Search results for: evidence for policy

Authors: Eli Avraham

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The Arab Spring was widely covered in the global media and the number of Western tourists traveling to the area began to fall. The goal of this study was to analyze which media strategies marketers in Middle Eastern countries chose to employ in their attempts to repair the negative image of the area in the wake of the Arab Spring. Several studies were published concerning image-restoration strategies of destinations during crises around the globe; however, these strategies were not part of an overarching theory, conceptual framework or model from the fields of crisis communication and image repair. The conceptual framework used in the current study was the ‘multi-step model for altering place image’, which offers three types of strategies: source, message and audience. Three research questions were used: 1.What public relations crisis techniques and advertising campaign components were used? 2. What media policies and relationships with the international media were adopted by Arab officials? 3. Which marketing initiatives (such as cultural and sports events) were promoted? This study is based on qualitative content analysis of four types of data: 1) advertising components (slogans, visuals and text); (2) press interviews with Middle Eastern officials and marketers; (3) official media policy adopted by government decision-maker (e.g. boycotting or arresting newspeople); and (4) marketing initiatives (e.g. organizing heritage festivals and cultural events). The data was located in three channels from December 2010, when the events started, to September 31, 2013: (1) Internet and video-sharing websites: YouTube and Middle Eastern countries' national tourism board websites; (2) News reports from two international media outlets, The New York Times and Ha’aretz; these are considered quality newspapers that focus on foreign news and tend to criticize institutions; (3) Global tourism news websites: eTurbo news and ‘Cities and countries branding’. Using the ‘multi-step model for altering place image,’ the analysis reveals that Middle Eastern marketers and officials used three kinds of strategies to repair their countries' negative image: 1. Source (cooperation and media relations; complying, threatening and blocking the media; and finding alternatives to the traditional media) 2. Message (ignoring, limiting, narrowing or reducing the scale of the crisis; acknowledging the negative effect of an event’s coverage and assuring a better future; promotion of multiple facets, exhibitions and softening the ‘hard’ image; hosting spotlight sporting and cultural events; spinning liabilities into assets; geographic dissociation from the Middle East region; ridicule the existing stereotype) and 3. Audience (changing the target audience by addressing others; emphasizing similarities and relevance to specific target audience). It appears that dealing with their image problems will continue to be a challenge for officials and marketers of Middle Eastern countries until the region stabilizes and its regional conflicts are resolved.

Keywords: Arab spring, cultural events, image repair, Middle East, tourism marketing

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Authors: Haji Mohammad Zulfan Farhi Bin Haji Sulaini, Mohammad Azeezudde’en Bin Mohd Ismaon

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The demands placed on military athletes extend beyond physical prowess to encompass cognitive resilience in high-stress environments. This study investigates the effects of resilience training on the cognitive performance of military athletes, shedding light on the potential benefits and implications for optimizing their overall readiness. In a rapidly evolving global landscape, armed forces worldwide are recognizing the importance of cognitive resilience alongside physical fitness. The study employs a mixed-methods approach, incorporating quantitative cognitive assessments and qualitative data from military athletes undergoing resilience training programs. Cognitive performance is evaluated through a battery of tests, including measures of memory, attention, decision-making, and reaction time. The participants, drawn from various branches of the military, are divided into experimental and control groups. The experimental group undergoes a comprehensive resilience training program, while the control group receives traditional physical training without a specific focus on resilience. The initial findings indicate a substantial improvement in cognitive performance among military athletes who have undergone resilience training. These improvements are particularly evident in domains such as attention and decision-making. The experimental group demonstrated enhanced situational awareness, quicker problem-solving abilities, and increased adaptability in high-stress scenarios. These results suggest that resilience training not only bolsters mental toughness but also positively impacts cognitive skills critical to military operations. In addition to quantitative assessments, qualitative data is collected through interviews and surveys to gain insights into the subjective experiences of military athletes. Preliminary analysis of these narratives reveals that participants in the resilience training program report higher levels of self-confidence, emotional regulation, and an improved ability to manage stress. These psychological attributes contribute to their enhanced cognitive performance and overall readiness. Moreover, this study explores the potential long-term benefits of resilience training. By tracking participants over an extended period, we aim to assess the durability of cognitive improvements and their effects on overall mission success. Early results suggest that resilience training may serve as a protective factor against the detrimental effects of prolonged exposure to stressors, potentially reducing the risk of burnout and psychological trauma among military athletes. This research has significant implications for military organizations seeking to optimize the performance and well-being of their personnel. The findings suggest that integrating resilience training into the training regimen of military athletes can lead to a more resilient and cognitively capable force. This, in turn, may enhance mission success, reduce the risk of injuries, and improve the overall effectiveness of military operations. In conclusion, this study provides compelling evidence that resilience training positively impacts the cognitive performance of military athletes. The preliminary results indicate improvements in attention, decision-making, and adaptability, as well as increased psychological resilience. As the study progresses and incorporates long-term follow-ups, it is expected to provide valuable insights into the enduring effects of resilience training on the cognitive readiness of military athletes, contributing to the ongoing efforts to optimize military personnel's physical and mental capabilities in the face of ever-evolving challenges.

Keywords: military athletes, cognitive performance, resilience training, cognitive enhancement program

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Authors: Kavita Goel, Donald Winchester

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In a world of information overload and work complexities, academics often struggle to create an online instructional environment enabling efficient and effective student learning. Research has established that students’ learning styles are different, some learn faster when taught using audio and visual methods. Attributes like prior knowledge and mental effort affect their learning. ‘Cognitive load theory’, opines learners have limited processing capacity. Cognitive load depends on the learner’s prior knowledge, the complexity of content and tasks, and instructional environment. Hence, the proper allocation of cognitive resources is critical for students’ learning. Consequently, a lecturer needs to understand the limits and strengths of the human learning processes, various learning styles of students, and accommodate these requirements while designing online assessments. As acknowledged in the cognitive load theory literature, visual and auditory explanations of worked examples potentially lead to a reduction of cognitive load (effort) and increased facilitation of learning when compared to conventional sequential text problem solving. This will help learner to utilize both subcomponents of their working memory. Instructional design changes were introduced at the case site for the delivery of the postgraduate business subjects. To make effective use of auditory and visual modalities, video recorded lectures, and key concept webinars were delivered to students. Videos were prepared to free up student limited working memory from irrelevant mental effort as all elements in a visual screening can be viewed simultaneously, processed quickly, and facilitates greater psychological processing efficiency. Most case study students in the postgraduate programs are adults, working full-time at higher management levels, and studying part-time. Their learning style and needs are different from other tertiary students. The purpose of the audio and visual interventions was to lower the students cognitive load and provide an online environment supportive to their efficient learning. These changes were expected to impact the student’s learning experience, their academic performance and retention favourably. This paper posits that these changes to instruction design facilitates students to integrate new knowledge into their long-term memory. A mixed methods case study methodology was used in this investigation. Primary data were collected from interviews and survey(s) of students and academics. Secondary data were collected from the organisation’s databases and reports. Some evidence was found that the academic performance of students does improve when new instructional design changes are introduced although not statistically significant. However, the overall grade distribution of student’s academic performance has changed and skewed higher which shows deeper understanding of the content. It was identified from feedback received from students that recorded webinars served as better learning aids than material with text alone, especially with more complex content. The recorded webinars on the subject content and assessments provides flexibility to students to access this material any time from repositories, many times, and this enhances students learning style. Visual and audio information enters student’s working memory more effectively. Also as each assessment included the application of the concepts, conceptual knowledge interacted with the pre-existing schema in the long-term memory and lowered student’s cognitive load.

Keywords: cognitive load theory, learning style, instructional environment, working memory

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Authors: Olia Kanevskaia

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Standardization has been in the limelight of numerous academic studies. Typically described as ‘any set of technical specifications that either provides or is intended to provide a common design for a product or process’, standards do not only set quality benchmarks for products and services, but also spur competition and innovation, resulting in advantages for manufacturers and consumers. Their contribution to globalization and technology advancement is especially crucial in the Information and Communication Technology (ICT) and telecommunications sector, which is also characterized by a weaker state-regulation and expert-based rule-making. Most of the standards developed in that area are interoperability standards, which allow technological devices to establish ‘invisible communications’ and to ensure their compatibility and proper functioning. This type of standard supports a large share of our daily activities, ranging from traffic coordination by traffic lights to the connection to Wi-Fi networks, transmission of data via Bluetooth or USB and building the network architecture for the Internet of Things (IoT). A large share of ICT standards is developed in the specialized voluntary platforms, commonly referred to as Standards Development Organizations (SDOs), which gather experts from various industry sectors, private enterprises, governmental agencies and academia. The institutional architecture of these bodies can vary from semi-public bodies, such as European Telecommunications Standards Institute (ETSI), to industry-driven consortia, such as the Internet Engineering Task Force (IETF). The past decades witnessed a significant shift of standard setting to those institutions: while operating independently from the states regulation, they offer a rather informal setting, which enables fast-paced standardization and places technical supremacy and flexibility of standards above other considerations. Although technical norms and specifications developed by such nongovernmental platforms are not binding, they appear to create significant regulatory impact. In the United States (US), private voluntary standards can be used by regulators to achieve their policy objectives; in the European Union (EU), compliance with harmonized standards developed by voluntary European Standards Organizations (ESOs) can grant a product a free-movement pass. Moreover, standards can de facto manage the functioning of the market when other regulative alternatives are not available. Hence, by establishing (potentially) mandatory norms, SDOs assume regulatory functions commonly exercised by States and shape their own legal order. The purpose of this paper is threefold: First, it attempts to shed some light on SDOs’ institutional architecture, focusing on private, industry-driven platforms and comparing their regulatory frameworks with those of formal organizations. Drawing upon the relevant scholarship, the paper then discusses the extent to which the formulation of technological standards within SDOs constitutes a private legal order, operating in the shadow of governmental regulation. Ultimately, this contribution seeks to advise whether a state-intervention in industry-driven standard setting is desirable, and whether the increasing regulatory importance of SDOs should be addressed in legislation on standardization.

Keywords: private order, standardization, standard-setting organizations, transnational law

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Authors: Yu-Hsin Tsai

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A new, mandated county regional plan system has been initiated since 2010 nationwide in Taiwan, with its role situated in-between the policy-led cross-county regional plan and the blueprint-led city plan. This new regional plan contain both urban and rural areas in one single plan, which provides a more complete planning territory, i.e., city region within the county’s jurisdiction, and to be executed and managed effectively by the county government. However, the full picture of its functions and characteristics seems still not totally clear, compared with other levels of plans; either are planning goals and issues that can be most appropriately dealt with at this spatial scale. In addition, the extent to which the inclusion of sustainability ideal and measures to cope with climate change are unclear. Based on the above issues, this study aims to clarify the roles of county regional plan, to analyze the extent to which the measures cope with sustainability, climate change, and forecasted declining population, and the success factors and issues faced in the planning process. The methodology applied includes literature review, plan quality evaluation, and interview with officials of the central and local governments and urban planners involved for all the 23 counties in Taiwan. The preliminary research results show, first, growth management related policies have been widely implemented and expected to have effective impact, including incorporating resources capacity to determine maximum population for the city region as a whole, developing overall vision of urban growth boundary for all the whole city region, prioritizing infill development, and use of architectural land within urbanized area over rural area to cope with urban growth. Secondly, planning-oriented zoning is adopted in urban areas, while demand-oriented planning permission is applied in the rural areas with designated plans. Then, public participation has been evolved to the next level to oversee all of government’s planning and review processes due to the decreasing trust in the government, and development of public forum on the internet etc. Next, fertile agricultural land is preserved to maintain food self-supplied goal for national security concern. More adoption-based methods than mitigation-based methods have been applied to cope with global climate change. Finally, better land use and transportation planning in terms of avoiding developing rail transit stations and corridor in rural area is promoted. Even though many promising, prompt measures have been adopted, however, challenges exist to surround: first, overall urban density, likely affecting success of UGB, or use of rural agricultural land, has not been incorporated, possibly due to implementation difficulties. Second, land-use related measures to mitigating climate change seem less clear and hence less employed. Smart decline has not drawn enough attention to cope with predicted population decrease in the next decade. Then, some reluctance from county’s government to implement county regional plan can be observed vaguely possibly since limits have be set on further development on agricultural land and sensitive areas. Finally, resolving issue on existing illegal factories on agricultural land remains the most challenging dilemma.

Keywords: city region plan, sustainability, global climate change, growth management

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Authors: Elena Sherstoboeva, Elena Karzanova

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This paper explores the impact of the annexation of Crimea on the regulation of live performances and tour management of Russian pop music performers in Ukraine and of Ukrainian performers in Russia. Without a doubt, the cultural relationship between Russia and Ukraine is not limited to this issue. Yet concert markets tend to respond particularly rapidly to political, economic, and social changes, especially in Russia and Ukraine, where the high level of digital piracy means that the music businesses mainly depend upon income from performances rather than from digital rights sales. This paper argues that the rules formed in both countries after Russia’s annexation of Crimea in 2014 have contributed to the separation of a single cultural space that had existed in Soviet and Post-Soviet Russia and Ukraine before the annexation. These rules have also facilitated performers’ self-censorship and increased the politicisation of the music businesses in the two neighbouring countries. This study applies a comparative socio-legal approach to study Russian and Ukrainian live events and tour regulation. A qualitative analysis of Russian and Ukrainian national and intergovernmental legal frameworks is applied to examine formal regulations. Soviet and early post-Soviet laws and policies are also studied, but only to the extent that they help to track the changes in the Russian–Ukrainian cultural relationship. To identify and analyse the current informal rules, the study design includes in-depth semi-structured interviews with 30 live event or tour managers working in Russia and Ukraine. A case study is used to examine how the Eurovision Song Contest, an annual international competition, has played out within the Russian–Ukrainian conflict. The study suggests that modern Russian and Ukrainian frameworks for live events and tours have developed Soviet regulatory traditions when cultural policies served as a means of ideological control. At the same time, contemporary regulations mark a considerable perspective shift, as the previous rules have been aimed at maintaining close cultural connections between the Russian and Ukrainian nations. Instead of collaboration, their current frameworks mostly serve as forms of repression, implying that performers must choose only one national market in which to work. The regulatory instruments vary and often impose limitations that typically exist in non-democratic regimes to restrict foreign journalism, such as visa barriers or bans on entry. The more unexpected finding is that, in comparison with Russian law, Ukrainian regulations have created more obstacles to the organisation of live tours and performances by Russian artists in Ukraine. Yet this stems from commercial rather than political factors. This study predicts that the more economic challenges the Russian or Ukrainian music businesses face, the harsher the regulations will be regarding the organisation of live events or tours in the other country. This study recommends that international human rights organisations and non-governmental organisations develop and promote specific standards for artistic rights and freedoms, given the negative effects of the increasing politicisation of the entertainment business and cultural spheres to freedom of expression and cultural rights and pluralism.

Keywords: annexation of Crimea, artistic freedom, censorship, cultural policy

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Authors: Catherine P. Bradshaw, Elise T. Pas, Katrina J. Debnam, Jessika H. Bottiani, Michael Rosenberg

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Worldwide, ethnically and culturally diverse students are at increased risk for school failure, discipline problems, and dropout. Despite decades of concern about this issue of disparities in education and other fields (e.g., 'school to prison pipeline'), there has been limited empirical examination of models that can actually reduce these gaps in schools. Moreover, few studies have examined the effectiveness of in-service teacher interventions and supports specifically designed to reduce discipline disparities and improve student engagement. This session provides an overview of the evidence-based Double Check model which serves as a framework for teachers to use culturally-responsive strategies to engage ethnically and culturally diverse students in the classroom and reduce discipline problems. Specifically, Double Check is a school-based prevention program which includes three core components: (a) enhancements to the school-wide Positive Behavioral Interventions and Supports (PBIS) tier-1 level of support; (b) five one-hour professional development training sessions, each of which addresses five domains of cultural competence (i.e., connection to the curriculum, authentic relationships, reflective thinking, effective communication, and sensitivity to students’ culture); and (c) coaching of classroom teachers using an adapted version of the Classroom Check-Up, which intends to increase teachers’ use of effective classroom management and culturally-responsive strategies using research-based motivational interviewing and data-informed problem-solving approaches. This paper presents findings from a randomized controlled trial (RCT) testing the impact of Double Check, on office discipline referrals (disaggregated by race) and independently observed and self-reported culturally-responsive practices and classroom behavior management. The RCT included 12 elementary and middle schools; 159 classroom teachers were randomized either to receive coaching or serve as comparisons. Specifically, multilevel analyses indicated that teacher self-reported culturally responsive behavior management improved over the course of the school year for teachers who received the coaching and professional development. However, the average annual office discipline referrals issued to black students were reduced among teachers who were randomly assigned to receive coaching relative to comparison teachers. Similarly, observations conducted by trained external raters indicated significantly more teacher proactive behavior management and anticipation of student problems, higher student compliance, less student non-compliance, and less socially disruptive behaviors in classrooms led by coached teachers than classrooms led teachers randomly assigned to the non-coached condition. These findings indicated promising effects of the Double Check model on a range of teacher and student outcomes, including disproportionality in office discipline referrals among Black students. These results also suggest that the Double Check model is one of only a few systematic approaches to promoting culturally-responsive behavior management which has been rigorously tested and shown to be associated with improvements in either student or staff outcomes indicated significant reductions in discipline problems and improvements in behavior management. Implications of these findings are considered within the broader context of globalization and demographic shifts, and their impacts on schools. These issues are particularly timely, given growing concerns about immigration policies in the U.S. and abroad.

Keywords: ethnically and culturally diverse students, student engagement, school-based prevention, academic achievement

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Authors: Hari K. Adhikari, Keshab Sharma, K. C. Apil

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The Gorkha Nepal earthquake of moment magnitude (Mw) 7.8 hit the central region of Nepal on April 25, 2015; with the epicenter about 77 km northwest of Kathmandu Valley. This paper aims to explore challenges of reconstruction in the rural earthquake-stricken areas of Nepal. The Gorkha earthquake on April 25, 2015, has significantly affected the livelihood of people and overall economy in Nepal, causing severe damage and destruction in central Nepal including nation’s capital. A larger part of the earthquake affected area is difficult to access with rugged terrain and scattered settlements, which posed unique challenges and efforts on a massive scale reconstruction and rehabilitation. 800 thousand buildings were affected leaving 8 million people homeless. Challenge of reconstruction of optimum 800 thousand houses is arduous for Nepal in the background of its turmoil political scenario and weak governance. With significant actors involved in the reconstruction process, no appreciable relief has reached to the ground, which is reflected over the frustration of affected people. The 2015 Gorkha earthquake is one of most devastating disasters in the modern history of Nepal. Best of our knowledge, there is no comprehensive study on reconstruction after disasters in modern Nepal, which integrates the necessary information to deal with challenges and opportunities of reconstructions. The study was conducted using qualitative content analysis method. Thirty engineers and ten social mobilizes working for reconstruction and more than hundreds local social workers, local party leaders, and earthquake victims were selected arbitrarily. Information was collected through semi-structured interviews and open-ended questions, focus group discussions, and field notes, with no previous assumption. Author also reviewed literature and document reviews covering academic and practitioner studies on challenges of reconstruction after earthquake in developing countries such as 2001 Gujarat earthquake, 2005 Kashmir earthquake, 2003 Bam earthquake and 2010 Haiti earthquake; which have very similar building typologies, economic, political, geographical, and geological conditions with Nepal. Secondary data was collected from reports, action plans, and reflection papers of governmental entities, non-governmental organizations, private sector businesses, and the online news. This study concludes that inaccessibility, absence of local government, weak governance, weak infrastructures, lack of preparedness, knowledge gap and manpower shortage, etc. are the key challenges of the reconstruction after 2015 earthquake in Nepal. After scrutinizing different challenges and issues, study counsels that good governance, integrated information, addressing technical issues, public participation along with short term and long term strategies to tackle with technical issues are some crucial factors for timely and quality reconstruction in context of Nepal. Sample collected for this study is relatively small sample size and may not be fully representative of the stakeholders involved in reconstruction. However, the key findings of this study are ones that need to be recognized by academics, governments, and implementation agencies, and considered in the implementation of post-disaster reconstruction program in developing countries.

Keywords: Gorkha earthquake, reconstruction, challenges, policy

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Authors: Wissam Saliba, Mandy Nicholson

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Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

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Authors: Adam J. Bowen

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Abstract— Should robots have rights or legal protections. Often debates concerning whether robots and AI should be afforded rights focus on conditions of personhood and the possibility of future advanced forms of AI satisfying particular intrinsic cognitive and moral attributes of rights-holding persons. Such discussions raise compelling questions about machine consciousness, autonomy, and value alignment with human interests. Although these are important theoretical concerns, especially from a future design perspective, they provide limited guidance for addressing the moral and legal standing of current and near-term AI that operate well below the cognitive and moral agency of human persons. Robots and AI are already being pressed into service in a wide range of roles, especially in healthcare and biomedical contexts. The design and large-scale implementation of robots in the context of core societal institutions like healthcare systems continues to rapidly develop. For example, we bring them into our homes, hospitals, and other care facilities to assist in care for the sick, disabled, elderly, children, or otherwise vulnerable persons. We enlist surgical robotic systems in precision tasks, albeit still human-in-the-loop technology controlled by surgeons. We also entrust them with social roles involving companionship and even assisting in intimate caregiving tasks (e.g., bathing, feeding, turning, medicine administration, monitoring, transporting). There have been advances to enable severely disabled persons to use robots to feed themselves or pilot robot avatars to work in service industries. As the applications for near-term AI increase and the roles of robots in restructuring our biomedical practices expand, we face pressing questions about the normative implications of human-robot interactions and collaborations in our collective worldmaking, as well as the moral and legal status of robots. This paper argues that robots operating in public and private spaces be afforded some protections as either moral patients or legal agents to establish prohibitions on robot abuse, misuse, and mistreatment. We already implement robots and embed them in our practices and institutions, which generates a host of human-to-machine and machine-to-machine relationships. As we interact with machines, whether in service contexts, medical assistance, or home health companions, these robots are first encountered in relationship to us and our respective roles in the encounter (e.g., surgeon, physical or occupational therapist, recipient of care, patient’s family, healthcare professional, stakeholder). This proposal aims to outline a framework for establishing limiting factors and determining the extent of moral or legal protections for robots. In doing so, it advocates for a relational approach that emphasizes the priority of mapping the complex contextually sensitive roles played and the relations in which humans and robots stand to guide policy determinations by relevant institutions and authorities. The relational approach must also be technically informed by the intended uses of the biomedical technologies in question, Design History Files, extensive risk assessments and hazard analyses, as well as use case social impact assessments.

Keywords: biomedical robots, robot ethics, robot laws, human-robot interaction

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Authors: Vladislav Grigorovitch, Marina Grigorovitch, David Pearlmutter, Erez Gal

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The concept of “electric island” is involved with achieving the balance between the self-power generation ability of each educational institution and energy consumption demand. Photo-Voltaic (PV) solar system installed on the roofs of educational buildings is a common way to absorb the available solar energy and generate electricity for self-consumption and even for returning to the grid. The main objective of this research is to develop and implement an “electric island” monitoring infrastructure for promoting energy efficiency in educational buildings. A microscale monitoring methodology will be developed to provide a platform to estimate energy consumption performance classified by rooms and subspaces rather than the more common macroscale monitoring of the whole building. The monitoring platform will be established on the experimental sites, enabling an estimation and further analysis of the variety of environmental and physical conditions. For each building, separate measurement configurations will be applied taking into account the specific requirements, restrictions, location and infrastructure issues. The direct results of the measurements will be analyzed to provide deeper understanding of the impact of environmental conditions and sustainability construction standards, not only on the energy demand of public building, but also on the energy consumption habits of the children that study in those schools and the educational and administrative staff that is responsible for providing the thermal comfort conditions and healthy studying atmosphere for the children. A monitoring methodology being developed in this research is providing online access to real-time data of Interferential Therapy (IFTs) from any mobile phone or computer by simply browsing the dedicated website, providing powerful tools for policy makers for better decision making while developing PV production infrastructure to achieve “electric islands” in educational buildings. A detailed measurement configuration was technically designed based on the specific conditions and restriction of each of the pilot buildings. A monitoring and analysis methodology includes a large variety of environmental parameters inside and outside the schools to investigate the impact of environmental conditions both on the energy performance of the school and educational abilities of the children. Indoor measurements are mandatory to acquire the energy consumption data, temperature, humidity, carbon dioxide and other air quality conditions in different parts of the building. In addition to that, we aim to study the awareness of the users to the energy consideration and thus the impact on their energy consumption habits. The monitoring of outdoor conditions is vital for proper design of the off-grid energy supply system and validation of its sufficient capacity. The suggested outcomes of this research include: 1. both experimental sites are designed to have PV production and storage capabilities; 2. Developing an online information feedback platform. The platform will provide consumer dedicated information to academic researchers, municipality officials and educational staff and students; 3. Designing an environmental work path for educational staff regarding optimal conditions and efficient hours for operating air conditioning, natural ventilation, closing of blinds, etc.

Keywords: sustainability, electric island, IOT, smart building

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Authors: Andrew D. Henshaw

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The research examines the influence of familial and kinship based leadership on the resilience of politically violent organizations. Organizations of this type frequently fight in the same conflicts though are called 'terrorist' or 'insurgent' depending on political foci of the time, and thus different approaches are used to combat them. The research considers them correlated phenomena with significant overlap and identifies strengths and vulnerabilities in resilience processes. The research employs paired case studies to examine resilience in organizations under significant external pressure, and achieves this by measuring three variables. 1: Organizational robustness in terms of leadership and governance. 2. Bounce-back response efficiency to external pressures and adaptation to endogenous and exogenous shock. 3. Perpetuity of operational and attack capability, and political legitimacy. The research makes three hypotheses. First, familial/kinship leadership groups have a significant effect on organizational resilience in terms of informal operations. Second, non-familial/kinship organizations suffer in terms of heightened security transaction costs and social economics surrounding recruitment, retention, and replacement. Third, resilience in non-familial organizations likely stems from critical external supports like state sponsorship or powerful patrons, rather than organic resilience dynamics. The case studies pair familial organizations with non-familial organizations. Set 1: The Haqqani Network (HQN) - Pair: Lashkar-e-Toiba (LeT). Set 2: Jemaah Islamiyah (JI) - Pair: The Abu Sayyaf Group (ASG). Case studies were selected based on three requirements, being: contrasting governance types, exposure to significant external pressures and, geographical similarity. The case study sets were examined over 24 months following periods of significantly heightened operational activities. This enabled empirical measurement of the variables as substantial external pressures came into force. The rationale for the research is obvious. Nearly all organizations have some nexus of familial interconnectedness. Examining familial leadership networks does not provide further understanding of how terrorism and insurgency originate, however, the central focus of the research does address how they persist. The sparse attention to this in existing literature presents an unexplored yet important area of security studies. Furthermore, social capital in familial systems is largely automatic and organic, given at birth or through kinship. It reduces security vetting cost for recruits, fighters and supporters which lowers liabilities and entry costs, while raising organizational efficiency and exit costs. Better understanding of these process is needed to exploit strengths into weaknesses. Outcomes and implications of the research have critical relevance to future operational policy development. Increased clarity of internal trust dynamics, social capital and power flows are essential to fracturing and manipulating kinship nexus. This is highly valuable to external pressure mechanisms such as counter-terrorism, counterinsurgency, and strategic intelligence methods to penetrate, manipulate, degrade or destroy the resilience of politically violent organizations.

Keywords: Counterinsurgency (COIN), counter-terrorism, familial influence, insurgency, intelligence, kinship, resilience, terrorism

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Authors: Arzyana Sunkar, Yanto Santosa, Siti Badriyah Rushayati

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Indonesia has experienced annual forest fires that have rapidly destroyed and degraded its forests. Fires in the peat swamp forests of Riau Province, have set the stage for problems to worsen, this being the ecosystem most prone to fires (which are also the most difficult, to extinguish). Despite various efforts to curb deforestation, and forest degradation processes, severe forest fires are still occurring. To find an effective solution, the basic causes of the problems must be identified. It is therefore critical to have an in-depth understanding of the underlying causal factors that have contributed to deforestation and forest degradation as a whole, in order to attain reductions in their rates. An assessment of the drivers of deforestation and forest degradation was carried out, in order to design and implement measures that could slow these destructive processes. Research was conducted in Giam Siak Kecil–Bukit Batu Biosphere Reserve (GSKBB BR), in the Riau Province of Sumatera, Indonesia. A biosphere reserve was selected as the study site because such reserves aim to reconcile conservation with sustainable development. A biosphere reserve should promote a range of local human activities, together with development values that are in line spatially and economically with the area conservation values, through use of a zoning system. Moreover, GSKBB BR is an area with vast peatlands, and is experiencing forest fires annually. Various factors were analysed to assess the drivers of deforestation and forest degradation in GSKBB BR; data were collected from focus group discussions with stakeholders, key informant interviews with key stakeholders, field observation and a literature review. Landsat satellite imagery was used to map forest-cover changes for various periods. Analysis of landsat images, taken during the period 2010-2014, revealed that within the non-protected area of core zone, there was a trend towards decreasing peat swamp forest areas, increasing land clearance, and increasing areas of community oil-palm and rubber plantations. Fire was used for land clearing and most of the forest fires occurred in the most populous area (the transition area). The study found a relationship between the deforested/ degraded areas, and certain distance variables, i.e. distance from roads, villages and the borders between the core area and the buffer zone. The further the distance from the core area of the reserve, the higher was the degree of deforestation and forest degradation. Research findings suggested that agricultural expansion may be the direct cause of deforestation and forest degradation in the reserve, whereas socio-economic factors were the underlying driver of forest cover changes; such factors consisting of a combination of socio-cultural, infrastructural, technological, institutional (policy and governance), demographic (population pressure) and economic (market demand) considerations. These findings indicated that local factors/problems were the critical causes of deforestation and degradation in GSKBB BR. This research therefore concluded that reductions in deforestation and forest degradation in GSKBB BR could be achieved through ‘local actor’-tailored approaches such as community empowerment

Keywords: Actor-led solution, community empowerment, drivers of deforestation and forest degradation, Giam Siak Kecil – Bukit Batu Biosphere Reserve

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Authors: Claire Williams

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Randomised controlled Trials (RCTs) of efficacy are still perceived as the gold standard for the generation of evidence, and whilst advances in data collection methods are well developed, this progress has not been matched for the reporting of adverse events (AEs). Assessment and reporting of AEs in clinical trials are fraught with human error and inefficiency and are extremely time and resource intensive. Recent research conducted into the quality of reporting of AEs during clinical trials concluded it is substandard and reporting is inconsistent. Investigators commonly send reports to sponsors who are incorrectly categorised and lacking in critical information, which can complicate the detection of valid safety signals. In our presentation, we will describe an electronic data capture system, which has been designed to support clinical trial processes by reducing the resource burden on investigators, improving overall trial efficiencies, and making trials safer for patients. This proprietary technology was developed using expertise proven in the delivery of the world’s first prospective, phase 3b real-world trial, ‘The Salford Lung Study, ’ which enabled robust safety monitoring and reporting processes to be accomplished by the remote monitoring of patients’ EHRs. This technology enables safety alerts that are pre-defined by the protocol to be detected from the data extracted directly from the patients EHR. Based on study-specific criteria, which are created from the standard definition of a serious adverse event (SAE) and the safety profile of the medicinal product, the system alerts the investigator or study team to the safety alert. Each safety alert will require a clinical review by the investigator or delegate; examples of the types of alerts include hospital admission, death, hepatotoxicity, neutropenia, and acute renal failure. This is achieved in near real-time; safety alerts can be reviewed along with any additional information available to determine whether they meet the protocol-defined criteria for reporting or withdrawal. This active surveillance technology helps reduce the resource burden of the more traditional methods of AE detection for the investigators and study teams and can help eliminate reporting bias. Integration of multiple healthcare data sources enables much more complete and accurate safety data to be collected as part of a trial and can also provide an opportunity to evaluate a drug’s safety profile long-term, in post-trial follow-up. By utilising this robust and proven method for safety monitoring and reporting, a much higher risk of patient cohorts can be enrolled into trials, thus promoting inclusivity and diversity. Broadening eligibility criteria and adopting more inclusive recruitment practices in the later stages of drug development will increase the ability to understand the medicinal products risk-benefit profile across the patient population that is likely to use the product in clinical practice. Furthermore, this ground-breaking approach to AE detection not only provides sponsors with better-quality safety data for their products, but it reduces the resource burden on the investigator and study teams. With the data taken directly from the source, trial costs are reduced, with minimal data validation required and near real-time reporting enables safety concerns and signals to be detected more quickly than in a traditional RCT.

Keywords: more comprehensive and accurate safety data, near real-time safety alerts, reduced resource burden, safer trials

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Authors: Mohamed Abdelmongy

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Autologous Blood for Conjunctival Autograft Fixation in Primary Pterygium Surgery: A Systematic Review and Meta-analysis Hossam Zein1,2, Ammar Ismail1,3, Mohamed Abdelmongy1,4, Sherif Elsherif1,5,6, Ahmad Hassanen1,4, Basma Muhammad2, Fathy Assaf1,3, Ahmed Elsehili1,7, Ahmed Negida1,7, Shin Yamane9, Mohamed M. Abdel-Daim8,9 and Kazuaki Kadonosono9 https://www.ncbi.nlm.nih.gov/pubmed/30277146 BACKGROUND: Pterygium is a benign ocular lesion characterized by triangular fibrovascular growth of conjunctival tissue over the cornea. Patients complain of the bad cosmetic appearance, ocular surface irritation and decreased visual acuity if the pterygium is large enough to cause astigmatism or encroach on the pupil. The definitive treatment of pterygium is surgical removal. However, outcomes are compromised by recurrence . The aim of the current study is to systematically review the current literature to explore the efficacy and safety of fibrin glue, suture and autologous blood coagulum for conjunctivalautograft fixation in primary pterygium surgery. OBJECTIVES: To assess the effectiveness of fibrin glue compared to sutures and autologous blood coagulum in conjunctival autografting for the surgical treatment of pterygium. METHODS: During preparing this manuscript, we followed the steps adequately illustrated in the Cochrane Handbook for Systematic Reviews of Interventions version 5.3, and reported it according to the preferred reporting of systematic review and meta-analysis (PRISMA) statement guidelines. We searched PubMed, Ovid (both through Medline), ISI Web of Science, and Cochrane Central Register of Controlled Trials (Central) through January 2017, using the following keywords “Pterygium AND (blood OR glue OR suture)” SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that met the following criteria: 1) comparing autologous blood vs fibrin glue for conjunctivalautograft fixation in primary pterygium surgery 2) comparing autologous blood vs sutures for conjunctivalautograft fixation in primary pterygium surgery DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed trial quality, and extracted data using standard methodological procedures expected by Cochrane. The extracted data included A) study design, sample size, and main findings, B) Baseline characteristics of patients included in this review including their age, sex, pterygium site and grade, and graft size. C) Study outcomes comprising 1) primary outcomes: recurrence rate 2) secondary outcomes: graft stability outcomes (graft retraction, graft displacement), operation time (min) and postoperative symptoms (pain, discomfort, foreign body sensation, tearing) MAIN RESULTS: We included 7 RCTs and The review included662eyes (Blood: 293; Glue: 198; Suture: 171). we assess the 1) primary outcomes: recurrence rate 2) secondary outcomes: graft stability outcomes (graft retraction, graft displacement), operation time (min) and postoperative symptoms (pain, discomfort, foreign body sensation, tearing) CONCLUSIONS: Autologous blood for conjunctivalautograft fixation in pterygium surgery is associated with lower graft stability than fibrin glue or sutures. It was not inferior to fibrin glue or sutures regarding recurrence rate. The overall quality of evidence is low. Further well designed RCTs are needed to fully explore the efficacy of this new technique.

Keywords: pterygium, autograft, ophthalmology, cornea

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Authors: Jonathan Nii Laryea Ashong, Samuel Opare

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Current sustainable cities debate focuses on the formidable problems for the Ghana’s largest urban and rural agglomerations, the majority of all urban dwellers continue to reside in far smaller urban settlements. It is estimated that by year 2030, almost all the Ghana’s population growth will likely be intense in urban areas including Nkawkaw in the Kwahu West Municipality of Ghana. Nkawkaw is situated on the road and former railway between Accra and Kumasi, and lies about halfway between these cities. It is also connected by road to Koforidua and Konongo. According to the 2013 census, Nkawkaw has a settlement population of 61,785. Many international agencies, government and private architectures’ are been asked to adequately recognize the naming of streets and property addressing system among the 170 districts across Ghana. The naming of streets and numbering of properties is to assist Metropolitan, Municipal and District Assemblies to manage the processes for establishing coherent address system nationally. Street addressing in the Nkawkaw in the Kwahu West Municipality which makes it possible to identify the location of a parcel of land, public places or dwellings on the ground based on system of names and numbers, yet agreement on how to progress towards it remains elusive. Therefore, reliable and effective development control for proper street naming and property addressing systems are required. The Intelligent Addressing (IA) technology from the UK is being used to name streets and properties in Ghana. The intelligent addressing employs the technique of unique property Reference Number and the unique street reference number which would transform national security and other service providers’ ability to respond rapidly to distress calls. Where name change is warranted following the review of existing streets names, the Physical Planning Department (PPDs) shall, in consultation with the relevant traditional authorities and community leadership (or relevant major stakeholders), select a street name in accordance with the provisions of the policy and the processes outlined for street name change for new development. In the case of existing streets with no names, the respective PPDs shall, in consultation with the relevant traditional authorities and community leadership (or relevant major stakeholders), select a street name in accordance with the requirements set out in municipality. Naming of access ways proposed for new developments shall be done at the time of developing sector layouts (subdivision maps) for the designated areas. In the case of private gated developments, the developer shall submit the names of the access ways as part of the plan and other documentation forwarded to the Municipal District Assembly for approval. The names shall be reviewed first by the PPD to avoid duplication and to ensure conformity to the required standards before submission to the Assembly’s Statutory Planning Committee for approval. The Kwahu West Municipality is supposed to be self-sustaining, providing basic services to inhabitants as a result of proper planning layouts, street naming and property addressing system that prevail in the area. The implications of these future projections are discussed.

Keywords: Nkawkaw, Kwahu west municipality, street naming, property, addressing system

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Authors: Merrick Lopez, Aashish Abraham, Melissa Egge, Marissa Hood, Jui Shah

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A 3 year old male with unknown medical history presented initially with encephalopathy, intubated for respiratory failure, and admitted to the pediatric intensive care unit (PICU) with refractory shock. During resuscitation in the emergency department, he was found to be in severe metabolic acidosis with a pH of 7.03 and escalated on vasopressor drips for hypotension. His initial sodium was 174. He was noted to have burn injuries to his scalp, forehead, right axilla, bilateral arm creases and lower legs. He had rhabdomyolysis (initial creatinine kinase 5,430 U/L with peak levels of 62,340 normal <335 U/L), cardiac injury (initial troponin 88 ng/L with peak at 145 ng/L, normal <15ng/L), hypernatremia (peak 174, normal 140), hypocalcemia, liver injury, acute kidney injury, and neuronal loss on magnetic resonance imaging (MRI). Soft restraints and a shock collar were found in the home. He was critically ill for 8 days, but was gradually weaned off drips, extubated, and started on feeds. Discussion Electrical injury, specifically lightning injury is an uncommon but devastating cause of injury in pediatric patients. This patient with suspected abusive use of a dog shock collar presented similar to a lightning strike. Common entrance points include the hands and head, similar to our patient with linear wounds on his forehead. When current enters, it passes through tissues with the least resistance. Nerves, blood vessels, and muscles, have high fluid and electrolyte content and are commonly affected. Exit points are extremities: our child who had circumferential burns around his arm creases and ankles. Linear burns preferentially follow areas of high sweat concentration, and are thought to be due to vaporization of water on the skin’s surface. The most common cause of death from a lightning strike is due to cardiopulmonary arrest. The massive depolarization of the myocardium can result in arrhythmias and myocardial necrosis. The patient presented in cardiogenic shock with evident cardiac damage. Electricity going through vessels can lead to vaporization of intravascular water. This can explain his severe hypernatremia. He also sustained other internal organ injuries (adrenal glands, pancreas, liver, and kidney). Electrical discharge also leads to direct skeletal muscle injury in addition to prolonged muscular spasm. Rhabdomyolysis, the acute damage of muscle, leads to release of potentially toxic components into the circulation which could lead to acute renal failure. The patient had severe rhabdomyolysis and renal injury. Early hypocalcemia has been consistently demonstrated in patients with rhabdomyolysis. This was present in the patient and led to increased vasopressor needs. Central nervous system injuries are also common which can include encephalopathy, hypoxic injury, and cerebral infarction. The patient had evidence of brain injury as seen on MRI. Conclusion Electrical injuries due to lightning strikes and abusive use of a dog shock collar are rare, but can both present in similar ways with respiratory failure, shock, hypernatremia, rhabdomyolysis, brain injury, and multiorgan damage. Although rare, it is essential for early identification and prompt management for acute and chronic complications in these children.

Keywords: cardiogenic shock, dog shock collar, lightning strike, rhabdomyolysis

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Authors: Sara Dragisic

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Using the theoretical analysis of the birth of biopolitics that Foucault performed through the history of liberalism and neoliberalism, in this paper we will try to show how, precisely through problematizing the role of international institutions, the model of governance differs from previous ways of objectifying body and life. Are the state and its mechanisms still a Leviathan to fight against, or can it be even the driver of resistance against the proponents of modern governance and the biopolitical power? Do paradigmatic examples of biopolitics still appear through sovereignty and (international) law, or is it precisely this sphere that shows a significant dose of incompetence and powerlessness in relation to, not only the economic sphere (Foucault’s critique of neoliberalism) but also the new politics of freedom? Have the struggle for freedom and human rights, as well as the war on terrorism, opened a new spectrum of biopolitical processes, which are manifested precisely through new international institutions and humanitarian discourse? We will try to answer these questions, in the following way. On the one hand, we will show that the views of authors such as Agamben and Hardt and Negri, in whom the state and sovereignty are seen as enemies to be defeated or overcome, fail to see how such attempts could translate into the politicization of life like it is done in many examples through the doctrine of liberal interventionism and humanitarianism. On the other hand, we will point out that it is precisely the humanitarian discourse and the defense of the right to intervention that can be the incentive and basis for the politicization of the category of life and lead to the selective application of human rights. Zizek example of the killing of United Nations workers and doctors in a village during the Vietnam War, who were targeted even before police or soldiers, because they were precisely seen as a powerful instrument of American imperialism (as they were sincerely trying to help the population), will be focus of this part of the analysis. We’ll ask the question whether such interpretation is a kind of liquidation of the extreme left of the political (Laclau) or on this basis can be explained at least in part the need to review the functioning of international organizations, ranging from those dealing with humanitarian aid (and humanitarian military interventions) to those dealing with protection and the security of the population, primarily from growing terrorism. Based on the above examples, we will also explain how the discourse of terrorism itself plays a dual role: it can appear as a tool of liberal biopolitics, although, more superficially, it mostly appears as an enemy that wants to destroy the liberal system and its values. This brings us to the basic problem that this paper will tackle: do the mechanisms of institutional struggle for human rights and freedoms, which is often seen as opposed to the security mechanisms of the state, serve the governance of citizens in such a way that the latter themselves participate in producing biopolitical governmental practices? Is the freedom today "nothing but the correlative development of apparatuses of security" (Foucault)? Or, we can continue this line of Foucault’s argumentation and enhance the interpretation with the important question of what precisely today reflects the change in the rationality of governance in which society is transformed from a passive object into a subject of its own production. Finally, in order to understand the skills of biopolitical governance in modern civil society, it is necessary to pay attention to the status of international organizations, which seem to have become a significant place for the implementation of global governance. In this sense, the power of sovereignty can turn out to be an insufficiently strong power of security policy, which can go hand in hand with freedom policies, through neoliberal governmental techniques.

Keywords: neoliberalism, Foucault, sovereignty, biopolitics, international organizations, NGOs, Agamben, Hardt&Negri, Zizek, security, state power

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Authors: Viktorya Sargsyan, Arax Hovhannesyan, Karine Abelyan

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Introduction: During the last decade, scientific studies have proven the importance of Early Childhood Development (ECD) interventions. These interventions are shown to create strong foundations for children’s intellectual, emotional and physical well-being, as well as the impact they have on learning and economic outcomes for children as they mature into adulthood. Many children in rural Armenia fail to reach their full development potential due to lack of early brain stimulation (playing, singing, reading, etc.) from their parents, and lack of community tools and services to follow-up children’s neurocognitive development. This is exacerbated by high rates of stunting and anemia among children under 3(CU3). This research study tested the effectiveness of an integrated ECD and Maternal, Newborn and Childhood Health (MNCH) model, called “Go Baby, Go!” (GBG), against the traditional (MNCH) strategy which focuses solely on preventive health and nutrition interventions. The hypothesis of this quasi-experimental study was: Children exposed to GBG will have better neurocognitive and nutrition outcomes compared to those receiving only the MNCH intervention. The secondary objective was to assess the effect of GBG on parental child care and nutrition practices. Methodology: The 14 month long study, targeted all 1,300 children aged 0 to 23 months, living in 43 study communities the in Gavar and Vardenis regions (Gegharkunik province, Armenia). Twenty-three intervention communities, 680 children, received GBG, and 20 control communities, 630 children, received MCHN interventions only. Baseline and evaluation data on child development, nutrition status and parental child care and nutrition practices were collected (caregiver interview, direct child assessment). In the intervention sites, in addition to MNCH (maternity schools, supportive supervision for Health Care Providers (HCP), the trained GBG facilitators conducted six interactive group sessions for mothers (key messages, information, group discussions, role playing, video-watching, toys/books preparation, according to GBG curriculum), and two sessions (condensed GBG) for adult family members (husbands, grandmothers). The trained HCPs received quality supervision for ECD counseling and screening. Findings: The GBG model proved to be effective in improving ECD outcomes. Children in the intervention sites had 83% higher odd of total ECD composite score (cognitive, language, motor) compared to children in the control sites (aOR 1.83; 95 percent CI: 1.08-3.09; p=0.025). Caregivers also demonstrated better child care and nutrition practices (minimum dietary diversity in intervention site is 55 percent higher compared to control (aOR=1.55, 95 percent CI 1.10-2.19, p =0.013); support for learning and disciplining practices (aOR=2.22, 95 percent CI 1.19-4.16, p=0.012)). However, there was no evidence of stunting reduction in either study arm. he effect of the integrated model was more prominent in Vardenis, a community which is characterised by high food insecurity and limited knowledge of positive parenting skills. Conclusion: The GBG model is effective and could be applied in target areas with the greatest economic disadvantages and parenting challenges to improve ECD, care practices and developmental outcomes. Longitudinal studies are needed to view the long-term effects of GBG on learning and school readiness.

Keywords: early childhood development, integrated interventions, parental practices, quasi-experimental study

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Authors: Muhammad Hanif Amiri, Edris Sadeqy, Ahmad Freed Osman

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International Conference on Architectural Engineering and Skyscraper (ICAES 2016) on January 18 - 19, 2016 is aimed to exchange new ideas and application experiences face to face, to establish business or research relations and to find global partners for future collaboration. Therefore, we are very keen to participate and share our issues in order to get valuable feedbacks of the conference participants. Urbanization is a controversial issue all around the world. Substandard and unplanned urbanization has many implications on a social, cultural and economic situation of population life. Unplanned and illegal construction has become a critical issue in Afghanistan particularly Kabul city. In addition, lack of municipal bylaws, poor municipal governance, lack of development policies and strategies, budget limitation, low professional capacity of ainvolved private sector in development and poor coordination among stakeholders are the other factors which made the problem more complicated. The main purpose of this research paper is to review urbanization pattern of Kabul city and find out the improvement solutions and to evaluate the increasing of population density which caused vast illegal and unplanned development which finally converts the Kabul city to a slam area as the whole. The Kabul city Master Plan was reviewed in the year 1978 and revised for the planned 2million population. In 2001, the interim administration took place and the city became influx of returnees from neighbor countries and other provinces of Afghanistan mostly for the purpose of employment opportunities, security and better quality of life, therefore, Kabul faced with strange population growth. According to Central Statistics Organization of Afghanistan population of Kabul has been estimated approx. 5 million (2015), however a new Master Plan has been prepared in 2009, but the existing challenges have not been dissolved yet. On the other hand, 70% of Kabul population is living in unplanned (slam) area and facing the shortage of drinking water, inexistence of sewerage and drainage network, inexistence of proper management system for solid waste collection, lack of public transportation and traffic management, environmental degradation and the shortage of social infrastructure. Although there are many problems in Kabul city, but still the development of 22 townships are in progress which caused the great attraction of population. The research is completed with a detailed analysis on four main issues such as elimination of duplicated administrations, Development of regions, Rehabilitation and improvement of infrastructure, and prevention of new townships establishment in Kabul Central Core in order to mitigate the problems and constraints which are the foundation and principal to find the point of departure for an objective based future development of Kabul city. The closure has been defined to reflect the stage-wise development in light of prepared policy and strategies, development of a procedure for the improvement of infrastructure, conducting a preliminary EIA, defining scope of stakeholder’s contribution and preparation of project list for initial development. In conclusion this paper will help the transformation of Kabul city.

Keywords: development of regions, illegal construction, population density, urbanization pattern

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Authors: Alison C. Essary, Victor Trastek

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Introduction: The current state of the health care system in the U.S. is characterized by an unprecedented number of people living with multiple chronic conditions, unsustainable rise in health care costs, inadequate access to care, and wide variation in health outcomes throughout the country. An estimated two-thirds of Americans are living with two or more chronic conditions, contributing to 75% of all health care spending. In 2013, the School for the Science of Health Care Delivery (SHCD) was charged with redesigning the health care system through education and research. Faculty in business, law, and public policy, and thought leaders in health care delivery, administration, public health and health IT created undergraduate, graduate, and executive academic programs to address this pressing need. Faculty and students work across disciplines, and with community partners and employers to improve care delivery and increase value for patients. Methods: Curricula apply content in health care administration and operations within the clinical context. Graduate modules are team-taught by faculty across academic units to model team-based practice. Seminars, team-based assignments, faculty mentoring, and applied projects are integral to student success. Cohort-driven models enhance networking and collaboration. This observational study evaluated two years of admissions data, and one year of graduate data to assess program outcomes and inform the current graduate-level curricula. Descriptive statistics includes means, percentages. Results: Fall 2013, the program received 51 applications. The mean GPA of the entering class of 37 students was 3.38. Ninety-seven percent of the fall 2013 cohort successfully completed the program (n=35). Sixty-six percent are currently employed in the health care industry (n=23). Of the remaining 12 graduates, two successfully matriculated to medical school; one works in the original field of study; four await results on the MCAT or DAT, and five were lost to follow up. Attrition of one student was attributed to non-academic reasons. Fall 2014, the program expanded to include both on-ground and online cohorts. Applications were evenly distributed between on-ground (n=70) and online (n=68). Thirty-eight students enrolled in the on-ground program. The mean GPA was 3.95. Ninety-five percent of students successfully completed the program (n=36). Thirty-six students enrolled in the online program. The mean GPA was 3.85. Graduate outcomes are pending. Discussion: Challenges include demographic variability between online and on-ground students; yet, both profiles are similar in that students intend to become change agents in the health care system. In the past two years, on-ground applications increased by 31%, persistence to graduation is > 95%, mean GPA is 3.67, graduates report admission to six U.S. medical schools, the Mayo Medical School integrates SHCD content within their curricula, and there is national interest in collaborating on industry and academic partnerships. This places SHCD at the forefront of developing innovative curricula in order to improve high-value, patient-centered care.

Keywords: delivery science, education, health care delivery, high-value care, innovation in education, patient-centered

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Authors: Olayeye Olubunmi Shola

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Amidst increasing global environmental concerns, sustainable urban planning has emerged as a vital strategy in counteracting the negative impacts of urbanization on the environment. However, the emphasis on sustainability often disregards crucial elements of fairness and equal participation within urban settings. This abstract presents a comprehensive overview of the challenges, objectives, significance, and methodologies for addressing social inequalities in the development of eco-cities, with a specific focus on Abuja, Nigeria. Sustainable urban planning, particularly in the context of developing eco-cities, aims to construct cities prioritizing environmental sustainability and resilience. Nonetheless, a significant gap exists in addressing the enduring social disparities within these initiatives. Equitable distribution of resources, access to services, and social inclusivity are essential components that must be integrated into urban planning frameworks for cities that are genuinely sustainable and habitable. Abuja, the capital city of Nigeria, provides a distinctive case for examining the intersection of sustainability and social justice in urban planning. Despite the urban development, Abuja grapples with challenges such as socio-economic disparities, unequal access to essential services, and inadequate housing among its residents. Recognizing and redressing these disparities within the framework of eco-city development is critical for nurturing an inclusive and sustainable urban environment. The primary aim of this study is to scrutinize and pinpoint the social discrepancies within Abuja's initiatives for eco-city development. Specific objectives include: Evaluating the current socio-economic landscape of Abuja to identify disparities in resource, service, and infrastructure access. Comprehending the existing sustainable urban planning initiatives and their influence on social fairness. Suggesting strategies and recommendations to improve fairness and inclusivity within Abuja's plans for eco-city development. This research holds substantial importance for urban planning practices and policy formulation, not only in Abuja but also on a global scale. By highlighting the crucial role of social equity and inclusivity in the development of eco-cities, this study aims to provide insights that can steer more comprehensive, people-centered urban planning practices. Addressing social disparities within sustainability initiatives is crucial for achieving genuinely sustainable and fair urban spaces. The study will employ qualitative and quantitative methodologies. Data collection will involve surveys, interviews, and observations to capture the diverse experiences and perspectives of various social groups within Abuja. Furthermore, quantitative data on infrastructure, service access, and socio-economic indicators will be collated from government reports, academic sources, and non-governmental organizations. Analytical tools such as Geographic Information Systems (GIS) will be utilized to map and visualize spatial disparities in resource allocation and service access. Comparative analyses and case studies of successful interventions in other cities will be conducted to derive applicable strategies for Abuja's context. In conclusion, this study aims to contribute to the discourse on sustainable urban planning by advocating for equity and inclusivity in the development of eco-cities. By centering on Abuja as a case study, it aims to provide practical insights and solutions for the creation of more fair and sustainable urban environments.

Keywords: fairness, sustainability, geographical information system, equity

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Authors: Joy Chiu, Colin Hemez, Emma Ryan, Jia Sun, Robert Dubrow, Michael Pascucilla

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The popularity of recreational boating is on the rise in the United States, which raises numerous national-level challenges in the management of air and water pollution, aquatic habitat destruction, and waterway access. The need to control sewage discharge from recreational vessels underlies all of these challenges. The release of raw human waste into aquatic environments can lead to eutrophication and algal blooms; can increase human exposure to pathogenic viruses, bacteria, and parasites; can financially impact commercial shellfish harvest/fisheries and marine bathing areas; and can negatively affect access to recreational and/or commercial waterways to the detriment of local economies. Because of the damage that unregulated sewage discharge can do to environments and human health/marine life, recreational vessels in the United States are required by law to 'pump-out' sewage from their holding tanks into sewage treatment systems in all designated 'no discharge areas'. Many pump-out boats, which transfer waste out of recreational vessels, are operated and maintained using funds allocated through the Federal Clean Vessel Act (CVA). The East Shore District Health Department of Branford, Connecticut is protecting this estuary by pioneering the design and construction of the first-in-the-nation zero-emissions, the solar-electric pump-out boat of its size to replace one of its older traditional gasoline-powered models through a Connecticut Department of Energy and Environmental Protection CVA Grant. This study, conducted in collaboration with the East Shore District Health Department, the Connecticut Department of Energy and Environmental Protection, States Organization for Boating Access and Connecticut’s CVA program coordinators, had two aims: (1) To perform a national assessment of pump-out boat programs, supplemented by a limited international assessment, to establish best pump-out boat practices (regardless of how the boat is powered); and (2) to estimate the cost, greenhouse gas emissions, and environmental and public health impacts of solar-electric versus traditional gasoline-powered pump-out boats. A national survey was conducted of all CVA-funded pump-out program managers and selected pump-out boat operators to gauge best practices; costs associated with gasoline-powered pump-out boat operation and management; and the regional, cultural, and policy-related issues that might arise from the adoption of solar-electric pump-out boat technology. We also conducted life-cycle analyses of gasoline-powered and solar-electric pump-out boats to compare their greenhouse gas emissions; production of air, soil and water pollution; and impacts on human health. This work comprises the most comprehensive study into pump-out boating practices in the United States to date, in which information obtained at local, state, national, and international levels is synthesized. This study aims to enable CVA programs to make informed recommendations for sustainable pump-out boating practices and identifies the challenges and opportunities that remain for the wide adoption of solar-electric pump-out boat technology.

Keywords: pump-out boat, marine water, solar-electric, zero emissions

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Authors: Stephanie Giordano, Rosa Plasencia

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In the USA, in 2013, public service systems such as Medicaid, aging, and disability systems undertook an effort to measure the quality of service delivery by examining the experiences and outcomes of those receiving public services. The goal of this effort was to develop a survey to measure the experiences and outcomes of those receiving public services, with the goal of measuring system performance for quality improvement. The performance indicators were developed through with input from directors of state aging and disability service systems, along with experts and stakeholders in the field across the United States. This effort, National Core Indicators –Aging and Disabilities (NCI-AD), grew out of National Core Indicators –Intellectual and Developmental Disabilities, an effort to measure developmental disability (DD) systems across the States. The survey tool and administration protocol underwent multiple rounds of testing and revision between 2013 and 2015. The measures in the final tool – called the Adult Consumer Survey (ACS) – emphasize not just important indicators of healthcare access and personal safety but also includes indicators of system quality based on person-centered outcomes. These measures indicate whether service systems support older adults and people with disabilities to live where they want, maintain relationships and engage in their communities and have choice and control in their everyday lives. Launched in 2015, the NCI-AD Adult Consumer Survey is now used in 23 states in the US. Surveys are conducted by NCI-AD trained surveyors via direct conversation with a person receiving public long-term services and supports (LTSS). Until 2020, surveys were only conducted in person. However, after a pilot to test the reliability of videoconference and telephone survey modes, these modes were adopted as an acceptable practice. The nature of the survey is that of a “guided conversation” survey administration allows for surveyor to use wording and terminology that is best understand by the person surveyed. The survey includes a subset of questions that may be answered by a proxy respondent who knows the person well if the person is receiving services in unable to provide valid responses on their own. Surveyors undergo a standardized training on survey administration to ensure the fidelity of survey administration. In addition to the main survey section, a Background Information section collects data on personal and service-related characteristics of the person receiving services; these data are typically collected through state administrative record. This information is helps provide greater context around the characteristics of people receiving services. It has also been used in conjunction with outcomes measures to look at disparity (including by race and ethnicity, gender, disability, and living arrangements). These measures of quality are critical for public service delivery systems to understand the unique needs of the population of older adults and improving the lives of older adults as well as people with disabilities. Participating states may use these data to identify areas for quality improvement within their service delivery systems, to advocate for specific policy change, and to better understand the experiences of specific populations of people served.

Keywords: quality of life, long term services and supports, person-centered practices, aging and disability research, survey methodology

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Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

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Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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Authors: Laura Butabayeva, Svetlana Ismagulova, Gulbarshin Nogaibayeva, Maiya Temirbayeva, Aidana Zhussip

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Over the years of independence, Kazakhstan has not only ratified international documents regulating the rights of children to Inclusive education, but also developed its own inclusive educational policy. Along with this, the state pays particular attention to high school students' preparedness for professional self-determination. However, a number of problematic issues in this field have been revealed, such as the lack of systemic mechanisms coordinating stakeholders’ actions in preparing schoolchildren for a conscious choice of in-demand profession, meeting their individual capabilities and special educational needs (SEN). The analysis of the state’s current situation indicates school graduates’ adaptation to the labor market does not meet existing demands of the society. According to the Ministry of Labor and Social Protection of the Population of the Republic of Kazakhstan, about 70 % of Kazakhstani school graduates find themselves difficult to choose a profession, 87 % of schoolchildren make their career choice under the influence of parents and school teachers, 90 % of schoolchildren and their parents have no idea about the most popular professions on the market. The results of the study conducted by KorlanSyzdykova in 2016 indicated the urgent need of Kazakhstani school graduates in obtaining extensive information about in- demand professions and receiving professional assistance in choosing a profession in accordance with their individual skills, abilities, and preferences. The results of the survey, conducted by Information and Analytical Center among heads of colleges in 2020, showed that despite significant steps in creating conditions for students with SEN, they face challenges in studying because of poor career guidance provided to them in schools. The results of the study, conducted by the Center for Inclusive Education of the National Academy of Education named after Y. Altynsarin in the state’s general education schools in 2021, demonstrated the lack of career guidance, pedagogical and psychological support for children with SEN. To investigate these issues, the further study was conducted to examine the state of students’ career guidance and socialization, taking into account their SEN. The hypothesis of this study proposed that to prepare school graduates for a conscious career choice, school teachers and specialists need to develop their competencies in early identification of students' interests, inclinations, SEN and ensure necessary support for them. The state’s 5 regions were involved in the study according to the geographical location. The triangulation approach was utilized to ensure the credibility and validity of research findings, including both theoretical (analysis of existing statistical data, legal documents, results of previous research) and empirical (school survey for students, interviews with parents, teachers, representatives of school administration) methods. The data were analyzed independently and compared to each other. The survey included questions related to provision of pedagogical support for school students in making their career choice. Ethical principles were observed in the process of developing the methodology, collecting, analyzing the data and distributing the results. Based on the results, methodological recommendations on students’ career guidance for school teachers and specialists were developed, taking into account the former’s individual capabilities and SEN.

Keywords: career guidance, children with special educational needs, inclusive education, Kazakhstan

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Authors: Farideh Namvar, Rosfarizan Mohamed

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In the field of nanotechnology, the use of various biological units instead of toxic chemicals for the reduction and stabilization of nanoparticles, has received extensive attention. This use of biological entities to create nanoparticles has designated as “Green” synthesis and it is considered to be far more beneficial due to being economical, eco-friendly and applicable for large-scale synthesis as it operates on low pressure, less input of energy and low temperatures. The lack of toxic byproducts and consequent decrease in degradation of the product renders this technique more preferable over physical and classical chemical methods. The variety of biomass having reduction properties to produce nanoparticles makes them an ideal candidate for fabrication. Metal oxide nanoparticles have been said to represent a "fundamental cornerstone of nanoscience and nanotechnology" due to their variety of properties and potential applications. However, this also provides evidence of the fact that metal oxides include many diverse types of nanoparticles with large differences in chemical composition and behaviour. In this study, iron oxide nanoparticles (Fe3O4-NPs) were synthesized using a rapid, single step and completely green biosynthetic method by reduction of ferric chloride solution with brown seaweed (Sargassum muticum) water extract containing polysaccharides as a main factor which acts as reducing agent and efficient stabilizer. Antimicrobial activity against six microorganisms was tested using well diffusion method. The resulting S-IONPs are crystalline in nature, with a cubic shape. The average particle diameter, as determined by TEM, was found to be 18.01 nm. The S-IONPs were efficiently inhibited the growth of Listeria monocytogenes, Escherichia coli and Candida species. Our favorable results suggest that S-IONPs could be a promising candidate for development of future antimicrobial therapies. The nature of biosynthesis and the therapeutic potential by S-IONPs could pave the way for further research on design of green synthesis therapeutic agents, particularly nanomedicine, to deal with treatment of infections. Further studies are needed to fully characterize the toxicity and the mechanisms involved with the antimicrobial activity of these particles. Antioxidant activity of S-IONPs synthesized by green method was measured by ABTS (2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (IC50= 1000µg) radical scavenging activity. Also, with the increasing concentration of S-IONPs, catalase gene expression compared to control gene GAPDH increased. For anti-angiogenesis study the Ross fertilized eggs were divided into four groups; the control and three experimental groups. The gelatin sponges containing albumin were placed on the chorioalantoic membrane and soaked with different concentrations of S-IONPs. All the cases were photographed using a photo stereomicroscope. The number and the lengths of the vessels were measured using Image J software. The crown rump (CR) and weight of the embryo were also recorded. According to the data analysis, the number and length of the blood vessels, as well as the CR and weight of the embryos reduced significantly compared to the control (p < 0.05), dose dependently. The total hemoglobin was quantified as an indicator of the blood vessel formation, and in the treated samples decreased, which showed its inhibitory effect on angiogenesis.

Keywords: anti-angiogenesis, antimicrobial, antioxidant, biosynthesis, iron oxide (fe3o4) nanoparticles, sargassum muticum, seaweed

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Authors: Ruth Leitch, Joanne Hughes

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This paper presents the findings of a three-year government-funded study (ILiAD) that aimed to understand the reasons for differential educational achievement within and between socially and economically deprived areas in Northern Ireland. Previous international studies have concluded that there is a positive correlation between deprivation and underachievement. Our preliminary secondary data analysis suggested that the factors involved in educational achievement within multiple deprived areas may be more complex than this, with some areas of high multiple deprivation having high levels of student attainment, whereas other less deprived areas demonstrated much lower levels of student attainment, as measured by outcomes on high stakes national tests. The study proposed that no single explanation or disparate set of explanations could easily account for the linkage between levels of deprivation and patterns of educational achievement. Using a social capital perspective that centralizes the connections within and between individuals and social networks in a community as a valuable resource for educational achievement, the ILiAD study involved a multi-level case study analysis of seven community sites in Northern Ireland, selected on the basis of religious composition (housing areas are largely segregated by religious affiliation), measures of multiple deprivation and differentials in educational achievement. The case study approach involved three (interconnecting) levels of qualitative data collection and analysis - what we have termed Micro (or community/grassroots level) understandings, Meso (or school level) explanations and Macro (or policy/structural) factors. The analysis combines a statistical mapping of factors with qualitative, in-depth data interpretation which, together, allow for deeper understandings of the dynamics and contributory factors within and between the case study sites. Thematic analysis of the qualitative data reveals both cross-cutting factors (e.g. demographic shifts and loss of community, place of the school in the community, parental capacity) and analytic case studies of explanatory factors associated with each of the community sites also permit a comparative element. Issues arising from the qualitative analysis are classified either as drivers or inhibitors of educational achievement within and between communities. Key issues that are emerging as inhibitors/drivers to attainment include: the legacy of the community conflict in Northern Ireland, not least in terms of inter-generational stress, related with substance abuse and mental health issues; differing discourses on notions of ‘community’ and ‘achievement’ within/between community sites; inter-agency and intra-agency levels of collaboration and joined-up working; relationship between the home/school/community triad and; school leadership and school ethos. At this stage, the balance of these factors can be conceptualized in terms of bonding social capital (or lack of it) within families, within schools, within each community, within agencies and also bridging social capital between the home/school/community, between different communities and between key statutory and voluntary organisations. The presentation will outline the study rationale, its methodology, present some cross-cutting findings and use an illustrative case study of the findings from a community site to underscore the importance of attending to community differences when trying to engage in research to understand and improve educational attainment for all.

Keywords: educational achievement, multiple deprivation, community case studies, social capital

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Authors: Jia H. Wong, Jingli Zhang, Habsah Mohamad, Iswatun H. Abdullah Ripain, Muhammad Bilal, Amelia J. Lloyd, Abdul A. Mohamed Yusoff, Jafri M. Abdullah

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Epilepsy is one of the most common neurological diseases affecting more than 50 million of people worldwide. Epilepsy is a state of recurrent, spontaneous seizures with multiple syndromes and symptoms of different causes of brain dysfunction, prognosis, and treatments; characterized by transient, occasional and stereotyped interruptions of behavior whereby the excitatory-inhibitory activities within the central nervous system (CNS) are thrown out of balance due to various kinds of interferences. The goal of antiepileptic treatment is to enable patients to be free from seizures or to achieve control of seizures through surgical treatment and/or pharmacotherapy. Pharmacotherapy through AED plays an important role especially in countries with epilepsy treatment gap due to costs and availability of health facilities, skills and resources, yet there are about one-third of the people with epilepsy have drug-resistant seizures. Hence, this poses considerable challenges to the healthcare system and the effort in providing cost-effective treatment as well as the search for alternatives to treatment and management of epilepsy. Enhancement of γ-aminobutyric acid (GABA)-mediated inhibitory neurotransmission is one of the key mechanisms of actions of antiepileptic drugs. GABA type > a receptors (GABAAR) are ligand-gated ion channels that mediate rapid inhibitory neurotransmission upon the binding of GABA with a heteropentameric structure forming a central pore that is permeable to the influx of chloride ions in its activated state. The major isoform of GABAA receptors consists of two α1, two β2, and one γ2 subunit. It is the most abundantly expressed combinations in the brain and the most commonly researched through Xenopus laevis oocytes. With the advancing studies on ethnomedicine and traditional treatments using medicinal plants, increasing evidence reveal that spice and herb plants with medicinal properties play an important role in the treatment of ailments within communities across different cultures. Capsaicin is the primary natural capsaicinoid in hot peppers of plant genus Capsicum, consist of an aromatic ring, an amide linkage and a hydrophobic side chain. The study showed that capsaicins conferred neuroprotection in status epilepticus mouse models through anti-ictogenic, hypothermic, antioxidative, anti-inflammatory, and anti-apoptotic actions in a dose-dependent manner. In this study, five capsaicin derivatives were tested for their ability to increase the GABA-induced chloride current on α1β2γ2S of GABAAR expressed on Xenopus laevis oocytes using the method of two-microelectrode voltage clamp. Two of the capsaicin derivatives, IS5 (N-(4-hydroxy-3-methoxybenzyl)-3-methylbutyramide) and IS10 (N-(4-hydroxy-3-methoxybenzyl)-decanamide) at a concentration of 30µM were able to significantly increase the GABA-induced chloride current with p=0.002 and p=0.026 respectively. This study were able to show the enhancement effect of two capsaicin derivatives with moderate length of hydrocarbon chain on this receptor subtype, revealing the promising inhibitory activity of capsaicin derivatives through enhancement of GABA-induced chloride current and further investigations should be carried out to verify its antiepileptic effects in animal models.

Keywords: α1β2γ2 GABAA receptors, α1β2γ2S, antiepileptic, capsaicin derivatives, two-microelectrode voltage clamp, Xenopus laevis oocytes

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Authors: Boris Nemzer, Nebiyu Abshiru, Z. B. Pietrzkowski

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Coffee cherry is one of the most ubiquitous agricultural commodities which possess nutritional and human health beneficial properties. Between the two most widely used coffee cherries Coffea arabica (Arabica) and Coffea canephora (Robusta), Coffea arabica remains superior due to its sensory properties and, therefore, remains in great demand in the global coffee market. In this study, the phytochemical contents and pharmacokinetics of Coffeeberry® Energy (CBE), a commercially available Arabica whole coffee fruit caffeine extract, are investigated. For phytochemical screening, 20 mg of CBE was dissolved in an aqueous methanol solution for analysis by mass spectrometry (MS). Quantification of caffeine and chlorogenic acids (CGAs) contents of CBE was performed using HPLC. For the bioavailability study, serum samples were collected from human subjects before and after 1, 2 and 3 h post-ingestion of 150mg CBE extract. Protein precipitation and extraction were carried out using methanol. Identification of compounds was performed using an untargeted metabolomic approach on Q-Exactive Orbitrap MS coupled to reversed-phase chromatography. Data processing was performed using Thermo Scientific Compound Discover 3.3 software. Phytochemical screening identified a total of 170 compounds, including organic acids, phenolic acids, CGAs, diterpenoids and hydroxytryptamine. Caffeine & CGAs make up more than, respectively, 70% & 9% of the total CBE composition. For serum samples, a total of 82 metabolites representing 32 caffeine- and 50 phenolic-derived metabolites were identified. Volcano plot analysis revealed 32 differential metabolites (24 caffeine- and 8 phenolic-derived) that showed an increase in serum level post-CBE dosing. Caffeine, uric acid, and trimethyluric acid isomers exhibited 4- to 10-fold increase in serum abundance post-dosing. 7-Methyluric acid, 1,7-dimethyluric acid, paraxanthine and theophylline exhibited a minimum of 1.5-fold increase in serum level. Among the phenolic-derived metabolites, iso-feruloyl quinic acid isomers (3-, 4- and 5-iFQA) showed the highest increase in serum level. These compounds were essentially absent in serum collected before dosage. More interestingly, the iFQA isomers were not originally present in the CBE extract, as our phytochemical screen did not identify these compounds. This suggests the potential formation of the isomers during the digestion and absorption processes. Pharmacokinetics parameters (Cmax, Tmax and AUC0-3h) of caffeine- and phenolic-derived metabolites were also investigated. Caffeine was rapidly absorbed, reaching a maximum concentration (Cmax) of 10.95 µg/ml in just 1 hour. Thereafter, caffeine level steadily dropped from the peak level, although it did not return to baseline within the 3-hour dosing period. The disappearance of caffeine from circulation was mirrored by the rise in the concentration of its methylxanthine metabolites. Similarly, serum concentration of iFQA isomers steadily increased, reaching maximum (Cmax: 3-iFQA, 1.54 ng/ml; 4-iFQA, 2.47 ng/ml; 5-iFQA, 2.91 ng/ml) at tmax of 1.5 hours. The isomers remained well above the baseline during the 3-hour dosing period, allowing them to remain in circulation long enough for absorption into the body. Overall, the current study provides evidence of the potential health benefits of a uniquely formulated whole coffee fruit product. Consumption of this product resulted in a distinct serum profile of bioactive compounds, as demonstrated by the more than 32 metabolites that exhibited a significant change in systemic exposure.

Keywords: phytochemicals, mass spectrometry, pharmacokinetics, differential metabolites, chlorogenic acids

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