of broadcast news stories. More recent work (Glavas and Somasundaran, 2020) has explored utilizing neural networks to address topic segmentation. ... TIAGE: A Benchmark for Topic-Shift Aware Dialog Modeling Conference Paper Jan 2021 Huiyuan Xie <here is a image 5389d3b5bbc19150-67663e83cff64cd8> Zhenghao Liu <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Chenyan Xiong <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ann Copestake ... The main advances of political media analysis have been observed in political and social sciences, especially for challenging tasks for humans, such as news media bias [56]. In summary, research in computer science studies political text in social networks, especially regarding topic, event and sentiment detection [78,138,141], which we will elaborate on further in Chapter 4. It also includes works on news analysis that discover topics [43] , memes [89] and sentiments [5], oftentimes with specific focus on blogs [49] and financial news [145]. Political news articles often attract studies for challenging tasks even for humans, e.g., ideological perspective analysis [95] and fact checking [165]. ... Revealing hidden patterns in political news and social media with machine learning Thesis Full-text available Nov 2021 <here is a image 1ebc59dfcf2d7671-c983477994c8efaa> Konstantina Lazaridou As part of our everyday life we consume breaking news and interpret it based on our own viewpoints and beliefs. We have easy access to online social networking platforms and news media websites, where we inform ourselves about current affairs and often post about our own views, such as in news comments or social media posts. The media ecosystem enables opinions and facts to travel from news sources to news readers, from news article commenters to other readers, from social network users to their followers, etc. The views of the world many of us have depend on the information we receive via online news and social media. Hence, it is essential to maintain accurate, reliable and objective online content to ensure democracy and verity on the Web. To this end, we contribute to a trustworthy media ecosystem by analyzing news and social media in the context of politics to ensure that media serves the public interest. In this thesis, we use text mining, natural language processing and machine learning techniques to reveal underlying patterns in political news articles and political discourse in social networks. Mainstream news sources typically cover a great amount of the same news stories every day, but they often place them in a different context or report them from different perspectives. In this thesis, we are interested in how distinct and predictable newspaper journalists are, in the way they report the news, as a means to understand and identify their different political beliefs. To this end, we propose two models that classify text from news articles to their respective original news source, i.e., reported speech and also news comments. Our goal is to capture systematic quoting and commenting patterns by journalists and news commenters respectively, which can lead us to the newspaper where the quotes and comments are originally published. Predicting news sources can help us understand the potential subjective nature behind news storytelling and the magnitude of this phenomenon. Revealing this hidden knowledge can restore our trust in media by advancing transparency and diversity in the news. Media bias can be expressed in various subtle ways in the text and it is often challenging to identify these bias manifestations correctly, even for humans. However, media experts, e.g., journalists, are a powerful resource that can help us overcome the vague definition of political media bias and they can also assist automatic learners to find the hidden bias in the text. Due to the enormous technological advances in artificial intelligence, we hypothesize that identifying political bias in the news could be achieved through the combination of sophisticated deep learning modelsxi and domain expertise. Therefore, our second contribution is a high-quality and reliable news dataset annotated by journalists for political bias and a state-of-the-art solution for this task based on curriculum learning. Our aim is to discover whether domain expertise is necessary for this task and to provide an automatic solution for this traditionally manually-solved problem. User generated content is fundamentally different from news articles, e.g., messages are shorter, they are often personal and opinionated, they refer to specific topics and persons, etc. Regarding political and socio-economic news, individuals in online communities make use of social networks to keep their peers up-to-date and to share their own views on ongoing affairs. We believe that social media is also an as powerful instrument for information flow as the news sources are, and we use its unique characteristic of rapid news coverage for two applications. We analyze Twitter messages and debate transcripts during live political presidential debates to automatically predict the topics that Twitter users discuss. Our goal is to discover the favoured topics in online communities on the dates of political events as a way to understand the political subjects of public interest. With the up-to-dateness of microblogs, an additional opportunity emerges, namely to use social media posts and leverage the real-time verity about discussed individuals to find their locations. That is, given a person of interest that is mentioned in online discussions, we use the wisdom of the crowd to automatically track her physical locations over time. We evaluate our approach in the context of politics, i.e., we predict the locations of US politicians as a proof of concept for important use cases, such as to track people that are national risks, e.g., warlords and wanted criminals. ... Two other techniques are the detection cost function and the decision error tradeoff (DET) curve. They are discussed in Fiscus and Doddington [127] , Martin et al. [128]. ... A History and Theory of Textual Event Detection and Recognition Article Full-text available Jan 2020 <here is a image ef3963baaa69a22c-c4b991d6fce41203> Yanping Chen Zehua Ding <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Qinghua Zheng <here is a image 275a04e01137464f-26b3c87950437214> Nazaraf Shah There is large and growing amounts of textual data that contains information about human activities. Mining interesting knowledge from this textual data is a challenging task because it consists of unstructured or semistructured text that are written in natural language. In the field of artificial intelligence, event-oriented techniques are helpful in addressing this problem, where information retrieval (IR), information extraction (IE) and graph methods (GMs) are three of the most important paradigms in supporting event-oriented processing. In recent years, due to information explosions, textual event detection and recognition have received extensive research attention and achieved great success. Many surveys have been conducted to retrospectively assess the development of event detection. However, until now, all of these surveys have focused on only a single aspect of IR, IE or GMs. There is no research that provides a complete introduction or a comparison of IR, IE, and GMs. In this article, a survey about these techniques is provided from a broader perspective, and a convenient and comprehensive comparison of these techniques is given. The hallmark of this article is that it is the first survey that combines IR, IE and GMs in a single frame and will therefore benefit researchers by acting as a reference in this field. ... It uses vector space model (VSM) for representing topics, and then makes use of the K-means algorithm for text clustering which documents are compared using cosine similarity. The authors study how K in K-means affects topic detection and finally, they use TDT evaluation method (Fiscus & Doddington, 2002) to evaluate system performance. In (Zhang & Li, 2011) Zhang and Li study topic detection according to the news corpus. ... A review of approaches for topic detection in Twitter Article Jun 2020 <here is a image 31215cb1702a7df8-c983d2e1cfb90463> Zeynab Mottaghinia <here is a image 1f409d1f5b79f3e5-c1129be8303f331d> Mohammad Reza Feizi Derakhshi <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Leili Farzinvash <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Pedram Salehpour Online social media such as Twitter are growing so rapidly. Recently, Twitter has become one of the popular microblogging services on the Internet. It lets millions of users to communicate and interact by sending short messages of up to 140 characters. The massive amount of information over the web from Twitter requires an automatic tool that can determine the topics that people are talking about. The Topic Detection task is concentrated on discovering the main topics automatically. In this article at first, we explore different approaches to detect topics of tweets. Then, we will classify these topic detection approaches to four classes of categories, including with word embedding or without word embedding, specified or unspecified, offline (RED) or online (NED), and supervised or unsupervised. Finally, we will discuss the studied approaches in detail. ... Models for topic detection [19] - [23] can be divided into two main categories: deterministic models and probabilistic models. Deterministic models treat topics and texts as points in space through Vector Space Models (VSM) [24]. ... State of the Art Models for Fake News Detection Tasks Conference Paper Full-text available Apr 2020 Wissam Antoun Rim Achour <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Fady Baly <here is a image 43d373cd72559c75-665ce828864c214e> Hazem M. Hajj This paper presents state of the art methods for addressing three important challenges in automated fake news detection: fake news detection, domain identification, and bot identification in tweets. The proposed solutions achieved first place in a recent international competition on fake news. For fake news detection, we present two models. The winning model in the competition combines similarity between the embedding of each article’s title and the embedding of the top five corresponding google search results. The new model relies on advances in Natural Language Understanding (NLU) end to end deep learning models to identify stylistic differences between legitimate and fake news articles. This second model was developed after the competition and outperforms the winning approach. For news domain detection, the winning model is a hybrid approach composed of named entity features concatenated with semantic embeddings derived from end to end models. For twitter bot detection, we propose to use the following features: duration between account creation and tweet date, presence of a tweet’s link, presence of user’s location, other tweet’s features, and the tweets’ metadata. Experiments include insights into the importance of the different features and the results indicate the superior performances of all proposed models. ... Models for topic detection [19] - [23] can be divided into two main categories: deterministic models and probabilistic models. Deterministic models treat topics and texts as points in space through Vector Space Models (VSM) [24]. ... State of the Art Models for Fake News Detection Tasks Conference Paper Full-text available Apr 2020 <here is a image 46fd16e0fc6ba31b-8644cb86f0710819> Wissam Antoun <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Fady Baly Rime Achour <here is a image 43d373cd72559c75-665ce828864c214e> Hazem M. Hajj This paper presents state of the art methods for addressing three important challenges in automated fake news detection: fake news detection, domain identification, and bot identification in tweets. The proposed solutions achieved first place in a recent international competition on fake news. For fake news detection, we present two models. The winning model in the competition combines similarity between the embedding of each article's title and the embedding of the top five corresponding google search results. The new model relies on advances in Natural Language Understanding (NLU) end to end deep learning models to identify stylistic differences between legitimate and fake news articles. This second model was developed after the competition and outperforms the winning approach. For news domain detection, the winning model is a hybrid approach composed of named entity features concatenated with semantic embeddings derived from end to end models. For twitter bot detection, we propose to use the following features: duration between account creation and tweet date, presence of a tweet's link, presence of user's location, other tweet's features, and the tweets' metadata. Experiments include insights into the importance of the different features and the results indicate the superior performances of all proposed models. ... Events detection and news monitoring from multiple sources of media had been the focus of researchers since the last decade. In 1998, Topic Detection and Tracking (TDT) research program explored state of the art in detecting new events in a stream of broadcast news stories [10] [11] . TDT tasks are concerned with detecting events from static documents in traditional media, such as the work of [12]. ... Lessons Learned from Event Detection from Arabic Tweets: The Case of Jordan Flash Floods near Dead Sea Conference Paper Aug 2019 <here is a image 9ef54e10db5af38c-090738c04fbd678e> Fatima Shannag <here is a image 696a91c34885dc17-ae159056a98bd1e5> Bassam Hammo Event detection ... Fiscus and Doddington (Fiscus, 2002 ) in the scope of the Topic Detection and Tracking project gave the following definitions of event: event is "something that happens at some specific time and place along with all necessary preconditions and unavoidable consequences." Becker et al. (2010) adopts an event definition used in an earlier study on broadcast news: "An event is something that occurs in a certain place at a certain time." ... Event Detection and Classification in Hungarian Natural Texts Article Jul 2019 <here is a image 5663a7e6303f48be-059f940e356827e0> Zoltán Subecz ... Events detection and news monitoring from multiple sources of media had been the focus of researchers since the last decade. In 1998, Topic Detection and Tracking (TDT) research program explored state of the art in detecting new events in a stream of broadcast news stories [10] [11] . TDT tasks are concerned with detecting events from static documents in traditional media, such as the work of [12]. ... Lessons Learned from Event Detection from Arabic Tweets: The Case of Jordan Flash Floods near Dead Sea Conference Paper Fatima B. Shannag <here is a image 696a91c34885dc17-ae159056a98bd1e5> Bassam Hammo Event detection is essential for decision makers to understand the events surrounding their real world. Social media microblogging platforms play a significant role in our life. One of these platforms is Twitter, which has an extreme high exchange rate and accordingly has become a valuable and relevant source for many political and social events. Event detection from social media attracted the attention of researchers in different natural languages. Extracting and detecting events from Arabic tweets is still under investigation. In this paper, we have used the Python Natural Language Toolkit (NLTK) library to develop two classifiers for filtering and detecting extracted events from Arabic tweets. The first classifier filters the collected tweets using two passes. The first pass identifies the hashtags while the second pass does a shallow analysis on the tweets content. The second classifier analyzes the text extracted from the tweets. As a case study, we present the tragic events of the Jordan flash floods near the Dead Sea. The model successfully filtered all the collected tweets and picked the ones describing the incidents within that region. Analyzed data revealed important information to learn from this lesson for the future. The solution can be generalized and adapted to other problems. ... Below are de¯nitions of important terminology that appear in this paper. First, the following three terms follow the de¯nitions in the Topic Detection and Tracking (TDT) workshop series organized by NIST [22] . ... Summarization of Multiple News Videos Considering the Consistency of Audio-Visual Contents Article Ye Zhang Ryunosuke Tanishige <here is a image 9a7ef6267e3ed51d-b6fca5d97846722c> Ichiro Ide <here is a image 676c33ea57b3e809-ef7b224f90539b78> H. Murase News videos are valuable multimedia information on real-world events. However, due to the incremental nature of the contents, a sequence of news videos on a related news topic could be redundant and lengthy. Thus, a number of methods have been proposed for their summarization. However, there is a problem that most of these methods do not consider the consistency between the auditory and visual contents. This becomes a problem in the case of news videos, since both contents do not always come from the same source. Considering this, in this paper, we propose a method for summarizing a sequence of news videos considering the consistency of auditory and visual contents. The proposed method first selects key-sentences from the auditory contents (Closed Caption) of each news story in the sequence, and next selects a shot in the news story whose “Visual Concepts” detected from the visual contents are the most consistent with the selected key-sentence. In the end, the audio segment corresponding to each key-sentence is synthesized with the selected shot, and then these clips are concatenated into a summarized video. Results from subjective experiments on summarized videos on several news topics show the effectiveness of the proposed method. ... In [25] J. Allan, C. Wade, and A. Bolivar, performed novelty detection at the sentence level. Authors of [26] . J. G. Fiscus and G. R. Doddington performed work on Topic detection and tracking. ... Novelty Detection in BBC Sports News Streams Article Full-text available Mar 2018 Wankhede Rohit <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Sachin Deshmukh <here is a image 9ed6e5833e7eb194-45ab61369c5eab1a> Rajkumar S Jagdale In this paper we illustrate various methods for processing document and analysis at document as well as textual level . We explore the basic various approaches of document similarities .This paper helps to take an overview about text mining. The paper gives a view of the basic evaluation techniques of distance measurement used for document similarities, along with their performance accuracy according to the survey obtained as given by their use. It also describes some crucial methods in sentiment analysis by use of dictionaries like nrc, bing, afinn. We will take a analysis of variant data ranging from common words to unique words appeared. The methods such as LSH will give a statistical view of documents represented as tokens and later into buckets or stems. The results are further represented using clustering. ... As is usual in the literature [8] , we measure the effectiveness of the detection task by the detection accuracy. Additionally, we show Detection error trade-off (DET) curves based on the official TDT3 evaluation scripts using standard settings, which are originate from the standard TDT evaluation procedure [23, 24] . DET plots show the trade-off between miss and false alarm probability for the full range of thresholds and provide a more comprehensive illustration of effectiveness than single value metrics [25] . ... Predicting Future Rumors Article Full-text available CHINESE J ELECTRON <here is a image 71ac362c6bc79bd2-d5a62078672dfafe> Dominik Wurzer <here is a image f6f1b0343a9413cb-faab03150375797f> Yumeng Qin Recent uproar of fake news and misinformation on social media platforms has sparked the interest in the scientific community to automatically detect and refute them. The most popular research task to counteract misinformation, Rumour detection, requires repeated signals to reach adequate detection accurate. Consequently, rumour detection recognizes rumours only when they have started spreading and causing harm. We introduce a new task called "rumour prediction" that assesses the possibility of a document arriving from a social media stream becoming a rumour in the future. Note that rumour prediction differentiates itself from rumour detection through instant decision making. This allows refuting misinforma-tion before it spreads and causes harm. Our approach to rumour prediction harnesses content based features in combination with novelty based features and pseudo feedback. Our experiments show that we are able to accurately predict , whether a document will become a rumour in the future. Additionally, we show how rumour prediction can significantly improve the accuracy of state-of-the-art Rumour detection systems. ... In the remainder of this part, we cite some works belonging to the second category. Note that there is a difference between 'topic' and 'event' as emphasized in [21] : ... Real-Time Event Localization and Detection Over Social Networks Using Apache Intelligence Conference Paper Oct 2017 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Sarra Hasni <here is a image 149705235d444d8e-4ea3cbeb3ea6ccee> Sami Faiz Today, the event detection activity is becoming increasingly more complex with the emergence of the Big Data phenomenon. More specifically, different social networks and microblogging services are leading to the massive explosion of data describing the real world. Multiple conducted works highlight the role of textual data as the simplest form to report actualities and to describe real-time events. But, the variety of the proposed solutions with high complexity degrees reveals big challenges that are hidden behind the nature of those data. A concentrated study around some established works for event detection over textual data published on social networks allows us to meet limits of proposed solutions. These limits are the main areas of research leading to the proposal of a new approach for a real-time localization and detection of events over textual data posted on social networks. This approach takes benefit from a set of Apache platforms for efficient treatment of the huge streams of data. ... Toutes les sous-tâches du TDT sont évaluées en tant que tâche de détection (Fiscus, Doddington et al., 1999 ; Fiscus et Doddington, 2002) , par une procédure binaire considérant les sorties du système comme vraies ou fausses par rapport aux sorties attendues. ... Appariement de contenus textuels dans le domaine de la presse en ligne : Développement et adaptation d'un système de recherche d'information Thesis Nov 2017 <here is a image 827112d9221915c9-eb3be3add44cf2f3> Adèle Désoyer L’objectif de cette thèse, menée dans un cadre industriel, est d’apparier des contenus textuels médiatiques. Plus précisément, il s’agit d’apparier à des articles de presse en ligne des vidéos pertinentes, pour lesquelles nous disposons d’une description textuelle. Notre problématique relève donc exclusivement de l’analyse de matériaux textuels, et ne fait intervenir aucune analyse d’image ni de langue orale. Surviennent alors des questions relatives à la façon de comparer des objets textuels, ainsi qu’aux critères mobilisés pour estimer leur degré de similarité. L’un de ces éléments est selon nous la similarité thématique de leurs contenus, autrement dit le fait que deux documents doivent relater le même sujet pour former une paire pertinente. Ces problématiques relèvent du domaine de la recherche d’information (RI), dans lequel nous nous ancrons principalement. Par ailleurs, lorsque l’on traite des contenus d’actualité, la dimension temporelle est aussi primordiale et les problématiques qui l’entourent relèvent de travaux ayant trait au domaine du Topic Detection and Tracking (TDT) dans lequel nous nous inscrivons également. Le système d’appariement développé dans cette thèse distingue donc différentes étapes qui se complètent. Dans un premier temps, l’indexation des contenus fait appel à des méthodes de Traitement Automatique des Langues (TAL) pour dépasser la représentation classique des textes en sacs de mots. Ensuite, deux scores sont calculés pour rendre compte du degré de similarité entre deux contenus : l’un relatif à leur similarité thématique, basé sur un modèle vectoriel de RI ; l’autre à leur proximité temporelle, basé sur une fonction empirique. Finalement, un modèle de classification appris à partir de paires de documents, décrites par ces deux scores et annotées manuellement, permet d’ordonnancer les résultats. L’évaluation des performances du système a elle aussi fait l’objet de questionnements dans ces travaux de thèse. Les contraintes imposées par les données traitées et le besoin particulier de l’entreprise partenaire nous ont en effet contraint à adopter une alternative au protocole classique d’évaluation en RI, le paradigme de Cranfield. ... Topic detection and tracking is a long studied task [8] and many approaches have already been attempted. Non-negative matrix factorization is used in the field of text mining to factorize and thereby decrease the dimension of a large matrix [11]. ... Towards a Topic Discovery and Tracking System with Application to News Items Conference Paper Full-text available Oct 2017 Daniel Brüggermann Yannik Hermey Carsten Orth <here is a image b720a7d82e48fdba-4870f18f282c6647> Gerasimos (Jerry) Spanakis Rapid proliferation of the World Wide Web led to an enormous increase in the availability of textual corpora. In this paper, the problem of topic detection and tracking is considered with application to news items. The proposed approach explores two algorithms (Non-Negative Matrix Factorization and a dynamic version of Latent Dirichlet Allocation (DLDA)) over discrete time steps and makes it possible to identify topics within storylines as they appear and track them through time. Moreover, emphasis is given to the visualization and interaction with the results through the implementation of a graphical tool (regardless the approach). Experimental analysis on Reuters RCV1 corpus and the Reuters 2015 archive reveals that explored approaches can be effectively used as tools for identifying topic appearances and their evolutions while at the same time allowing for an efficient visualization. ... One of the track tasks included in the Topic Detection and Tracking (TDT) (Fiscus and Doddington 2002) is topic detection, where systems cluster streamed stories into bins depending on the topics being discussed. The techniques of topic modelling, such as PLSA (Hofmann 2001) and LDA (Blei et al. 2003), have shown to be effective for topic detection. ... Topic detection and tracking on heterogeneous information Article Full-text available Aug 2018 J INTELL INF SYST Long Chen Huaizhi Zhang <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Joemon M. Jose <here is a image fa6c11cfca741f5f-dd70ad3fc98eb43f> Peter Triantafillou Given the proliferation of social media and the abundance of news feeds, a substantial amount of real-time content is distributed through disparate sources, which makes it increasingly difficult to glean and distill useful information. Although combining heterogeneous sources for topic detection has gained attention from several research communities, most of them fail to consider the interaction among different sources and their intertwined temporal dynamics. To address this concern, we studied the dynamics of topics from heterogeneous sources by exploiting both their individual properties (including temporal features) and their inter-relationships. We first implemented a heterogeneous topic model that enables topic–topic correspondence between the sources by iteratively updating its topic–word distribution. To capture temporal dynamics, the topics are then correlated with a time-dependent function that can characterise its social response and popularity over time. We extensively evaluate the proposed approach and compare to the state-of-the-art techniques on heterogeneous collection. Experimental results demonstrate that our approach can significantly outperform the existing ones. ... The Topic Detection and Tracking program by Jonathan G. Fiscus and George R. Doddington [16] gave the following definitions of the event: Event is "something that happens at some specific time and place along with all necessary preconditions and unavoidable consequences"; ... Event-Radar: Real-time Local Event Detection System for Geo-Tagged Tweet Streams Article Aug 2017 Sibo Zhang Yuan Cheng Deyuan Ke The local event detection is to use posting messages with geotags on social networks to reveal the related ongoing events and their locations. Recent studies have demonstrated that the geo-tagged tweet stream serves as an unprecedentedly valuable source for local event detection. Nevertheless, how to effectively extract local events from large geo-tagged tweet streams in real time remains challenging. A robust and efficient cloud-based real-time local event detection software system would benefit various aspects in the real-life society, from shopping recommendation for customer service providers to disaster alarming for emergency departments. We use the preliminary research GeoBurst as a starting point, which proposed a novel method to detect local events. GeoBurst+ leverages a novel cross-modal authority measure to identify several pivots in the query window. Such pivots reveal different geo-topical activities and naturally attract related tweets to form candidate events. It further summarises the continuous stream and compares the candidates against the historical summaries to pinpoint truly interesting local events. We mainly implement a website demonstration system Event-Radar with an improved algorithm to show the real-time local events online for public interests. Better still, as the query window shifts, our method can update the event list with little time cost, thus achieving continuous monitoring of the stream. Auto-clustering of Financial Reports Based on Formatting Style and Author’s Fingerprint Chapter Jan 2023 <here is a image 49d3ae0184332577-c1ef5db5c3108799> Braulio Blanco <here is a image 746033e5640ea5eb-af9be989e3112eb6> Mats Brorsson Maciej Zurad We present a new clustering algorithm of financial reports that is based on the reports’ formatting and style. The algorithm uses layout and content information to automatically generate as many clusters as needed. This allows us to reduce the effort of labeling the reports in order to train text-based machine learning models for extracting person or company names, addresses, financial categories, etc. In addition, the algorithm also produces a set of sub-clusters inside each cluster, where each sub-cluster corresponds to a set of reports made by the same author (person or firm). The information about sub-clusters allows us to evaluate the change in the author over time.We have applied the algorithm to a dataset with over 38,000 financial reports (last Annual Account presented by a company) from the Luxembourg Business Registers (LBR) and found 2,165 clusters between 2 and 850 documents with a median of 4 and an average of 14. When adding 2,500 new documents to the existing cluster set (previous annual accounts presented by companies), we found that 67.3% of the financial reports were placed in the correct cluster and sub-cluster. From the remaining documents, 65% were placed in a different subcluster because the company changed the formatting style, which is expected and correct behavior. Finally, labeling 11% of the entire dataset, we can replicate these labels up to 72% of the dataset, keeping a high feature coverage.KeywordsClusteringNLPMachine learningUnstructured dataFinancial reports Semantic Similarity Analysis between Future Topics and Their Neighbors in Topic Networks for Network-based Topic Evolution Conference Paper Dec 2022 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Sukhwan Jung <here is a image a41338178631c6d3-a6110155ecccf4b7> Aviv Segev Comparisons of the Economist Topics on Three Countries from 1991 Through 2016 Article Sep 2022 Shesen Guo Ganzhou Zhang New topic modeling technique has been increasingly used in research of communication for quick discovery of latent topics that are spread across huge volumes of text. This work intends to analyze and compare the topics automatically generated by Latent Dirichlet Allocation (LDA). The data for building LDA model in this work is based on 38,124 articles published from 1991 through 2016 in one of the world’s most influential political and economic magazines, The Economist. The retrieved documents for generating topics are divided into three countries of the UK, the US, and China in order to observe topical differences between these ingroup or outgroup countries in The Economist coverage. The work analyzes interpretability, overall weight distributions, and historical changing patterns of the topics using LDA model diagnostics. It discusses the hot or increasing trends using regression coefficient. The work also tentatively explores the relationship between the media agenda and events. Cross-Domain Transfer Learning Prediction of COVID-19 Popular Topics Based on Knowledge Graph Article Full-text available Mar 2022 Xiaolin Chen Qixing Qu Chengxi Wei Shudong Chen The significance of research on public opinion monitoring of social network emergencies is becoming increasingly important. As a platform for users to communicate and share information online, social networks are often the source of public opinion about emergencies. Considering the relevance and transmissibility of the same event in different social networks, this paper takes the COVID-19 outbreak as the background and selects the platforms Weibo and TikTok as the research objects. In this paper, first, we use the transfer learning model to apply the knowledge obtained in the source domain of Weibo to the target domain of TikTok. From the perspective of text information, we propose an improved TC-LDA model to measure the similarity between the two domains, including temporal similarity and conceptual similarity, which effectively improves the learning effect of instance transfer and makes up for the problem of insufficient sample data in the target domain. Then, based on the results of transfer learning, we use the improved single-pass incremental clustering algorithm to discover and filter popular topics in streaming data of social networks. Finally, we build a topic knowledge graph using the Neo4j graph database and conduct experiments to predict the evolution of popular topics in new emergencies. Our research results can provide a reference for public opinion monitoring and early warning of emergencies in government departments. A graphical decomposition and similarity measurement approach for topic detection from online news Article Apr 2021 INFORM SCIENCES Kejing Xiao Zhaopeng Qian Biao Qin Topic detection aims to discover valuable topics from the massive online news. It can help people to capture what is happening in real world and alleviate the burden of information overload. It also has great significance since the online news is experiencing an explosive growth. Topic detection is typically transformed into a document clustering problem, whose core idea is to cluster news documents that report on the same topic to the same group based on document similarity. Due to the complex structure and long length of news documents, the similarity measurement of news is very challenging. Existing term-based methods represent news documents based on a set of informative keywords in the document with a vector space model (VSM) and then the relationship between documents is calculated by cosine similarity. However, VSM ignores the relationship between words and has sparse semantics, which leads to low precision of topic detection. In recent years, the probabilistic methods and the graph analytical methods have been proposed for topic detection. However, both of them have high time complexity. To cope with these problems, we first present a novel document representation approach based on graphical decomposition, which decomposes each news document into different semantic units and then relationship between the semantic units is constructed to form a capsule semantic graph (CSG). The CSG can retain the relationship between words and alleviate the sparse semantics compared to VSM representation. We next introduce the graph kernel to measure the similarity between the CSGs based on their substructures. Finally, we use an incremental clustering method to cluster the news documents, in which the documents are represented by CSGs and the similarity between documents is calculated by graph kernel. The experiment results on three standard datasets show that our method obtains higher precision, recall and F1 score than several state-of-the-art methods. Moreover, the experiment results on a large news dataset show that our CSG-SM has lower time complexity than probabilistic methods and graph analytical methods. Identification and Prediction of Emerging Topics through Their Relationships to Existing Topics Conference Paper Dec 2020 Sukhwan Jung <here is a image 8f03d595a81aa706-8b9ab62236f9db49> Rituparna Datta <here is a image a41338178631c6d3-a6110155ecccf4b7> Aviv Segev Re-Evaluation of On-Line Hot Topic Discovery Model Chapter Jan 2011 Hamid Nemati <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Hui-Min Ye <here is a image 8448731737288528-2d37460a9650f4c7> Sushil K. Sharma <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Huinan Xu As a major medium for information transmission, Internet plays an important role in diffusing and spreading news on web. Some governments attach great importance and pay lot of effort trying to detect, track the development of events and forecast emergency on internet. On the basis of the researches in the field of topic detection and tracking, we proposed a model for hot topic discovery that would pick out hot topics by automatically detecting, clustering and weighting topics on the websites within a time period. We also introduced a topic index approach in following the growth of topics, which is useful to analyze and forecast the development of topics on web. A PDDL based Disaster Storyline Generation Approach Conference Paper Jul 2020 Mingrong Tang Jinxin Ni Qifeng Zhou Events in Tweets: Graph Based Techniques Article Sep 2020 <here is a image 7c66bc995e4401d3-bcefae3f45d47fb6> Abhaya Kumar Pradhan <here is a image 6f17403fa00b7f3d-5796b51aced00d5f> Hrushikesha Mohanty Rajendra Prasad Lal Introduction Mining Twitter streaming posts (i.e. tweets) to find events or the topics of interest has become a hot research problem. In the last decade, researchers have come up with various techniques like bag-of-words techniques, statistical methods, graph-based techniques, topic modelling approaches, NLP and ontology-based approaches, machine learning and deep learning methods for detecting events from tweets. Among these techniques, the graph-based technique is efficient in capturing the latent structural semantics in the tweet content by modelling word co-occurrence relationships as a graph and able to capture the activity dynamics by modelling the user-tweet and user-user interactions. Discussion This article presents an overview of different event detection techniques and their methodologies. Specifically, this paper focuses on graph-based event detection techniques in Twitter and presents a critical survey on these techniques, their evaluation methodologies and datasets used. Further, some challenges in the area of event detection in Twitter along with future directions of research are presented. Conclusion A Microblogging services and online social networking sites like Twitter provides a massive amount of valuable information on real-world happenings. There is a need for mining this information, which will help in understanding the social interest and effective decision making on various emergencies. However, event detection techniques need to be efficient in terms of time and memory and accurate for processing such voluminous, noisy and fastarriving information from Twitter. Automated classification of social network messages into Smart Cities dimensions Article Aug 2020 FUTURE GENER COMP SY <here is a image 8ce30f4741b0a3b4-3860120c4a840774> Luciana Bencke <here is a image 65b08eda8e63b3de-9dd797d137c12f5b> Cristian Cechinel <here is a image 27bdd8cc1cbea95d-2cac620777ad9787> Roberto Munoz A Smart City can be defined as a high-tech city with several public and private services capable to strategically solve (or mitigate) problems normally generated by rapid urbanization. Different models of indicators have been developed to follow cities’ evolution to become a Smart City. An example of such model is the standard 37120 from the International Organization for Standardization (ISO) that proposes a set of dimensions and indicators (e.g. Transportation, Recreation, Solid Waste) for services and quality of life for sustainable cities and communities. It has been common to find official social network profiles of organizations and governmental entities related to the services they provide or are responsible for (water, waste, transportation, cultural events, etc.) and that are used by citizens as a gateway to directly interact and communicate their complains and problems about those services. The present paper proposes to apply machine learning algorithms over the urban data generated by social networks in order to create classifiers to automatically categorize citizens messages according to the different cities services dimensions. For that, two distinct text datasets in Portuguese were collected from two social networks: Twitter (1,950 tweets) and Colab.re (65,066 posts). The texts were mapped according to the different ISO 37120 categories, preprocessed and mined through the use of 8 algorithms implemented in Scikit-Learn. Initial results pointed out the feasibility of the proposal with models achieving average F1-measures around 55% for F1-macro and 78% for F1-micro when using Linear Vector Classification, Logistic Regression, Decision Tree and Complement Naive Bayes. However, as the datasets were highly unbalanced, the performances of the models vary significantly for each ISO category, with the best results occurring for Wastewater, Water & Sanitation, Energy and Transportation. The classifiers generated here can be integrated on a number of different city services and systems such as: governmental support decision systems, customer complain systems, communities dashboards, police offices, transportation’s companies, cultural producers, environmental agencies, and recyclers’ companies. Experiments with Cross-Language Speech Retrieval for Lower-Resource Languages Chapter Feb 2020 Suraj Nair Anton Ragni Ondrej Klejch Douglas W. Oard Cross-language speech retrieval systems face a cascade of errors due to transcription and translation ambiguity. Using 1-best speech recognition and 1-best translation in such a scenario could adversely affect recall if those 1-best system guesses are not correct. Accurately representing transcription and translation probabilities could therefore improve recall, although possibly at some cost in precision. The difficulty of the task is exacerbated when working with languages for which limited resources are available, since both recognition and translation probabilities may be less accurate in such cases. This paper explores the combination of expected term counts from recognition with expected term counts from translation to perform cross-language speech retrieval in which the queries are in English and the spoken content to be retrieved is in Tagalog or Swahili. Experiments were conducted using two query types, one focused on term presence and the other focused on topical retrieval. Overall, the results show that significant improvements in ranking quality result from modeling transcription and recognition ambiguity, even in lower-resource settings, and that adapting the ranking model to specific query types can yield further improvements. A General Framework for First Story Detection Utilizing Entities and Their Relations Article Jan 2020 Nikolaos Emmanouil Panagiotou Cem Akkaya Kostas Tsioutsiouliklis <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Dimitrios Gunopulos News portals, such as Yahoo News or Google News, collect large amounts of news articles from a variety of sources on a daily basis. Only a small portion of these documents can be selected and displayed on the homepage. Thus, there is a strong preference for major, recent events. In this work, we propose a scalable First Story Detection (FSD) pipeline that identifies fresh news. This pipeline is used in order to instantiate a variety of FSD approaches. In addition, we suggest a novel FSD technique that in comparison to existing systems, relies on relation extraction algorithms and exploits the named entities and their relations in order to decide about the freshness of an article. We evaluate our technique by instantiating existing state of art FSD techniques within our generic pipeline. As ground truth we use multiple datasets that cover different categories. Experimental results demonstrate that our FSD method in many cases provides an improvement over state-of-the-art techniques. In addition, we show using a large synthetic dataset that our general FSD pipeline has constant space and time requirements and is suitable for very high volume streams. Tracking Aspects in News Documents Conference Paper Nov 2018 Maoto Inoue Takao Miura Studies on a multidimensional public opinion network model and its topic detection algorithm Article May 2019 INFORM PROCESS MANAG Guanghui Wang Yuxue Chi Yijun Liu Yufei Wang “We the Media” networks are real time and open, and such networks lack a gatekeeper system. As netizens’ comments on emergency events are disseminated, negative public opinion topics and confrontations concerning those events also spread widely on “We the Media” networks. Gradually, this phenomenon has attracted scholarly attention, and all social circles attach importance to the phenomenon as well. In existing topic detection studies, a topic is mainly defined as an “event” from the perspective of news-media information flow, but in the “We the Media” era, there are often many different views or topics surrounding a specific public opinion event. In this paper, a study on the detection of public opinion topics in “We the Media” networks is presented, starting with the characteristics of the elements found in public opinions on “We the Media” networks; such public opinions are multidimensional, multilayered and possess multiple attributes. By categorizing the elements’ attributes using social psychology and system science categories as references, we build a multidimensional network model oriented toward the topology of public opinions on “We the Media” networks. Based on the real process by which multiple topics concerning the same event are generated and disseminated, we designed a topic detection algorithm that works on these multidimensional public opinion networks. As a case study, the “Explosion in Tianjin Port on August 12, 2015″ accident was selected to conduct empirical analyses on the algorithm's effectiveness. The theoretical and empirical research findings of this paper are summarized along the following three aspects. 1. The multidimensional network model can be used to effectively characterize the communication characteristics of multiple topics on “We the Media” networks, and it provided the modeling ideas for the present paper and for other related studies on “We the Media” public opinion networks. 2. Using the multidimensional topic detection algorithm, 70% of the public opinion topics concerning the case study event were effectively detected, which shows that the algorithm is effective at detecting topics from the information flow on “We the Media” networks. 3. By defining the psychological scores of single and paired Chinese keywords in public opinion information, the topic detection algorithm can also be used to judge the sentiment tendencies of each topic, which can facilitate a timely understanding of public opinion and reveal negative topics under discussion on “We the Media” networks. Framework for Real-World Event Detection Through Online Social Networking Sites: Proceedings of GUCON 2018 Chapter Jan 2019 M. P. S. Bhatia Veena Tayal <here is a image d10b2f7738fec4bc-538ea7065ab6d905> Jitendra Kumar Verma Ritesh Srivastava A Cross-Layer Routing Protocol for Wireless Sensor Networks: Proceedings of GUCON 2018 Chapter Full-text available Jan 2019 <here is a image 169072f7cfe9e3d6-f8d7f9c1ce2632b2> Pallavi Yarde <here is a image c26fbfbb348b467a-300fa90e8c884f40> Sumit Srivastava Kumkum Garg POMon: From Simple Keyword Matching to Stream-Based Live Probabilistic Topic Matching Conference Paper Oct 2018 <here is a image f7123abf4f27b8b1-2a866feae64a614a> Kun Ma Xuewei Niu <here is a image 24027434a25951e0-2c5bb33dc7462676> Ziqiang Yu Ke Ji Stochastic Approach to Aspect Tracking Chapter May 2018 Maoto Inoue Takao Miura Topic classification and clustering on Indonesian complaint tweets for bandung government using supervised and unsupervised learning Conference Paper Aug 2017 Timothy Pratama <here is a image 694788528872e3e3-e0bf55ac150596e9> Ayu Purwarianti Real-Time Unspecified Major Sub-Events Detection in the Twitter Data Stream That Cause the Change in the Sentiment Score of the Targeted Event Article Oct 2017 Ritesh Srivastava M.P.S. Bhatia Twitter behaves as a social sensor of the world. The tweets provided by the Twitter Firehose reveal the properties of big data (i.e. volume, variety, and velocity). With millions of users on Twitter, the Twitter's virtual communities are now replicating the real-world communities. Consequently, the discussions of real world events are also very often on Twitter. This work has performed the real-time analysis of the tweets related to a targeted event (e.g. election) to identify those potential sub-events that occurred in the real world, discussed over Twitter and cause the significant change in the aggregated sentiment score of the targeted event with time. Such type of analysis can enrich the real-time decision-making ability of the event bearer. The proposed approach utilizes a threestep process: (1) Real-time sentiment analysis of tweets (2) Application of Bayesian Change Points Detection to determine the sentiment change points (3) Major sub-events detection that have influenced the sentiment of targeted event. This work has experimented on Twitter data of Delhi Election 2015. The det curve in assessment of detection task performance Article Jan 1997 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> A. Martin George R. Doddington <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Terri Kamm <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mark A. Przybocki The DET curve in assessment of decision task performance Conference Paper Jan 1997 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> A. Martin George R. Doddington <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Terri Kamm <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mark A. Przybocki We introduce the DET Curve as a means of representing performance on detection tasks that involve a tradeoff of error types. We discuss why we prefer it to the traditional ROC Curve and offer several examples of its use in speaker recognition and language recognition. We explain why it is likely to produce approximately linear curves. We also note special points that may be included on these curves, how they are used with multiple targets, and possible further applications. Large, Multilingual, Broadcast News Corpora For Cooperative Research in Topic Detection And Tracking: The TDT-2 and TDT-3 Corpus Efforts Article Full-text available Sep 2000 <here is a image 3411504a02ed0c23-99d9e1dd3b6d1b80> Christopher Cieri <here is a image ab77adfb5e5a98e5-f1ad58690c13579e> David Graff <here is a image 4fe82fe8c328435f-ceeaaf9b648b09cc> Mark Liberman <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Stephanie Strassel This paper describes the creation and content two corpora, TDT-2 and TDT-3, created for the DARPA sponsored Topic Detection and Tracking project. The research goal in the TDT program is to create the core technology of a news understanding system that can process multilingual news content categorizing individual stories according to the topic(s) they describe. The research tasks include segmentation of the news streams into individual stories, detection of new topics, identification of the first story to discuss any topic, tracking of all stories on selected topics and detection of links among stories discussing the same topics. The corpora contain English and Chinese broadcast television and radio, newswires, and text from web sites devoted to news. For each source there are texts or text intermediaries; for the broadcast stories the audio is also available. Each broadcast is also segment to show start and end times of all news stories. LDC staff have defined news topics in the corpor... The DET curve in assessment of detection task performance Conference Paper Sep 1997 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> A. Martin George R. Doddington Terri Kamm <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mark A. Przybocki Results of the 1999 topic detection and tracking evaluation in Mandarin and English Conference Paper Oct 2000 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Jonathan G. Fiscus George R. Doddington Text Segmentation Using Exponential Models Article Dec 2002 Doug Beeferman Adam Berger John Lafferty This paper introduces a new statistical approach to partitioning text automatically into coherent segments. Our approach enlists both short-range and long-range language models to help it sniff out likely sites of topic changes in text. To aid its search, the system consults a set of simple lexical hints it has learned to associate with the presence of boundaries through inspection of a large corpus of annotated data. We also propose a new probabilistically motivated ' error metric for use by the natural language processing and information retrieval communities, intended to supersede precision and recall for appraising segmentation algorithms. Qualitative assessment of our algorithm as well as evaluation using this new metric demonstrate the effective- ness of our approach in two very different domains, Wall Street Journal articles and the TDT Corpus, a collection of newswire articles and broadcast news transcripts. NIST's 1998 topic detection and tracking evaluation (TDT2) Jun 2000 Jon Fiscus George R. Doddington John S. Garofolo <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> A. Martin This paper presents a summary of the 1998 Topic Detection and Tracking (TDT) tasks and the results of the 1998 TDT evaluation. The purpose of TDT is to develop technologies for retrieval and automatic organization of Broadcast News and Newswire stories and to evaluate the performance of those technologies. The TDT project builds on and extends the technologies of Automatic Speech Recognition and Document Retrieval with three tasks: 1) Story Segmentation, 2) Topic Detection and 3) Topic Tracking. Each of the tasks simulates a hypothetical operational system that requires incoming data to be processed time synchronously. The 1998 TDT evaluation (TDT2) continues the work of the TDT pilot study conducted in 1997 (TDT1) and is the first open evaluation of TDT tasks. Overview of the Eighth Text REtrieval Conference (TREC-8)”, NIST Special Publication 500-246: The Eighth Text REtrieval Conference
https://www.researchgate.net/publication/234826832_Topic_Detection_and_Tracking_Evaluation_Overview
PIONEER CO., INC. v. TALO | 462 F.2d 1106 (1972) | 2d110611315 | Leagle.com Rehearing and Rehearing En Banc Denied August 15 1972. CLARK Associate Justice. This case comes here from the dismissal...2d110611315 PIONEER CO., INC. v. TALON, INC. No. 71-1620. View Case Cited Cases 462 F.2d 1106 (1972) PIONEER CO., INC., Appellant, v. TALON, INC. and Donahue Sales Corporation, Appellees. United States Court of Appeals, Eighth Circuit. https://leagle.com/images/logo.png Submitted April 13, 1972. Decided June 29, 1972. Rehearing and Rehearing Denied August 15, 1972. Attorney(s) appearing for the Case Sydney C. Berde, Berde, Leonard & Weinblatt, St. Paul, Minn., for appellant. Harold F. Baker, J. Coleman Bean, Howrey, Simon, Baker & Murchison, Washington, D. C., for appellees; Robert M. Bowen, Levitt, Palmer, Bowen, Bearmon & Rotman, Minneapolis, Minn., of counsel. Before Mr. Justice CLARK, and MATTHES and LAY, Circuit Judges. United States Court of Appeals, Eighth Circuit. Rehearing and Rehearing En Banc Denied August 15, 1972. CLARK, Associate Justice. This case comes here from the dismissal of the amended complaint of the appellant, Pioneer Co., Inc., which was filed against Talon, Inc. and Donahue Sales Corporation, appellees, alleging a violation of Section 1 of the Sherman Act, 15 U.S.C. § 1, upon the ground that the action was barred by the four-year statute of limitation, 15 U.S.C. § 15b. The statute says that the action is barred "unless commenced within four years after the cause of action accrued." The trial court, after an evidentiary hearing on the issue, held that the cause of action accrued on July 24, 1964, and the suit having been filed on August 28, 1968, found it barred. We find that the statute began to run on September 4, 1964, the date that two orders Pioneer had placed with Talon were refused and from which it suffered injury. 1. The facts adduced at the hearing on the motion to dismiss reveal a flagrant violation of the antitrust laws by Talon and Donahue. 1Their brief in this court recites that Pioneer began jobbing Talon zippers as a wholesaler in 1959 and during the next five years made some $7000 of sales of Talon zippers. James Ciliberti, a Donahue salesman in Minneapolis, received a telephone call on July 14, 1964, from Walter Salmon, Donahue's marketing director in New York, requesting him to investigate an advertisement in the Minneapolis paper on July 1, 1964, by Shoppers City Stores offering Talon zippers at discount prices. 2After verifying that Pioneer sold Talon zippers to Shoppers City Stores at a discount, Mr. Ciliberti requested Mr. Rose, President of Pioneer to repurchase the zippers from Shoppers City Stores. When Rose was not able to do so, Mr. Ciliberti purchased all of the Talon zippers on the display counters at Shoppers City Stores. Mr. Ciliberti again talked to Mr. Salmon who told Mr. Ciliberti that Donahue was terminating all shipment of Talon zippers to Pioneer. On July 24th Mr. Ciliberti completed purchasing the remaining Talon zippers in other Shoppers City Stores and advised Mr. Rose that Donahue would no longer sell Talon zippers to Pioneer, that Pioneer was to return all Talon inventory and that all business relations were terminated. Rose testified that he was a discount wholesaler and had Talon stock in his warehouse for sale to retailers; that he had received no formal commitment from anyone that orders would not be accepted; and that he continued to send in orders to Donahue for Talon zippers. The "first notification" that he received was on September 4th. It was sent to his order clerk and was signed by Mr. Salmon. It advised that the two orders he had "recently placed" would not be filled because "a decision had been made to discontinue sales to jobbers whose requirements [462 F.2d 1108] have been modest, due to inconvenience and additional cost of dealing with such jobbers." There was no mention of any previous termination of business relations, return of inventory, etc. 2. It appears to us that Pioneer was acting as a wholesale jobber to retailers engaged in the sale of sundries to drug, variety, food, department and discount stores in Minnesota, Wisconsin, Iowa, North and South Dakota. Pioneer was not a formal full-time dealer or distributor but merely placed orders with manufacturers and distributors on individual order forms as a wholesaler and without any formal contract with either Talon or Donahue. It had been placing written orders with Donahue for Talon zippers on a very moderate basis of about $1500 a year. He had previously discounted Talon zippers below the manufacturers' suggested price. The two orders that he placed and which were refused on September 4, 1964, were a separate cause of action and in the light of the continuing conspiracy 3were not barred by the statute since the suit was filed in August, 1968. As the Supreme Court said in Zenith Radio Corp. v. Hazeltine Research Inc.,401 U.S. 321, 91 S.Ct. 795, 28 L.Ed. 2d 77 (1971), "a cause of action accrues and the statute begins to run when a defendant commits an act that injures a plaintiff's business . . . In the context of a continuing conspiracy . . . this has usually been understood to mean that each time a plaintiff is injured by an act of the defendants a cause of action accrues to him to recover the damages caused by that act and that, as to those damages, the statute of limitations runs from the commission of the act." At 338, 91 S.Ct. at 806. And as the court has likewise said in Highland Supply Corp. v. Reynolds Metal Co.,327 F.2d 725, 732 (8 Cir. 1964): "It is well settled that where a private cause of action under the antitrust laws is based on a continued invasion of one's rights, his cause of action accrues from day to day as his rights are invaded to his damage." The Ninth Circuit has held likewise. See Hoopes v. Union Oil Co.,374 F.2d 480, 486 (9 Cir. 1967). See also Steiner v. Twentieth Century Fox Film Corp.,232 F.2d 190, 194 (9 Cir. 1956). Also see Muskin Shoe Co. v. United Shoe Machinery Corp.,167 F.Supp. 106(D.C.Md.1958). See also Laitram Corporation v. Deepsouth Packing Company,279 F.Supp. 883, 889-890 (E.D.La.1968). Talon and Donahue depend upon Emich Motor Corp. v. General Motors Corporation,229 F.2d 714(7 Cir. 1956) and similar cases. These cases are wholly consistent with our result. Emich was a formal dealer and contractual agent for General Motors. It cancelled the Emich dealership and limitation began to run on that act as of the date of cancellation. Emich sued to recover damages occurring subsequent thereto as well as flowing therefrom. Pioneer, on the contrary, suffered a continuing conspiracy to prevent it from wholesaling Talon zippers at discount prices; it subsequently placed orders which were refused because of the continuing conspiracy. It had no contract, as did Emich, and there was nothing to cancel— only orders to refuse which Talon and Donahue did refuse on September 4th. It is, therefore, clear that even though Donahue gave notice, it terminated nothing of legal significance. See 2361 State Corporation v. Sealy Inc.,263 F.Supp. 845, 851 (N.D.Ill.1967). Subsequent orders placed in due course were rejected because of the continuing conspiracy and specific damage resulted. This is not a case where a single act causes damages that are suffered over a long period of time. Here, to maintain their manufacturers' price, Talon and Donahue were obliged to continue their violation of the antitrust laws by refusing [462 F.2d 1109] to sell to Pioneer on its request. Since the record shows continued refusals until at least September 4, 1964, the action is not barred. Nor is Crummer Co. v. Du Pont,223 F.2d 238(5 Cir. 1955) inconsistent. There Crummer brought an action in 1949 alleging that a conspiracy to drive him from business was commenced in 1941 and continued until 1948. Crummer contended that one cause of action accrued when the last overt act occurred and covered all of the acts alleged. The Fifth Circuit did not agree. Here Talon and Donahue say that the cause of action for all acts and injuries accrues when the first act is committed, a position that the Fifth Circuit specifically repudiated. Id. at 247, 248. Likewise Talon and Donahue's reliance on Laundry Equipment Sales Corp. v. Borg-Warner Corp.,334 F.2d 788(7 Cir. 1964) is also misplaced. There plaintiff failed to claim that any overt act within the statutory period caused plaintiff any damage and thus the action was barred. In the instant case, however, it is quite clear that appellees' continued refusals to deal caused new injury to Pioneer each time an order was refused. 4 Finally, Garelick v. Goerlich's Inc.,323 F.2d 854(6 Cir. 1963) actually supports Pioneer. There the court denied recovery simply because the injuries flowing from the subsequent acts caused no damage to Garelick. He had asked by telephone to be re-instated as distributor; Goerlich's Inc.'s representative answered that the appropriate official would return the call; but he never did so. Later a Goerlich's travelling representative called at Garelick's office soliciting orders. Someone in the office stated that he was certainly surprised at the call since Goerlich had refused to sell Garelick previously. The representative then said he would take it up with his principal but nothing further was heard. At p. 856. Garelick did nothing further about either of these incidents. On the other hand Pioneer, after Ciliberti's call concerning Shoppers continued to send in orders to Talon and Donahue. The teaching of the case is clear—the subsequent acts must result in damage. It follows from what we have said that Pioneer is entitled to bring this action for all damages suffered as a result of Talon and Donahue's refusal to deal after August 28, 1964. The record before us having been made solely on the limitation issue is not sufficient for damage purposes. In addition to the damages flowing from the denial of orders on account of the conspiracy Pioneer would also be entitled to such other damage that it suffered by reason of the loss of accounts, such as Shoppers, that flow from the conspiracy; as well as the refusal of other manufacturers and distributors who may have refused to deal with Pioneer because of the action of Talon and Donahue. Where the impact of the conspiracy is not clearly ascertainable as to time or exactness the trial court may find it fair to apply the principles announced in Delta Theaters v. Paramount Pictures,158 F.Supp. 644(E.D.La.1958), and Schenley Industries, Inc. v. N. J. Wine & Spirit Wholesalers Association,272 F.Supp. 872(D.N.J. 1967), and permit recovery of all damages suffered within the statutory period. Reversed and remanded. FootNotes * Associate Justice Tom C. Clark, United States Supreme Court, retired is sitting by designation. 1. Talon, Inc., is a manufacturer of zippers, and Donahue Sales Corporation is its national sales agent. 2. The New York buyer for J. C. Penney Company or "a member of management" had called Salmon, advising that a communication from Penney's store in Twin Cities had reported that Shoppers City was selling Talon zippers considerably below preprinted retail price. 3. Defendants entered into a consent order with the Federal Trade Commission in 1970, agreeing to "forthwith cease and desist from" the acts and practices alleged in this case. F.T.C. Docket No. C-1713 (March 25, 1970). The conspiracy against Pioneer apparently continued until that date. 4. That Pioneer was on an order to order basis was made clear during the cross-examination of Mr. Rose, the owner of Pioneer; Q. But you had no formal agreement here? A. No. No formal agreement. Q. Where you have no formal agreement you have no formal termination? A. It would follow that, yes.
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Single-shot quantitative phase gradient microscopy using a system of multifunctional metasurfaces | Request PDF Request PDF | Single-shot quantitative phase gradient microscopy using a system of multifunctional metasurfaces | Quantitative phase imaging (QPI) of transparent samples plays an essential role in multiple biomedical applications, and miniaturizing these... | Find, read and cite all the research you need on ResearchGate Single-shot quantitative phase gradient microscopy using a system of multifunctional metasurfaces February 2020 Nature Photonics 14(2) DOI: 10.1038/s41566-019-0536-x Authors: MohammadSadegh Faraji-Dana Show all 5 authors Hide Abstract and Figures Quantitative phase imaging (QPI) of transparent samples plays an essential role in multiple biomedical applications, and miniaturizing these systems will enable their adoption into point-of-care and in vivo applications. Here, we propose a compact quantitative phase gradient microscope (QGPM) based on two dielectric metasurface layers, inspired by a classical differential interference contrast (DIC) microscope. Owing to the multifunctionality and compactness of the dielectric metasurfaces, the QPGM simultaneously captures three DIC images to generate a quantitative phase gradient image in a single shot. The volume of the metasurface optical system is on the order of 1 mm³. Imaging experiments with various phase resolution samples verify the capability to capture quantitative phase gradient data, with phase gradient sensitivity better than 92.3 mrad μm⁻¹ and single-cell resolution. The results showcase the potential of metasurfaces for developing miniaturized QPI systems for label-free cellular imaging and point-of-care devices. Schematic of a metasurface-based QPGM and its operation principle a, Schematic of the QPGM employing two metasurface layers, where the second layer is composed of three separate metasurface lenses. The first metasurface, together with each of the lenses in the second metasurface layer, forms a different image of the object. A polarizer and the polarization-sensitive metasurfaces then result in three interference patterns. b, Illustration of the roles of the two metasurface layers. Metasurface 1 makes two sheared focuses for TE and TM polarizations and splits the field in three different directions towards the three lenses in the second layer. With the polarizer, the three metasurface lenses in layer 2 form three DIC images (I1, I2 and I3) having different phase offsets between the TE and TM polarizations. The combination of the two layers forms the QPGM shown on the right. c, A binary phase sample with unity amplitude used as an example target. d, Set of three DIC images of the phase sample shown in c. e, PGI formed from combining I1, I2 and I3 from d, showing the phase gradient along the y axis. The y axis lies along the shear direction of the system. … Design and fabrication of the metasurfaces a, Schematics of a uniform array of rectangular nanoposts (top) and a single unit cell (bottom), showing the parameter definitions. The rectangular amorphous silicon nanoposts are located on a fused-silica substrate, cladded by an 8-μm-thick SU-8 layer for protection. The transmission phase of the two orthogonal polarizations can be independently controlled using the nanoposts. The amorphous silicon layer is 664 nm thick, and the lattice constant is 380 nm. b, Schematic side views of metasurface layers 1 (left) and 2 (right), showing the gold apertures used to block unwanted diffraction and the external noise. c, Schematic top views of metasurface layers 1 (left) and 2 (right). A magnified view of the array of nanoposts is shown at the centre. d, Optical images of the fabricated metasurfaces. Nine copies of the fabricated metasurface-based QPGM system are shown. e, SEM images of a portion of the fabricated metasurfaces. Scale bars, 2 μm (left) and 1 μm (right). … Imaging experiment with the QPGM based on two separate metasurface layers a, Three DIC images of a 314-nm-thick QPI 1951-USAF resolution target captured by the QPGM. Scale bars, 25 μm. b, The PGI calculated from the DIC images in a. Scale bar, 25 μm. c, The PGIs captured for three parts of the phase targets with thicknesses of 105 nm, 207 nm and 314 nm (left to right), respectively. Scale bars, 15 μm. d, Thicknesses of seven different phase targets calculated by the QPGM, and those measured by AFM. The plotted thicknesses estimated with the QPGM are averaged over 100 arbitrarily chosen points on the sample edges. Error bars represent standard deviations of the estimated values. e, Schematic of a sea urchin cell and its corresponding PGIs. Scale bars, 40 μm. f, Schematic of the miniaturized optical set-up. The microscope consists of the two metasurfaces shown in Fig. 2d, a CMOS image sensor and a linear polarizer attached to the sensor. g, Three DIC images captured by the set-up in f. The 314-nm-thick resolution target used in a is imaged. Scale bars, 50 μm. h, The PGI calculated from the DIC images in g. Scale bar, 50 μm. … Imaging with the doublet QPGM formed from monolithic integration of two metasurface layers on the same substrate a, Schematic of the miniaturized QPGM using the double-sided metasurface from different viewing angles. The two metasurface layers are patterned on the two sides of a 1-mm-thick fused-silica substrate. b, Optical images of bottom (left) and top (right) views of the 8 × 8 array of the doublet QPGM, in addition to enlarged images for portions of the devices. Scale bars, 200 μm c, PGIs captured using the doublet QPGM from the same parts of the resolution target as used in Fig. 3c. Scale bars, 15 μm. d, Thicknesses of seven different parts of the phase target calculated from the PGIs captured by the metasurface QPGM, and those measured by AFM. The plotted thicknesses estimated with the QPGM are averaged over 100 arbitrarily chosen points on the sample edges. Error bars represent standard deviations of the estimated values. … Figures - available from: Nature Photonics This content is subject to copyright. Terms and conditions apply. Articles https:/ / doi.org /10.1038/ s41566-019-0536-x 1 T . J. Watson Laboratory of Applied Ph ysics and Kavli Nanoscience Institute, California Institute of T echnology, Pasadena, CA, USA. 2 Department of Electrical Engineering, California Institute of T echnology, Pasadena, CA, USA. *e-mail: faraon@caltech.edu O ptical phase microscopy techniques hav e been widely investigated for imagin g transparent specimens like cells 1 – 4 . For these weakly scattering samples, ph ase information represents the optical path difference o f lig ht passing through the cell, which is usually directly related to its morpho logical and chemical properties 3 . Moreov er, phase imagin g techniques do not require contrast agen ts and avoid several issues faced in fluores - cence microscopy such as photo bleaching and phototo xicity 5 . Although convention al phase imaging methods such as phase con - trast 1 and differential interference con trast (DIC) microscopy 2 only capture qualitativ e phase information, quan t itative phase imaging (QPI) has been rapidly growing in the past two decades 3 , 4 , 6 . For example, techniques like digital hologra phic microscopy 7 , tomo - graphic QPI 8 , 9 , Fourier ptyc hography 10 and lensless im aging 11 over - come limitations of quali tative phase imaging methods to acquire quantit ative ph ase dat a. Miniaturized microscopes have garnered gr eat interest in recen t decades 12 – 14 because they enable and facilitate in vivo biological imaging in freely moving objects 14 and in portable ap plications. Miniaturized systems have o nly been demonstrated as different forms of ampli tude imaging modules such as single-photon 12 or two-photon 13 fluorescence microscopes. This is ma inly because QPI systems usually require an in terference ‘set-up ’ to retrieve the phase information, and such set-ups n eed complicated and bulky optical systems. This left the miniaturized QPI microscopes that are of interest in va rious fields such as biomedicine 4 out o f reach until now . Dielectric metasurfaces are a category of diffractive optical elements consisting of na noscatterers 15 , 16 that enab le the con - trol of light in subwa velength scales 17 – 22 . In addition, metasur - faces can simultaneously pr ovide multiple distinct functionalities through various schemes such as spatial multi plexing 23 , 24 or more sophisticated designs of the nanoscatt erers 25 , 26 . These capabilities, compactness, low weight and co mpatibility with con ventional nanofabrication pr o cesses have made them suitable can didates for miniaturized optical devices such as miniaturized microscopes 27 , on-chip spectrometers 28 , 29 and endoscopes 30 . In addi tion, verti - cal integration of multi ple metasurfaces has been introduced to achieve enhanced functionalities 31 – 34 . Despite these great advances, applications of m etasurfaces for QPI have not p reviously been explored. Although different types of spa ti al field differentiator , which may be regarded as qualitativ e phase imaging devices, have been proposed, their investigation has been limited to o ptical com - puting and optical signal processing 35 , 36 . Here, we pro pose a miniaturized quantitative pha se gradient microscope (QPGM) inspired by the classical DI C microscope and based on an integrated system of m ultifunctional dielectric meta - surfaces. As we fully exploit the two unique pr operties of metasur - faces, compactness and multifunctionality , via both polarization and spatial multiplexing methods, two metasurface la yers that are cascaded vertically operate as a miniaturized QPGM. W e experi - mentally demonstrate that the millimetre-scale op tical device can capture quan titative phase gradient images (PGI s) f rom phase resolution targets and b iological samples. Results Concept of the metasurface-based QPGM. Figure 1a illustrates the concept of a miniaturized QPGM con sisting of two cascaded metasurface layers. The roles of each lay er are explained visually in Fig. 1b . Metasurface lay er 1 captures two images f or transverse elec- tric (TE) and transverse magnetic (TM) polarizations with focal points that are separat ed along the y axis. In addition, it spli ts the captured light equally int o three separate directions towar ds the three metasurface lenses in layer 2. T o implement this multifunc - tionality , polarization 20 and spatial multi plexing techniques 23 , 24 are employed in the design of metasurface layer 1 (see Su pplementary Note 1 for details). M et asurface layer 2, which is composed of three birefringent off-axis lenses, forms thr ee DIC images with three different phase offsets between the TE and TM polarizations. Effectively , each metasurface of the second layer constitu tes a s epa - rate DIC microscope system with the metasurface lay er 1. With two linear polarizers at the input an d output aligned to 45° and − 45°, Single-shot quantitative phase gr adient microscopy using a system of multifunctional metasurf aces Hyounghan K won 1,2 , Ehsan Arbabi  1,2 , Seyedeh Mahsa Kamali 1,2 , MohammadSadegh Far aji-Dana 1,2 and Andrei Far aon  1, 2 * Quantitative phase imaging (QPI) of transpar ent samples plays an essential role in multiple biomedical applications, and miniaturizing these systems will enable their adoption into point-of-care and invivo applications. Here, w e propose a compact quantitative phase gradient microscope ( QGPM) based on two dielectric metasurface layers, inspired by a classical differential interference contrast (DIC) microscope. Owing to the multifunctionalit y and compactness of the dielectric metasurfaces, the QPGM simultaneously captures three DIC images to generate a quantitativ e phase gradient image in a single shot. The volume of the metasurface optical system is on the order of 1 mm 3 . Imaging experiments with various phase r esolution samples verify the capability to capture quantitative phase gradient data, with phase gradient sensitivit y better than 92.3 mrad μ m − 1 and single-cell resolution. The results showcase the potential of metasurfac es for developing miniaturized QPI systems for label-free cellular imaging and point-of-care devices. NATURE PHO TONICS | VOL 14 | FEBRUARY 2020 | 109–114 | www .nature.com/ naturephotonics 109 Content courtesy of Springer Nature, terms of use apply. Rights reserved ... Conventionally, phase imaging is achieved with rather complex and bulky setups, ranging from Zernike phase-contrast and differential-interference-contrast microscopy to quantitative techniques based on interferometry [1] or non-interferometric methods [3,4]. More recently, newly developed free-space nanophotonics and flat-optics platforms have also been applied to the demonstration of similar phase imaging systems, with the potential advantage of more compact dimensions and enhanced design flexibility [5][6][7][8] [9] [10][11][12]. In this work, we report the development of image sensors that can measure the phase gradient of the incident optical field directly with the simplest possible setup, i.e., a standard camera or microscope without any external optical elements other than the imaging lenses. ... ... As a result, these devices require polarized illumination for maximum detection efficiency. 9 If the metasurface just described is fabricated on the illumination window of an image sensor, the device responsivity can be expected to vary with angles of incidence exactly as in the color map of Fig. 2(c), regardless of the photodetector operating principle. Here, for convenience, we employ a Ge metal-semiconductor-metal (MSM) photoconductor, which simply consists of two Au contacts deposited on the top surface of a Ge substrate. ... Asymmetric metasurface photodetectors for single-shot quantitative phase imaging Preprint Full-text available Jun 2023 Jianing Liu Hao Wang Yuyu Li Roberto Paiella The visualization of pure phase objects by wavefront sensing has important applications ranging from surface profiling to biomedical microscopy, and generally requires bulky and complicated setups involving optical spatial filtering, interferometry, or structured illumination. Here we introduce a new type of image sensors that are uniquely sensitive to the local direction of light propagation, based on standard photodetectors coated with a specially designed plasmonic metasurface that creates an asymmetric dependence of responsivity on angle of incidence around the surface normal. The metasurface design, fabrication, and angle-sensitive operation are demonstrated using a simple photoconductive detector platform. The measurement results, combined with computational imaging calculations, are then used to show that a standard camera or microscope based on these metasurface pixels can directly visualize phase objects without any additional optical elements, with state-of-the-art minimum detectable phase contrasts below 10 mrad. Furthermore, the combination of sensors with equal and opposite angular response on the same pixel array can be used to perform quantitative phase imaging in a single shot, with a customized reconstruction algorithm which is also developed in this work. By virtue of its system miniaturization and measurement simplicity, the phase imaging approach enabled by these devices is particularly significant for applications involving space-constrained and portable setups (such as point-of-care imaging and endoscopy) and measurements involving freely moving objects. ... It obtains information through interferometric phenomena caused by the superposition of waves. This technique is still vigorously used in the field of wavefront measurement [4][5][6] [7] . Bon and coworkers demonstrated that quadriwave lateral shearing interferometry enables precise measurements of the phase shift introduced by live cells in a single imaging process [7]. Kwon et al. achieved quantitative phase gradient imaging based on two dielectric metasurface layers. ... ... This technique is still vigorously used in the field of wavefront measurement [4][5][6][7]. Bon and coworkers demonstrated that quadriwave lateral shearing interferometry enables precise measurements of the phase shift introduced by live cells in a single imaging process [7] . Kwon et al. achieved quantitative phase gradient imaging based on two dielectric metasurface layers. ... One-Dimensional High-Resolution Wavefront Sensor Enabled by Subwavelength Compound Gratings Article Full-text available Apr 2023 Yunlong Meng Xinyu Shen Junyang Xie Cheng Yang Angle sensors are widely used for wavefront measurements, which is attributed to their integration and robustness. Currently, commercial sensors are available with pixel sizes in the order of wavelengths. However, the spatial resolution of angle sensors still lags far behind. Here, we report a one-dimensional, high-resolution wavefront sensor. It was produced by introducing subwavelength compound gratings above the pixels. The gratings involved could be replaced by the sensor’s intrinsic readout circuitry without additional operation. The experimental results showed that it had a spatial resolution of 1.4 µm, two orders of magnitude higher than that of the Shack–Hartmann wavefront sensor. The significant increase in spatial resolution enables angle sensors to reconstruct complex wavefronts accurately. ... Phase contrast imaging can capture only qualitative phase information, while acquiring quantitative phase data is a rapidly growing demand for more sophisticated analysis. Inspired by a classical differential interference contrast microscope (DIC), Andrei Faraon's group proposed a miniaturized quantitative phase gradient microscope (QPGM) based on two dielectric metasurface layers [see Fig. 29(e)] [235] . Combining Fig. 29 Enhanced microscopy imaging. ... ... (d) Spiral metalens for phase contrast imaging [233] . (e) Single-shot quantitative phase gradient microscopy using a system of multifunctional metasurfaces [235] . both polarization and spatial multiplexing methods, the cascaded metasurfaces can simultaneously capture three DIC images to generate a quantitative phase gradient image in a single shot. ... ... The wavefront sensing has great potential for the field of QPI endoscopes due to its simple setup: only a grating is needed before the imaging sensor. With state-of-the-art metasurface gratings reported previously [45, 46], the QPI technique could be made compatible with existing endoscopes, opening up possibilities for auxiliary observation within a highly compact system. This technique can help fluorescent endoscopes, optical coherence tomography endoscopes, and electronic endoscopes for fast labelfree endogenous contrast imaging, diagnosing with quantitative phase information, and tomographic imaging. ... The flexible endoscope is a minimally invasive tool in clinical settings, but most of them only provide qualitative amplitude information and require puncture biopsy or exogenous staining for diagnosis. These limitations restrict their use for rapid investigation. Here, we developed a fiber-bundle-based gradient light interference endoscopic microscopy (FGLIM) in reflection geometry for quantitative phase imaging of unlabeled thick samples. FGLIM provides the phase information by wavefront modulation using chessboard grating and phase-shifting. FGLIM system features high lateral and axial resolutions of 1.2 and 8.3 {\mu}m, respectively, with a probe diameter of 2.5 mm. By testing pathologic slices and thick opaque mammalian tissue ex vivo, FGLIM identifies normal and tumor glandular structures, secreta, and tomographic skin layers. With the potential for direct morphological and phase measurement, high resolution, and thin fiber tip, the label-free FGLIM could be an attractive tool for various clinical applications. ... The capability of arbitrary wavefront manipulation and desirable multifunctionality distinguish metasurfaces in a wide range of applications, such as metalens [19][20][21][22], holograms [23,24], augmented reality [25,26], and analog computing [27][28][29], including spatial differentiation [30][31][32]. In the past several years, metasurface-assisted QPI as well as quantitative phase gradient imaging (QPGI) methods have been demonstrated [33] [34] [35][36]. They provide a comparable space-bandwidth product and phase sensitivity in traditional methods, while largely simplifying the conventional bulky systems by leveraging the compactness and high compatibility of metasurfaces. ... Single-shot quantitative amplitude and phase imaging based on a pair of all-dielectric metasurfaces Quantitative amplitude and phase imaging (QAPI) has been an effective technique to examine label-free biomedical samples. Simple and reliable QAPI techniques realized by replacing conventional bulky optical elements with planar structures will improve the system portability and facilitate in vivo imaging applications. Here, we propose a single-shot QAPI method realized by simply inserting a pair of all-dielectric geometric phase metasurfaces into a traditional microscope. The first metasurface splits a linearly polarized incident beam into two circularly polarized components and the following metasurface deflects the two beams back toward their initial directions. The metasurface pair generates two laterally displaced replicas of the input object, of which the interference forms a retardance image with a bias retardation controlled by an analyzer. The amplitude and phase information of the object is reconstructed from four retardance images simultaneously recorded by a polarized camera. The metasurface pair can be placed near any conjugate plane of the object, which provides a flexible and robust configuration for QAPI, demonstrating its wide usage in live imaging. Differential interference contrast (DIC) microscopy allows high-contrast, low-phototoxicity, and label-free imaging of transparent biological objects, and has been applied in the field of cellular morphology, cell segmentation, particle tracking, optical measurement and others. Commercial DIC microscopy based on Nomarski or Wollaston prism resorts to the interference of two polarized waves with a lateral differential offset (shear) and axial phase shift (bias). However, the shear generated by these prisms is limited to the rectilinear direction, unfortunately resulting in anisotropic contrast imaging. Here we propose an ultracompact metasurface-assisted isotropic DIC (i-DIC) microscopy based on a grand original pattern of radial shear interferometry, that converts the rectilinear shear into rotationally symmetric along radial direction, enabling single-shot isotropic imaging capabilities. The i-DIC presents a complementary fusion of typical meta-optics, traditional microscopes and integrated optical system, and showcases the promising and synergetic advancements in edge detection, particle motion tracking, and label-free cellular imaging. To accurately obtain the phase distribution of an optical surface under test, the accurate phase extraction algorithm is essential. To overcome the phase shift error, a random two-step phase shifting algorithm, which can be used in the fluctuating and non-uniform background intensity and modulation amplitude, Lissajous ellipse fitting, and least squares iterative phase shifting algorithm (LEF&LSI PSA), is proposed; pre-filtering interferograms are not necessary, but they can get relatively accurate phase distribution and unknown phase shift value. The simulation and experiment verify the correctness and feasibility of the LEF & LSI PSA.
https://www.researchgate.net/publication/336866864_Single-shot_quantitative_phase_gradient_microscopy_using_a_system_of_multifunctional_metasurfaces
Prophylactic abdominal drainage for pancreatic surgery - Cheng, Y - 2016 | Cochrane Library Abdomen; Device Removal [adverse effects, mortality]; Drainage [*methods, mortality]; Length of Stay; Pancreas [*surgery]; Postoperative Complications [mortality, *prevention & control]; Randomized Controlled Trials as Topic; Time Factors Prophylactic abdominal drainage for pancreatic surgery Information DOI: https://doi.org/10.1002/14651858.CD010583.pub3 Copy DOI Database: Cochrane Database of Systematic Reviews Version published: 21 October 2016 see what's new Type: Intervention Stage: Review Cochrane Editorial Group: Cochrane Gut Group Copyright: Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Article metrics Altmetric: Authors Yao Cheng Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, China Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China Jie Xia a The Key Laboratory of Molecular Biology on Infectious Diseases, Chongqing Medical University, Chongqing, China Joint first author Mingliang Lai Department of Clinical Laboratory, Jiangjin Central Hospital, Chongqing, China Nansheng Cheng Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, China Sirong He Correspondence to:Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, China hesirong2016@sina.com Contributions of authors Conceiving the review: YC. Designing the review: NC. Co‐ordinating the review: SH. Designing search strategies: YC, NC. Study selection: ML, JX. Data extraction: ML, JX. Writing the review: YC, SH. Providing general advice on the review: NC. Securing funding for the review: SH. Performing previous work that was the foundation of the current study: YC. Sources of support Internal sources Chongqing Medical University, China. Provided funding for the review. External sources No sources of support supplied Declarations of interest YC: none known. JX: none known. ML: none known. NC: none known. SH: none known. Acknowledgements We acknowledge the contribution of authors of previous version of this review: Su Peng, Chen Yang, Jiong Lu, Sijia Wu, and Rongxing Zhou. We acknowledge the help and support of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group. The authors would also like to thank the following editors and peer referees who provided comments to improve the review: Sarah Rhodes (Editor), Adam Berger, Alfretta Vanderheyden, and Paul Moayyedi (Editor), and to Megan Prictor for copy editing the review. The methods section of this review is based on a standard template used by Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group. Version history Published Title Stage Authors Version 2021 Dec 18 Show revisionsProphylactic abdominal drainage for pancreatic surgeryReviewSirong He, Jie Xia, Wei Zhang, Mingliang Lai, Nansheng Cheng, Zuojin Liu, Yao Chenghttps://doi.org/10.1002/14651858.CD010583.pub5 Revision date This is the date when the review was published Event Description2021 Feb 08New citation required and conclusions have changedSearches rerun; three new RCTs with 508 participants identified and included in analyses; review updated accordingly. Conclusions changed for comparison of active drain versus passive drain. Author order changed.2021 Feb 08New search has been performedSearches rerun; three additional trials found 2018 Jun 21 Show revisionsProphylactic abdominal drainage for pancreatic surgeryReviewWei Zhang, Sirong He, Yao Cheng, Jie Xia, Mingliang Lai, Nansheng Cheng, Zuojin Liuhttps://doi.org/10.1002/14651858.CD010583.pub4 Revision date This is the date when the review was published Event Description2017 Nov 15New citation required but conclusions have not changedSearches rerun, one additional trial found2017 Nov 15New search has been performedOne trial added; new evidence incorporated 2016 Oct 21 Show revisionsProphylactic abdominal drainage for pancreatic surgeryReviewYao Cheng, Jie Xia, Mingliang Lai, Nansheng Cheng, Sirong Hehttps://doi.org/10.1002/14651858.CD010583.pub3 Revision date This is the date when the review was published Event Description2016 Aug 28New citation required but conclusions have not changedSearches rerun, two additional trials found2016 Aug 28New search has been performedSearches rerun and new evidence incorporated 2015 Aug 21 Show revisionsProphylactic abdominal drainage for pancreatic surgeryReviewSu Peng, Yao Cheng, Chen Yang, Jiong Lu, Sijia Wu, Rongxing Zhou, Nansheng Chenghttps://doi.org/10.1002/14651858.CD010583.pub2 Revision date This is the date when the review was published Event Description 2013 Jun 12 Show revisionsProphylactic abdominal drainage for pancreatic surgeryProtocolYao Cheng, Chen Yang, Yixin Lin, Jiong Lu, Sijia Wu, Rongxing Zhou, Nansheng Chenghttps://doi.org/10.1002/14651858.CD010583 Revision date This is the date when the review was published Event Description Differences between protocol and review Because overall infectious complications were not reported, we chose a type of infectious complication (intra‐abdominal infection) for the 'Summary of findings' table. Keywords MeSH Medical Subject Headings (MeSH) Keywords Abdomen; Device Removal [adverse effects, mortality]; Drainage [*methods, mortality]; Length of Stay; Pancreas [*surgery]; Postoperative Complications [mortality, *prevention & control]; Randomized Controlled Trials as Topic; Time Factors; Medical Subject Headings Check Words Humans; PICOs PICOs Population Intervention Comparison Outcome The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome. Figures and Tables - Figure 1 Study flow diagram. Figures and Tables - Figure 2 Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies. Figures and Tables - Figure 3 Risk of bias summary: review authors' judgements about each risk of bias item for each included study. Figures and Tables - Analysis 1.1 Comparison 1 Drain use versus no drain use, Outcome 1 Mortality (30 days). Figures and Tables - Analysis 1.2 Comparison 1 Drain use versus no drain use, Outcome 2 Mortality (90 days). Figures and Tables - Analysis 1.3 Comparison 1 Drain use versus no drain use, Outcome 3 Intra‐abdominal infection. Figures and Tables - Analysis 1.4 Comparison 1 Drain use versus no drain use, Outcome 4 Wound infection. Figures and Tables - Analysis 1.5 Comparison 1 Drain use versus no drain use, Outcome 5 Drain‐related complications. Figures and Tables - Analysis 1.6 Comparison 1 Drain use versus no drain use, Outcome 6 Morbidity. Figures and Tables - Analysis 1.7 Comparison 1 Drain use versus no drain use, Outcome 7 Length of hospital stay (days). Figures and Tables - Analysis 1.8 Comparison 1 Drain use versus no drain use, Outcome 8 Additional open procedures for postoperative complications. Figures and Tables - Analysis 1.9 Comparison 1 Drain use versus no drain use, Outcome 9 Additional radiological interventions for postoperative complications. Figures and Tables - Analysis 2.1 Comparison 2 Active drain versus passive drain, Outcome 1 Mortality (30 days). Figures and Tables - Analysis 2.2 Comparison 2 Active drain versus passive drain, Outcome 2 Intra‐abdominal infection. Figures and Tables - Summary of findings for the main comparison. Drain use versus no drain use for pancreatic surgery Drain use versus no drain use for pancreatic surgery Patient or population:people undergoing elective open pancreatic resections Intervention:drain use versus no drain use Outcomes Illustrative comparative risks* (95% CI) Relative effect (95% CI) No of participants (studies) Quality of the evidence (GRADE) Comments Assumed risk Corresponding risk No drain use Drain use Mortality (30 days) Study population RR 0.78(0.31 to 1.99)711(3 studies)⊕⊕⊝⊝ low 1,2,3‐ 34 per 1000 27 per 1000(11 to 68) Moderate 31 per 1000 24 per 1000(10 to 62) Mortality (90 days) Study population RR 0.24(0.05 to 1.1)134(1 study)⊕⊕⊝⊝ low 1,3,4‐ 121 per 1000 29 per 1000(6 to 133) Moderate 121 per 1000 29 per 1000(6 to 133) Intra‐abdominal infection Study population RR 0.89(0.36 to 2.2)711(3 studies)⊕⊝⊝⊝ very low 1,2,3,5‐ 85 per 1000 76 per 1000(31 to 187) Moderate 66 per 1000 59 per 1000(24 to 145) Drain‐related complicationsSee commentSee commentNot estimable179(1 study)⊕⊕⊝⊝ low 1,3,4There was 1 drain‐related complication in the drainage group. The drainage tube was broken. Morbidity Study population RR 1.04(0.93 to 1.16)711(3 studies)⊕⊕⊕⊝ moderate 1,3‐ 620 per 1000 645 per 1000(577 to 720) Moderate 596 per 1000 620 per 1000(554 to 691) Length of hospital stayThe mean length of hospital stay in the no drain group was 13.8 daysThe mean length of hospital stay in the drain groups was 0.66 days lower(1.6 lower to 0.29 higher) MD ‐0.66(‐1.60 to 0.29)711(3 studies)⊕⊕⊕⊝ moderate 1,3‐*The basis for the assumed risk(e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk(and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effectof the intervention (and its 95% CI). CI:confidence interval; MD:mean difference; RR:risk ratio.GRADE Working Group grades of evidence High quality:Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality:Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality:Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality:We are very uncertain about the estimate. 1Downgraded one level for serious risk of bias. 2Downgraded one level for serious imprecision (the confidence interval of risk ratio overlapped 0.75 and 1.25, very few events). 3Publication bias could not be assessed because of the few trials. 4Downgraded one level for serious imprecision (small sample sizes, very few events). 5Downgraded one level for serious heterogeneity. Active drain versus passive drain for pancreatic surgery Patient or population:people undergoing elective open pancreatic resections Intervention:active drain versus passive drain Outcomes Illustrative comparative risks* (95% CI) Relative effect (95% CI) No of participants (studies) Quality of the evidence (GRADE) Comments Assumed risk Corresponding risk Passive drain Active drain Mortality (30 days) Study population RR 2.86(0.12 to 69.06)160(1 study)⊕⊝⊝⊝ very low 1,2,3‐ 0 per 1000 0 per 1000(0 to 0) Moderate 0 per 1000 0 per 1000(0 to 0) Intra‐abdominal infection Study population RR 0.19(0.01 to 3.9)160(1 study)⊕⊝⊝⊝ very low 1,2,3‐ 26 per 1000 5 per 1000(0 to 100) Moderate 26 per 1000 5 per 1000(0 to 101) Morbidity Study population RR 0.68(0.41 to 1.15)160(1 study)⊕⊕⊝⊝ low 1,3,4‐ 321 per 1000 218 per 1000(131 to 369) Moderate 321 per 1000 218 per 1000(132 to 369) Length of hospital stayThe mean length of hospital stay in the passive drain was 14.5 daysThe mean length of hospital stay in the active drain was 1.9 days lower(3.67 to 0.13 lower) MD ‐1.90(‐3.67 to ‐0.13)160(1 study)⊕⊕⊝⊝ low 1,3,5‐*The basis for the assumed risk(e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk(and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effectof the intervention (and its 95% CI). CI:confidence interval; MD:mean difference; RR:risk ratio.GRADE Working Group grades of evidence High quality:Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality:Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality:Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality:We are very uncertain about the estimate. 1Downgraded one level for serious risk of bias. 2Downgraded two levels for very serious imprecision (small sample sizes, very few events, confidence intervals of risk ratios overlapped 0.75 and 1.25). 3Publication bias could not be assessed because of the few trials. 4Downgraded one level for serious imprecision (small sample sizes, very few events). 5Downgraded one level due to serious imprecision (total population size was less than 400). Early versus late drain removal for pancreatic surgery Patient or population:people undergoing elective open pancreatic resections Intervention:early versus late drain removal Outcomes Illustrative comparative risks* (95% CI) Relative effect (95% CI) No of participants (studies) Quality of the evidence (GRADE) Comments Assumed risk Corresponding risk Late drain removal Early drain removal Mortality (30 days)See commentSee commentNot estimable114(1 study)⊕⊕⊝⊝ low 1,2,3There was no mortality in either group. Morbidity Study population RR 0.63(0.43 to 0.93)114(1 study)⊕⊕⊝⊝ low 1,2,3‐ 614 per 1000 387 per 1000(264 to 571) Moderate 614 per 1000 387 per 1000(264 to 571) Length of hospital stay (days)The mean length of hospital stay in the late removal group was 10.8 daysThe mean length of hospital stay in the early removal group was 2.1 days lower(4.17 to 0.03 lower) MD ‐2.10(‐4.17 to ‐0.03)114(1 study)⊕⊕⊝⊝ low 1,2,4‐*The basis for the assumed risk(e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk(and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effectof the intervention (and its 95% CI). CI:confidence interval; MD:mean difference; RR:risk ratio.GRADE Working Group grades of evidence High quality:Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality:Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality:Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality:We are very uncertain about the estimate. 1Downgraded one level due to serious risk of bias. 2Publication bias could not be assessed because of the few trials. 3Downgraded one level for serious imprecision (small sample sizes, very few events). 4Downgraded one level due to serious imprecision (total population size was fewer than 400).
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010583.pub3/information
Salem Church Associates v. New Castle County | Court of Chancery of Delaware | 10-06-2006 | www.anylaw.com Research the case of Salem Church Associates v. New Castle County, from the Court of Chancery of Delaware, 10-06-2006. AnyLaw is the FREE and Friendly legal research service that gives you unlimited access to massive amounts of valuable legal data. Salem Church Associates v. New Castle County MEMORANDUM OPINION Date Submitted: May 16, 2006 I. INTRODUCTION A developer, in 1987, purchased approximately 100 acres of undeveloped property in New Castle County, Delaware from landowners who, thirteen years earlier, had obtained exploratory sketch plan approval for the development of more than 600 residential units. The land remained fallow for many years afterwards. In an attempt to begin again the process of obtaining final approval for the subdivision project, the developer made several unsuccessful attempts to obtain approvals for the two remaining development stages-preliminary plan approval and final record plan approval. The developer was eventually informed by New Castle County (the "County") that the exploratory sketch plan approval given to the developer's predecessors in interest was still in effect and that, if the developer submitted a preliminary plan in compliance with environmental and traffic standards existing as of the exploratory sketch plan's approval, then final record plan approval could be granted. The developer alleges that it relied on the County's assurances and that, while on the cusp of final record plan approval, various County and State of Delaware (the "State") officials conspired to push legislation through the General Assembly that would have the effect of preventing final approval of the subdivision project. Instead of having to comply with environmental and traffic standards in existence at the time its predecessors initiated the subdivision project, the developer must now comply with current standards. The developer seeks injunctive and declaratory relief against both the County and the State to prevent the enforcement and application of the state law to its subdivision project, bringing claims based on a variety of theories-including vested rights, equitable estoppel, due process, equal protection, and unlawful taking. Before the Court are the County and State's motions to dismiss. II. BACKGROUND 1 On May 17, 2001, the Governor signed into law Senate Bill No. 143 ("SB 143"). 2The law amended 9 Del. C. § 2659(c), which, as amended, provides, in part: All subdivision or land development applications heretofore or hereafter filed or submitted to New Castle County that do not receive final approval from New Castle County government within 5 years from the date of application shall be subject to the environmental standards contained in Chapter 40, Articles 5 and 10, of the New Castle County Code, as may be amended, and the traffic impact standards contained in Chapter 40, Articles 5 and 11, of the New Castle County Code, as may be amended. 3 Plaintiff Salem Church (Delaware) Associates ("Salem Church" or "Plaintiff") is a Delaware general partnership owned by Frank E. Acierno ("Acierno"). 4On July 21, 1987, Salem Church acquired approximately 100 acres (the "Parcel") from owners who, in 1974 and following the County's decision to rezone the lands to the category of Diversified Planned Unit Development, had obtained approval of an Exploratory Sketch Plan for a proposed subdivision development of 688 residential units and 25,000 square feet of commercial space. 5 The Parcel became known as "French Park." 6Salem Church's predecessors in interest never obtained any further approvals for French Park's development. 7 Following its purchase of the Parcel, Salem Church made several unsuccessful attempts to obtain additional development approvals. 8According to the Amended Complaint (the "Complaint"), one of these attempts was made on July 1, 1999, when Salem Church formally requested recordation of the Record Major Subdivision Plan that it had submitted on September 21, 1988, after what it thought was approval of its Preliminary Plan on December 2, 1987. 9In response, the County informed Salem Church in a July 14, 1999 opinion letter (the "County Opinion Letter") that it had never obtained Preliminary Plan approval and had never properly submitted a Record Major Subdivision Plan. 10Significantly, the County also informed Salem Church that the original Exploratory Sketch Plan submitted in 1974 was still active and that, after submission of a revised Preliminary Plan conforming to the rules and regulations existing as of the Exploratory Sketch Plan's submission in 1974, Final Record Plan approval for French Park could then be granted. 11Salem Church was then advised that the County's Department of Land Use's (the "Department") decision was final and could be appealed to the County's Planning Board within twenty days. 12 Later in 1999, Salem Church received additional direction by the County to proceed with submission of its Preliminary Plan, and, on or around June 14, 2000, an application and Preliminary Plan were submitted for the County's approval. 13 The submission was based on the original Exploratory Sketch Plan's proposed number of residential units, although it did not call for any commercial development. 14After Salem Church's submission, a revised preliminary plan review comment letter was sent to Salem Church on March 28, 2001. That letter, according to Salem Church, granted Preliminary Plan approval for the French Park project and authorized the filing of a final record plan if certain technical requirements were satisfied. 15 Salem Church alleges that, by the time SB 143 was enacted, it had already acquired a vested right to the specific French Park plan. 20Central to Salem Church's claims is its allegation that County and State officials acted "in bad faith, with an intent and motive to deny Salem Church its property rights and to carry out a political and personal vendetta against Acierno." 21Specifically, the Complaint alleges that "[t]he County enlisted the assistance of State officials because the County knew it could not legally change the rules for French Park since the County Code and the County Opinion Letter had already 'grandfathered' French Park." 22 Salem Church states in its Complaint that SB 143 was "designed specifically to decimate the Preliminary Plan" 23and was the product of a "conspiracy" among a small number of political allies, some of whom had an "extreme personal dislike of Acierno." 24 As Salem Church saw it, "SB 143 did not have any effect on the previously approved Preliminary Plan." 25Therefore, on January 20, 2003, Salem Church's counsel requested that the County complete its review of the final record plan for French Park. 26On February 24, 2003, the County responded that it was the final decision of the Department that such a review would not be completed and that, should Salem Church wish to continue with the French Park plan, it would have to submit a revised exploratory sketch plan in conformity with current environmental and traffic impact standards. 27On March 12, 2003, Salem Church appealed to the Planning Board to reverse the Department's final decision. 28On March 20, 2003, the County informed Salem Church that the Department's decision, set forth in the McCombs Letter on May 30, 2001, was final and that its appeal was time-barred for not having been filed within twenty days of the McCombs Letter. 29 Relying upon representations the County made in the County Opinion Letter (that final record plan approval for French Park would be given if Salem Church submitted a revised Preliminary Plan conforming to County Code provisions that existed in 1974), Salem Church incurred substantial engineering, legal, and governmental application fees. At bottom, Salem Church alleges that, but for the enactment of SB 143, final record plan approval for French Park was a virtual certainty. 30 III. CONTENTIONS Confronted with the choice of abandoning its plans for French Park or bringing them into compliance with existing environmental and traffic standards, Salem Church has petitioned this Court to estop equitably and permanently enjoin the County and the State (collectively, the "Defendants") from enforcing SB 143 against the French Park plan. Salem Church also seeks a declaratory judgment to the same effect. Salem Church brings claims based on the vested rights and equitable estoppel doctrines, and has also raised several discrete constitutional claims based on procedural and substantive due process, equal protection, and unlawful governmental takings. Salem Church also seeks a declaratory judgment to the effect that SB 143 did not affect its right to move forward with the approval process for the Exploratory Sketch Plan from 1974. The Defendants have moved to dismiss this action on two grounds: (1) the claims set forth in the Complaint are not ripe; and (2) the Complaint fails to state claims for which relief may be granted, justifying its dismissal as a matter of law. With respect to Salem Church's constitutional claims and its request that the Court construe SB 143 in its favor, the Defendants argue that they are not ripe because Salem Church has failed to exhaust available administrative remedies. As to all claims, the Defendants also argue that Salem Church's allegations, as set forth in the Complaint, cannot be read to sustain such causes of action. IV. ANALYSIS As noted, the Defendants have moved to dismiss the Complaint under Court of Chancery Rule 12(b)(1) on ripeness and exhaustion grounds and under Court of Chancery Rule 12(b)(6), for Salem Church's failure to state claims upon which relief can be granted. A. Motion to Dismiss Under Court of Chancery Rule 12(b)(1) Both the County and the State have moved, pursuant to Court of Chancery Rule 12(b)(1), that the Court dismiss Salem Church's claims as barred by the ripeness doctrine. 31"Ripeness, the simple question of whether a suit has been brought at the correct time, goes to the very heart of whether a court has subject matter jurisdiction." 32A chief purpose of the ripeness doctrine is the conservation of judicial resources. 33Closely related to the ripeness doctrine, the doctrine of exhaustion often serves as a precondition for a finding of ripeness. 34That doctrine provides that "where a remedy before an administrative agency is provided, relief must be sought by exhausting this remedy before the courts will either review any action by the agency or provide an independent remedy." 35The Defendants contend that Salem Church could have, and, thus, should have, appealed to the County Planning Board the Department's determination that SB 143 precludes further processing of its original French Park application. The exhaustion of administrative remedies is not a jurisdictional or an absolute requirement; it is a judicially created doctrine, which courts exercise discretionally. 36Levinson v. Delaware Compensation Rating Bureau, Inc. 37teaches that Delaware law strongly favors exhaustion of administrative remedies before seeking judicial intervention. 38The oft-cited policy rationale for the doctrine's application "is one of maintaining the proper relationship between the courts and administrative agencies." 39In other words, the doctrine seeks to relieve courts from having to interfere with an administrative body's "sifting process" when issues have yet to run their course and when an administrative body might resolve the dispute without unnecessary or premature judicial action. 40 1. Exhaustion with Respect to Salem Church's Vested Rights and Due Process Claims For the exhaustion doctrine to be applicable in this case, Salem Church must first have had an available administrative remedy before it challenged the County's interpretation and application of SB 143 in this forum. Section 40.31.510 of the County's Unified Development Code provides that an applicant may appeal within twenty days an adverse decision pertaining to its application to the agency or board conferred with jurisdiction to hear the appeal. 41Table 40.30.110 expressly provides the County Planning Board with jurisdiction to hear appeals with respect to major subdivision review decisions. 42 On May 30, 2001, Salem Church was informed, by way of the McCombs Letter, that, because of SB 143's enactment, French Park's Preliminary Plan approval had been rescinded and that the French Park application had become subject to the then-current environmental and traffic requirements set forth in Articles 10 and 11 in the Unified Development Code. Salem Church did not timely appeal McComb's determination to the Planning Board. The County cites this failure as precluding Salem Church from bringing forth its claims here and argues that courts uniformly recognize that claims such as those asserted by Salem Church cannot be ripe until the agency makes a final decision as to how it will apply the statute or regulations at issue to the land in question. 43Salem Church, however, has cited several grounds why an appeal to the Planning Board was unnecessary, notably that: the Planning Board lacked authority under the Delaware Code to hear administrative appeals concerning subdivision plans; no appeal was required under County Code § 40.31.510; and, under the Eastern Shore decision, an appeal to the Planning Board was unnecessary because it is vested only with jurisdiction to consider appeals of decisions based on County Code provisions, not constitutional claims. As an initial matter, the Planning Board did have the authority to consider an appeal of the Department's decision and that-absent other considerations-is the proper starting point for a party wishing to challenge a decision by the County during the major subdivision review process. 44 The question in this case centers not on whether the Planning Board could have found an action by the State, enactment of SB 143, unconstitutional-it could not have-but on whether the Planning Board could have arrived at a determination that SB 143 did not apply to French Park. Or, as the County puts it, if Salem Church "took an appeal to the Planning Board regarding the Department's subdivision interpretation, the Planning Board might have agreed with [Salem Church's] arguments and might have reversed the decision." 45 Because the exhaustion doctrine is one of discretion, the strong presumption favoring exhaustion may be overcome by a showing that the interest of justice so requires. 46One circumstance where courts may refrain from requiring exhaustion is if administrative review would be futile. 47The burden of showing that an administrative review would be futile is, necessarily, a high one, 48and Delaware courts have often rejected futility arguments. 49For the reasons that follow, the Court concludes that the unique facts permit a finding that an appeal to the Planning Board would have been objectively futile. Thus, Salem Church's claims, other than its takings claim, cannot be dismissed under the doctrines of ripeness or exhaustion of administrative remedies. Determining futility, in this instance, starts with the language of the statute. The parties accept the well-settled principle that, in construing a statute, the plain meaning of the words chosen by the General Assembly controls. 50The parties, however, do not agree on the plain meaning of SB 143. Salem Church argues that SB 143's emphasis is on "applications," not "plans," and that this means the French Park plan remained unaffected because Salem Church filed its "application" on June 14, 2000, not in 1974. The application to which Salem Church refers is the "SLD-1 Form (Application for Plan Review)," that Salem Church filed as part of its revised preliminary plan review. 51The effect of Salem Church's interpretation is that it would not have had to comply with current environmental and traffic standards so long as it received final record plan approval by June 14, 2005, five years after applying for Preliminary Plan approval. The County counters by pointing out that an application has three distinct parts- exploratory, preliminary, and final record plan-and that "[u]nless all three stages are completed, there is no 'subdivision' of land, the application is not completed, and there is no final approval." 52 The exploratory plan for French Park was submitted by Salem Church's predecessors in interest in 1974. 53Salem Church was informed in the County's Opinion Letter in 1999 that the 1974 exploratory plan was still in effect and that what was next required was a preliminary plan, which Salem Church filed on June 14, 2000 in accordance with standards existing at the time the exploratory plan was approved in 1974. Based on that sequence of facts as pleaded, the SLD-1 Form that Salem Church filed in 2000 (in conjunction with its revised preliminary plan) was one of three component parts to a subdivision application. Salem Church's reading of SB 143 to allow that the five-year time frame to start anew whenever approval is sought for any of the separate steps in the subdivision or land development process would contravene the language and purpose of SB 143, as expressed by the General Assembly. SB 143 is not ambiguous-it provides that all unapproved subdivision applications "heretofore or hereafter" that have not received final approval from the County within five years from the date of application must comply with current County environmental and traffic impact standards. It is undisputed that, when SB 143 was enacted on May 17, 2001, Salem Church had yet to receive final record plan approval and the application for French Park had been filed decades earlier. 54With these facts, the Planning Board could not have read SB 143 as not applicable to the French Park plan; thus, an appeal by Salem Church seeking an alternative interpretation would have been futile. Salem Church also claims that 9 Del. C. § 2659(c), as amended by SB 143, has no effect over the French Park plan because of § 2659(b), 55which provides that "[n]othing in this subchapter shall serve to invalidate any comprehensive plan, land development regulation, land use, development, development order or development permit which presently exists or which hereafter validly comes into existence prior to the date when full compliance with this subchapter is required." 56 The shortcoming of Salem Church's argument is that it has not held (and has never held) any of the approvals itemized in Section 2659(b). For example, the "development permit" to which Section 2659(b) refers is defined to include "any building permit, zoning permit, subdivision approval, rezoning, certificate of occupancy, special exception, variance or any other official action of local government having the effect of permitting the development of land." 57Salem Church never received "subdivision approval" and was never the beneficiary of "any other official action of local government having the effect of permitting [the Parcel's] development . . . ." In short, the focus of Section 2659(b) is to avoid invalidating specific final approvals, including final subdivision approvals. With respect to its efforts to obtain approval to develop French Park, Salem Church had achieved nothing more than satisfying certain interim, discrete stage requirements. In short, 9 Del. C. § 2659(b) affords no protection to Salem Church because Salem Church had nothing to protect within its scope. Moreover, the legislative history reveals that SB 143 was intended to apply to subdivision applications for projects, such as French Park, that did not obtain final record plan approval within five years of application. On May 3, 2001, one of the sponsors of the legislation stated on the Senate floor: Senate Bill 143 applies only to New Castle County and it basically allows for a sunsetting provision on land use that the applications have not been completed within five years. It allows for environmental and traffic consideration to take place when the plans have not been approved within that time frame. There are approximately four areas currently in New Castle County that this would apply to. It would also apply forward in setting a five-year limit on any new plans that would apply. One of these has been publicized very recently in the paper, and you know, unfortunately, if you have some plans that are filed 30 years ago and never acted on and then 30 years later, you come down the road, the environmental impact on our land and our citizens has changed considerably, and so has the traffic in the area. 58 On May 10, 2001, another sponsor of the legislation, stated on the House floor that: . . . in a nutshell, what this legislation would do would provide the subdivision or land development applications that do not receive final approval within five years of the date of application-they will be subject to the new constraints under the Unified Development Code adopted several years ago in New Castle County. 59 As he further explained: I am faced, along with [other legislators serving districts in the area of French Park] with an impending situation in the Route 40 corridor area where a subdivision plan that was filed in 1974 and has laid fallow for 30 years is about to proceed and result in 688 apartments and townhouses being constructed in an area that is . . . environmentally sensitive, in an area that where infrastructure cannot support that type of growth, in an area where dynamics have completely changed in that 30 years. 60 Finally, the General Manager of the County's Department of Land Use stated on the House floor that "[SB 143] only applies to applications, not to recorded plans. Once that plan is recorded, it goes on." 61The legislative history could not be clearer, given the statements made when SB 143 was before the General Assembly, that SB 143 was intended to apply to the French Park plan which had not yet been fully approved. In sum, the County's Planning Board simply could not have arrived at a different interpretation as to how the Parcel would be affected; any appeal by Salem Church would have been a futile one. 62 2. Exhaustion with Respect to Salem Church's Takings Claim Salem Church also brings a takings claim. 63Section 40.31.600 of the County's Uniform Development Code expressly requires that "[a] landowner who has been denied all or substantially all economically viable use of property through the application of [County law] may apply for relief after exhausting all other available avenues of appeal to a County body." 64Salem Church has not alleged that it brought a beneficial use appeal, as provided for by § 40.31.600. Indeed, it argues that it was not required to seek such a determination before bringing its claim. The Court concludes otherwise. As noted by the United States Supreme Court: a landowner may not establish a taking before a land-use authority has the opportunity, using its own reasonable procedures, to decide and explain the reach of a challenged regulation. Under our ripeness rules a takings claim based on a law or regulation which is alleged to go too far in burdening property depends upon the landowner's first having followed reasonable and necessary steps to allow regulatory agencies to exercise their full discretion in considering development plans for the property, including the opportunity to grant any variances or waivers allowed by law. 65 The County, thus, could and did require a landowner, such as Salem Church, to seek a beneficial use review before asserting a takings claim. Accordingly, exhaustion of the remedy afforded by § 40.31.600 of the Unified Development Code was a necessary precursor to the filing of a takings claim and Salem Church's takings claim against the County, therefore, must be dismissed. 66 B. Motion to Dismiss Under Court of Chancery Rule 12(b)(6) A motion to dismiss under Court of Chancery Rule 12(b)(6), requires the Court to accept the well-pleaded facts alleged in the complaint and to view those facts, and all reasonable inferences that may be drawn from them, in the light most favorable to the plaintiff. 67The Court need not, however, accept as true conclusory allegations that are unsupported by facts contained in the complaint. Also, the Court may consider documents integral to the complaint and incorporated by reference therein. 68Although the Court "is not required to accept every strained interpretation of the allegations proposed by the plaintiff," 69it may dismiss a claim only when it appears "with reasonable certainty that there is no set of facts which would entitle the plaintiff to relief." 70 1. Vested Rights and Equitable Estoppel Salem Church invokes the vested rights doctrine, as well as the equitable estoppel doctrine, in its effort to prevent SB 143 from precluding final record plan approval for its French Park plan. 71These doctrines, despite having distinct theoretical foundations, frequently overlap. 72 a. Vested Rights According to Salem Church, by the time SB 143 was enacted, it had already obtained vested rights in its French Park plan. 73The inquiry in determining whether one has a vested right claim is prescribed in In re 244 Acres of Land v. Delaware Agricultural Lands Foundation. 74Rejecting the perceived rigidity of the "permit plus" approach that Delaware courts had relied upon since Shellburne, Inc. v. Roberts, 75the Delaware Supreme Court concluded that a new test was needed to consider more fairly "the complexity of present day real estate development." 76As the Court explained: [T]he test should involve 'a weighing of such factors as the nature, extent and degree of the public interest to be served by the ordinance amendment on the one hand and, on the other hand, the nature, extent and degree of the developer's reliance on the state of the ordinance under which he has proceeded . . . .' 77 And "[in] the final analysis," the Delaware Supreme Court concluded that "good faith reliance on existing standards is the test." 78 In In re 244.5 Acres, the owner of a residential development challenged a fifty-foot setback requirement for any "new subdivision development" adjacent to agricultural preservation districts. Immediately after purchasing its property in May 1996, the developer incurred substantial engineering and consulting expenditures to develop its project. Shortly after incurring these costs and receiving conditional approval from the Dover Planning Commission, an owner of adjacent property filed an application to create an agricultural preservation district. That application received final approval and was recorded in February 1998 (and, thus, the fifty-foot setback became applicable), four months before the developer received its final approval from the municipal authority. The developer brought suit, seeking, among other things, a declaratory judgment that the fifty-foot setback requirement did not apply to its property. The Superior Court found that the developer did not have a vested right because it lacked building permits when the preservation district was created and, thus, was a "new subdivision" subject to the setback requirement. The Delaware Supreme Court reversed, adopting a new formulation of the vested rights test and concluding that the developer's project could "hardly be characterized as a 'new subdivision'" when it had engaged in "extensive efforts" to secure all necessary approvals. The vested rights analysis requires a balancing of interests-the public interest served by a particular law's enforcement and the private interests of a plaintiff who has relied on the state of the law at the time it acted. 79In assessing a regulation's public benefit or purpose, Delaware courts have been willing to conclude that certain legislative enactments served a negligible public interest or were passed without any public purpose at all. For example, in Wilmington Materials, Inc. v. Town of Middletown, 80this Court, noting the inequity that would result if it permitted retroactive application of a municipality's last minute zoning amendment to prohibit concrete pipe plants, observed: The Zoning Code amendment was not adopted out of "police power" considerations, i.e., policy concerns for the health, safety or general or moral welfare of the community. Those broad issues had already been resolved when the Code was adopted in January, 1987, only 23 months before, after an extensive study and hearing process. Rather, the purpose for the zoning amendment, was to prevent a lawful use of the land by [the plaintiff], motivated by a vocal protest movement that included a petition signed by many objecting citizens. 81 In In re 244.5 Acres, the Supreme Court found the public interest served by enforcement of the fifty-foot setback requirement "[was] minimal since the setback [was] not intended to preclude all development and the farmland activities sought to be promoted [were] already in place." 82The public interest served by SB 143's enactment, however, is far from minimal. Section 2659(c), as amended by SB 143, requires that all new subdivision and land development applications more than five years old comply with current environmental and traffic impact standards as set forth in Chapter 40, Articles 5, 10, and 11 of the New Castle County Code. 83The environmental standards of Articles 5 and 10 affect substantial concerns, such as floodplains, riparian buffers, wetlands, critical natural areas, air quality, sewers, recharge areas, drainageways, and spillage from above ground storage; 84the traffic impact standards established in Articles 5 and 11 involve impact studies and traffic mitigation measures that help "ensure that development occurs only where there are adequate transportation facilities in place, or programmed for construction." 85A review of the legislative history of SB 143 reveals that there was a strong public interest in addressing the impact of development on environmental and traffic conditions. When SB 143 was being considered before the General Assembly, several legislators cited concerns about the "miserable" state of traffic intersections and the potential for new development to exacerbate traffic congestion, 86the need to curb development in "critical natural area[s]" because of downstream flooding, 87and the need to balance growth with protection of the environment. 88Even if, as the Complaint asserts, certain individual members of the General Assembly also had other motivations, this Court will not engage in an inquiry into individual motivations when the legislative history demonstrates that SB 143 was grounded in such strong public interest concerns. 89 Consideration of Salem Church's private reliance interest is also necessary.Salem Church alleges that it has expended more than $133,000 in engineering and government application fees. 90The County disputes this calculation and asserts that, in any event, it is a "paltry sum when compared with the overall cost of the French Park project." 91Salem Church also alleges that it relied on statements by County officials, particularly the County's Opinion Letter in 1999 that final record plan approval could be received. 92In specific, the County Opinion Letter stated that Salem Church could submit a revised Preliminary Plan conforming "to the rules and regulations existing as of August 27, 1974." 93 In balancing the public and private interests, the Court is reminded of the Delaware Supreme Court's declaration in In re 244.5 Acres: "[i]n the final analysis, good faith reliance on existing standards is the test." 94Given this stage of the proceedings, the Court cannot conclude that Salem Church's private interests are outweighed by the public interests behind SB 143, particularly when Salem Church alleges that, in reliance on the County's Opinion Letter, it expended considerable resources, paid various fees, obtained substantial mortgage financing, and submitted a revised Preliminary Plan. When that plan was approved on March 28, 2001, Salem Church was both informed that several other items needed to be addressed before it could receive record plan approval and warned that the Preliminary Plan would be considered expired "[i]f a complete Record Plan submission [was] not made within eighteen (18) months of [March 28, 2001]." 95 Most of the outstanding items, Salem Church alleges, were filed by May 15, 2001. Just two days later, however, SB 143 was signed into law. 96 For these reasons, the Court concludes that Salem Church has sufficiently pleaded facts that would indicate that it relied in good faith on the County's statements of July 14, 1999 and March 28, 2001, and that its vested rights claim does not fail as a matter of law. In addition to challenging the sufficiency of Salem Church's vested rights allegation, the Defendants also argue that its vested rights claim fails because of the passage of time. In contrast to In re 244.5 Acres, where the developer acted expeditiously, Salem Church and its predecessors have dawdled. This case, thus, in addition to the balancing of public and private developer interests, requires assessment of the effect of the pace of the development effort. After providing a chronological account of the principal efforts taken by the developer in In re 244.5 Acres, the Delaware Supreme Court observed, "There is no indication, however, that the [developer] delayed its efforts to secure all approvals necessary to begin construction." 97Thus, delay may defeat a vested rights claim. Securing approval of a subdivision in New Castle County involves, for current purposes, the submission and approval of three items: an exploratory plan, a preliminary plan, and a final record plan. In 1987, Salem Church purchased the Parcel, which had already been the subject of a proposed residential subdivision development. Thirteen years earlier, in 1974, the previous owners had obtained approval of an exploratory sketch plan for French Park. In its Complaint, Salem Church has acknowledged that no other approvals for French Park were obtained between 1987 and 1997. In early May 1999, Salem Church "once again began the process of seeking final subdivision plan approval for French Park." 98After meeting with County planning staff, Salem Church was informed in the County Opinion Letter of July 14, 1999 that the exploratory plan of 1974 was still in effect, that French Park had yet to receive preliminary and record plan approvals, and that Salem Church could proceed by submitting a revised preliminary plan that conformed to rules and regulations existing as of 1974. Salem Church was subsequently advised on October 15, 1999 to "proceed ahead with the preliminary plan" and to "start as soon as [it could] so there are no problems." 99On June 14, 2000, Salem Church submitted its revised preliminary plan. Salem Church argues that the County's Opinion Letter in 1999 and its filing in 2000 serve as the pertinent reference points in judging whether there was unreasonable delay. The Defendants' view is that the reference point is much earlier; that Salem Church's situation is in stark contrast to the developer's in In re 244.5 Acres, where all necessary approvals had been secured within a two-year period. 100The Defendants, thus, argue that, under the new vested rights test articulated in In re 244.5 Acres, Salem Church's vested rights claim is time-barred. The short answer to the timeliness debate is that, at this stage of the proceedings, Salem Church enjoys the benefit of all favorable inferences. Determination of whether Salem Church unreasonably delayed in securing necessary approvals (and thereby lost any rights that may have previously been obtained) requires a more fact-intensive inquiry and cannot be resolved on a motion to dismiss. 101 b. Equitable Estoppel Salem Church also contends that the Defendants should be equitably estopped from applying SB 143 to the Preliminary and Final Record Plans for French Park. 102The County Opinion Letter of July 14, 1999, in which the County indicated that Salem Church could submit a revised preliminary plan, serves as the pertinent reference point for Salem Church's alleged reliance and its estoppel claim. Equitable estoppel arises "when a party by his conduct intentionally or unintentionally leads another, in reliance upon that conduct, to change position to his detriment." 103To establish estoppel, Salem Church must demonstrate by clear and convincing evidence that: (1) it lacked knowledge or the means of discovering the truth of the facts in question, (2) it reasonably relied on the conduct of the parties-the State and the County-against whom estoppel is being asserted, and (3) suffered a prejudicial change in position in reliance on the conduct. 104In the context of land development, Delaware courts have also recognized equitable estoppel claims where (1) a party, acting in good faith, upon some act or omission of the government, and (2) makes a substantial change of position or incurs extensive obligations and expenses, and (3) it would be highly inequitable or unjust to impair or destroy rights that the landowner has acquired. 105 Application of the doctrine of equitable estoppel to governmental actions is rare. 106Generally, courts will not depart from their traditional cautiousness in applying the doctrine "unless there are exceptional circumstances which make it highly inequitable or oppressive to enforce the regulations." 107 The Court, for the limited purpose of evaluating Salem Church's equitable estoppel claim, assumes that, but for enactment of SB 143, the County, perhaps as a result of the County Opinion Letter or the March 28, 2001 "approval," would have been precluded from relying upon the passage of time to reject the French Park plans. 108There is, however, no basis for equitable estoppel against the State because the State did nothing upon which Salem Church relied. In the absence of conduct upon which there has been reliance, the elements of equitable estoppel cannot be satisfied. 109Moreover, because the subsequently enacted state law required certain conduct by the County-in this instance, rejection of the French Park application-the County could not have avoided its obligation to comply with State law by asserting that it promised some permit to Salem Church or, more specifically, that it is otherwise estopped from abiding by state law. It is fundamental that municipalities must act in accordance with state law. 110In sum, Salem Church has alleged no basis for an equitable estoppel claim against the State and, because of the supremacy of state law, it has no equitable estoppel claim against the County either. 111 2. Due Process Claims a. Substantive Due Process Salem Church alleges that the Defendants engaged in a scheme to prevent French Park from achieving final approval, with the passage and application of SB 143, thereby depriving Salem Church of substantive due process. 112 Salem Church supports its substantive due process claims 113with allegations that the County's actions were in bad faith and "of such an extreme and egregious nature that they 'shock the conscience.'" 114In particular, Salem Church cites the personal animus toward Acierno by "[o]ne of the chief County proponents of [SB 143]," the New Castle County Executive. 115Even in the "plaintiff-friendly" context of a motion to dismiss, Salem Church has not alleged facts that would support its substantive due process claim against the County. Courts have generally held that even if a municipality is guided by political motivations, unrelated to an application, that is not enough to "shock the conscience" under a substantive due process analysis, particularly where the municipality, as the County here, can justify its actions as related to some legitimate goal. 116 Furthermore, it was the General Assembly, not the County, that passed SB 143 and thereafter the County necessarily was under the obligation to follow State law and apply 9 Del. C. §2659(c). 117For these reasons, Salem Church has not stated a substantive due process claim against the County. Second, with respect to the State, Salem Church has failed to state a substantive due process claim because the Complaint is bereft of facts which would support a conclusion that the State lacked a rational basis in enacting SB 143. The inquiry into whether a certain statute complies with substantive due process notions centers on finding some rational relationship to a legitimate government interest. 118As the Delaware Supreme Court recognized, "[w]ithin these limits, the court will not assume to disturb the legislative action. . . . With the policy or wisdom of the act [being of] no concern." 119The consequence is that there is a "strong presumption of validity and those attacking the rationality of the legislative classification have the burden to negate every conceivable basis which might support it." 120 SB 143 amended the state statutes through which the County has been delegated land use authority in order to assure compliance with current environmental and traffic standards-standards that applied to all unapproved subdivision applications older than five years and not solely to Salem Church's; standards closely related to the public health and welfare. Statutes of this nature have been accorded considerable deference by the courts as being within the purview of the State's police powers. 121Therefore, as a matter of law, the State's enactment of SB 143 cannot serve as a basis for Salem Church's substantive due process claim when the State was acting within its legitimate police powers. Furthermore, Salem Church's allegations of conspiracy and bad faith legislative efforts-colorful as they are-are immaterial. As Salem Church's briefing explains, "The [General Assembly's] transcript of debate regarding SB 143 clearly establishes that the specific focus of the legislation was to stop and kill French Park's final approval . . . ." 122The Court, however, may take note of other portions of the transcripts. 123What is evident from these transcripts is that legislators, in addition to recognizing that properties other than French Park would also be affected by the legislation, noted concerns about environmental effects and traffic congestion and the need to update standards that were more than two decades old. 124Such expressions of legislative intent are more than sufficient to satisfy the substantive due process requirement that legislation bear a rational relationship to a legitimate government interest. 125 Specifically, Salem Church's Complaint alleges that State and County elected officials had the "intent and motive" to prevent final record plan approval for French Park by passing SB 143. 126Allegations of sheer political motives driving passage of SB 143, however, are insufficient as a matter of law to prove affirmative misconduct. 127The Court need not inquire into the motives of individual legislators in passing an act of the General Assembly, let alone one that has passed overwhelmingly. The General Assembly, acting within its authority, retains "full and unrestrained authority to exercise its discretion in any manner it seeks fit in its wisdom or even folly to adopt." 128Accordingly, Salem Church's substantive due process claim against the State fails. b. Procedural Due Process The Court now turns to whether Salem Church has sufficiently alleged facts to plead a procedural due process violation under Article I, §§ 7 and 9 of the Delaware Constitution. 129A procedural due process claim requires proof that there was some protected property interest and that deprivation of that protected interest occurred without notice and opportunity to be heard meaningfully. 130 First, Salem Church alleges that, at the time SB 143 was enacted, it had already acquired a vested right in the French Park plan. 131For purposes of deciding whether Salem Church has adequately pleaded a procedural due process claim, the Court may assume, without deciding, that Salem Church had reached a point in which it had an actual property interest. 132 Second, Salem Church alleges that it was denied "advance notice or opportunity to be heard in order to contest the interpretation of SB 143 . . . and [that] no post-deprivation administrative appeal . . . was available." 133Salem Church has not sufficiently alleged that it was denied notice or an opportunity to challenge the County's decision in the McCombs Letter to rescind Preliminary Plan approval of French Park. County Code § 40.31.510 expressly provided an appeal right-a right that Salem Church chose not to exercise timely. Additionally, with respect to the State's actions, Salem Church's allegation that it was not properly given notice or a pre-deprivation hearing is without merit. In passing SB 143, the General Assembly was, not surprisingly, acting in a legislative capacity. Legislative acts, though, cannot form the basis for a procedural due process claim. 134In Bi-Metallic Investment Co. v. State Board of Equalization of Colorado, 135Justice Holmes explained: Where a rule of conduct applies to more than a few people, it is impracticable that every one should have a direct voice in its adoption . . . [g]eneral statutes within the state power are passed that affect the person or property of individuals, sometimes to the point of ruin, without giving them a chance to be heard." 136 In addition, SB 143 did not target only French Park. It was general in nature, applying to "[a]ll subdivision or land development applications heretofore or hereafter" filed that have failed to receive final approval within five years from the date of application. 137In short, Salem Church was entitled to no more notice or opportunity to be heard than anyone else. Accordingly, the Complaint fails to state a claim with respect to procedural due process and cannot withstand Defendants' motion to dismiss. 3. Equal Protection Claim Salem Church also brings forth an equal protection claim against the State for its "intentional decision to single out the French Park plan for elimination based upon a bad faith desire to advance officials' political interests and harm Acierno." 138The basis for this claim is a "class of one" theory, in which a plaintiff asserts intentionally different treatment from others similarly situated and a lack of a rational basis for that different treatment. 139In Rogin v. Bensalem Township, 140the Third Circuit noted that, in bringing an equal protection claim based on the passage and application of various zoning amendments, a plaintiff would have to show that the amendments "so lack[ed] rationality that they constitute[d] a constitutionally impermissible denial of equal protection." 141Although SB 143 concerned subdivision and land development applications, and not zoning, the Court would similarly require of Salem Church that, in alleging an equal protection violation by SB 143's passage and subsequent application, it plead facts sufficient to show that SB 143 lacked any rational basis. Salem Church has not done so. As explained earlier, in passing SB 143, members of the General Assembly legitimately could have plausibly, rationally, and reasonably based their decision on both existing and emerging environmental and traffic concerns of constituents, and the need to require older subdivision plans that had yet to receive final record plan approval to comply with current standards. 142The rational basis review which the Court undertakes does not require (or allow) it "to judge the wisdom, fairness, or logic of legislative choices." 143Salem Church appears to be inviting the Court do exactly that. Furthermore, it is difficult to discern how Salem Church could sustain an equal protection claim when it was hardly in a class of its own. SB 143, by its terms, applied to "all" subdivision plans that had been unapproved for more than five years and, as the transcript of the General Assembly's debate reveals, legislators were aware that properties other than French Park were likely to be affected. 144Accordingly, the Court concludes that Salem Church has failed to allege facts which set forth an equal protection claim. 4. Takings Claim Salem Church also contends that the State and County's actions constituted an unlawful taking under Article I, § 8 of the Delaware Constitution. 145 Under Delaware law, takings claims generally take two forms: an actual physical taking by the government, or a regulation that denies all economically beneficial or productive use of the land. 146Salem Church characterizes the Defendants' alleged taking as confiscatory in nature, and not merely regulatory, because of the effect SB 143's enactment had on what Salem Church considers to be its vested property right in the French Park plan. 147 A fair reading of the Complaint indicates, however, that Salem Church's takings claim is essentially a regulatory one-the enactment and enforcement of SB 143 are alleged to have affected Salem Church's proposed use. Here, the sine qua non for a regulatory takings claim by Salem Church would be a showing that § 2659(c), as amended by SB 143, leaves the Parcel without economic or productive value. 148 This, of course, has not been alleged by Salem Church in its Complaint. SB 143 requires Salem Church to bring its more (much more) than five year old plan into compliance with the County's current environmental and traffic impact standards, which, not surprisingly, are different from those that existed in 1974. There is no allegation by Salem Church that SB 143 renders the Parcel worthless; indeed, Salem Church has not even alleged that the costs of complying with current standards would be prohibitive. In short, there is no total taking. To the extent that Salem Church alleges a temporary or partial taking, 149the Court notes that, where a regulation imposes limitations on land that fall short of eliminating all economically beneficial use, a taking nonetheless may still have occurred depending on several factors. 150These factors, set forth by the United States Supreme Court in Penn Central Transportation Co. v. City of New York, 151include (1) a regulation's economic effect on the landowner, (2) the extent to which the regulation interferes with reasonable investment-backed expectations, and (3) the character of the government action. 152Salem Church's allegations do not bring its takings claims within the ambit of Penn Central. First, Salem Church does not allege how the application of SB 143 to its Parcel impacts it economically. Presumably, it would be more costly for Salem Church to comply with current environmental and traffic impact standards, but beyond the bare allegation that it has suffered a taking the Court cannot conclude that SB 143 fell just short of eliminating all economically beneficial use of its Parcel. Second, it cannot fairly be determined from the Complaint how Salem Church's intended use of its Parcel is so bound up with its investment-backed expectations that a statutory change-in this case, one governing the "lifespan" of a subdivision application before it must comply with new, or current, environmental and traffic impact standards-invariably results in a taking. In other words, mere compliance with a regulation that may be objectionable to a landowner does not automatically establish a taking. As the Supreme Court in Penn Central recognized, the argument that developers "may establish a 'taking' simply by showing that they have been denied the ability to exploit a property interest that they heretofore had believed was available for development is quite simply untenable." 153 Finally, the character of the government regulation does not support a finding that SB 143 resulted in a temporary taking. As noted previously, the record indicates that there was a rational basis behind the enactment of SB 143, notably concerns about the effect on the environmental and traffic conditions with increased development. Even Salem Church has acknowledged that the additional environmental and traffic impact regulations imposed by SB 143 might even have a beneficial public effect. 154Any argument by Salem Church that SB 143 is distinct from other development legislation because of the alleged "conspiracy" between certain State and County officials pushing for its enactment, however, is insufficient to support a finding that, as a matter of law, SB 143 resulted in a regulatory taking. Accordingly, Salem Church has failed to allege the facts necessary to sustain a takings claim. V. CONCLUSION For the foregoing reasons, the Amended Complaint will be dismissed except with respect to Salem Church's vested rights claim. 155An implementing order will be entered. 1. The Background is drawn from the Amended Complaint and the documents duly incorporated in, or referenced by, the Amended Complaint. 2. 73 Del. Laws, c. 33 (2001). 3. 9 Del. C. § 2659(c). 4. Plaintiff's Amended Complaint ("Compl.") ¶¶ 1, 14. 5. Id. ¶¶ 4--5. 6. Id. ¶ 5. 7. Id. 8. Id. ¶ 7. 9. Id. ¶ 8. To be precise, the June 1, 1999 letter from Plaintiff's counsel to the County's Department of Land Use never stated that Plaintiff's Exploratory Sketch Plan was approved; instead, Plaintiff's counsel noted that they had been "found acceptable." Compl. Ex. 4. 10. Compl. Ex. 5. 11. Compl. ¶¶ 9--10. 12. Id. ¶ 9; Ex. 5. 13. Id. ¶¶10--11. The Complaint incorporated several exhibits by reference. Two of them were the Department's "SLD-1 Form (Application for Plan Review)" and the Preliminary Plan for French Park. Exs. 7--8. The Plaintiff contends that the enacted legislation at issue emphasizes only "applications," not "plans." See infra Part IV.A.1. 14. Compl. ¶ 11. 15. Id. ¶ 13. The Complaint simply states that the County "approved the Preliminary Plan" and "gave Salem Church the go ahead to file a final record plan for French Park." Id. It does not relate that certain items were outstanding and required for French Park's final record plan submission. This fact, although alluded later on by Salem Church in its Complaint, see id. ¶ 17, was reflected by the County engineer's comment letter of March 28, 2001. Ex. 10. Although the Court may typically only consider facts alleged in the complaint on a motion to dismiss, it may also be proper to consider documents referred to in the complaint. See In re GM (Hughes) S'holder Litig., 897 A.2d 162, 169 (Del. 2006). Here, the Court may consider the comment letter because it was both referred to in the Complaint and explicitly incorporated by reference. Compl. ¶ 13. 16. Compl. ¶ 17. 17. Id. ¶ 19. 18. Id. ¶ 20; Ex. 10. 19. Id. 20. Id. ¶ 19. 21. Id. ¶ 30; see also id. ¶ 15 (". . . State legislation was prepared and introduced in the Delaware General Assembly in order to attempt to take away the ability of Salem Church to receive final record approval for French Park. At all times, the County and State officials intended to deprive Salem Church of its vested rights to develop [the Parcel] in accordance with the 1974 rezoning and Exploratory Plan approvals, as well as the Preliminary Plan approval in 2001."). 22. Id. ¶ 14. 23. Id. ¶ 20. 24. Id. ¶ 16. 25. Id. ¶ 28. 26. Id. ¶ 24. 27. Id. ¶ 25; Ex. 20. 28. Id. ¶ 26; Ex. 21. 29. Id. ¶ 27; Ex. 22. 30. Id. ¶ 30. 31. E. Shore Envtl., Inc. v. Kent County Dep't of Planning, 2002 WL 244690, at *3 (Del. Ch. Feb. 1, 2002). It is the Plaintiff's burden to demonstrate that subject matter jurisdiction exists. See, e.g., Christiana Town Ctr., LLC v. New Castle County, 2003 WL 21314499, at *3 (Del. Ch. June 6, 2003) (citations omitted); Buckson v. Town of Camden, 2001 WL 1671443, at *3 (Del. Ch. Dec. 4, 2001) (citing DONALD J. WOLFE, JR. & MICHAEL A. PITTENGER, CORPORATE AND COMMERCIAL PRACTICE IN THE DELAWARE COURT OF CHANCERY § 2-3[a], at 2-17 (2000)). 32. Bebchuck v. CA, Inc., 902 A.2d 737, 740 (Del. Ch. 2006). 33. Tenneco Automotive Inc. v. El Paso Corp., 2001 WL 1641744, at *6 (Del. Ch. Nov. 29, 2001) (citing Schick Inc. v. Amalgamated Clothing & Textile Workers Union, 533 A.2d 1235, 1239 (Del. Ch. 1987)). 34. See Eastern Shore, 2002 WL 244690, at *5, *7. 35. Id. at *5 (citation omitted). 36. Thus, even though the Defendants have moved under Court of Chancery Rule 12(b)(1), the question is not whether the Court has subject matter jurisdiction, which it does, but whether, as the result of the exercise of the Court's discretion, it should exercise that jurisdiction under the circumstances presented here. 37. 616 A.2d 1182 (Del. 1992). 38. Id. at 1189--90. 39. Id. at 1187. 40. See id.; see also Eastern Shore, 2002 WL 244690, at *5 (noting that "[t]he purpose of the exhaustion-of-remedies requirement is to 'prevent judicial interference in the administrative process and to allow the agencies an opportunity to develop a complete factual record, apply their expertise and discretion, and possibly resolve the conflict without judicial intervention'") (citing 5 BASIL J. MEZINES ET AL., ADMINISTRATIVE LAW § 49.01 (Matthew Bender, 2001)). 41. Specifically, County Code § 40.31.510 states that "[a]n applicant pursuing approval of a land use application who is aggrieved by a finding, decision, or interpretation of a decision maker made in response to review of such application may appeal such action to the jurisdictionally approved agency pursuant to Table 40.30.110." The applicant shall cause the appeal to be filed within twenty days of the written decision, and "no appeal to a court of law or equity may be taken until all remedies made available by [Chapter 40 of the New Castle County Code] have been exhausted." 42. See NCC Code Table 40.30.110. The French Park project was a major subdivision. 43. See Eastern Shore, 2002 WL 244690, at *7 ("For a constitutional challenge to a land-use decision to be ripe, the local governmental authorities must arrive at a final, definitive position regarding how they will apply the regulations at issue to the particular land in question.") (citations and alterations omitted); see also Acierno v. Mitchell, 6 F.3d 970, 974 (3d Cir. 1993) (noting that when an applicant fails to take available appeals, its constitutional claims will be found to be unripe). 44. First, despite Salem Church's assertion that the County Code does not authorize the creation of an administrative appeal mechanism for review of decisions on subdivision plans, the General Assembly, pursuant to 9 Del. C. § 1101, has given the County broad statutory authority to enact policies and procedures that the General Assembly could have authorized by specific enumeration. That is, under the State's "home rule" statutes, the County is given great flexibility to discharge its functions, except as otherwise limited by the State's Constitution or its statutes. See Schadt v. Latchford, 843 A.2d 689, 691 (Del. 2004); Green v. Sussex County, 668 A.2d 770, 774 (Del. Super. 1995), aff'd,667 A.2d 1319 (Del. Aug. 2, 1995) (TABLE) ("[W]ith the increasingly complex and fluid problems arising today which must be resolved by local government, the General Assembly has enacted home rule statutes which in many cases override pre-existing, specific statutory grants of power, the purpose of which is to give local governments the flexibility required to discharge their functions."). Although Salem Church correctly notes that 9 Del. C. § 1304 does not expressly delegate to the Planning Board an appeal function, there is nothing in that statute, other statutes, or the Constitution that prohibits the Planning Board from hearing administrative appeals either. Thus, the County properly granted the Planning Board jurisdiction to hear appeals of subdivision plan applications, including staff decisions. Second, Salem Church asserts that an administrative appeal of the County's decision in the McCombs Letter was unnecessary because County Code § 40.31.510 states that an applicant "may," not "shall," appeal to the Planning Board. The County expected that appellate administrative relief would be sought in advance of judicial involvement: Section 40.31.510 makes plain that "no appeal to a court of law or equity may be taken until all remedies made available by [Chapter 40] have been exhausted." The exhaustion doctrine, however, is premised upon available administrative review; a disgruntled applicant cannot so facilely avoid an administrative appeal because the administrative regulation uses "may" instead of shall as a right to an appeal is conferred. Finally, Salem Church cites the Court's decision in Eastern Shore to argue that an appeal to the Planning Board was unnecessary because it was vested only with jurisdiction to consider appeals of decisions based on County Code provisions, not constitutional claims. See Eastern Shore, 2002 WL 244690, at *5--*6 (finding that the rationale for the exhaustion doctrine does not apply where the issues do not involve administrative expertise). In that decision, however, the Court found that exhaustion was unnecessary only where the plaintiff was not challenging the substantive correctness of an administrative body's decision. Id. at *6 (citing Kejand, Inc. v. Town of Dewey Beach, 1996 WL 422333, at *3 (Del. Ch. July 2, 1996)). The plaintiff in Eastern Shore was not required to exhaust administrative remedies through the Board of Adjustment because the plaintiff never challenged the "substantive correctness" of the Department of Planning's decision, but rather claimed detrimental reliance on earlier advice by a county official that its intended use had specifically been "grandfathered." Id. at *2, *6. Unlike the plaintiff in Eastern Shore, however, Salem Church clearly challenges the substantive correctness of the County's interpretation of SB 143. See Compl. ¶ 28 (stating that "SB 143 did not have any effect on the previously approved Preliminary Plan" and did not affect the County's obligation to approve and record it"). 45. Def. County's Reply Br. in Supp. of Its Mot. to Dismiss Pl.'s Compl. ("County's Reply Br.") at 36. 46. See Levinson, 616 A.2d at 1190 (citation and quotation omitted). 47. Id.; see, e.g., Toll Bros. v. Wicks, 2006 WL 1829875, at *8 (Del. Ch. June 21, 2006). 48. See Kejand, Inc. v. Town of Dewey Beach, 1996 WL 422333, at *3 (Del. Ch. July 2, 1996) (stating that there must be a "clear showing of futility"). 49. See, e.g., Levinson, 616 A.2d at 1190--91; Hundley v. O'Donnell, 1998 WL 842293, at *2, n.5 (Del. Ch. Dec. 1, 1998); Kejand, 1996 WL 422333, at *3. 50. See Cantinca v. Fontana, 884 A.2d 468, 471 (Del. 2005). 51. Compl. ¶ 11; Ex. 7. 52. County's Reply Br. at 36. 53. Compl. ¶ 5. 54. Compl. ¶ 17, Ex. 13; Pl.'s Ans. Br. in Opp'n to County's Second Mot. to Dismiss at 36--37. 55. Compl. ¶ 42. 56. 9 Del. C. § 2659(c). See Compl. ¶ 42. 57. 9 Del. C. § 2652(8). 58. See Unofficial Senate Debate Tr.,Pl.'s J.A. to Briefs in Supp. of Its Mot. to Compel and in Opp'n to the State's Mot. to Dismiss ("Pl.'s J.A.") Ex. 12A at 2--3. 59. See Unofficial House Debate Tr., Pl.'s J.A. Ex. 12B at 3. 60. Id. at 4. French Park's Exploratory Sketch Plan showed 688 residential units. French Park is in the "Route 40 corridor." 61. Id. at 7. 62. Although there may be some doubt as to whether the doctrine of exhaustion of administrative remedies may be invoked to preclude judicial review of a vested rights claim, see, e.g., Nathan v. Martin, 317 A.2d 110, 111 n.1 (Del. Super. 1974) (noting that the Court has not been called upon to determine whether exhaustion of administrative remedies is not a prerequisite to a vested rights claim), there is no compelling reason why a vested rights claim should be treated differently from other similar claims. See, e.g., Hanson Aggregates Southeast, Inc. v. City of Raleigh, 2004 WL 1725745, at *3--*4 (N.C. Ct. App. Aug. 3, 2004); Southwest Remediation, Inc. v. City of Tucson, 36 P.3d 1208, 1214 (Ariz. Ct. App. 2001). The Planning Board could not have reviewed Salem Church's vested rights claim as such. At most, it could have concluded that SB 143 did not apply to French Park, thereby obviating all of Salem Church's problems which it alleges resulted from enactment of SB 143. Under different circumstances, the Planning Board might have concluded that the French Park plans could have gone forward as a result of statutory or regulatory interpretation or by resolving certain factual disputes in a manner favorable to the landowner; under those different circumstances, judicial deference to the administrative process might have been appropriate. Indeed, one can envision circumstances where it may make a difference if the controlling legislative act is one of the State or one of the County because the Planning Board, one would assume, has greater latitude in interpreting and applying the County Code. See, e.g., State Farm Auto. Ins. Co. v. Mundorf, 659 A.2d 215, 220 (Del. 1995) ("Although the interpretation of a regulation is ultimately a question of law for a court to decide, substantial weight and deference is accorded to the construction of a regulation enacted by an agency which is also charged with its enforcement."); Thomson v. Dep't of Transp., 1988 WL 61554, at *2 (Del. May 19, 1988) ("Judicial deference is usually given to an administrative agency's construction of its own rules in recognition of its expertise in a given field."). Because the source of Salem Church's frustration is state legislation, a county agency, within our governmental hierarchy, see, e.g., 4th Generation Ltd. v. Bd. of Adjustment of the City of Rehoboth Beach, 1987 WL 14867 (Del. Super. July 16, 1987) (noting "the well-settled rule that a municipality cannot act in conflict with state laws"), has no apparent authority to avoid the obvious consequences of a state statute and, thus, any claim that, in this instance, the Planning Board could have fairly resolved the dispute is illusory. The State also contends that the claims against it should be dismissed because of Salem Church's failure to exhaust County administrative remedies. With the conclusion that exhaustion of County administrative remedies for County purposes was not required, it follows that the State cannot successfully invoke the exhaustion doctrine either. In short, no relief for constitutional violations by the State can be provided by any County agency, in part because the Planning Board, for example, lacks the expertise, the experience, and the jurisdiction to address such questions. As Salem Church argues, "but for the actions of the State in approving SB 143, the French Park plan would have been finally approved a short time [after SB 143's enactment]." Pl.'s Ans. Br. in Opp'n to Def. State of Delaware's Mot. to Dismiss at 13. That allegation forms the basis for the constitutional claims brought by Salem Church against the State, claims that the State may not now avoid simply by invoking ripeness notions. 63. For present purposes, a "takings claim" challenges a regulatory scheme that deprives a landowner of all (or substantially all) beneficial use of its land. It should be differentiated from a vested rights claim, see infra, which seeks relief from governmental action that deprives the landowner of specific rights, otherwise authorized by regulatory acts, with respect to its property. 64. NCC Code § 40.31.600 (emphasis added). 65. Tahoe-Sierra Pres. Council v. Tahoe Reg'l Planning Agency, 535 U.S. 302. 339--40 (2002) (quoting Palazzolo v. Rhode Island, 533 U.S. 606, 620--21 (2001)). See also Murray v. State, 124 P.3d 1261, 1269 (Or. 2005); Molo Oil Co. v. City of Dubuque, 692 N.W.2d 686, 693--94 (Iowa 2005). 66. The State has also argued that Salem Church's taking claims against it are not properly before this Court. It, however, has identified no comparable State administrative procedure for ascertaining remaining beneficial use and has offered no reason why, if the State's conduct independently accomplished a taking, Salem Church should not be able to tender its claim at this time. The State properly points out that the more appropriate forum for a takings claim would be in the Superior Court with an inverse condemnation action. That does not necessarily deprive this Court of subject matter jurisdiction when the takings claim is part of a broader litany of woes that-if warranted-may be remedied in equity. Thus, the takings claim against the State will not be dismissed for failure to exhaust administrative remedies or lack of subject matter jurisdiction. 67. Anglo Am. Sec. Fund, L.P. v. S.R. Global Int'l Fund, L.P., 829 A.2d 143, 148--49 (Del. Ch. 2003). 68. Id. at 49. 69. In re GM (Hughes) S'holder Litig., 897 A.2d at 168. 70. Palese v. Del. State Lottery Office, 2006 WL 1875915, at *2 (Del. Ch. June 29, 2006). 71. Compl. ¶ 37. 72. See Wilmington Materials, Inc. v. Town of Middletown, 1988 WL 135507, at *7 (Del. Ch. Dec. 16, 1988) (recognizing that, while the equitable estoppel doctrine derives from equity and the vested rights doctrine demonstrates principles of property and constitutional law, both may be applied interchangeably). 73. Compl. ¶¶ 19, 22, 29, 30, 34, 37, 46. 74. 808 A.2d 753 (Del. 2002). 75. 224 A.2d 250 (Del. 1966). In Shellburne, the Supreme Court ruled that the acquisition of a vested right requires more than issuance of a building permit. What is required is "a substantial change of position, expenditures, or incurrence of obligations, made lawfully and in good faith under the permit, before the land owner becomes entitled to complete the construction and to use the premises for a purpose prohibited by a subsequent zoning change." Id. at 254. 76. In re 244.5 Acres, 808 A.2d at 757. 77. Id. at 757--58. 78. Id. at 758. 79. See id. at 757--58. 80. 1988 WL 135507 (Del. Ch. Dec. 16, 1988). 81. Id. at *9. 82. In re 244.5 Acres, 808 A.2d at 758. 83. 9 Del. C. § 2659(c). 84. NCC Code, ch. 40, Articles 5 and 10. 85. NCC Code, ch., 40, Articles 5 and 11; NCC Code § 40.11.000. 86. See Unofficial House Debate Tr., Pl.'s J.A. Ex. 12B at 10--11. 87. See id. at 12. 88. See Unofficial Senate Debate Tr., Pl.'s J.A. Ex. 12A at 20. 89. Salem Church, in its Complaint, alleges that bad faith motives were the driving force behind SB 143's enactment and casts aspersions on a number of County and State officials. Compl. ¶¶ 14--17, 21--22, 30. Even if the Court were to take the alleged motivations of the three legislators identified in the Complaint as true, the Court cannot ignore that SB 143 passed overwhelmingly in the General Assembly, with only two House members voting in opposition. See Unofficial Senate and House Trs., Pl.'s J.A. Exs. 12A, 12B. 90. Compl. ¶ 29. 91. Def. New Castle County's Opening Br. in Supp. of Its Mot. to Dismiss Compl. ("County's Opening Br.") at 36; see also County's Reply Br. at 32. But see Wilmington Materials, Inc., 1988 WL 135507, at *8 (noting further that "[w]hat level of expenditure will suffice to constitute substantial reliance cannot be determined by any magic formula" and that any inquiry is fact specific and "must take into account all relevant circumstances"). 92. Compl. ¶ 11. 93. Compl. Ex. 5. 94. 808 A.2d at 757. 95. Compl. Ex. 10. 96. Ultimately, a motion to dismiss provides the Court with a poor forum for conducting a balancing test, especially because all reasonable inferences must be drawn in favor of the nonmoving party. 97. 808 A.2dat 757. It does not appear to be a new concept to consider delay in assessing vested rights claims. More than fifteen years ago, the Ninth Circuit held that a developer's vested rights claim failed when "it did not act expeditiously enough in proceeding with the development [of its project]." See Lakeview Dev. Corp. v. City of South Lake Tahoe, 915 F.2d 1290, 1298 (9th Cir. 1990). The Ninth Circuit further noted that: [A] government's commitment to a 'planned unit development' is necessarily conditioned on the developer's proceeding at a pace reasonably close to that contemplated at the time the project was approved. If the public is to be deprived of its power to control pollution and other problems caused by overdevelopment, it should be deprived only to the extent necessary to ensure private parties a reasonable degree of certainty about the legal status of their investments. Id. at 1299. The court also concluded that the developer's estoppel claim could not be asserted when it "did not proceed at a pace even reasonably close to that anticipated." Id. 98. Compl. ¶ 8. 99. Compl. Ex. 6. 100. It is undisputed that Salem Church had obtained no approvals for at least a ten-year period following its purchase of French Park in 1987. See id. ¶ 7. 101. Cf. Ohrstrom v. Harris Trust Co., 1998 WL 44983, at *1 n.13 (Del. Ch. Jan. 28, 1998) (acknowledging that it would be inappropriate to raise an affirmative defense of laches in a motion to dismiss where such a defense suggests a factual inquiry) (citing Harman v. Masoneilan Int'l, Inc., 442 A.2d 487, 503 (Del. Super. 1982) ("An essential element for application of the doctrine of laches is a finding of unreasonable delay. Such a factual question is usually only properly disposed of by summary judgment after discovery or at trial.")) (internal citation omitted); see also Khanna v. McMinn, 2006 WL 1388744, at *25 (Del. Ch. May 9, 2006) ("The motion to dismiss, with respect to the Defendants' affirmative defense of laches, is reviewed under Court of Chancery Rule 12(b)(6). Because the Court is unable to discern with reasonable certainty from the complaint that laches applies, the Court cannot grant the Defendants' motion on this ground at this time."). 102. Compl. ¶¶ 31--35. 103. Walton v. Beale, 2006 WL 265489, at *4 (Del. Ch. Jan. 30, 2006) (quoting Wilson v. Am. Ins. Co., 209 A.2d 902, 903--04 (Del. 1967)). 104. See Copeland v. Kramarck, 2006 WL 2521444, at *3 (Del. Ch. Aug. 23, 2006) (citing DONALD J. WOLFE, JR. & MICHAEL A. PITTENGER, CORPORATE AND COMMERCIAL PRACTICE IN THE DELAWARE COURT OF CHANCERY § 11.1 (2005)). 105. See DiSabatino v. New Castle County, 781 A.2d 698, 702 (Del. Ch. 2000); Wilmington Materials, 1988 WL 135507, at *6; Miller v. Bd. of Adjustment of Dewey Beach, 521 A.2d 642, 645--46 (Del. Super. 1986). 106. See Acierno v. New Castle County, 2000 WL 718346, at *10 (D.Del. May 23, 2000) (noting that "Delaware courts have approved its application in only a handful of cases"). Special deference has been given to legislative enactments "adopted to protect the public." Kejand, Inc. v. Bd. of Adjustment of the Town of Dewey Beach, 1993 WL 189536, at *3 (Del. Super. Mar. 19, 1993), aff'd, 634 A.2d 938 (Del. 1993) (TABLE) (noting that equitable estoppel will not be invoked "where to do so would render ineffective the operation of a policy adopted to protect the public"). 107. Miller, 521 A.2d at 646 (emphasis added); see Two South Corp. v. City of Wilmington, 1989 WL 76291, at *7 (Del. Ch. July 11, 1989) ("However, because of the public interest involved- particularly where the governmental body acts in furtherance of its police power-the estoppel doctrine is applied cautiously, and generally only where the circumstances require its application to prevent manifest injustice.") (citations omitted); see also Motiva Enters. LLC v. Secretary of the Dept. of Natural Res. & Envtl. Control, 745 A.2d. 234, 250 (Del. Super. 1999) (recognizing that "courts have applied the reasoning and rationale of traditional equitable estoppel against the government very narrowly" and that some courts in the context of estoppel against the government have required a showing of "affirmative misconduct"). 108. Indeed, without the intervention of SB 143, the equitable estoppel claim would have survived a motion to dismiss by the County. 109. It should be noted that even the County Opinion Letter may be read as conditioned upon intervening State law. 110. See, e.g., 4th Generation Ltd., 1987 WL 14867 at *8. 111. To the extent that Salem Church suggests that County and State conduct (including the alleged motivations of various state legislators) leading to enactment of SB 143 implicates equitable estoppel principles, see Part IV.B.2.a infra. 112. Compl. ¶¶ 16, 30. 113. See, e.g., County Concrete Corp. v. Twp. of Roxbury, 442 F.3d 159, 169 (3d Cir. 2006) (quoting Nicholas v. Pa. State Univ., 227 F.3d 133, 139 (3d Cir. 2000)) (holding "non-legislative state action violates substantive due process if 'arbitrary, irrational, or tainted by improper motive,' or if 'so egregious that it 'shocks the conscience'") (emphasis added); Blain v. Twp. of Radnor, 167 Fed. Appx. 330, 333 (3d Cir. 2006) (citing County of Sacramento v. Lewis, 523 U.S. 833, 846 (1998)) ("In land-use cases, only executive action that 'shocks the conscience' constitutes a substantive due process violation.")); United Artists Theatre Circuit, Inc. v. Twp. of Warrington, PA, 316 F.3d 392, 399--400 (3d. Cir. 2003) (holding that "executive action violates substantive due process only when it shocks the conscience"); see also Mirzakhalili v. Chagnon, 2000 WL 1724326, at *19 n.77 (Del. Ch. Nov. 9, 2000)) (noting that a "more difficult burden" might apply to substantive due process claims and citing Fagan v. City of Vineland, 22 F.3d 1296, 1303 (3d Cir. 1994), for the proposition that a plaintiff must show that governmental employees acted with "conscience shocking behavior" to sustain a substantive due process claim). 114. Compl. ¶¶ 16, 30. 115. Id. ¶ 16. 116. See, e.g., Thornbury Noble, Ltd. v. Thornbury Twp., 112 Fed. Appx. 185, 188 (3d Cir. 2004). As for the County's actions in lobbying for SB 143's enactment, the County argues that it is protected from suit under the Noerr-Pennington doctrine. See United Mine Workers v. Pennington, 381 U.S. 657 (1965), which has been held to protect both private persons and government officials' First Amendment right to petition any branch of government. See Mariana v. Fisher, 338 F.3d 189, 199--200 (3d Cir. 2003). Salem Church argues that the doctrine is inapposite because no Delaware court has ever applied it, but it has offered no persuasive reason for this Court to ignore its principles. As the Third Circuit recognized in Mariana, the petitioning of one's government is "crucial" to a modern democracy. Id. at 200. Certain County officials may have been motivated by considerations other than environmental and traffic safety, but the Court will not inquire further into the County's motives for advocating enactment of SB 143. See Pennington, 381 U.S. at 670 ("Noerr shields . . . a concerted effort to influence public officials regardless of intent or purpose."); Structure Bldg. Corp. v. Abella, 873 A.2d 601, 603 (N.J. Super. 2005) (finding irrelevant defendants' motives in lobbying a planning board). Indeed, restraint is particularly appropriate where it has been shown that there was at least some legitimate purpose for bringing incomplete subdivision plans into compliance with modern environmental and traffic standards. 117. See 4th Generation Ltd., 1987 WL 14867, at *8 (noting "the well settled rule that a municipality cannot act in conflict with state laws"). 118. Rogin v. Bensalem Twp., 616 F.2d 680, 689 (3d Cir. 1980). 119. State v. Hobson, 83 A.2d 846, 855--56 (Del. 1951) (internal citations omitted). 120. FCC v. Beach Commc'ns, Inc., 508 U.S. 307, 314--15 (1993) (internal citations and quotations omitted) (emphasis added); see Hobson, 83 A.2d at 856. 121. See e.g., Acierno v. New Castle County, 2000 WL 718346, at *5 (D.Del. May 23, 2000) (recognizing that the alleviation of traffic is a legitimate government interest); ALRO Assocs., L.P. v. Hayward, 2003 WL 22594526, at *9 (Del. Ch. Oct. 31, 2003) (stating that efforts to alleviate traffic congestion on public highways is manifestly a proper exercise of the State's police power); Oceanport Indus., Inc. v. Wilmington Stevedores, Inc., 636 A.2d 892, 906 (Del. 1994) ("The purpose of environmental regulation is to protect the public and ensure the environmental quality of our natural resources."). 122. Pl.'s Ans. Br. at 26--27. 123. See In re GM (Hughes) S'holder Litig., 897 A.2d at 170 ("The trial court may also take judicial notice of matters that are not subject to reasonable dispute."); see also D.R.E. 201(b) (providing that a "judicially noticed fact must be one not subject to reasonable dispute in that it is . . . capable of accurate and ready determination by resort to sources whose accuracy cannot reasonably be questioned"). 124. See Unofficial Senate Debate Tr., Pl.'s J.A. Ex. 12A at 6--11, 13--15, 17, 19--20; Unofficial House Debate Tr., Pl.'s J.A. Ex. 12B at 4, 11--14. 125. See Prices Corner Liquors, Inc. v. Del. Alcoholic Beverage Control Comm'n., 1995 WL 716802, at *2 (Del. Super. Nov. 13, 1995) (citing Nebbia v. New York, 291 U.S. 502 (1934); Pruneyard Shopping Ctr. v. Robins, 447 U.S. 74, 84 (1980). 126. Compl. ¶ 30. 127. As the Supreme Court stated in Arbour Park Civic Ass'n v. City of Newark, "when citizens and the governing authorities have a difference of opinion as to the desirability of municipal action, courts will not inquire into the motives of [legislators] . . . in making a determination as to the validity of an ordinance enacted within the scope of such legislative body's legitimate and properly exercised powers." 267 A.2d 904, 906 (Del. Ch. 1970). 128. State v. Schorr, 131 A.2d 158, 161 (Del. 1957); see also Hellman v. State, 784 A.2d 1058, 1068 (Del. 2001) ("Courts are not super-legislatures and it is not a proper judicial function to decide what is or is not wise legislative policy.") (citation omitted). 129. Compl. ¶ 37. 130. See Adjile, Inc. v. City of Wilmington, 2005 WL 1139577, at *7 (Del. May 12, 2005). 131. Compl. ¶ 19. 132. It may be that the procedural due process claim which Salem Church seeks to assert is related to the vested rights claim discussed above. The Court differentiates, hopefully for clarity, between the vested rights claim and a procedural due process claim. Cf. supra note 63. 133. Compl. ¶ 20. 134. Rogin, 616 F.2d at 693 (citing Bi-Metallic Inv. Co. v. State Bd. of Equalization of Colo., 239 U.S. 441 (1915)) ("Long ago, the Supreme Court decided that the protections of procedural due process do not extend to legislative actions.");see also Jocham v. Tuscola County, 239 F.Supp. 2d 714, 726 (D. Mich. 2003) (observing that "the legislative process itself provides all the process that is due" and that no authority "indicat[es] that citizens have the constitutional right to hold a legislature at rapt attention for five minutes in order to criticize policy with which they disagree"). 135. 239 U.S. 441 (1915). 136. Id. at 445. This analysis was, of course, in the context of federal due process rights. Salem Church has offered no reason for why Delaware's view would be different. 137. Compl. Ex. 12; 73 Del. Laws. c. 33 (S.B. 143). 138. Pl.'s Ans. Br. at 18. 139. See Village of Willowbrook v. Olech, 528 U.S. 562, 564--65 (2000) (recognizing and applying the "class of one" theory in an equal protection claim). 140. 616 F.2d 680 (3d Cir. 1980). 141. Id. at 688 (citation omitted). 142. See supra note 124. 143. See Acierno, 2000 WL 718346, at *6 (citing FCC v. Beach Commc'ns, 508 U.S. 307, 313 (1993)). 144. See supra note 124. 145. Compl. ¶ 37; Pl.'s Ans. Br. at 13, 19--20. As set forth in Part IV.A.2 supra, Salem Church failed to exhaust administrative remedies made available by the County to determine whether a "taking" occurred. 146. See Wilmington Hospitality, LLC v. New Castle County, 2004 WL 2419157, at *2 (Del. Super. Oct. 4, 2004); State v. Booker, 1992 WL 240386, at *2 (Del. Super. Sept. 2, 1992). 147. Pl.'s Ans. Br. at 19. As to the differences between a takings claim and a vested rights claim, see supra note 63. 148. See Palazzolo v. Rhode Island, 533 U.S. 606, 617 (2001) (recognizing that "a regulation which 'denies all economically beneficial or productive use of land' will require compensation under the Takings Clause") (citations omitted); see also supra note 146. 149. Salem Church's Answering Brief to the State's Motion to Dismiss stated that its Complaint "contains averments that allege a temporary taking of Acierno's property rights for more than four (4) years . . . ." See Pl.'s Ans. Br. at 14. 150. See Palazzolo, 533 U.S. at 617. 151. 438 U.S. 104 (1978). 152. See id. at 124; see also Wilmington Hospitality, LLC v. New Castle County, 2005 WL 1654024, at *3 (Del. Super. May 24, 2005) (considering the Penn Central factors in determining whether a temporary or partial regulatory taking has occurred). 153. Penn Central, 438 U.S. at 124 (citations omitted). 154. See Pl.'s Ans. Br. at 49. 155. With the conclusion in Part IV.A.1 supra, that SB 143 precludes County approval of the French Park plan, Salem Church's motion for partial summary judgment on its request for a declaratory judgment as to the applicability of SB 143 to French Park is denied. As for Salem Church's motion to compel discovery, limited discovery is appropriate for Salem Church to better develop the factual basis for its vested rights claim. Permitted discovery would not include, for example, investigation of the reasons for enactment of SB 143. As explained previously, courts do not inquire into the motives of individual legislators when the legislature has acted within the scope of its legitimate and properly exercised powers. See Arbour Park, 267 A.2d at 906; 5 MCQUILLIN MUN. CORP. § 16.90 (5th ed. 1996). See also DEL. CONST. art II, § 13 (1897); Shellburne, 238 A.2d at 337.
https://www.anylaw.com/case/salem-church-associates-v-new-castle-county/court-of-chancery-of-delaware/10-06-2006/VKa5SGYBTlTomsSB6j-g
Proclamation 10453—National Hunting and Fishing Day, 2022 | The American Presidency Project Proclamation 10453—National Hunting and Fishing Day, 2022 By the President of the United States of America A Proclamation Every year, tens of millions of Americans take to the great outdoors to hunt and fish. These time-honored traditions offer opportunities for sport and leisure, put food on our tables, and bring families and friends together. They embody the American spirit of adventure and resourcefulness and inspire gratitude for the beauty and bounty of our natural world. On National Hunting and Fishing Day, we celebrate America's hunters and anglers for strengthening our communities and recommit ourselves to conserving lands and waters so future generations can enjoy these beloved pastimes. Hunting and fishing are more than just hobbies—they also sustain livelihoods. They contribute billions of dollars annually to our Nation's economy and support over a million jobs in the United States. They bring important tourism dollars to communities and create new business opportunities for local entrepreneurs. To strengthen these industries, my Administration expanded hunting and fishing opportunities on 2.1 million acres of public lands last year, one of the largest increases in recent history. We have also proposed additional expansions to the number of Federal land and water units within the National Wildlife Refuge System where hunting and fishing are permitted. The future of hunting and fishing depends on our ability to conserve America's public lands and natural spaces. Over the years, the twin crises of biodiversity loss and climate change have made healthy fish and game harder to find. Hunters and anglers have been some of our Nation's earliest conservation leaders, and they continue to be an integral part of the solution. Additionally, for nearly a century, Federal programs that direct revenue from equipment and license sales have funded State and local conservation efforts throughout the country, bringing in more than $25.5 billion to date. To bolster the impact of these programs, my Administration recently announced a record investment of $1.5 billion in annual funding to support State and local wildlife and habitat conservation efforts and outdoor recreation. We also established the Federal Interagency Council on Outdoor Recreation to coordinate efforts between the Departments of the Interior, Agriculture, Defense-Civil Works, and Commerce to strengthen the outdoor recreation economy. And my Administration's America the Beautiful Initiative set a national goal of conserving at least 30 percent of our Nation's lands and waters by 2030, launching a decade-long effort to support locally led and voluntary conservation and restoration projects. This work is tied to our fight against the climate crisis, our pledge to drastically reduce emissions, and our duty to build a better, healthier world. As we reflect on the long-cherished traditions and cultural heritage of hunting and fishing, we recognize America's hunters and anglers in their pursuit of adventure and commitment to conserve our natural world. We recommit to strengthening the hunting and fishing industries in a responsible and sustainable way while supporting the people whose livelihoods depend on them. And we renew our efforts to build partnerships with hunters and anglers; agricultural and forest landowners; outdoor enthusiasts; Tribal Nations, States, and territories; local officials; and other important stakeholders to make public lands accessible to all Americans and keep our outdoor spaces healthy and resilient for generations to come. Now, Therefore, I, Joseph R. Biden Jr.,President of the United States of America, by virtue of the authority vested in me by the Constitution and the laws of the United States, do hereby proclaim September 24, 2022, as National Hunting and Fishing Day. I call upon all Americans to observe this day with appropriate programs and activities. In Witness Whereof,I have hereunto set my hand this twenty-third day of September, in the year of our Lord two thousand twenty-two, and of the Independence of the United States of America the two hundred and forty-seventh. JOSEPH R. BIDEN JR. NOTE: This proclamation was published in the Federal Registeron September 28. Joseph R. Biden, Proclamation 10453—National Hunting and Fishing Day, 2022 Online by Gerhard Peters and John T. Woolley, The American Presidency Project https://www.presidency.ucsb.edu/node/358064 Filed Under Categories Presidential Written Presidential Orders Proclamations
https://www.presidency.ucsb.edu/documents/proclamation-10453-national-hunting-and-fishing-day-2022
ARCHIVED - Narcotic Control Regulations Federal laws of canada Table of Contents Narcotic Control Regulations C.R.C., c. 1041 CONTROLLED DRUGS AND SUBSTANCES ACT Narcotic Control Regulations 1 [Repealed, SOR/2019-169, s. 2] Interpretation Marginal note:Definitions 2 (1)The following definitions apply in these Regulations. Act Actmeans the Controlled Drugs and Substances Act. ( Loi) advertisement advertisementincludes any representation by any means for the purpose of promoting, directly or indirectly, the sale or other disposal of a narcotic. ( publicité.) common-law partner common-law partner, in relation to an individual, means a person who is cohabiting with the individual in a conjugal relationship, having so cohabited for a period of at least one year. ( conjoint de fait) competent authority competent authoritymeans a public authority of a foreign country that is authorized under the laws of the country to approve the importation or exportation of narcotics into or from the country. ( autorité compétente) compound compoundincludes a preparation. ( composé) designated criminal offence designated criminal offencemeans (a)an offence involving the financing of terrorism against any of sections 83.02 to 83.04 of the Criminal Code; (b)an offence involving fraud against any of sections 380 to 382 of the Criminal Code; (c)the offence of laundering proceeds of crime against section 462.31 of the Criminal Code; (d)an offence involving a criminal organization against any of sections 467.11 to 467.13 of the Criminal Code; or (e)a conspiracy or an attempt to commit, being an accessory after the fact in relation to, or any counselling in relation to, an offence referred to in any of paragraphs (a) to (d). ( infraction désignée en matière criminelle) destroy destroymeans, in respect of a narcotic, to alter or denature it to such an extent that its consumption is rendered impossible or improbable. ( destruction) diacetylmorphine (heroin) diacetylmorphine (heroin)includes the salts of diacetylmorphine. ( diacétylmorphine (héroïne)) hospital hospitalmeans a facility (a)that is licensed, approved or designated by a province in accordance with the laws of the province to provide care or treatment to persons or animals suffering from any form of disease or illness; or (b)that is owned or operated by the Government of Canada or the government of a province and that provides health services. ( hôpital) international obligation international obligationmeans an obligation in respect of a narcotic set out in a convention, treaty or other multilateral or bilateral instrument that Canada has ratified or to which Canada adheres. ( obligation internationale) licensed dealer licensed dealermeans the holder of a licence issued under section 10.1. ( distributeur autorisé) methadone methadoneincludes the salts of methadone. ( méthadone) midwife midwifehas the same meaning as in section 1 of the New Classes of Practitioners Regulations. ( sage-femme) narcotic narcoticmeans, subject to subsection (2), (a)a controlled substance set out in the schedule; or (b)in respect of a midwife, nurse practitioner or podiatrist, a controlled substance set out in the schedule that the midwife, nurse practitioner or podiatrist may prescribe, possess or conduct an activity with, in accordance with sections 3 and 4 of the New Classes of Practitioners Regulations. ( stupéfiant) nurse practitioner nurse practitionerhas the same meaning as in section 1 of the New Classes of Practitioners Regulations. ( infirmier praticien) pharmacist pharmacistmeans a person who is entitled under the laws of a province to practise pharmacy and who is practising pharmacy in that province. ( pharmacien) podiatrist podiatristhas the same meaning as in section 1 of the New Classes of Practitioners Regulations. ( podiatre) prescription prescriptionmeans an authorization given by a practitioner that a stated amount of a narcotic be dispensed for the person named in it or the animal identified in it. ( ordonnance) qualified person in charge qualified person in chargemeans the individual designated under subsection 9.2(1). ( responsable qualifié) Security Directive Security Directivemeans the Directive on Physical Security Requirements for Controlled Substances and Drugs Containing Cannabis, as amended from time to time and published by the Government of Canada on its website. ( Directive en matière de sécurité) senior person in charge senior person in chargemeans the individual designated under section 9.1. ( responsable principal) test kit test kitmeans a kit (a)that contains a narcotic and a reagent system or buffering agent; (b)that is used during the course of a chemical or analytical procedure to test for the presence or quantity of a narcotic for a medical, laboratory, industrial, educational, law administration or enforcement, or research purpose; and (c)the contents of which are not intended or likely to be consumed by, or administered to, a person or an animal. ( nécessaire d’essai) verbal prescription narcotic verbal prescription narcoticmeans a narcotic that is contained in medication that may be prescribed verbally and that has the following characteristics: (a)it contains two or more medicinal ingredients that are not narcotics, in a recognized therapeutic dose; (b)it is not intended for parenteral administration; and (c)it does not contain diacetylmorphine (heroin), hydrocodone, methadone, oxycodone or pentazocine. ( stupéfiant d’ordonnance verbale) Marginal note:Exception (2)Despite subitem 2(2) of the schedule, the following are not narcotics for the purposes of these Regulations: (a)a drug in dosage form, as defined in subsection C.01.005(3) of the Food and Drug Regulations, that contains cocaine (benzoylmethylecgonine) or any of its salts unless the drug (i)has a drug identification number assigned to it under Division 1 of Part C of those Regulations, (ii)is authorized for sale under Division 5 of Part C of those Regulations, or (iii)is compounded by a pharmacist in accordance with or in anticipation of an authorization from a practitioner that a stated amount of the drug be dispensed for a person who is or will be named in the authorization; or (b)cocaine (benzoylmethylecgonine) or any of its salts or any drug that is not in dosage form that contains such a substance, unless the cocaine, salt or drug is to be compounded by a pharmacist in accordance with or in anticipation of an authorization from a practitioner that a stated amount of the drug be dispensed for a person who is or will be named in the authorization. SOR/78-154, s. 1 SOR/81-361, s. 1 SOR/85-588, s. 1 SOR/85-930, s. 1 SOR/86-173, s. 1 SOR/88-279, s. 1(F) SOR/90-189, s. 1 SOR/97-227, s. 1 SOR/2003-134, s. 1 SOR/2004-237, s. 1 SOR/2010-221, s. 1 SOR/2012-230, s. 14 SOR/2013-119, s. 200 SOR/2013-172, s. 3 SOR/2015-132, s. 1 SOR/2016-230, ss. 261, 278 SOR/2016-239, s. 2 SOR/2018-147, s. 1 SOR/2019-169, s. 3 2.1 [Repealed, SOR/2016-230, s. 262] Possession Marginal note:Authorized persons 3 (1)A person is authorized to possess a narcotic if the person has obtained the narcotic in accordance with these Regulations, in the course of activities conducted in connection with the administration or enforcement of an Act or regulation, or from a person who is exempt under section 56 of the Act from the application of subsection 5(1) of the Act with respect to that narcotic, and the person (a)requires the narcotic for their business or profession and is (i)a licensed dealer, (ii)a pharmacist, or (iii)a practitioner who is registered and entitled to practise in the province in which they possess the narcotic; (b)is a practitioner who is registered and entitled to practise in a province other than the province in which they possess the narcotic for emergency medical purposes only; (c)is a hospital employee or a practitioner in a hospital; (d)has obtained the narcotic for their own use (i)from a practitioner, (ii)in accordance with a prescription that was not issued or obtained in contravention of these Regulations, or (iii)from a pharmacist under section 36; (e)is a practitioner of medicine who received the narcotic under subsection 68(1) or (2) and their possession is for the purpose of providing or delivering it to a person referred to in subsection 68(3); (f)is an agent or mandatary of a practitioner of medicine who received the narcotic under subsection 68(1) and their possession is for the purpose of providing or delivering it to a person referred to in subsection 68(2); (g)is employed as an inspector, a member of the Royal Canadian Mounted Police, a police constable, a peace officer or a member of the technical or scientific staff of the Government of Canada, the government of a province or a university in Canada and their possession is in connection with that employment; (h)is not a practitioner of medicine referred to in paragraph (e) or an agent or mandatary referred to in paragraph (f), is exempted under section 56 of the Act with respect to the possession of that narcotic and their possession is for a purpose set out in the exemption; or (i)is the Minister. Marginal note:Agent or mandatary (2)A person is authorized to possess a narcotic if the person is acting as the agent or mandatary of any person who is authorized to possess it in accordance with any of paragraphs (1)(a) to (e), (h) and (i). Marginal note:Agent or mandatary — person referred to in paragraph (1)(g) (3)A person is authorized to possess a narcotic if (a)the person is acting as the agent or mandatary of a person who they have reasonable grounds to believe is a person referred to in paragraph (1)(g); and (b)their possession of the narcotic is for the purpose of assisting that person in the administration or enforcement of an Act or regulation. SOR/85-588, s. 2 SOR/85-930, s. 2 SOR/97-227, s. 2 SOR/99-124, s. 1 SOR/2012-230, s. 15 SOR/2013-119, s. 202 SOR/2013-172, s. 4 SOR/2016-230, s. 263 SOR/2016-239, s. 3 SOR/2018-37, s. 1 SOR/2018-69, ss. 75, 76 SOR/2018-147, s. 2 SOR/2019-169, s. 3 Test Kits Marginal note:Authorized activities 4A person may sell, possess or otherwise deal in a test kit if the following conditions are met: (a)a registration number has been issued for the test kit under section 6 and has not been cancelled under section 7; (b)the test kit bears, on its external surface, (i)the manufacturer’s name, (ii)the trade name or trademark, and (iii)the registration number; and (c)the test kit will be used for a medical, laboratory, industrial, educational, law administration or enforcement, or research purpose. 2014, c. 20, s. 366(E) SOR/2019-169, s. 3 Marginal note:Application for registration number 5 (1)The manufacturer of a test kit may obtain a registration number for it by submitting to the Minister an application containing (a)a detailed description of the design and construction of the test kit; (b)a detailed description of the narcotic and other substances, if any, contained in the test kit, including the qualitative and quantitative composition of each component; and (c)a description of the proposed use of the test kit. Marginal note:Signature and attestation (2)The application must (a)be signed and dated by the person authorized by the applicant for that purpose; and (b)include an attestation by that person that all of the information submitted in support of the application is correct and complete to the best of their knowledge. Marginal note:Additional information or document (3)The applicant must, not later than the date specified in the Minister’s written request to that effect, provide the Minister with any information or document that the Minister determines is necessary to complete the review of the application. SOR/2018-69, s. 71 SOR/2019-169, s. 3 Marginal note:Issuance of registration number 6On completion of the review of the application for a registration number, the Minister must issue a registration number for the test kit, preceded by the letters “TK”, if the Minister determines that the test kit will only be used for a medical, laboratory, industrial, educational, law administration or enforcement, or research purpose and that it contains (a)a narcotic and an adulterating or denaturing agent in such a manner, combination, quantity, proportion or concentration that the preparation or mixture has no significant drug abuse potential; or (b)such small quantities or concentrations of a narcotic as to have no significant drug abuse potential. SOR/81-22, s. 1 SOR/2019-169, s. 3 Marginal note:Cancellation of registration number 7The Minister must cancel the registration number for a test kit if (a)the test kit is removed from the market by the manufacturer; (b)the Minister has reasonable grounds to believe that the test kit is used or is likely to be used for any purpose other than a medical, laboratory, industrial, educational, law administration or enforcement, or research purpose; or (c)the Minister has reasonable grounds to believe that the cancellation is necessary to protect public health or safety, including to prevent a narcotic from being diverted to an illicit market or use. SOR/2019-169, s. 3 Licensed Dealers [ SOR/2004-237, s. 2 ] Authorized Activities Marginal note:General 8 (1)A licensed dealer may produce, assemble, sell, provide, transport, send, deliver, import or export a narcotic if they comply with these Regulations and the terms and conditions of their dealer’s licence and any permit issued under these Regulations. Marginal note:Qualified person in charge present (2)A licensed dealer may conduct an activity in relation to a narcotic at their site only if the qualified person in charge or an alternate qualified person in charge is present at the site. Marginal note:Permit — import and export (3)A licensed dealer must obtain a permit in order to import or export a narcotic. Marginal note:Possession for export (4)A licensed dealer may possess a narcotic for the purpose of exporting it if they have obtained it in accordance with these Regulations. Marginal note:Opium poppy — production (5)A licensed dealer may cultivate, propagate or harvest opium poppy only for scientific purposes. SOR/2004-237, s. 3 SOR/2013-119, s. 203 SOR/2016-123, s. 1 SOR/2016-230, ss. 264, 278 SOR/2018-147, s. 3 SOR/2019-169, s. 3 8.1 [Repealed, SOR/2019-169, s. 3] 8.2 [Repealed, SOR/2019-169, s. 3] 8.3 [Repealed, SOR/2019-169, s. 3] Dealer’s Licences Preliminary Requirements Marginal note:Eligible persons 9The following persons may apply for a dealer’s licence: (a)an individual who ordinarily resides in Canada; (b)a corporation that has its head office in Canada or operates a branch office in Canada; or (c)the holder of a position that includes responsibility for narcotics on behalf of the Government of Canada or of a government of a province, a police force, a hospital or a university in Canada. SOR/85-588, s. 3(F) SOR/2004-237, s. 4 SOR/2010-221, s. 3 SOR/2012-230, s. 17 SOR/2014-260, ss. 17, 27(F) SOR/2019-169, s. 3 Marginal note:Senior person in charge 9.1An applicant for a dealer’s licence must designate only one individual as the senior person in charge, who has overall responsibility for management of the activities with respect to narcotics that are specified in the licence application. The applicant may designate themself if the applicant is an individual. SOR/2004-237, s. 4 SOR/2019-169, s. 3 Marginal note:Qualified person in charge 9.2 (1)An applicant for a dealer’s licence must designate only one individual as the qualified person in charge, who is responsible for supervising the activities with respect to narcotics that are specified in the licence application and for ensuring that those activities comply with these Regulations. The applicant may designate themself if the applicant is an individual. Marginal note:Alternate qualified person in charge (2)An applicant for a dealer’s licence may designate an individual as an alternate qualified person in charge, who is authorized to replace the qualified person in charge when that person is absent. The applicant may designate themself if the applicant is an individual. Marginal note:Qualifications (3)Only an individual who meets the following requirements may be designated as a qualified person in charge or an alternate qualified person in charge: (a)they work at the site specified in the dealer’s licence; (b)they (i)are entitled or, if applicable, registered and entitled by a provincial professional licensing authority or a professional association in Canada and entitled to practise a profession that is relevant to their duties, such as pharmacist, practitioner, pharmacy technician or laboratory technician, (ii)hold a diploma, certificate or credential awarded by a post-secondary educational institution in Canada in a field or occupation that is relevant to their duties, such as pharmacy, medicine, dentistry, veterinary medicine, pharmacology, chemistry, biology, pharmacy technician, laboratory technician, pharmaceutical regulatory affairs or supply chain management or security, or (iii)hold a diploma, certificate or credential that is awarded by a foreign educational institution in a field or occupation referred to in subparagraph (ii) and hold (A)an equivalency assessmentas defined in subsection 73(1) of the Immigration and Refugee Protection Regulations, or (B)an equivalency assessment issued by an organization or institution that is responsible for issuing equivalency assessments and is recognized by a province; (c)they have sufficient knowledge of and experience with the use and handling of the narcotics specified in the dealer’s licence to properly carry out their duties; and (d)they have sufficient knowledge of the provisions of the Act and these Regulations that are applicable to the activities specified in the dealer’s licence to properly carry out their duties. Marginal note:Exception (4)An applicant for a dealer’s licence may designate an individual who does not meet any of the requirements of paragraph (3)(b) as a qualified person in charge or an alternate qualified person in charge if (a)no other individual working at the site meets those requirements; (b)those requirements are not necessary for the activities specified in the licence; and (c)the individual has sufficient knowledge — acquired from a combination of education, training or work experience — to properly carry out their duties. SOR/2004-237, s. 4 SOR/2010-221, ss. 4, 18(F) SOR/2014-260, s. 18 SOR/2019-169, s. 3 Marginal note:Ineligibility 9.3An individual is not eligible to be a senior person in charge, a qualified person in charge or an alternate qualified person in charge if, during the 10 years before the day on which the dealer’s licence application is submitted, (a)in respect of a designated substance offence or a designated criminal offence or a designated offenceas defined in subsection 2(1) of the Cannabis Act, the individual (i)was convicted as an adult, or (ii)was a young personwho received an adult sentence, as those terms are defined in subsection 2(1) of the Youth Criminal Justice Act; or (b)in respect of an offence committed outside Canada that, if committed in Canada, would have constituted a designated substance offence or a designated criminal offence or a designated offenceas defined in subsection 2(1) of the Cannabis Act, (i)the individual was convicted as an adult, or (ii)if they committed the offence when they were at least 14 years old but less than 18 years old, the individual received a sentence that was longer than the maximum youth sentence, as that term is defined in subsection 2(1) of the Youth Criminal Justice Act, that could have been imposed under that Act for such an offence. SOR/2004-237, s. 4 SOR/2019-169, s. 3 9.4 [Repealed, SOR/2019-169, s. 3] 9.5 [Repealed, SOR/2019-169, s. 3] 9.6 [Repealed, SOR/2019-169, s. 3] 9.7 [Repealed, SOR/2019-169, s. 3] 9.8 [Repealed, SOR/2019-169, s. 3] 9.9 [Repealed, SOR/2019-169, s. 3] 9.91 [Repealed, SOR/2019-169, s. 3] 9.92 [Repealed, SOR/2019-169, s. 3] Issuance of Licence Marginal note:Application 10 (1)A person who intends to conduct an activity referred to in section 8 must obtain a dealer’s licence for each site at which they intend to conduct activities by submitting an application to the Minister that contains the following information: (a)if the licence is requested by (i)an individual, the individual’s name, (ii)a corporation, its corporate name and any other name registered with a province under which it intends to conduct the activities specified in its dealer’s licence or by which it intends to identify itself, and (iii)the holder of a position described in paragraph 9(c), the applicant’s name and the title of the position; (b)the municipal address, telephone number and, if applicable, the email address of the proposed site and, if different from the municipal address, its mailing address; (c)the name, date of birth, telephone number and email address of the proposed senior person in charge; (d)with respect to each of the proposed qualified person in charge and any proposed alternate qualified person in charge, (i)their name, date of birth, telephone number and email address, (ii)the title of their position at the site, (iii)the name and title of the position of their immediate supervisor at the site, (iv)if applicable, the profession they practise that is relevant to their duties, the name of the province that authorizes them to practise it and their authorization number, and (v)their education, training and work experience that are relevant to their duties; (e)the activities that are to be conducted and the narcotics in respect of which each of the activities is to be conducted; (f)if the licence is requested to manufacture or assemble a product or compound that contains a narcotic, other than a test kit, a list that includes, for each product or compound, (i)the brand name of the product or the name of the compound, (ii)the drug identification number that is assigned to the product under section C.01.014.2 of the Food and Drug Regulations, if any, (iii)the name of the narcotic in the product or compound, (iv)the strength per unit of the narcotic in it, the number of units per package and the number of packages, (v)if it is to be manufactured or assembled by or for another licensed dealer under a custom order, the name, municipal address and licence number of the other licensed dealer, and (vi)if the applicant’s name appears on the label of the product or compound, a copy of the inner label, as defined in section A.01.010 of the Food and Drug Regulations; (g)if the licence is requested in order to produce a narcotic other than a product or compound that contains a narcotic, (i)the name of the narcotic, (ii)the quantity that the applicant expects to produce under their licence and the period during which that quantity would be produced, and (iii)if it is to be produced for another licensed dealer under a custom order, the name, municipal address and licence number of the other licensed dealer; (h)if the licence is requested for an activity that is not described in paragraph (f) or (g), the name of the narcotic for which the activity is to be conducted and the purpose of the activity; (i)a detailed description of the security measures in place at the site, determined in accordance with the Security Directive; and (j)a detailed description of the method for recording information that the applicant proposes to use for the purpose of section 28. Marginal note:Documents (2)An application for a dealer’s licence must be accompanied by the following documents: (a)if the applicant is a corporation, a copy of (i)the certificate of incorporation or other constituting instrument, and (ii)any document filed with the province in which its site is located that states its corporate name and any other name registered with the province under which the applicant intends to conduct the activities specified in its dealer’s licence or by which it intends to identify itself; (b)individual declarations signed and dated by each of the proposed senior person in charge, and qualified person in charge and any proposed alternate qualified person in charge, attesting that the person is not ineligible for a reason specified in section 9.3; (c)a document issued by a Canadian police force in relation to each person referred to in paragraph (b), indicating whether, during 10 years before the day on which the application is submitted, the person was convicted as specified in subparagraph 9.3(a)(i) or received a sentence as specified in subparagraph 9.3(a)(ii); (d)if any of the persons referred to in paragraph (b) has ordinarily resided in a country other than Canada during the 10 years before the day on which the application is submitted, a document issued by a police force of that country indicating whether in that period that person was convicted as specified in subparagraph 9.3(b)(i) or received a sentence as specified in subparagraph 9.3(b)(ii); (e)declaration, signed and dated by the proposed senior person in charge, attesting that the proposed qualified person in charge and any proposed alternate qualified person in charge have the knowledge and experience required under paragraphs 9.2(3)(c) and (d); and (f)if the proposed qualified person in charge or any proposed alternate qualified person in charge does not meet the requirement of subparagraph 9.2(3)(b)(i), either (i)a copy of the person’s diploma, certificate or credential referred to in subparagraph 9.2(3)(b)(ii) or (iii), or (ii)a detailed description of the education, training and work experience that is required under paragraph 9.2(4)(c), together with supporting evidence, such as a copy of a course transcript or an attestation by the person who provided the training. Marginal note:Signature and attestation (3)The application must (a)be signed and dated by the proposed senior person in charge; and (b)include an attestation by that person that (i)all of the information and documents submitted in support of the application are correct and complete to the best of their knowledge, and (ii)they have the authority to bind the applicant. Marginal note:Additional information and documents (4)The applicant must, not later than the date specified in the Minister’s written request to that effect, provide the Minister with any information or document that the Minister determines is necessary to complete the review of the application. SOR/2019-169, s. 3 Marginal note:Issuance 10.1Subject to section 10.3, on completion of the review of the licence application, the Minister must issue a dealer’s licence, with or without terms and conditions, that contains (a)the licence number; (b)the name of the licensed dealer, their corporate name or the title of the position they hold; (c)the activities that are authorized and the names of the narcotics in respect of which each activity may be conducted; (d)the municipal address of the site at which the dealer may conduct the authorized activities; (e)the security level at the site, determined in accordance with the Security Directive; (f)the effective date of the licence; (g)the expiry date of the licence, which must be not later than three years after its effective date; (h)any terms and conditions that the Minister has reasonable grounds to believe are necessary to (i)ensure that an international obligation is respected, (ii)ensure conformity with the requirements associated with the security level that is referred to in paragraph (e), or (iii)reduce a risk to public health or safety, including the risk of a narcotic being diverted to an illicit market or use; and (i)if the licensed dealer produces a narcotic, the quantity that they may produce and the authorized production period. SOR/2019-169, s. 3 Marginal note:Validity 10.2A dealer’s licence is valid until the expiry date set out in the licence or, if it is earlier, the date of the suspension or revocation of the licence under section 16 or 17. SOR/2019-169, s. 3 Marginal note:Refusal 10.3 (1)The Minister must refuse to issue a dealer’s licence if (a)the applicant may not apply for a licence under section 9; (b)during the 10 years before the day on which the licence application is submitted, the applicant has contravened (i)a provision of the Act, the Cannabis Actor their regulations, or (ii)a term or condition of a licence or permit issued to the applicant under any regulations made under the Act or issued to the applicant under the Cannabis Actor its regulations; (c)during the 10 years before the day on which the licence application is submitted, the proposed senior person in charge or qualified person in charge or any proposed alternate qualified person in charge was convicted as specified in subparagraph 9.3(a)(i) or (b)(i) or received a sentence as specified in subparagraph 9.3(a)(ii) or (b)(ii); (d)an activity for which the licence is requested would contravene an international obligation; (e)an activity for which the licence is requested is the cultivation, propagation or harvesting of opium poppy other than for scientific purposes; (f)the applicant does not have in place at the site the security measures set out in the Security Directive in respect of an activity for which the licence is requested; (g)the method referred to in paragraph 10(1)(j) does not permit the recording of information as required by section 28; (h)the applicant has not complied with the requirements of subsection 10(4) or the information or documents that they have provided are not sufficient to complete the review of the licence application; (i)the Minister has reasonable grounds to believe that the applicant has submitted false or misleading information or false or falsified documents in or in support of the licence application; (j)information received from a competent authority or the United Nations gives the Minister reasonable grounds to believe that the applicant has been involved in the diversion of a narcotic to an illicit market or use or has been involved in an activity that contravened an international obligation; or (k)the Minister has reasonable grounds to believe that the issuance of the licence would likely create a risk to public health or safety, including the risk of a narcotic being diverted to an illicit market or use. Marginal note:Exceptions (2)The Minister must not refuse to issue a licence under paragraph (1)(b) or (i) if the applicant meets the following conditions, unless the Minister has reasonable grounds to believe that it is necessary to do so to protect public health or safety, including to prevent a narcotic from being diverted to an illicit market or use: (a)the applicant does not have a history of non-compliance with the Act, the Cannabis Actor their regulations; and (b)the applicant has carried out, or signed an undertaking to carry out, the necessary corrective measures to ensure compliance with the Act, the Cannabis Actand their regulations. Marginal note:Notice (3)Before refusing to issue a licence, the Minister must send the applicant a notice that sets out the Minister’s reasons and gives the applicant an opportunity to be heard. SOR/2019-169, s. 3 Renewal of Licence Marginal note:Application 11 (1)To apply to renew a dealer’s licence, a licensed dealer must submit to the Minister an application that contains the information and documents referred to in subsections 10(1) and (2). Marginal note:Signature and attestation (2)The application must (a)be signed and dated by the senior person in charge of the site specified in the application; and (b)include an attestation by that person that (i)all of the information and documents submitted in support of the application are correct and complete to the best of their knowledge, and (ii)they have the authority to bind the licensed dealer. Marginal note:Additional information and documents (3)The licensed dealer must, not later than the date specified in the Minister’s written request to that effect, provide the Minister with any information or document that the Minister determines is necessary to complete the review of the application. SOR/2019-169, s. 3 Marginal note:Renewal 11.1 (1)Subject to section 11.3, on completion of the review of the renewal application, the Minister must issue a renewed dealer’s licence that contains the information specified in section 10.1. Marginal note:Terms and conditions (2)When renewing a dealer’s licence, the Minister may, if he or she has reasonable grounds to believe that it is necessary to do so, add a term or condition to it or modify or delete one in order to (a)ensure that an international obligation is respected; (b)ensure conformity with the requirements associated with the security level specified in the licence or the new level required as a result of the licence renewal; or (c)reduce a risk to public health or safety, including the risk of a narcotic being diverted to an illicit market or use. SOR/2019-169, s. 3 Marginal note:Validity 11.2A renewed dealer’s licence is valid until the expiry date set out in the licence or, if it is earlier, the date of the suspension or revocation of the licence under section 16 or 17. SOR/2019-169, s. 3 Marginal note:Refusal 11.3 (1)The Minister must refuse to renew a dealer’s licence if (a)the licensed dealer may no longer apply for a licence under section 9; (b)during the 10 years before the day on which the renewal application is submitted, the licensed dealer has contravened (i)a provision of the Act, the Cannabis Actor their Regulations, or (ii)a term or condition of a licence or permit issued to the dealer under a regulation made under the Act or issued to the dealer under the Cannabis Actor its regulations; (c)during the 10 years before the day on which the renewal application is submitted, the proposed senior person in charge or qualified person in charge or any proposed alternate qualified person in charge was convicted as specified in subparagraph 9.3(a)(i) or (b)(i) or received a sentence as specified in subparagraph 9.3(a)(ii) or (b)(ii); (d)an activity for which the renewal is requested would contravene an international obligation; (e)an activity for which the licence is requested is the cultivation, propagation or harvesting of opium poppy other than for scientific purposes; (f)the licensed dealer does not have in place at the site the security measures set out in the Security Directive in respect of an activity for which the renewal is requested; (g)the method referred to in paragraph 10(1)(j) does not permit the recording of information as required by section 28; (h)the licensed dealer has not complied with the requirements of subsection 11(3) or the information or documents that they have provided are not sufficient to complete the review of the renewal application; (i)the Minister has reasonable grounds to believe that the licensed dealer has submitted false or misleading information or false or falsified documents in or in support of the renewal application; (j)information received from a competent authority or the United Nations gives the Minister reasonable grounds to believe that the licensed dealer has been involved in the diversion of a narcotic to an illicit market or use or has been involved in an activity that contravened an international obligation; or (k)the Minister has reasonable grounds to believe that the renewal of the licence would likely create a risk to public health or safety, including the risk of a narcotic being diverted to an illicit market or use. Marginal note:Exceptions (2)The Minister must not refuse to renew a licence under paragraph (1)(b) or (i) if the licensed dealer meets the following conditions, unless the Minister has reasonable grounds to believe that it is necessary to do so to protect public health or safety, including to prevent a narcotic from being diverted to an illicit market or use: (a)the licensed dealer does not have a history of non-compliance with the Act or the Cannabis Actor their regulations; and (b)the licensed dealer has carried out, or signed an undertaking to carry out, the necessary corrective measures to ensure compliance with the Act, the Cannabis Actand their regulations. Marginal note:Notice (3)Before refusing to renew a licence, the Minister must send the licensed dealer a notice that sets out the Minister’s reasons and gives the dealer an opportunity to be heard. SOR/2019-169, s. 3 Amendment of Licence Marginal note:Application 12 (1)Before making a change affecting any information referred to in section 10.1 that is contained in their dealer’s licence, a licensed dealer must submit to the Minister an application to amend the licence that contains a description of the proposed amendment, as well as the information and documents referred to in section 10 that are relevant to the proposed amendment. Marginal note:Signature and attestation (2)The application must (a)be signed and dated by the senior person in charge of the site specified in the application; and (b)include an attestation by that person that (i)all of the information and documents submitted in support of the application are correct and complete to the best of their knowledge, and (ii)they have the authority to bind the licensed dealer. Marginal note:Additional information and documents (3)The licensed dealer must, not later than the date specified in the Minister’s written request to that effect, provide the Minister with any information or document that the Minister determines is necessary to complete the review of the application. SOR/2013-119, s. 208 SOR/2016-230, s. 278 SOR/2018-147, s. 8 SOR/2019-169, s. 3 Marginal note:Amendment 12.1 (1)Subject to section 12.3, on completion of the review of the amendment application, the Minister must amend the dealer’s licence. Marginal note:Terms and conditions (2)When amending a dealer’s licence, the Minister may, if he or she has reasonable grounds to believe that it is necessary to do so, add a term or condition to it or modify or delete one in order to (a)ensure that an international obligation is respected; (b)ensure conformity with the requirements associated with the security level specified in the licence or the new level required as a result of the amendment; or (c)reduce a risk to public health or safety, including the risk of a narcotic being diverted to an illicit market or use. SOR/2019-169, s. 3 Marginal note:Validity 12.2An amended dealer’s licence is valid until the expiry date set out in the licence or, if it is earlier, the date of the suspension or revocation of the licence under section 16 or 17. SOR/2019-169, s. 3 Marginal note:Refusal 12.3 (1)The Minister must refuse to amend a dealer’s licence if (a)an activity for which the amendment is requested would contravene an international obligation; (b)an activity for which the licence is requested is the cultivation, propagation or harvesting of opium poppy other than for scientific purposes; (c)the licensed dealer does not have in place at the site the security measures set out in the Security Directive in respect of an activity for which the amendment is requested; (d)the method referred to in paragraph 10(1)(j) does not permit the recording of information as required by section 28; (e)the licensed dealer has not complied with the requirements of subsection 12(3) or the information or documents that they have provided are not sufficient to complete the review of the amendment application; (f)the Minister has reasonable grounds to believe that the licensed dealer has submitted false or misleading information or false or falsified documents in or in support of the amendment application; or (g)the Minister has reasonable grounds to believe that the amendment of the licence would likely create a risk to public health or safety, including the risk of a narcotic being diverted to an illicit market or use. Marginal note:Exceptions (2)The Minister must not refuse to amend a licence under paragraph (1)(f) if the licensed dealer meets the following conditions, unless the Minister has reasonable grounds to believe that it is necessary to do so to protect public health or safety, including to prevent a narcotic from being diverted to an illicit market or use: (a)the licensed dealer does not have a history of non-compliance with the Act, the Cannabis Actor their regulations; and (b)the licensed dealer has carried out, or signed an undertaking to carry out, the necessary corrective measures to ensure compliance with the Act, the Cannabis Actand their Regulations. Marginal note:Notice (3)Before refusing to amend a licence, the Minister must send the licensed dealer a notice that sets out the Minister’s reasons and gives the dealer an opportunity to be heard. SOR/2019-169, s. 3 Changes Requiring Prior Approval by Minister Marginal note:Application 13 (1)A licensed dealer must obtain the Minister’s approval before making any of the following changes by submitting a written application to the Minister: (a)a change affecting the security measures in place at the site specified in the dealer’s licence; (b)the replacement of the senior person in charge; (c)the replacement of the qualified person in charge; or (d)the replacement or addition of an alternate qualified person in charge. Marginal note:Information and documents (2)The licensed dealer must provide the Minister with the following with respect to a change referred to in subsection (1): (a)in the case of a change affecting the security measures in place at the site specified in the dealer’s licence, details of the change; (b)in the case of the senior person in charge, (i)the information specified in paragraph 10(1)(c), and (ii)the declaration specified in paragraph 10(2)(b) and the documents specified in paragraphs 10(2)(c) and (d); and (c)in the case of the qualified person in charge or an alternate qualified person in charge, (i)the information specified in paragraph 10(1)(d), and (ii)the declarations specified in paragraphs 10(2)(b) and (e) and the documents specified in paragraphs 10(2)(c), (d) and (f). Marginal note:Additional information and documents (3)The licensed dealer must, not later than the date specified in the Minister’s written request to that effect, provide the Minister with any information or document that the Minister determines is necessary to complete the review of the application. SOR/2004-237, s. 6 SOR/2010-221, s. 8 SOR/2019-169, s. 3 Marginal note:Approval 13.1 (1)Subject to section 13.2, on completion of the review of the application for approval of the change, the Minister must approve the change. Marginal note:Terms and conditions (2)When approving a change, the Minister may, if he or she has reasonable grounds to believe that it is necessary to do so, add a term or condition to the licence or modify or delete one in order to (a)ensure that an international obligation is respected; (b)ensure conformity with the requirements associated with the security level specified in the licence; or (c)reduce a risk to public health or safety, including the risk of a narcotic being diverted to an illicit market or use. SOR/2010-221, s. 8 SOR/2014-260, s. 21 SOR/2019-169, s. 3 Marginal note:Refusal 13.2 (1)The Minister must refuse to approve the change if (a)during the 10 years before the day on which the application for approval of the change is submitted, the proposed senior person in charge or qualified person in charge or any proposed alternate qualified person in charge was convicted as specified in subparagraph 9.3(a)(i) or (b)(i) or received a sentence as specified in subparagraph 9.3(a)(ii) or (b)(ii); (b)the licensed dealer has not complied with the requirements of subsection 13(3) or the information or documents that they have provided are not sufficient to complete the review of the application for approval of the change; (c)the Minister has reasonable grounds to believe that the licensed dealer has submitted false or misleading information or false or falsified documents in or in support of the application for approval of the change; or (d)the Minister has reasonable grounds to believe that the change would likely create a risk to public health or safety, including the risk of a narcotic being diverted to an illicit market or use. Marginal note:Exceptions (2)The Minister must not refuse to approve a change under paragraph (1)(c) if the licensed dealer has carried out, or signed an undertaking to carry out, the necessary corrective measures to ensure compliance with the Act, the Cannabis Actand their regulations, unless the Minister has reasonable grounds to believe that it is necessary to do so to protect public health or safety, including to prevent a narcotic from being diverted to an illicit market or use. Marginal note:Notice (3)Before refusing to approve a change, the Minister must send the licensed dealer a notice that sets out the Minister’s reasons and gives the dealer an opportunity to be heard in respect of them. SOR/2010-221, s. 8 SOR/2019-169, s. 3 Changes Requiring Notice to Minister Marginal note:Prior notice 14 (1)A licensed dealer must notify the Minister in writing before (a)manufacturing or assembling a product or compound that is not set out in the most recent version of the list referred to in paragraph 10(1)(f) that has been submitted to the Minister; or (b)making a change to a product or compound that is set out in the list, if the change affects any of the information that has previously been submitted. Marginal note:Information and list (2)The notice must contain the information referred to in paragraph 10(1)(f) that is necessary to update the list and be accompanied by the revised version of the list. SOR/2004-237, s. 7 SOR/2019-169, s. 3 Marginal note:Notice — five days 14.1A licensed dealer must notify the Minister in writing within five days after a person ceases to act as the qualified person in charge or an alternate qualified person in charge. SOR/2019-169, s. 3 Marginal note:Notice — 10 days 14.2 (1)A licensed dealer must notify the Minister in writing within 10 days after one of the following changes occurs: (a)a person ceases to act as the senior person in charge; or (b)the licensed dealer ceases to manufacture or assemble a product or compound that is set out in the most recent version of the list referred to in paragraph 10(1)(f) that has been submitted to the Minister. Marginal note:Information and list (2)A notice submitted under paragraph (1)(b) must specify which information referred to in paragraph 10(1)(f) is being changed and be accompanied by the revised version of the list. SOR/2019-169, s. 3 Marginal note:Notice of cessation of activities 14.3 (1)A licensed dealer that intends to cease conducting activities at their site — whether on or before the expiry of their licence — must notify the Minister in writing to that effect at least 30 days before ceasing those activities. Marginal note:Content of notice (2)The notice must be signed and dated by the senior person in charge and contain the following information: (a)the expected date of the cessation of activities at the site; (b)a description of the manner in which any remaining narcotics on the site as of that date will be disposed of by the licensed dealer, including (i)if some or all of them will be sold or provided to another licensed dealer that will be conducting activities at the same site, the name of that dealer, (ii)if some or all of them will be sold or provided to another licensed dealer that will not be conducting activities at the same site, the name of that dealer and the municipal address of their site, and (iii)if some or all of them will be destroyed, the date on which and the municipal address of the location at which the destruction is to take place; (c)the municipal address of the location at which the licensed dealer’s documents will be kept after activities have ceased; and (d)the name, municipal address, telephone number and, if applicable, the email address of a person who the Minister may contact for further information after activities have ceased. Marginal note:Update (3)After having ceased to conduct the activities, the licensed dealer must submit to the Minister a detailed update of the information referred to in subsection (2) if it differs from what was set out in the notice. The update must be signed and dated by the senior person in charge. SOR/2019-169, s. 3 Changes to Terms and Conditions of Licence Marginal note:Addition of or modification to term or condition 15 (1)The Minister may, at any time other than at the issuance, renewal or amendment of a dealer’s licence, add a term or condition to it or modify one if the Minister has reasonable grounds to believe that it is necessary to do so to (a)ensure that an international obligation is respected; (b)ensure conformity with the requirements associated with the security level specified in the licence; or (c)reduce a risk to public health or safety, including the risk of a narcotic being diverted to an illicit market or use. Marginal note:Notice (2)Before adding a term or condition to a licence or modifying one, the Minister must send the licensed dealer a notice that sets out the Minister’s reasons and gives the dealer an opportunity to be heard. Marginal note:Urgent circumstances (3)Despite subsection (2), the Minister may add a term or condition to a licence or modify one without prior notice if the Minister has reasonable grounds to believe that it is necessary to do so to protect public health or safety, including to prevent a narcotic from being diverted to an illicit market or use. Marginal note:Urgent circumstances — notice (4)The addition or modification of a term or condition that is made under subsection (3) takes effect as soon as the Minister sends the licensed dealer a notice that (a)sets out the reasons for the addition or modification; (b)gives the dealer an opportunity to be heard; and (c)if applicable, specifies the corrective measures that must be carried out and the date by which they must be carried out. SOR/2004-237, s. 8 SOR/2019-169, s. 3 Marginal note:Deletion of term or condition 15.1 (1)The Minister may delete a term or condition of a dealer’s licence that the Minister determines is no longer necessary. Marginal note:Notice (2)The deletion takes effect as soon as the Minister sends the licensed dealer a notice to that effect. SOR/2019-169, s. 3 Suspension and Revocation of Licence Marginal note:Suspension 16 (1)The Minister must suspend a dealer’s licence without prior notice if the Minister has reasonable grounds to believe that it is necessary to do so to protect public health or safety, including to prevent a narcotic from being diverted to an illicit market or use. Marginal note:Notice (2)The suspension takes effect as soon as the Minister sends the licensed dealer a notice that (a)sets out the reasons for the suspension; (b)gives the dealer an opportunity to be heard; and (c)if applicable, specifies the corrective measures that must be carried out and the date by which they must be carried out. Marginal note:Reinstatement of licence (3)The Minister must reinstate the licence if the Minister has reasonable grounds to believe that the suspension is no longer necessary. SOR/2004-237, s. 9 SOR/2010-221, s. 9 SOR/2019-169, s. 3 Marginal note:Revocation 17 (1)Subject to subsection (2), the Minister must revoke a dealer’s licence if (a)the licensed dealer is no longer eligible to apply for a licence under section 9; (b)the licensed dealer requests the Minister to do so or informs the Minister of the loss or theft of the licence or the actual or potential unauthorized use of the licence; (c)the licensed dealer ceases to conduct activities at their site before the expiry of their licence; (d)the licensed dealer does not take the corrective measures specified in an undertaking or notice; (e)the licensed dealer has contravened (i)a provision of the Act, the Cannabis Actor their regulations, or (ii)a term or condition of a licence or permit issued to the dealer under a regulation made under the Act or issued to the dealer under the Cannabis Actor its regulations; (f)during the 10 years before the day on which the application is submitted, the senior person in charge, the qualified person in charge or any alternate qualified person in charge was convicted as specified in subparagraph 9.3(a)(i) or (b)(i) or received a sentence as specified in subparagraph 9.3(a)(ii) or (b)(ii); (g)the Minister has reasonable grounds to believe that the licensed dealer submitted false or misleading information or false or falsified documents in or in support of an application relating to the licence; or (h)information received from a competent authority or the United Nations gives the Minister reasonable grounds to believe that the licensed dealer has been involved in the diversion of a narcotic to an illicit market or use. Marginal note:Exceptions (2)The Minister must not revoke a dealer’s licence for a ground set out in paragraph (1)(e) or (g) if the licensed dealer meets the following conditions, unless the Minister has reasonable grounds to believe that it is necessary to do so to protect public health or safety, including to prevent a narcotic from being diverted to an illicit market or use: (a)the licensed dealer does not have a history of non-compliance with the Act, the Cannabis Actor their regulations; and (b)the licensed dealer has carried out, or signed an undertaking to carry out, the necessary corrective measures to ensure compliance with the Act, the Cannabis Actand their regulations. Marginal note:Notice (3)Before revoking a licence, the Minister must send the licensed dealer a notice that sets out the Minister’s reasons and gives the dealer an opportunity to be heard. SOR/2019-169, s. 3 Marginal note:Return of licence 17.1The licensed dealer must return the original of the licence to the Minister within 15 days after the effective date of the revocation. SOR/2019-169, s. 3 Import Permits Marginal note:Application 18 (1)A licensed dealer must submit to the Minister, before each importation of a narcotic, an application for an import permit that contains the following information: (a)their name, municipal address and dealer’s licence number; (b)with respect to the narcotic to be imported, (i)its name, as specified in the dealer’s licence, (ii)if it is a salt, the name of the salt, (iii)its quantity, and (iv)in the case of a raw material, its purity and its anhydrous content; (c)if the narcotic is contained in a product to be imported, (i)the brand name of the product, (ii)the drug identification number that has been assigned to the product under section C.01.014.2 of the Food and Drug Regulations, if any, and (iii)the strength per unit of the narcotic in the product, the number of units per package and the number of packages; (d)the name and municipal address of the exporter in the country of export from whom the narcotic is being obtained; (e)the name of the customs office where the importation is anticipated; and (f)each proposed mode of transportation and any proposed country of transit or transhipment. Marginal note:Signature and attestation (2)The application must (a)be signed and dated by the qualified person in charge or an alternate qualified person in charge; and (b)include an attestation by that person that all of the information submitted in support of the application is correct and complete to the best of their knowledge. Marginal note:Additional information and documents (3)The licensed dealer must, not later than the date specified in the Minister’s written request to that effect, provide the Minister with any information or document that the Minister determines is necessary to complete the review of the application. SOR/2019-169, s. 3 Marginal note:Issuance 18.1Subject to section 18.4, on completion of the review of the import permit application, the Minister must issue to the licensed dealer an import permit that contains (a)the permit number; (b)the information set out in subsection 18(1); (c)the effective date of the permit; (d)the expiry date of the permit, being the earlier of (i)a date specified by the Minister that is not more than 180 days after its effective date, and (ii)the expiry date of the dealer’s licence; and (e)any terms and conditions that the Minister has reasonable grounds to believe are necessary to (i)ensure that an international obligation is respected, or (ii)reduce a risk to public health or safety, including the risk of a narcotic being diverted to an illicit market or use. SOR/2019-169, s. 3 Marginal note:Validity 18.2An import permit is valid until the earliest of (a)the expiry date set out in the permit, (b)the date of the suspension or revocation of the permit under section 19 or 20, (c)the date of the suspension or revocation of the dealer’s licence under section 16 or 17, and (d)the date of the suspension or revocation of the export permit that applies to the narcotic to be imported and that is issued by the competent authority in the country of export. SOR/2019-169, s. 3 Marginal note:Return of permit 18.3If an import permit expires, the licensed dealer must return the original of the permit to the Minister within 15 days after its expiry. SOR/2019-169, s. 3 Marginal note:Refusal 18.4 (1)The Minister must refuse to issue an import permit if (a)the licensed dealer is not authorized by their dealer’s licence to import the relevant narcotic or their licence will expire before the date of importation; (b)the Minister has reasonable grounds to believe that the importation would contravene an international obligation; (c)the licensed dealer does not have in place at the site the security measures set out in the Security Directive in respect of the importation; (d)the licensed dealer has not complied with the requirements of subsection 18(3) or the information or documents that they have provided are not sufficient to complete the review of the permit application; (e)the Minister has reasonable grounds to believe that the licensed dealer has submitted false or misleading information or false or falsified documents in or in support of the permit application; (f)the licensed dealer has been notified that their application to renew or amend their licence will be refused; (g)the Minister has reasonable grounds to believe that the importation would contravene the laws of the country of export or any country of transit or transhipment; or (h)the Minister has reasonable grounds to believe that the issuance of the permit would likely create a risk to public health or safety, including the risk of a narcotic being diverted to an illicit market or use. Marginal note:Notice (2)Before refusing to issue the import permit, the Minister must send the licensed dealer a notice that sets out the Minister’s reasons and gives the dealer an opportunity to be heard. SOR/2019-169, s. 3 Marginal note:Providing copy of permit 18.5The holder of an import permit must provide a copy of the permit to the customs office at the time of importation. SOR/2019-169, s. 3 Marginal note:Declaration 18.6The holder of an import permit must provide the Minister, within 15 days after the day of release of the narcotic specified in the permit in accordance with the Customs Act, with a declaration that contains the following information: (a)their name and the numbers of their dealer’s licence and the import permit that applies to the narcotic; (b)with respect to the narcotic, (i)its name, as set out in the dealer’s licence, (ii)if it is a salt, the name of the salt, and (iii)its quantity; (c)if the narcotic is contained in a product that they have imported, (i)the brand name of the product, (ii)the drug identification number that has been assigned to the product under section C.01.014.2 of the Food and Drug Regulations, if any, and (iii)the strength per unit of the narcotic in the product, the number of units per package and the number of packages; and (d)the name of the customs office from which the narcotic was released and the date of the release. SOR/2019-169, s. 3 Marginal note:Suspension 19 (1)The Minister must suspend an import permit without prior notice if (a)the dealer’s licence is suspended; (b)the Minister has reasonable grounds to believe that the suspension is necessary to protect public health or safety, including to prevent a narcotic from being diverted to an illicit market or use; or (c)the importation would contravene the laws of the country of export or any country of transit or transhipment. Marginal note:Notice (2)The suspension takes effect as soon as the Minister sends the licensed dealer a notice that (a)sets out the reasons for the suspension; (b)gives the dealer an opportunity to be heard; and (c)if applicable, specifies the corrective measures that must be carried out and the date by which they must be carried out. Marginal note:Reinstatement of permit (3)The Minister must reinstate the import permit if the Minister has reasonable grounds to believe that the suspension is no longer necessary. SOR/2004-237, s. 10 SOR/2010-221, s. 10 SOR/2019-169, s. 3 Marginal note:Revocation 20 (1)Subject to subsection (2), the Minister must revoke an import permit if (a)the licensed dealer requests the Minister to do so or informs the Minister of the loss or theft of the permit or the actual or potential unauthorized use of the permit; (b)the licensed dealer does not carry out the corrective measures specified by the Minister under paragraph 19(2)(c) by the specified date; (c)the licensed dealer has contravened a term or condition of the permit; (d)the Minister has reasonable grounds to believe that the licensed dealer submitted false or misleading information or false or falsified documents in or in support of the application for the permit; (e)information received from a competent authority or the United Nations gives the Minister reasonable grounds to believe that the licensed dealer has been involved in the diversion of a narcotic to an illicit market or use; or (f)the dealer’s licence has been revoked. Marginal note:Exceptions (2)The Minister must not revoke an import permit for a ground set out in paragraph (1)(d) or 17(1)(e) or (g) if the licensed dealer meets the following conditions, unless the Minister has reasonable grounds to believe that it is necessary to do so to protect public health or safety, including to prevent a narcotic from being diverted to an illicit market or use: (a)the licensed dealer does not have a history of non-compliance with the Act, the Cannabis Actor their regulations; and (b)the licensed dealer has carried out, or signed an undertaking to carry out, the necessary corrective measures to ensure compliance with the Act, the Cannabis Actand their regulations. Marginal note:Notice (3)Before revoking an import permit, the Minister must send the licensed dealer a notice that sets out the Minister’s reasons and gives the dealer an opportunity to be heard. SOR/2019-169, s. 3 Marginal note:Return of permit 20.1If an import permit is revoked, the licensed dealer must return the original of the permit to the Minister within 15 days after the effective date of the revocation. SOR/2019-169, s. 3 Export Permits Marginal note:Application 21 (1)A licensed dealer must submit to the Minister, before each exportation of a narcotic, an application for an export permit that contains the following information and document: (a)their name, municipal address and dealer’s licence number; (b)with respect to the narcotic to be exported, (i)its name, as specified in the dealer’s licence, (ii)if it is a salt, the name of the salt, (iii)its quantity, and (iv)in the case of a raw material, its purity and its anhydrous content; (c)in the case of the exportation of a product that contains the narcotic, (i)the brand name of the product, (ii)the drug identification number that has been assigned to the product under section C.01.014.2 of the Food and Drug Regulations, if any, and (iii)the strength per unit of the narcotic in the product, the number of units per package and the number of packages; (d)the name and municipal address of the importer in the country of final destination; (e)the name of the customs office where the exportation is anticipated; (f)each proposed mode of transportation to be used and any proposed country of transit or transhipment; and (g)a copy of the import permit issued by the competent authority in the country of final destination that sets out the name of the importer and the municipal address of their site in that country. Marginal note:Signature and attestation (2)The application must (a)be signed and dated by the qualified person in charge or an alternate qualified person in charge; and (b)include an attestation by that person that, to the best of their knowledge, (i)the exportation does not contravene any requirement of the laws of the country of final destination or any country of transit or transhipment, and (ii)all of the information and documents submitted in support of the application are correct and complete. Marginal note:Additional information and documents (3)The licensed dealer must, not later than the date specified in the Minister’s written request to that effect, provide the Minister with any information or document that the Minister determines is necessary to complete the review of the application. SOR/2019-169, s. 3 Marginal note:Issuance 21.1Subject to section 21.4, on completion of the review of the export permit application, the Minister must issue to the licensed dealer an export permit that contains (a)the permit number; (b)the information set out in paragraphs 21(1)(a) to (f); (c)the effective date of the permit; (d)the expiry date of the permit, being the earliest of (i)a date specified by the Minister that is not more than 180 days after its effective date, (ii)the expiry date of the dealer’s licence, and (iii)the expiry date of the import permit issued by the competent authority in the country of final destination; and (e)any terms and conditions that the Minister has reasonable grounds to believe are necessary to (i)ensure that an international obligation is respected, or (ii)reduce a risk to public health or safety, including the risk of a narcotic being diverted to an illicit market or use. SOR/2019-169, s. 3 Marginal note:Validity 21.2An export permit is valid until the earliest of (a)the expiry date set out in the permit, (b)the date of the suspension or revocation of the permit under section 22 or 23, (c)the date of the suspension or revocation of the dealer’s licence under section 16 or 17, and (d)the date of the expiry, suspension or revocation of the import permit that applies to the narcotic to be exported and that is issued by the competent authority in the country of final destination. SOR/2019-169, s. 3 Marginal note:Return of permit 21.3If an export permit expires, the licensed dealer must return the original of the permit to the Minister within 15 days after its expiry. SOR/2019-169, s. 3 Marginal note:Refusal 21.4 (1)The Minister must refuse to issue an export permit if
https://laws-lois.justice.gc.ca/eng/Regulations/C.R.C.,_c._1041/20191209/P1TT3xt3.html
Re: [PATCH v35 10/13] target/avr: Add limited support for USART and 16 b Re: [PATCH v35 10/13] target/avr: Add limited support for USART and 16 b From : Aleksandar Markovic Subject : Re: [PATCH v35 10/13] target/avr: Add limited support for USART and 16 bit timer peripherals Date : Thu, 28 Nov 2019 11:55:02 +0100 On Thursday, November 28, 2019, Sarah Harris < address@hidden > wrote: Hi Aleksandar, > Sarah, thanks for taking your tome to respond! No problem! :) > do we fully support what is said in: > * 22.6.2 Sending Frames with 9 Data Bit > * 22.7.2 Receiving Frames with 9 Data Bits No, QEMU's character device system only supports 8 bit characters. Shorter characters can be padded easily, but longer is a problem. At the moment we just emit a warning and ignore the extra bit in UCSRnB (i.e. behave as if 8 bits was selected). > And the same question for section: > * 22.9 Multi-processor Communication Mode No, this was out of scope for testing use. This case is checked when writing to the UCSRnA register, `if (value & USART_CSRA_MPCM)`, and causes a warning. I don't know if we should crash instead, but at the moment we just log the warning and continue. (USART emulation will be incorrect from when this happens and until MPCM is disabled) OK. Thanks. All this sounds reasonable to me. Do you agree that we insert: /* * Limitation of this emulation: * *   * Sending and receiving frames with 9 data bits sre not supported *   * Multi-processor communication mode is not supported */ or a similar comment, close to the top of the file? Yours, Aleksandar Kind regards, Sarah Harris On Mon, 25 Nov 2019 19:57:48 +0100 Aleksandar Markovic < address@hidden > wrote: > On Mon, Nov 25, 2019 at 4:57 PM Sarah Harris < address@hidden > wrote: > > > > Hi Aleksandar, > > > > > - Is there a place in docs that explain its implementation in general? > > This implementation was based on the datasheet for the ATmega2560 ("ATmega640/1280/1281/2560/ 2561 datasheet" available from Microchip's website). > > (I'm not sure if posting a URL will trigger any spam filters, so I'll leave it for now) > > See section 22.10, "USART - Register Description". > > > > OK. > > > > - Why do cases 4, 5, 6 issue relatively unclear error message > > > ""update_char_mask(): Reserved character size <mode>"? Is there a > > > better wording perhaps? Where is justification in the doc for these > > > cases? > > The hardware can send/receive characters of various lengths, specified by settings in these configuration registers. > > The cases are defined in table 22-7, "UCSZn Bits Settings", which specifies that modes 4, 5, and 6 are reserved and should not be used. > > I'm not sure how better to explain this fault to the user; this is an edge case that I'd expect only an AVR developer testing their own program to see, so describing it in the same way as the datasheet seems a good idea. > > > > OK. I somehow missed table 22-7 while comparing the code and specs - my bad. > > > > - What would be the docs justification for case 7? Why is an error > > > message issued, but still "char_mask" is set, and I guess, further > > > processing will go on? Why the error message says "Nine bit character > > > requested"? Who said that (that *nine* bit characters were requested? > > > :-) > > Case 7 also comes from table 22-7, and specifies that the USART should send/receive 9 bits per character. > > For characters <= 8 bits it's easy to pad them to the 8 bit bytes that the character device subsystem operates on. > > For characters of 9 bits we'd have to throw away one bit, which seems like a bad thing to do. > > I decided it wasn't enough to justify crashing, but the user should be made aware that data is being lost and the output might not be what they would otherwise expect. > > > > Sarah, thanks for taking your tome to respond! Could you just explain > to me do we fully support what is said in: > > * 22.6.2 Sending Frames with 9 Data Bit > * 22.7.2 Receiving Frames with 9 Data Bits > > or perhaps there are some limitations? > > And the same question for section: > > * 22.9 Multi-processor Communication Mode > > Please note that I don't suggest amending or extending your > implementation, I just want to understand it better. > > Best regards, > Aleksandar > > > > Kind regards, > > Sarah Harris > > > > > > Aleksandar Markovic < address@hidden > wrote: > > > > > On Tue, Oct 29, 2019 at 10:25 PM Michael Rolnik < address@hidden > wrote: > > > > > > > > From: Sarah Harris < address@hidden > > > > > > > > > These were designed to facilitate testing but should provide enough function to be useful in other contexts. > > > > Only a subset of the functions of each peripheral is implemented, mainly due to the lack of a standard way to handle electrical connections (like GPIO pins). > > > > > > > > Signed-off-by: Sarah Harris < address@hidden > > > > > --- > > > >  hw/char/Kconfig                |   3 + > > > >  hw/char/Makefile.objs          |   1 + > > > >  hw/char/avr_usart.c            | 324 ++++++++++++++++++ > > > >  hw/misc/Kconfig                |   3 + > > > >  hw/misc/Makefile.objs          |   2 + > > > >  hw/misc/avr_mask.c             | 112 ++++++ > > > >  hw/timer/Kconfig               |   3 + > > > >  hw/timer/Makefile.objs         |   2 + > > > >  hw/timer/avr_timer16.c         | 605 ++++++++++++++++++++++++++++++ +++ > > > >  include/hw/char/avr_usart.h    |  97 ++++++ > > > >  include/hw/misc/avr_mask.h     |  47 +++ > > > >  include/hw/timer/avr_timer16.h |  97 ++++++ > > > >  12 files changed, 1296 insertions(+) > > > >  create mode 100644 hw/char/avr_usart.c > > > >  create mode 100644 hw/misc/avr_mask.c > > > >  create mode 100644 hw/timer/avr_timer16.c > > > >  create mode 100644 include/hw/char/avr_usart.h > > > >  create mode 100644 include/hw/misc/avr_mask.h > > > >  create mode 100644 include/hw/timer/avr_timer16.h > > > > > > > > diff --git a/hw/char/Kconfig b/hw/char/Kconfig > > > > index 40e7a8b8bb..331b20983f 100644 > > > > --- a/hw/char/Kconfig > > > > +++ b/hw/char/Kconfig > > > > @@ -46,3 +46,6 @@ config SCLPCONSOLE > > > > > > > >  config TERMINAL3270 > > > >      bool > > > > + > > > > +config AVR_USART > > > > +    bool > > > > diff --git a/hw/char/Makefile.objs b/hw/char/Makefile.objs > > > > index 02d8a66925..f05c1f5667 100644 > > > > --- a/hw/char/Makefile.objs > > > > +++ b/hw/char/Makefile.objs > > > > @@ -21,6 +21,7 @@ obj-$(CONFIG_PSERIES) += spapr_vty.o > > > >  obj-$(CONFIG_DIGIC) += digic-uart.o > > > >  obj-$(CONFIG_STM32F2XX_USART) += stm32f2xx_usart.o > > > >  obj-$(CONFIG_RASPI) += bcm2835_aux.o > > > > +common-obj-$(CONFIG_AVR_ USART) += avr_usart.o > > > > > > > >  common-obj-$(CONFIG_CMSDK_APB_ UART) += cmsdk-apb-uart.o > > > >  common-obj-$(CONFIG_ETRAXFS) += etraxfs_ser.o > > > > diff --git a/hw/char/avr_usart.c b/hw/char/avr_usart.c > > > > new file mode 100644 > > > > index 0000000000..9ca3c2a1cd > > > > --- /dev/null > > > > +++ b/hw/char/avr_usart.c > > > > @@ -0,0 +1,324 @@ > > > > +/* > > > > + * AVR USART > > > > + * > > > > + * Copyright (c) 2018 University of Kent > > > > + * Author: Sarah Harris > > > > + * > > > > + * Permission is hereby granted, free of charge, to any person obtaining a copy > > > > + * of this software and associated documentation files (the "Software"), to deal > > > > + * in the Software without restriction, including without limitation the rights > > > > + * to use, copy, modify, merge, publish, distribute, sublicense, and/or sell > > > > + * copies of the Software, and to permit persons to whom the Software is > > > > + * furnished to do so, subject to the following conditions: > > > > + * > > > > + * The above copyright notice and this permission notice shall be included in > > > > + * all copies or substantial portions of the Software. > > > > + * > > > > + * THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR > > > > + * IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, > > > > + * FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL > > > > + * THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER > > > > + * LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, > > > > + * OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN > > > > + * THE SOFTWARE. > > > > + */ > > > > + > > > > +#include "qemu/osdep.h" > > > > +#include "hw/char/avr_usart.h" > > > > +#include "qemu/log.h" > > > > +#include "hw/irq.h" > > > > +#include "hw/qdev-properties.h" > > > > + > > > > +static int avr_usart_can_receive(void *opaque) > > > > +{ > > > > +    AVRUsartState *usart = opaque; > > > > + > > > > +    if (usart->data_valid || !(usart->csrb & USART_CSRB_RXEN)) { > > > > +        return 0; > > > > +    } > > > > +    return 1; > > > > +} > > > > + > > > > +static void avr_usart_receive(void *opaque, const uint8_t *buffer, int size) > > > > +{ > > > > +    AVRUsartState *usart = opaque; > > > > +    assert(size == 1); > > > > +    assert(!usart->data_valid); > > > > +    usart->data = ""> > > > > +    usart->data_valid = true; > > > > +    usart->csra |= USART_CSRA_RXC; > > > > +    if (usart->csrb & USART_CSRB_RXCIE) { > > > > +        qemu_set_irq(usart->rxc_irq, 1); > > > > +    } > > > > +} > > > > + > > > > +static void update_char_mask(AVRUsartState *usart) > > > > +{ > > > > +    uint8_t mode = ((usart->csrc & USART_CSRC_CSZ0) ? 1 : 0) | > > > > +        ((usart->csrc & USART_CSRC_CSZ1) ? 2 : 0) | > > > > +        ((usart->csrb & USART_CSRB_CSZ2) ? 4 : 0); > > > > +    switch (mode) { > > > > +    case 0: > > > > +        usart->char_mask = 0b11111; > > > > +        break; > > > > +    case 1: > > > > +        usart->char_mask = 0b111111; > > > > +        break; > > > > +    case 2: > > > > +        usart->char_mask = 0b1111111; > > > > +        break; > > > > +    case 3: > > > > +        usart->char_mask = 0b11111111; > > > > +        break; > > > > +    case 4: > > > > +        /* Fallthrough. */ > > > > +    case 5: > > > > +        /* Fallthrough. */ > > > > +    case 6: > > > > +        qemu_log_mask( > > > > +            LOG_GUEST_ERROR, > > > > +            "%s: Reserved character size 0x%x\n", > > > > +            __func__, > > > > +            mode); > > > > +        break; > > > > +    case 7: > > > > +        qemu_log_mask( > > > > +            LOG_GUEST_ERROR, > > > > +            "%s: Nine bit character size not supported (forcing eight)\n", > > > > +            __func__); > > > > +        usart->char_mask = 0b11111111; > > > > +        break; > > > > +    default: > > > > +        assert(0); > > > > +    } > > > > +} > > > > + > > > > > > Hello, Michael. > > > > > > Please explain to me some details of update_char_mask(): > > > > > > - Is there a place in docs that explain its implementation in general? > > > > > > - Why do cases 4, 5, 6 issue relatively unclear error message > > > ""update_char_mask(): Reserved character size <mode>"? Is there a > > > better wording perhaps? Where is justification in the doc for these > > > cases? > > > > > > - What would be the docs justification for case 7? Why is an error > > > message issued, but still "char_mask" is set, and I guess, further > > > processing will go on? Why the error message says "Nine bit character > > > requested"? Who said that (that *nine* bit characters were requested? > > > :-) > > > > > > Sincerely, > > > Aleksandar > > > > > > > > > > > > > > > > > > > > > > +static void avr_usart_reset(DeviceState *dev) > > > > +{ > > > > +    AVRUsartState *usart = AVR_USART(dev); > > > > +    usart->data_valid = false; > > > > +    usart->csra = 0b00100000; > > > > +    usart->csrb = 0b00000000; > > > > +    usart->csrc = 0b00000110; > > > > +    usart->brrl = 0; > > > > +    usart->brrh = 0; > > > > +    update_char_mask(usart); > > > > +    qemu_set_irq(usart->rxc_irq, 0); > > > > +    qemu_set_irq(usart->txc_irq, 0); > > > > +    qemu_set_irq(usart->dre_irq, 0); > > > > +} > > > > + > > > > +static uint64_t avr_usart_read(void *opaque, hwaddr addr, unsigned int size) > > > > +{ > > > > +    AVRUsartState *usart = opaque; > > > > +    uint8_t data; > > > > +    assert(size == 1); > > > > + > > > > +    if (!usart->enabled) { > > > > +        return 0; > > > > +    } > > > > + > > > > +    switch (addr) { > > > > +    case USART_DR: > > > > +        if (!(usart->csrb & USART_CSRB_RXEN)) { > > > > +            /* Receiver disabled, ignore. */ > > > > +            return 0; > > > > +        } > > > > +        if (usart->data_valid) { > > > > +            data = "" & usart->char_mask; > > > > +            usart->data_valid = false; > > > > +        } else { > > > > +            data = ""> > > > > +        } > > > > +        usart->csra &= 0xff ^ USART_CSRA_RXC; > > > > +        qemu_set_irq(usart->rxc_irq, 0); > > > > +        qemu_chr_fe_accept_input(& usart->chr); > > > > +        return data; > > > > +    case USART_CSRA: > > > > +        return usart->csra; > > > > +    case USART_CSRB: > > > > +        return usart->csrb; > > > > +    case USART_CSRC: > > > > +        return usart->csrc; > > > > +    case USART_BRRL: > > > > +        return usart->brrl; > > > > +    case USART_BRRH: > > > > +        return usart->brrh; > > > > +    default: > > > > +        qemu_log_mask( > > > > +            LOG_GUEST_ERROR, > > > > +            "%s: Bad offset 0x%"HWADDR_PRIx"\n", > > > > +            __func__, > > > > +            addr); > > > > +    } > > > > +    return 0; > > > > +} > > > > + > > > > +static void avr_usart_write(void *opaque, hwaddr addr, uint64_t value, > > > > +                                unsigned int size) > > > > +{ > > > > +    AVRUsartState *usart = opaque; > > > > +    uint8_t mask; > > > > +    uint8_t data; > > > > +    assert((value & 0xff) == value); > > > > +    assert(size == 1); > > > > + > > > > +    if (!usart->enabled) { > > > > +        return; > > > > +    } > > > > + > > > > +    switch (addr) { > > > > +    case USART_DR: > > > > +        if (!(usart->csrb & USART_CSRB_TXEN)) { > > > > +            /* Transmitter disabled, ignore. */ > > > > +            return; > > > > +        } > > > > +        usart->csra |= USART_CSRA_TXC; > > > > +        usart->csra |= USART_CSRA_DRE; > > > > +        if (usart->csrb & USART_CSRB_TXCIE) { > > > > +            qemu_set_irq(usart->txc_irq, 1); > > > > +            usart->csra &= 0xff ^ USART_CSRA_TXC; > > > > +        } > > > > +        if (usart->csrb & USART_CSRB_DREIE) { > > > > +            qemu_set_irq(usart->dre_irq, 1); > > > > +        } > > > > +        data = ""> > > > > +        qemu_chr_fe_write_all(&usart-> chr, &data, 1); > > > > +        break; > > > > +    case USART_CSRA: > > > > +        mask = 0b01000011; > > > > +        /* Mask read-only bits. */ > > > > +        value = (value & mask) | (usart->csra & (0xff ^ mask)); > > > > +        usart->csra = value; > > > > +        if (value & USART_CSRA_TXC) { > > > > +            usart->csra ^= USART_CSRA_TXC; > > > > +            qemu_set_irq(usart->txc_irq, 0); > > > > +        } > > > > +        if (value & USART_CSRA_MPCM) { > > > > +            qemu_log_mask( > > > > +                LOG_GUEST_ERROR, > > > > +                "%s: MPCM not supported by USART\n", > > > > +                __func__); > > > > +        } > > > > +        break; > > > > +    case USART_CSRB: > > > > +        mask = 0b11111101; > > > > +        /* Mask read-only bits. */ > > > > +        value = (value & mask) | (usart->csrb & (0xff ^ mask)); > > > > +        usart->csrb = value; > > > > +        if (!(value & USART_CSRB_RXEN)) { > > > > +            /* Receiver disabled, flush input buffer. */ > > > > +            usart->data_valid = false; > > > > +        } > > > > +        qemu_set_irq(usart->rxc_irq, > > > > +            ((value & USART_CSRB_RXCIE) && > > > > +            (usart->csra & USART_CSRA_RXC)) ? 1 : 0); > > > > +        qemu_set_irq(usart->txc_irq, > > > > +            ((value & USART_CSRB_TXCIE) && > > > > +            (usart->csra & USART_CSRA_TXC)) ? 1 : 0); > > > > +        qemu_set_irq(usart->dre_irq, > > > > +            ((value & USART_CSRB_DREIE) && > > > > +            (usart->csra & USART_CSRA_DRE)) ? 1 : 0); > > > > +        update_char_mask(usart); > > > > +        break; > > > > +    case USART_CSRC: > > > > +        usart->csrc = value; > > > > +        if ((value & USART_CSRC_MSEL1) && (value & USART_CSRC_MSEL0)) { > > > > +            qemu_log_mask( > > > > +                LOG_GUEST_ERROR, > > > > +                "%s: SPI mode not supported by USART\n", > > > > +                __func__); > > > > +        } > > > > +        if ((value & USART_CSRC_MSEL1) && !(value & USART_CSRC_MSEL0)) { > > > > +            qemu_log_mask(LOG_GUEST_ERROR, "%s: Bad USART mode\n", __func__); > > > > +        } > > > > +        if (!(value & USART_CSRC_PM1) && (value & USART_CSRC_PM0)) { > > > > +            qemu_log_mask( > > > > +                LOG_GUEST_ERROR, > > > > +                "%s: Bad USART parity mode\n", > > > > +                __func__); > > > > +        } > > > > +        update_char_mask(usart); > > > > +        break; > > > > +    case USART_BRRL: > > > > +        usart->brrl = value; > > > > +        break; > > > > +    case USART_BRRH: > > > > +        usart->brrh = value & 0b00001111; > > > > +        break; > > > > +    default: > > > > +        qemu_log_mask( > > > > +            LOG_GUEST_ERROR, > > > > +            "%s: Bad offset 0x%"HWADDR_PRIx"\n", > > > > +            __func__, > > > > +            addr); > > > > +    } > > > > +} > > > > + > > > > +static const MemoryRegionOps avr_usart_ops = { > > > > +    .read = avr_usart_read, > > > > +    .write = avr_usart_write, > > > > +    .endianness = DEVICE_NATIVE_ENDIAN, > > > > +    .impl = {.min_access_size = 1, .max_access_size = 1} > > > > +}; > > > > + > > > > +static Property avr_usart_properties[] = { > > > > +    DEFINE_PROP_CHR("chardev", AVRUsartState, chr), > > > > +    DEFINE_PROP_END_OF_LIST(), > > > > +}; > > > > + > > > > +static void avr_usart_pr(void *opaque, int irq, int level) > > > > +{ > > > > +    AVRUsartState *s = AVR_USART(opaque); > > > > + > > > > +    s->enabled = !level; > > > > + > > > > +    if (!s->enabled) { > > > > +        avr_usart_reset(DEVICE(s)); > > > > +    } > > > > +} > > > > + > > > > +static void avr_usart_init(Object *obj) > > > > +{ > > > > +    AVRUsartState *s = AVR_USART(obj); > > > > +    sysbus_init_irq(SYS_BUS_ DEVICE(obj), &s->rxc_irq); > > > > +    sysbus_init_irq(SYS_BUS_ DEVICE(obj), &s->dre_irq); > > > > +    sysbus_init_irq(SYS_BUS_ DEVICE(obj), &s->txc_irq); > > > > +    memory_region_init_io(&s-> mmio, obj, &avr_usart_ops, s, TYPE_AVR_USART, 8); > > > > +    sysbus_init_mmio(SYS_BUS_ DEVICE(obj), &s->mmio); > > > > +    qdev_init_gpio_in(DEVICE(s), avr_usart_pr, 1); > > > > +    s->enabled = true; > > > > +} > > > > + > > > > +static void avr_usart_realize(DeviceState *dev, Error **errp) > > > > +{ > > > > +    AVRUsartState *s = AVR_USART(dev); > > > > +    qemu_chr_fe_set_handlers(&s-> chr, avr_usart_can_receive, > > > > +                             avr_usart_receive, NULL, NULL, > > > > +                             s, NULL, true); > > > > +    avr_usart_reset(dev); > > > > +} > > > > + > > > > +static void avr_usart_class_init( ObjectClass *klass, void *data) > > > > +{ > > > > +    DeviceClass *dc = DEVICE_CLASS(klass); > > > > + > > > > +    dc->reset = avr_usart_reset; > > > > +    dc->props = avr_usart_properties; > > > > +    dc->realize = avr_usart_realize; > > > > +} > > > > + > > > > +static const TypeInfo avr_usart_info = { > > > > +    .name          = TYPE_AVR_USART, > > > > +    .parent        = TYPE_SYS_BUS_DEVICE, > > > > +    .instance_size = sizeof(AVRUsartState), > > > > +    .instance_init = avr_usart_init, > > > > +    .class_init    = avr_usart_class_init, > > > > +}; > > > > + > > > > +static void avr_usart_register_types(void) > > > > +{ > > > > +    type_register_static(&avr_ usart_info); > > > > +} > > > > + > > > > +type_init(avr_usart_register_ types) > > > > diff --git a/hw/misc/Kconfig b/hw/misc/Kconfig > > > > index 2164646553..e79841e3a4 100644 > > > > --- a/hw/misc/Kconfig > > > > +++ b/hw/misc/Kconfig > > > > @@ -125,4 +125,7 @@ config MAC_VIA > > > >      select MOS6522 > > > >      select ADB > > > > > > > > +config AVR_MASK > > > > +    bool > > > > + > > > >  source macio/Kconfig > > > > diff --git a/hw/misc/Makefile.objs b/hw/misc/Makefile.objs > > > > index ba898a5781..3a8093be6a 100644 > > > > --- a/hw/misc/Makefile.objs > > > > +++ b/hw/misc/Makefile.objs > > > > @@ -82,3 +82,5 @@ common-obj-$(CONFIG_NRF51_SOC) += nrf51_rng.o > > > >  obj-$(CONFIG_MAC_VIA) += mac_via.o > > > > > > > >  common-obj-$(CONFIG_GRLIB) += grlib_ahb_apb_pnp.o > > > > + > > > > +obj-$(CONFIG_AVR_MASK) += avr_mask.o > > > > diff --git a/hw/misc/avr_mask.c b/hw/misc/avr_mask.c > > > > new file mode 100644 > > > > index 0000000000..3af82ed9c1 > > > > --- /dev/null > > > > +++ b/hw/misc/avr_mask.c > > > > @@ -0,0 +1,112 @@ > > > > +/* > > > > + * AVR Power Reduction > > > > + * > > > > + * Copyright (c) 2019 Michael Rolnik > > > > + * > > > > + * Permission is hereby granted, free of charge, to any person obtaining a copy > > > > + * of this software and associated documentation files (the "Software"), to deal > > > > + * in the Software without restriction, including without limitation the rights > > > > + * to use, copy, modify, merge, publish, distribute, sublicense, and/or sell > > > > + * copies of the Software, and to permit persons to whom the Software is > > > > + * furnished to do so, subject to the following conditions: > > > > + * > > > > + * The above copyright notice and this permission notice shall be included in > > > > + * all copies or substantial portions of the Software. > > > > + * > > > > + * THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR > > > > + * IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, > > > > + * FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL > > > > + * THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER > > > > + * LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, > > > > + * OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN > > > > + * THE SOFTWARE. > > > > + */ > > > > + > > > > +#include "qemu/osdep.h" > > > > +#include "hw/misc/avr_mask.h" > > > > +#include "qemu/log.h" > > > > +#include "hw/qdev-properties.h" > > > > +#include "hw/irq.h" > > > > + > > > > +#define DB_PRINT(fmt, args...) /* Nothing */ > > > > +/*#define DB_PRINT(fmt, args...) printf("%s: " fmt "\n", __func__, ## args)*/ > > > > + > > > > +static void avr_mask_reset(DeviceState *dev) > > > > +{ > > > > +    AVRMaskState *s = AVR_MASK(dev); > > > > + > > > > +    s->val = 0x00; > > > > + > > > > +    for (int i = 0; i < 8; i++) { > > > > +        qemu_set_irq(s->irq[i], 0); > > > > +    } > > > > +} > > > > + > > > > +static uint64_t avr_mask_read(void *opaque, hwaddr offset, unsigned size) > > > > +{ > > > > +    assert(size == 1); > > > > +    assert(offset == 0); > > > > +    AVRMaskState *s = opaque; > > > > + > > > > +    return (uint64_t)s->val; > > > > +} > > > > + > > > > +static void avr_mask_write(void *opaque, hwaddr offset, > > > > +                              uint64_t val64, unsigned size) > > > > +{ > > > > +    assert(size == 1); > > > > +    assert(offset == 0); > > > > +    AVRMaskState *s = opaque; > > > > +    uint8_t val8 = val64; > > > > + > > > > +    DB_PRINT("write %d to offset %d", val8, (uint8_t)offset); > > > > + > > > > +    s->val = val8; > > > > +    for (int i = 0; i < 8; i++) { > > > > +        qemu_set_irq(s->irq[i], (val8 & (1 << i)) != 0); > > > > +    } > > > > +} > > > > + > > > > +static const MemoryRegionOps avr_mask_ops = { > > > > +    .read = avr_mask_read, > > > > +    .write = avr_mask_write, > > > > +    .endianness = DEVICE_NATIVE_ENDIAN, > > > > +    .impl = {.max_access_size = 1} > > > > +}; > > > > + > > > > +static void avr_mask_init(Object *dev) > > > > +{ > > > > +    AVRMaskState *s = AVR_MASK(dev); > > > > +    SysBusDevice *busdev = SYS_BUS_DEVICE(dev); > > > > + > > > > +    memory_region_init_io(&s-> iomem, dev, &avr_mask_ops, s, TYPE_AVR_MASK, > > > > +            0x01); > > > > +    sysbus_init_mmio(busdev, &s->iomem); > > > > + > > > > +    for (int i = 0; i < 8; i++) { > > > > +        sysbus_init_irq(busdev, &s->irq[i]); > > > > +    } > > > > +    s->val = 0x00; > > > > +} > > > > + > > > > +static void avr_mask_class_init( ObjectClass *klass, void *data) > > > > +{ > > > > +    DeviceClass *dc = DEVICE_CLASS(klass); > > > > + > > > > +    dc->reset = avr_mask_reset; > > > > +} > > > > + > > > > +static const TypeInfo avr_mask_info = { > > > > +    .name          = TYPE_AVR_MASK, > > > > +    .parent        = TYPE_SYS_BUS_DEVICE, > > > > +    .instance_size = sizeof(AVRMaskState), > > > > +    .class_init    = avr_mask_class_init, > > > > +    .instance_init = avr_mask_init, > > > > +}; > > > > + > > > > +static void avr_mask_register_types(void) > > > > +{ > > > > +    type_register_static(&avr_ mask_info); > > > > +} > > > > + > > > > +type_init(avr_mask_register_ types) > > > > diff --git a/hw/timer/Kconfig b/hw/timer/Kconfig > > > > index a990f9fe35..4343bc23f3 100644 > > > > --- a/hw/timer/Kconfig > > > > +++ b/hw/timer/Kconfig > > > > @@ -34,3 +34,6 @@ config CMSDK_APB_TIMER > > > >  config CMSDK_APB_DUALTIMER > > > >      bool > > > >      select PTIMER > > > > + > > > > +config AVR_TIMER16 > > > > +    bool > > > > diff --git a/hw/timer/Makefile.objs b/hw/timer/Makefile.objs > > > > index dece235fd7..af0913ca3b 100644 > > > > --- a/hw/timer/Makefile.objs > > > > +++ b/hw/timer/Makefile.objs > > > > @@ -35,3 +35,5 @@ common-obj-$(CONFIG_CMSDK_APB_ TIMER) += cmsdk-apb-timer.o > > > >  common-obj-$(CONFIG_CMSDK_APB_ DUALTIMER) += cmsdk-apb-dualtimer.o > > > >  common-obj-$(CONFIG_MSF2) += mss-timer.o > > > >  common-obj-$(CONFIG_RASPI) += bcm2835_systmr.o > > > > + > > > > +obj-$(CONFIG_AVR_TIMER16) += avr_timer16.o > > > > diff --git a/hw/timer/avr_timer16.c b/hw/timer/avr_timer16.c > > > > new file mode 100644 > > > > index 0000000000..ac6ef73e77 > > > > --- /dev/null > > > > +++ b/hw/timer/avr_timer16.c > > > > @@ -0,0 +1,605 @@ > > > > +/* > > > > + * AVR 16 bit timer > > > > + * > > > > + * Copyright (c) 2018 University of Kent > > > > + * Author: Ed Robbins > > > > + * > > > > + * Permission is hereby granted, free of charge, to any person obtaining a copy > > > > + * of this software and associated documentation files (the "Software"), to deal > > > > + * in the Software without restriction, including without limitation the rights > > > > + * to use, copy, modify, merge, publish, distribute, sublicense, and/or sell > > > > + * copies of the Software, and to permit persons to whom the Software is > > > > + * furnished to do so, subject to the following conditions: > > > > + * > > > > + * The above copyright notice and this permission notice shall be included in > > > > + * all copies or substantial portions of the Software. > > > > + * > > > > + * THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR > > > > + * IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, > > > > + * FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL > > > > + * THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER > > > > + * LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
https://lists.gnu.org/archive/html/qemu-devel/2019-11/msg04795.html
Palaeos Vertebrates: Pteraspidomorphi: Heterostraci Pteraspidomorphi: Heterostraci Cyathaspidiformes Poraspis , a representativeCyathaspidiform Heterostracan , life reconstruction © Mikhail Tikhonov, original url Taxa on This Page Cyathaspidiformes X Heterostraci X The Heterostraci Heterostracan diversity (not to scale). Head shields in dorsal view and reconstructions in lateral view (B2, F2); A - Traquairaspidiformes ( Traquairaspis ); B - Cyathaspidiformes (B1, Poraspis ; B2, Anglaspis ); C - Amphiaspidida (C1, Kureykaspis ; C2, Eglonaspis ); D - Anchipteraspididae ( Anchipteraspis ); E - Protopteraspididae (El, Protopteraspis ; E2, Doryaspis ); F - Pteraspididae (Fl, Rhinopteraspis ; F2, Errivaspis ); G - Psammosteida (G1, Drepanaspis ; G2, Pycnosteus ).  From Janvier & Blieck (1993). The Heterostracans are an important lineage that includes such ostracoderm types as the pteraspids, cyathaspids, amphiaspids, and many other groups  They are restricted to the Silurian and Devonian periods (reaching their height during the Late Silurian and Early Devonian ), in the biogeographic provinces of Euramerica , Siberia and Tuva. The Heterostraci possess a large dermal armor of dentine and acellular bone ( aspidin ), which covers the head region and is pierced laterally by a pair of common external branchial openings. The armor consists of a variable number of plates, which in the amphiaspids of Siberia has fused into a rigid box, while in some other groups it is broken into numerous platelets or tesserae.  A number of types developed extraordinary spines and other elaborations The Heterostracans comprise two major monophyletic groups, the Pteraspidiformes and Cyathaspidiformes (each of which can be given the Linnaean rank of Order), and a number of minor groups (Traquairaspids, Corvaspids , Lepidaspis , and others), some of which may be general primitive forms.  MAK000112. An Early Success The Heterostraci are arguably the first widely diversified vertebrate clade. But for accidents of history or design (depending on your theoretical and metaphysical preferences), something looking a little like Athenaegis , our friend on the left, might now be studying a roughly rectangular slab of rock bearing the bones of our great ancestor: an osteostracan , or some similar form. Instead, we are here and the heterostracan is on the rocks, so to speak. ( Images of Athenaegis chattertoni courtesy of Dr. Mark Wilson , Univ. of Alberta Laboratory of Vertebrate Paleontology.) However, in the mid- Silurian , it was the Heterostraci who were lords of the vertebrate domain in what is now the Northern Hemisphere. The Heterostraci are first found in the lower Silurian, about the same time that most of the other major Paleozoic fish groups got their start. They apparently radiated rapidly and evolved a number diverse forms which are now difficult to fit into a cohesive picture, such as Lepidaspis, which looks something like a hot dog bun (or, more exactly, a kolache) with the sausage sticking out of one end. Unlike the ponderous osteostracans or fragile anaspids , the Heterostraci  possessed virtually no endoskeleton. Even their dermal plates were made up of acellular aspidine and dentine, requiring little metabolic investment beyond the initial cost of construction. Only one species ( Torpedaspis ) shows signs of subaponevrotic circulation, the layer of vessels that feeds the cells at the base of living bone. The inner surface of the dermal plates is smooth and shiny, showing no evidence of even cartilaginous attachments. The only evidence of endoskeletal material are the ambiguous indentations radial to the gill lamellae and traces of possible arcualia along the line of the notochord. The Heterostraci had other advantages, as well. Long before the teleostomes managed the trick, the Heterostraci developed a single common branchial opening, minimizing the surface exposed to parasites and avoiding multiple openings in the body wall. The symmetrical, diphycercal tail, not perfected by gnathostomes until the Cretaceous , was standard equipment on heterostracans in the Silurian. It is not clear whether heterostracans had precise muscular control of the tail -- their only mobile fin -- in the same way as fish of the gnathostome lineage. The tail, like the rest of the body, had no internal skeleton and was reinforced only by lines of scales. However, the Heterostraci were not conspicuously flattened fish. They do not seem to have the conventional design of bottom-dwelling fishes, although they are often depicted in that fashion. They may well have been slow and sloppy swimmers compared to later forms. The very fact that they are not found worldwide is a convincing argument that they cannot have been nektonic athletes.  Yet it is equally hard to see them as vertebrate barnacles. Simplicity has its virtues. However, by Mid-Devonian times, the Heterostraci were in relative decline. A few lines, notably the large psammosteids, staged a revival in the Late Devonian , but all were extinct before the Carboniferous .  The lesson may be that a simpler body plan gives a clade an evolutionary head start. However, the more complex body plans have a long term advantage because of their ability to adjust to varying conditions. Simplicity of structure necessarily implies simpler responses to the environment. Certainly, any given arrangement of greater complexity is likely to fail, since its needs and requirements are also likely to be complex. However, once conditions permit radiation of the more complex forms to begin, that radiation is likely to be more durable because it inherently contains more diversity. This diversity permits greater success by specialization in good times, and more niche survivors in bad.  ATW020510, revised ATW030512. The Cyathaspidiforms The Cyathaspidiformes probably include some fairly active swimmers, although the heavy Armour would presumably slow them down.  This clade has both streamlined and flattened forms, distinguished by a head shield ornamented by longitudinal dentine ridges, the dorsal (upper) shield fused into a single plate, and the presence of vertical flange scales on the tail.  They appear in the early Silurian with Athenaegis (the earliest known Heterostracan), but do not really diversify until the later part of the period ( Ludlow epoch).  By the end of the Early Devonian they were in decline, and died out at the Emsian/Eifelian (Early/ Middle Devonian ) boundary. The Cyathaspidida were quite long-lived types that appeared during the Late Silurian (Ludlovian) and continued to the end of the Early Devonian (Emsian epoch).  They are part of the endemic Euramerican fauna. They were generally streamlined forms with fusiform or cigar-shaped head-shields, and deep vertical flange scales arranged along the tail.  They were probably fairly active but short distance swimmers. These jawless fish may have used water jets from their branchial openings as a propulsive or stabilizing device, to compensate for the lack of paired fins.  The illustration at the right shows a Cyathaspidiform in anterior (front) view, illustrating this hypothesis of the stabilizing function of the water jet from the common external branchial openings (stipple). The Amphiaspidida were specialized forms limited to the first half of the Early Devonian ( Lochkovian and early to mid Pragian epochs) of the Siberian (Angoran) bio-region.  The head-armour is fused into a single unit, and the entire head was flattened, indicating that they were bottom- dwellers, and possibly even burrowers, who would lie mostly submerged in the sand or mud. Kureykaspis , buried in the sediment, showing the adorbital opening at the very front (far left) of the head The opening at the right (rear) is the common external branchial opening illustration from Janvier (1996: 301) In some forms, the front of the armour is elongated into a tube-shaped structure, and the eyes disappear ( Empedaspis, Pelurgaspis, Eglonaspis ).  In others ( Prosarctaspis, Kureykaspis (illustrated above), Olbiaspis, Gabreynspis ), there is a special opening, the adorbital opening , in front of the eyes, which has been variously interpreted as a spiracle, a 'pre-spiracle', or a single nostril. It is probably an inhalant opening that allowed these creatures to live half-buried in the bottom sediments, like modern rays.  MAK000112. Heterostraci : Athenaegis. Range: Early Silurian to Late Devonian . Phylogeny: Heterostracomorphi : Astraspidae + *: Cyathaspidiformes + Pteraspidiformes . Characters: Generally oblong, fusiform shape, with some species dorsoventrally flattened; fan-like lower oral plates; upper oral plate normally rigid; head normally covered with single large dorsal and ventral plates, typically elongated lateral branchial plates; orbits small; $ single pair of gill openings; possible prenasal sinus or naso pharyngeal tract partially separated from oral cavity; no indication of endoskeleton except head shield impressions of possible arcualia and possible gill arches; head shield has impressions of 2 SCCs, 8-10 transverse gills and possibly gill arch bones radial to gills; ventral plate shows median impression (lingual apparatus?); brain shows 3 segments (pineal, metencephalon or cerebellum, and medula oblongata); where known, posterior covered with large scales; large median dorsal and ventral ridge scales; no fins except caudal; caudal fin primitively di- (poly?-)phycercal with lines of scales rather than fin rays; tail may also be pad-like; no paired appendages; interior of plates smooth & shiny - no evidence of attachment for endoskeleton; sub aponevrotic circulation known only in one species ( Torpedaspis ); trilaminar dermal skeleton with basal laminar layer, cancelous aspidine central layer, and tuburculate dentine outer layer showing characteristic grebeshkis . Links: UALVP Fossil Models & Replicas ; Class Pterapisdomorphi ; Geol 437 jawless fishes (NOT \AGNATHA\), Fall, 1995 ; Heterostraci ; Gagnier ; V The four other mass extinctions (French); xrefer - Heterostraci ; Lecture Notes, Nat. Hist. Vert., Emporia State Univ. ; vista verde news - Frühe Wirbeltiere: Ohne Biss (German); handout9_14 ; 209 lec s02/20903s02.pdf Image: (R) after Janvier, P. (1993), Patterns of diversity in the skull of jawless fishes, in Hanken, J& BK Hall (eds.), The Skull , 2:131-188, U. Chicago Press. Image (L) Athenaegis chattertoni model courtesy of Dr. Mark Wilson, Univ. of Alberta. APW040316. Cyathaspidiformes : Range: Silurian to Early Devonian of North America and Russia. Phylogeny: Heterostraci : Pteraspidiformes + *: Corvaspididae + ( Cyathaspidida + Amphiaspidida ). Characters: parallel, finely crenulated dentine ridges form ornamentation of dermal plates; flange scales arranged in chevrons.
http://palaeos.com/_backup/vertebrates/pteraspidomorphi/heterostraci.html
Publications - Global Disability Innovation Hub The GDI Hub brings together academic excellence, innovative practice and co-creation; harnessing the power of technology for good. Type Conference Paper Themes Assistive & Accessible Technology Culture and Participation The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Giulia Barbareschi,Catherine Holloway, Katherine Arnold, Grace Magomere, Wycliffe Ambeyi Wetende, Gabriel Ngare, Joyce Olenja We present the findings of a case study of mobile technology use by People with Visual Impairment (VIPs) in Kibera, an informal settlement in Nairobi. We used contextual interviews, ethnographic observations and a co-design workshop to explore how VIPs use mobile phones in their daily lives, and how this use influences the social infrastructure of VIPs. Our findings suggest that mobile technology supports and shapes the creation of social infrastructure. However, this is only made possible through the existing support networks of the VIPs, which are mediated through four types of interaction: direct, supported, dependent and restricted. CHI '20: Proceedings of the 2020 CHI Conference; 2020 Abstract The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Living in an informal settlement with a visual impairment can be very challenging resulting in social exclusion. Mobile phones have been shown to be hugely beneficial to people with sight loss in formal and high-income settings. However, little is known about whether these results hold true for people with visual impairment (VIPs) in informal settlements. We present the findings of a case study of mobile technology use by VIPs in Kibera, an informal settlement in Nairobi. We used contextual interviews, ethnographic observations and a co-design workshop to explore how VIPs use mobile phones in their daily lives, and how this use influences the social infrastructure of VIPs. Our findings suggest that mobile technology supports and shapes the creation of social infrastructure. However, this is only made possible through the existing support networks of the VIPs, which are mediated through four types of interaction: direct, supported, dependent and restricted. The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Giulia Barbareschi, Catherine Holloway, Katherine Arnold, Grace Magomere, Wycliffe Ambeyi Wetende, Gabriel Ngare, and Joyce Olenja. 2020. The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya. In Proceedings of the 2020 CHI Conference on Human Factors in Computing Systems (CHI '20). Association for Computing Machinery, New York, NY, USA, 1–15.https://doi.org/10.1145/331383... The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Conference Paper Disability design and innovation in computing research in low resource settings Dafne Zuleima Morgado-Ramirez,Giulia Barbareschi, Maggie Kate Donovan-Hall, Mohammad Sobuh, Nida' Elayyan, Brenda T Nakandi, Robert Tamale Ssekitoleko, joyce Olenja, Grace Nyachomba Magomere, Sibylle Daymond, Jake Honeywill, Ian Harris, Nancy Mbugua, Laurence Kenney,Catherine Holloway 80% of people with disabilities worldwide live in low resourced settings, rural areas, informal settlements and in multidimensional poverty. ICT4D leverages technological innovations to deliver programs for international development. But very few do so with a focus on and involving people with disabilities in low resource settings. Also, most studies largely focus on publishing the results of the research with a focus on the positive stories and not the learnings and recommendations regarding research processes. ASSETS '20: Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility; 2020 Abstract Disability design and innovation in computing research in low resource settings 80% of people with disabilities worldwide live in low resourced settings, rural areas, informal settlements and in multidimensional poverty. ICT4D leverages technological innovations to deliver programs for international development. But very few do so with a focus on and involving people with disabilities in low resource settings. Also, most studies largely focus on publishing the results of the research with a focus on the positive stories and not the learnings and recommendations regarding research processes. In short, researchers rarely examine what was challenging in the process of collaboration. We present reflections from the field across four studies. Our contributions are: (1) an overview of past work in computing with a focus on disability in low resource settings and (2) learnings and recommendations from four collaborative projects in Uganda, Jordan and Kenya over the last two years, that are relevant for future HCI studies in low resource settings with communities with disabilities. We do this through a lens of Disability Interaction and ICT4D. Dafne Zuleima Morgado-Ramirez, Giulia Barbareschi, Maggie Kate Donovan-Hall, Mohammad Sobuh, Nida' Elayyan, Brenda T Nakandi, Robert Tamale Ssekitoleko, joyce Olenja, Grace Nyachomba Magomere, Sibylle Daymond, Jake Honeywill, Ian Harris, Nancy Mbugua, Laurence Kenney, and Catherine Holloway. 2020. Disability design and innovation in computing research in low resource settings. In Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility (ASSETS '20). Association for Computing Machinery, New York, NY, USA, Article 11, 1–7.https://doi.org/10.1145/337362... Type Workshop Themes Assistive & Accessible Technology Research Group Disability Interactions Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution Sahan Bulathwela, María Pérez-Ortiz,Catherine Holloway, John Shawe-Taylor This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies. Workshop on Machine Learning for the Developing World (ML4D) at the Conference on Neural Information Processing Systems 2021; 2021 Abstract Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution Artificial Intelligence (AI) in Education has been said to have the potential for building more personalised curricula, as well as democratising education worldwide and creating a Renaissance of new ways of teaching and learning. Millions of students are already starting to benefit from the use of these technologies, but millions more around the world are not. If this trend continues, the first delivery of AI in Education could be greater educational inequality, along with a global misallocation of educational resources motivated by the current technological determinism narrative. In this paper, we focus on speculating and posing questions around the future of AI in Education, with the aim of starting the pressing conversation that would set the right foundations for the new generation of education that is permeated by technology. This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies. Finally, we ask what would it take for this educational revolution to provide egalitarian and empowering access to education, beyond any political, cultural, language, geographical and learning ability barriers. Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution Type Workshop Themes Assistive & Accessible Technology Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts Tabish Ahmed, Sahan Bulathwela The informational needs of people are highly contextual and can depend on many different factors such as their current knowledge state, interests and goals [1, 2, 3]. However, an effective information retrieval companion should minimise the human effort required in i) expressing a human information need and ii) navigating a lengthy result set. Using topical representations of the user history (e.g. [4]) can immensely help formulating zero shot queries and refining short user queries that enable proactive information retrieval (IR). While the world has digital textual information in abundance, it can often be noisy (e.g. extracted through Automatic Speech Recognition (ASR), PDF text extraction etc.), leading to state-of-the-art neural models being highly sensitive to the noise producing sub-optimal results [5]. This demands denoising steps to refine both query and document representation. In this paper, we argue that Wikipedia, an openly available encyclopedia, can be a humanly intuitive knowledge base [6] that has the potential to provide the world view many noisy information Retrieval systems need. Published at the First Workshop on Proactive and Agent-Supported Information Retrieval at CIKM 2022; 2022 Abstract Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts Extracting useful information from the user history to clearly understand informational needs is a crucial feature of a proactive information retrieval system. Regarding understanding information and relevance, Wikipedia can provide the background knowledge that an intelligent system needs. This work explores how exploiting the context of a query using Wikipedia concepts can improve proactive information retrieval on noisy text. We formulate two models that use entity linking to associate Wikipedia topics with the relevance model. Our experiments around a podcast segment retrieval task demonstrate that there is a clear signal of relevance in Wikipedia concepts while a ranking model can improve precision by incorporating them. We also find Wikifying the background context of a query can help disambiguate the meaning of the query, further helping proactive information retrieval. Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts Type Book Research Group Disability Interactions Disability Interactions Creating Inclusive Innovations Catherine Holloway,Giulia Barbareschi ; 2021 Abstract Disability interactions (DIX) is a new approach to combining cross-disciplinary methods and theories from Human Computer Interaction (HCI), disability studies, assistive technology, and social development to co-create new technologies, experiences, and ways of working with disabled people. DIX focuses on the interactions people have with their technologies and the interactions which result because of technology use. A central theme of the approach is to tackle complex issues where disability problems are part of a system that does not have a simple solution. Therefore, DIX pushes researchers and practitioners to take a challenge-based approach, which enables both applied and basic research to happen alongside one another. DIX complements other frameworks and approaches that have been developed within HCI research and beyond. Traditional accessibility approaches are likely to focus on specific aspects of technology design and use without considering how features of large-scale assistive technology systems might influence the experiences of people with disabilities. DIX aims to embrace complexity from the start, to better translate the work of accessibility and assistive technology research into the real world. DIX also has a stronger focus on user-centered and participatory approaches across the whole value chain of technology, ensuring we design with the full system of technology in mind (from conceptualization and development to large-scale distribution and access). DIX also helps to acknowledge that solutions and approaches are often non-binary and that technologies and interactions that deliver value to disabled people in one situation can become a hindrance in a different context. Therefore, it offers a more nuanced guide to designing within the disability space, which expands the more traditional problem-solving approaches to designing for accessibility. This book explores why such a novel approach is needed and gives case studies of applications highlighting how different areas of focus—from education to health to work to global development—can benefit from applying a DIX perspective. We conclude with some lessons learned and a look ahead to the next 60 years of DIX. Type Conference Paper Themes Assistive & Accessible Technology Value beyond function: analyzing the perception of wheelchair innovations in Kenya Barbareschi, G; Daymond, S; Honeywill, J; Singh, A; Noble, D; Mbugua, N; Harris, I;Austin, V;Holloway, C The World Health Organization (WHO) defines Assistive Technology (AT) as “an umbrella term covering the systems and services related to the delivery of assistive products and services” [6]. This definition highlights how AT encompasses not only the physical and digital products used by millions of persons with disabilities (PWDs) worldwide, but also the systems and services that accompany the provision of these devices [78]. ASSETS '20: The 22nd International ACM SIGACCESS Conference on Computers and Accessibility.; 2020 Abstract Value beyond function: analyzing the perception of wheelchair innovations in Kenya Innovations in the field of assistive technology are usually evaluated based on practical considerations related to their ability to perform certain functions. However, social and emotional aspects play a huge role in how people with disabilities interact with assistive products and services. Over a five months period, we tested an innovative wheelchair service provision model that leverages 3D printing and Computer Aided Design to provide bespoke wheelchairs in Kenya. The study involved eight expert wheelchair users and five healthcare professionals who routinely provide wheelchair services in their community. Results from the study show that both users and providers attributed great value to both the novel service delivery model and the wheelchairs produced as part of the study. The reasons for their appreciation went far beyond the practical considerations and were rooted in the fact that the service delivery model and the wheelchairs promoted core values of agency, empowerment and self-expression. Value beyond function: analyzing the perception of wheelchair innovations in Kenya Type Conference Paper Themes Assistive & Accessible Technology Culture and Participation Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh Nusrat Jahan,Giulia Barbareschi, Clara Aranda Jan, Charles Musungu Mutuku, Naemur Rahman,Victoria Austin,Catherine Holloway Worldwide it is estimated that there are over a billion people who live with some form of disability[1]. Approximately 80% of people with disabilities live in low-and-middle income countries (LMICs). The combination of an inaccessible environment compounded by socio-economic factors such as poverty and stigma, makes it more likely for people with disabilities to be marginalised and excluded from society[1]. Assistive Technologies (ATs) are known to bridge the accessibility gaps and allow for greater social inclusion. However, there is a lack of adequate access to ATs in LMICs, combined with often poorly designed services, which only magnifies these challenges, thus limiting the opportunities for persons with disabilities to live an independent life[2]. Despite the importance of AT, access to AT globally is inadequate with only 10 percent of those in need having access to the ATs that they need[2]. 2020 IEEE Global Humanitarian Technology Conference Abstract Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh Globally, mobile technology plays a significant role connecting and supporting people with disabilities. However, there has been limited research focused on understanding the impact of mobile technology in the lives of persons with disabilities in low or middle- income countries. This paper presents the findings of a participatory photovoice study looking at the role that mobile phones play in the daily lives of 16 persons with disabilities in Kenya and Bangladesh. Participants used a combination of pictures and voice recordings to capture their own stories and illustrate the impact that mobile phone use has on their lives. Through thematic analysis, we categorized the benefits of mobile phones captured by participants as 1) Improved social connection; 2) Increased independence and 3) Access to opportunities. While mobile phones are ubiquitously used for communication, for persons with disabilities they become essential assistive technologies that bridge barriers to opportunities which are not accessible otherwise. Our paper adds evidence to the need for mobile phones for persons with disabilities to enable communication and connectivity in support of development. Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh N. Jahan et al., "Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh," 2020 IEEE Global Humanitarian Technology Conference (GHTC), Seattle, WA, USA, 2020, pp. 1-8, doi: 10.1109/GHTC46280.2020.9342934. Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh Type Conference Paper Themes Assistive & Accessible Technology Research Group Local Productions A Preliminary Study to Understand How Mainstream Accessibility and Digital Assistive Technologies Reaches People in Lower- and Middle-Income Countries Tigmanshu Bhatnagar, George Torrens, Ben Oldfrey, Priya MorjariaFelipe Ramos Barajas, Katherine PerryandCatherine Holloway Access to information on digital platforms not only facilitates education, employment, entertainment, social interaction but also facilitates critical governmental services, ecommerce, healthcare services and entrepreneurship [1]. Article 9 of United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) enforces its signatories to commit to provide full accessibility to every citizen of the nation [2]. This has helped to spearhead accessibility directives such as the European Accessibility Act [3] that aims to improve the functioning of markets for accessible products and services. Such directives contribute to ensure that mainstream digital technologies (smartphones, computers etc.) are accessible for everyone and without being socially remarkable, they are able to assist in daily living. Additionally, there is evidence that improving access in mainstream technologies improves product experience and usability for everyone [4]. However, mainstream access has not been fully realized, leading to inferior opportunities for people with disabilities, a disparity which is more prominent in lower and middle-income countries [5]. RESNA Annual Conference; 2021 A Preliminary Study to Understand How Mainstream Accessibility and Digital Assistive Technologies Reaches People in Lower- and Middle-Income Countries Type Toolkit Innovate Now Toolkit As an entrepreneur, learning how to solve problems by creating and experimenting with different strategies is a core pillar of the entrepreneurial mindset you need to succeed. However, there’s rarely a single correct way to solve problems as an entrepreneur, so you need to learn how to create and compare different solutions. The open entrepreneurship toolkit is a set of learning materials that can help you and your team do just that. Covering the domains of user, product, market and business development, the set of cards have been designed to be used by two or more group members to actively experiment with different solutions. Innovate Now Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design Troy Bodkin Doctoral Thesis. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process. Loughborough University Abstract Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design For many years, the biggest issue that causes discomfort and hygiene issues for patients with lower limb amputations have been the interface between body and prosthetic, the socket. Often made of an inflexible, solid polymer that does not allow the residual limb to breathe or perspire and with no consideration for the changes in size and shape of the human body caused by changes in temperature or environment, inflammation, irritation and discomfort often cause reduced usage or outright rejection of the prosthetic by the patient in their day to day lives. To address these issues and move towards a future of improved quality of life for patients who suffer amputations, Loughborough University formed the Next Generation Prosthetics research cluster. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process. The research presented in this thesis is based on three primary studies. The first study involved the conception of a CAD criteria, deciding what features are needed to represent the various properties the future socket outlined by the research cluster needs. These criteria were then used for testing three CAD systems, one each from the Parametric, Non Uniform Rational Basis Spline (NURBS) and Polygon archetypes respectively. The result of these tests led to the creation of a hybrid control workflow, used as the basis for finding improvements. The second study explored emerging CAD solutions, various new systems or plug-ins that had opportunities to improve the control model. These solutions were tested individually in areas where they could improve the workflow, and the successful solutions were added to the hybrid workflow to improve and reduce the workflow further. The final study involved taking the knowledge gained from the literature and the first two studies in order to theorise how an ideal CAD system for producing future prosthetic sockets would work, with considerations for user interface issues as well as background CAD applications. The third study was then used to inform the final deliverable of this research, a software design specification that defines how the system would work. This specification was written as a challenge to the CAD community, hoping to inform and aid future advancements in CAD software. As a final stage of research validation, a number of members of the CAD community were contacted and interviewed about their feelings of the work produced and their feedback was taken in order to inform future research in this area. Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design Bodkin, Troy L. (2017): Specifying a hybrid, multiple material CAD system for next-generation prosthetic design. Loughborough University. Thesis.https://hdl.handle.net/2134/25...; Share Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Giulia Barbareschi Doctoral Thesis. This thesis makes two contributions to facilitate wheelchair users’ engagement in the participatory design process for ATs, while being mindful of the burden of participation. The first contribution is a framework that provides a modular structure guiding the participatory design process from initial problem identification and analysis to facilitating collaborations between wheelchair users and designers. The framework identifies four factors determining the need and adoption process for ATs: (i) People focuses on the target population, (ii) Person includes personal characteristics, (iii) Activity refers to the challenges associated with the task, and (iv) Context encompasses the effect of the environment in which the activity takes place. The second contribution constitutes a rich picture of personal and external elements influencing real world wheelchair transfers that emerged from four studies carried out to investigate the effect of the framework factors on the design process for ATs. UCL (University College London) Abstract YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Transferring independently to and from their wheelchair is an essential routine task for many wheelchair users but it can be physically demanding and can lead to falls and upper limb injuries that reduce the person’s independence. New assistive technologies (ATs) that facilitate the performance of wheelchair transfers have the potential to allow wheelchair users to gain further independence. To ensure that users’ needs are addressed by ATs, the active involvement of wheelchair users in the process of design and development is critical. However, participation can be burdensome for many wheelchair users as design processes where users are directly involved often require prolonged engagement. This thesis makes two contributions to facilitate wheelchair users’ engagement in the participatory design process for ATs, while being mindful of the burden of participation. The first contribution is a framework that provides a modular structure guiding the participatory design process from initial problem identification and analysis to facilitating collaborations between wheelchair users and designers. The framework identifies four factors determining the need and adoption process for ATs: (i) People focuses on the target population, (ii) Person includes personal characteristics, (iii) Activity refers to the challenges associated with the task, and (iv) Context encompasses the effect of the environment in which the activity takes place. The second contribution constitutes a rich picture of personal and external elements influencing real world wheelchair transfers that emerged from four studies carried out to investigate the effect of the framework factors on the design process for ATs. A related outcome based on these contributions is a framing document to share knowledge between wheelchair users and designers to provide focus and promote an equal collaboration among participants. YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Barbareschi, Giulia. “YouTransfer, YouDesign : a Participatory Approach to Design Assistive Technology for Wheelchair Transfers / Giulia Barbareschi.” Thesis (Ph.D.)--University College London, 2018., 2018. Print. Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Understanding wrist splint user needs and personalisation through codesign Charlotte Pyatt A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy at Loughborough University. Loughborough University Abstract Understanding wrist splint user needs and personalisation through codesign Wrist splints are a common treatment for rheumatoid arthritis, however their effectiveness is compromised by patients not wearing splints as often as prescribed. Previous research has identified a number of reasons for non-compliance, but typically lacks insights that could lead to improved splint design. This thesis investigates the motivators for patients to wear and not wear their wrist splints and, the impact of personalisation of splint appearance on patient wear. The work is based on the premise that digital design and manufacturing processes, such as Computer-Aided Design (CAD) and 3D Printing, can produce bespoke splints on demand. The research begins with a literature review across the core areas of: splinting, additive manufacture, product appearance and personalisation. This literature review identifies gaps in knowledge from which research questions are established for the work. The research employs a qualitative, generative design research approach and, follows a codesign framework employing telling, making and enacting tools. The thesis is made up of three studies. The first study is a sensitisation study and uses design probes to prepare the participants for the research and begin exploring the problem space. The second is a comprehensive study into participants splint wear behaviour and uses context mapping and scenario picture card tools to investigate the motivators for participants to wear and not wear wrist splints, along with positive and negative outcomes or wearing/not wearing splints. The final study uses a personalisation toolkit to elicit patient needs for a future wrist splint design and investigate self-reported expectations regarding compliance of patients who used the toolkit. The research finds that patient compliance is affected by practical and aesthetic limitations of current splints. It identifies 4 motivating factors to wear a splint and 10 motivating factors to not wear a splint. Additionally, it identifies 6 positive outcomes of wearing splints, 6 negative outcomes of wearing splints, 3 positive outcomes of not wearing splints and 3 negative outcomes of not wearing splints. Requirements for an improved splint design are established and form the basis of the design for a prototype personalisation toolkit. Testing of this toolkit reveals that patients are keen to own more than one splint and personalise splints to match the scenario in which it is to be worn. Patients reported that they expected to be more compliant with a personalised splint when compared to their current splint. Understanding wrist splint user needs and personalisation through codesign Pyatt, Charlotte (2018): Understanding wrist splint user needs and personalisation through codesign. Loughborough University. Thesis.https://doi.org/10.26174/thesi...; Understanding wrist splint user needs and personalisation through codesign Join the GDI Hub Expert Bench Help us with your existing expertise, skills or knowledge.
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Equinix Inc Q2 2018 Earnings Call Summary - Brief - 2018/08/08 - Thomson StreetEvents ...This was qtr. of many new highs with continued momentum in key metrics as go-to-market engine and interconnection strategy drove results. 1. Record bookings in all three regions driven by robust growth across verticals with particular momentum in cross-regional activity. a. b. Co. now serves 48% of Fortune 500 and 33% of Global 2000 companies. Both up 1% QoverQ. i. ii. Demonstrates highly attractive land and expand dynamics with lighthouse customers. c. Channel sales stepped up to over 20% of bookings, and accounted for half of Co.'s new logos, driven by solid performance across regions and across partner types. d. Power of global platform continues with over 50% of Co.'s revenue coming from customers deployed across all three regions, and 85% from customers deployed across multiple metros. i. Both metrics up 1% QoverQ. 2. Revenues $1.262b as reported. Up 9% YoverY. a. b. Above top end of guidance range on FX-neutral basis. c. Adjusted EBITDA and AFFO both up over 6% YoverY, which includes... Equinix Inc Q2 2018 Earnings Call Summary Equinix Inc Q2 2018 Earnings Call Summary Published Aug 08, 2018 17 pages (10116 words) — Published Aug 08, 2018 Price US$ 54.00 | Buy this Report Now About This Report Abstract:Edited Brief of EQIX earnings conference call or presentation 8-Aug-18 9:30pm GMT Brief Excerpt:...This was qtr. of many new highs with continued momentum in key metrics as go-to-market engine and interconnection strategy drove results. 1. Record bookings in all three regions driven by robust growth across verticals with particular momentum in cross-regional activity. a. b. Co. now serves 48% of Fortune 500 and 33% of Global 2000 companies. Both up 1% QoverQ. i. ii. Demonstrates highly attractive land and expand dynamics with lighthouse customers. c. Channel sales stepped up to over 20% of bookings, and accounted for half of Co.'s new logos, driven by solid performance across regions and across partner types. d. Power of global platform continues with over 50% of Co.'s revenue coming from customers deployed across all three regions, and 85% from customers deployed across multiple metros. i. Both metrics up 1% QoverQ. 2. Revenues $1.262b as reported. Up 9% YoverY. a. b. Above top end of guidance range on FX-neutral basis. c. Adjusted EBITDA and AFFO both up over 6% YoverY, which includes... Report Type:Brief Source: Thomson StreetEvents Company: Equinix Inc Ticker EQIX Time 9:30pm GMT Format: PDF The following is excerpted from the question-and-answer section of the transcript. (Questions from industry analysts are provided in full, but answers are omitted - download the transcript to see the full question-and-answer session) Question:Erik Peter Rasmussen - Stifel, Nicolaus & Company, Incorporated, Research Division - Analyst : Just 2 quick. First, I guess, in terms of the Infomart in Dallas, you had that now closed in the quarter. Are you seeing any surprise -- any positive surprises to your prior expectations? And then what are your plans for the adjacent land and time line for future development? And then in terms of the interconnection, obviously, we're talking about 100 Gb right now, but the industry continues to migrate and we're even hearing of 400 Gb. Is this also coming up more with discussions with your customers? Table Of Contents Equinix Inc Q3 2018 Earnings Call Summary– 2018-11-01 – US$ 54.00 – Edited Brief of EQIX earnings conference call or presentation 1-Nov-18 9:30pm GMT Equinix Inc Q3 2018 Earnings Call Transcript– 2018-11-01 – US$ 54.00 – Edited Transcript of EQIX earnings conference call or presentation 1-Nov-18 9:30pm GMT Equinix Inc at Bank of America Merrill Lynch Media, Communications & Entertainment Conference Transcript– 2018-09-06 – US$ 54.00 – Edited Transcript of EQIX presentation 6-Sep-18 7:00pm GMT Equinix Inc at KeyBanc Capital Markets Technology Leadership Forum Transcript– 2018-08-13 – US$ 54.00 – Edited Transcript of EQIX presentation 13-Aug-18 7:00pm GMT Equinix Inc Analyst Day Transcript– 2018-06-20 – US$ 54.00 – Edited Transcript of EQIX corporate analyst meeting</ 20-Jun-18 2:00pm GMT Equinix Inc at Nasdaq Investor Conference Transcript– 2018-06-12 – US$ 54.00 – Edited Transcript of EQIX presentation 12-Jun-18 11:15am GMT Equinix Inc at REITWeek: NAREIT's Investor Forum Transcript– 2018-06-06 – US$ 54.00 – Edited Transcript of EQIX presentation 6-Jun-18 1:30pm GMT Equinix Inc Q1 2018 Earnings Call Summary– 2018-05-02 – US$ 54.00 – Edited Brief of EQIX earnings conference call or presentation 2-May-18 9:30pm GMT Equinix Inc Q1 2018 Earnings Call Transcript– 2018-05-02 – US$ 54.00 – Edited Transcript of EQIX earnings conference call or presentation 2-May-18 9:30pm GMT
https://www.alacrastore.com/thomson-streetevents-transcripts/Q2-2018-Equinix-Inc-Earnings-Call-B11634856
Absence epilepsy: When the brain is like 'an orchestra without a conductor' -- ScienceDaily New contributions to the field of epilepsy have opened a window into the cellular events that occur in the brain during absence seizures. Absence epilepsy: When the brain is like 'an orchestra without a conductor' Summary: New contributions to the field of epilepsy have opened a window into the cellular events that occur in the brain during absence seizures. At first, the teacher described her six-year-old student as absentminded, a daydreamer. The boy was having difficulty paying attention in class. As the teacher watched the boy closely, she realized that he was not daydreaming. He often blanked out for a few seconds and wouldn't respond when she called his name. On occasion, he would blink a lot and his eyes would roll up. The teacher talked to the boy's parents about his concerning behavior. His parents took him to the doctor and, after a few tests, he was diagnosed with absence epilepsy and prescribed medication. Absence epilepsy is the most common type of seizure disorders in children. "In about 80 percent of children with absence seizures, the episodes usually stop around puberty. The other 20 percent will continue to have seizures," said first and corresponding author Dr. Jochen Meyer, instructor of neurology and neuroscience at Baylor College of Medicine. "Absence seizures, even if they stop, are a disabling disorder because they cause children to be momentarily absent during periods of their formative years." "Many of these children also present with attention deficit disorder that can persist in about 40 percent of patients despite being treated with medication and even after the seizures stop," said co-first author Dr. Atul Maheshwari, assistant professor of neurology and neuroscience at Baylor. "We need to have a better understanding of what happens in the brain during absence seizures." And that is what the researchers achieved in this study. They used a new technology called 2-photon microscopy that allowed them to visualize the firing activity of many individual neurons simultaneously in the brains of awake mice. They combined these observations with electroencephalograms that measured the electrical patterns of the same area of the brain. The results were completely unexpected. 'It's like listening to an orchestra without a conductor' Researchers have known for decades that people having an absence seizure present with a typical electroencephalogram showing a spike-and-wave pattern of electrical activity that repeats for the duration of the seizure. "The spike-and-wave pattern is very reproducible, and it's during this period of time that the child would stop and stare. But nobody had studied what the brain cells themselves were doing during one of these episodes," said co-author Dr. Jeffrey Noebels, professor of neurology, neuroscience, and molecular and human genetics and director of the Blue Bird Circle Developmental Neurogenetics Laboratory at Baylor. The researchers took a closer look at the firing activity of neurons in an area of the visual cortex of a genetic mouse model of absence epilepsy. They used the new 2-photon microscopy technology to see the firing activity of many brain cells at the same time, in a way similar to people using Google maps to zoom in to look at a group of individual houses in a neighborhood. "We had predicted from the spike-and-wave pattern of the brain waves that the behavior of the brain cells during a seizure also would be a rhythmical activity. Instead, we saw an uncoordinated firing activity, which was a big surprise," said Noebels, who also holds the Cullen Endowed Chair in Neurogenetics. "It was always thought that during the 'spike' cells would fire, and during the 'wave' they would be quiet. That repeated pattern of spike-and-wave is the signature of this kind of epilepsy, so we assumed that it was based on the behavior of the cells that were generating the brain waves. But in fact we found that there appears to be no uniform connection between the cell behavior and the brain waves." "Normally the human brain, like an orchestra, is playing beautiful music and every player can understand what the others are playing. We thought that when a seizure started, the 'orchestra of neurons' would play extremely loud and intense music. And when the seizure ended, the neurons would go back to playing monotonous music," Maheshwari said. "Instead, we found that during an absence seizure the volume of the music went down and the 'musicians' were playing music without coordinating with others. Most of them were not playing at all, as if the conductor was not there anymore. When the seizure ended, it was like the conductor had returned and organized the musicians to play harmoniously again." Interestingly, the reduction in brain cell activity began several seconds before the rhythmic spike-and-wave signature in the electroencephalogram started. "It might be of interest in the future to further investigate whether the reduction in cellular activity that precedes the seizures could be used to predict them," Meyer said. The researchers' contribution to the field of epilepsy has opened a window into the cellular events that occur in the brain during absence seizures. "Now that we know that the 'orchestra' is disorganized, we can look for ways to treat the underlying causes of the seizures at the cellular level," Maheshwari said. Absence seizures can happen 100 times a day, but they are subtle and last only a few seconds, so they are often underdiagnosed or diagnosed late because they are easily mistaken for daydreaming. Story Source: Materialsprovided byBaylor College of Medicine. Note: Content may be edited for style and length. Journal Reference: Jochen Meyer, Atul Maheshwari, Jeffrey Noebels, Stelios Smirnakis. Asynchronous suppression of visual cortex during absence seizures in stargazer mice. Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-04349-8 Cite This Page: MLA APA Chicago Baylor College of Medicine. "Absence epilepsy: When the brain is like 'an orchestra without a conductor'." ScienceDaily. ScienceDaily, 19 June 2018. <www.sciencedaily.com/releases/2018/06/180619173553.htm>. Baylor College of Medicine. (2018, June 19). Absence epilepsy: When the brain is like 'an orchestra without a conductor'. ScienceDaily. Retrieved July 6, 2023 from www.sciencedaily.com/releases/2018/06/180619173553.htm Baylor College of Medicine. "Absence epilepsy: When the brain is like 'an orchestra without a conductor'." ScienceDaily. www.sciencedaily.com/releases/2018/06/180619173553.htm (accessed July 6, 2023).
https://www.sciencedaily.com/releases/2018/06/180619173553.htm
Safety of Magnetic Resonance Imaging in Non-MRI Conditional Pacemakers and ICD Devices - Full Text View - ClinicalTrials.gov Safety of Magnetic Resonance Imaging in Non-MRI Conditional Pacemakers and ICD Devices The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. ClinicalTrials.gov Identifier: NCT02906189 Recruitment Status : Unknown Verified September 2016 by Michael Morris, Banner Health. Recruitment status was:  Recruiting First Posted : September 20, 2016 Last Update Posted : September 20, 2016 Sponsor: Banner Health Michael Morris, Banner Health Study Details Study Description Brief Summary: The primary objective of the study is to determine the safety of MRI in patients with non-MRI conditional pacemakers. The secondary objective is to determine if there are clinically relevant parameter changes in the devices. Condition or disease Intervention/treatment Arrhythmias, Cardiac Radiation: MRI Study Design Layout table for study information Study Type : Observational Estimated Enrollment : 1500 participants Observational Model: Cohort Time Perspective: Prospective Official Title: Safety of Magnetic Resonance Imaging in Non-MRI Conditional Pacemakers and ICD Devices Study Start Date : September 2016 Estimated Primary Completion Date : September 2021 Estimated Study Completion Date : September 2021 MedlinePlus related topics: Arrhythmia MRI Scans Outcome Measures Primary Outcome Measures : Death during the MRI scan [ Time Frame: Immediate ] Secondary Outcome Measures : Decrease in battery voltage >0.04v [ Time Frame: 6 months ] Change in pacing lead impedance ≥ 50 Ω [ Time Frame: 6 months ] Change in high-voltage lead impedance ≥ 3 Ω [ Time Frame: 6 months ] Increase in pacing threshold ≥ 0.50 V @ 0.4 ms [ Time Frame: 6 months ] Decrease in P wave measurement ≥ 50% [ Time Frame: 6 months ] Decrease in R wave measurement ≥ 25% [ Time Frame: 6 months ] Generator failure requiring immediate replacement [ Time Frame: Immediate ] Lead failure requiring immediate replacement [ Time Frame: Immediate ] New onset atrial or ventricular arrhythmia during MRI [ Time Frame: Immediate ] Loss of pacemaker capture during MRI [ Time Frame: Immediate ] Eligibility Criteria Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information Information from the National Library of Medicine Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. Layout table for eligibility information Ages Eligible for Study: 18 Years to 85 Years   (Adult, Older Adult) Sexes Eligible for Study: All Accepts Healthy Volunteers: No Sampling Method: Non-Probability Sample Study Population Patients with non-MRI conditional pacemakers and ICDs referred for clinically indicated MRI scans. Criteria Inclusion Criteria. All patients with non-MRI conditional pacemakers and ICDs between the ages of 18-85 will be eligible to participate. Medical records will be reviewed to confirm the date and make/model of device implanted. Ordering physician discusses the MRI request with radiologist, documenting that there is no appropriate alternate imaging test. Patient must have an appointment with a cardiologist/electrophysiologist prior to MRI. Banner Health policy for standard of care guidelines involving patients receiving MRI's will be followed. Exclusion Criteria. Patients will be excluded from MRI based on the Department of Radiology protocol. Additional exclusion criteria include: ICD and pacemaker dependent, Pacemaker inserted before 2002, Epicardial leads, fractured leads, abandoned leads, or temporary pacemakers (post-coronary artery bypass graft temporary epicardial pacing wires are acceptable), Patient not awake or unable communicate, Battery voltage at elective replacement interval, implanted non-MRI conditional device (other than pacemaker/ICD). Contacts and Locations Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02906189 Contacts Layout table for location contacts Contact: Michael Morris, MD 602-839-4850 michael.morris@bannerhealth.com Locations Layout table for location information United States, Arizona Banner University Medical Center Phoenix Recruiting Phoenix, Arizona, United States, 85004 Contact: Michael Morris, MD    602-839-4850 michael.morris@bannerhealth.com Sponsors and Collaborators Banner Health Investigators Layout table for investigator information Principal Investigator: Michael Morris, MD Banner University Medical Center Layout table for additonal information Responsible Party: Michael Morris, Clinical Assistant Professor, Banner Health ClinicalTrials.gov Identifier: NCT02906189 History of Changes Other Study ID Numbers: 1608820677 First Posted: September 20, 2016 Key Record Dates Last Update Posted: September 20, 2016 Last Verified: September 2016 Individual Participant Data (IPD) Sharing Statement: Plan to Share IPD: No Disclaimer Customer Support U.S. Department of Health and Human Services
https://clinicaltrials.gov/ct2/show/study/NCT02906189
E-Library - Information At Your Fingertips: Printer Friendly 803 Phil. 419 FIRST DIVISION [ G.R. No. 193156. January 18, 2017 ] IVQ LANDHOLDINGS, INC., PETITIONER, VS. REUBEN BARBOSA, RESPONDENT. R E S O L U T I O N LEONARDO-DE CASTRO, J.: In this petition for review on certiorari [1] under Rule 45 of the Rules of Court, petitioner IVQ Landholdings, Inc. (IVQ) assails the Decision [2] dated December 9, 2009 and the Resolution [3] dated July 30, 2010 of the Court of Appeals in CA-G.R. CV No. 90609. The decision of the appellate court affirmed the Decision [4] dated June 15, 2007 of the Regional Trial Court (RTC) of Quezon City, Branch 222 in Civil Case No. Q04-52842, which adjudicated in favor of herein respondent Reuben Barbosa (Barbosa) the ownership of the property subject of this case and ordered the cancellation of IVQ's certificate of title thereto. The resolution of the appellate court denied the Motion for Reconsideration [5] and the Supplemental Motion for Reconsideration [6] filed by IVQ regarding the Court of Appeals' decision. The Facts On June 10, 2004, Barbosa filed a Petition for Cancellation and Quieting of Titles [7] against Jorge Vargas III, Benito Montinola, IVQ, and the Register of Deeds of Quezon City, which case was docketed as Civil Case No. Q04-52842 in the RTC of Quezon City, Branch 222. Barbosa averred that on October 4, 1978, he bought from Therese Vargas a parcel of land identified as Lot 644-C-5 located on Visayas Avenue, Culiat, Quezon City (subject property). Thereafter, Therese Vargas surrendered to Barbosa the owner's duplicate copy of her title, Transfer Certificate of Title (TCT) No. 159487. In the Deed of Absolute Sale in favor of Barbosa and in the copy of Therese Vargas's TCT No. 159487, the subject property was described as: A parcel of land (Lot 644-C-5 of the subdivision plan, LRC, Psd-14038, being a portion of Lot 644-C, Fls-2544-D, LRC, Record No. 5975); situated in the District of Culiat, Quezon City, Island of Luzon. x x x containing an area of THREE THOUSAND FOUR HUNDRED FIFTY-­TWO (3,452) square meters, more or less. [8] Barbosa said that he took possession of the subject property and paid real estate taxes thereon in the name of Therese Vargas. Sometime in 2003, Barbosa learned that Therese Vargas's name was cancelled and replaced with that of IVQ in the tax declaration of the subject property. Upon investigation, Barbosa found out that the subject property was previously registered in the name of Kawilihan Corporation under TCT No. 71507. Therese Vargas acquired the subject property from Kawilihan Corporation and the date of entry of her TCT No. 159487 was November 6, 1970. On the other hand, IVQ supposedly bought the subject property from Jorge Vargas III who, in turn, acquired it also from Kawilihan Corporation. The date of entry of Jose Vargas III's TCT No. 223019 was October 14, 1976. This title was later reconstituted and re-numbered as TCT No. RT-76391. The title of IVQ, TCT No. 253434, was issued on August 6, 2003. Barbosa argued that even without considering the authenticity of Jorge Vargas III's title, Therese Vargas's title bore an earlier date. Barbosa, thus, prayed for the trial court to issue an order directing the Office of the Register of Deeds of Quezon City to cancel Jorge Vargas III's TCT No. 223019 and IVQ's TCT No. 253434 and adjudicating ownership of the subject property to him. [9] In their Answer [10] to the above petition, Jose Vargas III, Benito Montinola, and IVQ (respondents in the court a quo ) countered that the alleged title from where Barbosa's title was allegedly derived from was the one that was fraudulently acquired and that Barbosa was allegedly part of a syndicate that falsified titles for purposes of "land grabbing." They argued that it was questionable that an alleged lot owner would wait for 30 years before filing an action to quiet title. They prayed for the dismissal of the petition and, by way of counterclaim, sought the award of moral and exemplary damages, attorney's fees and costs of suit. The Register of Deeds of Quezon City neither filed an answer to Barbosa's petition nor participated in the trial of the case. During trial, Barbosa testified, inter alia , that he is the owner of the subject property that he bought from Therese Vargas. The property was at that time registered in her name under TCT No. 159487. Barbosa took possession of the subject property seven days after he bought the same and he employed a caretaker to live therein. Before Therese Vargas, the owner of the property was Kawilihan Corporation, which company was owned by Jorge Vargas. [11] Barbosa stated that the subject property remained registered in the name of Therese Vargas as he entrusted her title to another person for custody but the said person went to Canada. Barbosa paid real estate taxes on the subject property in the name of Kawilihan Corporation from 1978 until 2002. From 2003 to 2006, he paid real estate taxes thereon in the name of Therese Vargas. [12] Barbosa added that in the year 2000, Santiago Sio Soy Une, allegedly the president of Lisan Realty and Development Corporation (Lisan Realty), presented to Barbosa's caretaker a Deed of Sale with Assumption of Mortgage, [13] which was allegedly executed by Jorge Vargas III and Lisan Realty involving the subject property. Barbosa then went on to compile documents on the transactions relating to the subject property. Barbosa testified that in the Deed of Sale with Assumption of Mortgage of Jorge Vargas III and Santiago Sio Soy Une, the Friar Land Survey (FLS) number was denominated as FLS-2554-D, while in the title of Therese Vargas it was FLS-2544-D. Barbosa obtained a certification from the Lands Management Bureau that FLS-2554-D was not listed in their electronic data processing (EDP) listing, as well as a certification from the DENR that FLS-2554-D had no records in the Land Survey Records Section of said office. On the other hand, he obtained a certification from the Lands Management Bureau that Lot 644 subdivided under FLS-2544-D was listed in their records. [14] Barbosa also learned that IVQ was registered with the Securities and Exchange Commission only on June 5, 1998. Moreover, on January 7, 2004, IVQ filed Civil Case No. Q-17499(04), which is a petition for the cancellation of an adverse claim filed by Santiago Sio Soy Une ( Exhibit "RR" ). In a portion of the transcript of stenographic notes (TSN) in said case, it was stated that IVQ bought the property from Therese Vargas, not from Jorge Vargas III. [15] Barbosa furthermore secured a certification from the EDP Division of the Office of the City Assessor in Quezon City that there were no records of real property assessments in the name of Jorge Vargas III as of August 15, 2006. Moreover, Barbosa stated that Atty. Jesus C. Apelado, Jr., the person who notarized the March 3, 1986 Deed of Absolute Sale between Jorge Vargas III and IVQ, was not authorized to do so as Atty. Apelado was only admitted as a member of the Philippine Bar in 1987. Also, the notarial register entries, i.e. , the document number, page number, book number and series number, of the Deed of Absolute Sale in favor of IVQ were exactly the same as those in the special power of attorney (SPA) executed by Jorge Vargas III in favor of Benito Montinola, who signed the Deed of Absolute Sale on behalf of Jorge Vargas III. The Deed of Absolute Sale and the SPA were notarized by different lawyers but on the same date. [16] On the part of the respondents in the court a quo , they presented a lone witness, Atty. Erlinda B. Espejo. Her testimony was offered to prove that she was the legal consultant of IVQ; that IVQ's TCT No. 253434 was acquired from Jorge Vargas III through TCT No. RT-76391; that Jorge Vargas III's title was mortgaged at Philippine National Bank (PNB), Bacolod; that Benito Montinola, the attorney-in-fact of Jorge Vargas III, sold the subject property to Lisan Realty who in turn assigned its rights to IVQ and; that IVQ redeemed the property from PNB. Barbosa's counsel offered to stipulate on the offer so that the witness' testimony could already be dispensed with. [17] As to the supposed sale to Lisan Realty and Lisan Realty's assignment of rights to IVQ, the counsel for Barbosa agreed to stipulate on the same if the transactions were annotated in Jorge Vargas III's title. The counsel for IVQ said that they were so annotated. Upon inquiry of the trial court judge, the counsel for IVQ clarified that the transfers or assignment of rights were done at the time that the subject property was mortgaged with PNB. The property was then redeemed by IVQ on behalf of Jorge Vargas III. [18] The Decision of the RTC On June 15, 2007, the RTC granted Barbosa's petition and ordered the cancellation of IVQ's TCT No. 253434. [19] The trial court noted that while the original copy of the Deed of Absolute Sale in favor of Barbosa was not presented during trial, Barbosa presented secondary evidence by submitting to the court a photocopy of said deed and the deed of sale in favor of his predecessor-in-interest Therese Vargas, as well as his testimony. The RTC ruled that Barbosa was able to establish the existence and due execution of the deeds of sale in his favor and that of Therese Vargas. The Certification [20] dated February 12, 2004 from the Office of the Clerk of Court and Ex-Officio Sheriff of the RTC, Manila stated that the page on which the Deed of Sale dated October 4, 1978 in favor of Barbosa might have been probably entered was torn. This, however, did not discount the possibility that said deed was actually notarized and recorded in the missing notarial records page. Moreover, the RTC found that Barbosa adduced evidence that proved the payment [21] of Therese Vargas to Jorge Vargas, as well as the payment of Barbosa to Therese Vargas. The RTC further observed that Therese Vargas's TCT No. 159487 and Jorge Vargas III's TCT No. 223019 bear more or less identical technical descriptions of Lot 644-C-5, except for their friar survey plan numbers. However, the Lands Management Bureau and Land Survey Records Section of the DENR, NCR issued certifications attesting that their respective offices had no record of FLS-2554-D, the land survey number in the certificates of title held by Jorge Vargas III and IVQ. On the other hand, Barbosa presented a certified true copy of the subdivision survey plan FLS-2544-D from the Lands Management Bureau, thereby bolstering his claim that the title of Therese Vargas was an authentic transfer of the title of Kawilihan Corporation. Therese Vargas's TCT No. 159487 was also issued earlier in time than Jorge Vargas III's TCT No. 223019. Not only was the original of Therese Vargas's TCT No. 159487 presented in court, but the same was also proven to have existed according to the Certification from the LRA dated October 6, 2003 that Judicial Form No. 109-D with Serial No. 1793128 - pertaining to TCT No. 159487 - was issued by an authorized officer of the Register of Deeds of Quezon City. In contrast, the RTC noted that IVQ was not able to prove its claim of ownership over the subject property. The deed of sale in favor of IVQ, which was supposedly executed in 1986, was inscribed only in 2003 on Jorge Vargas III's TCT No. RT-76391 that was reconstituted back in 1993. Instead of substantiating their allegations, respondents in the court a quo opted to offer stipulations, such as on the matter of Lisan Realty's assignment of its rights of ownership over the subject property in favor of IVQ. However, the said assignment was not reflected in the title of Jorge Vargas III. The RTC likewise found it perplexing that when IVQ filed a petition for cancellation of encumbrance in Jorge Vargas III's title, docketed as LRC No. Q-17499 (04), it alleged therein that it acquired the subject property from Therese Vargas, not Jorge Vargas III. The trial court added that while there is no record of tax declarations and payment of real estate taxes in the name of Jorge Vargas III, Therese Vargas declared the subject property for taxation purposes in her name and, thereafter, Barbosa paid real estate taxes thereon in her name. On the other hand, the only tax declaration that IVQ presented was for the year 2006. The RTC also opined that while Barbosa was not able to sufficiently establish his possession of the subject property as he failed to put on the witness stand the caretaker he had authorized to occupy the property, IVQ also did not gain control and possession of the subject property because the same continued to be in the possession of squatters. To impugn the above decision of the trial court, IVQ, alone, filed a Motion for Reconsideration/New Trial/Reopening of Trial [22] under the representation of a new counsel. [23] In its Motion for Reconsideration, IVQ argued that the RTC erred in concluding that Barbosa's title is superior to its title. [24] IVQ alleged that Barbosa submitted forged and spurious evidence before the trial court. On the other hand, in its Motion for New Trial, IVQ alleged that it was defrauded by its former counsel, Atty. Leovigildo Mijares, which fraud prevented it from fully presenting its case in court. IVQ also averred that it found newly-discovered evidence, which it could not have discovered and produced during trial. In an Order [25] dated November 28, 2007, the trial court denied IVQ's Motion for Reconsideration/New Trial/Reopening of Trial for lack of merit. IVQ's Appeal in the Court of Appeals IVQ interposed an appeal [26] to the Court of Appeals. In its Appellant's Brief, IVQ first laid down its version of the facts, to wit: On 12 March 1976, Kawilihan Corporation, represented by its President and Chairman of the Board Jorge B. Vargas, executed a Deed of Absolute Sale x x x, whereby he sold the subject property to appellant Vargas, III. On 14 October 1976, TCT No. 71507 was cancelled and in lieu thereof TCT No. 223019 x x x was issued in the name of appellant Vargas, III who on 23 December 1976 executed a Special Power of Attorney x x x in favor of appellant Benito C. Montinola, Jr. with power among other things to mortgage the subject property for and in behalf of appellant Vargas, III. On 25 December 1976, appellant Vargas, III mortgaged the subject property to the Philippine National Bank (PNB), Victorias Branch, Negros Occidental as security for a loan in the principal amount of P506,000.00. On 04 October 1978, Therese Vargas executed a Deed of Absolute Sale x x x wherein she sold the subject property to appellee Barbosa who however did not register the said sale with the Registry of Deeds of Quezon City. It appears that Therese Vargas was able to secure TCT No. 159487 x x x in her name on 06 November 1970 covering the subject property. Meanwhile, appellant Vargas, III executed another Special Power of Attorney x x x in favor of appellant Montinola, Jr. with power among other things to sell the subject property for and in behalf of appellant Vargas, III. Thus, on 03 March 1986, during the effectivity of the mortgage contract with PNB, appellant Montinola sold the subject property to appellant IVQ for and in consideration of the amount of P450,000.00. [27] After the alleged sale of the subject property to IVQ, the following incidents transpired: When appellant Vargas, III failed to pay his loan, PNB foreclosed the mortgage and in the public auction that followed, the subject property was sold to PNB. A Certificate of Sale was issued in favor of PNB but the latter did not cause the registration of the certificate of sale right away. Sometime in 1991, appellant Montinola, Jr. caused the filing of a Petition for Reconstitution of TCT No. 223019 which was granted in 1993. Consequently, TCT No. RT-76391 was issued, in the name of appellant Vargas, III, in lieu ofTCT No. 223019. On 13 July 1993, the Certificate of Sale in favor of PNB was inscribed on appellant Vargas, III's new title. On 17 February 1994, appellant Vargas, III executed a Deed of Sale with Assumption of Mortgage x x x wherein he sold to Lisan Realty and Development Corporation (Lisan Realty) the subject property with the latter assuming the loan balance with PNB. On 23 June 1994, appellant IVQ, for and in behalf of defendant Vargas, III, redeemed the subject property from PNB and on 24 June 1994, the Certificate of Redemption was annotated at the dorsal portion of TCT No. RT-76390. On 21 August 2000, Lisan Realty caused the annotation of an Affidavit of Adverse Claim x x x on TCT No. RT-76390. Thereafter, appellant IVQ filed a Petition for Cancellation of Encumbrance x x x with the Regional Trial Court of Quezon City, Branch 220, docketed as LRC Case No. Q-17499 (04). On 06 August 2003, the Register of Deeds of Quezon City cancelled TCT No. RT-76390 and in lieu thereof TCT No. 253434 was issued in the name of appellant IVQ. On 11 February 2004, the Regional Trial Court of Quezon City, Branch 220 rendered a Decision x x x granting appellant IVQ's Petition for Cancellation of Encumbrance and ordering the cancellation of the annotation of the adverse claim on TCT No. 253434. In August 2004, appellant IVQ instituted [a] Complaint x x x for unlawful detainer with the Metropolitan Trial Court of Quezon City, Branch 38 against several persons who were occupying the subject property without any right whatsoever. The case was docketed as Civil Case No. 38-33264. On 26 October 2004, the Metropolitan Trial Court of Quezon City, Branch 38 rendered a Decision x x x in favor of appellant IVQ ordering the defendants therein to vacate the subject property. [28] The Court of Appeals, however, paid no heed to IVQ's appeal as it affirmed the ruling of the RTC. The appellate court held that Barbosa was able to prove his ownership over the subject property, while IVQ presented a rather flimsy account on the transfer of the subject property to its name. IVQ filed a Motion for Reconsideration and a Supplemental Motion for Reconsideration on the above judgment, but the Court of Appeals denied the same in its assailed Resolution dated July 30, 2010. IVQ's Petition for Review on Certiorari IVQ instituted before this Court the instant petition for review on certiorari on August 20, 2010, which prayed for the reversal of the above rulings of the Court of Appeals. In a Resolution [29] dated September 29, 2010 , the Court initially denied IVQ's petition for its failure to show that the Court of Appeals committed any reversible error in its assailed rulings. IVQ filed a Motion for Reconsideration [30] on the denial of its petition. To prove that its title to the subject property is genuine, IVQ averred that the Deed of Absolute Sale in favor of Jorge Vargas III was notarized by Atty. Jejomar C. Binay, then a notary public for Mandaluyong. IVQ attached to its motion for reconsideration, among others, a photocopy of a Certification [31] dated October 8, 2010 from the Office of the Clerk of Court of the RTC of Pasig City that "ATTY. JEJOMAR C. BINAY was appointed Notary Public for and in the Province of Rizal for the year 1976" and that he "submitted his notarial reports for the period January, 1976 up to December, 1976." IVQ also attached a photocopy of the Deed of Absolute Sale in favor of Jorge Vargas III obtained from the records of the National Archives on October 14, 2010. [32] To prove that Barbosa's claim of ownership is spurious, IVQ attached to its motion for reconsideration the following documents: (1) a photocopy of a Certification dated October 27, 2010 from the Office of the Bar Confidant of the Supreme Court that Espiridion J. Dela Cruz, the notary public who supposedly notarized the Deed of Absolute Sale in favor of Therese Vargas, is not a member of the Philippine Bar; [33] (2) a photocopy of the Certification dated October 19, 2010 from the National Archives of the Philippines that a copy of the Deed of Absolute Sale in favor of Therese Vargas is not extant in the files of said office; [34] (3) a Certification dated October 12, 2010 from the Office of the Clerk of Court and Ex-Officio Sheriff of the RTC of Manila, stating that the notarial entries of Atty. Santiago R. Reyes in the Deed of Absolute Sale between Therese Vargas and Barbosa Doc. No. 1947, Page 92, Book No. XIV, Series of 1978 - actually pertained to a different deed of sale; [35] (4) photocopies of pages 90, 91 and 92, Book XIV, Series of 1978 of Atty. Santiago R. Reyes's notarial records, which were reproduced from the National Archives on October 14, 2010, showing that the Deed of Absolute Sale between Therese Vargas and Barbosa was not found therein; [36] (5) a photocopy of a Certification dated October 14, 2010 of the City Treasurer's Office of the City of Manila, stating that Residence Certificate No. A-423263 - the residence certificate number of Therese Vargas in the Deed of Absolute Sale in favor of Barbosa - was not among those allotted to the City of Manila; [37] and (6) a letter dated October 20, 2010 from Director Porfirio R. Encisa, Jr. of the LRA Department on Registration, explaining that the land survey number of FLS-2554-D in IVQ's TCT No. 253434 was a mere typographical error and it should have been FLS-2544-D. [38] In a Resolution [39] dated December 15, 2010, the Court denied IVQ's Motion for Reconsideration. Undaunted, IVQ filed a Second Motion for Reconsideration, [40] arguing that it was able to submit new pieces of documentary evidence that surfaced for the first time when its Motion for Reconsideration was submitted by its new counsel. IVQ entreated the Court to consider the same in the higher interest of justice. Barbosa opposed [41] the above motion, countering that the same is a prohibited pleading. Barbosa maintained that it was impossible for IVQ to acquire ownership over the subject property as the latter was only incorporated on June 5, 1998. Thus, IVQ could not have bought the property from Jorge Vargas III on March 3, 1986 or subsequently redeemed the property in 1994. In a Resolution [42] dated June 6, 2011, the Court reinstated IVQ's petition and required Barbosa to comment thereon. Barbosa moved for a reconsideration [43] of the said resolution, citing IVQ's lack of legal personality when it supposedly purchased the subject property and IVQ's inconsistent statements as to how it acquired the same. The Court treated the above motion of Barbosa as his comment to IVQ's petition and required IVQ to file a reply thereto. [44] In its Reply, [45] IVQ primarily argued that Barbosa did not bother to refute the allegations and the evidence on the spuriousness of his title and instead sought to divert the issue by attacking IVQ's corporate existence. The Court, thereafter, gave due course to the petition and required the parties to submit their respective memoranda. [46] In its memorandum, [47] IVQ avers that while the evidence supporting its case surfaced for the first time after its petition was filed with this Court, peculiar circumstances involving the actuations of IVQ's former counsel and Barbosa's introduction of spurious documents warrant the suspension of procedural rules in the interest of justice. IVQ insists that Barbosa was not able to prove his claim by preponderance of evidence. Upon the other hand, Barbosa contends that IVQ could not legally claim ownership of the subject property as this claim is anchored on a Deed of Absolute Sale executed by Jorge Vargas III on March 3, 1986 while IVQ was incorporated only on June 5, 1998. Barbosa also points out that the Deed of Absolute Sale in favor of IVQ was signed only by Jorge Vargas III's representative, Benito Montinola. There is no corresponding signature on the part of the vendee. Barbosa adopts entirely the findings of the RTC and the Court of Appeals that the sale in favor of Therese Vargas is the one to be legally sustained. The Ruling of the Court Without ruling on the merits of this case, the Court finds that there is a need to reassess the evidence adduced by the parties to this case and thereafter reevaluate the findings of the lower courts. To recall, Barbosa initiated this case before the trial court via a petition for cancellation and quieting of titles. As held in Secuya v. De Selma , [48] In an action to quiet title, the plaintiffs or complainants must demonstrate a legal or an equitable title to, or an interest in, the subject real property. Likewise, they must show that the deed, claim, encumbrance or proceeding that purportedly casts a cloud on their title is in fact invalid or inoperative despite its prima facieappearance of validity or legal efficacy. This point is clear from Article 476 of the Civil Code, which reads: "Whenever there is cloud on title to real property or any interest therein, by reason of any instrument, record, claim, encumbrance or proceeding which is apparently valid or effective but is in truth and in fact invalid, ineffective, voidable or unenforceable, and may be prejudicial to said title, an action may be brought to remove such cloud or to quiet title." "An action may also be brought to prevent a cloud from being cast upon title to real property or any interest therein." (Emphasis supplied; citations omitted.) The Court also stressed in Santiago v. Villamor [49] that in civil cases, the plaintiff must establish his cause of action by preponderance of evidence; otherwise, his suit will not prosper. In the instant case, the trial court and the Court of Appeals adjudicated the subject property in favor of Barbosa and directed the cancellation of IVQ's certificate of title. The trial court found that Barbosa was able to substantiate the transfer of ownership of the subject property from Kawilihan Corporation to Therese Vargas and then to Barbosa. Specifically, Barbosa established the existence and execution of the Deed of Absolute Sale dated September 11, 1970 between Kawilihan Corporation and Therese Vargas, as well as the Deed of Absolute Sale dated October 4, 1978 between Therese Vargas and Barbosa. In like manner, the trial court ruled that Barbosa adduced evidence that purportedly proved the payment of Therese Vargas to Kawilihan Corporation, and the payment of Barbosa to Therese Vargas. Also, the trial court found that Barbosa was able to prove the validity of Therese Vargas's TCT No. 159487. Moreover, the friar land survey number in Therese Vargas's TCT No. 159487- FLS-2544-D - was the one found to be extant in the records of Lands Management Bureau, not FLS-2554-D, the survey number in the certificates of title of Jorge Vargas III and IVQ. On the other hand, the trial court found that IVQ failed to establish its claim of ownership over the subject property, given the inconsistent statements on how the property was transferred from Kawilihan Corporation to Jorge Vargas III and eventually to IVQ. Before this Court, however, IVQ adduced new pieces of documentary evidence that tended to cast doubt on the veracity of Barbosa's claim of ownership. To impugn the validity of the Deed of Absolute Sale between Kawilihan Corporation and Therese Vargas, IVQ submitted a copy of the Certification from the Office of the Bar Confidant that Espiridion J. Dela Cruz, the notary public who supposedly notarized the said deed, is not a member of the Philippine Bar. IVQ also submitted a copy of the Certification from the National Archives, stating that the Deed of Absolute Sale in favor of Therese Vargas was not found in their records. Anent the Deed of Absolute Sale between Therese Vargas and Barbosa, IVQ presented a Certification from the Office of the Clerk of Court and Ex-Officio Sheriff of the RTC of Manila, stating that the notarial entries of Atty. Santiago R. Reyes in said deed, i.e. , Doc. No. 1947, Page 92, Book No. XIV, Series of 1978, pertained to a deed of sale between other individuals. Also, the Deed of Absolute Sale in favor of Barbosa was not found in the photocopies of pages 90, 91, and 92 of the aforesaid notarial records of Atty. Santiago R. Reyes, which pages were reproduced from the National Archives. IVQ also submitted a Certification from the City Treasurer's Office of the City of Manila, stating that Therese Vargas's Residence Certificate No. A-423263 in the Deed of Absolute Sale in favor of Barbosa was not among those allotted to the City of Manila. Furthermore, IVQ submitted a letter from Director Porfirio R. Encisa, Jr. of the LRA Department of Registration, stating that the survey number FLS-2554-D in IVQ's TCT No. 253434 was a typographical error and the same should have been FLS-2544-D. On the other hand, to bolster its claim of ownership over the subject property, IVQ presented a copy of the Deed of Absolute Sale [50] dated March 12, 1976 between Kawilihan Corporation and Jorge Vargas III that was obtained from the records of the National Archives. IVQ also submitted a copy of the Certification from the Office of the Clerk of Court of the RTC of Pasig City that Atty. Jejomar C. Binay, the officer who notarized the said deed, was indeed appointed as a notary public for the province of Rizal for the year 1976 and the latter submitted his notarial reports for the said year. Interestingly, despite the claim of both parties that their respective titles could be traced to TCT No. 71507 in the name of Kawilihan Corporation, neither of them thought to submit a certified true copy of the cancelled TCT No. 71507, which would have indicated to whom the subject property had in fact been transferred. The parties likewise admit in their pleadings that there is an on-going investigation being conducted by the LRA on the authenticity and genuineness of the certificates of title involved in the present case and to date, the LRA has not issued any official report pertaining to said investigation. After reviewing the factual and procedural antecedents of this case, the Court deems it appropriate that further proceedings be undertaken in order to verify the authenticity and veracity of the parties' certificates of title and other documentary evidence. For sure, the Court is aware that the aforesaid evidence belatedly introduced by IVQ are not technically newly-discovered evidence, given that the same could have been discovered and produced at the trial of the case had IVQ exercised reasonable diligence in obtaining them. [51] Nonetheless, we find that the above evidence cannot simply be brushed aside on this ground alone. The same are too material to ignore and are relevant in ultimately resolving the question of ownership of the subject property. In Mangahas v. Court of Appeals , [52] we recognized the long line of jurisprudence that: [I]t is always in the power of this Court to suspend its own rules, or to except a particular case from its operation, whenever the purposes of justice require it. This Court is mindful of the policy of affording litigants the amplest opportunity for the determination of their cases on the merits and of dispensing with technicalities whenever compelling reasons so warrant or when the purpose of justice requires it. (Citations omitted.) Indeed, the alleged defects in the notarization of the Deed of Absolute Sale dated September 11, 1970 between Kawilihan Corporation and Therese Vargas and the Deed of Absolute Sale dated October 4, 1978 between Therese Vargas and Barbosa are by no means trivial. As the Court stressed in Vda. De Rosales v. Ramos [53] : The importance attached to the act of notarization cannot be overemphasized. Notarization is not an empty, meaningless, routinary act. It is invested with substantive public interest, such that only those who are qualified or authorized may act as notaries public. Notarization converts a private document into a public document thus making that document admissible in evidence without further proof of its authenticity. A notarial document is by law entitled to full faith and credit upon its face. Courts, administrative agencies and the public at large must be able to rely upon the acknowledgment executed by a notary public and appended to a private instrument. x x x          x x x          x x x The notary public is further enjoined to record in his notarial registry the necessary information regarding the document or instrument notarized and retain a copy of the document presented to him for acknowledgment and certification especially when it is a contract. The notarial registry is a record of the notary public's official acts. Acknowledged documents and instruments recorded in it are considered public document. If the document or instrument does not appear in the notarial records and there is no copy of it therein, doubt is engendered that the document or instrument was not really notarized, so that it is not a public document and cannot bolster any claim made based on this document. x x x. (Citations omitted.) Furthermore, in Bitte v. Jonas , [54] the Court had occasion to discuss the consequence of an improperly notarized deed of absolute sale. Thus - Article 1358 of the New Civil Code requires that the form of a contract transmitting or extinguishing real rights over immovable property should be in a public document. x x x. x x x          x x x          x x x Not having been properly and validly notarized, the deed of sale cannot be considered a public document. It is an accepted rule, however, that the failure to observe the proper form does not render the transaction invalid. It has been settled that a sale of real property, though not consigned in a public instrument or formal writing is, nevertheless, valid and binding among the parties, for the time-honored rule is that even a verbal contract of sale or real estate produces legal effects between the parties. Not being considered a public document, the deed is subject to the requirement of proof under Section 20, Rule 132, which reads: Section 20. Proof of private document . - Before any private document offered as authentic is received in evidence its due execution and authenticity must be proved either: (a) By anyone who saw the document executed or written; or (b) By evidence of the genuineness of the signature or handwriting of the maker. Any other private document need only be identified as that which it is claimed to be. Accordingly, the party invoking the validity of the deed of absolute sale had the burden of proving its authenticity and due execution. x x x. (Emphasis supplied; citations omitted.) In the instant case, should the Deeds of Absolute Sale in favor of Therese Vargas and Barbosa, respectively, be found to be indeed improperly notarized, the trial court would have erred in admitting the same in evidence without proof of their authenticity and in relying on the presumption regarding the regularity of their execution. Barbosa would then have the additional burden of proving the authenticity and due execution of both deeds before he can invoke their validity in establishing his claim of ownership. Therefore, IVQ should be allowed to formally offer in evidence the documents it belatedly submitted to this Court and that Barbosa should equally be given all the opportunity to refute the same or to submit controverting evidence. Given that the Court is not a trier of facts and there still are factual matters that need to be evaluated, the proper recourse is to remand the case to the Court of Appeals for the conduct of further proceedings. In Manotok IV v. Heirs of Homer L. Barque , [55] the Court explained the propriety of resorting to the above procedure in this wise: At the same time, the Court recognizes that there is not yet any sufficient evidence for us to warrant the annulment of the Manotok title. All that the record indicates thus far is evidence not yet refuted by clear and convincing proof that the Manotok's claim to title is flawed. To arrive at an ultimate determination, the formal reception of evidence is in order. This Court is not a trier of fact or otherwise structurally capacitated to receive and evaluate evidence de novo. However, the Court of Appeals is sufficiently able to undertake such function. The remand of cases pending with this Court to the Court of Appeals for reception of further evidence is not a novel idea. It has been undertaken before - in Republic v. Court of Appeals and more recently in our 2007 Resolution in Manotok v. Court of Appeals . Our following explanation in Manotok equally applies to this case: Under Section 6 of Rule 46, which is applicable to original cases for certiorari , the Court may, whenever necessary to resolve factual issues, delegate the reception of the evidence on such issues to any of its members or to an appropriate court, agency or office. The delegate need not be the body that rendered the assailed decision. The Court of Appeals generally has the authority to review findings of fact. Its conclusions as to findings of fact are generally accorded great respect by this Court. It is a body that is fully capacitated and has a surfeit of experience in appreciating factual matters, including documentary evidence. In fact, the Court had actually resorted to referring a factual matter pending before it to the Court of Appeals. In Republic v. Court of Appeals , this Court commissioned the former Thirteenth Division of the Court of Appeals to hear and receive evidence on the controversy, x x x. The Court of Appeals therein received the evidence of the parties and rendered a "Commissioner's Report" shortly thereafter. Thus, resort to the Court of Appeals is not a deviant procedure. The provisions of Rule 32 should also be considered as governing the grant of authority to the Court of Appeals to receive evidence in the present case. Under Section 2, Rule 32 of the Rules of Court, a court may, motu proprio , direct a reference to a commissioner when a question of fact, other than upon the pleadings, arises upon motion or otherwise, in any stage of a case, or for carrying a judgment or order into effect. The order of reference can be limited exclusively to receive and report evidence only, and the commissioner may likewise rule upon the admissibility of evidence. The commissioner is likewise mandated to submit a report in writing to the court upon the matters submitted to him by the order of reference. In Republic , the commissioner's report formed the basis of the final adjudication by the Court on the matter. The same result can obtain herein. (Emphasis supplied; citations omitted.) Aside from receiving and evaluating evidence relating to the pieces of documentary evidence submitted by IVQ to this Court, the Court of Appeals may likewise receive any other additional evidence that the parties herein may submit on their behalf. The Court, in particular, deems it necessary for the parties to submit a certified true copy of TCT No. 71507 that is registered in the name of Kawilihan Corporation, if possible. As previously discussed, neither of the parties submitted the same before the trial court and no explanation was likewise offered for this omission. As TCT No. 71507 is ultimately the title from which the certificates of title of Therese Vargas and Jorge Vargas III supposedly emanated, the same may indicate which of the two subsequent titles cancelled it. It would likewise be expedient for the parties to submit evidence as to the character of their possession of the subject property, given that the trial court ruled that neither of them were able to prove their possession thereof. The Court further reiterates its directive to the parties to submit information as to the results of the investigation of the Task Force Titulong Malinis of the LRA regarding the authenticity ofTCT No. 159487 registered in the name of Therese Vargas and TCT No. 223019 registered in the name of Jorge Vargas III. After the conclusion of its proceedings, the Court of Appeals is directed to submit to this Court a detailed Report on its findings and conclusions within three months from notice of this Resolution. Said report, along with all the additional evidence that will be offered by the parties, shall be thoroughly considered in order to determine with finality the issue of ownership of the subject property. WHEREFORE , the case is REMANDED to the Court of Appeals for the purpose of hearing and receiving evidence, including but not limited to, those specifically required by the Court in this Resolution. The Court of Appeals is directed to conclude the proceedings and submit to this Court a Report on its findings and recommended conclusions within three (3) months from notice of this Resolution. The Court of Appeals is further directed to raffle this case immediately upon receipt of this Resolution. This Resolution is immediately executory. SO ORDERED. Sereno, C.J., (Chairperson), Velasco, Jr. , * Del Castillo , and Caguioa, JJ. , concur. * Per Raffle dated January 16, 2017. [1] Rollo , pp. 3-63. [2] Id. at 64-76; penned by Associate Justice Amelita G. Tolentino with Associate Justices Estela M. Perlas-Bernabe (now a member of this Court) and Stephen C. Cruz concurring. [3] Id. at 77-80. [4] Id. at 129-136; penned by Judge Rogelio M. Pizarro. [5] CA rollo , pp. 168-183. [6] Id. at 189-199. [7] Rollo , pp. 105-109. [8] Records, Vol. I, pp. 7-8. [9] Barbosa attached to his petition (1) a photocopy of the Deed of Absolute Sale in his favor ( Annex "A" ); (2) a photocopy of Therese Vargas's TCT No. 159487 ( Annex "B" ); (3) a photocopy of a tax declaration of the subject property in the name of IVQ ( Annex "C" ); (4) a photocopy of Jose Vargas III's TCT No. 223019 ( Annex "D" ); (5) a photocopy of a Barangay Certification, stating that Therese Vargas is the owner of the subject property ( Annex "E" ); and (6) a photocopy of a tax declaration of the subject property in the name of Therese Vargas ( Annex "F" ). (Records, Vol. I, pp. 7-16.) [10] Records, Vol. I, pp. 39-42. [11] Jorge Vargas is also referred to as "Jorge Vargas, Sr." and "Jorge B. Vargas" in other parts of the records. [12] TSN, June 29, 2006, pp. 7-25. [13] Id. at 31. Santiago Sio Soy Une was also referred to as "Santiago Suysusuni" in other parts of the records. [14] TSN, June 29, 2006, pp. 47-51. [15] TSN, August 22, 2006, pp. 13-17. [16] Id. at 19-32. [17] TSN, February 15, 2007, pp. 3-4. [18] Id. at 10-11. [19] Rollo , p. 136. [20] Records, Vol. I, p. 105. [21] Id. at 121. [22] Rollo , pp. 137-160. [23] Records, Vol. I, pp. 696-698. [24] Rollo , p. 139. [25] Id. at 182-185. [26] Records, Vol. II, pp. 812-813. [27] CA rollo , pp. 40-41. [28] Id. at 41-43. [29] Rollo , p. 192. [30] Id. at 199-249. [31] Id. at 250. [32] Id. at 251-254. [33] Id. at 268. [34] Id. at 269. [35] Id. at 273. [36] Id. at 275-280. [37] Id. at 281. [38] Id. at 282. [39] Id. at 283-284. [40] Id. at 299-348. [41] Id. at 350-351. [42] Id. at 360. [43] Id. at 353-359. [44] Id. at 364. [45] Id. at 368-381. [46] Id. at 414-415. [47] Id. at 416-469. [48] 383 Phil. 126, 134 (2000). [49] 699 Phil. 297, 303-304 (2012). [50] Rollo , pp. 251-254. [51] See Custodio v. Sandiganbayan , 493 Phil. 194 (2005). [52] 588 Phil. 61, 82 (2008). [53] 433 Phil. 8, 15-16 (2002). [54] G.R. No. 212256, December 9, 2015. [55] 595 Phil. 87, 148-149 (2008). 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Reslizumab in Patients With Severe Asthma Who Failed to Respond to Omalizumab - Full Text View - ClinicalTrials.gov is coming. Check it out now. Hide glossary Glossary Study record managers: refer to the Data Element Definitions if submitting registration or results information. Search for terms Accepts healthy volunteers A type of eligibility criteria that indicates whether people who do not have the condition/disease being studied can participate in that clinical study. Active comparator arm An arm type in which a group of participants receives an intervention/treatment considered to be effective (or active) by health care providers. Adverse event An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of time after the study has ended. This change may or may not be caused by the intervention/treatment being studied. Age or age group A type of eligibility criteria that indicates the age a person must be to participate in a clinical study. This may be indicated by a specific age or the following age groups: The age groups are: Child (birth-17) Adult (18-64) Older Adult (65+) All-cause mortality A measure of all deaths, due to any cause, that occur during a clinical study. Allocation A method used to assign participants to an arm of a clinical study. The types of allocation are randomized allocation and nonrandomized. Arm A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment , or no intervention, according to the trial's protocol . Arm type A general description of the clinical trial arm. It identifies the role of the intervention that participants receive. Types of arms include experimental arm , active comparator arm , placebo comparator arm , sham comparator arm , and no intervention arm . Baseline characteristics Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age, sex/gender, race and ethnicity, and study-specific measures (for example, systolic blood pressure, prior antidepressant treatment). Canceled submission Indicates that the study sponsor or investigator recalled a submission of study results before quality control (QC) review took place. If the submission was canceled on or after May 8, 2018, the date is shown. After submission of study results, a study record cannot be modified until QC review is completed, unless the submission is canceled. Certain agreements Information required by the Food and Drug Administration Amendments Act of 2007 . In general, this is a description of any agreement between the sponsor of a clinical study and the principal investigator (PI) that does not allow the PI to discuss the results of the study or publish the study results in a scientific or academic journal after the study is completed. Certification A sponsor or investigator may submit a certification to delay submission of results information if they are applying for FDA approval of a new drug or device, or new use of an already approved drug or device. A sponsor or investigator who submits a certification can delay results submission up to 2 years after the certification/extension first submitted date, unless certain events occur sooner. See Delay Results Type in the Results Data Element definitions for more information about this certification. Certification/extension first posted The date on which information about a certification to delay submission of results or an extension request was first available on ClinicalTrials.gov. ClinicalTrials.gov does not indicate whether the submission was a certification or extension request. There is typically a delay between the date the study sponsor or investigator submitted the certification or extension request and the first posted date . Certification/extension first submitted The date on which the study sponsor or investigator first submitted a certification or an extension request to delay submission of results. A sponsor or investigator who submits a certification can delay results submission up to 2 years after this date, unless certain events occur sooner. There is typically a delay between the date the certification or extension request was submitted and the date the information is first available on ClinicalTrials.gov ( certification/extension first posted ). 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For example, if you choose Illinois as the state , identifying "Chicago" as the city and "100 miles" as the distance will find all studies listing a location within 100 miles of Chicago. Clinical study A research study involving human volunteers (also called participants) that is intended to add to medical knowledge. There are two types of clinical studies: interventional studies (also called clinical trials) and observational studies . Clinical trial Another name for an interventional study . ClinicalTrials.gov identifier (NCT number) The unique identification code given to each clinical study upon registration at ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Collaborator An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting. Condition/disease The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks. Contact The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions. Country In the search feature, the Country field is used to find clinical studies with locations in a specific country. For example, if you choose the United States, you can then narrow your search by selecting a state and identifying a city and distance . Cross-over assignment A type of intervention model describing a clinical trial in which groups of participants receive two or more interventions in a specific order. For example, two-by-two cross-over assignment involves two groups of participants. One group receives drug A during the initial phase of the trial, followed by drug B during a later phase. The other group receives drug B during the initial phase, followed by drug A. So during the trial, participants "cross over" to the other drug. All participants receive drug A and drug B at some point during the trial but in a different order, depending on the group to which they are assigned. Data Monitoring Committee (DMC) A group of independent scientists who monitor the safety and scientific integrity of a clinical trial . The DMC can recommend to the sponsor that the trial be stopped if it is not effective, is harming participants, or is unlikely to serve its scientific purpose. Members are chosen based on the scientific skills and knowledge needed to monitor the particular trial. Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0) A phase of research used to describe exploratory trials conducted before traditional phase 1 trials to investigate how or whether a drug affects the body. They involve very limited human exposure to the drug and have no therapeutic or diagnostic goals (for example, screening studies, microdose studies). Eligibility criteria The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers , has age or age group requirements, or is limited by sex . Enrollment The number of participants in a clinical study. The "estimated" enrollment is the target number of participants that the researchers need for the study. Exclusion criteria A type of eligibility criteria . These are reasons that a person is not allowed to participate in a clinical study. Expanded access A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the U.S. Food and Drug Administration (FDA) . Also called compassionate use. There are different expanded access types . For more information, see FDA Expanded Access: Information for Patients . Expanded access status Available: Expanded access is currently available for this investigational treatment, and patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied. No longer available: Expanded access was available for this intervention previously but is not currently available and will not be available in the future. Temporarily not available: Expanded access is not currently available for this intervention but is expected to be available in the future. Approved for marketing: The intervention has been approved by the U.S. Food and Drug Administration for use by the public. Expanded access type Describes the category of expanded access under U.S. Food and Drug Administration (FDA) regulations. There are three types of expanded access: Individual Patients : Allows a single patient, with a serious disease or condition who cannot participate in a clinical trial, access to a drug or biological product that has not been approved by the FDA . This category also includes access in an emergency situation. Intermediate-size Population : Allows more than one patient (but generally fewer patients than through a Treatment IND/Protocol) access to a drug or biological product that has not been approved by the FDA . This type of expanded access is used when multiple patients with the same disease or condition seek access to a specific drug or biological product that has not been approved by the FDA . Treatment IND/Protocol : Allows a large, widespread population access to a drug or biological product that has not been approved by the FDA . This type of expanded access can only be provided if the product is already being developed for marketing for the same use as the expanded access use. Experimental arm An arm type in which a group of participants receives the intervention/treatment that is the focus of the clinical trial. Extension request In certain circumstances, a sponsor or investigator may request an extension to delay the standard results submission deadline (generally one year after the primary completion date ). The request for an extension must demonstrate good cause (for example, the need to preserve the scientific integrity of an ongoing masked trial). All requests must be reviewed and granted by the National Institutes of Health. See Delay Results Type in the Results Data Element definitions for more information. Factorial assignment A type of intervention model describing a clinical trial in which groups of participants receive one of several combinations of interventions. For example, two-by-two factorial assignment involves four groups of participants. Each group receives one of the following pairs of interventions: (1) drug A and drug B, (2) drug A and a placebo, (3) a placebo and drug B, or (4) a placebo and a placebo. So during the trial, all possible combinations of the two drugs (A and B) and the placebos are given to different groups of participants. FDAAA 801 Violations A FDAAA 801 Violation is shown on a study record when the U.S. Food and Drug Administration (FDA) has issued a Notice of Noncompliance to the responsible party of an applicable clinical trial. A Notice of Noncompliance indicates that the FDA has determined the responsible party was not in compliance with the registration or results reporting requirements for the clinical trial under the Food and Drug Administration Amendments Act of 2007, Section 801 (FDAAA 801). The National Library of Medicine (NLM) is required by FDAAA 801 to add information to a study record about any FDAAA 801 Violation. This information is provided by the FDA. There are three categories of information that may be included: Violation: Shown when the FDA issues a Notice of Noncompliance and posts the Notice of Noncompliance on its designated webpage. There are three types of violations: Failure to submit required clinical trial information Submission of false or misleading clinical trial information Failure to submit primary and secondary outcomes Correction: Shown when the FDA confirms that the responsible party has updated the study record to correct the violation and posts the correction notice on its designated webpage. Because of the time for FDA review and processing, there may be a delay between the date when the study record was updated and the addition of correction information to the FDAAA 801 Violation information. Penalty: Shown when the FDA imposes a penalty for the violation and posts the penalty notice on its designated webpage. First posted The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date. First submitted The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date). First submitted that met QC criteria The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria. Food and Drug Administration Amendments Act of 2007, Section 801 (FDAAA 801) U.S. Public Law 110-85, which was enacted on September 27, 2007. Section 801 of FDAAA amends Section 402 of the U.S. Public Health Service Act to expand ClinicalTrials.gov and create a clinical study results database . For more information on FDAAA 801, see the History, Policies, and Laws page on this site. Funder type Describes the organization that provides funding or support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting. Organizations listed as sponsors and collaborators for a study are considered the funders of the study. ClinicalTrials.gov refers to four types of funders: U.S. National Institutes of Health Other U.S. Federal agencies (for example, Food and Drug Administration, Centers for Disease Control and Prevention, or U.S. Department of Veterans Affairs) Industry (for example: pharmaceutical and device companies) All others (including individuals, universities, and community-based organizations) Gender-based eligibility A type of eligibility criteria that indicates whether eligibility to participate in a clinical study is based a person's self-representation of gender identity or gender (yes, no). Gender is distinct from sex . Group/cohort A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes. Human subjects protection review board A group of people who review, approve, and monitor the clinical study's protocol . Their role is to protect the rights and welfare of people participating in a study (referred to as human research subjects), such as reviewing the informed consent form . The group typically includes people with varying backgrounds, including a community member, to make sure that research activities conducted by an organization are completely and adequately reviewed. Also called an institutional review board, or IRB, or an ethics committee. For more information, see Participating in Studies on this site. Inclusion criteria A type of eligibility criteria . These are the reasons that a person is allowed to participate in a clinical study. Informed consent A process used by researchers to communicate to potential and enrolled participants the risks and potential benefits of participating in a clinical study. For more information, see Participating in Studies on this site. Informed consent form (ICF) The document used in the informed consent or process. Intervention model The general design of the strategy for assigning interventions to participants in a clinical study. Types of intervention models include: single group assignment , parallel assignment , cross-over assignment , and factorial assignment . Intervention/treatment A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise. Interventional study (clinical trial) A type of clinical study in which participants are assigned to groups that receive one or more intervention/treatment (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. The assignments are determined by the study's protocol . Participants may receive diagnostic, therapeutic, or other types of interventions. Investigator A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator . Last update posted The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date. Last update submitted The most recent date on which the study sponsor or investigator submitted changes to a study record to ClinicalTrials.gov. There is typically a delay of a few days between the last update submitted date and when the date changes are posted on ClinicalTrials.gov (the last update posted date). Last update submitted that met QC criteria The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria. Last verified The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown . Listed location countries Countries in which research facilities for a study are located. A country is listed only once, even if there is more than one facility in the country. The list includes all countries as of the last update submitted date; any country for which all facilities were removed from the study record are listed under removed location countries . Location terms In the search feature, the Location terms field is used to narrow a search by location-related terms other than Country, State, and City or distance. For example, you may enter a specific facility name (such as National Institutes of Health Clinical Center) or a part of a facility name (such as Veteran for studies listing Veterans Hospital or Veteran Affairs in the facility name). Note: Not all study records include this level of detail about locations. Masking A clinical trial design strategy in which one or more parties involved in the trial, such as the investigator or participants, do not know which participants have been assigned which interventions. Types of masking include: open label, single blind masking, and double-blind masking. NCT number A unique identification code given to each clinical study record registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier . No intervention arm An arm type in which a group of participants does not receive any intervention/treatment during the clinical trial. Observational study A type of clinical study in which participants are identified as belonging to study groups and are assessed for biomedical or health outcomes. Participants may receive diagnostic, therapeutic, or other types of interventions, but the investigator does not assign participants to a specific interventions/treatment . A patient registry is a type of observational study. Observational study model The general design of the strategy for identifying and following up with participants during an observational study . Types of observational study models include cohort, case-control, case-only, case-cross-over, ecologic or community studies, family-based, and other. Other adverse event An adverse event that is not a serious adverse event , meaning that it does not result in death, is not life-threatening, does not require inpatient hospitalization or extend a current hospital stay, does not result in an ongoing or significant incapacity or interfere substantially with normal life functions, and does not cause a congenital anomaly or birth defect; it also does not put the participant in danger and does not require medical or surgical intervention to prevent one of the results listed above. Other study IDs Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers. Other terms In the search feature, the Other terms field is used to narrow a search. For example, you may enter the name of a drug or the NCT number of a clinical study to limit the search to study records that contain these words. Outcome measure For clinical trials , a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies , a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure . Parallel assignment A type of intervention model describing a clinical trial in which two or more groups of participants receive different interventions. For example, a two-arm parallel assignment involves two groups of participants. One group receives drug A, and the other group receives drug B. So during the trial, participants in one group receive drug A "in parallel" to participants in the other group, who receive drug B. Participant flow A summary of the progress of participants through each stage of a clinical study, by study arm or group/cohort . This includes the number of participants who started, completed, and dropped out of the study. Patient registry A type of observational study that collects information about patients' medical conditions and/or treatments to better understand how a condition or treatment affects patients in the real world. Phase The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA) . The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0) , Phase 1 , Phase 2 , Phase 3 , and Phase 4 . Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions. Phase 1 A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to determine the drug's most frequent and serious adverse events and, often, how the drug is broken down and excreted by the body. These trials usually involve a small number of participants. Phase 2 A phase of research to describe clinical trials that gather preliminary data on whether a drug works in people who have a certain condition/disease (that is, the drug's effectiveness). For example, participants receiving the drug may be compared to similar participants receiving a different treatment, usually an inactive substance (called a placebo ) or a different drug. Safety continues to be evaluated, and short-term adverse events are studied. Phase 3 A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. These studies typically involve more participants. Phase 4 A phase of research to describe clinical trials occurring after FDA has approved a drug for marketing. They include postmarket requirement and commitment studies that are required of or agreed to by the study sponsor. These trials gather additional information about a drug's safety, efficacy, or optimal use. Phase Not Applicable Describes trials without FDA-defined phases , including trials of devices or behavioral interventions. Placebo An inactive substance or treatment that looks the same as, and is given in the same way as, an active drug or intervention/treatment being studied. Placebo comparator arm An arm type in which a group of participants receives a placebo during a clinical trial. Primary completion date The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure . Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "estimated" primary completion date is the date that the researchers think will be the primary completion date for the study. Primary outcome measure In a clinical study's protocol , the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment . Most clinical studies have one primary outcome measure, but some have more than one. Primary purpose The main reason for the clinical trial . The types of primary purpose are: treatment, prevention, diagnostic, supportive care, screening, health services research, basic science, and other. Principal investigator (PI) The person who is responsible for the scientific and technical direction of the entire clinical study. Protocol The written description of a clinical study. It includes the study's objectives, design, and methods. It may also include relevant scientific background and statistical information. Quality control (QC) review National Library of Medicine (NLM) staff perform a limited review of submitted study records for apparent errors, deficiencies, or inconsistencies. NLM staff identify potential major and advisory issues and provide comments directly to the study sponsor or investigator. Major issues identified in QC review must be addressed or corrected (see First submitted that met QC criteria and Results first submitted that met QC criteria ). Advisory issues are suggestions to help improve the clarity of the record. NLM staff do not verify the scientific validity or relevance of the submitted information. The study sponsor or investigator is responsible for ensuring that the studies follow all applicable laws and regulations. Randomized allocation A type of allocation strategy in which participants are assigned to the arms of a clinical trial by chance. Recruitment status Not yet recruiting: The study has not started recruiting participants. Recruiting: The study is currently recruiting participants. Enrolling by invitation: The study is selecting its participants from a population, or group of people, decided on by the researchers in advance. These studies are not open to everyone who meets the eligibility criteria but only to people in that particular population, who are specifically invited to participate. Active, not recruiting: The study is ongoing, and participants are receiving an intervention or being examined, but potential participants are not currently being recruited or enrolled. Suspended: The study has stopped early but may start again. Terminated: The study has stopped early and will not start again. Participants are no longer being examined or treated. Completed: The study has ended normally, and participants are no longer being examined or treated (that is, the last participant's last visit has occurred). Withdrawn: The study stopped early, before enrolling its first participant. Unknown: A study on ClinicalTrials.gov whose last known status was recruiting; not yet recruiting; or active, not recruiting but that has passed its completion date, and the status has not been last verified within the past 2 years. Registration The process of submitting and updating summary information about a clinical study and its protocol , from its beginning to end, to a structured, public Web-based study registry that is accessible to the public, such as ClinicalTrials.gov. Removed location countries Countries that appeared under listed location countries but were removed from the study record by the sponsor or investigator. Reporting group A grouping of participants in a clinical study that is used for summarizing the data collected during the study. This grouping may be the same as or different from a study arm or group. Responsible party The person responsible for submitting information about a clinical study to ClinicalTrials.gov and updating that information. Usually the study sponsor or investigator. Results database A structured online system, such as the ClinicalTrials.gov results database, that provides the public with access to registration and summary results information for completed or terminated clinical studies. A study with results available on ClinicalTrials.gov is described as having the results "posted." Note: The ClinicalTrials.gov results database became available in September 2008. Older studies are unlikely to have results available in the database. Results delayed Indicates that the sponsor or investigator submitted a certification or extension request . Results first posted The date on which summary results information was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay between the date the study sponsor or investigator first submits summary results information (the results first submitted date) and the results first posted date. Some results information may be available at an earlier date if Results First Posted with QC Comments . Results first posted with QC comments The date on which summary results information was first available on ClinicalTrials.gov with quality control review comments from the National Library of Medicine (NLM) identifying major issues that must be addressed by the sponsor or investigator. As of January 1, 2020, initial results submissions for applicable clinical trials (ACTs) that do not meet quality control review criteria will be publicly posted on ClinicalTrials.gov with brief standardized major comments. Accordingly, the Results First Posted with QC Comments date may be earlier than the Results First Posted date for an ACT with summary results information that is not consistent with NLM quality control review criteria. Results first submitted The date on which the study sponsor or investigator first submits a study record with summary results information. There is typically a delay between the results first submitted date and when summary results information becomes available on ClinicalTrials.gov (the results first posted date). Results first submitted that met QC criteria The date on which the study sponsor or investigator first submits a study record with summary results information that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit results information one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria. Results returned after quality control review The date on which the National Library of Medicine provided quality control (QC) review comments to the study sponsor or investigator. The sponsor or investigator must address major issues identified in the review comments. If there is a date listed for results returned after quality control review, but there is not a subsequent date listed for results submitted to ClinicalTrials.gov , this means that the submission is pending changes by the sponsor or investigator. Results submitted to ClinicalTrials.gov Indicates that the study sponsor or investigator has submitted summary results information for a clinical study to ClinicalTrials.gov but the quality control (QC) review process has not concluded. The results submitted date indicates when the study sponsor or investigator first submitted summary results information or submitted changes to summary results information. Submissions with changes are typically in response to QC review comments from the National Library of Medicine (NLM). If there is a date listed for results submitted to ClinicalTrials.gov, but there is not a subsequent date listed for results returned after quality control review , this means that the submission is pending review by NLM. Secondary outcome measure In a clinical study's protocol , a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure. Serious adverse event An adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above. Sex A type of eligibility criteria that indicates the sex of people who may participate in a clinical study (all, female, male). Sex is a person's classification as female or male based on biological distinctions. Sex is distinct from gender-based eligibility . Sham comparator arm An arm type in which a group of participants receives a procedure or device that appears to be the same as the actual procedure or device being studied but does not contain active processes or components. Single group assignment A type of intervention model describing a clinical trial in which all participants receive the same intervention/treatment. Sort studies by In Advanced Search, the Sort studies by option is used to change the order of studies listed on the Search Results page. You can sort by Relevance or Newest First: Relevance: Studies that best match your search terms appear higher in the search results list. This is the default display for all searches. Newest First: Studies with the most recent First posted dates appear higher in the search results list. Sponsor The organization or person who initiates the study and who has authority and control over the study. State In the search feature, the State field is used to find clinical studies with locations in a specific state within the United States. If you choose United States in the Country field, you can search for studies with locations in a specific state. Statistical analysis plan (SAP) The written description of the statistical considerations and methods for analyzing the data collected in the clinical study . Status Indicates the current recruitment status or the expanded access status . Study completion date The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures , secondary outcome measures , and adverse events (that is, the last participant's last visit). The "estimated" study completion date is the date that the researchers think will be the study completion date. Study design The investigative methods and strategies used in the clinical study. Study documents Refers to the type of documents that the study sponsor or principal investigator may add to their study record . These include a study protocol , statistical analysis plan , and informed consent form . Study IDs Identifiers that are assigned to a clinical study by the study's sponsor , funders, or others. They include unique identifiers from other trial study registries and National Institutes of Health grant numbers. Note: ClinicalTrials.gov assigns a unique identification code to each clinical study registered on ClinicalTrials.gov. Also called the NCT number , the format is "NCT" followed by an 8-digit number (for example, NCT00000419). Study record An entry on ClinicalTrials.gov that contains a summary of a clinical study's protocol information, including the recruitment status ; eligibility criteria; contact information; and, in some cases, summary results. Each study record is assigned a ClinicalTrials.gov identifier, or NCT number . Study registry A structured online system, such as ClinicalTrials.gov, that provides the public with access to summary information about ongoing and completed clinical studies. Study results A study record that includes the summary results posted in the ClinicalTrials.gov results database . Summary results information includes participant flow , baseline characteristics , outcome measures , and adverse events (including serious adverse events ). Study start date The actual date on which the first participant was enrolled in a clinical study. The "estimated" study start date is the date that the researchers think will be the study start date. Study type Describes the nature of a clinical study . Study types include interventional studies (also called clinical trials), observational studies (including patient registries ), and expanded access . Submitted date The date on which the study sponsor or investigator submitted a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. Title The official title of a protocol used to identify a clinical study or a short title written in language intended for the lay public. Title acronym The acronym or initials used to identify a clinical study (not all studies have one). For example, the title acronym for the Women's Health Initiative is "WHI." U.S. Agency for Healthcare Research and Quality (AHRQ) An agency within the U.S. Department of Health and Human Services. AHRQ's mission is to produce evidence to make health care safer, higher quality, more accessible, equitable, and affordable, and to work within the U.S. Department of Health and Human Services and with other partners to make sure that the evidence is understood and used. U.S. Food and Drug Administration (FDA) An agency within the U.S. Department of Health and Human Services. The FDA is responsible for protecting the public health by making sure that human and veterinary drugs, vaccines and other biological products, medical devices, the Nation's food supply, cosmetics, dietary supplements, and products that give off radiation are safe, effective, and secure. Unknown A type of recruitment status . It identifies a study on ClinicalTrials.gov whose last known status was recruiting; not yet recruiting; or active, not recruiting but that has passed its completion date, and the status has not been verified within the past 2 years. Studies with an unknown status are considered closed studies. Key Record Dates ClinicalTrials.gov Identifier: NCT03074942 Brief Title: Reslizumab in Patients With Severe Asthma Who Failed to Respond to Omalizumab First Submitted : February 28, 2017 First Submitted that Met QC Criteria : March 3, 2017 First Posted : March 9, 2017 Last Update Submitted that Met QC Criteria : May 10, 2018 Last Update Posted : May 16, 2018 To Top Copyright Privacy Accessibility Viewers and Players Freedom of Information Act USA.gov HHS Vulnerability Disclosure U.S. National Library of Medicine U.S. National Institutes of Health U.S. Department of Health and Human Services
https://clinicaltrials.gov/ct2/keydates/NCT03074942
Lactic acid bacteria and the human gastrointestinal tract | Request PDF Request PDF | Lactic acid bacteria and the human gastrointestinal tract | This review summarises the effects of lactic acid bacteria on lactose malabsorption, bacterial/viral or antibiotic associated diarrhoea, and... | Find, read and cite all the research you need on ResearchGate Article Literature Review Lactic acid bacteria and the human gastrointestinal tract June 1999 European Journal of Clinical Nutrition53(5):339-50 DOI: 10.1038/sj.ejcn.1600773 Source PubMed Authors: <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Hanne D Hove Rigshospitalet <here is a image f2f62089ad6ff61c-d19572ff1996375a> H Nørgaard H Nørgaard <here is a image c72b11f6db2ffb7c-b1a194a26fae90d4> Per Brøbech Rigshospitalet Abstract This review summarises the effects of lactic acid bacteria on lactose malabsorption, bacterial/viral or antibiotic associated diarrhoea, and describes the impact of lactic acid bacteria on cancer and the fermentative products in the colon. Eight studies (including 78 patients) demonstrated that lactase deficient subjects absorbed lactose in yogurt better than lactose in milk, while two studies (25 patients) did not support this. Two studies (22 patients) showed that unfermented acidophilus milk was absorbed better than milk, while six studies (68 patients) found no significant differences. Addition of lactose hydrolysing enzyme, lactase, to milk improved lactose malabsorption in seven studies (131 lactose malabsorbers), while one study (10 malabsorbers) demonstrated no improvement. Lactic acid bacteria alleviated travellers' diarrhoea in one study (94 individuals) while a study including 756 individuals was borderline statistically significant. One study (50 individuals) did not find an effect of lactic acid bacteria on travellers' diarrhoea. Six studies (404 infants) demonstrated a significant effect of lactic acid bacteria on infant diarrhoea, while one study (40 infants) did not. Lactic acid bacteria moderated antibiotic associated diarrhoea in three studies (66 individuals), while two studies (117 individuals) were insignificant. Lactase deficient subjects benefit from a better lactose absorption after ingestion of yoghurt compared with milk and from milk added lactase, whereas ingestion of unfermented acidophilus milk does not seem to improve lactose absorption. The majority of studies support that lactic acid bacteria alleviate bacterial/viral induced diarrhoea, especially in infants, while the effect on antibiotic associated diarrhoea is less clear. Experimental studies indicate an effect of lactic bacteria on human cell cancer lines, but clinical evidence is lacking. A 'stabilising' effect of lactic acid bacteria on the colonic flora has not been documented. ... Intestinal stem cells convert lactate into pyruvate and enhance oxidative metabolism, leading to reactive oxygen species (ROS)-induced intra-cellular signaling for differentiation [49]. Although, a limited number of gut microbes exists in small intestine, some small intestinal microbes, including Lactobacillus spp., play significant roles in the regulation of host metabolism and immunity [50] . In addition to host cells, commensal bacteria not only aid in carbohydrate digestion through the release of lactase, which hydrolyzes lactose to glucose, but also produce carbohydrate metabolites, resulting in the maintenance of gut homeostasis [50]. ... ... Although, a limited number of gut microbes exists in small intestine, some small intestinal microbes, including Lactobacillus spp., play significant roles in the regulation of host metabolism and immunity [50]. In addition to host cells, commensal bacteria not only aid in carbohydrate digestion through the release of lactase, which hydrolyzes lactose to glucose, but also produce carbohydrate metabolites, resulting in the maintenance of gut homeostasis [50] . In metagenomic and metatranscriptomic analyses with human ileostomy, the small intestine has been shown to be enriched with genes expressing Streptococcus spp., allowing phosphotransferase systems to take up monosaccharides and carry out carbohydrate metabolism, including glycolysis and pentose phosphate pathways [45], and consequently produce lactate ( Figure 1). ... ... A metabolite of linoleic acid (ω6) is arachidonic acid, which is further metabolized into leukotrienes, lipoxins, prostaglandins, and thromboxane-prostanoid. The major metabolites of α-linolenic acid (ω3) are eicosapentaenoic acids and docosapentaenoic acids, which serve as precursors to specialized pro-resolving mediators, such as resolvins, protectins, and maresins Although, a limited number of gut microbes exists in small intestine, some small intestinal microbes, including Lactobacillus spp., play significant roles in the regulation of host metabolism and immunity [50] . In addition to host cells, commensal bacteria not only aid in carbohydrate digestion through the release of lactase, which hydrolyzes lactose to glucose, but also produce carbohydrate metabolites, resulting in the maintenance of gut homeostasis [50]. ... Regulation of Gastrointestinal Immunity by Metabolites Article Full-text available Jan 2021 Bon-Hee Gu Myunghoo Kim <here is a image 573db427e268a648-24dead83d458bac5> Cheol-Heui Yun The gastrointestinal tract contains multiple types of immune cells that maintain the balance between tolerance and activation at the first line of host defense facing non-self antigens, including dietary antigens, commensal bacteria, and sometimes unexpected pathogens. The maintenance of homeostasis at the gastrointestinal tract requires stringent regulation of immune responses against various environmental conditions. Dietary components can be converted into gut metabolites with unique functional activities through host as well as microbial enzymatic activities. Accumulating evidence demonstrates that gastrointestinal metabolites have significant impacts on the regulation of intestinal immunity and are further integrated into the immune response of distal mucosal tissue. Metabolites, especially those derived from the microbiota, regulate immune cell functions in various ways, including the recognition and activation of cell surface receptors, the control of gene expression by epigenetic regulation, and the integration of cellular metabolism. These mucosal immune regulations are key to understanding the mechanisms underlying the development of gastrointestinal disorders. Here, we review recent advancements in our understanding of the role of gut metabolites in the regulation of gastrointestinal immunity, highlighting the cellular and molecular regulatory mechanisms by macronutrient-derived metabolites. ... Formula-fed infants show a greater diversity in their gut bacteria with a higher abundance of families from the Firmicutes phylum [7,8]. Lactate producers such as Bifidobacteriaceae, Lactobacillaceae, Enterococcaceae, and Streptococcaceae have been shown to protect infants against antibiotic-and enteropathogen-induced diarrhea [9] , inflammatory responses [10], and atopic dermatitis [11]. Bifidobacteria possess the fed in a 6 week intervention study involving 4-6 month old infants who were about to start consuming solid foods [31]. ... ... Microorganisms 2021, 9, 2089 3 of 17 galacto-and fructooligosaccharides were found to enhance gut bifidobacteria when fed in a 6 week intervention study involving 4-6 month old infants who were about to start consuming solid foods [31]. Inulin is another well-characterized prebiotic that has been shown to beneficially affect the gut microbiome of children [32,33] and is often used as a supplement in many food products formulated for children. ... Complementary Food Ingredients Alter Infant Gut Microbiome Composition and Metabolism In Vitro Article Full-text available Oct 2021 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Shanthi Parkar <here is a image 717be72b38541272-c62933e80fbbfd65> Douglas Ian Rosendale <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Halina Stoklosinski <here is a image cdb5dabcea3c2d8c-3281048648a8bd01> Pramod Gopal We examined the prebiotic potential of 32 food ingredients on the developing infant microbiome using an in vitro gastroileal digestion and colonic fermentation model. There were significant changes in the concentrations of short-chain fatty-acid metabolites, confirming the potential of the tested ingredients to stimulate bacterial metabolism. The 16S rRNA gene sequencing for a subset of the ingredients revealed significant increases in the relative abundances of the lactate- and acetate-producing Bifidobacteriaceae, Enterococcaceae, and Lactobacillaceae, and lactate- and acetate-utilizing Prevotellaceae, Lachnospiraceae, and Veillonellaceae. Selective changes in specific bacterial groups were observed. Infant whole-milk powder and an oat flour enhanced Bifidobacteriaceae and lactic acid bacteria. A New Zealand-origin spinach powder enhanced Prevotellaceae and Lachnospiraceae, while fruit and vegetable powders increased a mixed consortium of beneficial gut microbiota. All food ingredients demonstrated a consistent decrease in Clostridium perfringens, with this organism being increased in the carbohydrate-free water control. While further studies are required, this study demonstrates that the selected food ingredients can modulate the infant gut microbiome composition and metabolism in vitro. This approach provides an opportunity to design nutrient-rich complementary foods that fulfil infants’ growth needs and support the maturation of the infant gut microbiome. ... Although, limited numbers of gut microbes exist in the small intestine, some small intestinal microbes, including lactobacillus spp. play a significant role in regulation of host metabolism and immunity [46] . In addition to host cells, commensal bacteria not only help carbohydrate digestion by releasing lactase that hydrolyze lactose to glucose, but also produce carbohydrate metabolites resulting in the maintenance of gut homeostasis [46]. ... ... play a significant role in regulation of host metabolism and immunity [46]. In addition to host cells, commensal bacteria not only help carbohydrate digestion by releasing lactase that hydrolyze lactose to glucose, but also produce carbohydrate metabolites resulting in the maintenance of gut homeostasis [46] . In metagenomic and metatranscriptome analyses with human ileostomy, small intestine is enriched with Streptococcus sp. ... Regulation of Gastrointestinal Immunity by Metabolites Full-text available Dec 2020 Bon-Hee Gu Myunghoo Kim <here is a image 573db427e268a648-24dead83d458bac5> Cheol-Heui Yun The gastrointestinal tract contains multiple types of immune cells that maintain the balance between tolerance and activation at the first line of host defense facing non-self antigens, including dietary antigens, commensal bacteria, and sometimes unexpected pathogens. Maintaining homeostasis at the gastrointestinal tract requires stringent regulation of the immune responses against various environmental conditions. Diet can be converted into gut metabolites which have unique functional activities through host as well as microbial enzymatic activities. Accumulating evidences demonstrate that gastrointestinal metabolites have significant impacts on the regulation of intestinal immunity and further integrate immune response of distal mucosal tissue. Metabolites, especially derived from microbiota, regulate immune cell functions by various ways including recognition and activation of cell surface receptors, controlling of gene expression by epigenetic regulation and integration of cellular metabolism. These mucosal immune regulations are key to understand underlying mechanism for the development of gastrointestinal disorders. Here, we review the recent advancement of our understanding on the role of gut metabolites in the regulation of gastrointestinal immunity with highlighting the cellular and molecular regulatory mechanisms by macronutrients-derived metabolites. ... The inverse relationship between LP genotype and relative abundances of Bifidobacterium supports the notion that the mammalian lactase enzyme and bacterial b-galactosidase enzyme are in direct competition for lactose. Bifidobacteria are important lactose degraders (35, 36) and may have helped adult hosts extract energy from milk after domestication of dairy-producing animals and before selection on the LP alleles. After the rise of pastoralism, lactose-metabolizing bacteria likely had a positive effect on the fitness of hosts in the absence of LP alleles (29). ... ... After the rise of pastoralism, lactose-metabolizing bacteria likely had a positive effect on the fitness of hosts in the absence of LP alleles (29). Later, the beneficial host allele arose and replaced the microbiota function, becoming nearly fixed in some populations (23, 35) . The production of b-galactosidase by Bifidobacterium (or functionally redundant microbes) may also have relaxed the selection pressure on the LP allele by reducing the fitness differences between LCT genotypes. ... The role of the microbiota in human genetic adaptation Getting to the guts of local evolution The microbiota of mammals is a product of coevolution. However, humans exhibit a range of adaptive peculiarities that can be quite geographically specific. The human microbiota also displays a variety of community compositions and a range of overlapping and redundant metabolic characteristics that can alter host physiology. For example, lactase persistence is a genetic characteristic of European populations, but in populations lacking the lactase gene, milk sugar digestion is endowed by the microbiota instead. Suzuki and Ley review the evidence for the role that the microbiota plays in local adaptation to new and changing human circumstances. Science , this issue p. eaaz6827 ... Bifidobacterium: You can also find it in some dairy products. It may help ease the symptoms of irritable bowel syndrome [3, 4] . ... ... Probiotics are not all alike. For example, if a specific kind of Lactobacillus helps prevent an illness, that doesn't necessarily mean that another kind of Lactobacillus would have the same effect or that any of the Bifidobacterium probiotics would do the same thing [4] . ... Probiotics: How Do We Know ... На 7 добу після припинення введення консерванту значення цього показника статистично не відрізняється від визначеного в тварин у нормі. Із даних літератури відомо, що основними продуцентами оцтової кислоти у товстому кишечнику є бактерії родів Bifidobacterium, Lactobacillus, Actinomyces, Ruminococcus [9, 14]. Як з'ясовано раніше проведеними дослідженнями складу мікробіоти тов стого кишечника щурів за впливу 10 мг/кг ніпазолу, чисельність представників родів Bifido bacterium, Lactobacillus за цих умов зменшується [16]. ... ... 2, Г, Д). Основними продуцентами пропіо нової кислоти є бактерії родів Veillonella, Propionibacterium, Arachnia, Anaerovibrio; валеріанової, ізовалеріанової -Megasphaera, Clostridium; масляної -Acidaminococcus, Bacteroides, Clostridium, Eubacterium, Lachnospira, Butyrivibrio, Gemmiger, Coprococcus, Fusobacterium [9, 14]. Концентрації перелічених жирних кислот за введення ніпазолу змінюються прямо пропорційно із виявленими збільшеннями чисельності таких мікроорганізмів як Clostridium, Fusobacterium у складі мікробіоти порожнини кишечника щурів [16]. ... Short chain fatty acids pattern in rat intestine content under nipasol effect The qualitative and quantitative composition of the short chain fatty acids (SFA) (acetic, propionic, butyric, isovaleric, valeric and capric) in the colonic content of the rats, which were orally given preservative nipasol (10 mg/kg) has been studied. It was shown that the content of acetic acid was lower on the 7-th and 14-th days of the experiment in comparison with control group of animals. The amount of propionic and butyric acids in the colonic content was increased on the 7-th day, but on the 14-th days of the experiment it was decreased, however, this amount was higher, than in control group of rats. Concentrations of isovaleric and valeric acids on the 7-th and 14-th days of the experiment exceeded normal limits. After cessation of nipasol introduction on the 7-th day (21-th day of the experiment) the amount of fatty acids almost returned to baseline. Analysis of C2-C4-acids profile after nipasol introduction revealed a decrease in the concentration of acetic acid and an increase in the levels of butyric and propionic acids. Obtained results provide a possibility to suggest that the level of SFA in the colonic content is an important indicator of changes in gastrointestinal microbocenosis under the influence of different factors. ... Probiotics are the live supplement or organisms that can be consumed to improve the health benefits. These probiotics improve the immunity [22] . LABs are useful probiotics which has several health benefits for humans as well as animals. ... SCREENING AND CHARACTERIZATION OF BACTERIOCIN PRODUCING HETEROLACTIC STRAINS OF BACTERIA FROM NATIVE FOOD SOURCES The use of bacteriocinogenic lactic acid bacteria (LAB) isolated directly from foods for food bio preservation is a novel approach. LABs belong to wide group of Gram-positive, non-spore forming, cocci, rods are usually non motile and are capable to ferment carbohydrates forming lactic acid as a product which is also known as probiotic bacteria. They are generally regarded as safe (GRAS) by Food and Drug Administration (FDA) and qualified presumption of safety (QPS) that has been published by European Food Safety Authority (EFSA) for their use as a starter Cultures and probiotics. In the absence of antibiotics, organisms with stable hetero resistance can maintain their resistance, whereas those with unstable hetero resistance can revert again. Bacterial hetero resistance is caused by genetically unreliable amplification of Tandem genes or a physiological mechanism. To know more about the shelf life of Heterolactic strains that are isolated and tested for Bacteriocin (Nisin A) properties. The goal is to raise awareness about the spread of antagonistic property through the food chain and the proper use of food source across the board. ... The negative effects of increasing glucose molarity on BG01-4 TM growth were only observed outside the optimum pH range (pH 7-8) and indicates that BG01-4 TM growth intestinally may be greatly impacted at pH<7 l or >8 during the following 1-2 h after feeding, as post-meal consumption will result in an increase of luminal glucose [110]. The negative impact of rising glucose molarity on BG01-4 TM growth outside of the pH range 7-8 suggests that if BG01-4 TM is consumed at around the same time as a meal, growth of BG01-4 TM outside of the optimum pH range (7-8) will be greatly impeded by the high luminal glucose levels [93,116, 117] . Moreover, BG01-4 TM expressed the lowest growth rates at pH 5, with an increasing glucose molarity observed to further restrict growth (Fig. 2a). ... Attempts to limit sporulation in the probiotic strain Bacillus subtilis BG01-4TM through mutation accumulation and selection The use of bacterial spores in probiotics over viable loads of bacteria has many advantages, including the durability of spores, which allows spore-based probiotics to effectively traverse the various biochemical barriers present in the gastrointestinal tract. However, the majority of spore-based probiotics developed currently aim to treat adults, and there is a litany of differences between the adult and infant intestinal systems, including the immaturity and low microbial species diversity observed within the intestines of infants. These differences are only further exacerbated in premature infants with necrotizing enterocolitis (NEC) and indicates that what may be appropriate for an adult or even a healthy full-term infant may not be suited for an unhealthy premature infant. Complications from using spore-based probiotics for premature infants with NEC may involve the spores remaining dormant and adhering to the intestinal epithelia, the out-competing of commensal bacteria by spores, and most importantly the innate antibiotic resistance of spores. Also, the ability of Bacillus subtilis to produce spores under duress may result in less B. subtilis perishing within the intestines and releasing membrane branched-chain fatty acids. The isolate B. subtilis BG01-4 TM is a proprietary strain developed by Vernx Biotechnology through accumulating mutations within the BG01-4 TM genome in a serial batch culture. Strain BG01-4 TM was provided as a non-spore-forming B. subtilis , but a positive sporulation status for BG01-4 TM was confirmed through in vitro testing and suggested that selection for the sporulation defective genes could occur within an environment that would select against sporulation. The durability of key sporulation genes was ratified in this study, as the ability of BG01-4 TM to produce spores was not eliminated by the attempts to select against sporulation genes in BG01-4 TM by the epigenetic factors of high glucose and low pH. However, a variation in the genes in isolate BG01-4-8 involved in the regulation of sporulation is believed to have occurred during the mutation selection from the parent strain BG01-4 TM . An alteration in selected sporulation regulation genes is expected to have occurred from BG01-4 TM to BG01-4-8, with BG01-4-8 producing spores within 24 h, ~48 h quicker than BG01-4 TM . ... Only when the cell membrane permeability increases due to cell death or damage, LDH will leak out of the cell ( Korzeniewski & Callewaert, 1983;Patel & Markx, 2008). Therefore, the activity of extracellular LDH can be used as an index to measure the cytotoxicity of test substance (AFRC, 1989; Hove et al., 1999; Gusils et al., 1999). In this study, BS048 did not lead to significant changes in extracellular LDH activity, indicating that the plasma membrane of the HD11 cells was not damaged and that the use of BS048 was safe and displayed no visible cytotoxicity. ... Effect of Bacillus Subtilis on Immune Function of Hd11 Chicken Macrophages Poultry is frequently contaminated by Salmonella, a pathogen leading to human health concern worldwide. This study aimed to evaluate the effect of Bacillus subtilis (BS)strain 048 (BS048) on the activation, phagocytosis, sterilization, cytokine secretion, and nitrogen oxide synthesis of HD11 chicken macrophages subjected to Salmonella enteritidis challenge, using lipopolysaccharide treatment as a negative control. The results showed: (1) BS048 had no significant effect on extracellular lactate dehydrogenase activity (p>0.05), while lipopolysaccharide treatment significantly increased extracellular lactate dehydrogenase activity (p<0.05);(2)BS048 significantly upregulated the expression levels of pro-inflammatory cytokines (interleukin (IL)-1â and IL-6), anti-inflammatory cytokines(IL-10 and transforming growth factor-â1), and anti-viral cytokine, interferon-â (p<0.01); (3)BS048 significantly upregulated the mRNA expression level of the inducible nitric oxide synthase and its activity as well as extracellular nitrogen oxide level (p<0.01). In conclusion, BS048 could improve anti-inflammatory and immune functions of HD11 chicken macrophages, without cytotoxic effects on these cells. Keywords: Bacillus subtilis ; chicken macrophage; immune function; inducible nitric oxide synthase; Salmonella ... LABs are also found on host organisms mostly associated with digestive and excretory tissues (Pessione, 2012). Diet and health status determines the number and diversity of LABs found on host organisms (Hove et al., 1999) . Fermentation is a centuries-old process that is widely used in the production of various foods by human societies all over the world (Mishra et al., 2017). ... Molecular evolution and population genetics of glutamate decarboxylase acid resistance pathway in lactic acid bacteria <here is a image 798789deda7c3021-998663b3e5646123> Efe Sezgin <here is a image cafd5d34f18cc248-d5da1a4d24bad117> Burcu Tekin Glutamate decarboxylase (GAD) pathway (GDP) is a major acid resistance mechanism enabling microorganisms’ survival in low pH environments. We aimed to study the molecular evolution and population genetics of GDP in Lactic Acid Bacteria (LAB) to understand evolutionary processes shaping adaptation to acidic environments comparing species where the GDP genes are organized in an operon structure (Levilactobacillus brevis) versus lack of an operon structure (Lactiplantibacillus plantarum). Within species molecular population genetic analyses of GDP genes in L. brevis and L. plantarum sampled from diverse fermented food and other environments showed abundant synonymous and non-synonymous nucleotide diversity, mostly driven by low frequency changes, distributed throughout the coding regions for all genes in both species. GAD genes showed higher level of replacement polymorphism compared to transporter genes (gadC and YjeM) for both species, and GAD genes that are outside of an operon structure showed even higher level of replacement polymorphism. Population genetic tests suggest negative selection against replacement changes in all genes. Molecular structure and amino acid characteristics analyses showed that in none of the GDP genes replacement changes alter 3D structure or charge distribution supporting negative selection against non-conservative amino acid changes. Phylogenetic and between species divergence analyses suggested adaptive protein evolution on GDP genes comparing phylogenetically distant species, but conservative evolution comparing closely related species. GDP genes within an operon structure showed slower molecular evolution and higher conservation. All GAD and transporter genes showed high codon usage bias in examined LAB species suggesting high expression and utilization of acid resistance genes. Substantial discordances between species, GAD, and transporter gene tree topologies were observed suggesting molecular evolution of GDP genes do not follow speciation events. Distribution of operon structure on the species tree suggested multiple independent gain or loss of operon structure in LABs. In conclusion, GDP genes in LABs exhibit a dynamic molecular evolutionary history shaped by gene loss, gene transfer, negative and positive selection to maintain its active role in acid resistance mechanism, and enable organisms to thrive in acidic environments. ... Colon has the highest gut microflora concentration, about 10 12-14 ml -1 . It is observed that the malabsorbed lactose is fermented by the lactic acid bacteria present in the ilea and colon followed by the production of SCFA and gases (Hove et al., 1999) . In this process, the malabsorbed lactose is broken down by the lactase enzyme present in the lactic acid bacteria (Swallow, 2003) into glucose and galactose which is then absorbed (Fig. 2) in the small intestine. ... Lactose Intolerance: A Review for facts and fictions Milk is assumed to be a complete food, due to its high nutritional status. Regular consumption of milk reduces the problems of nutrition deficiency. Milk contains sugar, mainly lactose in higher amount and lactose, with other ingredients of milk, also contributes to maintain the energy level of body. But, in some cases a problem arises due to the intake of lactose mainly owing to the deficiency of ?-galactosidase (Lactase) enzyme. Deficiency of lactase enzyme in human body, results in inefficiency of body for degrading the lactose into its smaller constituents. Un-degraded/ undigested lactose consumed by the bacteria and converts it into several acids and gases, which results in arise of several types of intestinal disorders. In this article, main focus is given on the lactose intolerance, its types, and remedies. ... Therefore, lactose intolerance is the inability to digest lactose caused by the lower expression of lactase. Bifidobacteria are known to have the ability to digest lactose, 407 indicating that they compensate for reduced lactase activity in the host. Another well-replicated locus in microbiome composition is ABO. ... Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies CHEM REV The human microbiome is composed of a collection of dynamic microbial communities that inhabit various anatomical locations in the body. Accordingly, the coevolution of the microbiome with the host has resulted in these communities playing a profound role in promoting human health. Consequently, perturbations in the human microbiome can cause or exacerbate several diseases. In this Review, we present our current understanding of the relationship between human health and disease development, focusing on the microbiomes found across the digestive, respiratory, urinary, and reproductive systems as well as the skin. We further discuss various strategies by which the composition and function of the human microbiome can be modulated to exert a therapeutic effect on the host. Finally, we examine technologies such as multiomics approaches and cellular reprogramming of microbes that can enable significant advancements in microbiome research and engineering. ... The only two exceptions thus far have been the LCT and ABO loci, which are the basis for the lactase persistence trait and ABO blood group system, respectively. Across studies, the lactase nonpersistence genotypes at LCT were associated with higher intestinal levels of bifidobacteria, which are able to break down lactose [47] , and one study further provided evidence that the lead variant at LCT was causally associated with multiple dietary and metabolic phenotypes, including obesity and type 2 diabetes (T2D) [46]. By comparison, taxa associated with ABO were not the same across the three datasets in which this locus was identified [40,41,43]. ... Role of gut microbe-derived metabolites in cardiometabolic diseases: Systems based approach <here is a image 276c04039d8cda80-cff72f61302ea1d5> Yang Cao <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ruben Aquino-Martinez <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Evan Hutchison <here is a image 57934d78770515e0-d9e416b75d45113b> Federico E Rey Background: The gut microbiome influences host physiology and cardiometabolic diseases by interacting directly with intestinal cells or by producing molecules that enter the host circulation. Given the large number of microbial species present in the gut and the numerous factors that influence gut bacterial composition, it has been challenging to understand the underlying biological mechanisms that modulate risk of cardiometabolic disease. Scope of the review: Here we discuss a systems-based approach that involves simultaneously examining individuals in populations for gut microbiome composition, molecular traits using "omics" technologies, such as circulating metabolites quantified by mass spectrometry, and clinical traits. We summarize findings from landmark studies using this approach and discuss future applications. Major conclusions: Population-based integrative approaches have identified a large number of microbe-derived or microbe-modified metabolites that are associated with cardiometabolic traits. The knowledge gained from these studies provide new opportunities for understanding the mechanisms involved in gut microbiome-host interactions and may have potentially important implications for developing novel therapeutic approaches. ... These alleles have been under selective pressure due to animal domestication and consumption of milk after weaning, which has driven an increase in the frequency of lactase-persistence alleles 22 . Interestingly, the lactase non-persistence genotype is associated with higher gut abundance of bifidobacteria, which have the ability to degrade lactose 23 , and this association is dependent on milk consumption 19 . ... Challenges and future directions for studying effects of host genetics on the gut microbiome <here is a image 4b12496cf3f9d3d3-e381426ebd80a18f> Serena Sanna <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Alexander M Kurilshikov Adriaan van der Graaf Alexandra Zhernakova The human gut microbiome is a complex ecosystem that is involved in its host’s metabolism, immunity and health. Although interindividual variations in gut microbial composition are mainly driven by environmental factors, some gut microorganisms are heritable and thus can be influenced by host genetics. In the past 5 years, 12 microbial genome-wide association studies (mbGWAS) with >1,000 participants have been published, yet only a few genetic loci have been consistently confirmed across multiple studies. Here we discuss the state of the art for mbGWAS, focusing on current challenges such as the heterogeneity of microbiome measurements and power issues, and we elaborate on potential future directions for genetic analysis of the microbiome. This Perspective discusses the analytical issues concerning heterogeneity and power encountered in microbial genome-wide association studies and highlights potential future directions for genetic analysis of the microbiome. ... In vertebrates, there are more microbial cells within the gastrointestinal (GI) tract than total cells within the body-proper (Hove et al., 1999) . The microorganisms most commonly observed are bacteria and yeast. ... Assessment of Probiotics Addition in Poultry Production: A Review <here is a image 5526c895339906c6-44937826d0c564dc> V. K. Vidyarthi Poultry is one of the fastest growing segments of agriculture and animal husbandry sector. Feed is one of the largest items of expenditure in poultry production and it alone accounts to 70% of total poultry production. The constant increase in the cost of poultry feed ingredients and compounded feed is making less profit to poultry farmers. To minimize the cost of feeding, several feed additives (as growth promoter) like synthetic hormone and antibiotics have been extensively used for enhancing poultry production in recent years. To avoid the health hazards of antimicrobials to human as well as poultry, in recent years, a probiotics as feed additives for better and safe production in poultry was employed. Probiotic are "mono or defined mixed culture of live microorganisms which when applied to animals, beneficially affect the host by improving the properties of the indigenous micro biota". Various species are used in probiotic preparations i.e. Lactobacillus bulgaricus, L. acidophillus, L. casei, L. helveticus, L. salvarius, L. plantarum, L. faecalis, Streptococcus thermophillus, Enterococcus faecium, Enterobactris faecalis, Bifidobacteria species, Saccharomyces cerevisiae and Toulopsis sphaerica. However, Lactobacilli and Streptococci are most commonly used treatments of bacteria in the production of probiotics. In this review, the effect of probiotics on growth rate, body weight gain, feed intake, feed conversion efficiency, survivability of probiotics in GIT, mineral metabolism, cholesterol metabolism, dose rate of probiotics, carcass characteristics and sensory quality of chicken meat was discussed. ... Previous studies have shown that lactose digestion and the symptoms of lactose intolerance can be improved using probiotics that modify gut pH, express β-gal, and exert positive effects on intestinal activity and overall colonic microbiota (de Vrese et al., 2001;Kopp-Hoolihan, 2001;Roberfroid, 2000a;Rolfe, 2000;Awaisheh, 2011). It has been demonstrated that lactic acid bacteria ferment lactose to produce lactate, hydrogen, methane, carbon dioxide and short-chain fatty acids (Hove et al., 1999; Ibrahim and Gyawali, 2013;Awaisheh et al., 2016). During fermentation, lactase present in lactic acid bacteria cleaves unabsorbed lactose to glucose and galactose and is then absorbed into the body. ... Fermented foods and probiotics: An approach to lactose intolerance <here is a image 28000d7e05052c97-6a4d79347e81fb24> Salam Ibrahim <here is a image e1b91ff109313206-561b8c34550a0f40> Rabin Gyawali <here is a image 7a1c8be74514419f-560fa6ca6676206e> Saddam S Awaisheh <here is a image 239be2a2ff693ef7-e552bb595358db4c> Albert Ivanov Krastanov The aim of this review was to present various topics related to lactose intolerance with special attention given to the role of fermented foods and probiotics in alleviating gastrointestinal symptoms. Lactose intolerance is a common digestive problem in which the human body is unable to digest lactose, known as milk sugar. Lactose intolerance can either be hereditary or a consequence of intestinal diseases. Recent work has demonstrated that fermented dairy products and probiotics can modify the metabolic activities of colonic microbiota and may alleviate the symptoms of lactose intolerance. We suggest that, lactose free dairy products could be recommended as alternatives for the alleviation of lactose intolerance and for the promotion of human health and wellness. ... The major source of endogenous production of L-lactate is skeletal muscles and intestines but also occurs as a result of hypoperfusion or bacterial fermentation in tissues (Hove et al., 1999) . Increased lactate concentration has a reliable prognostic value of determining the severity of endotoxemia and monitoring mortality in ruminants due to inflammatory conditions (Coghe et al., 2000). ... Assessing the Correlation between Metabolic Parameters and Risk Factors in Transition Cows <here is a image 72890388be0bd6e1-26e0f43b18f9779e> Songül Erdoğan <here is a image d4e63c40c839652e-c80fc92f0c1c9146> Deniz Alic Ural Our objective in this study was to evaluate the correlation between metabolic parameters included beta-hydroxybutyric acid, nonesterified fatty acids, magnesium, calcium and lactate as being continuous variables and some factors (age, lactation number, lactation stage, body condition score and feeding type) in transition cows. For this purpose, clinically healthy appearance Holstein cows (n=53) from different farms were assessed for analyzing at transition period. Blood samples were collected and measuring of parameters were done with cow-side devices weekly during the study. As a result, it has been seen that beta-hydroxybutyric acid, nonesterified fatty acids and calcium were affected by lactation stage with statistically significant (p<0.01). Moreover, effect of body condition score on nonesterified fatty acids was found to statistically higher in 2 ... Regarding food safety, lactic acid bacteria are considered safe and free from restrictions (Oliveira et al, 2015). They are identified as active in the fight against pathogenic bacteria (Ganzle, 1999;Duarte, 2013 (Hove et al, 1999) . Therefore, although there are procedures designed to combat the presence of lactic acid bacteria in alcoholic fermentation must (Ventura, 2007), their application would not appear to increase the safety of the product or its sensory quality. ... Advance in the characterization of alambic cachaça: ethyl lactate Article Full-text available Amazile Biagioni Maia Lorena Simão Marinho <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> David Lee Nelson In the current methodology for the analysis of cachaça, the limit of 200 mg/100 mL ethanol established in Brazilian legislation for the totality of esters present in cachaça is measured exclusively by the dosage of ethyl acetate, the principal ester in cachaça produced on an industrial scale (continuous distillation), whose asepsis procedures applied to the broth are focused on combating the activity of bacteria. However, it is known that producers of alembic cachaça (batch distillation) ferment the fresh juice, which naturally incorporates lactic bacteria from the environment. A survey of the analysis records of 300 samples, corresponding to 110 cachaça brands, was performed. The analyses were performed using the recommended laboratory methods and gas chromatography. The extensive occurrence of ethyl lactate was found in varying proportions, but with the same order of magnitude as ethyl acetate. It was concluded that, in addition to the olfactory peculiarities related to the particular contents in each brand, the simple presence of ethyl lactate (above a level that can be referred to as traces) permits one to infer whether the cachaça originates from alembic or from industrial production. ... The stomach is a harsh environment, its pH is usually around 3.0 and the bile salt concentration is 0.03% to 0.3% [ 18]. Lactobacillus can colonize and live in the stomach which depend mainly on its acid and bile salt resistant [ 19, 20], acid and bile salt resistance are also important indicators for screening Lactobacillus as probiotics [ 21]. Although some studies have shown that Lactobacillus can inhibit the H. pylori growth and reduce in ammation, but they did not study the acid and bile salt resistant of Lactobacillus, which will be affected in further development of Lactobacillus as probiotics to play against H. pylori in human gastric. ... Resistant gastric environment of Lactobacillus crispatus from stomach inhibits Helicobacter pylori colonization and attenuates gastric inflammation Preprint Full-text available Ning Wang <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Fangyuan Mao Wei-Wei Huang Gang Guo Background Recent studies have shown that gastric-derived Lactobacillus can inhibit the colonization of H. pylori and attenuate gastric inflammation in conventional animals, but the resistant of Lactobacillus to gastric environment is still unknown. Here, we aimed to screen the candidate Lactobacillus that could adapt to the harsh gastric environment and inhibit the colonization of H. pylori. Results In vitro, the growth rate of seven Lactobacillus strains in different pH and bile salt concentration were tested, the size of inhibition zone and adhesion rate of H. pylori when Lactobacillus exist were measured. In gnotobiotic mice models, we examined the amount of colonization of L. crispatus and H. pylori by qRT-PCR and evaluated the inflammation in the gastric tissue by the content of MPO and H&E stain. In vitro experiments showed L. crispatus had a better growth rate than other six Lactobacilluses in pH 2.5 to 4.5; under the 0.2% bile salt concentration, other bacteria did not grow except for L. crispatus; L. crispatus yielded 24.2 mm of mean inhibitory zone diameters; the adhesion rate of H. pylori only reached 41.3% in H. pylori-L. crispatus group(HLG). In vivo, the amount of colonization of H. pylori in HLG is fifteen times less than that in H. pylori group (HG) (p ... They provide several benefits for humans. Among them are better resistance to infections, stimulation of the immune system and better absorption of minerals and lactose (Hove et al., 1999; Caire et al., 2000). The probiotic activity of some strains with the ability to colonize the intestinal epithelium strengthening to stabilize the intestinal microflora, especially after antibiotic treatment, has been well described in previous researches (Piard and Desmazeaud, 1992;Gasson, 1993;Gardiner et al., 2002;Kearney et al., 2008). ... Influence of Spirulina platensis powder on the starter culture viability in probiotic yoghurt containing spinach during cold storage Article Full-text available <here is a image 6eee5c773e21b9d3-b0031cdef747749c> Vajiheh Fadaei F Mohamadi-Alasti K Khosravi-Darani Functional foods are among the topical issues in nutrition, nutritional foods, medicine and health fields. Considering the unique properties of Spirulina platensis, it can be used to enrich yogurt. The main purpose of this research was to monitor the influence of the powdered Cyanobacterium Spirulina platensis added to the yoghurt containing Lactobacillus acidophilus and spinach on the survival of yogurt starter culture during the refrigerated storage. The cell viability of yoghurt starter cultures (Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus) and Lactobacillus acidophilus under refrigeration conditions in yoghurts prepared with (0.3, 0.5 and 0.8 (w/w) %) the addition of Spirulina powder and with (10 and 13 (w/w) %) spinach was investigated. The yoghurts were prepared under hygienic laboratory conditions. The samples of yoghurts were stored at 4 °C and investigated on days 1, 7, 14 and 21. Viable counts of the lactic acid bacteria were above 6 log cfumL-1 of all "Spirulina powder" added at the end of the storage period. The results showed the positive effect of S. platensis powder on the survival of the lactic acid bacteria during the storage of probiotic yoghurt containing spinach (P≤0.01). It was determined that Spirulina powder added to yoghurt is a good medium for lactic acid bacteria during the 21 days of the refrigerated storage. According to final results, the probiotic yoghurt sample containing 0.5 % (w/w) Spirulina platensis and 10 %(w/w) spinach was selected as the preference treatment. ... When these mechanisms alter, the number of commensal bacteria may decrease in favor of pathogenic microorganisms. Therefore intestinal diseases may initiate and progress (Hove et al. 1999; Ojetti et al. 2009;Pessione 2012). When the number of enteric pathogens in the gastrointestinal tract (GIS) increases to a certain level above microbiota, they may penetrate and cause an infection (Sekirov et al. 2010). ... Adhesion mechanisms of lactic acid bacteria: conventional and novel approaches for testing Article Full-text available WORLD J MICROB BIOT <here is a image 6cd9758bc7cb605b-3e0be5331cc4d854> Duygu Alp Hakan Kuleaşan Adhesion ability is a primary criterion for the selection of probiotic microorganisms. Lactic acid bacteria contribute the majority of microorganisms with probiotic properties. They have several important mechanisms for intestinal epithelial cell adhesion. In order to adhere to the intestinal cells, they generally use various structures such as flagella, pili, S layer proteins, lipoteichoic acid, exopolysaccharides and mucus binding proteins. Various in vitro experiments were designed or study models were developed to reveal the mechanisms they utilize for binding to the intestinal cells, yet, the mechanisms for their adhesion are not fully explained. The major disadvantage of conventional models is the lack of layers forming the intestinal mucosa. Besides, these models omit the presence of natural microbiota, digestive conditions and the presence of a food matrix. Because of the disadvantages of existing models, natural tissues or novel applications like 3D organ cultures, which are better able to mimic in vivo conditions, are preferred. ... and Bifidobacterium spp. Scientific evidences for benefits from probiotics for human involves alleviations of the symptoms of lactose intolerance [2] and reduction of the duration of acute infectious gastroenteritidis in children [3]. Some other benefits include improving of the condition of the intestinal tract (traveler's and antibiotic-associated diarrhea), a decreasing prevalence of vaginal infections, an increasing immune function and a decrease of the cholesterol and lipid levels [1,4,5]. ... Microbiological evaluation of 10 commercial probiotic products available in Poland Article Full-text available <here is a image 2414240248d9d57e-3e16ae1b4d166cb3> Izabela Korona-Glowniak <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Radoslaw Siwiec Iwona Łuszczewska-Sierakowska Anna Malm The aim of this study was to analyze the quality of 10 commonly available commercial probiotic products used in Poland. These items were tested for the total viable bacterial count, and for identifying the isolated strains. This was performed using the Polymerase Chain Reaction method. The results showed that five of the tested products had not the applicable number of viable bacteria declared by manufacturer. Moreover, not all declared probiotic strains were found in three of the tested products during analyses. It is clear that a regular control of probiotic products needs be introduced that can guarantee its beneficial properties. ... In contrast, probiotic bacteria, such as strains of the lactic acid bacteria (LAB), like Lactobacillus spp., Streptococcus spp., Enterococcus spp. or Pediococcus spp., and of bifidobacteria, are recognized for their beneficial effects on the human intestinal microbiota and overall health for a long time [17] [18] [19][20]. Moreover, recent studies give strongly evidence on their strain-and disease-dependent probiotic efficacy [21]. ... Culture Dependent and Independent Analysis of Potential Probiotic Bacterial Genera and Species Present in the Phyllosphere of Raw Eaten Produce Article Full-text available <here is a image acb959bb3a65ac0c-3f8fd6349c4eaeeb> Sascha Patz <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Katja Witzel <here is a image 765b82877f9edb5c-9481cf1d8a942b17> Ann-Christin Scherwinski <here is a image 571723b0e2fb2064-4178bce11c828007> Silke Ruppel The plant phyllosphere is colonized by a complex ecosystem of microorganisms. Leaves of raw eaten vegetables and herbs are habitats for bacteria important not only to the host plant, but also to human health when ingested via meals. The aim of the current study was to determine the presence of putative probiotic bacteria in the phyllosphere of raw eaten produce. Quantification of bifidobacteria showed that leaves of Lepidium sativum L., Cichorium endivia L., and Thymus vulgaris L. harbor between 103 and 106 DNA copies per gram fresh weight. Total cultivable bacteria in the phyllosphere of those three plant species ranged from 105 to 108 CFU per gram fresh weight. Specific enrichment of probiotic lactic acid bacteria from C. endivia, T. vulgaris, Trigonella foenum-graecum L., Coriandrum sativum L., and Petroselinum crispum L. led to the isolation of 155 bacterial strains, which were identified as Pediococcus pentosaceus, Enterococcus faecium, and Bacillus species, based on their intact protein pattern. A comprehensive community analysis of the L. sativum leaves by PhyloChip hybridization revealed the presence of genera Bifidobacterium, Lactobacillus, and Streptococcus. Our results demonstrate that the phyllosphere of raw eaten produce has to be considered as a substantial source of probiotic bacteria and point to the development of vegetables and herbs with added probiotic value. ... Sun et al., (2005) suggested that Lactobacillus PG has anti-tumor effects. Lactic acid bacteria can produce bacteriocins (antimicrobially active substances) and they can also alleviate bacterial/viral diarrhea, especially in infants (Hove et al., 1999) . Some strains and species of LAB have antioxidant activity and can decrease the risk of ROS accumulation. ... Transcriptomic responses of Caco-2 cells to Lactobacillus rhamnosus GG and Lactobacillus plantarum J26 against oxidative stress <here is a image 7db2cbc7b54390af-5a4f30c7708ddc03> Yichao Hou Xuesong Li Xinyu Liu <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Yujun Jiang Oxidative stress is the basic reason for aging and age-related diseases. In this study, we investigated the protective effect of 2 strains of lactic acid bacteria (LAB), Lactobacillus rhamnosus GG and L. plantarum J26, against oxidative stress in Caco-2 cells, and gave an overview of the mechanisms of lactic acid bacteria antioxidant activity using digital gene expression profiling. The 2 LAB strains provided significant protection against hydrogen peroxide (H2O2)-induced reduction in superoxide dismutase activity and increase in glutathione peroxidase activity in Caco-2 cells. However, inactive bacteria had little effect on alleviating oxidation stress in Caco-2 cells. Eight genes related to oxidative stress-FOSB, TNF, PPP1R15A, NUAK2, ATF3, TNFAIP3, EGR2, and FBN2-were significantly upregulated in H2O2-induced Caco-2 cells compared with untreated Caco-2 cells. After incubation of the H2O2-induced Caco-2 cells with L. rhamnosus GG and L. plantarum J26, 5 genes (TNF, EGR2, NUAK2, FBN2, and TNFAIP3) and 2 genes (NUAK2 and FBN2) were downregulated, respectively. In addition, the Kyoto Encyclopedia of Genes and Genomes indicated that some signaling pathways associated with inflammation, immune response, and apoptosis, such as Janus kinase/signal transducers and activators of transcription (Jak-STAT), mitogen-activated protein kinase (MAPK), nuclear factor-κB, and tumor necrosis factor, were all negatively modulated by the 2 strains, especially L. rhamnosus GG. In this paper, we reveal the mechanism of LAB in relieving oxidative stress and provide a theoretical basis for the rapid screening and evaluation of new LAB resources. ... Yoghurt is a food that is rich in protein, unsaturated fatty acids, calcium, phosphorus, magnesium, zinc and Vitamin B (Gilliland, 1989;McKinley, 2005). Because of its probiotic characteristics (Lourens-Hattingh and Viljoen, 2001), yoghurt boosts the immune system and provides resistance to infections in addition to regulating intestinal flora (Hove et al., 1999; Plessas et al., 2012). About the rate of consumption, yoghurt ranks third among milk products, following cheese and butter. ... The effect of fruits to the characteristics of fruit yogurt <here is a image 1aafdc58a569aced-327b2ebcaf099423> Ufuk Kamber <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Sezen Harmankaya This study investigated the effects of yoghurt on the chemical (titratable acidity and pH), microbiological (L. delbrueckii subsp. bulgaricus, S. thermophilus, mould and yeast counts) and sensory properties of yoghurt that was prepared with fruit (strawberry, apricot, banana, peach) (at a ratio of 20%) during the incubation (checked at 0, 90 and 210 minutes) and storage (checked at 1, 3 and 7 days) periods. When compared to plain yoghurt, the values of the traits analysed during this study were found to be significantly different about both the different fruits and the time intervals. The average acidity counts at the end of the storage period were found to be highest in strawberry yoghurt (0.665 LA), while apricot yoghurt was found to have the lowest pH rate (-0.390 pH). The average count of L. delbrueckii subsp. bulgaricus at the end of the storage period was found to be highest in strawberry yoghurt (2.983 log 10 cfu/ml), while peach yoghurt was found to have the lowest rate of L. delbrueckii subsp. bulgaricus (1.568 log 10 cfu/ml). The highest rate of S. thermophilus was found in peach yoghurt (2.648 log 10 cfu/ml), while the lowest rate was in banana yoghurt (1.301 log 10 cfu/ml). The highest yeast count was found in plain yoghurt (3.264 log 10 cfu/ml) and the lowest mould count was in banana yoghurt (2.246 log 10 cfu/ml). Sensory analysis of the fruit yoghurts revealed that, while the type of fruit had no statistically significant effect on the sensory characteristics, the most popular were banana and strawberry yoghurts. The results confirmed that the varieties of added fruit affected the pH and acidity rates of the yoghurt and influenced the development of microflora, so we concluded that these factors could consequently affect the product’s shelf life. ... Assimilation of cholesterol 79,80 Lactose intolerance [79][80][81] Control viral, bacterial and antibiotic associated diarrheal diseases 79,80, [83] [84][85] Inflammatory bowel disease 79 Allergies and atopic dermatitis 86,87 Colonic carcinogens 88,89 Control of pathogenic bacteria 91,92 Stimulation of the immune system on the gut mucosal surface 93 In recent years, the genomes of several probiotic species have been sequenced, thus paving the way to the application of 'omics' technologies to the investigation of probiotic activities. 60 Moreover, although recombinant probiotics have been constructed, the industrial application of genetically engineered bacteria is still hampered by legal issues and by a rather negative general public opinion in the food sector. ... Lactic acid bacteria: their applications in foods ... Live lactic acid bacteria intake through dairy products have myriad beneficial effects on the gastrointestinal tract of human beings ranging from correction of lactose malabsorption, alleviation of viral and drug induced diarrhea, post-operative pouchitis, irritable bowel syndrome, inflammatory bowel syndrome, anti-neoplastic effects on human cell line, maintenance of normal insulin level in blood and also helpful to enhance the absorption of fatty acids through intestine. LAB produce these beneficial effects by restoration of normal intestinal flora, elimination of intestinal pathogens, reinforcement of intestinal barrier capacity to foreign antigens, stimulation of nonspecific immunity such as phagocytosis, stimulation of humoral immunity and production of anti-inflammatory products [4, 5,6]. Beneficial microorganisms also have positive effect on lactose intolerance and malabsorption. ... Isolation and Molecular Identification of Lactic Acid Bacteria (Lab) from Nile Tilapia (Oreochromis niloticus) as Potential Pathogen Antagonist <here is a image 113da0aef55020bc-5e7d2b5fa0d85950> Jacqueline Viste Bagunu <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Evelyn Totaan <here is a image 5bd5803786d63520-9ef9a84a504a217b> Christian Pangilinan Five lactic acid bacterial isolates from the intestinal tract of Nile Tilapia (Oreochromis niloticus) were tested for their antagonistic activity against common human pathogens. Only three were identified using 16S rRNA gene sequencing as Pediococcus pentosaceus (isolates TI-8 and TI-11) and Enterococcus avium (TI-17) showing 99% homology. Among the isolates, TI-8 and T1-11 (P. pentosaceus) viable cell cultures were found to have the highest inhibitory activity against Escherichia coli ATCC 25922, surpassing that of the positive control, Tetracyline. Though showing significant inhibition also to Pseudomonas aeruginosa BIOTECH 1335, Staphylococcus aureus BIOTECH 1582, Salmonella enteriditis BIOTECH 1963, Salmonella typhimurium BIOTECH 1826, and Vibrio cholerae BIOTECH 1967, T1-17 (Enterococcus avium) is not effective against S. aureus BIOTECH 1582. On the other hand, T1-8 and T1-11 (P. pentosaceus) cell free supernatant cultures exhibited inhibitory activity against P. aeruginosa BIOTECH 1335, S. aureus BIOTECH 1582, S. enteriditis BIOTECH 1963, S. typhimurium BIOTECH 1826, and V. cholerae BIOTECH 1967.-76 The LAB isolate T1-17 (E. avium) exhibited an inhibitory activity against S. enteriditis BIOTECH and V. cholerae BIOTECH 1967. T1-11 (P. pentosaceus) was susceptible to Tetracycline and Amoxicillin; T1-8 (P. pentosaceus) was susceptible to Amoxicillin and Cephalexin; and T1-17 (E. avium) was susceptible to Amoxicillin. ... Lactic acid bacteria (LAB) are a heterogeneous group of Grampositive, facultative anaerobic microorganisms commonly found on flowers and in the intestinal tracts of humans as well as many different animals (Endo et al. 2011;Hammes and Hertel 2006;He et al. 2011; Hove et al. 1999; Neveling et al. 2012). These bacteria, as intestinal microflora, play a crucial role in nutrient assimilation, in modulation of the immune response, and in the mitigation and prevention of divers intestinal disorders (Asama et al. 2015;Evans and Lopez 2004;Gilliland 1990;Jack et al. 1995;Servin 2004). ... The molecular and phenotypic characterization of fructophilic lactic acid bacteria isolated from the guts of Apis mellifera L. derived from a Polish apiary <here is a image 90392635828b66c0-b3973a41eb1148fa> Aneta A Ptaszyńska <here is a image eff6eda72badcbed-9ed1816f5cda1267> Wanda Grazyna Małek This paper describes taxonomic position, phylogeny, and phenotypic properties of 14 lactic acid bacteria (LAB) originating from an Apis mellifera guts. Based on the 16S rDNA and recA gene sequence analyses, 12 lactic acid bacteria were assigned to Lactobacillus kunkeei and two others were classified as Fructobacillus fructosus. Biochemically, all isolated lactic acid bacteria showed typical fructophilic features and under anaerobic conditions grew well on fructose, but poorly on glucose. Fast growth of bacteria on glucose was noted in the presence of oxygen or fructose as external electron acceptors. The residents of honeybee guts were classified as heterofermentative lactic acid bacteria. From glucose, they produced almost equimolar amounts of lactic acid, acetic acid, and trace amounts of ethanol. Furthermore, they inhibited the growth of the major honeybee pathogen, Paenibacillus larvae, meaning that the LAB studied may have the health-conferring properties of probiotics. ... Além disso, mesmo em concentrações menores, o ácido butírico produzido pode rancificar a gordura do pescado, causando odores e sabores desagradáveis (KOCHHAR, 1996). HOVE et al. (1999) citam que as BAL estão amplamente distribuídas na natureza e habitam o trato digestivo, respiratório superior e urogenital inferior dos animais. Algumas, como Lactobacillus sp., são ubíquos no ser humano, encontradas na boca, intestino e outros sítios, e, caso presentes no alimento, indicam contaminação por má manipulação (TAVARES e SERAFINI, 2003). ... QUALIDADE MICROBIOLÓGICA DE FILÉS DE TRUTA ARCO-ÍRIS NO RJ, BRASIL Carla Cristina Chaves da SILVA <here is a image 3a190223a5b7d95b-bcab9e5d287cd987> André Luiz Medeiros de Souza Carolina Riscado POMBO <here is a image 59191caa32942bf0-3ec9190e7dbc40b2> Eliana de Fátima Marques de Mesquita ... For example, anaerobic bacteria from the families Bacteriodaceae and Clostridiaceae are found in high abundance in the large intestine [27], whilst in the small intestine, fast-growing facultative anaerobes such as Lactobacillaceae and Enterobacteriaceae are dominant families of the microbial community, which "tolerate the combined effects of bile acids and antimicrobials while still effectively competing with both the host and other bacteria for the simple carbohydrates that are available in this region of the gastrointestinal tract" [27]. Studies of orally administered lactic acid bacteria have demonstrated that the lactic acid bacterial counts in the small intestine increase after ingestion [28] [29] [30][31]. Evidence indicates that particular Lactobacillus probiotic strains can strengthen and preserve the intestinal barrier in an in vitro model of necrotising enterocolitis [32], increase the expression of genes involved in TJ formation [33], and increase barrier integrity of intestinal epithelial cell (IEC) monolayers as measured by trans epithelial electrical resistance (TEER) [34][35][36]. ... Metabolism of Caprine Milk Carbohydrates by Probiotic Bacteria and Caco-2:HT29–MTX Epithelial Co-Cultures and Their Impact on Intestinal Barrier Integrity <here is a image e98348b929f4bd9d-dcdabcb7fda69ea4> Adrian L Cookson <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Warren Mcnabb The development and maturation of the neonatal intestine is generally influenced by diet and commensal bacteria, the composition of which, in turn, can be influenced by the diet. Colonisation of the neonatal intestine by probiotic Lactobacillus strains can strengthen, preserve, and improve barrier integrity, and adherence of probiotics to the intestinal epithelium can be influenced by the available carbon sources. The goal of the present study was to examine the role of probiotic lactobacilli strains alone or together with a carbohydrate fraction (CF) from caprine milk on barrier integrity of a co-culture model of the small intestinal epithelium. Barrier integrity (as measured by trans epithelial electrical resistance (TEER)), was enhanced by three bacteria/CF combinations (Lactobacillus rhamnosus HN001, L. plantarum 299v, and L. casei Shirota) to a greater extent than CF or bacteria alone. Levels of occludin mRNA were increased for all treatments compared to untreated co-cultures, and L. plantarum 299v in combination with CF had increased mRNA levels of MUC4, MUC2 and MUC5AC mucins and MUC4 protein abundance. These results indicate that three out of the four probiotic bacteria tested, in combination with CF, were able to elicit a greater increase in barrier integrity of a co-culture model of the small intestinal epithelium compared to that for either component alone. This study provides additional insight into the individual or combined roles of microbe–diet interactions in the small intestine and their beneficial contribution to the intestinal barrier. ... 15,26 Additionally, the two isolated strains produced only L-lactic acid and not D-lactic acid, which is a feature of the Bifidobacterium genus. 27 Both isolates were therefore considered as presumptive Bifidobacterium spp. Molecular biological methods were then used to provide more definitive evidence that these two isolated strains were Bifidobacterium spp. ... Screening and selection of Bifidobacterium strains isolated from human feces capable of utilizing resistant starch: Bifidobacterium utilizing resistant starch Hyun-Joong Kim Sang Ick Shin Sang-Jun Lee <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Chang Joo Lee ... Lactic acid-producing (LAP) bacteria produce lactic acid and is used in a variety of dairy products to improve nutritional and rheological properties of the products (Mayo, vanSinderen, & Ventura, 2008). Moreover, LAP bacteria improve host digestion and intestinal lining (Hove, Norgaard, & Mortensen, 1999; Vigsnaes et al., 2013). Therefore, to understand the responses of LAP bacteria toward polysaccharide treatments, most of the LAP bacteria were subset and comparatively analyzed. ... Mushroom polysaccharides from Ganoderma lucidum and Poria cocos reveal prebiotic functions Ganoderma lucidum and Poria cocos are the medicinal mushrooms that have been used as traditional Chinese medicines and consumed as functional foods. We hypothesized that these mushroom polysaccharides could contribute to health benefits, in part, by modulating gut microbiota (GM). In this study, mushroom poly-saccharides derived from fruiting bodies and mycelia were administrated daily (750 mg/kg) to 6 weeks-old C57BL/6J mice for 15 days. Then, mice GM was evaluated using ERIC-PCR and 16S amplicon sequencing. A total of 2.59 million high-quality reads (> 200 bp) were processed and evaluated for GM profiling. Polysaccharides reduced OTUs diversity and significantly (p < .01) remodeled GM compositions. Bacteria that have been reported for anti-obesity, SCFA-producer, polysaccharides/xylan degradation, and lactic acid production were significantly (p < .05) abundant in mice treated with polysaccharides. We conclude that these polysaccharides act as prebiotics to modulate GM composition thereby potentially contribute to the health promotion effects of G. lucidum and P. cocos. ... Lactic acid-producing (LAP) bacteria produce lactic acid and is used in a variety of dairy products to improve nutritional and rheological properties of the products (Mayo, vanSinderen, & Ventura, 2008). Moreover, LAP bacteria improve host digestion and intestinal lining (Hove, Norgaard, & Mortensen, 1999; Vigsnaes et al., 2013). Therefore, to understand the responses of LAP bacteria toward polysaccharide treatments, most of the LAP bacteria were subset and comparatively analyzed. ... Mushroom polysaccharides from Ganoderma lucidum and Poria cocos reveal prebiotic functions <here is a image 6689bece41dc71cc-cb9ae3f09fce069e> Imran Khan <here is a image 5c9d61f93f5e4d36-1cce076d86d4b4a6> Guoxin Huang <here is a image a6fced5552b5b7a0-45c7c4df81cabf0e> Xiaoang Li <here is a image f59204ed42a91ac0-b5e0ee6196f0ac88> W.L.Wendy Hsiao ... Conserving as much as possible genes in larger genomes of some Lactobacillus species increases the flexibility of the whole species to resist various environmental conditions which may, in turn, be helpful to occupy varied ecological niches (for example, vegetables, dairy products, and the gastrointestinal tract (GIT) of various kinds of animals [86] [87][88]. ... Probiotic characters of Bifidobacterium and Lactobacillus are a result of the ongoing gene acquisition and genome minimization evolutionary trends <here is a image 9dddb3580ee5d133-3653ae4cbba72002> Hossein Nahrevanian <here is a image e2dbcd69cf93a202-5d021809f55a1531> Mohammad Pourshafie Bifidobacterium and Lactobacillus are the main probiotic genera. Collectively, these two genera harbor over 200 species among which are many strains have been introduced as probiotics. These health-promoting microbes confer health benefits upon the host and so used in food productions and as supplements. Considering the economic importance of probiotics, the biochemistry, genomics, phylogeny and physiology of such genera have been exhaustively studied. According to the genomic data, the probiotic capabilities are strain specific which may be a result of the niche-specialization of the genomes of these bacteria to certain ecological niches like gastrointestinal tract of a diverse range of animals. These microbes have a wide distribution but the culture-based studies and either genomics data suggest selective affinity of some Lactobacillus and either Bifidobacterium species to certain ecological niches. An ongoing genome degradation, which is thought to be a result of passage through an evolutionary bottleneck, is the major trend in the evolution of lactobacilli. Further, evolutionary events resulted into two categories of lactobacilli: habitat generalists and habitat specialists. In place, the main trend in the evolution of bifidobacteria tend to be the gene acquisition. However, probiotic features are the results of a co-evolutionary relationship between these bacteria and their hosts and the aforementioned evolutionary tends have driven the evolution of these probiotic genera. ... As lactase activity decreases, the lactose moiety remains intact and then reaches the large intestine, where it is metabolized by gut microbes. This fermentation process produces hydrogen, methane, carbon dioxide and lactate [352] , molecules which have the potential to cause bloating, abdominal cramps, nausea and symptoms typical of lactose intolerance. This lactose-lactase system is suggested to act as a biological timer, controlling birth spacing in human and eventual weaning. ... Human Milk and Allergic Diseases: An Unsolved Puzzle <here is a image 6b52556f8111fc7e-d07da4b8e35d59c2> Daniel Munblit <here is a image ba5cc320db9211ab-66bff7e3f984b983> Alba Boix Amorós There is conflicting evidence on the protective role of breastfeeding in relation to the development of allergic sensitisation and allergic disease. Studies vary in methodology and definition of outcomes, which lead to considerable heterogeneity. Human milk composition varies both within and between individuals, which may partially explain conflicting data. It is known that human milk composition is very complex and contains variable levels of immune active molecules, oligosaccharides, metabolites, vitamins and other nutrients and microbial content. Existing evidence suggests that modulation of human breast milk composition has potential for preventing allergic diseases in early life. In this review, we discuss associations between breastfeeding/human milk composition and allergy development. ... LAB are useful probiotics. Their beneficial effects were revealed by a Russian Scientist E. Metchnikoff (1845-1919) who proposed that extended longevity of people of Balkan could be attributed to their practice of ingesting fermented milk products [30] . ... The Influence of Asparagus on the Growth of Probiotic Bacteria in Orange Juice Functional properties of natural food sources create alternative to develop new food product. The consumption of foods and beverages containing probiotic microorganisms is a growing, global consumer trend. The comparative evaluation of orange juice inoculated with Lactobacillus species with known probiotic properties was performed. The prebiotics used in orange juice is raw asparagus root powder. After that measure the growth of bacteria after one day. To measure the growth of probiotic bacteria in orange juice at first measure the absorbance of the orange juice. Next Pour plate was done to observe the growth of probiotic bacteria. To observe the sustainability of probiotics in orange juice these test were done after two or three day’s interval. When bacterial colony grows on petri dish biochemical test was conducted and got positive result. Which mean that asparagus influence the growth of probiotic bacteria. This study suggests that asparagus extract exert a positive effect on growth of lactic acid bacteria in orange juice. ... (Fuller, 1991;Kim and Gilliland, 1983;McFarland et al., 1995; Hove et al., 1999; Nguyen et al., 2007). (Berrada et al., 1991;Bouhnik et al., 1992;Marteau et al., 1993;Cross et al., 2002;De Moreno de LeBlanc et al., 2008). ... The Development and Characterization of a pH Dependent Matrix Tablet Containing Probiotics ... Lactase expression is tightly regulated and is progressively turned off in most children around 2-3 years of age ( Figure 1). Decreased lactase activity leads to the passage of lactose to the large intestine, where it is metabolized by microbes, thereby releasing hydrogen, methane, carbon dioxide, and lactate [19] . These fermentation products cause bloating, abdominal cramps, and nausea, which are the typical symptoms of lactose intolerance. ... Breastfed at Tiffany's The importance of breast milk for the growing infant is undisputed; breastfeeding decreases infantile mortality by tenfold and decreases the incidence of infectious diseases. Despite its recognized benefits, the structural richness of breast milk has also impeded the characterization of the multiple effects of milk components on infant physiology. However, the important roles of some components of breast milk are beginning to be dissected. For instance, molecules such as immunoglobulin A (IgA) and milk oligosaccharides protect from gastrointestinal infections and influence the development of the gut microbiota. Deciphering the complex composition of breast milk brings to light multifaceted contributions that combine to make breast milk the ultimate personalized medicine. 3L, three-Lactobacilli on recovering of microbiome and immune-damage by cyclophosphamide chemotherapy —A pilot experiment in rats— Jan 2023 Shousong Yue Zhenzhong Zhang Fei Bian <here is a image 69fd43c07bfde98b-9a09ca8e8f08da32> Jean-François Jeff Picimbon Purpose We examined the impact of using a probiotic containing three different Lactobacilli (3L) on the gut microbiome of rats following cyclophosphamide (CTX) treatment. CTX corresponded to chemotherapy which is used for human cancer treatment and known to have adversive effects on the immune system. Methods We conducted our experiment with ten rats in five different experimental groups which included control, CTX treated, and then low, medium, and high probiotic treatment with CTX treatment. Of these ten rats in each group, we sequenced the stool of three of them using both ITS and 16S sequencing. We then went on to examine the taxonomic composition of these samples to determine whether probiotic treatment helped the rat’s microbiome return to similar structure as the control rats. Results We used Illumina MiSeq sequencing to generate sequencing data from microbial genomic DNA libraries, which is useful for testing the effects of 3L on bacteria and fungi. Microbiome analysis, phylogenetic and classification reports, and community data have all backed up the experiments and findings that 3L had a significant positive impact on the microbiome. Furthermore, the effect on specific metabolic pathways aids in deriving the study’s conclusion (use of 3L in chemotherapy) to the mode of action, mechanistically by correcting microbiota composition and enhancing specific gut metabolic functions. Conclusions Through experimental results using an in vivo model, we suggested the role of novel natural probiotics 3L, 3 Lactobacilli in the establishment of a strong and sustainable beneficial healthy gut flora, after CTX chemotherapy. We suggested some new adjuvants to chemotherapy as drugs + lactobacillus treament using the rat CTX model (immunosuppression caused by cyclophosphamide). Furthermore, in numerous studies that reported the use of probiotics involving Lactobacillus in post-chemo or post-surgical procedures, we proposed a new probiotic formulation (L. acidophilus + L. casei + L. plantarum) to be further studied and explored in the prevention of health condition loss by alteration of the general immune system. 3L, three-Lactobacilli on recovering of microbiome and immune-damage by cyclophosphamide chemotherapy —A pilot experiment— Dec 2022 Shousong Yue Zhenzhong Zhang Fei Bian <here is a image 69fd43c07bfde98b-9a09ca8e8f08da32> Jean-François Jeff Picimbon Purpose We examined the impact of using a probiotic containing three different Lactobacilli(3L) on the gut microbiome of rats following cyclophosphamide (CTX) treatment. CTX corresponded to chemotherapy which is used for human cancer treatment and known to have adversive effects on the immune system. Methods We conducted our experiment with ten rats in five different experimental groups which included control, CTX treated, and then low, medium, and high probiotic treatment with CTX treatment. Of these ten rats in each group, we sequenced the stool of three of them using both ITS and 16S sequencing. We then went on to examine the taxonomic composition of these samples to determine whether probiotic treatment helped the rat’s microbiome return to similar structure as the control rats. Results We used Illumina MiSeq sequencing to generate sequencing data from microbial genomic DNA libraries, which is useful for testing the effects of 3L on bacteria and fungi. Microbiome analysis, phylogenetic and classification reports, and community data have all backed up the experiments and findings that 3L had a significant positive impact on the microbiome. Furthermore, the effect on specific metabolic pathways aids in deriving the study’s conclusion (use of 3L in chemotherapy) to the mode of action, mechanistically by correcting microbiota composition and enhancing specific gut metabolic functions. Conclusions Through experimental results using an in vivo model, we suggested the role of novel natural probiotics 3L, 3 Lactobacilli in the establishment of a strong and sustainable beneficial healthy gut flora, after CTX chemotherapy. We suggested some new adjuvants to chemotherapy as drugs + lactobacillus treament using the rat CTX model (immunosuppression caused by cyclophosphamide). Furthermore, in numerous studies that reported the use of probiotics involving Lactobacillusin post-chemo or post-surgical procedures, we proposed a new probiotic formulation (L. acidophilus + L. casei + L. plantarum) to be further studied and explored in the prevention of health condition loss by alteration of the general immune system. 3L, three-Lactobacilli on recovering of microbiome and immune-damage by cyclophosphamide chemotherapy Sep 2022 Shousong Yue Zhenzhong Zhang Fei Bian <here is a image 69fd43c07bfde98b-9a09ca8e8f08da32> Jean-François Jeff Picimbon Background We examined the impact of using a probiotic containing three different Lactobacilli (3L) on the gut microbiome of rats following cyclophosphamide (CTX) treatment. CTX corresponded to chemotherapy which is used for human cancer treatment and known to have adversive effects on the immune system. Methods We conducted our experiment with ten rats in five different experimental groups which included control, CTX treated, and then low, medium, and high probiotic treatment with CTX treatment. Of these ten rats in each group, we sequenced the stool of three of them using both ITS and 16S sequencing. We then went on to examine the taxonomic composition of these samples to determine whether probiotic treatment helped the rat’s microbiome return to similar structure as the control rats. Results We used Illumina MiSeq sequencing to generate sequencing data from microbial genomic DNA libraries, which is useful for testing the effects of 3L on bacteria and fungi. Microbiome analysis, phylogenetic and classification reports, and community data have all backed up the experiments and findings that 3L had a significant positive impact on the microbiome. Furthermore, the effect on specific metabolic pathways aids in deriving the study’s conclusion (use of 3L in chemotherapy) to the mode of action, mechanistically by correcting microbiota composition and enhancing specific gut metabolic functions. Conclusions Through experimental results using an in vivo model, we suggested the role of novel natural probiotics 3L, 3 Lactobacilli in the establishment of a strong and sustainable beneficial healthy gut flora, after CTX chemotherapy. We suggested some new adjuvants to chemotherapy as drugs + lactobacillus treament using the rat CTX model (immunosuppression caused by cyclophosphamide). Furthermore, in numerous studies that reported the use of probiotics involving Lactobacillus in post-chemo or post-surgical procedures, we proposed a new probiotic formulation (L. acidophilus + L. casei + L. plantarum) to be further studied and explored in the prevention of health condition loss by alteration of the general immune system. Role of probiotics and prebiotics in digestion, metabolism, and immunity Chapter Jan 2022 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Shilia Jacob <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Tejaswini Baral <here is a image edaffeb1d644b6e2-a2e6fbea955475b8> Sonal Sekhar Mahadev Rao Probiotics are microbes that help maintain and stabilize the intestinal flora, resist pathogenic colonization in the gastrointestinal tract, modulate the immune system, improve vitamin synthesis, absorption of mineral salts, and enhance the production of short-chain fatty acids, bacteriocin, and other antimicrobial substances. Prebiotic substances are nondigestible oligosaccharides that influence the intestinal flora by improving the microbial flora's saccharolytic activity. The development of the microbial flora starts at birth and gets altered with varying physiological changes that occur with aging. Multiple studies have shown that probiotics and prebiotics help manage several disease conditions, including infectious and inflammatory conditions. Their roles in metabolism have also been well explored. This chapter briefly discusses the role of probiotics and prebiotics in digestion, metabolism, and immunity. Relationship between diarrhea and intestinal lactase activity Article Jun 2021 Yi Wu Zhou-Jin Tan Lactase is one of the most important functional enzymes in the intestine, and it is closely related to diarrhea. Traditional Chinese medicine (TCM) has unique advantages in the treatment of diarrhea, but its curative effect mechanism on diarrhea is still unclear. In this paper, we discuss the relationship between diarrhea caused by different factors and intestinal lactase activity, and the relationship between diarrhea treatment by TCM and intestinal lactase activity. The activity of lactase in the intestinal tract can be increased by TCM, because TCM is helpful to repair the intestinal mucosa and regulate intestinal microbiota. TCM may improve the activity of intestinal lactase by regulating bacterial gene expression of lactase, and its specific mechanism is worthy of further study. A report on serine proteases and their regulation. Recent Trends in Pharmaceutical Sciences. JPS Scientific Publications, India. Eds. P. Saranraj, Vasavi Dathar & K. Kolanjinathan. ISBN: 978-81-943168-5-5. <here is a image e50fdea57eddd6ff-e3deda4ceeac46d5> Pushpanjali Pendyala <here is a image f24c8342b51093ae-22a4cf157eb53fea> Vasavi Dathar Proteolysis, the mechanism of protein degradation required for various cellular processes is achieved by proteases. Proteases are the enzymes that cleave specific substrates in a closely regulated manner during proteolysis. They are involved in every aspect of cellular life and form 2% of the genome in most of the organisms. Based on their catalytic mechanisms proteases are classified into five major groups named serine, cysteine, aspartyl, threonine and metallo- proteases (Barrett et al., 2003). Mis-regulation of proteases may result in severe pathophysiological conditions such as ulcer, tumor formation, vascular remodeling, atherosclerosis etc. Among different classes of proteases, serine proteases form the major portion of protease family. Serine proteases are endoproteases and catalyze bond hydrolysis in a polypeptide chain. They display active catalytic triad of aspartine, histidine and serine residues which is characteristic to these proteases. Digestion of human milk fat in healthy infants Aug 2020 NUTR RES <here is a image d92b4d0d652f619e-a66fdf2398dea8e7> Xuan He <here is a image 7d87c870e5cd3067-7885f2e6b2bd1fde> Shannon McClorry <here is a image 5f15e234cfba2acd-8ce6cf6f59ef889f> Olle Hernell <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Carolyn Slupsky Lipid digestion is critical for infant development, and yet the interconnection between lipid digestion and the microbiota is largely under studied. This review focuses on digestion of the human milk fat globule and summarizes current understanding of the mechanisms underlying this process in infants. We first discuss the partial hydrolysis of milk fat in the stomach, which leads to rearrangement of lipid droplets, creating a lipid-water interface necessary for duodenal lipolysis. In the first few months of life, secretion of pancreatic triglyceride lipase (PTL), phospholipase A2, and bile salts is immature. The dominant lipases aiding fat digestion in the newborn small intestine are therefore pancreatic lipase-related protein 2 (PLRP2) and bile salt-stimulated lipase (BSSL) from both the exocrine pancreas and milk. We summarize the interaction between ionic fatty acids and cations to form insoluble fatty acid soaps, and how it is influenced by various factors including cation availability, pH, bile salt concentration, as well as saturation and chain-length of fatty acids. We further argue that the formation of the soap complex does not contribute to lipid bioavailability. Next, the possible roles that the gut microbiota play in lipid digestion and absorption are discussed. Finally, we provide a perspective on how the manufacturing process of infant formula and dairy products may alter the physical properties and structure of lipid droplets, thereby altering the rate of lipolysis. Multi-omic profiling reveals associations between the gut mucosal microbiome, the metabolome, and host DNA methylation associated gene expression in patients with colorectal cancer BMC MICROBIOL Qing Wang <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Jianzhong Ye <here is a image 7fcb1d4479edb5b9-63c2c99ddd257993> Daiqiong Fang Lanjuan Li Background: The human gut microbiome plays a critical role in the carcinogenesis of colorectal cancer (CRC). However, a comprehensive analysis of the interaction between the host and microbiome is still lacking. Results: We found correlations between the change in abundance of microbial taxa, butyrate-related colonic metabolites, and methylation-associated host gene expression in colonic tumour mucosa tissues compared with the adjacent normal mucosa tissues. The increase of genus Fusobacterium abundance was correlated with a decrease in the level of 4-hydroxybutyric acid (4-HB) and expression of immune-related peptidase inhibitor 16 (PI16), Fc Receptor Like A (FCRLA) and Lymphocyte Specific Protein 1 (LSP1). The decrease in the abundance of another potentially 4-HB-associated genus, Prevotella 2, was also found to be correlated with the down-regulated expression of metallothionein 1 M (MT1M). Additionally, the increase of glutamic acid-related family Halomonadaceae was correlated with the decreased expression of reelin (RELN). The decreased abundance of genus Paeniclostridium and genus Enterococcus were correlated with increased lactic acid level, and were also linked to the expression change of Phospholipase C Beta 1 (PLCB1) and Immunoglobulin Superfamily Member 9 (IGSF9) respectively. Interestingly, 4-HB, glutamic acid and lactic acid are all butyrate precursors, which may modify gene expression by epigenetic regulation such as DNA methylation. Conclusions: Our study identified associations between previously reported CRC-related microbial taxa, butyrate-related metabolites and DNA methylation-associated gene expression in tumour and normal colonic mucosa tissues from CRC patients, which uncovered a possible mechanism of the role of microbiome in the carcinogenesis of CRC. In addition, these findings offer insight into potential new biomarkers, therapeutic and/or prevention strategies for CRC. Pro-/Anti-Inflammatory Food Supplements: Probiotics and Prebiotics Jan 2020 <here is a image a944e132716244b2-5a65e956dcbfbd4a> Huseyin Eseceli Probiotics are living microorganisms, meaning “for life” and consist of two parts, “pro” and “biota,” and prebiotics are indigestible carbohydrates that increase the number and activities of colon bacteria and the effectiveness of probiotics. Probiotic consumption has been reported to have many positive effects, such as increasing immune response, balancing the colony, and increasing endogenous defense capacity of cells. The aim of prebiotics is to grow probiotic bacteria, thus improving the gastrointestinal and immune systems. Recent studies have shown that probiotics may have an impact on gastrointestinal system diseases. It has been shown to stimulate the proliferation of beneficial microorganisms in prebiotics and assist in the probiotic effect. The most commonly used probiotics and prebiotics are lactic acid bacteria that are types of Lactobacillus and Bifidobacterium. Prebiotics are naturally present in nutrients. Probiotics and prebiotics are used to prevent many diseases. Microbioma do Leite Humano, in Dinâmica da composição do leite humano e suas implicações clínicas. ILSI Brasil 2019 May 2019 <here is a image bbbba8e3ffec8e73-22b5dedcf7577d56> Carla R Taddei <here is a image ff804623df987eb3-7f40ada16c28c868> Rubens Feferbaum Nutrient Considerations in Lactose Intolerance Chapter Dec 2017 <here is a image 9e5661e241040052-875bb97d04dde2de> Steve Hertzler <here is a image f0e968943b6b011f-e115bf25254c09f6> Dennis A Savaiano Abby Dilk Fabrizis L. Suarez This chapter reviews the genetics and pathophysiology of lactose maldigestion, attempts to correct common misconceptions concerning the frequency and severity of lactose intolerance symptoms, and provides dietary strategies to minimize symptoms of intolerance. Lactic Acid Fermented Products as Vehicles for Probiotics Chapter Jan 2003 José Luis Parada M E Sambucetti <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Angela Zuleta María Esther Río For thousands of years microbial cultures have been used to ferment foods and prepare different kind of products. Unstable primary foodstuffs such milk, meat and vegetables can be conserved for relatively long periods of time (Table 1), maintaining their nutritious and caloric value by the use of lactic acid fermentation. Several traditional soured milks such as kefir, koumis, leben and others were used as foods and often therapeutically, before the existence of the actual knowledge on probiotics. The origins of cultured dairy products can be traced in the Bíble and the sacred books of Hinduism. Metchnikoff at the beginning of the XX century proposed the beneficial effects of the lactic acid bacteria (LAB) on health and longevity. The Oral Administration of Lactic Acid Bacteria Increase the Mucosal Intestinal Immunity in Response to Enteropathogens May 1990 Gabriela Perdigón <here is a image 3791122425b412c3-e10d999c6de00404> Susana Alvarez <here is a image a7f230a9864e6948-39e46760b92e9ab2> María Elena Fatima Nader-Macías A. Pesce de Ruiz Holgado The present studies were designed to investigate the effect of orally administered Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus delbrueckii spp., bulgaricus, and Streptococcus salivarius ssp. thermophilus on local mucosal immunity in response to enteropathogens. Normal mice were protected against Salmonella typhimurium infection by previous feeding with L. casei and S. salivarius spp. thermophilus, while L. acidophilus and L. delbrueckii spp. bulgaricus were not effective. The protective effect of L. casei against S. typhimurium was associated mainly to IgA production in intestinal secretions. We observed significant differences in the intestinal fluid anti-Salmonella agglutinin titers between the Salmonella-challenged control group (without lactobacilli feeding) and mice pretreated with L. casei. The level of immunoglobulins from intestinal fluid of mice fed previously with lactic acid bacteria was measured by radial immunodiffusion assay showing in all cases an increase in the immunoglobulin concentrations. By Immunoelectrophoresis methods, we observed the presence of two lines of immunoprecipitation. When we used monospecific serum, we detected the presence of IgG and IgA. Elisa tests showed high levels of IgA to S. typhimurium in intestinal secretions of mice pretreated with L. casei, while L. acidophilus and L. delbrueckii spp. bulgaricus groups showed values at slightly higher levels than the controls. The levels of IgG to S. typhimurium were similar to controls in all cases. We did not observe antibodies against the pathogen in intestinal fluid from mice fed with S. salivarius spp. thermophilus. However, we detected anti-Streptococcus antibodies. These results show that only L. casei increases the IgA production secreted to the intestinal lumen, providing adequate defenses at mucosal surfaces, and suggest that this microorganism could be used as oral adjuvant especially to prevent enteric infections. Antitumor Activity of Yogurt Components Article Jan 1983 G.V. Reddy <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Bev Friend K.M. Shahani R. E. FARMER Male swiss mice were implanted with Ehrlich ascites tumor cells and fed ad libitum either yogurt or yogurt components. Ad libitum feeding of yogurt for 7 consecutive days after tumor implantation significantly (P<0.05) inhibited cell counts by 24 to 28% and DNA synthesis by 23 to 31%. When milk or 1.5% lactic acid was fed, there was no significant effect. Feeding yogurt for 7 d before implantation, in addition to yogurt feeding for 7 d after implantation, did not increase inhibition. The level of inhibition was decreased, however, when feeding was initiated more than 1 d after tumor implantation. While yogurt effectively inhibited initial tumor growth, continuous feeding from day 1 until death had no significant effect on the survival rate of the mice. Centrifugal separation of yogurt into solids and supernatant fluid fractions revealed that the antitumor activity was localized in the solids fraction; the supernatant fluid possessed no activity. Concentration of the solids fraction did not significantly increase the antitumor activity. Milk consumption, symptom response, and lactose digestion in milk intolerance1'2 Jul 1987 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Jorge L Rosado <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Lindsay Allen Noel W Solomons The experience of adverse gastrointestinal symptoms (gas, abdominal pain, and diarrhea) after the oralingestion of 360 mL whole milk was investigated in 25 adults who claimed to be milk intolerant. The level of customary milk consumption by all subjects was low compared with that of 13 control subjects who denied a history of milk intolerance. After drinking the milk, which was accompanied by a hydrogen breath test, most of the subjects experienced some of their accustomed intestinal discomfort and the degree of intolerance was similar for the nine (36%) who proved to be true lactose-maldigester subjects and the 16 (64%) who hadflathydrogenbreathresponses, ie, who were classified as lactose-digester subjects. There is a subpopulation of lactose-intolerant milk- rejector individuals thatabsorbs lactose efficiently and responds to other milk-related factor(s) with the same subjective symptoms and dietary conduct as do true lactose-maldigester individuals. Am JClin Nuir l987;45:1457-60. Ecological control of the gastrointestinal tract. The role of probiotic flora Article Jan 1998 <here is a image 78751d243dafb609-31b547fbf605e183> Stig B.S Bengmark Lactobacillemia--Report of nine cases:: Important clinical and therapeutic considerations Article Jun 1978 AM J MED <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Arnold Bayer <here is a image 9417758d63c12686-031202425360fc29> Anthony W Chow David Betts Lucien B. Guze Serious infections due to lactobacilli have been rarely cited. We report our findings in nine recent patients with lactobacillemia. In the combined literature and current experience, endocarditis and sepsis from localized suppuration were the most common clinical syndromes, most frequently arising from prior oropharyngeal infections. Lactobacillus endocarditis showed a predilection for left-sided cardiac involvement (100 per cent) and systemic arterial embolization (55 per cent). The nine clinical isolates were tested for minimal inhibitory and bactericidal concentrations (MICs and MBCs) against five drugs with broad gram-positive spectrums; of note, these organisms demonstrated a high incidence of both unachievable MBCs (64 per cent) and widely disparate (greater than 100 fold) MIC:MBC ratios (38 per cent). This is in accord with observations in Lactobacillus endocarditis of poor in vivo clinical response despite "appropriate" regimens and achievable MICs of the organisms. Bactericidal synergistic studies on two endocarditis isolates indicated that the penicillins plus aminoglycosides may be potentially useful in the treatment of deep-seated Lactobacillus infections when single antimicrobials fail to achieve a cure. The normal colonic bacterial flora Article May 1975 M J Hill <here is a image 2cc22eb4c9920d41-9d1edb0c3d3b801e> Bohumil Sawdon Drasar Colonic bacteria can be studied by identifying and enumerating the major groups or by studying their biochemical activities. The recto sigmoid flora is similar to the faeces but differs from that found in the region of the ileocaecal junction. The major species is Bacteroides fragilis. E coli and Strep. viridans also are common. Lack of good selective media makes the less frequent organisms difficult to count. Luminal flora are easily counted but the mucosal flora may be quite different and difficult to identify. Diet is known to affect faecal flora but the changes take place slowly. Colonic flora cause hydrolysis of glycosides followed by fermentation of the monosaccharide. This reaction may produce either toxic or therapeutic effects. The enterohepatic circulation plays an important role in this. It is also important in the production of ammonia from amino acids and urea, acting through bacterial urease. Control of nitrogen metabolism in hepatic coma is achieved by either reducing nitrogen intake, getting rid of ammonia producing organisms, shortening the time available for organisms to produce ammonia by giving purgatives and enemas, or retaining the ammonia in the gut by using lactulose to lower the pH. Gut bacteria deconjugate bile acids mainly in the ileum, by dehydroxylation occurring in the large bowel, and contribute to the total faecal loss of bile acids. Colon carcinogens may be unsaturated bile acids produced by anaerobic gut organisms commonly found in human faeces in areas of high colon cancer incidence and rarely found where the incidence of colon cancer is low. In a recent trial, concentrations of faecal bile acids and nuclear dehydrogenating clostridia were much higher in patients with colon cancer than in a control group. It may be possible to use these tests in the future to predict colon cancer. (Hennessy - Dublin) Survival of bifidobacteria ingested via fermented milk during their passage through the human small intestine: An in vivo study using intestinal perfusion Feb 1992 Yoram Bouhnik <here is a image 6bdf3a0f156cb776-b22e97b577a87840> Philippe Pochart Philippe Marteau
https://www.researchgate.net/publication/12928554_Lactic_acid_bacteria_and_the_human_gastrointestinal_tract
People ex rel. Brenza v. Anderson, No. 32159 - Illinois - Case Law - VLEX 887937372 0: [object Object]. 1: [object Object]. 2: [object Object]. 3: [object Object]. 4: [object Object]. 5: [object Object] Illinois People ex rel. Brenza v. Anderson, No. 32159 Court Supreme Court of Illinois Writing for the Court HERSHEY Citation 103 N.E.2d 629,411 Ill. 252 Parties PEOPLE ex rel. BRENZA, County Collector v. ANDERSON et al. Docket Number No. 32159 Decision Date 24 January 1952 Page 629 103 N.E.2d 629 411 Ill. 252 PEOPLE ex rel. BRENZA, County Collector v. ANDERSON et al. No. 32159. Supreme Court of Illinois. [411 Ill. 253] Page 631 Adelbert Brown, of Chicago, for appellants. John S. Boyle, State's Atty., of Chicago (Gordon B. Nash, and Edward E. Plusdrak, Chicago, of counsel), for appellee. HERSHEY, Justice. This is a direct appeal from a judgment of the county court of Cook County. Jurisdiction of this court is invoked on the grounds that public revenue is involved. Objections concerning more than 2000 parcels of real estate were filed [411 Ill. 254] to the county collector's application for judgment for sale of real estate for delinquent 1947 taxes, and for judgment fixing the correct amount of any taxes paid under protest. The cause was heard on its merits and a judgment was entered sustaining objections to certain 1947 taxes of six major taxing bodies of the city of Chicago and overruling objections to the levy for Cook County's bond and interest fund. The objectors appeal from that part of the judgment overruling their objections, while the county collector has filed a cross appeal to review that part of the judgment which sustained objections to taxes of the six taxing bodies. The cross appeal of the county collector is based solely on the ground that the county court erred in entering judgment in favor of the objectors because there was no evidence that they had paid under protest at least seventy-five per cent of the taxes to which objections were made, as required by statute. We will consider this assignment of error first, since, if it be well taken, it might not be necessary to dispose of the other errors assigned. An examination of pertinent sections of the Revenue Act relating to procedural requirements, where application is made for judgment for sale of real estate for delinquent taxes, must precede any determination of the question presented. Section 232 of the act provides that the county Page 632 collector shall transcribe into a record prepared for that purpose, and known as the tax judgment, sale, redemption, and forfeiture record, the list of delinquent lands and lots and of lands and lots upon which taxes have been paid under protest, which shall be made out in numerical order, and contain all the information necessary to be recorded, at least five days before the day on which application for judgment is made. Among the things required to be set forth in the record is the name of the owner, if known; a proper description of the real estate; the year or years for which the taxes are due, or for which they have been paid under protest; the amount of taxes paid under protest;[411 Ill. 255] the valuation on which the tax is extended; and the costs and total amount of charges against such real estate. (Ill.Rev.Stat.1949, chap. 120, par. 713.) By section 225 of the act it is provided that at any time after the first day of September next after all such delinquent taxes on real estate shall become due, or next after any taxes are paid under protest in any year, the collector shall give notice, by newspaper publication, of the intended application for judgment for sale of such delinquent real estate, and for judgment fixing the correct amount of any tax paid under protest. (Ill.Rev.Stat.1949, chap. 120, par. 706.) The record of delinquent property required by section 232 of the act serves as a declaration or complaint in the proceedings to obtain judgment for delinquent taxes, while the published notice serves as process. People ex rel. Anderson v. Chicago & Eastern Illinois Railway Co., 386 Ill. 239 , 53 N.E.2d 921 . This delinquent list and the statutory supplemental certificate and collector's affidavit constitute the evidence to be presented to the court on application for judgment in order to make out a prima facie case. The list constitutes the source of the power of the court to enter judgment. Without it there is no showing that the taxes were delinquent, the amount of such delinquency, or the amount of tax paid under protest, and no statement of ownership and description of the real estate assessed. The delinquent list required by the statute is indispensable in all cases unless there is, in the record, a stipulation that a prima facie showing has been made, or is expressly waived. People ex rel. County Collector v. Kribs, 381 Ill. 417 , 45 N.E.2d 846 . In the instant case a stipulation was entered into, by which it was specifically agreed that the collector has duly made out a prima facie case. The effect of the stipulation was to admit that the collector had proved the pertinent matters set out in the delinquent list for the year 1947. Among the matters thus proved were the list of lands and lots upon which taxes had been paid under protest, the name of the [411 Ill. 256] owner, the amount of taxes paid under protest, a description of the real estate, the valuation on which the tax was extended, and the total amount of charges against the real estate. In the absence of objection, or defense interposed, the court could, on the showing made, enter judgment for the unpaid balance of any tax which had been paid under protest. Objections, however, were filed to the application for judgment for sale of delinquent real estate and for judgment fixing the correct amount of taxes paid under protest. Section 194 of the act provides that if any person shall desire to object to all or any part of a real-estate tax for any year, pursuant to the provisions of section 235 of the act, for any reason other than that the real estate is not subject to taxation, such person shall first pay at least 75 per cent of the tax. Payment of the tax is required to be accompanied by a prescribed form... 10 practice notes Smith v. D. R. G., Inc., No. 58171 United States United States Appellate Court of Illinois June 17, 1975 ...to obtain judgment for delinquent taxes; the notices required by section 706 and 711 serve as process. (People ex rel. Brenza v. Anderson, 411 Ill. 252 , 103 N.E.2d 629; People ex rel. Anderson v. Chicago and Eastern Illinois Railway Co., 386 Ill. 239, 53 N.E.2d 921.) Compliance with both th...... People ex rel. Jones v. Adams, No. 75--109 United States United States Appellate Court of Illinois July 9, 1976 ...real estate taxes under protest, to their written objections. Ill.Rev.Stat.1971, ch. 120, par. 716; People ex rel. Brenza v. Anderson, 411 Ill. 252 , 103 N.E.2d 629; People ex rel. Voorhees v. Chicago, Burlington & Quincy Railroad, 386 Ill. 200, 53 N.E.2d 963. The defendants' failure to do s...... Pohrer v. Title Ins. Co. of Minnesota, No. 85 C 8832. United States United States District Courts. 7th Circuit. United States District Court (Northern District of Illinois) January 14, 1987 ...Central Illinois Public Service Co. v. Miller, 42 Ill.2d 542, 545-546, 248 N.E.2d 89, 91 (1969); People ex rel. Brenza v. Anderson, 411 Ill. 252 , 260, 103 N.E.2d 629, 634-35 (1952). A tax levy occurs only once, although taxes may be extended and collected over a number of years. The extensi...... Central Illinois Public Service Co. v. Miller, No. 41683 United States Supreme Court of Illinois May 28, 1969 ...(People ex rel. Hicks v. New York, Chicago and St. Louis Railroad Co., 323 Ill. 493, 154 N.E. 193; People ex rel. Brenza v. Anderson, 411 Ill. 252 , 103 N.E.2d 629.) Section 6--6 of article 6 of the Park District Code, (Ill.Rev.Stat.1965, ch. 105, par. 6--6) states that a certified copy of a...... 10 cases Smith v. D. R. G., Inc., No. 58171 United States United States Appellate Court of Illinois June 17, 1975 ...to obtain judgment for delinquent taxes; the notices required by section 706 and 711 serve as process. (People ex rel. Brenza v. Anderson, 411 Ill. 252 , 103 N.E.2d 629; People ex rel. Anderson v. Chicago and Eastern Illinois Railway Co., 386 Ill. 239, 53 N.E.2d 921.) Compliance with both th...... People ex rel. Jones v. Adams, No. 75--109 United States United States Appellate Court of Illinois July 9, 1976 ...real estate taxes under protest, to their written objections. Ill.Rev.Stat.1971, ch. 120, par. 716; People ex rel. Brenza v. Anderson, 411 Ill. 252 , 103 N.E.2d 629; People ex rel. Voorhees v. Chicago, Burlington & Quincy Railroad, 386 Ill. 200, 53 N.E.2d 963. The defendants' failure to do s...... Pohrer v. Title Ins. Co. of Minnesota, No. 85 C 8832. United States United States District Courts. 7th Circuit. United States District Court (Northern District of Illinois) January 14, 1987 ...Central Illinois Public Service Co. v. Miller, 42 Ill.2d 542, 545-546, 248 N.E.2d 89, 91 (1969); People ex rel. Brenza v. Anderson, 411 Ill. 252 , 260, 103 N.E.2d 629, 634-35 (1952). A tax levy occurs only once, although taxes may be extended and collected over a number of years. The extensi...... Central Illinois Public Service Co. v. Miller, No. 41683 United States Supreme Court of Illinois May 28, 1969 ...(People ex rel. Hicks v. New York, Chicago and St. Louis Railroad Co., 323 Ill. 493, 154 N.E. 193; People ex rel. Brenza v. Anderson, 411 Ill. 252 , 103 N.E.2d 629.) Section 6--6 of article 6 of the Park District Code, (Ill.Rev.Stat.1965, ch. 105, par. 6--6) states that a certified copy of a......
https://case-law.vlex.com/vid/people-ex-rel-brenza-887937372
The atmospheric hydrologic cycle in the ACME v0.3 model (Journal Article) | DOE PAGES The U.S. Department of Energy's Office of Scientific and Technical Information Title: The atmospheric hydrologic cycle in the ACME v0.3 model Full Record References ( 73 ) Cited by ( 5 ) Images Figures / Tables ( 24 ) Other Related Research Abstract We examine the global water cycle characteristics in the Accelerated Climate Modeling for Energy v0.3 model (a close relative to version 5.3 of the Community Atmosphere Model) in atmosphere-only simulations spanning the years 1980–2005. We evaluate the simulations using a broad range of observational and reanalysis datasets, examine how the simulations change when the horizontal resolution is increased from 1° to 0.25, and compare the simulations against models participating in the the Atmosphere Model Intercomparison Project of the 5th Coupled Model Intercomparison Project (CMIP5). Particular effort has been made to evaluate the model using the best available observational estimates and verifying model biases with additional datasets when differences are known to exist among the observations. Regardless of resolution, the model exhibits several biases: global-mean precipitation, evaporation, and precipitable water are too high, light precipitation occurs too frequently, and the atmospheric residence time of water is too short. Many of these biases are shared by the multi-model mean climate of models participating in CMIP5. The reasons behind regional biases in precipitation are discussed by examining how different fields, such as local evaporation and transport of water vapor, contribute to the bias. Although increasing the horizontal resolution does not drastically change the more » water cycle, it does lead to a few differences: an increase in global mean precipitation rate, an increase in the fraction of total precipitation that falls over land, more frequent heavy precipitation (>30 mm day -1 ), and a decrease in precipitable water. One of the most notable changes is the shift of precipitation produced by the convective parameterization to that produced by the large-scale microphysics parameterization. We analyze how changes in moisture and circulation with resolution contribute to this shift in the precipitation partitioning. Because changing horizontal resolution requires some re-tuning, the effect of that tuning was evaluated by performing an additional simulation at 1 but using the tunings from the 0.25 simulation. In conclusion, the evaluation shows that the more frequent heavy precipitation, the decrease in precipitable water, and the shift from convective to large-scale precipitation are predominantly due to resolution changes, while tuning changes have a major influence on the global mean precipitation and the land/ ocean partitioning of precipitation. « less Authors: Terai, Christopher R. [1] ; Search DOE PAGES for author "Terai, Christopher R." Search DOE PAGES for ORCID "0000-0002-2433-0472" Search orcid.org for ORCID "0000-0002-2433-0472" Caldwell, Peter M. [1] ; Klein, Stephen A. [1] ; Tang, Qi [1] ; Branstetter, Marcia L. [2] Search DOE PAGES for author "Branstetter, Marcia L." Search DOE PAGES for ORCID "0000-0003-1035-0250" Search orcid.org for ORCID "0000-0003-1035-0250" + Show Author Affiliations Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Cloud Processes Research Group Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States) Publication Date: 2017-07-28 Research Org.: Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC) Sponsoring Org.: USDOE Office of Science (SC), Biological and Environmental Research (BER); USDOE Office of Science (SC), Advanced Scientific Computing Research (ASCR) OSTI Identifier: 1468074 Alternate Identifier(s): OSTI ID: 1461872 Grant/Contract Number: AC05-00OR22725; AC02-06CH11357; AC02-05CH11231; AC52-07NA27344 Resource Type: Accepted Manuscript Journal Name: Climate Dynamics Additional Journal Information: Journal Volume: 50; Journal Issue: 9-10; Journal ID: ISSN 0930-7575 Publisher: Springer-Verlag Country of Publication: United States Language: English Subject: 54 ENVIRONMENTAL SCIENCES ; Water cycle ; Precipitation ; Climate modeling ; Horizontal resolution ; Model evaluation Citation Formats MLA APA Chicago BibTeX Terai, Christopher R., Caldwell, Peter M., Klein, Stephen A., Tang, Qi, and Branstetter, Marcia L. The atmospheric hydrologic cycle in the ACME v0.3 model . United States: N. p., 2017. Web. doi:10.1007/s00382-017-3803-x. Copy to clipboard Terai, Christopher R., Caldwell, Peter M., Klein, Stephen A., Tang, Qi, & Branstetter, Marcia L. The atmospheric hydrologic cycle in the ACME v0.3 model . United States. https://doi.org/10.1007/s00382-017-3803-x Copy to clipboard Terai, Christopher R., Caldwell, Peter M., Klein, Stephen A., Tang, Qi, and Branstetter, Marcia L. Fri . "The atmospheric hydrologic cycle in the ACME v0.3 model". United States. https://doi.org/10.1007/s00382-017-3803-x. https://www.osti.gov/servlets/purl/1468074. Copy to clipboard @article{osti_1468074, title = {The atmospheric hydrologic cycle in the ACME v0.3 model}, author = {Terai, Christopher R. and Caldwell, Peter M. and Klein, Stephen A. and Tang, Qi and Branstetter, Marcia L.}, abstractNote = {We examine the global water cycle characteristics in the Accelerated Climate Modeling for Energy v0.3 model (a close relative to version 5.3 of the Community Atmosphere Model) in atmosphere-only simulations spanning the years 1980–2005. We evaluate the simulations using a broad range of observational and reanalysis datasets, examine how the simulations change when the horizontal resolution is increased from 1° to 0.25, and compare the simulations against models participating in the the Atmosphere Model Intercomparison Project of the 5th Coupled Model Intercomparison Project (CMIP5). Particular effort has been made to evaluate the model using the best available observational estimates and verifying model biases with additional datasets when differences are known to exist among the observations. Regardless of resolution, the model exhibits several biases: global-mean precipitation, evaporation, and precipitable water are too high, light precipitation occurs too frequently, and the atmospheric residence time of water is too short. Many of these biases are shared by the multi-model mean climate of models participating in CMIP5. The reasons behind regional biases in precipitation are discussed by examining how different fields, such as local evaporation and transport of water vapor, contribute to the bias. Although increasing the horizontal resolution does not drastically change the water cycle, it does lead to a few differences: an increase in global mean precipitation rate, an increase in the fraction of total precipitation that falls over land, more frequent heavy precipitation (>30 mm day-1), and a decrease in precipitable water. One of the most notable changes is the shift of precipitation produced by the convective parameterization to that produced by the large-scale microphysics parameterization. We analyze how changes in moisture and circulation with resolution contribute to this shift in the precipitation partitioning. Because changing horizontal resolution requires some re-tuning, the effect of that tuning was evaluated by performing an additional simulation at 1 but using the tunings from the 0.25 simulation. In conclusion, the evaluation shows that the more frequent heavy precipitation, the decrease in precipitable water, and the shift from convective to large-scale precipitation are predominantly due to resolution changes, while tuning changes have a major influence on the global mean precipitation and the land/ ocean partitioning of precipitation.}, doi = {10.1007/s00382-017-3803-x}, journal = {Climate Dynamics}, number = 9-10, volume = 50, place = {United States}, year = {2017}, month = {7} } Copy to clipboard Journal Article: Free Publicly Available Full Text Accepted Manuscript (DOE) Publisher's Version of Record https://doi.org/10.1007/s00382-017-3803-x Copyright Statement Other availability Search WorldCat to find libraries that may hold this journal Citation Metrics: Cited by: 24 works Citation information provided by Web of Science Figures / Tables: Table 1: Set of tuning parameters and physics time steps that differ and are used in the NE120 simulations, NE30 simulations, NE30 simulation with NE120 tunings, and the atmosphere model used in the Community Earth System Model Large Ensemble (CESM LENS) project All figures and tables (24 total) Save / Share: Export Metadata Endnote RIS CSV / Excel XML JSON Save to My Library You must Sign In or Create an Account in order to save documents to your library. Facebook Twitter Email Print More share options ... LinkedIn Pinterest Tumblr Works referenced in this record: Convergence of aqua-planet simulations with increasing resolution in the Community Atmospheric Model, Version 3 journal , January 2008 Williamson, David L. Tellus A: Dynamic Meteorology and Oceanography, Vol. 60, Issue 5 DOI: 10.1111/j.1600-0870.2008.00339.x High-resolution simulations of global climate, part 1: present climate journal , November 2003 Duffy, P. B.; Govindasamy, B.; Iorio, J. P. Climate Dynamics, Vol. 21, Issue 5-6 DOI: 10.1007/s00382-003-0339-z Evaluation of the Hydrological Cycle in the ECHAM5 Model journal , August 2006 Hagemann, Stefan; Arpe, Klaus; Roeckner, Erich Journal of Climate, Vol. 19, Issue 16 DOI: 10.1175/jcli3831.1 Impact of the LMDZ atmospheric grid configuration on the climate and sensitivity of the IPSL-CM5A coupled model journal , July 2012 Hourdin, Frédéric; Foujols, Marie-Alice; Codron, Francis Climate Dynamics, Vol. 40, Issue 9-10 DOI: 10.1007/s00382-012-1411-3 CAM-SE: A scalable spectral element dynamical core for the Community Atmosphere Model journal , November 2011 Dennis, John M.; Edwards, Jim; Evans, Katherine J. The International Journal of High Performance Computing Applications, Vol. 26, Issue 1 DOI: 10.1177/1094342011428142 Contrasting roles of interception and transpiration in the hydrological cycle – Part 1: Temporal characteristics over land journal , January 2014 Wang-Erlandsson, L.; van der Ent, R. J.; Gordon, L. J. Earth System Dynamics, Vol. 5, Issue 2 DOI: 10.5194/esd-5-441-2014 How well can CMIP5 simulate precipitation and its controlling processes over tropical South America? journal , November 2012 Yin, Lei; Fu, Rong; Shevliakova, Elena Climate Dynamics, Vol. 41, Issue 11-12 DOI: 10.1007/s00382-012-1582-y An update on Earth's energy balance in light of the latest global observations journal , September 2012 Stephens, Graeme L.; Li, Juilin; Wild, Martin Nature Geoscience, Vol. 5, Issue 10 DOI: 10.1038/ngeo1580 The role of horizontal resolution in simulating drivers of the global hydrological cycle journal , September 2013 Demory, Marie-Estelle; Vidale, Pier Luigi; Roberts, Malcolm J. Climate Dynamics, Vol. 42, Issue 7-8 DOI: 10.1007/s00382-013-1924-4 Australia's CMIP5 submission using the CSIRO-Mk3.6 model journal , March 2013 Jeffrey, S.; Rotstayn, L.; Collier, M. Australian Meteorological and Oceanographic Journal, Vol. 63, Issue 1 DOI: 10.22499/2.6301.001 Previous Page 1 2 3 ... Next Page All References dataset (1) journal (71) text (1) Search Sort by: Sort by title Sort by date [ × clear filter / sort ] Works referencing / citing this record: Multi-model evaluation of the sensitivity of the global energy budget and hydrological cycle to resolution journal , December 2018 Vannière, Benoît; Demory, Marie-Estelle; Vidale, Pier Luigi Climate Dynamics, Vol. 52, Issue 11 DOI: 10.1007/s00382-018-4547-y Sensitivity of seasonal flood simulations to regional climate model spatial resolution journal , May 2019 Castaneda-Gonzalez, Mariana; Poulin, Annie; Romero-Lopez, Rabindranarth Climate Dynamics, Vol. 53, Issue 7-8 DOI: 10.1007/s00382-019-04789-y Model Resolution Sensitivity of the Simulation of North Atlantic Oscillation Teleconnections to Precipitation Extremes journal , October 2018 Mahajan, Salil; Evans, Katherine J.; Branstetter, Marcia L. Journal of Geophysical Research: Atmospheres, Vol. 123, Issue 20 DOI: 10.1029/2018jd028594 Regionally refined test bed in E3SM atmosphere model version 1 (EAMv1) and applications for high-resolution modeling journal , January 2019 Tang, Qi; Klein, Stephen A.; Xie, Shaocheng Geoscientific Model Development, Vol. 12, Issue 7 DOI: 10.5194/gmd-12-2679-2019 TheDiaTo (v1.0) – a new diagnostic tool for water, energy and entropy budgets in climate models journal , January 2019 Lembo, Valerio; Lunkeit, Frank; Lucarini, Valerio Geoscientific Model Development, Vol. 12, Issue 8 DOI: 10.5194/gmd-12-3805-2019 Previous Page 1 Next Page All Cited By journal (5) Search Sort by: Sort by title Sort by date [ × clear filter / sort ] Figures / Tables found in this record: Fig. 1 (p. 5) figure Fig. 2 (p. 8) figure Fig. 3 (p. 9) figure Fig. 4 (p. 10) figure Fig. 5 (p. 11) figure Fig. 6 (p. 12) figure Fig. 7 (p. 13) figure Fig. 8 (p. 14) figure Fig. 9 (p. 14) figure Fig. 10 (p. 15) figure Fig. 11 (p. 16) figure Fig. 12 (p. 17) figure 1 2 All Images figures (19) tables (5) Search Sort by figure / table title Sort by page order [ × clear filter / sort ] Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts. Similar Records in DOE PAGES and OSTI.GOV collections: Collaborative Research: Process-resolving Decomposition of the Global Temperature Response to Modes of Low Frequency Variability in a Changing Climate Technical Report Cai, Ming ; Deng, Yi El Niño-Southern Oscillation (ENSO) and Annular Modes (AMs) represent respectively the most important modes of low frequency variability in the tropical and extratropical circulations. The future projection of the ENSO and AM variability, however, remains highly uncertain with the state-of-the-art coupled general circulation models. A comprehensive understanding of the factors responsible for the inter-model discrepancies in projecting future changes in the ENSO and AM variability, in terms of multiple feedback processes involved, has yet to be achieved. The proposed research aims to identify sources of such uncertainty and establish a set of process-resolving quantitative evaluations of the existing predictions of more » the future ENSO and AM variability. The proposed process-resolving evaluations are based on a feedback analysis method formulated in Lu and Cai (2009), which is capable of partitioning 3D temperature anomalies/perturbations into components linked to 1) radiation-related thermodynamic processes such as cloud and water vapor feedbacks, 2) local dynamical processes including convection and turbulent/diffusive energy transfer and 3) non-local dynamical processes such as the horizontal energy transport in the oceans and atmosphere. Taking advantage of the high-resolution, multi-model ensemble products from the Coupled Model Intercomparison Project Phase 5 (CMIP5) soon to be available at the Lawrence Livermore National Lab, we will conduct a process-resolving decomposition of the global three-dimensional (3D) temperature (including SST) response to the ENSO and AM variability in the preindustrial, historical and future climate simulated by these models. Specific research tasks include 1) identifying the model-observation discrepancies in the global temperature response to ENSO and AM variability and attributing such discrepancies to specific feedback processes, 2) delineating the influence of anthropogenic radiative forcing on the key feedback processes operating on ENSO and AM variability and quantifying their relative contributions to the changes in the temperature anomalies associated with different phases of ENSO and AMs, and 3) investigating the linkages between model feedback processes that lead to inter-model differences in time-mean temperature projection and model feedback processes that cause inter-model differences in the simulated ENSO and AM temperature response. Through a thorough model-observation and inter-model comparison of the multiple energetic processes associated with ENSO and AM variability, the proposed research serves to identify key uncertainties in model representation of ENSO and AM variability, and investigate how the model uncertainty in predicting time-mean response is related to the uncertainty in predicting response of the low-frequency modes. The proposal is thus a direct response to the first topical area of the solicitation: Interaction of Climate Change and Low Frequency Modes of Natural Climate Variability. It ultimately supports the accomplishment of the BER climate science activity Long Term Measure (LTM): "Deliver improved scientific data and models about the potential response of the Earth's climate and terrestrial biosphere to increased greenhouse gas levels for policy makers to determine safe levels of greenhouse gases in the atmosphere." « less Observed and Simulated Sensitivities of Spring Greenup to Preseason Climate in Northern Temperate and Boreal Regions: Climate control on spring phenology Journal Article Xu, Xiyan ; Riley, William J. ; Koven, Charles D. ; ... - Journal of Geophysical Research. Biogeosciences Vegetation phenology plays an important role in regulating land-atmosphere energy, water, and trace-gas exchanges. Changes in spring greenup (SG) have been documented in the past half-century in response to ongoing climate change. We use normalized difference vegetation index generated from NOAA's advanced very high resolution radiometer data in the Global Inventory Modeling and Monitoring Study project over the 1982–2005 period, coupled with climate reanalysis (Climate Research Unit-National Centers for Environmental Prediction) to investigate the SG responses to preseason climate change in northern temperate and boreal regions. We compared these observed responses to the simulated SG responses to preseason climate inferred more » from the Earth system models (ESMs) participating in the Coupled Model Intercomparison Project Phase 5 (CMIP5) over 1982–2005. The observationally inferred SG suggests that there has been an advance of about 1 days per decade between 1982 and 2005 in the northern midlatitude to high latitude, with significant spatial heterogeneity. The spatial heterogeneity of the SG advance results from heterogeneity in the change of the preseason climate as well as varied vegetation responses to the preseason climate across biomes. The SG to preseason temperature sensitivity is highest in forests other than deciduous needleleaf forests, followed by temperate grasslands and woody savannas. The SG in deciduous needleleaf forests, open shrublands, and tundra is relatively insensitive to preseason temperature. Although the extent of regions where the SG is sensitive to preseason precipitation is smaller than the extent of regions where the SG is sensitive to preseason temperature, the biomes that are more sensitive to temperature are also more sensitive to precipitation, suggesting the interactive control of temperature and precipitation. Finally, in the mean, the CMIP5 ESMs reproduced the dominant latitudinal preseason climate trends and SG advances. However, large biases in individual ESMs for the preseason period, climate, and SG sensitivity imply needed model improvements to climate prediction and phenological process parameterizations. « less Cited by 13 https://doi.org/10.1002/2017JG004117 Full Text Available Using ARM Measurements to Understand and Reduce the Double ITCZ Biases in the Community Atmospheric Model Technical Report Zhang, Minghua 1. Understanding of the observed variability of ITCZ in the equatorial eastern Pacific. The annual mean precipitation in the eastern Pacific has a maximum zonal band north of the equator in the ITCZ where the maximum SST is located. During the boreal spring (referring to February, March, and April throughout the present paper), because of the accumulated solar radiation heating and oceanic heat transport, a secondary maximum of SST exists in the southeastern equatorial Pacific. Associated with this warm SST is also a seasonal transitional maximum of precipitation in the same region in boreal spring, exhibited as a weak double more » ITCZ pattern in the equatorial eastern Pacific. This climatological seasonal variation, however, varies greatly from year to year: double ITCZ in the boreal spring occurs in some years but not in other years; when there a single ITCZ, it can appear either north, south or at the equator. Understanding this observed variability is critical to find the ultimate cause of the double ITCZ in climate models. Seasonal variation of ITCZ south of the eastern equatorial Pacific: By analyzing data from satellites, field measurements and atmospheric reanalysis, we have found that in the region where spurious ITCZ in models occurs, there is a “seasonal cloud transition” — from stratocumulus to shallow cumulus and eventually to deep convection —in the South Equatorial Pacific (SEP) from September to April that is similar to the spatial cloud transition from the California coast to the equator. This seasonal transition is associated with increasing sea surface temperature (SST), decreasing lower tropospheric stability and large-scale subsidence. This finding of seasonal cloud transition points to the same source of model errors in the ITCZ simulations as in simulation of stratocumulus-cumulus-deep convection transition. It provides a test for climate models to simulate the relationships between clouds and large-scale atmospheric fields in a region that features a spurious double Inter-tropical Convergence Zone (ITCZ) in most models. This work is recently published in Yu et al. (2016). Interannual variation of ITCZ south of the eastern equatorial Pacific: By analyzing data from satellites, field measurements and atmospheric reanalysis, we have characterized the interannual variation of boreal spring precipitation in the eastern tropical Pacific and found the cause of the observed interannual variability. We have shown that ITCZ in this region can occur as a single ITCZ along the Equator, single ITCZ north of the Equator, single ITCZ south of the Equator, and double ITCZ on both sides of the Equator. We have found that convective instability only plays a secondary role in the ITCZ interannual variability. Instead, the remote impact of the Pacific basin-wide SST on the horizontal gradient of surface pressure and wind convergence is the primary driver of this interannual variability. Results point to the need to include moisture convergence in convection schemes to improve the simulation of precipitation in the eastern tropical Pacific. This result has been recently submitted for publication (Yu and Zhang 2016). 2. Improvement of model parameterizations to reduce the double ITCZ bias We analyzed the current status of climate model performance in simulating precipitation in the equatorial Pacific. We have found that the double ITCZ bias has not been reduced in CMIP5 models relative to CMIP4 models. We have characterized the dynamic structure of the common bias by using precipitation, sea surface temperature, surface winds and sea-level. Results are published in Zhang et al. (2015): Since cumulus convection plays a significant role in the double ITCZ behavior in models, we have used measurements from ARM and other sources to carry out a systematic analysis of the roles of shallow and deep convection in the CAM. We found that in both CAM4 and CAM5, when the intensity of deep convection decreases as a result of parameterization change, the intensity of shallow convection increases, leading to very different changes in precipitation partitions but little change in the total precipitation. The different precipitation partition however can manifest themselves in other measures of model performances including temperature and humidity. This study points to the need to treat model physical parameterizations as integrated system rather than individual components. Results from this study are published in Wang and Zhang (2013). Since shallow convection interacts with the deep convection scheme and surface turbulence to trigger the double ITCZ, we studied methods to improve the shallow convection scheme in climate models. We investigated the bulk budgets of the vertical velocity and its parameterization in convective cores, convective updrafts, and clouds by using large-eddy simulation (LES) of four shallow convection cases including one from ARM. We proposed optimal forms of the Simpson and Wiggert equation to calculate the vertical velocity in bulk mass flux convection schemes for convective cores, convective updrafts, and convective clouds as parameterization schemes. The new scheme is published in Wang and Zhang (2014). By using long-term radar-based ground measurements from ARM, we derived a scale-aware inhomogeneity parameterization of cloud liquid water in climate models. We found a relationship between the inhomogeneity parameter and the model grid size as well as atmospheric stability. This relationship is implemented in the CESM to describe the subgrid-scale cloud inhomogeneity. Relative to the default CESM with the finite-volume dynamic core at 2-degree resolution, the new parameterization leads to smaller cloud inhomogeneity and larger cloud liquid-water path in high latitudes, and the opposite effect in low latitudes, with the regional impact on shortwave cloud radiation effect of up to 10 W/m 2 . This is due to both the smaller (larger) grid size in high (low) latitudes in the longitude-latitude grid setting of CESM and the more stable (unstable) atmosphere. This parameterization is expected lead to more realistic simulation of tropical precipitation in high-resolution models. Results from this study are reported in Xie and Zhang (2015). « less https://doi.org/10.2172/1334768 Full Text Available High Resolution Model Intercomparison Project (HighResMIP v1.0) for CMIP6 Journal Article Haarsma, Reindert J. ; Roberts, Malcolm J. ; Vidale, Pier Luigi ; ... - Geoscientific Model Development (Online) Robust projections and predictions of climate variability and change, particularly at regional scales, rely on the driving processes being represented with fidelity in model simulations. The role of enhanced horizontal resolution in improved process representation in all components of the climate system is of growing interest, particularly as some recent simulations suggest both the possibility of significant changes in large-scale aspects of circulation as well as improvements in small-scale processes and extremes. However, such high-resolution global simulations at climate timescales, with resolutions of at least 50 km in the atmosphere and 0.25° in the ocean, have been performed at relatively more » few research centres and generally without overall coordination, primarily due to their computational cost. Assessing the robustness of the response of simulated climate to model resolution requires a large multi-model ensemble using a coordinated set of experiments. The Coupled Model Intercomparison Project 6 (CMIP6) is the ideal framework within which to conduct such a study, due to the strong link to models being developed for the CMIP DECK experiments and other model intercomparison projects (MIPs). Increases in high-performance computing (HPC) resources, as well as the revised experimental design for CMIP6, now enable a detailed investigation of the impact of increased resolution up to synoptic weather scales on the simulated mean climate and its variability. The High Resolution Model Intercomparison Project (HighResMIP) presented in this paper applies, for the first time, a multi-model approach to the systematic investigation of the impact of horizontal resolution. A coordinated set of experiments has been designed to assess both a standard and an enhanced horizontal-resolution simulation in the atmosphere and ocean. The set of HighResMIP experiments is divided into three tiers consisting of atmosphere-only and coupled runs and spanning the period 1950–2050, with the possibility of extending to 2100, together with some additional targeted experiments. This paper describes the experimental set-up of HighResMIP, the analysis plan, the connection with the other CMIP6 endorsed MIPs, as well as the DECK and CMIP6 historical simulations. Lastly, HighResMIP thereby focuses on one of the CMIP6 broad questions, “what are the origins and consequences of systematic model biases?”, but we also discuss how it addresses the World Climate Research Program (WCRP) grand challenges. « less Cited by 465 https://doi.org/10.5194/gmd-9-4185-2016 Full Text Available Euro-Atlantic winter storminess and precipitation extremes under 1.5 °C vs. 2 °C warming scenarios Journal Article Barcikowska, Monika J. ; Weaver, Scott J. ; Feser, Frauke ; ... - Earth System Dynamics (Online) Severe winter storms in combination with precipitation extremes pose a serious threat to Europe. Located at the southeastern exit of the North Atlantic's storm track, European coastlines are directly exposed to impacts by high wind speeds, storm floods and coastal erosion. In this study we analyze potential changes in simulated winter storminess and extreme precipitation, which may occur under 1.5 or 2°C warming scenarios. Here we focus on a first simulation suite of the atmospheric model CAM5 performed within the HAPPI project and evaluate how changes of the horizontal model resolution impact the results regarding atmospheric pressure, storm tracks, wind speed more » and precipitation extremes. The comparison of CAM5 simulations with different resolutions indicates that an increased horizontal resolution to 0.25° not only refines regional-scale information but also improves large-scale atmospheric circulation features over the Euro-Atlantic region. The zonal bias in monthly pressure at mean sea level and wind fields, which is typically found in low-resolution models, is considerably reduced. This allows us to analyze potential changes in regional- to local-scale extreme wind speeds and precipitation in a more realistic way. Our analysis of the future response for the 2°C warming scenario generally confirms previous model simulations suggesting a poleward shift and intensification of the meridional circulation in the Euro-Atlantic region. Additional analysis suggests that this shift occurs mainly after exceeding the 1.5°C global warming level, when the midlatitude jet stream manifests a strengthening northeastward. At the same time, this northeastern shift of the storm tracks allows an intensification and northeastern expansion of the Azores high, leading to a tendency of less precipitation across the Bay of Biscay and North Sea. Here, regions impacted by the strengthening of the midlatitude jet, such as the northwestern coasts of the British Isles, Scandinavia and the Norwegian Sea, and over the North Atlantic east of Newfoundland, experience an increase in the mean as well as daily and sub-daily precipitation, wind extremes and storminess, suggesting an important influence of increasing storm activity in these regions in response to global warming. « less Cited by 18 https://doi.org/10.5194/esd-9-679-2018 Full Text Available Similar Records
https://www.osti.gov/pages/biblio/1468074
JOSE T. BARBIETO v. CA GR No. 184645, (2009-10-30) Show opinions DIVISION [ GR No. 184645, Oct 30, 2009 ] JOSE T. BARBIETO v. CA + DECISION 619 Phil. 819 THIRD DIVISION [ G.R. No. 184645, October 30, 2009 ] JOSE T. BARBIETO, PETITIONER, VS. THE HONORABLE COURT OF APPEALS; MARY RAWNSLE V. LOPEZ, GRAFT INVESTIGATION AND PROSECUTION OFFICER II; EULOGIO S. CECILIO, DIRECTOR; EMILIO A. GONZALES III, DEPUTY OMBUDSMAN FOR THE MILITARY AND OTHER LAW ENFORCEMENT OFFICES; OMBUDSMAN MERCEDITAS GUTIERREZ; AND LIEUTENANT GENERAL ALEXANDER B. YANO, COMMANDING GENERAL, PHILIPPINE ARMY, RESPONDENTS. D E C I S I O N CHICO-NAZARIO, J.: This Petition for Certiorari under Rule 65 of the Revised Rules of Court assails the Resolutions dated 6 August 2008 [1] and 22 September 2008 [2] of the Court of Appeals in CA-G.R. SP. No. 102874, denying the prayer of petitioner Major General Jose T. Barbieto (Maj. Gen. Barbieto) for a temporary restraining order (TRO) and/or writ of preliminary injunction to enjoin his arrest and confinement, and/or lift the preventive suspension order issued by the Office of the Deputy Ombudsman for the Military and other Law Enforcement Offices (ODO-MOLEO) and the warrant of arrest and confinement issued by Lieutenant General Alexander B. Yano (Lt. Gen. Yano), Commanding General (CG) of the Philippine Army (PA). Facts of the Case Maj. Gen. Barbieto is the Division Commander of the 4 th Infantry Division, PA, Camp Edilberto Evangelista, Cagayan de Oro City. Several Complaint-Affidavits were filed before the ODO-MOLEO by various personnel of the 4 th Infantry Division, PA, against Maj. Gen. Barbieto and his alleged bagman Staff Sergeant Roseller A. Echipare (S/Sgt. Echipare), charging the latter two with grave misconduct and violation of Republic Act No. 6713. Maj. Gen. Barbieto and S/Sgt. Echipare, for allegedly committed the following: (a) extortion of amounts ranging from P25,000.00 to P30,000.00 from applicants in order to guarantee their enlistment in the Philippine Army; (b) extortion of money from soldiers seeking reinstatement, in exchange for Maj. Gen. Barbieto's approval of their reinstatement, despite previous disapproval of said soldiers' requests for reinstatement by the 4 th Infantry Division Reinstatement Board; and (c) anomalies in the clearing of payroll of the Balik Baril program fund of the Armed Forces of the Philippines (AFP). The administrative case against Maj. Gen. Barbieto and S/Sgt. Echipare was docketed as OMB-P-A-08-0201-B, and the criminal case was docketed as OMB-P-C-08-0204-B. [3] On 29 February 2008, ODO-MOLEO ordered [4] the preventive suspension of Maj. Gen. Barbieto and S/Sgt. Echipare for six months during the pendency of OMB-P-A-08-0201-B, the administrative case, thus: WHEREFORE in accordance with Section 24 of Republic Act 6770 and Section 9 Rule III of Administrative Order No. 7 respondents MAJOR GENERAL JOSE T. BARBIETO and SSGT ROSELLER A. ECHEPARE are hereby PREVENTIVELY SUSPENDED during the pendency of this case until its termination, but not to exceed the total period of six (6) months, without pay. In case of delay in the disposition of the case due to the fault, negligence or any cause attributable to the respondents, the period of such delay shall not be counted in computing the period of the preventive suspension. In accordance with Section 27, paragraph (1) of Republic Act 6770, this Order is immediately executory. Notwithstanding any motion, appeal or petition that may be filed by the respondents seeking relief from this Order, unless otherwise ordered by this office or by any court of competent jurisdiction, the implementation of this Order shall not be interrupted within the period prescribed. The Chief of Staff GENERAL HERMOGENES ESPERON of the Armed Forces of the Philippines is hereby directed to implement this Order immediately upon receipt hereof, and to notify this Office within five (5) days from said receipt of the status of said implementation. Maj. Gen. Barbieto filed a Motion for Reconsideration [5] of the foregoing Order. Simultaneous with the proceedings before the ODO-MOLEO, the Army Investigator General (AIG) was also conducting an investigation on the same charges against Maj. Gen. Barbieto and S/Sgt. Echipare. The AIG recommended, and Lt. Gen. Yano, as CG-PA, approved, the indictment of Maj. Gen. Barbieto for violations of Articles 55 (Officer Making Unlawful Enlistment), 96 (Conduct Unbecoming of an Officer and a Gentleman), and 97 (Conduct Prejudicial to Good Order and Military Discipline); and of S/Sgt. Echipare for violations of Articles 96 and 97, all of the Articles of War. [6] On 20 February 2008, Maj. Gen. Barbieto's 10-day leave of absence took effect to pave the way for an impartial investigation. On even date, S/Sgt. Echipare was arrested and confined at the Intelligence and Security Group Compound, Fort Bonifacio, Taguig City. [7] Lt. Gen. Yano subsequently issued on 13 March 2008 an Order for the "Arrest and Confinement of Major General Barbieto AFP and SSG Echipare PA," directing the Commander of the Headquarters and Headquarters Support Group (HHSG), PA, "to arrest and take responsibility of Major General Barbieto and SSG Echipare PA x x x and to restrict them to quarters pending investigation with the end view of a General Court Martial Trial." [8] Pursuant to this Order of Arrest, Maj. Gen. Barbieto was arrested and confined to cluster officer housing, while S/Sgt. Echipare was transferred to and detained at the Custodial Management Unit (CMU), HHSG, PA, on 18 March 2008. [9] On 10 April 2008, the Office of the Army Judge Advocate (OAJA), concurring in the findings of the Pre-Trial Investigation Panel, recommended the immediate trial of Maj. Gen. Barbieto and S/Sgt. Echipare before the General Court Martial and the endorsement of the case to the AFP General Headquarters for the conduct of General Court Martial Proceedings. [10] Without waiting for the resolution by the ODO-MOLEO of his Motion for Reconsideration of the preventive suspension order issued against him in OMB-P-A-08-0201-B, Maj. Gen. Barbieto filed before the Court of Appeals a Petition for Certiorari with Prayer for the Issuance of a Temporary Restraining Order (TRO) and/or Writ of Preliminary Injunction, [11] docketed as CA-G.R. SP. No. 102874. Maj. Gen. Barbieto specifically prayed for: (1) the issuance of a TRO enjoining respondents Mary Rawnsle V. Lopez (Lopez), Graft Investigation and Prosecution Officer II; Eulogio S. Cecilio, Director; Emilio A. Gonzalez, Deputy Ombudsman for MOLEO; and Orlando C. Casimiro, Acting Ombudsman, to lift and hold in abeyance the preventive suspension order; and ordering Alexander B. Yano, Lieutenant General, Commanding General of the Philippine Army to nullify the warrant of arrest and confinement of petitioner; (2) the setting of a hearing on the preliminary injunction; and (3) after hearing on the preliminary injunction, the issuance of an order granting the injunction and making the injunction permanent, and such other and further relief as the appellate court may deem just and equitable in the premises. [12] On 4 April 2008, the Court of Appeals directed respondents to submit, within 10 days, their comment stating the reasons or justifications why the TRO and/or writ of preliminary injunction Maj. Gen. Barbieto prayed for should not be issued. [13] After the parties submitted all the required pleadings, the Court of Appeals issued a Resolution on 6 August 2008, denying Maj. Gen. Barbieto's prayer for a TRO and/or writ of preliminary injunction. The appellate court held: After due consideration of the factual circumstances of the instant case, we find no compelling reason to issue an injunctive writ and/or temporary restraining order. The surrounding facts underpinning [Maj. Gen. Barbieto]'s plea for the issuance of an injunctive relief are intimately related to and inextricably intertwined with the issues raised in the instant Petition for Certiorari . Moreover, [Maj. Gen. Barbieto] failed to demonstrate extreme urgency, as well as great or irreparable injury that he may suffer while the instant Petition is pending adjudication. x x x. x x x x Here, [Maj. Gen. Barbieto] failed to at least show a clear and unmistakable right entitling him to the issuance of a writ of preliminary injunction and/or temporary restraining order. [14] (Emphasis supplied.) The dispositive portion of the Resolution reads: WHEREFORE , [Maj. Gen. Barbieto]'s prayer for the issuance of a temporary restraining order and/or writ of preliminary injunction is hereby DENIED . [15] Maj. Gen. Barbieto moved for reconsideration of the aforementioned Resolution, but the Court of Appeals, in its Resolution [16] dated 22 September 2008, refused to do so. The appellate court stressed that before there could be a question of whether to grant or deny the prayer for a writ of preliminary injunction, Maj. Gen. Barbieto, at the onset, should have established in his pleadings the existence of the grounds enumerated in Section 3, Rule 58 of the Revised Rules of Court. It stood by its pronouncement in the earlier Resolution that Maj. Gen. Barbieto failed to demonstrate urgency, as well as great or irreparable injury that he may suffer while his Petition in CA-G.R. SP No. 102874 is pending adjudication; hence, the necessity of a hearing did not even arise. The Court of Appeals further reasoned that it could properly deny Maj. Gen. Barbieto's prayer for preliminary injunctive relief since, being an ancillary remedy, the grant of the same, which would result in a premature resolution of the case, or will grant the principal objectives of the parties, before the merits could be passed, is proscribed. The Court of Appeals decreed in its 22 September 2008 Resolution: In fine, [Maj. Gen. Barbieto]'s Motion for Reconsideration proffers no substantial issue which may warrant reversal of the assailed Resolution. WHEREFORE , the instant Motion for Reconsideration is hereby DENIED for lack of merit. [17] Hence, Maj. Gen. Barbieto filed the instant Petition before this Court, raising the following issues: THE HONORABLE COURT OF APPEALS COMMITTED GRAVE ABUSE OF DISCRETION AMOUNTING TO LACK OR EXCESS OF JURISDICTION IN DENYING PETITIONER'S PRAYER FOR INJUNCTIVE RELIEF WITHOUT HEARING IN VIOLATION OF HIS RIGHT TO PROCEDURAL DUE PROCESS OF LAW. THE HONORABLE COURT OF APPEALS COMMITTED GRAVE ABUSE OF DISCRETION AMOUNTING TO LACK OR EXCESS OF JURISDICTION IN RULING THAT PETITIONER FAILED TO DEMONSTRATE EXTREME URGENCY AS WELL AS GREAT OR IRREPARABLE INJURY THAT HE MAY SUFFER THAT SHOULD MERIT THE GRANT OF INJUNCTIVE RELIEF. THE HONORABLE COURT OF APPEALS COMMITTED GRAVE ABUSE OF DISCRETION AMOUNTING TO LACK OR EXCESS OF JURISDICTION IN RULING THAT PETITIONER MAY BE FURTHER DEPRIVED OF THE PRIMORDIAL RIGHT TO LIBERTY GUARANTEED IN THE CONSTITUTION BY A MERE PROCEDURAL CONSIDERATION THAT THE INJUNCTIVE RELIEF IS INEXTRICABLY INTERTWINED WITH THE ISSUES RAISED IN THE PETITION. During the pendency of the present Petition, an Order, [18] prepared by respondent Lopez on 27 March 2008, but approved by Ombudsman Merceditas N. Gutierrez only on 7 November 2008, denied Maj. Gen. Barbieto's Motion for Reconsideration of the preventive suspension order previously issued against Maj. Gen. Barbieto and S/Sgt. Echipare in OMB-P-A-08-0201-B. The Order cited the power of the Office of the Ombudsman to preventively suspend any public officer under Republic Act No. 6770, otherwise known as the Ombudsman Act of 1989, provided that the essential requisites under Section 24 thereof are present. The Order pointed out that this power of the Office of the Ombudsman had long been respected by the Supreme Court. Maj. Gen. Barbieto's claim that he was denied his constitutional right to due process was rejected in this latest Ombudsman Order, because: The above-concept [of due process] is not a fixed or static one, as clearly acknowledged. What is due process of the law depends on circumstances, it varies with the subject matter and necessities of the situation (Bernas, Joaquin. The Constitution of the Republic of the Philippines, p. 114 ). Considering however, that this is an administrative case, the Supreme Court has recognized that there are two (2) types of preventive suspension. Preventive suspension as a preventive measure and suspension as penalty . x x x. x x x x In the instant case, it is clear that the suspension issued is a mere preliminary step and not a penalty. Thus, the strict adherence to the rudiments of notice and hearing need not be applied due to the immediate nature of the action. [19] The same Ombudsman Order rebuffed Maj. Gen. Barbieto's contention that there was forum shopping, given the existence of two similar administrative cases against him: one, OMB-P-A-08-0201-B before the Office of the Ombudsman; and two, before the military tribunal. OMB-P-A-08-0201-B determines Maj. Gen. Barbieto's fitness as a public officer; whereas the pending administrative case before the Provost Marshall General, PA, determines his fitness and efficiency as a military officer. Therefore, the ultimate ruling in said Ombudsman Order is as follows: WHEREFORE, premises considered, the Motion for Reconsideration dated 12 March 2008, is hereby DENIED for lack of merit. The Order dated 29 February 2008 is hereby AFFIRMED. [20] Arguments of the Parties Maj. Gen. Barbieto avers in the Petition [21] at bar that the Court of Appeals committed grave abuse of discretion amounting to lack or excess of jurisdiction in denying his prayer for preliminary injunctive relief without hearing, in violation of his right to procedural due process of law; in finding that he failed to demonstrate extreme urgency, as well as great or irreparable injury that he may suffer from respondents' acts, which would have merited the grant of a TRO and/or writ of preliminary injunction; and in ruling that the preliminary injunctive relief prayed for is inextricably intertwined with the issues raised in his Petition in CA-G.R. SP No. 102874. Maj. Gen. Barbieto insists that his right to procedural due process was violated by the Court of Appeals when said court denied his prayer for a TRO and/or writ of preliminary injunction without a hearing. Maj. Gen. Barbieto invoked Supreme Court Administrative Circular No. 20-95, which provides that "an application for TRO shall be acted upon only after all parties are heard in a summary hearing x x x." [22] Maj. Gen. Barbieto further argues that all elements to warrant the grant of a writ of preliminary injunction are present in this case. His preventive suspension, merely a step in the administrative investigation against him, had already expired on 28 August 2008, and yet, he remains to be under arrest and confinement. Maj. Gen. Barbieto stresses that the urgent need for the issuance of a TRO and/or writ of preliminary injunction by the Court of Appeals is evident from the fact that he is being continuously deprived of his right to liberty. The Office of the Ombudsman counters that Maj. Gen. Barbieto's reliance on Administrative Circular No. 20-95 is misplaced, for the same applies to trial courts only. Referring to Section 4, Rule VI of the 2002 Internal Rules of the Court of Appeals, the Office of the Ombudsman posits that procedural due process has been satisfied by the appellate court when the latter issued a resolution requiring the party, whose act was sought to be enjoined, to file a comment on the application for a TRO. The denial by the Court of Appeals of Maj. Gen. Barbieto's prayer for preliminary injunctive relief was grounded on both legal and logical considerations. The grant of the ancillary remedy of TRO and/or writ of preliminary injunction would have resulted in a premature resolution of the main case of certiorari in CA-G.R. SP No. 102874 before the merits of the latter could be passed upon. The Office of the Ombudsman contends, likewise, that the expiration of Maj. Gen. Barbieto's six-month preventive suspension on 28 August 2008 renders the issue on the propriety of such suspension moot and academic. There is nothing more that an injunctive relief could seek to enjoin. Maj. Gen. Barbieto's continued confinement is no longer due to the preventive suspension order of the Ombudsman, but pursuant to Lt. Gen. Yano's Order of Arrest. Lastly, the Office of the Ombudsman maintains that none of the requisites for the issuance of a TRO and/or writ of preliminary injunction exists in the instant case. Maj. Gen. Barbieto's proper recourse is to just await the resolution of his Petition for Certiorari in CA-G.R. SP No. 102874 still pending before the Court of Appeals, which involved the issue of the legality of his continued confinement. Lt. Gen. Yano substantially joins in and/or adopts the arguments of the Office of the Ombudsman. He additionally asserts that there is no reason to enjoin the enforcement of the Order of Arrest against Maj. Gen. Barbieto, citing his authority as CG-PA to issue the same, pursuant to the Articles of War. The Ruling of the Court At the onset, the Court must clarify that Maj. Gen. Barbieto is actually seeking a TRO and/or a writ of preliminary injunction to enjoin the implementation of two distinct orders, issued by two different persons, in two separate proceedings: (1) the preventive suspension order issued by the ODO-MOLEO in OMB-P-A-08-0201-B; and (2) the Order of Arrest issued by Lt. Gen. Yano as CG-PA in view of the impending General Court Martial Trial. The preventive suspension order issued by the ODO-MOLEO merely suspended Maj. Gen. Barbieto from his office for six months, pending the administrative proceedings against the latter. [23] There is nothing in said preventive suspension order of the ODO-MOLEO that directed Maj. Gen. Barbieto's arrest. His arrest and continued confinement is solely by virtue of Lt. Gen. Yano's Order. The Court takes note of the undisputed fact that Maj. Gen. Barbieto's six-month suspension, imposed by the ODO-MOLEO in an Order dated 28 February 2008 in OMB-P-A-08-0201-B, already expired on 28 August 2008 . Such an event necessarily renders this Petition moot and academic, insofar as the latter pertains to the said preventive suspension order issued by the ODO-MOLEO against Maj. Gen. Barbieto. Any ruling by this Court, whether affirming or reversing the denial by the appellate court of Maj. Gen. Barbieto's prayer for issuance of a TRO and/or writ of preliminary injunction to enjoin the implementation of said preventive suspension order, will no longer serve any practical purpose, because the act sought to be enjoined has long been consummated. [24] Time and again, courts have refrained from even expressing an opinion in a case where the issues have become moot and academic, there being no more justiciable controversy to speak of, so that a determination thereof would be of no practical use or value. [25] Where the issue has become moot and academic, there is no actual substantial relief to which Maj. Gen. Barbieto would be entitled and which would be negated by the dismissal of his Petition as regards the preventive suspension order of the ODO-MOLEO. [26] Similarly, the Court finds the present Petition, insofar as it concerns Lt. Gen. Yano's Order of Arrest against Maj. Gen. Barbieto, dismissible for lack of merit. Sine dubio, the grant or denial of a writ of preliminary injunction in a pending case rests on the sound discretion of the court taking cognizance of the case, since the assessment and evaluation of evidence towards that end involves findings of facts left to the said court for its conclusive determination. Hence, the exercise of judicial discretion by a court in injunctive matters must not be interfered with, except when there is grave abuse of discretion. [27] Grave abuse of discretion means such capricious and whimsical exercise of judgment as is equivalent to lack of jurisdiction. Mere abuse of discretion is not enough. It must be grave abuse of discretion, as when the power is exercised in an arbitrary or despotic manner by reason of passion or personal hostility, and must be so patent and so gross as to amount to an evasion of a positive duty or to a virtual refusal to perform the duty enjoined or to act at all in contemplation of law. [28] The Court of Appeals did not gravely abuse its discretion in refusing to issue a TRO and/or writ of preliminary injunction to enjoin the enforcement of Lt. Gen. Yano's Order of Arrest against Maj. Gen. Barbieto. Maj. Gen. Barbieto cannot rely on Supreme Court Administrative Circular No. 20-95, providing special rules for temporary restraining orders and preliminary injunctions, to support his claim that he was denied due process when the Court of Appeals denied his prayer for the issuance of a TRO and/or writ of preliminary injunction without first conducting a summary hearing. The whole text of said Administrative Circular is reproduced below: 1. Where an application for temporary restraining order (TRO) or writ of preliminary injunction is included in a complaint or any initiatory pleading filed with the trial court , such compliant or initiatory pleading shall be raffled only after notice to the adverse party and in the presence of such party or counsel. 2. The application for a TRO shall be acted upon only after all parties are heard in a summary hearing conducted within twenty-four (24) hours after the records are transmitted to the branch selected by raffle . The records shall be transmitted immediately after raffle. 3. If the matter is of extreme urgency, such that unless a TRO is issued, grave injustice and irreparable injury will arise, the Executive Judge shall issue the TRO effective only for seventy-two (72) hours from issuance but shall immediately summon the parties for conference and immediately raffle the case in their presence. Thereafter, before the expiry of the seventy-two (72) hours, the Presiding Judge to whom the case is assigned shall conduct a summary hearing to determine whether the TRO can be extended for another period until a hearing in the pending application for preliminary injunction can be conducted. In no case shall the total period of the TRO exceed twenty (20) days, including the original seventy-two (72) hours, for the TRO issued by the Executive Judge. 4. With the exception of the provisions which necessarily involve multiple-sala stations , these rules shall apply to single-sala stations especially with regard to immediate notice to all parties of all applications for TRO. For immediate compliance. (Emphases ours.) Maj. Gen. Barbieto overlooked that Supreme Court Administrative Circular No. 20-95 pertains to applications for TROs and/or writs of preliminary injunctions filed before trial courts, whether multi- sala or single- sala . The Court of Appeals has its own Internal Rules. Section 2, Rule IV of the 2002 Internal Rules of the Court of Appeals provides the following procedure in the case of a petition involving an urgent matter, such as an application for a TRO: Sec. 2. Action by the Presiding Justice. -When a petition involves an urgent matter, such as an application for writ of habeas corpus or temporary restraining order, and there is no way of convening the Raffle Committee or calling any of its members, the Presiding Justice may conduct the raffle or act on the petition , subject to raffle on the next working day in accordance with Rule III hereof. (Emphasis ours.) Noticeably, under the aforementioned circumstances, the Presiding Justice of the Court of Appeals may even, by himself, act on an urgent application for a TRO. There is no mention at all of the requirement that the Presiding Justice must hold a summary hearing prior to granting or denying such an application. As for a preliminary injunction, Section 4, Rule VI of the 2002 Internal Rules of the Court of Appeals lays down the following procedure: Sec. 4. Hearing on Preliminary Injunction.-- The requirement of a hearing on an application for preliminary injunction is satisfied with the issuance by the Court of a resolution served upon the party sought to be enjoined requiring him to comment on said application within a period of not more thanten (10) days from notice. Said party may attach to his comment documents which may show why the application for preliminary injunction should be denied. The Court may require the party seeking the injunctive relief to file his reply to the comment within five (5) days from receipt of the latter. If the party sought to be enjoined fails to file his comment as provided for in the preceding paragraph, the Court may resolve the application on the basis of the petition and its annexes. The preceding paragraphs, notwithstanding, the Court may, in its sound discretion, set the application for a preliminary injunction for hearing during which the parties may present their respective positions or submit evidence in support thereof. (Emphases ours.) Based on the foregoing rule, the Court of Appeals clearly satisfied the requirement of a hearing when, in its Resolution dated 4 April 2008 in CA-G.R. SP No. 102874, it directed respondents to submit their comment on Maj. Gen. Barbieto's prayer for the issuance of a TRO and/or writ of preliminary injunction within ten days from notice. [29] While it is true that the right to due process safeguards the opportunity to be heard and to submit any evidence one may have in support of his claim or defense, the Court has time and again held that where the opportunity to be heard, either through verbal arguments or pleadings, is accorded, and the party can "present its side" or defend its "interest in due course," there is no denial of due process. What the law proscribes is the lack of opportunity to be heard. [30] The last paragraph of Section 4, Rule VI of the 2002 Internal Rules of the Court of Appeals also proves false Maj. Gen. Barbieto's contention that the actual conduct of a hearing on an application for preliminary injunction is mandatory. Said rule explicitly states that the setting of a hearing on such an application is left to the sound discretion of the appellate court. Hence, it is not enough for Maj. Gen. Barbieto to show that no hearing on his application for TRO and/or preliminary injunction was conducted by the Court of Appeals, but he must also be able to convince this Court that the appellate court gravely abused its discretion in choosing not to conduct such a hearing. Maj. Gen. Barbieto likewise failed in this regard. The Court, in Philippine Ports Authority v. Cipres Stevedoring & Arrastre, Inc. , [31] provided the following elucidation on the general principles in issuing a writ of preliminary injunction: A preliminary injunction is an order granted at any stage of an action prior to judgment of final order, requiring a party, court, agency, or person to refrain from a particular act or acts. It is a preservative remedy to ensure the protection of a party's substantive rights or interests pending the final judgment in the principal action. A plea for an injunctive writ lies upon the existence of a claimed emergency or extraordinary situation which should be avoided for otherwise, the outcome of a litigation would be useless as far as the party applying for the writ is concerned. At times referred to as the "Strong Arm of Equity," we have consistently ruled that there is no power the exercise of which is more delicate and which calls for greater circumspection than the issuance of an injunction. It should only be extended in cases of great injury where courts of law cannot afford an adequate or commensurate remedy in damages;"in cases of extreme urgency; where the right is very clear; where considerations of relative inconvenience bear strongly in complainant's favor; where there is a willful and unlawful invasion of plaintiff's right against his protest and remonstrance, the injury being a continuing one, and where the effect of the mandatory injunction is rather to reestablish and maintain a preexisting continuing relation between the parties, recently and arbitrarily interrupted by the defendant, than to establish a new relation." For the writ to issue, two requisites must be present, namely, the existence of the right to be protected, and that the facts against which the injunction is to be directed are violative of said right. x x x. A writ of preliminary injunction may be granted only upon showing by the applicant of a clear and unmistakable right that is a right in esse . Maj. Gen. Barbieto claims that his right in esse that is being violated herein is his right to liberty. Indeed, Section I, Article III of the 1987 Constitution, guarantees that no person may be deprived of life, liberty, or property without due process of law. Also, the Republic of the Philippines, as a signatory to the Universal Declaration of Human Rights (UDHR), recognizes that everyone has the right to liberty and security of one's person. No one shall be subjected to arbitrary arrest or detention. No one shall be deprived of his liberty except on such grounds and in accordance with such procedure as are established by law. [32] Nevertheless, the right to liberty is not absolute. It bears to point out that while both the 1987 Constitution and the UDHR affirm the right of every person to liberty, they do concede that there are instances when a person must be deprived thereof for as long as due process of law has been observed. Thus, Maj. Gen. Barbieto cannot just invoke herein his fundamental right to liberty; upon him also falls the burden of proving that he is being deprived of such right without due process. To recall, Lt. Gen. Yano ordered Maj. Gen. Barbieto's arrest after the conduct of an investigation by and the recommendation of the AIG that Maj. Gen. Barbieto be charged before a court martial with violations of Articles 55 (Officer Making Unlawful Enlistment), 96 (Conduct Unbecoming of an Officer and Gentleman), and 97 (Conduct Prejudicial to Good Order and Military Discipline) of the Articles of War. Since Maj. Gen. Barbieto is being charged with serious offenses, Lt. Gen. Yano issued the Order of Arrest for the former under Article 70 of the Articles of War: Art. 70. Arrest or Confinement. - Any person subject to military law charged with crime or with a serious offense under these articles shall be placed in confinement or in arrest, as circumstances require ; but when charged with a minor offense only, such person shall not ordinarily be placed in confinement. Any person placed in arrest under the provisions of this Article, shall thereby be restricted to his barracks, quarters or tent, unless such limits shall be enlarged by proper authority. Any officer or cadet who breaks his arrest or who escapes from confinement, whether before or after trial or sentence and before he is set at liberty by proper authority, shall be dismissed from the service or suffer such other punishment as a court-martial may direct, and any other person subject to military law who escapes from confinement or who breaks his arrest, whether before or after trial or sentence and before he is set at liberty by proper authority, shall be punished as a court martial may direct. (Emphases ours.) Now, is Lt. Gen. Yano's issuance of the Order of Arrest under the aforedescribed circumstances violative of Maj. Gen. Barbieto's right to liberty and due process? The Court accords to Lt. Gen. Yano the presumption of good faith and regularity in the issuance of said Order of Arrest, having done the same in the course of the performance of his official duties. Other than this, the Court cannot make any more pronouncements on the matter. Suffice it to say that the need for a more extensive determination of said question, by itself, already negates Maj. Gen. Barbieto's insistence of a clear and well-established right that warrants the protection of a TRO and/or writ of preliminary injunction. Where the complainant's (or in this case, petitioner's) right is doubtful or disputed, injunction is not proper. [33] The Court must limit itself in the Petition at bar to the issue on the non-issuance by the Court of Appeals of a TRO and/or writ of preliminary injunction to prevent the enforcement of Maj. Gen. Barbieto's arrest. It must be careful not to preempt the resolution by the Court of Appeals of Maj. Gen. Barbieto's Petition for Certiorari in CA-G.R. SP No. 102874, wherein the propriety of his arrest and continued confinement is one of the central issues. The prevailing rule is that the courts should avoid issuing a writ of preliminary injunction that would in effect dispose of the main case without trial. Otherwise, there would be a prejudgment of the main case and a reversal of the rule on the burden of proof, since such issuance would assume the proposition that Maj. Gen. Barbieto is inceptively bound to prove. [34] WHEREFORE , the instant Petition is DISMISSED . The Resolutions dated 6 August 2008 and 22 September 2008 of the Court of Appeals in CA-G.R. SP No. 102874 are AFFIRMED . The Court of Appeals is DIRECTED to resolve petitioner Maj. Gen. Jose T. Barbieto's Petition for Certiorari in CA-G.R. SP No. 102874 with dispatch. Costs against petitioner. S O ORDERED. Quisumbing, * Carpio, (Chairperson), Peralta, and Abad, ** JJ. concur. * Per Special Order No. 755, dated 12 October 2009, signed by Chief Justice Reynato S. Puno designating Associate Justice Leonardo A. Quisumbing to replace Associate Justice Antonio Eduardo B. Nachura, who is on official leave. ** Per Special Order No. 753, dated 12 October 2009, signed by Chief Justice Reynato S. Puno designating Associate Justice Roberto A. Abad to replace Associate Justice Presbitero J. Velasco, Jr., who is on official leave. [1] Penned by Associate Justice Japar B. Dimaampao with Associate Justices Amelita G. Tolentino and Sixto C. Marella, Jr., concurring; rollo, pp. 30-33. [2] Rollo, pp. 23-25. [3] Id. at 185-186. [4] Id. at 131. [5] Id. at 187. [6] Id. at 45-75. [7] Id . [8] Id. [9] Id. [10] Id . [11] Id. at 187. [12] CA rollo , pp. 2-20. [13] Rollo , p. 182. [14] Id. at 32-33. [15] Id. at 33. [16] Id. at 23-25. [17] Id. at 25. [18] See Office of the Ombudsman's back-up file. [19] Id. at 3-4. [20] Id. at 6. [21] Rollo, pp. 3-18. [22] Paragraph (2) of Supreme Court Administrative Circular No. 20-95. [23] The authority of the ODO-MOLEO to suspend Maj. Gen. Barbieto is rooted in Section 24 of Republic Act No. 6770, which reads: SEC. 24. Preventive Suspension . -- The Ombudsman or his Deputy may preventively suspend any officer or employee under his authority pending an investigation, if in his judgment the evidence of guilt is strong, and (a) the charge against such officer or employee involves dishonesty, oppression or grave misconduct or neglect in the performance of duty; or (b) the charges would warrant removal from the service; or (c) the respondent's continued stay in office may prejudice the case filed against him. The preventive suspension shall continue until the case is terminated by the Office of the Ombudsman but not more than six months, without pay, except when the delay in the disposition of the case by the Office of the Ombudsman is due to the fault, negligence or petition of the respondent, in which case the period of such delay shall not be counted in computing the period of suspension herein provided. [24] Africa v. Sandiganbayan , 350 Phil. 846, 857-858 (1998). [25] Engaño v. Court of Appeals , G.R. No. 156959, 27 June 2006, 493 SCRA 323, 329. [26] Gancho-on v. Secretary of Labor and Employment , 337 Phil. 654, 658 (1997). [27] Cortez-Estrada v. Heirs of Domingo Samut , 491 Phil. 458, 473-474 (2005). [28] Neri v. Senate Committee on Accountability of Public Officers and Investigations, Senate Committee on Trade and Commerce, and Senate Committee on National Defense and Security , G.R. No. 180643, 25 March 2008, 549 SCRA 77, 131. [29] Rollo , p. 182. [30] Ko v. Philippine National Bank , G.R. Nos. 169131-32, 20 January 2006, 479 SCRA 298, 305-306. [31] G.R. No. 145742, 14 July 2005, 463 SCRA 358, 373-374. [32] See The Secretary of National Defense v. Manalo , G.R. No. 180906, 7 October 2008, 568 SCRA 1, 49-50. [33] Tayag v. Lacson , G.R. No. 134971, 25 March 2004, 426 SCRA 282, 299. [34] See Philippine Ports Authority v. Pier 8 Arrastre & Stevedoring Services, Inc. , G.R. Nos. 147861 & 155252, 18 November 2005, 475 SCRA 426, 441. tags
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windy & cold south - less windy north europe - uk forecast Thursday A cloudy and bitterly cold start to the morning across many eastern, southern and central parts of the country. There will be a few... UK Forecast - January 26, 2011 Windy & cold south Less windy north <here is a image 8e524f28116ea94a-007f44eac7cf7b50> ThursdayA cloudy and bitterly cold start to the morning across many eastern, southern and central parts of the country. There will be a few spots of rain on high ground, although for most it should be dry. A narrow but more persistent area of rain may turn to wet snow across parts of Essex, Suffolk and into the London area this morning. A stiff east to northeast wind is going to be blowing across more southern areas and this will be making it feel very cold here. To the north and west it will be brighter and dry with some sunny spells. Through the afternoon very little is going to change with southernScotland, much of England and eastern Wales seeing most of the cloud. It should be dry overall, although feeling cold in the stiff wind. Brighter spells through more western parts of Scotland, Wales and Ireland and generally dry too. Highs near 1 to 4C. <here is a image 92a5de18f545d212-28e1326ffecfb45a> Thursday NightA rather cloudy night to come across much of the country. Eastern andsouthern areasseeing most of the cloud, although there is going to be a tendency for this to be breaking during the second half of the night, allowing some clearer spells to develop. More northern and western areas seeing dry weather and clearer skies throughout. Staying windy to the south but much lighter winds to the north. Lows near -2 to -4C. <here is a image dceeca94a65d1c57-6d30d31607ba1ef7> FridayHigh pressure will be centred acrossnorthern Englandthrough Friday with a strong northeast flow affecting southern parts of the country, and an increasing southwest wind in northern Scotland. It is likely to be a dry day for all parts, although forecasting how much cloud there will be is proving tricky. It does seem that the south and east is likely to see most cloud, but this should be breaking up allowing sunny spells to come through. More sunshine to the north and west although the threat of some fog patches at first in northern England. Highs near 1 to 4C and feeling bitterly cold in the wind in the south. <here is a image 3a46d0874cbf3288-47070b08ee829bde> SaturdayPressure remains high across the country on Saturday, although the centre of the high pressure slips to the west of Ireland. Weak fronts push south through Scotland and northern England increasing cloud here and bringing a threat of some light rain. To the south there will be broken cloud and largely dry conditions. Some sunny spells are likely with the best of them always to the west. Although breezy, the winds will be lighter than the previous few days. Still feeling cold with highs of 5C in northern Scotland, 3 or 4C over much of England andWales. Weather Report  [January 26, 2011] Morning Call [Jan 26 - 07:01]<here is a image 9d7f2cd12a0d13b9-9c540a1dcfbf3d2b> Dull and damp-Breezy for many ...<here is a image 0333b4292a997f8a-5309624d44ea23ad> UK Forecast [Jan 26 - 17:29]<here is a image 9d7f2cd12a0d13b9-9c540a1dcfbf3d2b> Windy & cold south-Less windy north ...<here is a image 0333b4292a997f8a-5309624d44ea23ad> Week ahead [Jan 26 - 11:49]<here is a image 9d7f2cd12a0d13b9-9c540a1dcfbf3d2b> Generally dry-High pressure dominates ...<here is a image 0333b4292a997f8a-5309624d44ea23ad> Month ahead [Jan 25 - 21:50]<here is a image 9d7f2cd12a0d13b9-9c540a1dcfbf3d2b> Valid from 29/01 to 25/02 2011-Cold weather returning? ...<here is a image 0333b4292a997f8a-5309624d44ea23ad> Monthly Lookback [Jan 07 - 10:32]<here is a image 9d7f2cd12a0d13b9-9c540a1dcfbf3d2b> December 2010 Lookback-Coldest since 1890 ...<here is a image 0333b4292a997f8a-5309624d44ea23ad> Europe Forecast [Jan 26 - 07:00]<here is a image 9d7f2cd12a0d13b9-9c540a1dcfbf3d2b> Wet to south-Cold in the north ... Topics  [January 26, 2011] WMO: 2010 warmest ever year GENEVA, Jan 20, 2011 (AFP) - The UN's World Meteorological Organisation said Thursday that 2010 was ...<here is a image 0333b4292a997f8a-5309624d44ea23ad> Thousands of Russians jump in ice MOSCOW, Jan 19, 2011 (AFP) - Thousands of Russians jumped into holes cut in ice on Monday night and ...<here is a image 0333b4292a997f8a-5309624d44ea23ad> Brazil: The situation is dramatic NOVA FRIBURGO, Brazil, Jan 16, 2011 (AFP) - The Brazilian military took advantage of a break in the ...<here is a image 0333b4292a997f8a-5309624d44ea23ad>
https://www.woeurope.eu/weather/reports/uk-forecast/windy--cold-south-less-windy-north.2.20110126.htm