Search results for: design and development the information technology architecture
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 36097

Search results for: design and development the information technology architecture

817 Authentic Connection between the Deity and the Individual Human Being Is Vital for Psychological, Biological, and Social Health

Authors: Sukran Karatas

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Authentic energy network interrelations between the Creator and the creations as well as from creations to creations are the most important points for the worlds of physics and metaphysic to unite together and work in harmony, both within human beings, on the other hand, have the ability to choose their own life style voluntarily. However, it includes the automated involuntary spirit, soul and body working systems together with the voluntary actions, which involve personal, cultural and universal, rational or irrational variable values. Therefore, it is necessary for human beings to know the methods of existing authentic energy network connections to be able to communicate correlate and accommodate the physical and metaphysical entities as a proper functioning unity; this is essential for complete human psychological, biological and social well-being. Authentic knowledge is necessary for human beings to verify the position of self within self and with others to regulate conscious and voluntary actions accordingly in order to prevent oppressions and frictions within self and between self and others. Unfortunately, the absence of genuine individual and universal basic knowledge about how to establish an authentic energy network connection within self, with the deity and the environment is the most problematic issue even in the twenty-first century. The second most problematic issue is how to maintain freedom, equality and justice among human beings during these strictly interwoven network connections, which naturally involve physical, metaphysical and behavioral actions of the self and the others. The third and probably the most complicated problem is the scientific identification and the authentication of the deity. This not only provides the whole power and control over the choosers to set their life orders but also to establish perfect physical and metaphysical links as fully coordinated functional energy network. This thus indicates that choosing an authentic deity is the key-point that influences automated, emotional, and behavioral actions altogether, which shapes human perception, personal actions, and life orders. Therefore, we will be considering the existing ‘four types of energy wave end boundary behaviors’, comprising, free end, fixed end boundary behaviors, as well as boundary behaviors from denser medium to less dense medium and from less dense medium to denser medium. Consequently, this article aims to demonstrate that the authentication and the choice of deity has an important effect on individual psychological, biological and social health. It is hoped that it will encourage new researches in the field of authentic energy network connections to establish the best position and the most correct interrelation connections with self and others without violating the authorized orders and the borders of one another to live happier and healthier lives together. In addition, the book ‘Deity and Freedom, Equality, Justice in History, Philosophy, Science’ has more detailed information for those interested in this subject.

Keywords: deity, energy network, power, freedom, equality, justice, happiness, sadness, hope, fear, psychology, biology, sociology

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816 Influence of Structured Capillary-Porous Coatings on Cryogenic Quenching Efficiency

Authors: Irina P. Starodubtseva, Aleksandr N. Pavlenko

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Quenching is a term generally accepted for the process of rapid cooling of a solid that is overheated above the thermodynamic limit of the liquid superheat. The main objective of many previous studies on quenching is to find a way to reduce the total time of the transient process. Computational experiments were performed to simulate quenching by a falling liquid nitrogen film of an extremely overheated vertical copper plate with a structured capillary-porous coating. The coating was produced by directed plasma spraying. Due to the complexities in physical pattern of quenching from chaotic processes to phase transition, the mechanism of heat transfer during quenching is still not sufficiently understood. To our best knowledge, no information exists on when and how the first stable liquid-solid contact occurs and how the local contact area begins to expand. Here we have more models and hypotheses than authentically established facts. The peculiarities of the quench front dynamics and heat transfer in the transient process are studied. The created numerical model determines the quench front velocity and the temperature fields in the heater, varying in space and time. The dynamic pattern of the running quench front obtained numerically satisfactorily correlates with the pattern observed in experiments. Capillary-porous coatings with straight and reverse orientation of crests are investigated. The results show that the cooling rate is influenced by thermal properties of the coating as well as the structure and geometry of the protrusions. The presence of capillary-porous coating significantly affects the dynamics of quenching and reduces the total quenching time more than threefold. This effect is due to the fact that the initialization of a quench front on a plate with a capillary-porous coating occurs at a temperature significantly higher than the thermodynamic limit of the liquid superheat, when a stable solid-liquid contact is thermodynamically impossible. Waves present on the liquid-vapor interface and protrusions on the complex micro-structured surface cause destabilization of the vapor film and the appearance of local liquid-solid micro-contacts even though the average integral surface temperature is much higher than the liquid superheat limit. The reliability of the results is confirmed by direct comparison with experimental data on the quench front velocity, the quench front geometry, and the surface temperature change over time. Knowledge of the quench front velocity and total time of transition process is required for solving practically important problems of nuclear reactors safety.

Keywords: capillary-porous coating, heat transfer, Leidenfrost phenomenon, numerical simulation, quenching

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815 Review of Published Articles on Climate Change and Health in Two Francophone Newspapers: 1990-2015

Authors: Mathieu Hemono, Sophie Puig-Malet, Patrick Zylberman, Avner Bar-Hen, Rainer Sauerborn, Stefanie Schütte, Niamh Herlihi, Antoine Flahault et Anneliese Depoux

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Since the IPCC released its first report in 1990, an increasing number of peer-reviewed publications have reported the health risks associated with climate change. Although there is a large body of evidence supporting the association between climate change and poor health outcomes, the media is inconsistent in the attention it pays to the subject matter. This study aims to analyze the modalities and rhetoric in the media concerning the impact of climate change on health in order to better understand its role in information dissemination. A review was conducted of articles published between 1990 and 2015 in the francophone newspapers Le Monde and Jeune Afrique. A detailed search strategy including specific climate and health terminology was used to search the newspapers’ online databases. 1202 articles were identified as having referenced the terms climate change and health. Inclusion and exclusion criteria were applied to narrow the search to articles referencing the effects of climate change on human health and 160 articles were included in the final analysis. Data was extracted and categorized to create a structured database allowing for further investigation and analysis. The review indicated that although 66% of the selected newspaper articles reference scientific evidence of the impact of climate change on human health, the focus on the topic is limited major political events or is circumstances relating to public health crises. Main findings also include that among the many direct and indirect health outcomes, infectious diseases are the main health outcome highlighted in association with climate change. Lastly, the articles suggest that while developed countries have caused most of the greenhouse effect, the global south is more immediately affected. Overall, the reviewed articles reinforce the need for international cooperation in finding a solution to mitigate the effects of climate change on health. The manner in which scientific results are communicated and disseminated, impact individual and collective perceptions of the topic in the public sphere and affect political will to shape policy. The results of this analysis will underline the modalities of the rhetoric of transparency and provide the basis for a perception study of media discourses. This study is part of an interdisciplinary project called 4CHealth that confronts results of the research done on scientific, political and press literature to better understand how the knowledge on climate changes and health circulates within those different fields and whether and how it is translated to real world change.

Keywords: climate change, health, health impacts, communication, media, rhetoric, awareness, Global South, Africa

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814 Identifying the Needs for Renewal of Urban Water Infrastructure Systems: Analysis of Material, Age, Types and Areas: Case Study of Linköping in Sweden

Authors: Eman Hegazy, Stefan Anderberg, Joakim Krook

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Urban water infrastructure is crucial for efficient and reliable water supply in growing cities. With the growth of cities, the need for maintenance and renewal of these systems increases but often goes unfulfilled due to a variety of reasons, such as limited funding, political priorities, or lack of public awareness. Neglecting the renewal needs of these systems can lead to frequent malfunctions and reduced quality and reliability of water supply, as well as increased costs and health and environmental hazards. It is important for cities to prioritize investment in water infrastructure and develop long-term plans to address renewal needs. Drawing general conclusions about the rate of renewal of urban water infrastructure systems at an international or national level can be challenging due to the influence of local management decisions. In many countries, the responsibility for water infrastructure management lies with the municipal authorities, who are responsible for making decisions about the allocation of resources for repair, maintenance, and renewal. These decisions can vary widely based on factors such as local finances, political priorities, and public perception of the importance of water infrastructure. As a result, it is difficult to make generalizations about the rate of renewal across different countries or regions. In Sweden, the situation is not different, and the information from Svenskt Vatten indicates that the rate of renewal varies across municipalities and can be insufficient, leading to a buildup of maintenance and renewal needs. This study aims to examine the adequacy of the rate of renewal of urban water infrastructure in Linköping case city in Sweden. Using a case study framework, the study will assess the current status of the urban water system and the need for renewal. The study will also consider the role of factors such as proper identification processes, limited funding, competing for political priorities, and local management decisions in contributing to insufficient renewal. The study investigates the following questions: (1) What is the current status of water and sewerage networks in terms of length, age distribution, and material composition, estimated total water leakage in the network per year, damages, leaks, and outages occur per year, both overall and by district? (2) What are the main causes of these damages, leaks, and interruptions, and how are they related to lack of maintenance and renewal? (3) What is the current status of renewal work for the water and sewerage networks, including the renewal rate and changes over time, recent renewal material composition, and the budget allocation for renewal and emergency repairs? (4) What factors influence the need for renewal and what conditions should be considered in the assessment? The findings of the study provide insights into the challenges facing urban water infrastructure and identify strategies for improving the rate of renewal to ensure a reliable and sustainable water supply.

Keywords: case study, infrastructure, management, renewal need, Sweden

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813 Dietary Diversification and Nutritional Education: A Strategy to Improve Child Food Security Status in the Rural Mozambique

Authors: Rodriguez Diego, Del Valle Martin, Hargreaves Matias, Riveros Jose Luis

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Nutrient deficiencies due to a diet low in quantitative and qualitative terms, are prevalent throughout the developing world, especially in sub-Saharan Africa. Children and women of childbearing age are especially vulnerable. Limited availability, access and intake of animal foods at home and lack of knowledge about their value in the diet and the role they play in health, contribute to poor diet quality. Poor bioavailability of micronutrients in diets based on foods high in fiber and phytates, the low content of some micronutrients in these foods are further factors to consider. Goats are deeply embedded in almost every Sub-Saharan African rural culture, generally kept for their milk, meat, hair or leather. Goats have played an important role in African social life, especially in food security. Goat meat has good properties for human wellbeing, with a special role in lower income households. It has a high-quality protein (20 protein g/100 meat g) including all essential amino acids, good unsaturated/satured fatty acids relationship, and it is an important B-vitamin source with high micronutrients bioavailability. Mozambique has major food security problems, with poor food access and utilization, undiversified diets, chronic poverty and child malnutrition. Our objective was to design a nutritional intervention based on a dietary diversification, nutritional education, cultural beliefs and local resources, aimed to strengthen food security of children at Barrio Broma village (15°43'58.78"S; 32°46'7.27"E) in Chitima, Mozambique. Two surveys were conducted first of socio-productive local databases and then to 100 rural households about livelihoods, food diversity and anthropometric measurements in children under 5 years. Our results indicate that the main economic activity is goat production, based on a native breed with two deliveries per year in the absence of any management. Adult goats weighted 27.2±10.5 kg and raised a height of 63.5±3.8 cm. Data showed high levels of poverty, with a food diversity score of 2.3 (0-12 points), where only 30% of households consume protein and 13% iron, zinc, and B12 vitamin. The main constraints to food security were poor access to water and low income to buy food. Our dietary intervention was based on improving diet quality by increasing the access to dried goat meat, fresh vegetables, and legumes, and its utilization by a nutritional education program. This proposal was based on local culture and living conditions characterized by the absence of electricity power and drinkable water. The drying process proposed would secure the food maintenance under local conditions guaranteeing food safety for a longer period. Additionally, an ancient local drying technique was rescued and used. Moreover, this kind of dietary intervention would be the most efficient way to improve the infant nutrition by delivering macro and micronutrients on time to these vulnerable populations.

Keywords: child malnutrition, dietary diversification, food security, goat meat

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812 Trajectory Generation Procedure for Unmanned Aerial Vehicles

Authors: Amor Jnifene, Cedric Cocaud

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One of the most constraining problems facing the development of autonomous vehicles is the limitations of current technologies. Guidance and navigation controllers need to be faster and more robust. Communication data links need to be more reliable and secure. For an Unmanned Aerial Vehicles (UAV) to be useful, and fully autonomous, one important feature that needs to be an integral part of the navigation system is autonomous trajectory planning. The work discussed in this paper presents a method for on-line trajectory planning for UAV’s. This method takes into account various constraints of different types including specific vectors of approach close to target points, multiple objectives, and other constraints related to speed, altitude, and obstacle avoidance. The trajectory produced by the proposed method ensures a smooth transition between different segments, satisfies the minimum curvature imposed by the dynamics of the UAV, and finds the optimum velocity based on available atmospheric conditions. Given a set of objective points and waypoints a skeleton of the trajectory is constructed first by linking all waypoints with straight segments based on the order in which they are encountered in the path. Secondly, vectors of approach (VoA) are assigned to objective waypoints and their preceding transitional waypoint if any. Thirdly, the straight segments are replaced by 3D curvilinear trajectories taking into account the aircraft dynamics. In summary, this work presents a method for on-line 3D trajectory generation (TG) of Unmanned Aerial Vehicles (UAVs). The method takes as inputs a series of waypoints and an optional vector of approach for each of the waypoints. Using a dynamic model based on the performance equations of fixed wing aircrafts, the TG computes a set of 3D parametric curves establishing a course between every pair of waypoints, and assembling these sets of curves to construct a complete trajectory. The algorithm ensures geometric continuity at each connection point between two sets of curves. The geometry of the trajectory is optimized according to the dynamic characteristics of the aircraft such that the result translates into a series of dynamically feasible maneuvers. In summary, this work presents a method for on-line 3D trajectory generation (TG) of Unmanned Aerial Vehicles (UAVs). The method takes as inputs a series of waypoints and an optional vector of approach for each of the waypoints. Using a dynamic model based on the performance equations of fixed wing aircraft, the TG computes a set of 3D parametric curves establishing a course between every pair of waypoints, and assembling these sets of curves to construct a complete trajectory. The algorithm ensures geometric continuity at each connection point between two sets of curves. The geometry of the trajectory is optimized according to the dynamic characteristics of the aircraft such that the result translates into a series of dynamically feasible maneuvers.

Keywords: trajectory planning, unmanned autonomous air vehicle, vector of approach, waypoints

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811 Journey to Inclusive School: Description of Crucial Sensitive Concepts in the Context of Situational Analysis

Authors: Denisa Denglerova, Radim Sip

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Academic sources as well as international agreements and national documents define inclusion in terms of several criteria: equal opportunities, fulfilling individual needs, development of human resources, community participation. In order for these criteria to be met, the community must be cohesive. Community cohesion, which is a relatively new concept, is not determined by homogeneity, but by the acceptance of diversity among the community members and utilisation of its positive potential. This brings us to a central category of inclusion - appreciating diversity and using it to a positive effect. However, school diversity is a real phenomenon, which schools need to tackle more and more often. This is also indicated by the number of publications focused on diversity in schools. These sources present recent analyses of using identity as a tool of coping with the demands of a diversified society. The aim of this study is to identify and describe in detail the processes taking place in selected schools, which contribute to their pro-inclusive character. The research is designed around a multiple case study of three pro-inclusive schools. Paradigmatically speaking, the research is rooted in situational epistemology. This is also related to the overall framework of interpretation, for which we are going to use innovative methods of situational analysis. In terms of specific research outcomes this will manifest itself in replacing the idea of “objective theory” by the idea of “detailed cartography of a social world”. The cartographic approach directs both the logic of data collection and the choice of methods of their analysis and interpretation. The research results include detection of the following sensitive concepts: Key persons. All participants can contribute to promoting an inclusion-friendly environment; however, some do so with greater motivation than others. These could include school management, teachers with a strong vision of equality, or school counsellors. They have a significant effect on the transformation of the school, and are themselves deeply convinced that inclusion is necessary. Accordingly, they select suitable co-workers; they also inspire some of the other co-workers to make changes, leading by example. Employees with strongly opposing views gradually leave the school, and new members of staff are introduced to the concept of inclusion and openness from the beginning. Manifestations of school openness in working with diversity on all important levels. By this we mean positive manipulation with diversity both in the relationships between “traditional” school participants (directors, teachers, pupils) and school-parent relationships, or relationships between schools and the broader community, in terms of teaching methods as well as ways how the school culture affects the school environment. Other important detected concepts significantly helping to form a pro-inclusive environment in the school are individual and parallel classes; freedom and responsibility of both pupils and teachers, manifested on the didactic level by tendencies towards an open curriculum; ways of asserting discipline in the school environment.

Keywords: inclusion, diversity, education, sensitive concept, situational analysis

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810 South African Breast Cancer Mutation Spectrum: Pitfalls to Copy Number Variation Detection Using Internationally Designed Multiplex Ligation-Dependent Probe Amplification and Next Generation Sequencing Panels

Authors: Jaco Oosthuizen, Nerina C. Van Der Merwe

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The National Health Laboratory Services in Bloemfontien has been the diagnostic testing facility for 1830 patients for familial breast cancer since 1997. From the cohort, 540 were comprehensively screened using High-Resolution Melting Analysis or Next Generation Sequencing for the presence of point mutations and/or indels. Approximately 90% of these patients stil remain undiagnosed as they are BRCA1/2 negative. Multiplex ligation-dependent probe amplification was initially added to screen for copy number variation detection, but with the introduction of next generation sequencing in 2017, was substituted and is currently used as a confirmation assay. The aim was to investigate the viability of utilizing internationally designed copy number variation detection assays based on mostly European/Caucasian genomic data for use within a South African context. The multiplex ligation-dependent probe amplification technique is based on the hybridization and subsequent ligation of multiple probes to a targeted exon. The ligated probes are amplified using conventional polymerase chain reaction, followed by fragment analysis by means of capillary electrophoresis. The experimental design of the assay was performed according to the guidelines of MRC-Holland. For BRCA1 (P002-D1) and BRCA2 (P045-B3), both multiplex assays were validated, and results were confirmed using a secondary probe set for each gene. The next generation sequencing technique is based on target amplification via multiplex polymerase chain reaction, where after the amplicons are sequenced parallel on a semiconductor chip. Amplified read counts are visualized as relative copy numbers to determine the median of the absolute values of all pairwise differences. Various experimental parameters such as DNA quality, quantity, and signal intensity or read depth were verified using positive and negative patients previously tested internationally. DNA quality and quantity proved to be the critical factors during the verification of both assays. The quantity influenced the relative copy number frequency directly whereas the quality of the DNA and its salt concentration influenced denaturation consistency in both assays. Multiplex ligation-dependent probe amplification produced false positives due to ligation failure when ligation was inhibited due to a variant present within the ligation site. Next generation sequencing produced false positives due to read dropout when primer sequences did not meet optimal multiplex binding kinetics due to population variants in the primer binding site. The analytical sensitivity and specificity for the South African population have been proven. Verification resulted in repeatable reactions with regards to the detection of relative copy number differences. Both multiplex ligation-dependent probe amplification and next generation sequencing multiplex panels need to be optimized to accommodate South African polymorphisms present within the genetically diverse ethnic groups to reduce the false copy number variation positive rate and increase performance efficiency.

Keywords: familial breast cancer, multiplex ligation-dependent probe amplification, next generation sequencing, South Africa

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809 Research Project on Learning Rationality in Strategic Behaviors: Interdisciplinary Educational Activities in Italian High Schools

Authors: Giovanna Bimonte, Luigi Senatore, Francesco Saverio Tortoriello, Ilaria Veronesi

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The education process considers capabilities not only to be seen as a means to a certain end but rather as an effective purpose. Sen's capability approach challenges human capital theory, which sees education as an ordinary investment undertaken by individuals. A complex reality requires complex thinking capable of interpreting the dynamics of society's changes to be able to make decisions that can be rational for private, ethical and social contexts. Education is not something removed from the cultural and social context; it exists and is structured within it. In Italy, the "Mathematical High School Project" is a didactic research project is based on additional laboratory courses in extracurricular hours where mathematics intends to bring itself in a dialectical relationship with other disciplines as a cultural bridge between the two cultures, the humanistic and the scientific ones, with interdisciplinary educational modules on themes of strong impact in younger life. This interdisciplinary mathematics presents topics related to the most advanced technologies and contemporary socio-economic frameworks to demonstrate how mathematics is not only a key to reading but also a key to resolving complex problems. The recent developments in mathematics provide the potential for profound and highly beneficial changes in mathematics education at all levels, such as in socio-economic decisions. The research project is built to investigate whether repeated interactions can successfully promote cooperation among students as rational choice and if the skill, the context and the school background can influence the strategies choice and the rationality. A Laboratory on Game Theory as mathematical theory was conducted in the 4th year of the Mathematical High Schools and in an ordinary scientific high school of the Scientific degree program. Students played two simultaneous games of repeated Prisoner's Dilemma with an indefinite horizon, with two different competitors in each round; even though the competitors in each round will remain the same for the duration of the game. The results highlight that most of the students in the two classes used the two games with an immunization strategy against the risk of losing: in one of the games, they started by playing Cooperate, and in the other by the strategy of Compete. In the literature, theoretical models and experiments show that in the case of repeated interactions with the same adversary, the optimal cooperation strategy can be achieved by tit-for-tat mechanisms. In higher education, individual capacities cannot be examined independently, as conceptual framework presupposes a social construction of individuals interacting and competing, making individual and collective choices. The paper will outline all the results of the experimentation and the future development of the research.

Keywords: game theory, interdisciplinarity, mathematics education, mathematical high school

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808 Impact of National Institutions on Corporate Social Performance

Authors: Debdatta Mukherjee, Abhiman Das, Amit Garg

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In recent years, there is a growing interest about corporate social responsibility of firms in both academic literature and business world. Since business forms a part of society incorporating socio-environment concerns into its value chain, activities are vital for ensuring mutual sustainability and prosperity. But, until now most of the works have been either descriptive or normative rather than positivist in tone. Even the few ones with a positivist approach have mostly studied the link between corporate financial performance and corporate social performance. However, these studies have been severely criticized by many eminent authors on grounds that they lack a theoretical basis for their findings. They have also argued that apart from corporate financial performance, there must be certain other crucial influences that are likely to determine corporate social performance of firms. In fact, several studies have indicated that firms operating in distinct national institutions show significant variations in the corporate social responsibility practices that they undertake. This clearly suggests that the institutional context of a country in which the firms operate is a key determinant of corporate social performance of firms. Therefore, this paper uses an institutional framework to understand why corporate social performance of firms vary across countries. It examines the impact of country level institutions on corporate social performance using a sample of 3240 global publicly-held firms across 33 countries covering the period 2010-2015. The country level institutions include public institutions, private institutions, markets and capacity to innovate. Econometric Analysis has been mainly used to assess this impact. A three way panel data analysis using fixed effects has been used to test and validate appropriate hypotheses. Most of the empirical findings confirm our hypotheses and the economic significance indicates the specific impact of each variable and their importance relative to others. The results suggest that institutional determinants like ethical behavior of private institutions, goods market, labor market and innovation capacity of a country are significantly related to the corporate social performance of firms. Based on our findings, few implications for policy makers from across the world have also been suggested. The institutions in a country should promote competition. The government should use policy levers for upgrading home demands, like setting challenging yet flexible safety, quality and environment standards, and framing policies governing buyer information, providing innovative recourses to low quality goods and services and promoting early adoption of new and technologically advanced products. Moreover, the institution building in a country should be such that they facilitate and improve the capacity of firms to innovate. Therefore, the proposed study argues that country level institutions impact corporate social performance of firms, empirically validates the same, suggest policy implications and attempts to contribute to an extended understanding of corporate social responsibility and corporate social performance in a multinational context.

Keywords: corporate social performance, corporate social responsibility, institutions, markets

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807 Redefining Intellectual Humility in Indian Context: An Experimental Investigation

Authors: Jayashree And Gajjam

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Intellectual humility (IH) is defined as a virtuous mean between intellectual arrogance and intellectual self-diffidence by the ‘Doxastic Account of IH’ studied, researched and developed by western scholars not earlier than 2015 at the University of Edinburgh. Ancient Indian philosophical texts or the Upanisads written in the Sanskrit language during the later Vedic period (circa 600-300 BCE) have long addressed the virtue of being humble in several stories and narratives. The current research paper questions and revisits these character traits in an Indian context following an experimental method. Based on the subjective reports of more than 400 Indian teenagers and adults, it argues that while a few traits of IH (such as trustworthiness, respectfulness, intelligence, politeness, etc.) are panhuman and pancultural, a few are not. Some attributes of IH (such as proper pride, open-mindedness, awareness of own strength, etc.) may be taken for arrogance by the Indian population, while other qualities of Intellectual Diffidence such as agreeableness, surrendering can be regarded as the characteristic of IH. The paper then gives the reasoning for this discrepancy that can be traced back to the ancient Indian (Upaniṣadic) teachings that are still prevalent in many Indian families and still anchor their views on IH. The name Upanisad itself means ‘sitting down near’ (to the Guru to gain the Supreme knowledge of the Self and the Universe and setting to rest ignorance) which is equivalent to the three traits among the BIG SEVEN characterized as IH by the western scholars viz. ‘being a good listener’, ‘curious to learn’, and ‘respect to other’s opinion’. The story of Satyakama Jabala (Chandogya Upanisad 4.4-8) who seeks the truth for several years even from the bull, the fire, the swan and waterfowl, suggests nothing but the ‘need for cognition’ or ‘desire for knowledge’. Nachiketa (Katha Upanisad), a boy with a pure mind and heart, follows his father’s words and offers himself to Yama (the God of Death) where after waiting for Yama for three days and nights, he seeks the knowledge of the mysteries of life and death. Although the main aim of these Upaniṣadic stories is to give the knowledge of life and death, the Supreme reality which can be identical with traits such as ‘curious to learn’, one cannot deny that they have a lot more to offer than mere information about true knowledge e.g., ‘politeness’, ‘good listener’, ‘awareness of own limitations’, etc. The possible future scope of this research includes (1) finding other socio-cultural factors that affect the ideas on IH such as age, gender, caste, type of education, highest qualification, place of residence and source of income, etc. which may be predominant in current Indian society despite our great teachings of the Upaniṣads, and (2) to devise different measures to impart IH in Indian children, teenagers, and younger adults for the harmonious future. The current experimental research can be considered as the first step towards these goals.

Keywords: ethics and virtue epistemology, Indian philosophy, intellectual humility, upaniṣadic texts in ancient India

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806 Empowering Leaders: Strategies for Effective Management in a Changing World

Authors: Shahid Ali

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Leadership and management are essential components of running successful organizations. Both concepts are closely related but serve different purposes in the overall management of a company. Leadership focuses on inspiring and motivating employees towards a common goal, while management involves coordinating and directing resources to achieve organizational objectives efficiently. Objectives of Leadership and Management: Inspiring and motivating employees: A key objective of leadership is to inspire and motivate employees to work towards achieving the organization’s goals. Effective leaders create a vision that employees can align with and provide the necessary motivation to drive performance. Setting goals and objectives: Both leadership and management play a crucial role in setting goals and objectives for the organization. Leaders create a vision for the future, while managers develop plans to achieve specific objectives within the given timeframe. Implementing strategies: Leaders come up with innovative strategies to drive the organization forward, while managers are responsible for implementing these strategies effectively. Together, leadership and management ensure that the organization’s plans are executed efficiently. Contributions of Leadership and Management: Employee Engagement: Effective leadership and management can increase employee engagement and satisfaction. When employees feel motivated and inspired by their leaders, they are more likely to be engaged in their work and contribute to the organization’s success. Organizational Success: Good leadership and management are essential for navigating the challenges and changes that organizations face. By setting clear goals, inspiring employees, and making strategic decisions, leaders and managers can drive organizational success. Talent Development: Leaders and managers are responsible for identifying and developing talent within the organization. By providing feedback, training, and coaching, they can help employees reach their full potential and contribute effectively to the organization. Research Type: The research on leadership and management is typically quantitative and qualitative in nature. Quantitative research involves the collection and analysis of numerical data to understand the impact of leadership and management practices on organizational outcomes. This type of research often uses surveys, questionnaires, and statistical analysis to measure variables such as employee satisfaction, performance, and organizational success. Qualitative research, on the other hand, involves exploring the subjective experiences and perspectives of individuals related to leadership and management. This type of research may include interviews, observations, and case studies to gain a deeper understanding of how leadership and management practices influence organizational behavior and outcomes. In conclusion, leadership and management play a critical role in the success of organizations. Through effective leadership and management practices, organizations can inspire and motivate employees, set goals, and implement strategies to achieve their objectives. Research on leadership and management helps to understand the impact of these practices on organizational outcomes and provides valuable insights for improving leadership and management practices in the future.

Keywords: empowering, leadership, management, adaptability

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805 Cultural Identity and Self-Censorship in Social Media: A Qualitative Case Study

Authors: Nastaran Khoshsabk

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The evolution of communication through the Internet has influenced shaping and reshaping the self-presentation of social media users. Online communities both connect people and give voice to the voiceless allowing them to present themselves nationally and globally. People all around the world are experiencing censorship in different aspects of their life. Censorship can be externally imposed because of the political situations, or it can be self-imposed. Social media users choose the content they want to share and decide about the online audiences with whom they want to share this content. Most social media networks, such as Facebook, enable their users to be selective about the shared content and its availability to other people. However, sometimes instead of targeting a specific audience, users self-censor themselves or decide not to share various forms of information. These decisions are of particular importance in countries such as Iran where Internet is not the arena of free self-presentation and people are encouraged to stay away from political participation in the country and acting against the Islamic values. Facebook and some other social media tools are blocked in countries such as Iran. This project investigates the importance of social media in the life of Iranians to explore how they present themselves and construct their digital selves. The notion of cultural identity is applied in this research to explore the educational and informative role of social media in the identity formation and cultural representation of Facebook users. This study explores the self-censorship of Iranian adult Facebook users through their online self-representation and communication on the Internet. The data in this qualitative multiple case study have been collected through individual synchronous online interviews with the researcher’s Facebook friends and through the analysis of the participants’ Facebook profiles and activities over a period of six months. The data is analysed with an emphasis on the identity formation of participants through the recognition of the underlying themes. The exploration of online interviews is on the basis of participants’ personal accounts of self-censorship and cultural understanding through using social media. The driven codes and themes have been categorised considering censorship and place of culture on representation of self. Participants were asked to explain their views about censorship and conservatism through using social media. They reported their thoughts about deciding which content to share on Facebook and which to self-censor and their reasons behind these decisions. The codes and themes have been categorised considering censorship and its role in representation of idealised self. The ‘actual self’ showed to be hidden by an individual for different reasons such as its influence on their social status, academic achievements and job opportunities. It is hoped that this research will have implications for education contexts in countries that are experiencing social media filtering by offering an increased understanding of the importance of online communities; which can provide an educational environment to talk and learn about social taboos and constructing adults’ identity in virtual environment and through cultural self-presentation.

Keywords: cultural identity, identity formation, online communities, self-censorship

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804 Emotion Regulation and Executive Functioning Scale for Children and Adolescents (REMEX): Scale Development

Authors: Cristina Costescu, Carmen David, Adrian Roșan

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Executive functions (EF) and emotion regulation strategies are processes that allow individuals to function in an adaptative way and to be goal-oriented, which is essential for success in daily living activities, at school, or in social contexts. The Emotion Regulation and Executive Functioning Scale for Children and Adolescents (REMEX) represents an empirically based tool (based on the model of EF developed by Diamond) for evaluating significant dimensions of child and adolescent EFs and emotion regulation strategies, mainly in school contexts. The instrument measures the following dimensions: working memory, inhibition, cognitive flexibility, executive attention, planning, emotional control, and emotion regulation strategies. Building the instrument involved not only a top-down process, as we selected the content in accordance with prominent models of FE, but also a bottom-up one, as we were able to identify valid contexts in which FE and ER are put to use. For the construction of the instrument, we implemented three focus groups with teachers and other professionals since the aim was to develop an accurate, objective, and ecological instrument. We used the focus group method in order to address each dimension and to yield a bank of items to be further tested. Each dimension is addressed through a task that the examiner will apply and through several items derived from the main task. For the validation of the instrument, we plan to use item response theory (IRT), also known as the latent response theory, that attempts to explain the relationship between latent traits (unobservable cognitive processes) and their manifestations (i.e., observed outcomes, responses, or performance). REMEX represents an ecological scale that integrates a current scientific understanding of emotion regulation and EF and is directly applicable to school contexts, and it can be very useful for developing intervention protocols. We plan to test his convergent validity with the Childhood Executive Functioning Inventory (CHEXI) and Emotion Dysregulation Inventory (EDI) and divergent validity between a group of typically developing children and children with neurodevelopmental disorders, aged between 6 and 9 years old. In a previous pilot study, we enrolled a sample of 40 children with autism spectrum disorders and attention-deficit/hyperactivity disorder aged 6 to 12 years old, and we applied the above-mentioned scales (CHEXI and EDI). Our results showed that deficits in planning, bebavior regulation, inhibition, and working memory predict high levels of emotional reactivity, leading to emotional and behavioural problems. Considering previous results, we expect our findings to provide support for the validity and reliability of the REMEX version as an ecological instrument for assessing emotion regulation and EF in children and for key features of its uses in intervention protocols.

Keywords: executive functions, emotion regulation, children, item response theory, focus group

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803 Problem Solving in Mathematics Education: A Case Study of Nigerian Secondary School Mathematics Teachers’ Conceptions in Relation to Classroom Instruction

Authors: Carol Okigbo

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Mathematical problem solving has long been accorded an important place in mathematics curricula at every education level in both advanced and emerging economies. Its classroom approaches have varied, such as teaching for problem-solving, teaching about problem-solving, and teaching mathematics through problem-solving. It requires engaging in tasks for which the solution methods are not eminent, making sense of problems and persevering in solving them by exhibiting processes, strategies, appropriate attitude, and adequate exposure. Teachers play important roles in helping students acquire competency in problem-solving; thus, they are expected to be good problem-solvers and have proper conceptions of problem-solving. Studies show that teachers’ conceptions influence their decisions about what to teach and how to teach. Therefore, how teachers view their roles in teaching problem-solving will depend on their pedagogical conceptions of problem-solving. If teaching problem-solving is a major component of secondary school mathematics instruction, as recommended by researchers and mathematics educators, then it is necessary to establish teachers’ conceptions, what they do, and how they approach problem-solving. This study is designed to determine secondary school teachers’ conceptions regarding mathematical problem solving, its current situation, how teachers’ conceptions relate to their demographics, as well as the interaction patterns in the mathematics classroom. There have been many studies of mathematics problem solving, some of which addressed teachers’ conceptions using single-method approaches, thereby presenting only limited views of this important phenomenon. To address the problem more holistically, this study adopted an integrated mixed methods approach which involved a quantitative survey, qualitative analysis of open-ended responses, and ethnographic observations of teachers in class. Data for the analysis came from a random sample of 327 secondary school mathematics teachers in two Nigerian states - Anambra State and Enugu State who completed a 45-item questionnaire. Ten of the items elicited demographic information, 11 items were open-ended questions, and 25 items were Likert-type questions. Of the 327 teachers who responded to the questionnaires, 37 were randomly selected and observed in their classes. Data analysis using ANOVA, t-tests, chi-square tests, and open coding showed that the teachers had different conceptions about problem-solving, which fall into three main themes: practice on exercises and word application problems, a process of solving mathematical problems, and a way of teaching mathematics. Teachers reported that no period is set aside for problem-solving; typically, teachers solve problems on the board, teach problem-solving strategies, and allow students time to struggle with problems on their own. The result shows a significant difference between male and female teachers’ conception of problems solving, a significant relationship among teachers’ conceptions and academic qualifications, and teachers who have spent ten years or more teaching mathematics were significantly different from the group with seven to nine years of experience in terms of their conceptions of problem-solving.

Keywords: conceptions, education, mathematics, problem solving, teacher

Procedia PDF Downloads 69
802 What Is At Stake When Developing and Using a Rubric to Judge Chemistry Honours Dissertations for Entry into a PhD?

Authors: Moira Cordiner

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As a result of an Australian university approving a policy to improve the quality of assessment practices, as an academic developer (AD) with expertise in criterion-referenced assessment commenced in 2008. The four-year appointment was to support 40 'champions' in their Schools. This presentation is based on the experiences of a group of Chemistry academics who worked with the AD to develop and implement an honours dissertation rubric. Honours is a research year following a three-year undergraduate year. If the standard of the student's work is high enough (mainly the dissertation) then the student can commence a PhD. What became clear during the process was that much more was at stake than just the successful development and trial of the rubric, including academics' reputations, university rankings and research outputs. Working with the champion-Head of School(HOS) and the honours coordinator, the AD helped them adapt an honours rubric that she had helped create and trial successfully for another Science discipline. A year of many meetings and complex power plays between the two academics finally resulted in a version that was critiqued by the Chemistry teaching and learning committee. Accompanying the rubric was an explanation of grading rules plus a list of supervisor expectations to explain to students how the rubric was used for grading. Further refinements were made until all staff were satisfied. It was trialled successfully in 2011, then small changes made. It was adapted and implemented for Medicine honours with her help in 2012. Despite coming to consensus about statements of quality in the rubric, a few academics found it challenging matching these to the dissertations and allocating a grade. They had had no time to undertake training to do this, or make overt their implicit criteria and standards, which some admitted they were using - 'I know what a first class is'. Other factors affecting grading included: the small School where all supervisors knew each other and the students, meant that friendships and collegiality were at stake if low grades were given; no external examiners were appointed-all were internal with the potential for bias; supervisors’ reputations were at stake if their students did not receive a good grade; the School's reputation was also at risk if insufficient honours students qualified for PhD entry; and research output was jeopardised without enough honours students to work on supervisors’ projects. A further complication during the study was a restructure of the university and retrenchments, with pressure to increase research output as world rankings assumed greater importance to senior management. In conclusion, much more was at stake than developing a usable rubric. The HOS had to be seen to champion the 'new' assessment practice while balancing institutional demands for increased research output and ensuring as many honours dissertations as possible met high standards, so that eventually the percentage of PhD completions and research output rose. It is therefore in the institution's best interest for this cycle to be maintained as it affects rankings and reputations. In this context, are rubrics redundant?

Keywords: explicit and implicit standards, judging quality, university rankings, research reputations

Procedia PDF Downloads 332
801 Pesticides Monitoring in Surface Waters of the São Paulo State, Brazil

Authors: Fabio N. Moreno, Letícia B. Marinho, Beatriz D. Ruiz, Maria Helena R. B. Martins

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Brazil is a top consumer of pesticides worldwide, and the São Paulo State is one of the highest consumers among the Brazilian federative states. However, representative data about the occurrence of pesticides in surface waters of the São Paulo State is scarce. This paper aims to present the results of pesticides monitoring executed within the Water Quality Monitoring Network of CETESB (The Environmental Agency of the São Paulo State) between the 2018-2022 period. Surface water sampling points (21 to 25) were selected within basins of predominantly agricultural land-use (5 to 85% of cultivated areas). The samples were collected throughout the year, including high-flow and low-flow conditions. The frequency of sampling varied between 6 to 4 times per year. Selection of pesticide molecules for monitoring followed a prioritizing process from EMBRAPA (Brazilian Agricultural Research Corporation) databases of pesticide use. Pesticides extractions in aqueous samples were performed according to USEPA 3510C and 3546 methods following quality assurance and quality control procedures. Determination of pesticides in water (ng L-1) extracts were performed by high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) and by gas chromatography with nitrogen phosphorus (GC-NPD) and electron capture detectors (GC-ECD). The results showed higher frequencies (20- 65%) in surface water samples for Carbendazim (fungicide), Diuron/Tebuthiuron (herbicides) and Fipronil/Imidaclopride (insecticides). The frequency of observations for these pesticides were generally higher in monitoring points located in sugarcane cultivated areas. The following pesticides were most frequently quantified above the Aquatic life benchmarks for freshwater (USEPA Office of Pesticide Programs, 2023) or Brazilian Federal Regulatory Standards (CONAMA Resolution no. 357/2005): Atrazine, Imidaclopride, Carbendazim, 2,4D, Fipronil, and Chlorpiryfos. Higher median concentrations for Diuron and Tebuthiuron in the rainy months (october to march) indicated pesticide transport through surface runoff. However, measurable concentrations in the dry season (april to september) for Fipronil and Imidaclopride also indicates pathways related to subsurface or base flow discharge after pesticide soil infiltration and leaching or dry deposition following pesticide air spraying. With exception to Diuron, no temporal trends related to median concentrations of the most frequently quantified pesticides were observed. These results are important to assist policymakers in the development of strategies aiming at reducing pesticides migration to surface waters from agricultural areas. Further studies will be carried out in selected points to investigate potential risks as a result of pesticides exposure on aquatic biota.

Keywords: pesticides monitoring, são paulo state, water quality, surface waters

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800 Motivation and Constraints of Athletes’ Migration: Foreign Players in Korean Volleyball League (V-League)

Authors: Young Ik Suh, Sanghak Lee, Tywan G. Martin

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An increasing number of athletes, across all sports, are moving from their home countries to play in foreign countries. The migration of athletes, coaches, managers, and administrators within and between nations is an important aspect of the social and cultural changes taking place in modern, global sports. It is especially important to understand the context of these migrations as they are critical factors in the successful development of sports policies. In previous decades, efforts have been made to understand the motives of migrating athletes from a variety of sports, including rugby, cricket, baseball, and soccer. These studies focused on the athletes’ motivations, experiences as migrants, and recruit process. However, few studies have been conducted in order to understand athletes’ constraints of migration. The concept of constraints in leisure studies refers to the barriers that exist between an individual’s desire for participation and an individual’s real participation. The study of constraints is not a new topic in the fields of sports and recreation. In addition to understanding the motives that drive athletes to work or play in foreign countries, it is also important to recognize that negative dimensions exist that stop some athletes from migrating. Furthermore, little research has explored what makes athletes consider playing in small and unknown volleyball markets, such as the Korean Volleyball League (V-League). The V-League is a professional men’s and women’s volleyball league, started in 2005. It consists of seven men’s clubs, and six women’s clubs and each team has one foreign player. In addition, several limitations are placed on the foreign players, such as on height, position, and salary to play in the V-League. Thus, the main focus of the present research is to understand why foreign athletes (e.g., European, American, Brazil, etc.) are attracted to the V-League, which has a smaller market compared to its neighbors (i.e., China, Japan, and The Philippines). In addition, the current study seeks to identify the negative factors that prevent athletes from playing in the V-League. The participants for this study will be foreign volleyball players participating in the V-League. The investigators will provide a brief introduction to this study and inform the potential participants that they can choose whether to participate in this study. In terms of theoretical saturation, at least 12 participants are generally an adequate number to reach saturation, if they belong to a relatively homogenous group based on culture and ethnicity. This study utilizes a qualitative approach in order to understand the migration experiences foreign volleyball athletes playing in the V-League. The proposed study represents ongoing research to support work conducted by the investigators to understand the possible motivations and constraints for foreign volleyball players playing in the V-League. In addition, significant contributions to scholarship in the field of sports, psychology, and coaching studies will be an outcome of this study along with additions to the body of knowledge in several disciplines, including psychology, sociology, and social work.

Keywords: athletes’ migration, motivation, constraints, volleyball

Procedia PDF Downloads 256
799 An Elasto-Viscoplastic Constitutive Model for Unsaturated Soils: Numerical Implementation and Validation

Authors: Maria Lazari, Lorenzo Sanavia

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Mechanics of unsaturated soils has been an active field of research in the last decades. Efficient constitutive models that take into account the partial saturation of soil are necessary to solve a number of engineering problems e.g. instability of slopes and cuts due to heavy rainfalls. A large number of constitutive models can now be found in the literature that considers fundamental issues associated with the unsaturated soil behaviour, like the volume change and shear strength behaviour with suction or saturation changes. Partially saturated soils may either expand or collapse upon wetting depending on the stress level, and it is also possible that a soil might experience a reversal in the volumetric behaviour during wetting. Shear strength of soils also changes dramatically with changes in the degree of saturation, and a related engineering problem is slope failures caused by rainfall. There are several states of the art reviews over the last years for studying the topic, usually providing a thorough discussion of the stress state, the advantages, and disadvantages of specific constitutive models as well as the latest developments in the area of unsaturated soil modelling. However, only a few studies focused on the coupling between partial saturation states and time effects on the behaviour of geomaterials. Rate dependency is experimentally observed in the mechanical response of granular materials, and a viscoplastic constitutive model is capable of reproducing creep and relaxation processes. Therefore, in this work an elasto-viscoplastic constitutive model for unsaturated soils is proposed and validated on the basis of experimental data. The model constitutes an extension of an existing elastoplastic strain-hardening constitutive model capable of capturing the behaviour of variably saturated soils, based on energy conjugated stress variables in the framework of superposed continua. The purpose was to develop a model able to deal with possible mechanical instabilities within a consistent energy framework. The model shares the same conceptual structure of the elastoplastic laws proposed to deal with bonded geomaterials subject to weathering or diagenesis and is capable of modelling several kinds of instabilities induced by the loss of hydraulic bonding contributions. The novelty of the proposed formulation is enhanced with the incorporation of density dependent stiffness and hardening coefficients in order to allow the modeling of the pycnotropy behaviour of granular materials with a single set of material constants. The model has been implemented in the commercial FE platform PLAXIS, widely used in Europe for advanced geotechnical design. The algorithmic strategies adopted for the stress-point algorithm had to be revised to take into account the different approach adopted by PLAXIS developers in the solution of the discrete non-linear equilibrium equations. An extensive comparison between models with a series of experimental data reported by different authors is presented to validate the model and illustrate the capability of the newly developed model. After the validation, the effectiveness of the viscoplastic model is displayed by numerical simulations of a partially saturated slope failure of the laboratory scale and the effect of viscosity and degree of saturation on slope’s stability is discussed.

Keywords: PLAXIS software, slope, unsaturated soils, Viscoplasticity

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798 The Political Economy of Media Privatisation in Egypt: State Mechanisms and Continued Control

Authors: Mohamed Elmeshad

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During the mid-1990's Egypt had become obliged to implement the Economic Reform and Structural Adjustment Program that included broad economic liberalization, expansion of the private sector and a contraction the size of government spending. This coincided as well with attempts to appear more democratic and open to liberalizing public space and discourse. At the same time, economic pressures and the proliferation of social media access and activism had led to increased pressure to open a mediascape and remove it from the clutches of the government, which had monopolized print and broadcast mass media for over 4 decades by that point. However, the mechanisms that governed the privatization of mass media allowed for sustained government control, even through the prism of ostensibly privately owned newspapers and television stations. These mechanisms involve barriers to entry from a financial and security perspective, as well as operational capacities of distribution and access to means of production. The power dynamics between mass media establishments and the state were moulded during this period in a novel way. Power dynamics within media establishments had also formed under such circumstances. The changes in the country's political economy itself somehow mirrored these developments. This paper will examine these dynamics and shed light on the political economy of Egypt's newly privatized mass media in the early 2000's especially. Methodology: This study will rely on semi-structured interviews from individuals involved with these changes from the perspective of the media organizations. It also will map out the process of media privatization by looking at the administrative, operative and legislative institutions and contexts in order to attempt to draw conclusions on methods of control and the role of the state during the process of privatization. Finally, a brief discourse analysis will be necessary in order to aptly convey how these factors ultimately reflected on media output. Findings and conclusion: The development of Egyptian private, “independent” mirrored the trajectory of transitions in the country’s political economy. Liberalization of the economy meant that a growing class of business owners would explore opportunities that such new markets would offer. However the regime’s attempts to control access to certain forms of capital, especially in sectors such as the media affected the structure of print and broadcast media, as well as the institutions that would govern them. Like the process of liberalisation, much of the regime’s manoeuvring with regards to privatization of media had been haphazardly used to indirectly expand the regime and its ruling party’s ability to retain influence, while creating a believable façade of openness. In this paper, we will attempt to uncover these mechanisms and analyse our findings in ways that explain how the manifestations prevalent in the context of a privatizing media space in a transitional Egypt provide evidence of both the intentions of this transition, and the ways in which it was being held back.

Keywords: business, mass media, political economy, power, privatisation

Procedia PDF Downloads 224
797 Dueling Burnout: The Dual Role Nurse

Authors: Melissa Dorsey

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Moral distress and compassion fatigue plague nurses in the Cardiothoracic Intensive Care Unit (CTICU) and cause an unnecessary level of turnover. Dueling Burnout describes an initiative that was implemented in the CTICU to reduce the level of burnout the nurses endure by encouraging dual roles with collaborating departments. Purpose: Critical care nurses are plagued by burnout, moral distress, and compassion fatigue due to the intensity of care provided. The purpose of the dual role program was to decrease these issues by providing relief from the intensity of the critical care environment while maintaining full-time employment. Relevance/Significance: Burnout, moral distress, and compassion fatigue are leading causes of Cardiothoracic Critical Care (CTCU) turnover. A contributing factor to burnout is the workload related to serving as a preceptor for a constant influx of new nurses (RN). As a result of these factors, the CTICU averages 17% nursing turnover/year. The cost, unit disruption, and, most importantly, distress of the clinical nurses required an innovative approach to create an improved work environment and experience. Strategies/Implementation/Methods: In May 2018, a dual role pilot was initiated for nurses. The dual role constitutes .6 full-time equivalent hours (FTE) worked in CTICU in combination with .3 FTE worked in the Emergency Department (ED). ED nurses who expressed an interest in cross-training to CTICU were also offered the dual role opportunity. The initial hypothesis was that full-time employees would benefit from a change in clinical setting leading to increased engagement and job satisfaction. The dual role also presents an opportunity for professional development through the expansion of clinical skills in another specialty. Success of the pilot led to extending the dual role to areas beyond the ED. Evaluation/Outcomes/Results: The number of dual role clinical nurses has grown to 22. From the dual role cohort, only one has transferred out of CTICU. This is a 5% turnover rate for this group of nurses as compared to the average turnover rate of 17%. A role satisfaction survey conducted with the dual role cohort found that because of working in a dual role, 76.5% decreased their intent to leave, 100% decreased their level of burnout, and 100% reported an increase in overall job satisfaction. Nurses reported the ability to develop skills that are transferable between departments. Respondents emphasized the appreciation gained from working in multiple environments; the dual role served to transform their care. Conclusions/Implications: Dual role is an effective strategy to retain experienced nurses, decrease burnout and turnover, improve collaboration, and provide flexibility to meet staffing needs. The dual role offers RNs an expansion of skills, relief from high acuity and orientee demands, while improving job satisfaction.

Keywords: nursing retention, burnout, pandemic, strategic staffing, leadership

Procedia PDF Downloads 173
796 Mycotoxin Bioavailability in Sparus Aurata Muscle After Human Digestion and Intestinal Transport (Caco-2/HT-29 Cells) Simulation

Authors: Cheila Pereira, Sara C. Cunha, Miguel A. Faria, José O. Fernandes

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The increasing world population brings several concerns, one of which is food security and sustainability. To meet this challenge, aquaculture, the farming of aquatic animals and plants, including fish, mollusks, bivalves, and algae, has experienced sustained growth and development in recent years. Recent advances in this industry have focused on reducing its economic and environmental costs, for example, the substitution of protein sources in fish feed. Plant-based proteins are now a common approach, and while it is a greener alternative to animal-based proteins, there are some disadvantages, such as their putative content and intoxicants such as mycotoxins. These are naturally occurring plant contaminants, and their exposure in fish can cause health problems, stunted growth or even death, resulting in economic losses for the producers and health concerns for the consumers. Different works have demonstrated the presence of both AFB1 (aflatoxin B1) and ENNB1 (enniatin B1) in fish feed and their capacity to be absorbed and bioaccumulate in the fish organism after digestion, further reaching humans through fish ingestion. The aim of this work was to evaluate the bioaccessibility of both mycotoxins in samples of Sparus aurata muscle using a static digestion model based on the INFOGEST protocol. The samples were subjected to different cooking procedures – raw, grilled and fried – and different seasonings – none, thyme and ginger – in order to evaluate their potential reduction effect on mycotoxins bioaccessibility, followed by the evaluation of the intestinal transport of both compounds with an in vitro cell model composed of Caco-2/HT-29 co-culture monolayers, simulating the human intestinal epithelium. The bioaccessible fractions obtained in the digestion studies were used in the transport studies for a more realistic approach to bioavailability evaluation. Results demonstrated the effect of the use of different cooking procedures and seasoning on the toxin's bioavailability. Sparus aurata was chosen in this study for its large production in aquaculture and high consumption in Europe. Also, with the continued evolution of fish farming practices and more common usage of novel feed ingredients based on plants, there is a growing concern about less studied contaminants in aquaculture and their consequences for human health. In pair with greener advances in this industry, there is a convergence towards alternative research methods, such as in vitro applications. In the case of bioavailability studies, both in vitro digestion protocols and intestinal transport assessment are excellent alternatives to in vivo studies. These methods provide fast, reliable and comparable results without ethical restraints.

Keywords: AFB1, aquaculture, bioaccessibility, ENNB1, intestinal transport.

Procedia PDF Downloads 61
795 Non-Thermal Pulsed Plasma Discharge for Contaminants of Emerging Concern Removal in Water

Authors: Davide Palma, Dimitra Papagiannaki, Marco Minella, Manuel Lai, Rita Binetti, Claire Richard

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Modern analytical technologies allow us to detect water contaminants at trace and ultra-trace concentrations highlighting how a large number of organic compounds is not efficiently abated by most wastewater treatment facilities relying on biological processes; we usually refer to these micropollutants as contaminants of emerging concern (CECs). The availability of reliable end effective technologies, able to guarantee the high standards of water quality demanded by legislators worldwide, has therefore become a primary need. In this context, water plasma stands out among developing technologies as it is extremely effective in the abatement of numerous classes of pollutants, cost-effective, and environmentally friendly. In this work, a custom-built non-thermal pulsed plasma discharge generator was used to abate the concentration of selected CECs in the water samples. Samples were treated in a 50 mL pyrex reactor using two different types of plasma discharge occurring at the surface of the treated solution or, underwater, working with positive polarity. The distance between the tips of the electrodes determined where the discharge was formed: underwater when the distance was < 2mm, at the water surface when the distance was > 2 mm. Peak voltage was in the 100-130kV range with typical current values of 20-40 A. The duration of the pulse was 500 ns, and the frequency of discharge could be manually set between 5 and 45 Hz. Treatment of 100 µM diclofenac solution in MilliQ water, with a pulse frequency of 17Hz, revealed that surface discharge was more efficient in the degradation of diclofenac that was no longer detectable after 6 minutes of treatment. Over 30 minutes were required to obtain the same results with underwater discharge. These results are justified by the higher rate of H₂O₂ formation (21.80 µmolL⁻¹min⁻¹ for surface discharge against 1.20 µmolL⁻¹min⁻¹ for underwater discharge), larger discharge volume and UV light emission, high rate of ozone and NOx production (up to 800 and 1400 ppb respectively) observed when working with surface discharge. Then, the surface discharge was used for the treatment of the three selected perfluoroalkyl compounds, namely, perfluorooctanoic acid (PFOA), perfluorohexanoic acid (PFHxA), and pefluorooctanesulfonic acid (PFOS) both individually and in mixture, in ultrapure and groundwater matrices with initial concentration of 1 ppb. In both matrices, PFOS exhibited the best degradation reaching complete removal after 30 min of treatment (degradation rate 0.107 min⁻¹ in ultrapure water and 0.0633 min⁻¹ in groundwater), while the degradation rate of PFOA and PFHxA was slower of around 65% and 80%, respectively. Total nitrogen (TN) measurements revealed levels up to 45 mgL⁻¹h⁻¹ in water samples treated with surface discharge, while, in analogous samples treated with underwater discharge, TN increase was 5 to 10 times lower. These results can be explained by the significant NOx concentrations (over 1400 ppb) measured above functioning reactor operating with superficial discharge; rapid NOx hydrolysis led to nitrates accumulation in the solution explaining the observed evolution of TN values. Ionic chromatography measures confirmed that the vast majority of TN was under the form of nitrates. In conclusion, non-thermal pulsed plasma discharge, obtained with a custom-built generator, was proven to effectively degrade diclofenac in water matrices confirming the potential interest of this technology for wastewater treatment. The surface discharge was proven to be more effective in CECs removal due to the high rate of formation of H₂O₂, ozone, reactive radical species, and strong UV light emission. Furthermore, nitrates enriched water obtained after treatment could be an interesting added-value product to be used as fertilizer in agriculture. Acknowledgment: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 765860.

Keywords: CECs removal, nitrogen fixation, non-thermal plasma, water treatment

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794 Blackcurrant-Associated Rhabdovirus: New Pathogen for Blackcurrants in the Baltic Sea Region

Authors: Gunta Resevica, Nikita Zrelovs, Ivars Silamikelis, Ieva Kalnciema, Helvijs Niedra, Gunārs Lācis, Toms Bartulsons, Inga Moročko-Bičevska, Arturs Stalažs, Kristīne Drevinska, Andris Zeltins, Ina Balke

Abstract:

Newly discovered viruses provide novel knowledge for basic phytovirus research, serve as tools for biotechnology and can be helpful in identification of epidemic outbreaks. Blackcurrant-associated rhabdovirus (BCaRV) have been discovered in USA germplasm collection samples from Russia and France. As it was reported in one accession originating from France it is unclear whether the material was already infected when it entered in the USA or it became infected while in collection in the USA. Due to that BCaRV was definite as non-EU viruses. According to ICTV classification BCaRV is representative of Blackcurrant betanucleorhabdovirus specie in genus Betanucleorhabdovirus (family Rhabdoviridae). Nevertheless, BCaRV impact on the host, transmission mechanisms and vectors are still unknown. In RNA-seq data pool from Ribes plants resistance gene study by high throughput sequencing (HTS) we observed differences between sample group gene transcript heat maps. Additional analysis of the whole data pool (total 393660492 of 150 bp long read pairs) by rnaSPAdes v 3.13.1 resulted into 14424 bases long contig with an average coverage of 684x with shared 99.5% identity to the previously reported first complete genome of BCaRV (MF543022.1) using EMBOSS Needle. This finding proved BCaRV presence in EU and indicated that it might be relevant pathogen. In this study leaf tissue from twelve asymptomatic blackcurrant cv. Mara Eglite plants (negatively tested for blackcurrant reversion virus (BRV)) from Dobele, Latvia (56°36'31.9"N, 23°18'13.6"E) was collected and used for total RNA isolation with RNeasy Plant Mini Kit with minor modifications, followed by plant rRNA removal by a RiboMinus Plant Kit for RNA-Seq. HTS libraries were prepared using MGI Easy RNA Directional Library Prep Set for 16 reactions to obtain 150 bp pair-end reads. Libraries were pooled, circularized and cleaned and sequenced on DNBSEQ-G400 using PE150 flow cell. Additionally, all samples were tested by RT-PCR, and amplicons were directly sequenced by Sanger-based method. The contig representing the genome of BCaRV isolate Mara Eglite was deposited at European Nucleotide Archive under accession number OU015520. Those findings indicate a second evidence on the presence of this particular virus in the EU and further research on BCaRV prevalence in Ribes from other geographical areas should be performed. As there are no information on BCaRV impact on the host this should be investigated, regarding the fact that mixed infections with BRV and nucleorhabdoviruses are reported.

Keywords: BCaRV, Betanucleorhabdovirus, Ribes, RNA-seq

Procedia PDF Downloads 181
793 Knowledge, Attitudes, and Practices of Army Soldiers on Prehospital Trauma Care in Matara District

Authors: Hatharasinghe Liyanage Saneetha Chathaurika, Shreenika De Silva Weliange

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Background and Significance of the Study: Natural and human-induced disasters have become more common due to rapid development and climate change. Therefore hospitalization due to injuries has increased in the midst of advancement in medicine. Prehospital trauma care is critical in reducing morbidity and mortality following injury. Army soldiers are one of the first responder categories after a major disaster causing injury. Thus, basic life support measures taken by trained lay first responders is life-saving, it is important to build up their capacities by updating their knowledge and practices while cultivating positive attitudes toward it. Objective: To describe knowledge, attitudes and practices on prehospital trauma care among army soldiers in Matara District. Methodology: A descriptive cross sectional study was carried out among army soldiers in Matara district. The whole population was studied belonging to the above group during the study period. Self-administered questionnaire was used as the study instrument. Cross tabulations were done to identify the possible associations using chi square statistics. Knowledge and practices were categorized in to two groups as “Poor” and “Good” taking 50% as the cut off. Results: The study population consists of 266 participants (response rate 97.79%).The overall level of knowledge on prehospital trauma care is poor (78.6%) while knowledge on golden hour of trauma (77.1%), triage system (74.4%), cardio pulmonary resuscitation (92.5%) and transportation of patients with spinal cord injury (69.2%) was markedly poor. Good knowledge is significantly associated with advance age, higher income and higher level of education whereas it has no significant association with work duration. More than 80% of them had positive attitudes on most aspects of prehospital trauma care while majority thinks it is good to have knowledge on this topic and they would have performed better in disaster situations if they were trained on pre-hospital trauma care. With regard to the practice, majority (62.8%) is included in the group of poor level of practice. They lack practice on first-aid, cardiopulmonary resuscitation and safe transportation of the patients. Moreover, they had less opportunity to participate in drills/simulation programs done on disaster events. Good practice is significantly associated with advance age and higher level of education but not associated with level of income and working duration of army soldiers. Highly significant association was observed between the level of knowledge and level of practice on prehospital trauma care of army soldiers. It is observed that higher the knowledge practices become better. Conclusion: A higher proportion of army soldiers had poor knowledge and practice on prehospital trauma care while majority had positive attitudes regarding it. Majority lacks knowledge and practice in first-aid and cardiopulmonary resuscitation. Due to significant association observed between knowledge and practice it can be recommended to include a training session on prehospital trauma care in the basic military curriculum which will enhance the ability to act as first responders effectively. Further research is needed in this area of prehospital trauma care to enhance the qualitative outcome.

Keywords: disaster, prehospital trauma care, first responders, army soldiers

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792 Stent Surface Functionalisation via Plasma Treatment to Promote Fast Endothelialisation

Authors: Irene Carmagnola, Valeria Chiono, Sandra Pacharra, Jochen Salber, Sean McMahon, Chris Lovell, Pooja Basnett, Barbara Lukasiewicz, Ipsita Roy, Xiang Zhang, Gianluca Ciardelli

Abstract:

Thrombosis and restenosis after stenting procedure can be prevented by promoting fast stent wall endothelialisation. It is well known that surface functionalisation with antifouling molecules combining with extracellular matrix proteins is a promising strategy to design biomimetic surfaces able to promote fast endothelialization. In particular, REDV has gained much attention for the ability to enhance rapid endothelialization due to its specific affinity with endothelial cells (ECs). In this work, a two-step plasma treatment was performed to polymerize a thin layer of acrylic acid, used to subsequently graft PEGylated-REDV and polyethylene glycol (PEG) at different molar ratio with the aim to selectively promote endothelial cell adhesion avoiding platelet activation. PEGylate-REDV was provided by Biomatik and it is formed by 6 PEG monomer repetitions (Chempep Inc.), with an NH2 terminal group. PEG polymers were purchased from Chempep Inc. with two different chain lengths: m-PEG6-NH2 (295.4 Da) with 6 monomer repetitions and m-PEG12-NH2 (559.7 Da) with 12 monomer repetitions. Plasma activation was obtained by operating at 50W power, 5 min of treatment and at an Ar flow rate of 20 sccm. Pure acrylic acid (99%, AAc) vapors were diluted in Ar (flow = 20 sccm) and polymerized by a pulsed plasma discharge applying a discharge RF power of 200 W, a duty cycle of 10% (on time = 10 ms, off time = 90 ms) for 10 min. After plasma treatment, samples were dipped into an 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide (EDC)/N-hydroxysuccinimide (NHS) solution (ratio 4:1, pH 5.5) for 1 h at 4°C and subsequently dipped in PEGylate-REDV and PEGylate-REDV:PEG solutions at different molar ratio (100 μg/mL in PBS) for 20 h at room temperature. Surface modification was characterized through physico-chemical analyses and in vitro cell tests. PEGylated-REDV peptide and PEG were successfully bound to the carboxylic groups that are formed on the polymer surface after plasma reaction. FTIR-ATR spectroscopy, X -ray Photoelectron Spectroscopy (XPS) and contact angle measurement gave a clear indication of the presence of the grafted molecules. The use of PEG as a spacer allowed for an increase in wettability of the surface, and the effect was more evident by increasing the amount of PEG. Endothelial cells adhered and spread well on the surfaces functionalized with the REDV sequence. In conclusion, a selective coating able to promote a new endothelial cell layer on polymeric stent surface was developed. In particular, a thin AAc film was polymerised on the polymeric surface in order to expose –COOH groups, and PEGylate-REDV and PEG were successful grafted on the polymeric substrates. The REDV peptide demonstrated to encourage cell adhesion with a consequent, expected improvement of the hemocompatibility of these polymeric surfaces in vivo. Acknowledgements— This work was funded by the European Commission 7th Framework Programme under grant agreement number 604251- ReBioStent (Reinforced Bioresorbable Biomaterials for Therapeutic Drug Eluting Stents). The authors thank all the ReBioStent partners for their support in this work.

Keywords: endothelialisation, plasma treatment, stent, surface functionalisation

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791 Analysis of Aspergillus fumigatus IgG Serologic Cut-Off Values to Increase Diagnostic Specificity of Allergic Bronchopulmonary Aspergillosis

Authors: Sushmita Roy Chowdhury, Steve Holding, Sujoy Khan

Abstract:

The immunogenic responses of the lung towards the fungus Aspergillus fumigatus may range from invasive aspergillosis in the immunocompromised, fungal ball or infection within a cavity in the lung in those with structural lung lesions, or allergic bronchopulmonary aspergillosis (ABPA). Patients with asthma or cystic fibrosis are particularly predisposed to ABPA. There are consensus guidelines that have established criteria for diagnosis of ABPA, but uncertainty remains on the serologic cut-off values that would increase the diagnostic specificity of ABPA. We retrospectively analyzed 80 patients with severe asthma and evidence of peripheral blood eosinophilia ( > 500) over the last 3 years who underwent all serologic tests to exclude ABPA. Total IgE, specific IgE and specific IgG levels against Aspergillus fumigatus were measured using ImmunoCAP Phadia-100 (Thermo Fisher Scientific, Sweden). The Modified ISHAM working group 2013 criteria (obligate criteria: asthma or cystic fibrosis, total IgE > 1000 IU/ml or > 417 kU/L and positive specific IgE Aspergillus fumigatus or skin test positivity; with ≥ 2 of peripheral eosinophilia, positive specific IgG Aspergillus fumigatus and consistent radiographic opacities) was used in the clinical workup for the final diagnosis of ABPA. Patients were divided into 3 groups - definite, possible, and no evidence of ABPA. Specific IgG Aspergillus fumigatus levels were not used to assign the patients into any of the groups. Of 80 patients (males 48, females 32; mean age 53.9 years ± SD 15.8) selected for the analysis, there were 30 patients who had positive specific IgE against Aspergillus fumigatus (37.5%). 13 patients fulfilled the Modified ISHAM working group 2013 criteria of ABPA (‘definite’), while 15 patients were ‘possible’ ABPA and 52 did not fulfill the criteria (not ABPA). As IgE levels were not normally distributed, median levels were used in the analysis. Median total IgE levels of patients with definite and possible ABPA were 2144 kU/L and 2597 kU/L respectively (non-significant), while median specific IgE Aspergillus fumigatus at 4.35 kUA/L and 1.47 kUA/L respectively were significantly different (comparison of standard deviations F-statistic 3.2267, significance level p=0.040). Mean levels of IgG anti-Aspergillus fumigatus in the three groups (definite, possible and no evidence of ABPA) were compared using ANOVA (Statgraphics Centurion Professional XV, Statpoint Inc). Mean levels of IgG anti-Aspergillus fumigatus (Gm3) in definite ABPA was 125.17 mgA/L ( ± SD 54.84, with 95%CI 92.03-158.32), while mean Gm3 levels in possible and no ABPA were 18.61 mgA/L and 30.05 mgA/L respectively. ANOVA showed a significant difference between the definite group and the other groups (p < 0.001). This was confirmed using multiple range tests (Fisher's least significant difference procedure). There was no significant difference between the possible ABPA and not ABPA groups (p > 0.05). The study showed that a sizeable proportion of patients with asthma are sensitized to Aspergillus fumigatus in this part of India. A higher cut-off value of Gm3 ≥ 80 mgA/L provides a higher serologic specificity towards definite ABPA. Long-term studies would provide us more information if those patients with 'possible' APBA and positive Gm3 later develop clear ABPA, and are different from the Gm3 negative group in this respect. Serologic testing with clear defined cut-offs are a valuable adjunct in the diagnosis of ABPA.

Keywords: allergic bronchopulmonary aspergillosis, Aspergillus fumigatus, asthma, IgE level

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790 Interacting with Multi-Scale Structures of Online Political Debates by Visualizing Phylomemies

Authors: Quentin Lobbe, David Chavalarias, Alexandre Delanoe

Abstract:

The ICT revolution has given birth to an unprecedented world of digital traces and has impacted a wide number of knowledge-driven domains such as science, education or policy making. Nowadays, we are daily fueled by unlimited flows of articles, blogs, messages, tweets, etc. The internet itself can thus be considered as an unsteady hyper-textual environment where websites emerge and expand every day. But there are structures inside knowledge. A given text can always be studied in relation to others or in light of a specific socio-cultural context. By way of their textual traces, human beings are calling each other out: hypertext citations, retweets, vocabulary similarity, etc. We are in fact the architects of a giant web of elements of knowledge whose structures and shapes convey their own information. The global shapes of these digital traces represent a source of collective knowledge and the question of their visualization remains an opened challenge. How can we explore, browse and interact with such shapes? In order to navigate across these growing constellations of words and texts, interdisciplinary innovations are emerging at the crossroad between fields of social and computational sciences. In particular, complex systems approaches make it now possible to reconstruct the hidden structures of textual knowledge by means of multi-scale objects of research such as semantic maps and phylomemies. The phylomemy reconstruction is a generic method related to the co-word analysis framework. Phylomemies aim to reveal the temporal dynamics of large corpora of textual contents by performing inter-temporal matching on extracted knowledge domains in order to identify their conceptual lineages. This study aims to address the question of visualizing the global shapes of online political discussions related to the French presidential and legislative elections of 2017. We aim to build phylomemies on top of a dedicated collection of thousands of French political tweets enriched with archived contemporary news web articles. Our goal is to reconstruct the temporal evolution of online debates fueled by each political community during the elections. To that end, we want to introduce an iterative data exploration methodology implemented and tested within the free software Gargantext. There we combine synchronic and diachronic axis of visualization to reveal the dynamics of our corpora of tweets and web pages as well as their inner syntagmatic and paradigmatic relationships. In doing so, we aim to provide researchers with innovative methodological means to explore online semantic landscapes in a collaborative and reflective way.

Keywords: online political debate, French election, hyper-text, phylomemy

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789 Safety and Maternal Anxiety in Mother's and Baby's Sleep: Cross-sectional Study

Authors: Rayanne Branco Dos Santos Lima, Lorena Pinheiro Barbosa, Kamila Ferreira Lima, Victor Manuel Tegoma Ruiz, Monyka Brito Lima Dos Santos, Maria Wendiane Gueiros Gaspar, Luzia Camila Coelho Ferreira, Leandro Cardozo Dos Santos Brito, Deyse Maria Alves Rocha

Abstract:

Introduction: The lack of regulation of the baby's sleep-wake pattern in the first years of life affects the health of thousands of women. Maternal sleep deprivation can trigger or aggravate psychosomatic problems such as depression, anxiety and stress that can directly influence maternal safety, with consequences for the baby's and mother's sleep. Such conditions can affect the family's quality of life and child development. Objective: To correlate maternal security with maternal state anxiety scores and the mother's and baby's total sleep time. Method: Cross-sectional study carried out with 96 mothers of babies aged 10 to 24 months, accompanied by nursing professionals linked to a Federal University in Northeast Brazil. Study variables were maternal security, maternal state anxiety scores, infant latency and sleep time, and total nocturnal sleep time of mother and infant. Maternal safety was calculated using a four-point Likert scale (1=not at all safe, 2=somewhat safe, 3=very safe, 4=completely safe). Maternal anxiety was measured by State-Trait Anxiety Inventory, state-anxiety subscale whose scores vary from 20 to 80 points, and the higher the score, the higher the anxiety levels. Scores below 33 are considered mild; from 33 to 49, moderate and above 49, high. As for the total nocturnal sleep time, values between 7-9 hours of sleep were considered adequate for mothers, and values between 9-12 hours for the baby, according to the guidelines of the National Sleep Foundation. For the sleep latency time, a time equal to or less than 20 min was considered adequate. It is noteworthy that the latency time and the time of night sleep of the mother and the baby were obtained by the mother's subjective report. To correlate the data, Spearman's correlation was used in the statistical package R version 3.6.3. Results: 96 women and babies participated, aged 22 to 38 years (mean 30.8) and 10 to 24 months (mean 14.7), respectively. The average of maternal security was 2.89 (unsafe); Mean maternal state anxiety scores were 43.75 (moderate anxiety). The babies' average sleep latency time was 39.6 min (>20 min). The mean sleep times of the mother and baby were, respectively, 6h and 42min and 8h and 19min, both less than the recommended nocturnal sleep time. Maternal security was positively correlated with maternal state anxiety scores (rh=266, p=0.009) and negatively correlated with infant sleep latency (rh= -0.30. P=0.003). Baby sleep time was positively correlated with maternal sleep time. (rh 0.46, p<0.001). Conclusion: The more secure the mothers considered themselves, the higher the anxiety scores and the shorter the baby's sleep latency. Also, the longer the baby sleeps, the longer the mother sleeps. Thus, interventions are needed to promote the quality and efficiency of sleep for both mother and baby.

Keywords: sleep, anxiety, infant, mother-child relations

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788 Constitutive Androstane Receptor (CAR) Inhibitor CINPA1 as a Tool to Understand CAR Structure and Function

Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

Abstract:

This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

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