Search results for: coupled integrated dynamic analysis

Authors: K. O'Malley

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Background: The emergence and rapid evolution of large language models (LLMs) (i.e., models of generative artificial intelligence, or AI) has been unprecedented. ChatGPT is one of the most widely used LLM platforms. Using natural language processing technology, it generates customized responses to user prompts, enabling it to mimic human conversation. Responses are generated using predictive modeling of vast internet text and data swathes and are further refined and reinforced through user feedback. The popularity of LLMs is increasing, with a growing number of students utilizing these platforms for study and revision purposes. Notwithstanding its many novel applications, LLM technology is inherently susceptible to bias and error. This poses a significant challenge in the educational setting, where academic integrity may be undermined. This study aims to evaluate the performance of the latest iteration of ChatGPT (ChatGPT4.0) in standardized state medical licensing examinations. Methods: A considered search strategy was used to interrogate the PubMed electronic database. The keywords ‘ChatGPT’ AND ‘medical education’ OR ‘medical school’ OR ‘medical licensing exam’ were used to identify relevant literature. The search included all peer-reviewed literature published in the past five years. The search was limited to publications in the English language only. Eligibility was ascertained based on the study title and abstract and confirmed by consulting the full-text document. Data was extracted into a Microsoft Excel document for analysis. Results: The search yielded 345 publications that were screened. 225 original articles were identified, of which 11 met the pre-determined criteria for inclusion in a narrative synthesis. These studies included performance assessments in national medical licensing examinations from the United States, United Kingdom, Saudi Arabia, Poland, Taiwan, Japan and Germany. ChatGPT 4.0 achieved scores ranging from 67.1 to 88.6 percent. The mean score across all studies was 82.49 percent (SD= 5.95). In all studies, ChatGPT exceeded the threshold for a passing grade in the corresponding exam. Conclusion: The capabilities of ChatGPT in standardized academic assessment in medicine are robust. While this technology can potentially revolutionize higher education, it also presents several challenges with which educators have not had to contend before. The overall strong performance of ChatGPT, as outlined above, may lend itself to unfair use (such as the plagiarism of deliverable coursework) and pose unforeseen ethical challenges (arising from algorithmic bias). Conversely, it highlights potential pitfalls if users assume LLM-generated content to be entirely accurate. In the aforementioned studies, ChatGPT exhibits a margin of error between 11.4 and 32.9 percent, which resonates strongly with concerns regarding the quality and veracity of LLM-generated content. It is imperative to highlight these limitations, particularly to students in the early stages of their education who are less likely to possess the requisite insight or knowledge to recognize errors, inaccuracies or false information. Educators must inform themselves of these emerging challenges to effectively address them and mitigate potential disruption in academic fora.

Keywords: artificial intelligence, ChatGPT, generative ai, large language models, licensing exam, medical education, medicine, university

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Authors: Kavitha Madhu, Karthik K. Srinivasan, R. Sivanandan

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Indian traffic can be considered as mixed and heterogeneous due to the presence of various types of vehicles that operate with weak lane discipline. Consequently, vehicles can position themselves anywhere in the traffic stream depending on availability of gaps. The choice of lateral positioning is an important component in representing and characterizing mixed traffic. The field data provides evidence that the trajectory of vehicles in Indian urban roads have significantly varying longitudinal and lateral components. Further, the notion of headway which is widely used for homogeneous traffic simulation is not well defined in conditions lacking lane discipline. From field data it is clear that following is not strict as in homogeneous and lane disciplined conditions and neighbouring vehicles ahead of a given vehicle and those adjacent to it could also influence the subject vehicles choice of position, speed and acceleration. Given these empirical features, the suitability of using headway distributions to characterize mixed traffic in Indian cities is questionable, and needs to be modified appropriately. To address these issues, this paper attempts to analyze the time gap distribution between consecutive vehicles (in a time-sense) crossing a section of roadway. More specifically, to characterize the complex interactions noted above, the influence of composition, manoeuvre types, and lateral placement characteristics on time gap distribution is quantified in this paper. The developed model is used for evaluating various performance measures such as link speed, midblock delay and intersection delay which further helps to characterise the vehicular fuel consumption and emission on urban roads of India. Identifying and analyzing exact interactions between various classes of vehicles in the traffic stream is essential for increasing the accuracy and realism of microscopic traffic flow modelling. In this regard, this study aims to develop and analyze time gap distribution models and quantify it by lead lag pair, manoeuvre type and lateral position characteristics in heterogeneous non-lane based traffic. Once the modelling scheme is developed, this can be used for estimating the vehicle kilometres travelled for the entire traffic system which helps to determine the vehicular fuel consumption and emission. The approach to this objective involves: data collection, statistical modelling and parameter estimation, simulation using calibrated time-gap distribution and its validation, empirical analysis of simulation result and associated traffic flow parameters, and application to analyze illustrative traffic policies. In particular, video graphic methods are used for data extraction from urban mid-block sections in Chennai, where the data comprises of vehicle type, vehicle position (both longitudinal and lateral), speed and time gap. Statistical tests are carried out to compare the simulated data with the actual data and the model performance is evaluated. The effect of integration of above mentioned factors in vehicle generation is studied by comparing the performance measures like density, speed, flow, capacity, area occupancy etc under various traffic conditions and policies. The implications of the quantified distributions and simulation model for estimating the PCU (Passenger Car Units), capacity and level of service of the system are also discussed.

Keywords: lateral movement, mixed traffic condition, simulation modeling, vehicle following models

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Authors: Andrea Scapolo, Zaya Rustamova, Arturo Matute Castro

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The “Voices in Dissent” initiative aims at collecting and making available in a digital format, testimonies, letters, and other narratives produced by victims of political oppression from different geographical spaces across the Atlantic. By recovering silenced voices behind the official narratives, this open-access online database will provide indispensable tools for rewriting the history of authoritarian regimes from the margins as memory debates continue to provoke controversy among academic and popular transnational circles. In providing an extensive database of non-hegemonic discourses in a variety of political and social contexts, the project will complement the existing European and Latin-American studies, and invite further interdisciplinary and trans-national research. This digital resource will be available to academic communities and the general audience and will be organized geographically and chronologically. “Voices in Dissent” will offer a first comprehensive study of these personal accounts of persecution and repression against determined historical backgrounds and their impact on collective memory formation in contemporary societies. The digitalization of these texts will allow to run metadata analyses and adopt comparatist approaches for a broad range of research endeavors. Most of the testimonies included in our archive are testimonies of trauma: the trauma of exile, imprisonment, torture, humiliation, censorship. The research on trauma has now reached critical mass and offers a broad spectrum of critical perspectives. By putting together testimonies from different geographical and historical contexts, our project will provide readers and scholars with an extraordinary opportunity to investigate how culture shapes individual and collective memories and provides or denies resources to make sense and cope with the trauma. For scholars dealing with the epistemological and rhetorical analysis of testimonies, an online open-access archive will prove particularly beneficial to test theories on truth status and the formation of belief as well as to study the articulation of discourse. An important aspect of this project is also its pedagogical applications since it will contribute to the creation of Open Educational Resources (OER) to support students and educators worldwide. Through collaborations with our Library System, the archive will form part of the Digital Commons database. The texts collected in this online archive will be made available in the original languages as well as in English translation. They will be accompanied by a critical apparatus that will contextualize them historically by providing relevant background information and bibliographical references. All these materials can serve as a springboard for a broad variety of educational projects and classroom activities. They can also be used to design specific content courses or modules. In conclusion, the desirable outcomes of the “Voices in Dissent” project are: 1. the collections and digitalization of political dissent testimonies; 2. the building of a network of scholars, educators, and learners involved in the design, development, and sustainability of the digital archive; 3. the integration of the content of the archive in both research and teaching endeavors, such as publication of scholarly articles, design of new upper-level courses, and integration of the materials in existing courses.

Keywords: digital archive, dissent, open educational resources, testimonies, transatlantic studies

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Authors: Betül Gelengül Eki̇mci̇, Semra Günay Aktaş

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Festive, habitual activities celebrated on the specified date by a local community, are conducive to recognition of the region. The main function of festive events is to help gathering people via an annual celebration to create an atmosphere of understanding and the opportunity to participate in the joy of life. At the same time, festive events may serve as special occasions on which immigrants return home to celebrate with their family and community, reaffirming their identity and link to the community’s traditions. Festivals also support the local economy by bringing in different visitors to the region. The tradition of “Beet Brewing-Molasses Production,” which is held in İdrisyayla Village is an intangible cultural heritage with customs, traditions, and rituals carrying impacts of cuisine culture of Rumelian immigrants in the Ottoman. After the harvest of the beet plant in the autumn season of the year, Beet Brewing Molasses syrup is made by traditional production methods with co-op of the local community. Festive occurring brewing paste made process provided transmission of knowledge and experience to the young generations. Making molasses, which is a laborious process, is accompanied by folk games such as "sayacı," which is vital element of the festive performed in İdrisyayla. Performance provides enjoyable time and supporting motivation. Like other forms of intangible cultural heritage, “Beet Brewing-Molasses Festive in İdrasyayla is threatened by rapid urbanisation, young generation migration, industrialisation and environmental change. The festive events are threatened with gradual disappearance due to changes communities undergo in modern societies because it depends on the broad participation of practitioners. Ensuring the continuity of festive events often requires the mobilization of large numbers of individuals and the social, political and legal institutions and mechanisms of society. In 2015, Intangible cultural heritage research project with the title of "İdrisyayla Molasses Process" managed by the Eskişehir Governorship, City Directorate of Culture and Tourism and Anadolu University, project members took part in the festival organization to promote sustainability, making it visible, to encourage the broadest public participation possible, to ensure public awareness on the cultural importance. To preserve the originality of and encourage participation in the festive İdrisyayla, local associations, researchers and institutions created foundation and supports festive events, such as "sayacı" folk game, which is vital element of the festive performed in İdrisyayla. Practitioners find new opportunity to market İdrisyayla Molasses production. Publicity program through the press and exhibition made it possible to stress the cultural importance of the festive in İdrisyayla Village. The research reported here used a survey analysis to evaluate an affect of the festive after the spirit of the 2015 Festive in İdrisyayla Village. Particular attention was paid to the importance of the cultural aspects of the festival. Based on a survey of more than a hundred festival attendees, several recommendations are made to festival planners. Results indicate that the variety of festive activities and products offered for sale very important to attendees. The local participants care product sales rather than cultural heritage.

Keywords: agritourism, cultural tourism, festival, sustainable cultural heritage

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Authors: Soni T. L.

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Sustainable environmental stress is a major concern which needs immediate attention. This paper is an attempt to present participatory action research for sustainable agriculture. Being first and best culture, agriculture protects and improves the natural environment, the social and economic conditions of people, and safeguards the health and welfare of all groups. During course of time agriculture turned to agribusiness, then the values are not safeguarded. Moreover, in today’s busy life many are not taking efforts to take part in agriculture production. Then children are not getting the opportunity to understand agriculture and farming practices. So student initiatives are vital to make them aware. Here the programmes structured by the researcher come under the auspicious of National Service Scheme, a student-centered educational programme, organized by Ministry of Youth Affairs, Government of India. The twin objectives of the study are to examine the role of student initiatives for sustainable agriculture and the role of participatory action research in student initiatives. SWOT analysis is made to study strengths, weaknesses, threats and opportunities. The Methodology adopted is Participatory Action Research. The method is participatory in a sense there is collaboration through participation. The method is action, there is lab land experiences which is real. The method is research that there is documented lessons and creation of new knowledge. Plan of action cover measures adopted and strategies taken i.e., bhavana – kalpana – yojana – sadhana. Through the team effort, the team was successful in converting more than 10 hectares of barren land into cultivable land within and outside the campus. Team efforts of students saved a huge amount of labour cost and produced a huge quantity of organic output and the team was also successful in creating 1000 rain pits in the premises of College for rainwater harvesting. The findings include conveyance of the Message: Food Production is superior to Food donation. Moreover, the study fostered good work ethic and social responsibility among students. Students undertake innovative programmes underlying social and environmental issues and participants got increased opportunities to interact with local and less privileged and acquired increased awareness about real-life experiences which make them confident to interact with people and it resulted in the strengthening of social capital- cooperation, team spirit, social commitment among students. Participants promoted sustainable domestic efforts and ultimately environmental protection is ensured. Finally, there is recognition to the team, institution and the researcher at the university level, state level and at the national level. The learned lessons are, if the approach is good, the response is good and success generates success. Participatory action research is empowering experience for practitioners, focusing the combined time, energy and creativity of a committed group we should lead so many programmes which makes the institution centre of excellence. Authorities should take necessary steps for the Inclusion of community development activities in the curriculum. Action research is problem, client and action centered. So, we must adapt and adopt, coordinates and correlates measures which preserve and conserve the environment.

Keywords: participatory action research, student initiatives, sustainable development, sustainability

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Authors: Bangun F., Crevits B., Bellet T., Banet A., Boy G. A., Katili I.

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This paper seeks the incoherencies in cognitive process during an accident of Powered Two Wheelers (PTW) by understanding the factual sequences of events and causal relations for each case of accident. The principle of this approach is undertaking in-depth investigations on case per case of PTW accidents based on elaborate data acquisitions on accident sites that officially stamped in Police Crash Report (PCRs) 2012 of Medan with criteria, involved at least one PTW and resulted in serious injury and fatalities. The analysis takes into account four modules: accident chronologies, perpetrator, and victims, injury surveillance, vehicles and road infrastructures, comprising of traffic facilities, road geometry, road alignments and weather. The proposal for improvement could have provided a favorable influence on the chain of functional processes and events leading to collision. Decision Aiding Processes (DAP) assists in structuring different entities at different decisional levels, as each of these entities has its own objectives and constraints. The entities (A) are classified into 6 groups of accidents: solo PTW accidents; PTW vs. PTW; PTW vs. pedestrian; PTW vs. motor-trishaw; and PTW vs. other vehicles and consecutive crashes. The entities are also distinguished into 4 decisional levels: level of road users and street systems; operational level (crash-attended police officers or CAPO and road engineers), tactical level (Regional Traffic Police, Department of Transportation, and Department of Public Work), and strategic level (Traffic Police Headquarters (TCPHI)), parliament, Ministry of Transportation and Ministry of Public Work). These classifications will lead to conceptualization of Problem Situations (P) and Problem Formulations (I) in DAP context. The DAP concerns the sequences process of the incidents until the time the accident occurs, which can be modelled in terms of five activities of procedural rationality: identification on initial human features (IHF), investigation on proponents attributes (PrAT), on Injury Surveillance (IS), on the interaction between IHF and PrAt and IS (intercorrelation), then unravel the sequences of incidents; filtering and disclosure, which include: what needs to activate, modify or change or remove, what is new and what is priority. These can relate to the activation or modification or new establishment of law. The PrAt encompasses the problems of environmental, road infrastructure, road and traffic facilities, and road geometry. The evaluation model (MP) is generated to bridge P and I since MP is produced by the intercorrelations among IHF, PrAT and IS extracted from the PCRs 2012 of Medan. There are 7 findings of incoherences: lack of knowledge and awareness on the traffic regulations and the risks of accidents, especially when riding between 0 < x < 10 km from house, riding between 22 p.m.–05.30 a.m.; lack of engagements on procurement of IHF Data by CAPO; lack of competency of CAPO on data procurement in accident-sites; no intercorrelation among IHF and PrAt and IS in the database systems of PCRs; lack of maintenance and supervision on the availabilities and the capacities of traffic facilities and road infrastructure; instrumental bias with wash-back impacts towards the TCPHI; technical robustness with wash-back impacts towards the CAPO and TCPHI.

Keywords: decision aiding processes, evaluation model, PTW accidents, police crash reports

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Authors: Narottam Puri, Gurvinder Kaur

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Background: The National Accreditation Board for Hospitals & Healthcare Providers (NABH) is India’s apex standard setting accrediting body in health care which evaluates and accredits healthcare organizations. NABH requires accredited organizations to become reaccredited every three years. It is often though that once the initial accreditation is complete, the foundation is set and reaccreditation is a much simpler process. Fortis Hospital, Shalimar Bagh, a part of the Fortis Healthcare group is a 262 bed, multi-specialty tertiary care hospital. The hospital was successfully accredited in the year 2012. On completion of its first cycle, the hospital underwent a reaccreditation assessment in the year 2015. This paper aims to gain a better understanding of the challenges that accredited hospitals face when preparing for a renewal of their accreditations. Methods: The study was conducted using a cross-sectional mixed methods approach; semi-structured interviews were conducted with senior leadership team and staff members including doctors and nurses. Documents collated by the QA team while preparing for the re-assessment like the data on quality indicators: the method of collection, analysis, trending, continual incremental improvements made over time, minutes of the meetings, amendments made to the existing policies and new policies drafted was reviewed to understand the challenges. Results: The senior leadership had a concern about the cost of accreditation and its impact on the quality of health care services considering the staff effort and time consumed it. The management was however in favor of continuing with the accreditation since it offered competitive advantage, strengthened community confidence besides better pay rates from the payors. The clinicians regarded it as an increased non-clinical workload. Doctors felt accountable within a professional framework, to themselves, the patient and family, their peers and to their profession; but not to accreditation bodies and raised concerns on how the quality indicators were measured. The departmental leaders had a positive perception of accreditation. They agreed that it ensured high standards of care and improved management of their functional areas. However, they were reluctant in sparing people for the QA activities due to staffing issues. With staff turnover, a lot of work was lost as sticky knowledge and had to be redone. Listing the continual quality improvement initiatives over the last 3 years was a challenge in itself. Conclusion: The success of any quality assurance reaccreditation program depends almost entirely on the commitment and interest of the administrators, nurses, paramedical staff, and clinicians. The leader of the Quality Movement is critical in propelling and building momentum. Leaders need to recognize skepticism and resistance and consider ways in which staff can become positively engaged. Involvement of all the functional owners is the start point towards building ownership and accountability for standards compliance. Creativity plays a very valuable role. Communication by Mail Series, WhatsApp groups, Quizzes, Events, and any and every form helps. Leaders must be able to generate interest and commitment without burdening clinical and administrative staff with an activity they neither understand nor believe in.

Keywords: NABH, reaccreditation, quality assurance, quality indicators

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Authors: Amna Tariq Shah

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Amid the pandemic, the contemporary landscape has experienced accelerated growth in small business activities and an expanding digital marketplace, further exacerbating the issue of non-compliance among self-employed individuals through aggressive tax planning and evasion. This research seeks to address these challenges by developing strategic tax policies that promote voluntary compliance and improve taxpayer facilitation. The study employs the innovative MINDSPACE framework to examine three psychosocial factors—tax communication, tax literacy, and shaming—to optimize policy responses, address administrative shortcomings, and ensure adequate revenue collection for public goods and services. Preliminary findings suggest that incomprehensible communication from tax authorities drives individuals to seek alternative, potentially biased sources of tax information, thereby exacerbating non-compliance. Furthermore, the study reveals low tax literacy among Australian and Pakistani respondents, with many struggling to navigate complex tax processes and comprehend tax laws. Consequently, policy recommendations include simplifying tax return filing and enhancing pre-populated tax returns. In terms of shaming, the research indicates that Australians, being an individualistic society, may not respond well to shaming techniques due to privacy concerns. In contrast, Pakistanis, as a collectivistic society, may be more receptive to naming and shaming approaches. The study employs a mixed-method approach, utilizing interviews and surveys to analyze the issue in both jurisdictions. The use of mixed methods allows for a more comprehensive understanding of tax compliance behavior, combining the depth of qualitative insights with the generalizability of quantitative data, ultimately leading to more robust and well-informed policy recommendations. By examining evidence from opposite jurisdictions, namely a developed country (Australia) and a developing country (Pakistan), the study's applicability is enhanced, providing perspectives from two disparate contexts that offer insights from opposite ends of the economic, cultural, and social spectra. The non-comparative case study methodology offers valuable insights into human behavior, which can be applied to other jurisdictions as well. The application of the MINDSPACE framework in this research is particularly significant, as it introduces a novel approach to tax compliance behavior analysis. By integrating insights from behavioral economics, the framework enables a comprehensive understanding of the psychological and social factors influencing taxpayer decision-making, facilitating the development of targeted and effective policy interventions. This research carries substantial importance as it addresses critical challenges in tax compliance and administration, with far-reaching implications for revenue collection and the provision of public goods and services. By investigating the psychosocial factors that influence taxpayer behavior and utilizing the MINDSPACE framework, the study contributes invaluable insights to the field of tax policy. These insights can inform policymakers and tax administrators in developing more effective tax policies that enhance taxpayer facilitation, address administrative obstacles, promote a more equitable and efficient tax system, and foster voluntary compliance, ultimately strengthening the financial foundation of governments and communities.

Keywords: individual tax compliance behavior, psychosocial factors, tax non-compliance, tax policy

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Authors: Lam Hong Lan, Gabor Sarlos

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It is hard to search for best practices in promotion for local fashion brands in Vietnam as the industry is still very young. Local fashion start-ups have grown quickly in the last five years, thanks in part to the internet and social media. However, local designer/owners can face a huge challenge when competing with international brands in the Vietnamese market – and few local case studies are available for guidance. In response, this paper studied how local small- to medium-sized enterprises (SMEs) promote to their target customers in order to compete with international brands. Knowledge of both successful and unsuccessful approaches generated by this study is intended to both contribute to the academic literature on local fashion in Vietnam as well as to help local designers to learn from and improve their brand-building strategy. The primary study featured qualitative data collection via semi-structured depth interviews. Transcription and data analysis were conducted manually in order to identify success factors that local brands should consider as part of their promotion strategy. Purposive sampling of SMEs identified five designers in Ho Chi Minh City (the biggest city in Vietnam) and three designers in Hanoi (the second biggest) as interviewees. Participant attributes included: born in the 1980s or 1990s; familiar with internet and social media; designer/owner of a successful local fashion brand in the key middle market and/or mass market segments (which are crucial to the growth of local brands). A secondary study was conducted using social listening software to gather further qualitative data on what were considered to be successful or unsuccessful approaches to local fashion brand promotion on social media. Both the primary and secondary studies indicated that local designers had maximized their promotion budget by using owned media and earned media instead of paid media. Findings from the qualitative interviews indicate that internet and social media have been used as effective promotion platforms by local fashion start-ups. Facebook and Instagram were the most popular social networks used by the SMEs interviewed, and these social platforms were believed to offer a more affordable promotional strategy than traditional media such as TV and/or print advertising. Online stores were considered an important factor in helping the SMEs to reach customers beyond the physical store. Furthermore, a successful online store allowed some SMEs to reduce their business rental costs by maintaining their physical store in a cheaper, less central city area as opposed to a more traditional city center store location. In addition, the small comparative size of the SMEs allowed them to be more attentive to their customers, leading to higher customer satisfaction and rate of return. In conclusion, this study found that these kinds of cost savings helped the SMEs interviewed to focus their scarce resources on producing unique, high-quality collections in order to differentiate themselves from international brands. Facebook and Instagram were the main platforms used for promotion and brand-building. The main challenge to this promotion strategy identified by the SMEs interviewed was to continue to find innovative ways to maximize the impact of a limited marketing budget.

Keywords: Vietnam, SMEs, fashion brands, promotion, marketing, social listening

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Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi

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Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.

Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis

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Authors: Lewis Mehl-Madrona, Barbara Mainguy, Patrick McFarlane

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Introduction: There are many risk factors for attempting suicide, including young age, “minority stress,” which would include Transgender and Gender Diverse orientations (TGD). The rate of TGD youths for suicide attempts is 3 times higher than heterosexual cis-gender youth. Half of TGD youth have seriously contemplated taking their own lives; of those, about half attempted suicide; and 18% of the TGD teenagers reported suicidal thoughts linked to their gender identity. Native American TGD have a six times higher suicide attempt rate. Conventional mental health has not generally helped these individuals. Stigma and discrimination contribute to healthcare disparities. Storytelling plays a crucial role in the development of human culture and individual identities. Sharing narrative artwork, creative writing, and personal stories allow people to build trust and to share their vulnerabilities. This helps people become aware of themselves in relation to others and gain a sense of comfort that their stories are similar; they may also be transformed in the process. Art provides a means to reach people who are otherwise difficult to engage in services. Methods: TGD individuals are recruited through a snowballing procedure. Following a life story interview, participants complete a scale of gender dysphoria, identification with conventional masculinity, patient-reported anxiety, and depression measure, and a quality-of-life scale. The interview completes the Columbia Suicide Scale. Following this, an artist and a therapist works with the participant to create a story related to their gender identity using the six-part story method. This story is then rendered to an artists’ book, which combines narrative with art (drawings, collage, computer images, etc.) and can take the form of a graphic novella, a zine, or a comic book. The pages can range from plain to ornate, as can the covers. Participants describe their process of making the books as the work unfolds and then participate in an exit interview at the completion of their book, remarking on what has changed for them and how the process affected them. Results: Preliminary results show high levels of suicidal thoughts among this population, as expected. Participants participate enthusiastically in the life story interview process and in the construction of a story related to gender identity. They enthusiastically participate in the studio process of putting their story into the form of a graphic novel, zine, or comic book. Participants reported feeling more comfortable with their TGD identity after the process and more able to resist negative judgments of family members and society. Suicidal thoughts diminish, and participants reported improved emotional wellbeing. Quantitative analysis of questionnaire data is underway Conclusions: A process in which narrative therapy is combined with art therapy shows promise for attracting and helping TGD individuals to reduce their risk for suicide without the stigma of going for mental health treatment. This process can be done outside of conventional mental health settings, on college and University campuses. This can provide an exciting alternative pathway for minority stressed and stigmatized individuals to engage in reflective, psychotherapeutic work without the trappings of psychotherapy or mental health treatment.

Keywords: minority stress, narrative process, artists' books, life story interview

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Authors: Geraldine Macdonald, Oliver Perra, Nina O’Neill, Laura Neeson, Kathryn Higgins

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Background: Despite improvements in recent years, almost one in six children in Northern Ireland (NI) leaves primary school without achieving the expected level in English and Maths. By early adolescence, this ratio is one in five. In 2010-11, around 9000 pupils in NI had failed to achieve the required standard in literacy and numeracy by the time they left full-time education. This paper reports the findings of an experimental evaluation of a programmed designed to improve educational outcomes of a cohort of children starting primary school in areas of high social disadvantage in Northern Ireland. The intervention: ‘Ready to Learn’ comprised two key components: a literacy-rich After School programme (one hour after school, three days per week), and a range of activities and support to promote the engagement of parents with their children’s learning, in school and at home. The intervention was delivered between September 2010 and August 2013. Study aims and objectives: The primary aim was to assess whether, and to what extent, ‘Ready to Learn’ improved the literacy of socially disadvantaged children entering primary schools compared with children in schools without access to the programme. Secondary aims included assessing the programme’s impact on children’s social, emotional and behavioural regulation, and parents’ engagement with their children’s learning. In total, 505 children (almost all) participated in the baseline assessment for the study, with good retention over seven sweeps of data collection. Study design: The intervention was evaluated by means of a cluster randomized trial, with schools as the unit of randomization and analysis. It included a qualitative component designed to examine process and implementation, and to explore the concept of parental engagement. Sixteen schools participated, with nine randomized to the experimental group. As well as outcome data relating to children, 134 semi-structured interviews were conducted with parents over the three years of the study, together with 88 interviews with school staff. Results: Given the children’s ages, not all measures used were direct measures of reading. Findings point to a positive impact of “Ready to Learn” on children’s reading achievement (comprehension and fluency), as assessed by the York Assessment of Reading Comprehension (YARC) and decoding, assessed using the Word Recognition and Phonic Skills (WRaPS3). Effects were not large, but evidence suggests that it is unusual for an after school programme to clearly to demonstrate effects on reading skills. No differences were found on three other measures of literacy-related skills: British Picture Vocabulary Scale (BPVS-II), Naming Speed and Non-word Reading Tests from the Phonological Assessment Battery (PhAB) or Concepts about Print (CAP) – the last due to an age-related ceiling effect). No differences were found between the two groups on measures of social, emotional and behavioural regulation, and due to low levels of participation, it was not possible directly to assess the contribution of the parent component to children’s outcomes. The qualitative data highlighted conflicting concepts of engagement between parents and school staff. Ready to Learn is a promising intervention that merits further support and evaluation.

Keywords: after-school, education, literacy, parental engagement

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Authors: Jose L. Diego, Antonio Berlanga, Gregorio López, Diana López

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The Rayuela method is a success story, as it is part of a project selected by the European Commission to face the challenge launched by itself for achieving a better understanding of human factors, as well as social and organisational aspects that are able to solve issues in fighting against crime. Rayuela's method specifically focuses on the drivers of cyber criminality, including approaches to prevent, investigate, and mitigate cybercriminal behavior. As the internet has become an integral part of young people’s lives, they are the key target of the Rayuela method because they (as a victim or as a perpetrator) are the most vulnerable link of the chain. Considering the increased time spent online and the control of their internet usage and the low level of awareness of cyber threats and their potential impact, it is understandable the proliferation of incidents due to human mistakes. 51% of Europeans feel not well informed about cyber threats, and 86% believe that the risk of becoming a victim of cybercrime is rapidly increasing. On the other hand, Law enforcement has noted that more and more young people are increasingly committing cybercrimes. This is an international problem that has considerable cost implications; it is estimated that crimes in cyberspace will cost the global economy $445B annually. Understanding all these phenomena drives to the necessity of a shift in focus from sanctions to deterrence and prevention. As a research project, Rayuela aims to bring together law enforcement agencies (LEAs), sociologists, psychologists, anthropologists, legal experts, computer scientists, and engineers, to develop novel methodologies that allow better understanding the factors affecting online behavior related to new ways of cyber criminality, as well as promoting the potential of these young talents for cybersecurity and technologies. Rayuela’s main goal is to better understand the drivers and human factors affecting certain relevant ways of cyber criminality, as well as empower and educate young people in the benefits, risks, and threats intrinsically linked to the use of the Internet by playing, thus preventing and mitigating cybercriminal behavior. In order to reach that goal it´s necessary an interdisciplinary consortium (formed by 17 international partners) carries out researches and actions like Profiling and case studies of cybercriminals and victims, risk assessments, studies on Internet of Things and its vulnerabilities, development of a serious gaming environment, training activities, data analysis and interpretation using Artificial intelligence, testing and piloting, etc. For facilitating the real implementation of the Rayuela method, as a community policing strategy, is crucial to count on a Police Force with a solid background in trust-building and community policing in order to do the piloting, specifically with young people. In this sense, Valencia Local Police is a pioneer Police Force working with young people in conflict solving, through providing police mediation and peer mediation services and advice. As an example, it is an official mediation institution, so agreements signed by their police mediators have once signed by the parties, the value of a judicial decision.

Keywords: fight against crime and insecurity, avert and prepare young people against aggression, ICT, serious gaming and artificial intelligence against cybercrime, conflict solving and mediation with young people

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Authors: D. Muyama, M. Luyiga, P. Buyungo, D. Chemonges, M. Namukwaya, L. Ssekabembe, B. Lukwago, D. Kyamagwa

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Context: The study focuses on the sustainability of health interventions in Uganda, particularly in the private sector, beyond donor-funded project periods. The Population Services International (PSI) implemented the Women Health Project (WHP) to ensure continued access to quality family planning, cervical cancer screening, and post-abortion care services through private clinics. Research Aim: The aim of the study is to assess the continued access to quality family planning, cervical cancer screening, and post-abortion care services through the private sector after the closure or reduction in funding of the WHP. Methodology: PSI trained and mentored 83 clinics to establish functional systems in self-regulatory quality improvement, supply chain, referral, and demand creation. The clinics were also connected to the national reporting system and utilized Ministry of Health reporting tools. An assessment tool with six criteria was designed and used to evaluate the progress of the clinics. Clinics scoring 75% and above were considered independent and graduated from the program. Findings: Out of the 83 private clinics, 56 successfully met the graduation criteria and graduated from the program, while 25 lost interest and were gradually dropped. Two clinics failed to achieve the criteria due to leadership challenges. The 59 graduating clinics continued to provide high-quality family planning services, including IUD, implant, Depo-Provera, oral contraceptives, and post-abortion care. All graduating clinics were reassessed and found to still be capable of offering services, attributing their success to government stock availability and acquired skills through mentorships. The clinics expressed appreciation to PSI for the sustainable plan that allowed them to operate beyond the project period. Theoretical Importance: This study contributes to the understanding of sustainability planning and the importance of clinic owners' attitudes and buy-in for continued service provision. It emphasizes the implementation of sustainability plans through existing structures to leverage available resources and ensure continuity of care. Data Collection and Analysis Procedures: The study collected data through the assessment tool that evaluated the progress of clinics based on the established criteria. The tool was scored out of 100%, and clinics scoring above 75% were deemed independent. The findings were analyzed quantitatively to determine the success rate of clinics in meeting the graduation criteria. Questions Addressed: The study addresses the question of whether private clinics in Uganda can sustain the provision of family planning, cervical cancer screening, and post-abortion care services after the closure or reduction in funding of the WHP. Conclusion: The study concludes that the attitude and buy-in of clinic owners are essential for sustainability planning. Implementing sustainability plans through existing structures and leveraging available resources are crucial for the continuity of care after the end of a project or reduced funding. The findings highlight the importance of establishing sustainable plans to ensure continued access to essential health services beyond the project period. Contributions: This study contributes to the existing knowledge for programmers implementing or intending to implement donor-funded projects. It provides insights into designing sustainable plans that enable the independent operation of clinics even after the end of a project.

Keywords: graduation, family planning, systems strengthening, sustainability

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Authors: Ali Baker, Russel Krawitz

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This paper describes a rare occurrence where a potentially fatal complication of COVID-19 infection (MIS-A) was misdiagnosed as an acute abdomen. As most patients with this syndrome present with fever and gastrointestinal symptoms, they may inadvertently fall under the care of the surgical unit. However, unusual imaging findings and a poor response to anti-microbial therapy should prompt clinicians to suspect a non-surgical etiology. More than half of MIS-A patients require ICU admission and vasopressor support. Prompt referral to a physician is key, as the cornerstone of treatment is IVIG and corticosteroid therapy. A 32 year old woman presented with right sided abdominal pain and fevers. She had also contracted COVID-19 two months earlier. Abdominal examination revealed generalised right sided tenderness. The patient had raised inflammatory markers, but other blood tests were unremarkable. CT scan revealed extensive lymphadenopathy along the ileocolic chain. The patient proved to be a diagnostic dilemma. She was reviewed by several surgical consultants and discussed with several inpatient teams. Although IV antibiotics were commenced, the right sided abdominal pain, and fevers persisted. Pan-culture returned negative. A mild cholestatic derangement developed. On day 5, the patient underwent preparation for colonoscopy to assess for a potential intraluminal etiology. The following day, the patient developed sinus tachycardia and hypotension that was refractory to fluid resuscitation. That patient was transferred to ICU and required vasopressor support. Repeat CT showed peri-portal edema and a thickened gallbladder wall. On re-examination, the patient was Murphy’s sign positive. Biliary ultrasound was equivocal for cholecystitis. The patient was planned for diagnostic laparoscopy. The following morning, a marked rise in cardiac troponin was discovered, and a follow-up echocardiogram revealed moderate to severe global systolic dysfunction. The impression was post-COVID MIS with myocardial involvement. IVIG and Methylprednisolone infusions were commenced. The patient had a great response. Vasopressor support was weaned, and the patient was discharged from ICU. The patient continued to improve clinically with oral prednisolone, and was discharged on day 17. Although MIS following COVID-19 infection is well-described syndrome in children, only recently has it come to light that it can occur in adults. The exact incidence is unknown, but it is thought to be rare. A recent systematic review found only 221 cases of MIS-A, which could be included for analysis. Symptoms vary, but the most frequent include fever, gastrointestinal, and mucocutaneous. Many patients progress to multi-organ failure and require vasopressor support. 7% succumb to the illness. The pathophysiology of MIS is only partly understood. It shares similarities with Kawasaki disease, macrophage activation syndrome, and cytokine release syndrome. Importantly, by definition, the patient must have an absence of severe respiratory symptoms. It is thought to be due to a dysregulated immune response to the virus. Potential mechanisms include reduced levels of neutralising antibodies and autoreactive antibodies that promote inflammation. Further research into MIS-A is needed. Although rare, this potentially fatal syndrome should be considered in the unwell surgical patient who has recently contracted COVID-19 and poses a diagnostic dilemma.

Keywords: acute-abdomen, MIS, COVID-19, ICU

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Authors: Ankush, Harshit Sosan Lakra, Rachita Kuthial

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Climate change poses significant challenges to vulnerable communities, particularly indigenous populations in ecologically sensitive regions. Jharkhand, located in the heart of India, is home to several indigenous communities, including the Particularly Vulnerable Tribal Groups (PVTGs). The Indigenous architecture of the region functions as a significant reservoir of climate adaptation wisdom. It explores the architectural analysis encompassing the construction materials, construction techniques, design principles, climate responsiveness, cultural relevance, adaptation, integration with the environment and traditional wisdom that has evolved through generations, rooted in cultural and socioeconomic traditions, and has allowed these communities to thrive in a variety of climatic zones, including hot and dry, humid, and hilly terrains to withstand the test of time. Despite their historical resilience to adverse climatic conditions, PVTG tribal communities face new and amplified challenges due to the accelerating pace of climate change. There is a significant research void that exists in assimilating their traditional practices and local wisdom into contemporary climate resilience initiatives. Most of the studies place emphasis on technologically advanced solutions, often ignoring the invaluable Indigenous Local knowledge that can complement and enhance these efforts. This research gap highlights the need to bridge the disconnect between indigenous knowledge and contemporary climate adaptation strategies. The study aims to explore and leverage indigenous knowledge of vernacular architecture as a strategic tool for enhancing climatic resilience among PVTGs of the region. The first objective is to understand the traditional wisdom of vernacular architecture by analyzing and documenting distinct architectural practices and cultural significance of PVTG communities, emphasizing construction techniques, materials and spatial planning. The second objective is to develop culturally sensitive climatic resilience strategies based on findings of vernacular architecture by employing a multidisciplinary research approach that encompasses ethnographic fieldwork climate data assessment considering multiple variables such as temperature variations, precipitation patterns, extreme weather events and climate change reports. This will be a tailor-made solution integrating indigenous knowledge with modern technology and sustainable practices. With the involvement of indigenous communities in the process, the research aims to ensure that the developed strategies are practical, culturally appropriate, and accepted. To foster long-term resilience against the global issue of climate change, we can bridge the gap between present needs and future aspirations with Traditional wisdom, offering sustainable solutions that will empower PVTG communities. Moreover, the study emphasizes the significance of preserving and reviving traditional Architectural wisdom for enhancing climatic resilience. It also highlights the need for cooperative endeavors of communities, stakeholders, policymakers, and researchers to encourage integrating traditional Knowledge into Modern sustainable design methods. Through these efforts, this research will contribute not only to the well-being of PVTG communities but also to the broader global effort to build a more resilient and sustainable future. Also, the Indigenous communities like PVTG in the state of Jharkhand can achieve climatic resilience while respecting and safeguarding the cultural heritage and peculiar characteristics of its native population.

Keywords: vernacular architecture, climate change, resilience, PVTGs, Jharkhand, indigenous people, India

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Authors: Alebiosu Olugbenga Shadrak, Victor Victoria

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Honey bees exhibit preferences in their foraging behaviour on pollen and nectar for food and honey production, respectively. Melissopalynology is the study of pollen in honey and other honey products. Several work have been conducted on the palynological studies of honeys from the southern parts of Nigeria but with relatively scant records from the Northern region of the country. This present study aimed at revealing the favourably visited plants by honey bees, Apis melifera var. adansonii, at some apiaries in Northern Nigeria, as well as determining the quality of honeys produced. Honeys were harvested and collected from four apiaries of the region, namely: Sarkin Dawa missionary bee farm, Taraba State; Eleeshuwa Bee Farm, Keffi, Nassarawa State, Bulus Beekeeper Apiaries, Kagarko, Kaduna State and Mai Gwava Bee Farm, Kano State. These honeys were acetolysed for palynological microscopic analysis and subjected to standard treatment methods for the determination of their proximate composition and sugar profiling. Fresh anthers of two dominantly represented plants in the honeys were then collected for the quantification of their pollen protein contents, using the micro-kjeldhal procedure. A total of 30 pollen types were identified in the four honeys, and some of them were common to the honeys. A classification method for expressing pollen frequency class was employed: Senna cf. siamea, Terminalia cf. catappa, Mangifera indica, Parinari curatelifolia, Vitellaria paradoxa, Elaeis guineensis, Parkia biglobosa, Phyllantus muellerianus and Berlina Grandiflora, as “Frequent” (16-45%); while the others are either Rare (3-15%) or Sporadic (less than 3 %). Pollen protein levels of the two abundantly represented plants, Senna siamea (15.90mg/ml) and Terminalia catappa (17.33mg/ml) were found to be considerably lower. The biochemical analyses revealed varying amounts of proximate composition, non-reducing sugar and total sugar levels in the honeys. The results of this study indicate that pollen and nectar of the “Frequent” plants were preferentially foraged by honeybees in the apiaries. The estimated pollen protein contents of Senna same and Terminalia catappa were considerably lower and not likely to have influenced their favourable visitation by honeybees. However, a relatively higher representation of Senna cf. siamea in the pollen spectrum might have resulted from its characteristic brightly coloured and well scented flowers, aiding greater entomophily. Terminalia catappa, Mangifera indica, Elaeis guineensis, Vitellaria paradoxa, and Parkia biglobosa are typical food crops; hence they probably attracted the honeybees owing to the rich nutritional values of their fruits and seeds. Another possible reason for a greater entomophily of the favourably visited plants are certain nutritional constituents of their pollen and nectar, which were not investigated in this study. The nutritional composition of the honeys was observed to fall within the safe limits of international norms, as prescribed by Codex Alimentarius Commission, thus they are good honeys for human consumption. It is therefore imperative to adopt strategic conservation steps in ensuring that these favourably visited plants are protected from indiscriminate anthropogenic activities and also encourage apiarists in the country to establish their bee farms more proximally to the plants for optimal honey yield.

Keywords: honeybees, melissopalynology, preferentially foraged, nutritional, bee farms, proximally

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Authors: Bridget J. Kenny, Elizabeth Hoban, Jo Williams

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Adolescent pregnancy presents a significant public health challenge for Cambodia. Despite declines in the overall fertility rate, the adolescent fertility rate is increasing. Adolescent pregnancy is particularly problematic in the Northeast provinces of Ratanak Kiri and Mondul Kiri where 34 percent of girls aged between 15 and 19 have begun childbearing; this is almost three times Cambodia’s national average of 12 percent. Language, cultural and geographic barriers have restricted qualitative exploration of the sexual and reproductive health (SRH) challenges that face indigenous adolescents in Northeast Cambodia. The current study sought to address this gap by exploring the SRH practices of adolescent mothers from indigenous populations in Ratanak Kiri Province. Twenty-two adolescent mothers, aged between 15 and 19, were recruited from seven indigenous villages in Ratanak Kiri Province and asked to participate in a combined body mapping exercise and semi-structured interview. Participants were given a large piece of paper (59.4 x 84.1 cm) with the outline of a female body and asked to draw the female reproductive organs onto the ‘body map’. Participants were encouraged to explain what they had drawn with the purpose of evoking conversation about their reproductive bodies. Adolescent mothers were then invited to participate in a semi-structured interview to further expand on topics of SRH. The qualitative approach offered an excellent avenue to explore the unique SRH challenges that face indigenous adolescents in rural Cambodia. In particular, the use of visual data collection methods reduced the language and cultural barriers that have previously restricted or prevented qualitative exploration of this population group. Thematic analysis yielded six major themes: (1) understanding of the female reproductive body, (2) contraceptive knowledge, (3) contraceptive use, (4) barriers to contraceptive use, (5) sexual practices, (6) contact with healthcare facilities. Participants could name several modern contraceptive methods and knew where they could access family planning services. However, adolescent mothers explained that they gained this knowledge during antenatal care visits and consequently participants had limited SRH knowledge, including contraceptive awareness, at the time of sexual initiation. Fear of the perceived side effects of modern contraception, including infertility, provided an additional barrier to contraceptive use for indigenous adolescents. Participants did not cite cost or geographic isolation as barriers to accessing SRH services. Child marriage and early sexual initiation were also identified as important factors contributing to the high prevalence of adolescent pregnancy in this population group. The findings support the Ministry of Education, Youth and Sports' (MoEYS) recent introduction of SRH education into the primary and secondary school curriculum but suggest indigenous girls in rural Cambodia require additional sources of SRH information. Results indicate adolescent girls’ first point of contact with healthcare facilities occurs after they become pregnant. Promotion of an effective continuum of care by increasing access to healthcare services during the pre-pregnancy period is suggested as a means of providing adolescents girls with an additional avenue to acquire SRH information.

Keywords: adolescent pregnancy, contraceptive use, family planning, sexual and reproductive health

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Authors: Fossarello Maurizio, Mattana Giorgio, Tatti Filippo.

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The most widely performed surgical procedure in Open-Angle Glaucoma (OAG) is trabeculectomy. Although this filtering procedure is extremely effective, surgical failure and postoperative complications are reported. Due to the its invasive nature and possible complications, trabeculectomy is usually reserved, in practice, for patients who are refractory to medical and laser therapy. Recently, a number of micro-invasive surgical techniques (MIGS: Micro-Invasive Glaucoma Surgery), have been introduced in clinical practice. They meet the criteria of micro-incisional approach, minimal tissue damage, short surgical time, reliable IOP reduction, extremely high safety profile and rapid post-operative recovery. Xen45 Gel Implant (Allergan, Dublin, Ireland) is one of the MIGS alternatives, and consists in a porcine gelatin tube designed to create an aqueous flow from the anterior chamber to the subconjunctival space, bypassing the resistance of the trabecular meshwork. In this study we report the results of this technique as a favorable option in the treatment of OAG for its benefits in term of efficacy and safety, either alone or in combination with cataract surgery. This is a retrospective, single-center study conducted in consecutive OAG patients, who underwent Xen45 Gel Stent implantation alone or in combination with phacoemulsification, from October 2018 to June 2019. The primary endpoint of the study was to evaluate the reduction of both IOP and number of antiglaucoma medications at 12 months. The secondary endpoint was to correlate filtering bleb morphology evaluated by means of anterior segment OCT with efficacy in IOP lowering and eventual further procedures requirement. Data were recorded on Microsoft Excel and study analysis was performed using Microsoft Excel and SPSS (IBM). Mean values with standard deviations were calculated for IOPs and number of antiglaucoma medications at all points. Kolmogorov-Smirnov test showed that IOP followed a normal distribution at all time, therefore the paired Student’s T test was used to compare baseline and postoperative mean IOP. Correlation between postoperative Day 1 IOP and Month 12 IOP was evaluated using Pearson coefficient. Thirty-six eyes of 36 patients were evaluated. As compared to baseline, mean IOP and the mean number of antiglaucoma medications significantly decreased from 27,33 ± 7,67 mmHg to 16,3 ± 2,89 mmHg (38,8% reduction) and from 2,64 ± 1,39 to 0,42 ± 0,8 (84% reduction), respectively, at 12 months after surgery (both p < 0,001). According to bleb morphology, eyes were divided in uniform group (n=8, 22,2%), subconjunctival separation group (n=5, 13,9%), microcystic multiform group (n=9, 25%) and multiple internal layer group (n=14, 38,9%). Comparing to baseline, there was no significative difference in IOP between the 4 groups at month 12 follow-up visit. Adverse events included bleb function decrease (n=14, 38,9%), hypotony (n=8, 22,2%) and choroidal detachment (n=2, 5,6%). All eyes presenting bleb flattening underwent needling and MMC injection. The higher percentage of patients that required secondary needling was in the uniform group (75%), with a significant difference between the groups (p=0,03). Xen45 gel stent, either alone or in combination with phacoemulsification, provided a significant lowering in both IOP and medical antiglaucoma treatment and an elevated safety profile.

Keywords: anterior segment OCT, bleb morphology, micro-invasive glaucoma surgery, open angle glaucoma, Xen45 gel implant

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Authors: Hsin-Yu Lee, Ming-Zhong Li, Wen-Hsi Chiu, Su-Fen Cheng, Shwu-Wen Lin

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Background: The use of medical terminology is essential to professional nurses on clinical practice. However, most nursing students consider traditional lecture-based teaching of medical terminology as boring and overly conceptual and lack motivation to learn. It is thus an issue to be discussed on how to enhance nursing students’ self-directed learning and improve learning outcomes of medical terminology. Digital game-based learning is a learner-centered way of learning. Past literature showed that the most common game-based learning for language education has been immersive games and teaching games. Thus, this study selected role-playing games (RPG) and digital puzzle games for observation and comparison. It is interesting to explore whether digital game-based learning has positive impact on nursing students’ learning of medical terminology and whether students can adapt well on this type of learning. Results can be used to provide references for institutes and teachers on teaching medical terminology. These instructions give you guidelines for preparing papers for the conference. Use this document as a template if you are using Microsoft Word. Otherwise, use this document as an instruction set. The electronic file of your paper will be formatted further at WASET. Define all symbols used in the abstract. Do not cite references in the abstract. Do not delete the blank line immediately above the abstract; it sets the footnote at the bottom of this column. Page margins are 1,78 cm top and down; 1,65 cm left and right. Each column width is 8,89 cm and the separation between the columns is 0,51 cm. Objective: The purpose of this research is to explore respectively the impact of RPG and puzzle game on nursing students’ self-directed learning and technology acceptance. The study further discusses whether different game types bring about different influences on students’ self-directed learning and technology acceptance. Methods: A quasi-experimental design was adopted in this study so that repeated measures between two groups could be conveniently conducted. 103 nursing students from a nursing college in Northern Taiwan participated in the study. For three weeks of experiment, the experiment group (n=52) received “traditional teaching + RPG” while the control group (n=51) received “traditional teaching + puzzle games”. Results: 1. On self-directed learning: For each game type, there were significant differences for the delayed tests of both groups as compared to the pre and post-tests of each group. However, there were no significant differences between the two game types. 2. On technology acceptance: For the experiment group, after the intervention of RPG, there were no significant differences concerning technology acceptance. For the control group, after the intervention of puzzle games, there were significant differences regarding technology acceptance. Pearson-correlation coefficient and path analysis conducted on the results of the two groups revealed that the dimension were highly correlated and reached statistical significance. Yet, the comparison of technology acceptance between the two game types did not reach statistical significance. Conclusion and Recommend: This study found that through using different digital games on learning, nursing students have effectively improved their self-directed learning. Students’ technology acceptances were also high for the two different digital game types and each dimension was significantly correlated. The results of the experimental group showed that through the scenarios of RPG, students had a deeper understanding of medical terminology, which reached the ‘Understand’ dimension of Bloom’s taxonomy. The results of the control group indicated that digital puzzle games could help students memorize and review medical terminology, which reached the ‘Remember’ dimension of Bloom’s taxonomy. The findings suggest that teachers of medical terminology could use digital games to assist their teaching according to their goals on cognitive learning. Adequate use of those games could help improve students’ self-directed learning and further enhance their learning outcome on medical terminology.

Keywords: digital game-based learning, medical terminology, nursing education, self-directed learning, technology acceptance model

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Authors: Bryan Jenkins

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Introduction: The expansion of irrigation in the Canterbury region has led to the sustainability limits being reached for water availability and the cumulative effects of land use intensification. The institutional framework under New Zealand’s Resource Management Act was found to be an inadequate basis for managing water at sustainability limits. An alternative paradigm for water management was developed based on collaborative governance and nested adaptive systems. This led to the formulation and implementation of the Canterbury Water Management Strategy. Methods: The nested adaptive system approach was adopted. Sustainability issues were identified at multiple spatial and time scales and defined potential failure pathways for the water resource system. These included biophysical and socio-economic issues such as water availability, cumulative effects on water quality due to land use intensification, projected changes in climate, public health, institutional arrangements, economic outcomes and externalities, and, social effects of changing technology. This led to the derivation of sustainability strategies to address these failure pathways. The collaborative governance approach involved stakeholder participation and community engagement to decide on a regional strategy; regional and zone committees of community and rūnanga (Māori groups) members to develop implementation programmes for the strategy; and, farmer collectives for operational management. Findings: The strategy identified improvements in the efficiency of use of water already allocated was more effective in improving water availability than a reliance on increased storage alone. New forms of storage with less adverse impacts were introduced, such as managed aquifer recharge and off-river storage. Reductions of nutrients from land use intensification by improving management practices has been a priority. Solutions packages for addressing the degradation of vulnerable lakes and rivers have been prepared. Biodiversity enhancement projects have been initiated. Greater involvement of Māori has led to the incorporation of kaitiakitanga (resource stewardship) into implementation programmes. Emerging issues are the need for improved integration of surface water and groundwater interactions, increased use of modelling of water and financial outcomes to guide decision making, and, equity in allocation among existing users as well as between existing and future users. Conclusions: However, sustainability analysis indicates that the proposed levels of management interventions are not sufficient to achieve community targets for water management. There is a need for more proactive recovery and rehabilitation measures. Managing to environmental limits is not sufficient, rather managing adaptive cycles is needed. Better measurement and management of water use efficiency is required. Proposed implementation packages are not sufficient to deliver desired water quality outcomes. Greater attention to targets important to environmental and recreational interests is needed to maintain trust in the collaborative process. Implementation programmes don’t adequately address climate change adaptations and greenhouse gas mitigation. Affordability is a constraint on adaptive capacity of farmers and communities. More funding mechanisms are required to implement proactive measures. The legislative and institutional framework needs to be changed to incorporate water framework legislation, regional sustainability strategies and water infrastructure coordination.

Keywords: collaborative governance, irrigation management, nested adaptive systems, sustainable water management

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Authors: Carmen García Sánchez

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The UN's 17 Sustainable Development Goals – specifically the nº 3 and nº 11- urgently call for new architectural design solutions at different design scales to increase human contact with nature in the health and wellbeing promotion of primarily urban communities. The discipline of Interior Design offers an important alternative to large-scale nature-inclusive actions which are not always possible due to space limitations. These circumstances provide an immense opportunity to integrate biophilic design, a complex emerging and under-developed approach that pursues sustainable design strategies for increasing the human-nature connection through the experience of the built environment. Biophilic design explores the diverse ways humans are inherently inclined to affiliate with nature, attach meaning to and derive benefit from the natural world. It represents a biological understanding of architecture which categorization is still in progress. The internationally renowned Danish domestic architecture built in the 1950´s and early 1960´s - a golden age of Danish modern architecture - left a leading legacy that has greatly influenced the domestic sphere and has further led the world in terms of good design and welfare. This study examines how four existing post-war domestic buildings establish a dialogue with nature and her variations over time. The case-studies unveil both memorable and unique biophilic resources through sophisticated and original design expressions, where transformative processes connect the users to the natural setting and reflect fundamental ways in which they attach meaning to the place. In addition, fascinating analogies in terms of this nature interaction with particular traditional Japanese architecture inform the research. They embody prevailing lessons for our time today. The research methodology is based on a thorough literature review combined with a phenomenological analysis into how these case-studies contribute to the connection between humans and nature, after conducting fieldwork throughout varying seasons to document understanding in nature transformations multi-sensory perception (via sight, touch, sound, smell, time and movement) as a core research strategy. The cases´ most outstanding features have been studied attending the following key parameters: 1. Space: 1.1. Relationships (itineraries); 1.2. Measures/scale; 2. Context: Context: Landscape reading in different weather/seasonal conditions; 3. Tectonic: 3.1. Constructive joints, elements assembly; 3.2. Structural order; 4. Materiality: 4.1. Finishes, 4.2. Colors; 4.3. Tactile qualities; 5. Daylight interplay. Departing from an artistic-scientific exploration this groundbreaking study provides sustainable practical design strategies, perspectives, and inspiration to boost humans´ contact with nature through the experience of the interior built environment. Some strategies are associated with access to outdoor space or require ample space, while others can thrive in a dense urban context without direct access to the natural environment. The objective is not only to produce knowledge, but to phase in biophilic design in the built environment, expanding its theory and practice into a new dimension. Its long-term vision is to efficiently enhance the health and well-being of urban communities through daily interaction with Nature.

Keywords: sustainability, biophilic design, architectural design, interior design, nature, Danish architecture, Japanese architecture

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Authors: Neusa Fernanda Torres, Buyisile Chibi, Lyn E. Middleton, Vernon P. Solomon, Tivani P. Mashamba-Thompson

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Background: Self-medication with antibiotics (SMA) is a global concern, with a higher incidence in low and middle-income countries (LMICs). Despite intense world-wide efforts to control and promote the rational use of antibiotics, continuing practices of SMA systematically exposes individuals and communities to the risk of antibiotic resistance and other undesirable antibiotic side effects. Moreover, it increases the health systems costs of acquiring more powerful antibiotics to treat the resistant infection. This review thus maps evidence on the factors influencing self-medication with antibiotics in these settings. Methods: The search strategy for this review involved electronic databases including PubMed, Web of Knowledge, Science Direct, EBSCOhost (PubMed, CINAHL with Full Text, Health Source - Consumer Edition, MEDLINE), Google Scholar, BioMed Central and World Health Organization library, using the search terms:’ Self-Medication’, ‘antibiotics’, ‘factors’ and ‘reasons’. Our search included studies published from 2007 to 2017. Thematic analysis was performed to identify the patterns of evidence on SMA in LMICs. The mixed method quality appraisal tool (MMAT) version 2011 was employed to assess the quality of the included primary studies. Results: Fifteen studies met the inclusion criteria. Studies included population from the rural (46,4%), urban (33,6%) and combined (20%) settings, of the following LMICs: Guatemala (2 studies), India (2), Indonesia (2), Kenya (1), Laos (1), Nepal (1), Nigeria (2), Pakistan (2), Sri Lanka (1), and Yemen (1). The total sample size of all 15 included studies was 7676 participants. The findings of the review show a high prevalence of SMA ranging from 8,1% to 93%. Accessibility, affordability, conditions of health facilities (long waiting, quality of services and workers) as long well as poor health-seeking behavior and lack of information are factors that influence SMA in LMICs. Antibiotics such as amoxicillin, metronidazole, amoxicillin/clavulanic, ampicillin, ciprofloxacin, azithromycin, penicillin, and tetracycline, were the most frequently used for SMA. The major sources of antibiotics included pharmacies, drug stores, leftover drugs, family/friends and old prescription. Sore throat, common cold, cough with mucus, headache, toothache, flu-like symptoms, pain relief, fever, running nose, toothache, upper respiratory tract infections, urinary symptoms, urinary tract infection were the common disease symptoms managed with SMA. Conclusion: Although the information on factors influencing SMA in LMICs is unevenly distributed, the available information revealed the existence of research evidence on antibiotic self-medication in some countries of LMICs. SMA practices are influenced by social-cultural determinants of health and frequently associated with poor dispensing and prescribing practices, deficient health-seeking behavior and consequently with inappropriate drug use. Therefore, there is still a need to conduct further studies (qualitative, quantitative and randomized control trial) on factors and reasons for SMA to correctly address the public health problem in LMICs.

Keywords: antibiotics, factors, reasons, self-medication, low and middle-income countries (LMICs)

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Authors: Yong H Sheng, Beatriz Garcillán, Eden Whitlock, Yukli Freedman, SiLing Yang, M Arifur Rahman, Nicholas Weber, Fabienne Mackay

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Chronic lymphocytic leukemia (CLL) is closely associated with immune dysfunction, yet the mechanisms underlying this immune deficiency remain poorly understood. Transmembrane Activator and CAML Interactor (TACI), a receptor known for its role in IL-10 regulation and autoimmunity, to the best of our knowledge has not been investigated in the context of anti-tumor immunity or its impact on CLL progression. This study addresses the gap by exploring the role of TACI in regulating CLL cells within the tumor microenvironment and its broader effects on disease progression and immune competence. We utilized the Eµ-TCL1 mouse model to generate CLL mice deficient in TACI and examined the consequences of TACI loss in adoptive transfer models over a five-week period. Comprehensive transcriptomic analysis, including RNA sequencing and microarray, was employed to determine TACI’s influence on the CLL gene expression profile. Additionally, we studied TACI’s direct role in CLL cell migration and immune modulation using patient-derived CLL cells in culture and Patient-Derived Xenograph (PDX) models. Our findings demonstrate that TACI signaling plays a pivotal role in promoting CLL progression and immune suppression. Loss of TACI signaling significantly inhibited CLL development and enhanced immune functionality. When TACI+/+ or TACI-/- TCL1 CLL cells were transferred into wild-type recipient mice, those receiving TACI-deficient cells showed reduced disease progression and lower incidence of CLL. Mice with TACI-/- CLL cells exhibited normalized serum levels of pro-inflammatory cytokines IL-6 and IL-10, restored proportions of T-cell subsets, and improved immune compartment function compared to counterparts with TACI+/+ CLL cells. Mechanistically, TACI-deficient CLL cells expressed significantly lower levels of IL-10, TNF, and inhibitory receptors such as PD-L1 and PD-L2. These cells also display restored circulating immunoglobulin levels and responses to T cell-dependent antigens, highlighting a recovery of immune competence. Further mechanistic studies revealed that TACI signaling drives CLL cell migration and homing to the spleen, where these cells actively establish an immunosuppressive microenvironment that supports immune evasion and tumor growth. Patient-derived CLL cells and PDX models confirmed TACI’s direct role in enhancing CLL cell migration and fostering immune suppression, emphasizing its critical function in the tumor microenvironment. By disrupting TACI signaling, we observed a reduction in CLL-associated immune suppression and tumor progression, offering a promising therapeutic avenue. This study establishes, for the first time, that targeting TACI disrupts key mechanisms underlying CLL progression while preserving vital immune functions. Unlike existing treatments that often impair immunity and lead to infection-related complications, TACI inhibition offers the dual benefit of controlling disease and maintaining immune homeostasis. These findings provide a strong rationale for developing therapeutic strategies that inhibit TACI as a means to improve outcomes in CLL patients. Beyond its implications for CLL, this research underscores the broader importance of TACI in regulating immune-tumor interactions, paving the way for future studies into its role in other malignancies.

Keywords: chronic lymphocytic leukemia, TACI, IL-10, immune suppression

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Authors: Azeem Tariq, Stephane De Tourdonnet, Lars Stoumann Jensen, Reiner Wassmann, Bjoern Ole Sander, Quynh Duong Vu, Trinh Van Mai, Andreas De Neergaard

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Rice growing area is increasing to meet the food demand of increasing population. Mostly, rice is growing on lowland, small landholder fields in most part of the world, which is one of the major sources of greenhouse gases (GHG) emissions from agriculture fields. The strategies such as, altering water and residues (carbon) management practices are assumed to be essential to mitigate the GHG emissions from flooded rice system. The actual implementation and potential of these measures on small farmer fields is still challenging. A field study was conducted on red river delta in Northern Vietnam to identify the potential challenges and barriers to the small rice farmers for implementation of climate smart rice practices. The objective of this study was to develop and access the feasibility of climate smart rice prototypes under actual farmer conditions. Field and scientific oriented framework was used to meet our objective. The methodological framework composed of six steps: i) identification of stakeholders and possible options, ii) assessment of barrios, drawbacks/advantages of new technologies, iii) prototype design, iv) assessment of mitigation potential of each prototype, v) scenario building and vi) scenario assessment. A farm survey was conducted to identify the existing farm practices and major constraints of small rice farmers. We proposed the two water (pre transplant+midseason drainage and early+midseason drainage) and one straw (full residue incorporation) management option keeping in views the farmers constraints and barriers for implementation. To test new typologies with existing prototypes (midseason drainage, partial residue incorporation) at farmer local conditions, a participatory field experiment was conducted for two consecutive rice seasons at farmer fields. Following the results of each season a workshop was conducted with stakeholders (farmers, village leaders, cooperatives, irrigation staff, extensionists, agricultural officers) at local and district level to get feedbacks on new tested prototypes and to develop possible scenarios for climate smart rice production practices. The farm analysis survey showed that non-availability of cheap labor and lacks of alternatives for straw management influence the small farmers to burn the residues in the fields except to use for composting or other purposes. Our field results revealed that application of early season drainage significantly mitigates (40-60%) the methane emissions from residue incorporation. Early season drainage was more efficient and easy to control under cooperate manage system than individually managed water system, and it leads to both economic (9-11% high rice yield, low cost of production, reduced nutrient loses) and environmental (mitigate methane emissions) benefits. The participatory field study allows the assessment of adaptation potential and possible benefits of climate smart practices on small farmer fields. If farmers have no other residue management option, full residue incorporation with early plus midseason drainage is adaptable and beneficial (both environmentally and economically) management option for small rice farmers.

Keywords: adaptation, climate smart agriculture, constrainsts, smallholders

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Authors: Jana Heimel, Franziska Drescher, Lauren Ugur, Graciela Kuchle

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Sharing platforms are a widely investigated field. However, there is a research gap with a lack of focus on ‘real’ (non-profit-orientated) sharing platforms. The research project addresses this gap by conducting an empirical study on a private peer-to-peer (P2P) network to investigate cooperative behavior from a socio-psychological perspective. In recent years the conversion from possession to accessing is increasingly influencing different sectors, particularly the traveling industry. The number of people participating in hospitality exchange platforms like Airbnb, Couchsurfing, and Warmshowers (WS) is rapidly growing. WS is an increasingly popular online community that is linking cycling tourists and locals. It builds on the idea of the “sharing economy” as a not-for-profit hospitality network for bicycle tourists. Hosts not only provide a sleeping berth and warm shower free of charge but also offer additional services to their guests, such as cooking and washing clothes for them. According to previous studies, they are motivated by the idea of promoting cultural experience and forming new friendships. Trust and reciprocity are supposed to play major roles in the success of such platforms. The objective of this research project is to analyze the reciprocity behavior within the WS community. Reciprocity is the act of giving and taking among each other. Individuals feel obligated to return a favor and often expect to increase their own chances of receiving future benefits for themselves. Consequently, the drivers that incite giving and taking, as well as the motivation for hosts and guests, are examined. Thus, the project investigates a particular tourism offer that contributes to sustainable tourism by analyzing P2P resp. cyclist-to-cyclist, C2C) tourism. C2C tourism is characterized by special hospitality and generosity. To find out what motivations drive the hosts and which determinants drive the sharing cycling economy, an empirical study has been conducted globally through an online survey. The data was gathered through the WS community and comprised responses from more than 10,000 cyclists around the globe. Next to general information mostly comprising quantitative data on bicycle tourism (year/tour distance, duration and budget), qualitative information on traveling with WS as well as hosting was collected. The most important motivations for a traveler is to explore the local culture, to save money, and to make friends. The main reasons to host a guest are to promote the use of bicycles and to make friends, but also to give back and pay forward. WS members prefer to stay with/host cyclists. The results indicate that C2C tourists share homogenous characteristics and a similar philosophy, which is crucial for building mutual trust. Members of WS are generally extremely trustful. The study promotes an ecological form of tourism by combining sustainability, regionality, health, experience and the local communities' cultures. The empirical evidence found and analyzed, despite evident limitations, enabled us to shed light, especially on the issue of motivations and social capital, and on the functioning of ‘sharing’ platforms. Final research results are intended to promote C2C tourism around the globe to further replace conventional by sustainable tourism.

Keywords: bicycle tourism, homogeneity, reciprocity, sharing economy, trust

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Authors: Parag Katira, Frederika Rentzeperis, Zuzanna Nowicka, Giada Fiandaca, Thomas Veith, Jack Farinhas, Noemi Andor

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Resource limitations shape the outcome of competitions between genetically heterogeneous pre-malignant cells. One example of such heterogeneity is in the ploidy (DNA content) of pre-malignant cells. A whole-genome duplication (WGD) transforms a diploid cell into a tetraploid one and has been detected in 28-56% of human cancers. If a tetraploid subclone expands, it consistently does so early in tumor evolution, when cell density is still low, and competition for nutrients is comparatively weak – an observation confirmed for several tumor types. WGD+ cells need more resources to synthesize increasing amounts of DNA, RNA, and proteins. To quantify resource limitations and how they relate to ploidy, we performed a PAN cancer analysis of WGD, PET/CT, and MRI scans. Segmentation of >20 different organs from >900 PET/CT scans were performed with MOOSE. We observed a strong correlation between organ-wide population-average estimates of Oxygen and the average ploidy of cancers growing in the respective organ (Pearson R = 0.66; P= 0.001). In-vitro experiments using near-diploid and near-tetraploid lineages derived from a breast cancer cell line supported the hypothesis that DNA content influences Glucose- and Oxygen-dependent proliferation-, death- and migration rates. To model how subpopulations with variable DNA content compete in the resource-limited environment of the human brain, we developed a stochastic state-space model of the brain (S3MB). The model discretizes the brain into voxels, whereby the state of each voxel is defined by 8+ variables that are updated over time: stiffness, Oxygen, phosphate, glucose, vasculature, dead cells, migrating cells and proliferating cells of various DNA content, and treat conditions such as radiotherapy and chemotherapy. Well-established Fokker-Planck partial differential equations govern the distribution of resources and cells across voxels. We applied S3MB on sequencing and imaging data obtained from a primary GBM patient. We performed whole genome sequencing (WGS) of four surgical specimens collected during the 1ˢᵗ and 2ⁿᵈ surgeries of the GBM and used HATCHET to quantify its clonal composition and how it changes between the two surgeries. HATCHET identified two aneuploid subpopulations of ploidy 1.98 and 2.29, respectively. The low-ploidy clone was dominant at the time of the first surgery and became even more dominant upon recurrence. MRI images were available before and after each surgery and registered to MNI space. The S3MB domain was initiated from 4mm³ voxels of the MNI space. T1 post and T2 flair scan acquired after the 1ˢᵗ surgery informed tumor cell densities per voxel. Magnetic Resonance Elastography scans and PET/CT scans informed stiffness and Glucose access per voxel. We performed a parameter search to recapitulate the GBM’s tumor cell density and ploidy composition before the 2ⁿᵈ surgery. Results suggest that the high-ploidy subpopulation had a higher Glucose-dependent proliferation rate (0.70 vs. 0.49), but a lower Glucose-dependent death rate (0.47 vs. 1.42). These differences resulted in spatial differences in the distribution of the two subpopulations. Our results contribute to a better understanding of how genomics and microenvironments interact to shape cell fate decisions and could help pave the way to therapeutic strategies that mimic prognostically favorable environments.

Keywords: tumor evolution, intra-tumor heterogeneity, whole-genome doubling, mathematical modeling

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Authors: Caroline Lindlar, Eva Jakob

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Female entrepreneurs often face significant barriers in accessing funding due to biases from business angels, venture capitalists, and financial institutions, which tend to favor male entrepreneurs. These biases contribute to persistent funding disparities, with female entrepreneurs receiving less financial support than their male counterparts. The situation worsens when female entrepreneurs have prior experiences with venture failure, which diminishes their attractiveness to traditional investors. Venture failure, defined as the cessation of operations due to declining revenues, rising costs, or ownership changes, plays a substantial role in shaping funding opportunities. In response, female entrepreneurs frequently turn to alternative funding sources such as crowdlending, where gender biases are often reversed in favor of women, particularly when their ventures emphasize social value creation. While existing research highlights the positive impact of gender on crowdfunding success, it remains unclear how venture failure, known to negatively bias female entrepreneurs in traditional funding contexts, interacts with the positive effects of gender in crowdlending. This interaction is particularly relevant because crowdlending often involves non-professional funders who make repeated investment decisions under uncertainty, based on limited information and past experiences. Given that approximately one-third of ventures fail to deliver promised returns, the role of gender bias after failure in crowdlending is an important area of investigation. This study addresses How failure affects crowd funders’ gender bias in future funding decisions? Drawing on social role and role congruity theory, we posit that societal perceptions of women as more communal conflict with the agentic qualities traditionally associated with entrepreneurship. This incongruence may result in reduced confidence in the success of female entrepreneurs after failure, limiting their access to future funding. However, we also hypothesize that social framing may mitigate this bias by aligning perceptions of female entrepreneurs with traits such as warmth and caring, enhancing their appeal after failure. To test these assertions, it conducted a between-subject audio vignette experiment with 155 participants who listened to entrepreneur pitches manipulated by gender (male vs. female) and venture framing (social vs. commercial). Participants made initial investment decisions, received failure-related news about the venture, and then made subsequent investment decisions. Pre-tests with 159 participants ensured the validity and reliability of the experimental manipulations. Moreover, we did a metric conjoint analysis with 100 participants, and they had to decide between different crowdfunding campaigns based on the attributes of previous failure, gender, and venture mission. it findings reveal that failure activates gender biases in crowdlending. Female-led ventures receive significantly less funding after failure compared to male-led ventures, suggesting the positive bias toward female entrepreneurs in the pre-funding phase does not persist post-failure. Moreover, framing a venture as socially oriented exacerbates the negative effect of failure for female entrepreneurs, as they secure fewer funds after failure compared to male entrepreneurs leading similar social ventures. This indicates that role-congruent framing does not mitigate gender bias after failure. This study contributes to research on gender in entrepreneurship by exploring how failure impacts future funding for female entrepreneurs. It also expands social crowdfunding literature by examining social value framing and adds to the entrepreneurial failure literature by focusing on crowd funders’ post-failure behavior.

Keywords: gender bias, crowdfunding, investment failure, investment behavior, social entrepreneurship

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Authors: Àidan Higgins

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Higher education will be crucial in the coming decades in helping to make Ireland a nation is known for innovation, competitive enterprise, and ongoing academic success, as well as a desirable location to live and work with a high quality of life, vibrant culture, and inclusive social structures. Higher education institutions will actively connect with each student community, society, and business; they will help students develop a sense of place and identity in Ireland and provide the tools they need to contribute significantly to the global community. It will also serve as a catalyst for novel ideas through research, many of which will become the foundation for long-lasting inventive businesses in the future as part of the 2030 National Strategy on Education focuses on change and developing our education system with a focus on how we carry out Research. The emphasis is central to knowledge transfer and a consistent research framework with exploiting opportunities and having the necessary expertise. The newly formed Technological Universities (TU) in Ireland are based on a government initiative to create a new type of higher education institution that focuses on applied and industry-focused research and education. The basis of the TU is to bring together two or more existing institutes of technology to create a larger and more comprehensive institution that offers a wider range of programs and services to students and industry partners. The TU model aims to promote collaboration between academia, industry, and community organizations to foster innovation, research, and economic development. The TU model also aims to enhance the student experience by providing a more seamless pathway from undergraduate to postgraduate studies, as well as greater opportunities for work placements and engagement with industry partners. Additionally, the TUs are designed to provide a greater emphasis on applied research, technology transfer, and entrepreneurship, with the goal of fostering innovation and contributing to economic growth. A project is a collection of organised tasks carried out precisely to produce a singular output (product or service) within a given time frame. Project management is a set of activities that facilitates the successful implementation of a project. The significant differences between research and development projects are the (lack of) precise requirements and (the inability to) plan an outcome from the beginning of the project. The evaluation criteria for a research project must consider these and other "particularities" in works; for instance, proving something cannot be done may be a successful outcome. This study intends to explore how a newly established multi-campus technological university manages research projects effectively. The study will identify the potential and difficulties of managing research projects, the tools, resources and processes available in a multi-campus Technological University context and the methods and approaches employed to deal with these difficulties. Key stakeholders like project managers, academics, and administrators will be surveyed as part of the study, which will also involve an explorative investigation of current literature and data. The findings of this study will contribute significantly to creating best practices for project management in this setting and offer insightful information about the efficient management of research projects within a multi-campus technological university.

Keywords: project management, research and research-related projects, multi-campus technology university, processes

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