Search results for: long-term disaster management system

Authors: Ece A. Irmak, Amdulla O. Mekhrabov, M. Vedat Akdeniz

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There is a growing interest on the synthesis and characterization of nanoalloys since the unique chemical, and physical properties of nanoalloys can be tuned and, consequently, new structural motifs can be created by varying the type of constituent elements, atomic and magnetic ordering, as well as size and shape of the nanoparticles. Due to the fine size effects, magnetic nanoalloys have considerable attention with their enhanced mechanical, electrical, optical and magnetic behavior. As an important magnetic nanoalloy, the novel application area of Fe-Ni based nanoalloys is expected to be widened in the chemical, aerospace industry and magnetic biomedical applications. Noble metals have been using in biomedical applications for several years because of their surface plasmon properties. In this respect, iron-nickel nanoalloys are promising materials for magnetic biomedical applications because they show novel properties such as superparamagnetism and surface plasmon resonance property. Also, there is great attention for the usage Fe-Ni based nanoalloys as radar absorbing materials in aerospace and stealth industry due to having high Curie temperature, high permeability and high saturation magnetization with good thermal stability. In this study, FeNi₃ bimetallic nanoalloys were synthesized by mechanical alloying in a planetary high energy ball mill. In mechanical alloying, micron size powders are placed into the mill with milling media. The powders are repeatedly deformed, fractured and alloyed by high energy collision under the impact of balls until the desired composition and particle size is achieved. The experimental studies were carried out in two parts. Firstly, dry mechanical alloying with high energy dry planetary ball milling was applied to obtain FeNi₃ nanoparticles. Secondly, dry milling was followed by surfactant-assisted ball milling to observe the surfactant and solvent effect on the structure, size, and properties of the FeNi₃ nanoalloys. In the first part, the powder sample of iron-nickel was prepared according to the 1:3 iron to nickel ratio to produce FeNi₃ nanoparticles and the 1:10 powder to ball weight ratio. To avoid oxidation during milling, the vials had been filled with Ar inert gas before milling started. The powders were milled for 80 hours in total and the synthesis of the FeNi₃ intermetallic nanoparticles was succeeded by mechanical alloying in 40 hours. Also, regarding the particle size, it was found that the amount of nano-sized particles raised with increasing milling time. In the second part of the study, dry milling of the Fe and Ni powders with the same stoichiometric ratio was repeated. Then, to prevent agglomeration and to obtain smaller sized nanoparticles with superparamagnetic behavior, surfactants and solvent are added to the system, after 40-hour milling time, with the completion of the mechanical alloying. During surfactant-assisted ball milling, heptane was used as milling medium, and as surfactants, oleic acid and oleylamine were used in the high energy ball milling processes. The characterization of the alloyed particles in terms of microstructure, morphology, particle size, thermal and magnetic properties with respect to milling time was done by X-ray diffraction, scanning electron microscopy, energy dispersive spectroscopy, vibrating-sample magnetometer, and differential scanning calorimetry.

Keywords: iron-nickel systems, magnetic nanoalloys, mechanical alloying, nanoalloy characterization, surfactant-assisted ball milling

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Authors: Joanna Wielochowska, Aneta Wielochowska

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Whilst the relationship between scientific areas such as cognitive psychology, neurobiology and philosophy of mind has been emphasized in recent decades of scientific research, concepts and discoveries made in both fields overlap and complement each other in their quest for answers to similar questions. The object of the following case study is to describe, analyze and illustrate the nature and characteristics of a certain cognitive experience which appears to display features of synaesthesia, or rather high-level synaesthesia (ideasthesia). The following research has been conducted on the subject of two authors, monozygotic twins (both polysynaesthetes) experiencing involuntary associations of identical nature. Authors made attempts to identify which cognitive and conceptual dependencies may guide this experience. Operating on self-introduced nomenclature, the described phenomenon- multi-dimensional processing of textual and visual information- aims to define a relationship that involuntarily and immediately couples the content introduced by means of text or image a sensation of appearing in a certain place in the mind’s eye. More precisely: (I) defining a concept introduced by means of textual content during activity of reading or writing, or (II) defining a concept introduced by means of visual content during activity of looking at image(s) with simultaneous sensation of being allocated to a given place in the mind’s eye. A place can be then defined as a cognitive representation of a certain concept. During the activity of processing information, a person has an immediate and involuntary feel of appearing in a certain place themselves, just like a character of a story, ‘observing’ a venue or a scenery from one or more perspectives and angles. That forms a unique and unified experience, constituting a background mental landscape of text or image being looked at. We came to a conclusion that semantic allocations to a given place could be divided and classified into the categories and subcategories and are naturally linked with an individual’s semantic knowledge-base. A place can be defined as a representation one’s unique idea of a given concept that has been established in their semantic knowledge base. A multi-level structure of selectivity of places in the mind’s eye, as a reaction to a given information (one stimuli), draws comparisons to structures and patterns found in botany. Double-flowered varieties of flowers and a whorl system (arrangement) which is characteristic to components of some flower species were given as an illustrative example. A composition of petals that fan out from one single point and wrap around a stem inspired an idea that, just like in nature, in philosophy of mind there are patterns driven by the logic specific to a given phenomenon. The study intertwines terms perceived through the philosophical lens, such as definition of meaning, subjectivity of meaning, mental atmosphere of places, and others. Analysis of this rare experience aims to contribute to constantly developing theoretical framework of the philosophy of mind and influence the way human semantic knowledge base and processing given content in terms of distinguishing between information and meaning is researched.

Keywords: information and meaning, information processing, mental atmosphere of places, patterns in nature, philosophy of mind, selectivity, semantic knowledge base, senses, synaesthesia

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Authors: Lewis J. Woollin, Robert I. Davidson, Paul Watson, Philip J. Hyde

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Introduction: In-vitro testing of arthroplasty materials is of paramount importance when ensuring that they can withstand the performance requirements encountered in-vivo. One common machine used for in-vitro testing is a pin-on-plate tribometer, an early stage screening device that generates data on the wear characteristics of arthroplasty bearing materials. These devices test vertically loaded rotating cylindrical pins acting against reciprocating plates, representing the bearing surfaces. In this study, a pin-on-plate machine has been developed that provides several improvements over current technology, thereby progressing arthroplasty bearing research. Historically, pin-on-plate tribometers have been used to investigate the performance of arthroplasty bearing materials under conditions commonly encountered during a standard gait cycle; nominal operating pressures of 2-6 MPa and an operating frequency of 1 Hz are typical. There has been increased interest in using pin-on-plate machines to test more representative in-vivo conditions, due to the drive to test 'beyond compliance', as well as their testing speed and economic advantages over hip simulators. Current pin-on-plate machines do not accommodate the increased performance requirements associated with more extreme kinematic conditions, therefore a next-generation pin-on-plate tribometer has been developed to bridge the gap between current technology and future research requirements. Methodology: The design was driven by several physiologically relevant requirements. Firstly, an increased loading capacity was essential to replicate the peak pressures that occur in the natural hip joint during running and chair-rising, as well as increasing the understanding of wear rates in obese patients. Secondly, the introduction of mid-cycle load variation was of paramount importance, as this allows for an approximation of the loads present in a gait cycle to be applied and to test the fatigue properties of materials. Finally, the rig must be validated against previous-generation pin-on-plate and arthroplasty wear data. Results: The resulting machine is a twelve station device that is split into three sets of four stations, providing an increased testing capacity compared to most current pin-on-plate tribometers. The loading of the pins is generated using a pneumatic system, which can produce contact pressures of up to 201 MPa on a 3.2 mm² round pin face. This greatly exceeds currently achievable contact pressures in literature and opens new research avenues such as testing rim wear of mal-positioned hip implants. Additionally, the contact pressure of each set can be changed independently of the others, allowing multiple loading conditions to be tested simultaneously. Using pneumatics also allows the applied pressure to be switched ON/OFF mid-cycle, another feature not currently reported elsewhere, which allows for investigation into intermittent loading and material fatigue. The device is currently undergoing a series of validation tests using Ultra-High-Molecular-Weight-Polyethylene pins and 316L Stainless Steel Plates (polished to a Ra < 0.05 µm). The operating pressures will be between 2-6 MPa, operating at 1 Hz, allowing for validation of the machine against results reported previously in the literature. The successful production of this next-generation pin-on-plate tribometer will, following its validation, unlock multiple previously unavailable research avenues.

Keywords: arthroplasty, mechanical design, pin-on-plate, total joint replacement, wear testing

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Authors: Mukondi Esther Nethavhakone

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In 2020 World Health Organization announced the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as Coronavirus disease 2019 (COVID-19) pandemic. To curb or contain the spread of the novel coronavirus (COVID 19), global governments implemented social distancing and lockdown regulations. Subsequently, it was no longer business as per usual, life as we knew it had changed, and so many aspects of people's lives were negatively affected, including financial and employment stability. Mainly, because companies/businesses had to put their operations on hold, some had to shut down completely, resulting in the loss of income for many people globally. Finances and employment insecurities are some of the issues that exacerbated many social issues that the world was already faced with, such as school drop-outs, teenage pregnancies, sexual assaults, gender-based violence, crime, child abuse, elderly abuse, to name a few. Expectedly the majority of the population's mental health state was threatened. This resulted in an increased number of people seeking mental healthcare services. The increasing need for mental healthcare services in Low and Middle-income countries proves to be a challenge because it is a well-known fact due to financial constraints and not well-established healthcare systems, mental healthcare provision is not as prioritised as the primary healthcare in these countries. It is against this backdrop that the researcher seeks to find viable, cost-effective, and accessible mental health solutions for low and middle-income countries amid the pressures of any pandemic. The researcher will undertake a systematic review of the technology-based mental health solutions that have been implemented/adopted by developed countries during COVID 19 lockdown and social distancing periods. This systematic review study aims to determine if low and middle-income countries can adopt the cost-effective version of digital mental health solutions for the healthcare system to adequately provide mental healthcare services during critical times such as pandemics (when there's an overwhelming diminish in mental health globally). The researcher will undertake a systematic review study through mixed methods. It will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The mixed-methods uses findings from both qualitative and quantitative studies in one review study. It will be beneficial to conduct this kind of study using mixed methods because it is a public health topic that involves social interventions and it is not purely based on medical interventions. Therefore, the meta-ethnographic (qualitative data) analysis will be crucial in understanding why and which digital methods work and for whom does it work, rather than only the meta-analysis (quantitative data) providing what digital mental health methods works. The data collection process will be extensive, involving the development of a database, table of summary of evidence/findings, and quality assessment process lastly, The researcher will ensure that ethical procedures are followed and adhered to, ensuring that sensitive data is protected and the study doesn't pose any harm to the participants.

Keywords: digital, mental health, covid, low and middle-income countries

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Authors: Helen S. Joyner (Melito), Mohammad Anvari

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Concentrated emulsions stabilized by proteins are systems of great importance in food, pharmaceutical and cosmetic products. Controlling emulsion rheology is critical for ensuring desired properties during formation, storage, and consumption of emulsion-based products. Studies on concentrated emulsions have focused on rheology of monodispersed systems. However, emulsions used for industrial applications are polydispersed in nature, and this polydispersity is regarded as an important parameter that also governs the rheology of the concentrated emulsions. Therefore, the objective of this study was to characterize rheological (small and large deformation behaviors) and microstructural properties of concentrated emulsions which were not truly monodispersed as usually encountered in food products such as margarines, mayonnaise, creams, spreads, and etc. The concentrated emulsions were prepared at different concentrations of fish gelatin (0.2, 0.4, 0.8% w/v in the whole emulsion system), oil-water ratio 80-20 (w/w), homogenization speed 10000 rpm, and 25oC. Confocal laser scanning microscopy (CLSM) was used to determine the microstructure of the emulsions. To prepare samples for CLSM analysis, FG solutions were stained by Fluorescein isothiocyanate dye. Emulsion viscosity profiles were determined using shear rate sweeps (0.01 to 100 1/s). The linear viscoelastic regions (LVRs) of the emulsions were determined using strain sweeps (0.01 to 100% strain) for each sample. Frequency sweeps were performed in the LVR (0.1% strain) from 0.6 to 100 rad/s. Large amplitude oscillatory shear (LAOS) testing was conducted by collecting raw waveform data at 0.05, 1, 10, and 100% strain at 4 different frequencies (0.5, 1, 10, and 100 rad/s). All measurements were performed in triplicate at 25oC. The CLSM results revealed that increased fish gelatin concentration resulted in more stable oil-in-water emulsions with homogeneous, finely dispersed oil droplets. Furthermore, the protein concentration had a significant effect on emulsion rheological properties. Apparent viscosity and dynamic moduli at small deformations increased with increasing fish gelatin concentration. These results were related to increased inter-droplet network connections caused by increased fish gelatin adsorption at the surface of oil droplets. Nevertheless, all samples showed shear-thinning and weak gel behaviors over shear rate and frequency sweeps, respectively. Lissajous plots, or plots of stress versus strain, and phase lag values were used to determine nonlinear behavior of the emulsions in LAOS testing. Greater distortion in the elliptical shape of the plots followed by higher phase lag values was observed at large strains and frequencies in all samples, indicating increased nonlinear behavior. Shifts from elastic-dominated to viscous dominated behavior were also observed. These shifts were attributed to damage to the sample microstructure (e.g. gel network disruption), which would lead to viscous-type behaviors such as permanent deformation and flow. Unlike the small deformation results, the LAOS behavior of the concentrated emulsions was not dependent on fish gelatin concentration. Systems with different microstructures showed similar nonlinear viscoelastic behaviors. The results of this study provided valuable information that can be used to incorporate concentrated emulsions in emulsion-based food formulations.

Keywords: concentrated emulsion, fish gelatin, microstructure, rheology

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Authors: Miguel Chen Austin, Denis Bruneau, Alain Sempey, Laurent Mora, Alain Sommier

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An experimental study in a Plus Energy House (PEH) prototype was conducted in August 2016. It aimed to highlight the energy charge and discharge of a concrete-slab floor submitted to the day-night-cycles heat exchanges in the southwestern part of France and to identify the heat transfer phenomena that take place in both processes: charge and discharge. The main features of this PEH, significant to this study, are the following: (i) a non-active slab covering the major part of the entire floor surface of the house, which include a concrete layer 68 mm thick as upper layer; (ii) solar window shades located on the north and south facades along with a large eave facing south, (iii) large double-glazed windows covering the majority of the south facade, (iv) a natural ventilation system (NVS) composed by ten automatized openings with different dimensions: four are located on the south facade, four on the north facade and two on the shed roof (north-oriented). To highlight the energy charge and discharge processes of the non-active slab, heat flux and temperature measurement techniques were implemented, along with airspeed measurements. Ten “measurement-poles” (MP) were distributed all over the concrete-floor surface. Each MP represented a zone of measurement, where air and surface temperatures, and convection and radiation heat fluxes, were intended to be measured. The airspeed was measured only at two points over the slab surface, near the south facade. To identify the heat transfer phenomena that take part in the charge and discharge process, some relevant dimensionless parameters were used, along with statistical analysis; heat transfer phenomena were identified based on this analysis. Experimental data, after processing, had shown that two periods could be identified at a glance: charge (heat gain, positive values) and discharge (heat losses, negative values). During the charge period, on the floor surface, radiation heat exchanges were significantly higher compared with convection. On the other hand, convection heat exchanges were significantly higher than radiation, in the discharge period. Spatially, both, convection and radiation heat exchanges are higher near the natural ventilation openings and smaller far from them, as expected. Experimental correlations have been determined using a linear regression model, showing the relation between the Nusselt number with relevant parameters: Peclet, Rayleigh, and Richardson numbers. This has led to the determination of the convective heat transfer coefficient and its comparison with the convective heat coefficient resulting from measurements. Results have shown that forced and natural convection coexists during the discharge period; more accurate correlations with the Peclet number than with the Rayleigh number, have been found. This may suggest that forced convection is stronger than natural convection. Yet, airspeed levels encountered suggest that it is natural convection that should take place rather than forced convection. Despite this, Richardson number values encountered indicate otherwise. During the charge period, air-velocity levels might indicate that none air motion occurs, which might lead to heat transfer by diffusion instead of convection.

Keywords: heat flux measurement, natural ventilation, non-active concrete slab, plus energy house

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Authors: Juliane Toce, Steven Holochwost

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A substantial and growing literature has demonstrated that arts education benefits young children’s socioemotional and cognitive development. Less is known about the capacity of arts-integrated instruction to yield benefits to similar domains, particularly among demographically and socioeconomically diverse groups of young children. However, the small literature on this topic suggests that arts-integrated instruction may foster young children’s socioemotional and cognitive development by presenting opportunities to 1) engage in instructional content in diverse ways, 2) experience and regulate strong emotions, 3) experience growth-oriented feedback, and 4) engage in collaborative work with peers. Start with the Art is a new program of arts-integrated instruction currently being implemented in four schools in a school district that serves students from a diverse range of backgrounds. The program employs a co-teaching model in which teaching artists and classroom teachers engage in collaborative lesson planning and instruction over the course of the academic year and is currently the focus of an impact study featuring a randomized-control design, as well as an implementation study, both of which are funded through an Educational Innovation and Research grant from the United States Department of Education. The paper will present the early results from the Start with the Art implementation study. These results will provide an overview of the extent to which the program was implemented in accordance with design, with a particular emphasis on the degree to which the four opportunities enumerated above (e.g., opportunities to engage in instructional content in diverse ways) were presented to students. There will be a review key factors that may influence the fidelity of implementation, including classroom teachers’ reception of the program and the extent to which extant conditions in the classroom (e.g., the overall level of classroom organization) may have impacted implementation fidelity. With the explicit purpose of creating a program that values and meets the needs of the teachers and students, Start with the Art incorporates the feedback from individuals participating in the intervention. Tracing its trajectory from inception to ongoing development and examining the adaptive changes made in response to teachers' transformative experiences in the post-pandemic classroom, Start with the Art continues to solicit input from experts in integrating artistic content into core curricula within educational settings catering to students from under-represented backgrounds in the arts. Leveraging the input from this rich consortium of experts has allowed for a comprehensive evaluation of the program’s implementation. The early findings derived from the implementation study emphasize the potential of arts-integrated instruction to incorporate restorative practices. Such practices serve as a crucial support system for both students and educators, providing avenues for children to express themselves, heal emotionally, and foster social development, while empowering teachers to create more empathetic, inclusive, and supportive learning environments. This all-encompassing analysis spotlights Start with the Art’s adaptability to any learning environment through the program’s effectiveness, resilience, and its capacity to transform - through art - the classroom experience within the ever-evolving landscape of education.

Keywords: arts-integration, social emotional learning, diverse learners, co-teaching, teaching artists, post-pandemic teaching

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Authors: Nada Poropat Jeletic, Gordana Hrzica

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Bilingual conversational corpora represent a meaningful and the most comprehensive data source for investigating the genuine contact phenomena in non-monitored bi-lingual speech productions. They can be particularly useful for bilingual research since some features of bilingual interaction can hardly be accessed with more traditional methodologies (e.g., elicitation tasks). The method of language sampling provides the resources for describing language interaction in a bilingual community and/or in bilingual situations (e.g. code-switching, amount of languages used, number of languages used, etc.). To capture these phenomena in genuine communication situations, such sampling should be as close as possible to spontaneous communication. Bilingual spoken corpus design is methodologically demanding. Therefore this paper aims at describing the methodological challenges that apply to the corpus design of the conversational corpus design of the Istrian Istrovenetian-Croatian Bilingual Corpus. Croatian is the first official language of the Croatian-Italian officially bilingual Istria County, while Istrovenetian is a diatopic subvariety of Venetian, a longlasting lingua franca in the Istrian peninsula, the mother tongue of the members of the Italian National Community in Istria and the primary code of informal everyday communication among the Istrian Italophone population. Within the CLARIN infrastructure, TalkBank is being used, as it provides relevant procedures for designing and analyzing bilingual corpora. Furthermore, it allows public availability allows for easy replication of studies and cumulative progress as a research community builds up around the corpus, while the tools developed within the field of corpus linguistics enable easy retrieval and analysis of information. The method of language sampling employed is kept at the level of spontaneous communication, in order to maximise the naturalness of the collected conversational data. All speakers have provided written informed consent in which they agree to be recorded at a random point within the period of one month after signing the consent. Participants are administered a background questionnaire providing information about the socioeconomic status and the exposure and language usage in the participants social networks. Recording data are being transcribed, phonologically adapted within a standard-sized orthographic form, coded and segmented (speech streams are being segmented into communication units based on syntactic criteria) and are being marked following the CHAT transcription system and its associated CLAN suite of programmes within the TalkBank toolkit. The corpus consists of transcribed sound recordings of 36 bilingual speakers, while the target is to publish the whole corpus by the end of 2020, by sampling spontaneous conversations among approximately 100 speakers from all the bilingual areas of Istria for ensuring representativeness (the participants are being recruited across three generations of native bilingual speakers in all the bilingual areas of the peninsula). Conversational corpora are still rare in TalkBank, so the Corpus will contribute to BilingBank as a highly relevant and scientifically reliable resource for an internationally established and active research community. The impact of the research of communities with societal bilingualism will contribute to the growing body of research on bilingualism and multilingualism, especially regarding topics of language dominance, language attrition and loss, interference and code-switching etc.

Keywords: conversational corpora, bilingual corpora, code-switching, language sampling, corpus design methodology

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Authors: Sum Lau, Wing Chung Cleo Lau, Wing Yan Chu, Long Ching Ip, Wan Yin Lo, Jo Long Sam Yau, Ka Ho Hui, Sze Yi Mak

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Biomedical engineering (BME) is an interdisciplinary subject where knowledge about biology and medicine is applied to novel applications, solving clinical problems. This subject is crucial for cities such as Hong Kong, where the burden on the medical system is rising due to reasons like the ageing population. Hong Kong, who is actively boosting technological advancements in recent years, sets BME, or biotechnology, as a major category, as reflected in the 2018-19 Budget, where biotechnology was one of the four pillars for development. Over the years, while resources in terms of money and space have been provided, there has been a lack of talents expressed by both the academia and industry. While exogenous factors, such as COVID, may have hindered talents from outside Hong Kong to come, endogenous factors should also be considered. In particular, since there are already a few local universities offering BME programmes, their curriculum or style of education requires to be reviewed to intensify the network of the BME community and support post-academic career development. It was observed that while undergraduate (UG) studies focus on knowledge teaching with some technical training and postgraduate (PG) programmes concentrate on upstream research, the programmes are generally confined to the academic sector and lack connections to the industry. In light of that, a “Biomedical Innovation and Outreach Programme 2022” (“B.I.O.2022”) was held to connect students and professors from academia with clinicians and engineers from the industry, serving as a comparative approach to conventional education methods (UG and PG programmes from tertiary institutions). Over 100 participants, including undergraduates, postgraduates, secondary school students, researchers, engineers, and clinicians, took part in various outreach events such as conference and site visits, all held from June to July 2022. As a case study, this programme aimed to tackle the aforementioned problems with the theme of “4Cs” (connection, communication, collaboration, and commercialisation). The effectiveness of the programme is investigated by its ability to serve as an adult and continuing education and the effectiveness of causing social change to tackle current societal challenges, with the focus on tackling the lack of talents engaging in biomedical engineering. In this study, B.I.O.2022 is found to be able to complement the traditional educational methods, particularly in terms of knowledge exchange between the academia and the industry. With enhanced communications between participants from different career stages, there were students who followed up to visit or even work with the professionals after the programme. Furthermore, connections between the academia and industry could foster the generation of new knowledge, which ultimately pointed to commercialisation, adding value to the BME industry while filling the gap in terms of human resources. With the continuation of events like B.I.O.2022, it provides a promising starting point for the development and relationship strengthening of a BME community in Hong Kong, and shows potential as an alternative way of adult education or learning with societal benefits.

Keywords: biomedical engineering, adult education for social change, comparative methods and principles, lifelong learning, faced problems, promises, challenges and pitfalls

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Authors: Priyanka Botny Srinath, Alessandro Suglia, Mel McKendrick

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Background: Organizational cultural studies integrate sociology and anthropology, portraying man as a creator of symbols, languages, beliefs, and ideologies -essentially, a creator and manager of meaning. In our research, we leverage analytical measures to discern whether an organization embodies a singular culture or a myriad of subcultures. Fast-forward to 2023, our research thesis focuses on digitally measuring culture, coining it as the "Work Culture Quotient." This entails conceptually mapping common experiential patterns to provide executives insights into the digital organization journey, aiding in understanding their current position and identifying future steps. Objectives: Finding the new age skills that help in defining the culture; understand the implications of post-COVID effects; derive a digital framework for measuring skillsets. Method: We conducted two comprehensive Delphi studies to distill essential insights. Delphi 1: Through a thematic analysis of interviews with 20 high-level leaders representing companies across diverse regions -India, Japan, the US, Canada, Morocco, and Uganda- we identified 20 key skills critical for cultivating a robust organizational culture. The skills are -influence, self-confidence, optimism, empathy, leadership, collaboration and cooperation, developing others, commitment, innovativeness, leveraging diversity, change management, team capabilities, self-control, digital communication, emotional awareness, team bonding, communication, problem solving, adaptability, and trustworthiness. Delphi 2: Subject matter experts were asked to complete a questionnaire derived from the thematic analysis in stage 1 to formalise themes and draw consensus amongst experts on the most important workplace skills. Results: The thematic analysis resulted in 20 workplace employee skills being identified. These skills were all included in the Delphi round 2 questionnaire. From the outputs, we analysed the data using R Studio for arriving at agreement and consensus, we also used sum of squares method to compare various agreements to extract various themes with a threshold of 80% agreements. This yielded three themes at over 80% agreement (leadership, collaboration and cooperation, communication) and three further themes at over 60% agreement (commitment, empathy, trustworthiness). From this, we selected five questionnaires to be included in the primary data collection phase, and these will be paired with the digital footprints to provide a workplace culture quotient. Implications: The findings from these studies bear profound implications for decision-makers, revolutionizing their comprehension of organizational culture. Tackling the challenge of mapping the digital organization journey involves innovative methodologies that probe not only external landscapes but also internal cultural dynamics. This holistic approach furnishes decision-makers with a nuanced understanding of their organizational culture and visualizes pivotal skills for employee growth. This clarity enables informed choices resonating with the organization's unique cultural fabric. Anticipated outcomes transcend mere individual cultural measurements, aligning with organizational goals to unveil a comprehensive view of culture, exposing artifacts and depth. Armed with this profound understanding, decision-makers gain tangible evidence for informed decision-making, strategically leveraging cultural strengths to cultivate an environment conducive to growth, innovation, and enduring success, ultimately leading to measurable outcomes.

Keywords: leadership, cooperation, collaboration, teamwork, work culture

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Authors: Noury Bakrim

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When dealing with motivation/arbitrariness, forming form (Forma Formans) and morphodynamics are to be grasped as relevant implications of enunciation/enactment, schematization within the specificity of language as sound/meaning articulation. Thus, the fact that a language is a form does not contradict stasis/dynamic enunciation (reflexivity vs double articulation). Moreover, some languages exemplify the role of the forming form, uttering, and schematization (roots in Semitic languages, the Chinese case). Beyond the evolutionary biosemiotic process (form/substance bifurcation, the split between realization/representation), non-isomorphism/asymmetry between linguistic form/norm and linguistic realization (phonetics for instance) opens up a new horizon problematizing the role of Brain – sensorimotor contribution in the continuous forming form. Therefore, we hypothesize biotization as both process/trace co-constructing motivation/forming form. Henceforth, referring to our findings concerning distribution and motivation patterns within Berber written texts (pulse based obstruents and nasal-lateral levels in poetry) and oral storytelling (consonant intensity clustering in quantitative and semantic/prosodic motivation), we understand consonant clustering, motivation and schematization as a complex phenomenon partaking in patterns of oral/written iconic prosody and reflexive metalinguistic representation opening the stable form. We focus our inquiry on both Amazigh and English clusters (/spl/, /spr/) and iconic consonant iteration in [gnunnuy] (to roll/tumble), [smummuy] (to moan sadly or crankily). For instance, the syllabic structures of /splaeʃ/ and /splaet/ imply an anamorphic representation of the state of the world: splash, impact on aquatic surfaces/splat impact on the ground. The pair has stridency and distribution as distinctive features which specify its phonetic realization (and a part of its meaning) /ʃ/ is [+ strident] and /t/ is [+ distributed] on the vocal tract. Schematization is then a process relating both physiology/code as an arthron vocal/bodily, vocal/practical shaping of the motor-articulatory system, leading to syntactic/semantic thematization (agent/patient roles in /spl/, /sm/ and other clusters or the tense uvular /qq/ at the initial position in Berber). Furthermore, the productivity of serial syllable sequencing in Berber points out different expressivity forms. We postulate two Components of motivated formalization: i) the process of memory paradigmatization relating to sequence modeling under sensorimotor/verbal specific categories (production/perception), ii) the process of phonotactic selection - prosodic unconscious/subconscious distribution by virtue of iconicity. Basing on multiple tests including a questionnaire, phonotactic/visual recognition and oral/written reproduction, we aim at patterning/conceptualizing consonant schematization and motivation among EFL and Amazigh (Berber) learners and speakers integrating biolinguistic hypotheses.

Keywords: consonant motivation and prosody, language and order of life, anamorphic representation, represented representation, biotization, sensori-motor and brain representation, form, formalization and schematization

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Authors: Majed Al Otaibi, Melissa Lessard-Beaudoin, Amel Loudghi, Raphael Chouinard-Watkins, Melanie Plourde, Frederic Calon, C. Alexandre Castellano, Stephen Cunnane, Helene Payette, Pierrette Gaudreau, Denis Gris, Rona K. Graham

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Introduction: Alzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction, and also alterations in attention, planning, language and overall cognitive function. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may therefore lead to the discovery of potential biomarkers and/or treatments for neurodegenerative diseases. Objectives: To determine if olfactory dysfunction predicts future cognitive impairment in the aging population and to characterize the olfactory system in a murine model expressing a genetic factor of AD. Method: For the human study, quantitative olfactory tests (UPSIT and OMT) have been done on 93 subjects (aged 80 to 94 years) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) cohort accepting to participate in the ORCA secondary study. The telephone Modified Mini Mental State examination (t-MMSE) was used to assess cognition levels, and an olfactory self-report was also collected. In a separate cohort, olfactory cortical volume was calculated using MRI results from healthy old adults (n=25) and patients with AD (n=18) using the AAL single-subject atlas and performed with the PNEURO tool (PMOD 3.7). For the murine study, we are using Western blotting, RT-PCR and immunohistochemistry. Result: Human Study: Based on the self-report, 81% of the participants claimed to not suffer from any problem with olfaction. However, based on the UPSIT, 94% of those subjects showed a poor olfactory performance and different forms of microsmia. Moreover, the results confirm that olfactory function declines with age. We also detected a significant decrease in olfactory cortical volume in AD individuals compared to controls. Murine study: Preliminary data demonstrate there is a significant decrease in expression levels of the proform of caspase-3 and the caspase substrate STK3, in the olfactory bulb of mice expressing human APOE4 compared with controls. In addition, there is a significant decrease in the expression level of the caspase-9 proform and caspase-8 active fragment. Analysis of the mature neuron marker, NeuN, shows decreased expression levels of both isoforms. The data also suggest that Iba-1 immunostaining is increased in the olfactory bulb of APOE4 mice compared to wild type mice. Conclusions: The activation of caspase-3 may be the cause of the decreased levels of STK3 through caspase cleavage and may play role in the inflammation observed. In the clinical study, our results suggest that seniors are unaware of their olfactory function status and therefore it is not sufficient to measure olfaction using the self-report in the elderly. Studying olfactory function and cognitive performance in the aging population will help to discover biomarkers in the early stage of the AD.

Keywords: Alzheimer's disease, APOE4, cognition, caspase, brain atrophy, neurodegenerative, olfactory dysfunction

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Authors: Jiri Nepereny, Vladimir Vrzal

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Staphylococcus intermedius/pseudintermedius bacteria are commonly found on the skin of healthy dogs and can cause pruritic skin diseases under certain circumstances (trauma, allergy, immunodeficiency, ectoparasitosis, endocrinological diseases, glucocorticoid therapy, etc.). These can develop into complicated superficial or deep pyoderma, which represent a large group of problematic skin diseases in dogs. These are predominantly inflammations of a secondary nature, associated with the occurrence of coagulase-positive Staphylococcus spp. A major problem is increased itching, which greatly complicates the healing process. The aim of this work is to verify the efficacy of the developed preparation Bacteriophage SI (Staphylococcus intermedius). The tested preparation contains a lysate of bacterial cells of S. intermedius host culture including culture medium and live virions of specific phage. Sodium Merthiolate is added as a preservative in a safe concentration. Validation of the efficacy of the product was demonstrated by monitoring the therapeutic effect after application to indicated cases from clinical practice. The indication for inclusion of the patient into the trial was an adequate history and clinical examination accompanied by sample collection for bacteriological examination and isolation of the specific causative agent. Isolate identification was performed by API BioMérieux identification system (API ID 32 STAPH) and rep-PCR typing. The suitability of therapy for a specific case was confirmed by in vitro testing of the lytic ability of the bacteriophage to lyse the specific isolate = formation of specific plaques on the culture isolate on the surface of the solid culture medium. So far, a total of 32 dogs of different sexes, ages and breed affiliations with different symptoms of staphylococcal dermatitis have been included in the testing. Their previous therapy consisted of more or less successful systemic or local application of broad-spectrum antibiotics. The presence of S. intermedius/pseudintermedius has been demonstrated in 26 cases. The isolates were identified as a S. pseudintermedius, in all cases. Contaminant bacterial microflora was always present in the examined samples. The test product was applied subcutaneously in gradually increasing doses over a period of 1 month. After improvement in health status, maintenance therapy was followed by application of the product once a week for 3 months. Adverse effects associated with the administration of the product (swelling at the site of application) occurred in only 2 cases. In all cases, there was a significant reduction in clinical signs (healing of skin lesions and reduction of inflammation) after therapy and an improvement in the well-being of the treated animals. A major problem in the treatment of pyoderma is the frequent resistance of the causative agents to antibiotics, especially the increasing frequency of multidrug-resistant and methicillin-resistant S. pseudintermedius (MRSP) strains. Specific phagolysate using for the therapy of these diseases could solve this problem and to some extent replace or reduce the use of antibiotics, whose frequent and widespread application often leads to the emergence of resistance. The advantage of the therapeutic use of bacteriophages is their bactericidal effect, high specificity and safety. This work was supported by Project FV40213 from Ministry of Industry and Trade, Czech Republic.

Keywords: bacteriophage, pyoderma, staphylococcus spp, therapy

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Authors: Caspar Goeke, Holger Finger, Dorena Diekamp, Peter König

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Online-based research has recently gained increasing attention from various fields of research in the cognitive sciences. Technological advances in the form of online crowdsourcing (Amazon Mechanical Turk), open data repositories (Open Science Framework), and online analysis (Ipython notebook) offer rich possibilities to improve, validate, and speed up research. However, until today there is no cross-platform integration of these subsystems. Furthermore, implementation of online studies still suffers from the complex implementation (server infrastructure, database programming, security considerations etc.). Here we propose and test a new JavaScript framework that enables researchers to conduct any kind of behavioral research in the browser without the need to program a single line of code. In particular our framework offers the possibility to manipulate and combine the experimental stimuli via a graphical editor, directly in the browser. Moreover, we included an action-event system that can be used to handle user interactions, interactively change stimuli properties or store participants’ responses. Besides traditional recordings such as reaction time, mouse and keyboard presses, the tool offers webcam based eye and face-tracking. On top of these features our framework also takes care about the participant recruitment, via crowdsourcing platforms such as Amazon Mechanical Turk. Furthermore, the build in functionality of google translate will ensure automatic text translations of the experimental content. Thereby, thousands of participants from different cultures and nationalities can be recruited literally within hours. Finally, the recorded data can be visualized and cleaned online, and then exported into the desired formats (csv, xls, sav, mat) for statistical analysis. Alternatively, the data can also be analyzed online within our framework using the integrated Ipython notebook. The framework was designed such that studies can be used interchangeably between researchers. This will support not only the idea of open data repositories but also constitutes the possibility to share and reuse the experimental designs and analyses such that the validity of the paradigms will be improved. Particularly, sharing and integrating the experimental designs and analysis will lead to an increased consistency of experimental paradigms. To demonstrate the functionality of the framework we present the results of a pilot study in the field of spatial navigation that was conducted using the framework. Specifically, we recruited over 2000 subjects with various cultural backgrounds and consequently analyzed performance difference in dependence on the factors culture, gender and age. Overall, our results demonstrate a strong influence of cultural factors in spatial cognition. Such an influence has not yet been reported before and would not have been possible to show without the massive amount of data collected via our framework. In fact, these findings shed new lights on cultural differences in spatial navigation. As a consequence we conclude that our new framework constitutes a wide range of advantages for online research and a methodological innovation, by which new insights can be revealed on the basis of massive data collection.

Keywords: cultural differences, crowdsourcing, JavaScript framework, methodological innovation, online data collection, online study, spatial cognition

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Authors: Jennifer Buz, Alvin Spivey

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The most common greenhouse gas emitted through human activities, carbon dioxide (CO2), is naturally consumed by plants during photosynthesis. This process is actively being monetized by companies wishing to offset their carbon dioxide emissions. For example, companies are now able to purchase protections for vegetated land due-to-be clear cut or purchase barren land for reforestation. Therefore, by actively preventing the destruction/decay of plant matter or by introducing more plant matter (reforestation), a company can theoretically offset some of their emissions. One of the biggest issues in the carbon credit market is validating and verifying carbon offsets. There is a need for a system that can accurately and frequently ensure that the areas sold for carbon credits have the vegetation mass (and therefore for carbon offset capability) they claim. Traditional techniques for measuring vegetation mass and determining health are costly and require many person-hours. Orbital Sidekick offers an alternative approach that accurately quantifies carbon mass and assesses vegetation health through satellite hyperspectral imagery, a technique which enables us to remotely identify material composition (including plant species) and condition (e.g., health and growth stage). How much carbon a plant is capable of storing ultimately is tied to many factors, including material density (primarily species-dependent), plant size, and health (trees that are actively decaying are not effectively storing carbon). All of these factors are capable of being observed through satellite hyperspectral imagery. This abstract focuses on speciation. To build a species classification model, we matched pixels in our remote sensing imagery to plants on the ground for which we know the species. To accomplish this, we collaborated with the researchers at the Teakettle Experimental Forest. Our remote sensing data comes from our airborne “Kato” sensor, which flew over the study area and acquired hyperspectral imagery (400-2500 nm, 472 bands) at ~0.5 m/pixel resolution. Coverage of the entire teakettle experimental forest required capturing dozens of individual hyperspectral images. In order to combine these images into a mosaic, we accounted for potential variations of atmospheric conditions throughout the data collection. To do this, we ran an open source atmospheric correction routine called ISOFIT1 (Imaging Spectrometer Optiman FITting), which converted all of our remote sensing data from radiance to reflectance. A database of reflectance spectra for each of the tree species within the study area was acquired using the Teakettle stem map and the geo-referenced hyperspectral images. We found that a wide variety of machine learning classifiers were able to identify the species within our images with high (>95%) accuracy. For the most robust quantification of carbon mass and the best assessment of the health of a vegetated area, speciation is critical. Through the use of high resolution hyperspectral data, ground-truth databases, and complex analytical techniques, we are able to determine the species present within a pixel to a high degree of accuracy. These species identifications will feed directly into our carbon mass model.

Keywords: hyperspectral, satellite, carbon, imagery, python, machine learning, speciation

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Authors: Anzal Abbas Jaffari, Wajiha Javed, Naseem Salahuddin

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Rationale: Rabies, a vaccine preventable disease, continues to be a critical public health issue as it kills around 2000-5000 people annually in Pakistan. Along with the disease spread among animals, the dog population remains a victim of brutal culling practices by the local authorities, which adversely affects ecosystem (sinking of poison in the soil – affecting vegetation & contaminating water) and the disease spread. The dog population has been exponentially rising primarily because a lack of a consolidated nationwide Animal Birth Control program and awareness among the local communities in general and children in particular. This is reflected in Pakistan’s low SARE score - 1.5, which makes the country trails behind other developing countries like Bangladesh (2.5) and Philippines (3.5).According to an estimate, the province of Sindh alone is home to almost 2.5 million dogs. The clustering of dogs in Peri-Urban areas and inner cities localities leads to an increase of reported dog bite cases in these areas specifically. Objective: Rabies Free Pakistan (RFP), which is a joint venture of Getz Pharma Private Limited and Indus Hospital & Health Network (IHHN); it was established in 2018 to eliminate Rabies from Pakistan by 2030 using the One Health Approach. Methodology: The RFP team is actively working on advocacy and policy front with both the Federal & Provincial government to ensure that all stakeholders currently involved in dog culling in Pakistan have a paradigm shift towards humane methods of vaccination and ABC. Along with the federal government, RFP aims to declare Rabies as a notifiable disease. Whereas RFP closely works with the provincial government of Sindh to initiate a province wide Rabies Control Program.RFP program follows international standards and WHO approved protocols for this program in Pakistan.RFP team has achieved various milestones in the fight against Rabies after successfully scaling up project operations and has vaccinated more than 30,000 dogs and neutered around 7,000 dogs since 2018. Recommendations: Effective implementation of Rabies program (MDV and ABC) requires a concentrated effort to address a variety of structural and policy challenges. This essentially demands a massive shift in the attitude of individuals towards rabies. The two most significant challenges in implementing a standard policy at the structural level are lack of institutional capacity, shortage of vaccine, and absence of inter-departmental coordination among major stakeholders: federal government, provincial ministry of health, livestock, and local bodies (including local councils). The lack of capacity in health care workers to treat dog bite cases emerges as a critical challenge at the clinical level. Conclusion: Pakistan can learn from the successful international models of Sri Lanka and Mexico as they adopted the One Health Approach to eliminate rabies like RFP. The WHO advised One Health approach provides the policymakers with an interactive and cross-sectoral guide, which involves all the essential elements of the eco system (including animals, humans, and other components).

Keywords: animal birth control, dog population, mass dog vaccination, one health, rabies elimination

Procedia PDF Downloads 182

Authors: Ning Chia

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Each of the three different language texts (Manchu, Russian, and Latin) of the 1689 Treaty of Nerchinsk bore official seals from Imperial Russia and Qing China. These seals have received no academic attention, yet they can reveal a site of a layered and shared material, cultural, political, and diplomatic world of the time in Eastern Eurasia. The very different seal selections from both empires while ratifying the Treaty of Beijing in 1860 have obtained no scholarly advertency either; they can also explicate a tremendously changed relationship with visual and material manifestation. Exploring primary sources in Manchu, Russian, and Chinese languages as well as the images of the visual seals, this study investigates the reasons and purposes of utilizing official seals for the treaty agreement. A refreshed understanding of Russian-Qing diplomacy will be developed by pursuing the following aspects: (i) Analyzing the iconographic meanings of each seal insignia and unearthing a competitive, yet symbols-delivered and seal-generated, 'dialogue' between the two empires (ii) Contextualizing treaty seals within the historical seal cultures, and discovering how domestic seal system in each empire’s political institution developed into treaty-defined bilateral relations (iii) Expounding the seal confiding in each empire’s daily governing routines, and annotating the trust in the seal as a quested promise from the opponent negotiator to fulfill the treaty terms (iv) Contrasting the two seal traditions along two civilization-lines, Eastern vs. Western, and dissecting how the two styles of seal emblems affected the cross-cultural understanding or misunderstanding between the two empires (v) Comprehending the history-making events from the substantial resources such as the treaty seals, and grasping why the seals for the two treaties, so different in both visual design and symbolic value, were chosen in the two relationship eras (vi) Correlating the materialized seal 'expression' and the imperial worldviews based on each empire’s national/or power identity, and probing the seal-represented 'rule under the Heaven' assumption of China and Russian rising role in 'European-American imperialism … centered on East Asia' (Victor Shmagin, 2020). In conclusion, the impact of official seals on diplomatic treaties needs profound knowledge in seal history, insignia culture, and emblem belief to be able to comprehend. The official seals in both Imperial Russia and Qing China belonged to a particular statecraft art in a specific material and visual form. Once utilized in diplomatic treaties, the meticulously decorated and politically institutionalized seals were transformed from the determinant means for domestic administration and social control into the markers of an empire’s sovereign authority. Overlooked in historical practice, the insignia seal created a wire of 'visual contest' between the two rival powers. Through this material lens, the scholarly knowledge of the Russian-Qing diplomatic relationship will be significantly upgraded. Connecting Russian studies, Qing/Chinese studies, and Eurasian studies, this study also ties material culture, political culture, and diplomatic culture together. It promotes the study of official seals and emblem symbols in worldwide diplomatic history.

Keywords: Russia-Qing diplomatic relation, Treaty of Beijing (1860), Treaty of Nerchinsk (1689), Treaty seals

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Authors: Jungyeol Hong, Dongjoo Park

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The primary purpose of this study is to develop a methodological framework to predict daily subway ridership at a station-level and to examine the association between subway ridership and bus demand incorporating commercial business facility in the vicinity of each subway station. The socio-economic characteristics, land-use, and built environment as factors may have an impact on subway ridership. However, it should be considered not only the endogenous relationship between bus and subway demand but also the characteristics of commercial business within a subway station’s sphere of influence, and integrated transit network topology. Regarding a statistical approach to estimate subway ridership at a station level, therefore it should be considered endogeneity and heteroscedastic issues which might have in the subway ridership prediction model. This study focused on both discovering the impacts of bus demand, commercial business characteristics, and network topology on subway ridership and developing more precise subway ridership estimation accounting for its statistical bias. The spatial scope of the study covers entire Seoul city in South Korea and includes 243 stations with the temporal scope set at twenty-four hours with one-hour interval time panels each. The data for subway and bus ridership was collected Seoul Smart Card data from 2015 and 2016. Three-Stage Least Square(3SLS) approach was applied to develop daily subway ridership model as capturing the endogeneity and heteroscedasticity between bus and subway demand. Independent variables incorporating in the modeling process were commercial business characteristics, social-economic characteristics, safety index, transit facility attributes, and dummies for seasons and time zone. As a result, it was found that bus ridership and subway ridership were endogenous each other and they had a significantly positive sign of coefficients which means one transit mode could increase another transportation mode’s ridership. In other words, two transit modes of subway and bus have a mutual relationship instead of the competitive relationship. The commercial business characteristics are the most critical dimension among the independent variables. The variables of commercial business facility rate in the paper containing six types; medical, educational, recreational, financial, food service, and shopping. From the model result, a higher rate in medical, financial buildings, shopping, and food service facility lead to increment of subway ridership at a station, while recreational and educational facility shows lower subway ridership. The complex network theory was applied for estimating integrated network topology measures that cover the entire Seoul transit network system, and a framework for seeking an impact on subway ridership. The centrality measures were found to be significant and showed a positive sign indicating higher centrality led to more subway ridership at a station level. The results of model accuracy tests by out of samples provided that 3SLS model has less mean square error rather than OLS and showed the methodological approach for the 3SLS model was plausible to estimate more accurate subway ridership. Acknowledgement: This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science and ICT (2017R1C1B2010175).

Keywords: subway ridership, bus ridership, commercial business characteristic, endogeneity, network topology

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Authors: Shari S. C. Shang, Lynn S. L. Chiu

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In the digital payment market, some consumers use only one payment wallet while many others play multi-homing with a variety of payment services. With the diffusion of new payment systems, we examined the determinants of the adoption of multi-homing behavior. This study aims to understand how a digital payment provider dynamically expands business touch points with cross-business strategies to enrich the digital ecosystem and avoid the trap of multi-homing in customers. By synthesizing platform ecosystem literature, we constructed a two-dimensional research framework with one determinant of user digital behavior from offline to online intentions and the other determinant of digital payment touch points from convenient accessibility to cross-business platforms. To explore on a broader scale, we selected 12 digital payments from 5 countries of UK, US, Japan, Korea, and Taiwan. With the interplays of user digital behaviors and payment touch points, we group the study cases into four types: (1) Channel Initiated: users originated from retailers with high access to in-store shopping with face-to-face guidance for payment adoption. Providers offer rewards for customer loyalty and secure the retailer’s efficient cash flow management. (2) Social Media Dependent: users usually are digital natives with high access to social media or the internet who shop and pay digitally. Providers might not own physical or online shops but are licensed to aggregate money flows through virtual ecosystems. (3) Early Life Engagement: digital banks race to capture the next generation from popularity to profitability. This type of payment aimed to give children a taste of financial freedom while letting parents track their spending. Providers are to capitalize on the digital payment and e-commerce boom and hold on to new customers into adulthood. (4) Traditional Banking: plastic credit cards are purposely designed as a control group to track the evolvement of business strategies in digital payments. Traditional credit card users may follow the bank’s digital strategy to land on different types of digital wallets or mostly keep using plastic credit cards. This research analyzed business growth models and inter-firms’ coopetition strategies of the selected cases. Results of the multiple case analysis reveal that channel initiated payments bundled rewards with retailer’s business discount for recurring purchases. They also extended other financial services, such as insurance, to fulfill customers’ new demands. Contrastively, social media dependent payments developed new usages and new value creation, such as P2P money transfer through network effects among the virtual social ties, while early life engagements offer virtual banking products to children who are digital natives but overlooked by incumbents. It has disrupted the banking business domains in preparation for the metaverse economy. Lastly, the control group of traditional plastic credit cards has gradually converted to a BaaS (banking as a service) model depending on customers’ preferences. The multi-homing behavior is not avoidable in digital payment competitions. Payment providers may encounter multiple waves of a multi-homing threat after a short period of success. A dynamic cross-business collaboration strategy should be explored to continuously evolve the digital ecosystems and allow users for a broader shopping experience and continual usage.

Keywords: digital payment, digital ecosystems, multihoming users, cross business strategy, user digital behavior intentions

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Authors: Alexandra Steed

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Alexandra Steed URBAN was commissioned to undertake the South Essex Green and Blue Infrastructure Study (SEGBI) on behalf of the Association of South Essex Local Authorities (ASELA): a partnership of seven neighboring councils within the Thames Estuary. Located on London’s doorstep, the 70,000-hectare region is under extraordinary pressure for regeneration, further development, and economic expansion, yet faces extreme challenges: sea-level rise and inadequate flood defenses, stormwater flooding and threatened infrastructure, loss of internationally important habitats, significant existing community deprivation, and lack of connectivity and access to green space. The brief was to embrace these challenges in the creation of a document that would form a key part of ASELA’s Joint Strategic Framework and feed into local plans and master plans. Thus, helping to tackle climate change, ecological collapse, and social inequity at a regional scale whilst creating a relationship and awareness between urban communities and the surrounding landscapes and nature. The SEGBI project applied a ‘land-based’ methodology, combined with a co-design approach involving numerous stakeholders, to explore how living infrastructure can address these significant issues, reshape future planning and development, and create thriving places for the whole community of life. It comprised three key stages, including Baseline Review; Green and Blue Infrastructure Assessment; and the final Green and Blue Infrastructure Report. The resulting proposals frame an ambitious vision for the delivery of a new regional South Essex Estuary (SEE) Park – 24,000 hectares of protected and connected landscapes. This unified parkland system will drive effective place-shaping and “leveling up” for the most deprived communities while providing large-scale nature recovery and biodiversity net gain. Comprehensive analysis and policy recommendations ensure best practices will be embedded within planning documents and decisions guiding future development. Furthermore, a Natural Capital Account was undertaken as part of the strategy showing the tremendous economic value of the natural assets. This strategy sets a pioneering precedent that demonstrates how the prioritisation of living infrastructure has the capacity to address climate change and ecological collapse, while also supporting sustainable housing, healthier communities, and resilient infrastructures. It was only achievable through a collaborative and cross-boundary approach to strategic planning and growth, with a shared vision of place, and a strong commitment to delivery. With joined-up thinking and a joined-up region, a more impactful plan for South Essex was developed that will lead to numerous environmental, social, and economic benefits across the region, and enhancing the landscape and natural environs on the periphery of one of the largest cities in the world.

Keywords: climate change, green and blue infrastructure, landscape architecture, master planning, regional planning, social equity

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Authors: Sara Dehaiman Alqahtani

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This study investigates the effects of cybersecurity breaches on critical audit outcomes, specifically focusing on auditor changes, engagement partner rotations, and the issuance of going concern opinions. Utilizing an extensive dataset of U.S.-based firms spanning from 2006 to 2023, the research employs propensity score matching (PSM) to address selection bias and control for confounding variables. The analysis reveals that, contrary to conventional expectations, firms that experience cybersecurity breaches are less likely to change their audit firms and engagement partners. Additionally, these breached firms are less likely to receive going concern opinions from their auditors. However, an exception is noted within the technology sector, where breached firms show a higher propensity to switch auditors, potentially to demonstrate a commitment to enhanced cybersecurity measures. The findings suggest a strong preference for continuity in auditor-client relationships following cybersecurity incidents. This preference underscores the importance of auditors' existing knowledge of a firm's systems and controls, which is deemed valuable during periods of heightened risk. The study extends the existing literature by moving beyond the well-documented impact of breaches on audit fees to explore other significant dimensions of the auditor-client relationship. It challenges the traditional assumption that increased risk from breaches leads to higher auditor turnover or more conservative audit opinions, highlighting instead a tendency towards maintaining stability. Methodologically, the research leverages PSM to create a balanced comparison between breached and non-breached firms, ensuring robustness in the findings. Logistic regression analyses further substantiate the associations between breaches and audit outcomes, controlling for various firm-specific characteristics such as size, financial performance, and industry classification. Supplemental analyses explore additional factors, including litigation risk, breach frequency, and industry-specific responses, providing a nuanced understanding of the dynamics at play. The study’s main contributions are threefold. First, it broadens the scope of research on cybersecurity breaches by examining their impact on auditor changes and going concern opinions, areas previously underexplored. Second, it offers empirical evidence that breached firms tend to retain their auditors and engagement partners, suggesting that continuity is valued over potential audit quality improvements through auditor changes. Third, it highlights sector-specific behaviors, particularly within the technology industry, where breaches do lead to higher auditor turnover, indicating industry-specific risk management strategies. Implications of this research are significant for auditors, clients, and regulators. Auditors may need to enhance their risk assessment frameworks to better incorporate cybersecurity risks, ensuring that audit practices remain robust in the face of evolving cyber threats. Clients should evaluate the benefits of retaining existing auditors against the potential advantages of engaging new auditors who might offer fresh perspectives and specialized cybersecurity expertise. Regulators might consider updating auditing standards to more explicitly address cybersecurity risks, ensuring that such threats are adequately reflected in audit procedures and disclosures. Overall, this study provides a comprehensive analysis of how cybersecurity breaches influence audit outcomes, revealing a preference for auditor continuity and questioning whether current auditing frameworks sufficiently account for cyber risks. By highlighting these trends, the research calls for a reassessment of audit practices and regulatory standards to better address the complexities introduced by the increasing prevalence of cyber threats in the digital age.

Keywords: cybersecurity breaches, auditor changes, engagement partner rotations, going concern opinions, auditor-client relationships, audit risk assessment

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Authors: Tatiana Butkova, Nikolai Kibrik, Kristina Malsagova, Alexander Izotov, Alexander Stepanov, Anna Kaysheva

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Relevance. The genetic risk of developing schizophrenia is determined by two factors: single nucleotide polymorphisms and gene copy number variations. The search for serological markers for early diagnosis of schizophrenia is driven by the fact that the first five years of the disease are accompanied by significant biological, psychological, and social changes. It is during this period that pathological processes are most amenable to correction. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) that are hypothesized to potentially influence the onset and development of the endogenous process. Materials and Methods It was analyzed 73 single nucleotide polymorphism variants. The study included 48 patients undergoing inpatient treatment at "Psychiatric Clinical Hospital No. 1" in Moscow, comprising 23 females and 25 males. Inclusion criteria: - Patients aged 18 and above. - Diagnosis according to ICD-10: F20.0, F20.2, F20.8, F21.8, F25.1, F25.2. - Voluntary informed consent from patients. Exclusion criteria included: - The presence of concurrent somatic or neurological pathology, neuroinfections, epilepsy, organic central nervous system damage of any etiology, and regular use of medication. - Substance abuse and alcohol dependence. - Women who were pregnant or breastfeeding. Clinical and psychopathological assessment was complemented by psychometric evaluation using the PANSS scale at the beginning and end of treatment. The duration of observation during therapy was 4-6 weeks. Total DNA extraction was performed using QIAamp DNA. Blood samples were processed on Illumina HiScan and genotyped for 652,297 markers on the Infinium Global Chips Screening Array-24v2.0 using the IMPUTE2 program with parameters Ne=20,000 and k=90. Additional filtration was performed based on INFO>0.5 and genotype probability>0.5. Quality control of the obtained DNA was conducted using agarose gel electrophoresis, with each tested sample having a volume of 100 µL. Results. It was observed that several SNPs exhibited gender dependence. We identified groups of single nucleotide polymorphisms with a membership of 80% or more in either the female or male gender. These SNPs included rs2661319, rs2842030, rs4606, rs11868035, rs518147, rs5993883, and rs6269.Another noteworthy finding was the limited combination of SNPs sufficient to manifest clinical symptoms leading to hospitalization. Among all 48 patients, each of whom was analyzed for deviations in 73 SNPs, it was discovered that the combination of involved SNPs in the manifestation of pronounced clinical symptoms of schizophrenia was 19±3 out of 73 possible. In study, the frequency of occurrence of single nucleotide polymorphisms also varied. The most frequently observed SNPs were rs4849127 (in 90% of cases), rs1150226 (86%), rs1414334 (75%), rs10170310 (73%), rs2857657, and rs4436578 (71%). Conclusion. Thus, the results of this study provide additional evidence that these genes may be associated with the development of schizophrenia spectrum disorders. However, it's impossible cannot rule out the hypothesis that these polymorphisms may be in linkage disequilibrium with other functionally significant polymorphisms that may actually be involved in schizophrenia spectrum disorders. It has been shown that missense SNPs by themselves are likely not causative of the disease but are in strong linkage disequilibrium with non-functional SNPs that may indeed contribute to disease predisposition.

Keywords: gene polymorphisms, genotyping, single nucleotide polymorphisms, schizophrenia.

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Authors: Loyd R. Hook, Maryam Moharek

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With the envisioned future growth of low altitude urban aircraft operations for airborne delivery service and advanced air mobility, strategies to coordinate and deconflict aircraft flight paths must be prioritized. Autonomous coordination and planning of flight trajectories is the preferred approach to the future vision in order to increase safety, density, and efficiency over manual methods employed today. Difficulties arise because any conflict resolution must be constrained by all other aircraft, all airspace restrictions, and all ground-based obstacles in the vicinity. These considerations make pair-wise tactical deconfliction difficult at best and unlikely to find a suitable solution for the entire system of vehicles. In addition, more traditional methods which rely on long time scales and large protected zones will artificially limit vehicle density and drastically decrease efficiency. Instead, strategic planning, which is able to respond to highly dynamic conditions and still account for high density operations, will be required to coordinate multiple vehicles in the highly constrained low altitude urban environment. This paper develops and evaluates such a planning algorithm which can be implemented autonomously across multiple aircraft and situations. Data from this evaluation provide promising results with simulations showing up to 10 aircraft deconflicted through a relatively narrow low-altitude urban canyon without any vehicle to vehicle or obstacle conflict. The algorithm achieves this level of coordination beginning with the assumption that each vehicle is controlled to follow an independently constructed flight path, which is itself free of obstacle conflict and restricted airspace. Then, by preferencing speed change deconfliction maneuvers constrained by the vehicles flight envelope, vehicles can remain as close to the original planned path and prevent cascading vehicle to vehicle conflicts. Performing the search for a set of commands which can simultaneously ensure separation for each pair-wise aircraft interaction and optimize the total velocities of all the aircraft is further complicated by the fact that each aircraft's flight plan could contain multiple segments. This means that relative velocities will change when any aircraft achieves a waypoint and changes course. Additionally, the timing of when that aircraft will achieve a waypoint (or, more directly, the order upon which all of the aircraft will achieve their respective waypoints) will change with the commanded speed. Put all together, the continuous relative velocity of each vehicle pair and the discretized change in relative velocity at waypoints resembles a hybrid reachability problem - a form of control reachability. This paper proposes two methods for finding solutions to these multi-body problems. First, an analytical formulation of the continuous problem is developed with an exhaustive search of the combined state space. However, because of computational complexity, this technique is only computable for pairwise interactions. For more complicated scenarios, including the proposed 10 vehicle example, a discretized search space is used, and a depth-first search with early stopping is employed to find the first solution that solves the constraints.

Keywords: strategic planning, autonomous, aircraft, deconfliction

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Authors: Mei Xuan Tan, Gim-Yang Maggie Pee, Mei Chee Tan

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Academic performance, in the form of scoring high grades in enrolled subjects, is not the only significant trait in achieving success. Engineering graduates with experience in working on hands-on projects in a team setting are highly sought after in industry upon graduation. Such projects are typically real world problems that require the integration and application of knowledge and skills from several disciplines. In a traditional university setting, subjects are taught in a silo manner with no cross participation from other departments or disciplines. This may lead to knowledge compartmentalization and students are unable to understand and connect the relevance and applicability of the subject. University instructors thus see this integration across disciplines as a challenging task as they aim to better prepare students in understanding and solving problems for work or future studies. To improve students’ academic performance and to cultivate various skills such as critical thinking, there has been a gradual uptake in the use of an active learning approach in introductory science and engineering courses, where lecturing is traditionally the main mode of instruction. This study aims to discuss the implementation and experience of a hands-on, interdisciplinary project that involves all the four core subjects taught during the term at the Singapore University of Technology Design (SUTD). At SUTD, an interdisciplinary design activity, named 2D, is integrated into the curriculum to help students reinforce the concepts learnt. A student enrolled in SUTD experiences his or her first 2D in Term 1. This activity. which spans over one week in Week 10 of Term 1, highlights the application of chemistry, physics, mathematics, humanities, arts and social sciences (HASS) in designing an engineering product solution. The activity theme for Term 1 2D revolved around “work and play”. Students, in teams of 4 or 5, used a scaled-down model of a chemical launcher to launch a projectile across the room. It involved the use of a small chemical combustion reaction between ethanol (a highly volatile fuel) and oxygen. This reaction generated a sudden and large increase in gas pressure built up in a closed chamber, resulting in rapid gas expansion and ejection of the projectile out of the launcher. Students discussed and explored the meaning of play in their lives in HASS class while the engineering aspects of a combustion system to launch an object using underlying principles of energy conversion and projectile motion were revisited during the chemistry and physics classes, respectively. Numerical solutions on the distance travelled by the projectile launched by the chemical launcher, taking into account drag forces, was developed during the mathematics classes. At the end of the activity, students developed skills in report writing, data collection and analysis. Specific to this 2D activity, students gained an understanding and appreciation on the application and interdisciplinary nature of science, engineering and HASS. More importantly, students were exposed to design and problem solving, where human interaction and discussion are important yet challenging in a team setting.

Keywords: active learning, collaborative learning, first year undergraduate, interdisciplinary, STEAM

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Authors: Ekaterina Zvorykina

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Nowadays, Arctic and Antarctic regions are distinguished to be one of the most important strategic resources for global development. Nonetheless, living conditions in Arctic regions still demand certain improvements. As soon as the region is rarely populated, one of the main points of interest is health accommodation of the people, who migrate to Arctic region for permanent and shift work. At Arctic and Antarctic latitudes, personnel face polar day and polar night conditions during the time of the year. It means that they are deprived of natural sunlight in winter season and have continuous daylight in summer. Firstly, the change in light intensity during 24-hours period due to migration affects circadian rhythms. Moreover, the controlled artificial light in winter is also an issue. The results of the recent studies on night shift medical professionals, who were exposed to permanent artificial light, have already demonstrated higher risks in cancer, depression, Alzheimer disease. Moreover, people exposed to frequent time zones change are also subjected to higher risks of heart attack and cancer. Thus, our main goals are to understand how high latitude work and living conditions can affect human health and how it can be prevented. In our study, we analyze molecular and cellular factors, which play important role in circadian rhythm change and distinguish main risk groups in people, migrating to high latitudes. The main well-studied index of circadian timing is melatonin or its metabolite 6-sulfatoxymelatonin. In low light intensity melatonin synthesis is disturbed and as a result human organism requires more time for sleep, which is still disregarded when it comes to working time organization. Lack of melatonin also causes shortage in serotonin production, which leads to higher depression risk. Melatonin is also known to inhibit oncogenes and increase apoptosis level in cells, the main factors for tumor growth, as well as circadian clock genes (for example Per2). Thus, people who work in high latitudes can be distinguished as a risk group for cancer diseases and demand more attention. Clock/Clock genes, known to be one of the main circadian clock regulators, decrease sensitivity of hypothalamus to estrogen and decrease glucose sensibility, which leads to premature aging and oestrous cycle disruption. Permanent light exposure also leads to accumulation superoxide dismutase and oxidative stress, which is one of the main factors for early dementia and Alzheimer disease. We propose a new screening system adjusted for people, migrating from middle to high latitudes and accommodation therapy. Screening is focused on melatonin and estrogen levels, sleep deprivation and neural disorders, depression level, cancer risks and heart and vascular disorders. Accommodation therapy includes different types artificial light exposure, additional melatonin and neuroprotectors. Preventive procedures can lead to increase of migration intensity to high latitudes and, as a result, the prosperity of Arctic region.

Keywords: circadian rhythm, high latitudes, melatonin, neuroprotectors

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Authors: Carina Emminger, Umut D. Cakmak, Evrim Burkut, Rene Preuer, Ingrid Graz, Zoltan Major

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Damping accompanies us daily in everyday life and is used to protect (e.g., in shoes) and make our life more comfortable (damping of unwanted motion) and calm (noise reduction). In general, damping is the absorption of energy which is either stored in the material (vibration isolation systems) or changed into heat (vibration absorbers). In case of the last, the damping mechanism can be split in active, passive, as well as semi-active (a combination of active and passive). Active damping is required to enable an almost perfect damping over the whole application range and is used, for instance, in sport cars. In contrast, passive damping is a response of the material due to external loading. Consequently, the material composition has a huge influence on the damping behavior. For elastomers, the material behavior is inherent viscoelastic, temperature, and frequency dependent. However, passive damping is not adjustable during application. Therefore, it is of importance to understand the fundamental viscoelastic behavior and the dissipation capability due to external loading. The objective of this work is to assess the limitation and applicability of viscoelastic material damping for applications in which currently coil-over shock absorbers are utilized. Coil-over shock absorbers are usually made of various mechanical parts and incorporate fluids within the damper. These shock absorbers are well-known and studied in the industry, and when needed, they can be easily adjusted during their product lifetime. In contrary, dampers made of – ideally – a single material are more resource efficient, have an easier serviceability, and are easier manufactured. However, they lack of adaptability and adjustability in service. Therefore, a case study with a remote-controlled sport car was conducted. The original shock absorbers were redesigned, and the spring-dashpot system was replaced by both an elastomer and a thermoplastic-elastomer, respectively. Here, five different formulations of elastomers were used, including a pure and an iron-particle filled thermoplastic poly(urethan) (TPU) and blends of two different poly(dimethyl siloxane) (PDMS). In addition, the TPUs were investigated as full and hollow dampers to investigate the difference between solid and structured material. To get comparative results each material formulation was comprehensively characterized, by monotonic uniaxial compression tests, dynamic thermomechanical analysis (DTMA), and rebound resilience. Moreover, the new material-based shock absorbers were compared with spring-dashpot shock absorbers. The shock absorbers were analyzed under monotonic and cyclic loading. In addition, an impact loading was applied on the remote-controlled car to measure the damping properties in operation. A servo-hydraulic high-speed linear actuator was utilized to apply the loads. The acceleration of the car and the displacement of specific measurement points were recorded while testing by a sensor and high-speed camera, respectively. The results prove that elastomers are suitable in damping applications, but they are temperature and frequency dependent. This is a limitation in applicability of viscous material damper. Feasible fields of application may be in the case of micromobility, like bicycles, e-scooters, and e-skateboards. Furthermore, the viscous material damping could be used to increase the inherent damping of a whole structure, e.g., in bicycle-frames.

Keywords: damper structures, material damping, PDMS, TPU

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Authors: S. M. Ashikur Elahee, Md. Zahidur Rahman, Md. Shofiqur Rahman

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This study evaluated the impact of different water interventions under WASH program on access of household's to safe drinking water. Following survey method, the study was carried out in two Upazila of South-west coastal region of Bangladesh namely Koyra from Khulna and Shymnagar from Satkhira district. Being an explanatory study, a total of 200 household's selected applying random sampling technique were interviewed using a structured interview schedule. The predicted probability suggests that around 62 percent household's are out of year-round access to safe drinking water whereby, only 25 percent household's have access at SPHERE standard (913 Liters/per person/per year). Besides, majority (78 percent) of the household's have not accessed at both indicators simultaneously. The distance from household residence to the water source varies from 0 to 25 kilometer with an average distance of 2.03 kilometers. The study also reveals that the increase in monthly income around BDT 1,000 leads to additional 11 liters (coefficient 0.01 at p < 0.1) consumption of safe drinking water for a person/year. As expected, lining up time has significant negative relationship with dependent variables i.e., for higher lining up time, the probability of getting access for both SPHERE standard and year round access variables becomes lower. According to ordinary least square (OLS) regression results, water consumption decreases at 93 liters for per person/year of a household if one member is added to that household. Regarding water consumption intensity, ordered logistic regression (OLR) model shows that one-minute increase of lining up time for water collection tends to reduce water consumption intensity. On the other hand, as per OLS regression results, for one-minute increase of lining up time, the water consumption decreases by around 8 liters. Considering access to Deep Tube Well (DTW) as a reference dummy, in OLR, the household under Pond Sand Filter (PSF), Shallow Tube Well (STW), Reverse Osmosis (RO) and Rainwater Harvester System (RWHS) are respectively 37 percent, 29 percent, 61 percent and 27 percent less likely to ensure year round access of water consumption. In line of health impact, different type of water born diseases like diarrhea, cholera, and typhoid are common among the coastal community caused by microbial impurities i.e., Bacteria, Protozoa. High turbidity and TDS in pond water caused by reduction of water depth, presence of suspended particle and inorganic salt stimulate the growth of bacteria, protozoa, and algae causes affecting health hazard. Meanwhile, excessive growth of Algae in pond water caused by excessive nitrate in drinking water adversely effects on child health. In lieu of ensuring access at SPHERE standard, we need to increase the number of water interventions at reasonable distance, preferably a half kilometer away from the dwelling place, ensuring community peoples involved with its installation process where collectively owned water intervention is found more effective than privately owned. In addition, a demand-responsive approach to supply of piped water should be adopted to allow consumer demand to guide investment in domestic water supply in future.

Keywords: access, impact, safe drinking water, Sphere standard, water interventions

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Authors: Manana Lobzhanidze

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The COVID-19 pandemic has made significant changes in migration processes, notably changes in the study migration process. The constraints caused by the COVID-19 pandemic led to changes in the studying process, which negatively affected its efficiency. The educational process has partially or completely shifted to distance learning; Both labor and study migration have increased significantly in the world. The employment and education market has become global and consequently, a number of challenges have arisen for employers, researchers, and businesses. The role of preparing qualified personnel in achieving high productivity is justified, the benefits for employers and employees are assessed on the one hand, and the role of study migration for the country’s development is examined on the other hand. Research methods. The research is based on methods of analysis and synthesis, quantitative and qualitative, groupings, relative and mean quantities, graphical representation, comparison, analysis and etc. In-depth interviews were conducted with experts to determine quantitative and qualitative indicators. Research findings. Factors affecting study migration are analysed in the paper and the environment that stimulates migration is explored. One of the driving forces of migration is considered to be the desire for receiving higher pay. Levels and indicators of study migration are studied by country. Comparative analysis has found that study migration rates are high in countries where the price of skilled labor is high. The productivity of individuals with low skills is low, which negatively affects the economic development of countries. It has been revealed that students leave the country to improve their skills during study migration. The process mentioned in the article is evaluated as a positive event for a developing country, as individuals are given the opportunity to share the technology of developed countries, gain knowledge, and then introduce it in their own country. The downside of study migration is the return of a small proportion of graduates from developed economies to their home countries. The article concludes that countries with emerging economies devote less resources to research and development, while this is a priority in developed countries, allowing highly skilled individuals to use their skills efficiently. The paper studies the national education system examines the level of competition in the education market and the indicators of educational migration. The level of competition in the education market and the indicators of educational migration are studied. The role of qualified personnel in achieving high productivity is substantiated, the benefits of employers and employees are assessed on the one hand, and the role of study migration in the development of the country is revealed on the other hand. The paper also analyzes the level of competition in the education and labor markets and identifies indicators of study migration. During the pandemic period, there was a great demand for the digital technologies. Open access to a variety of comprehensive platforms will significantly reduce study migration to other countries. As a forecast, it can be said that the intensity of the use of e-learning platforms will be increased significantly in the post-pandemic period. The paper analyzes the positive and negative effects of study migration on economic development, examines the challenges of study migration in light of the COVID-19 pandemic, suggests ways to avoid negative consequences, and develops recommendations for improving the study migration process in the post-pandemic period.

Keywords: study migration, COVID-19 pandemic, factors affecting migration, economic development, post-pandemic migration

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Palak V. Patel, Jessica Pixley, Steven R. Feldman

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Introduction: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and requires substantial resources to treat. When choosing between indicated therapies, providers consider their associated adverse effects, efficacy, cosmesis, and function preservation. The patient’s tumor burden, infiltrative risk, and risk of tumor recurrence are also considered. Treatment cost is often left out of these discussions. This can lead to financial toxicity, which describes the harm and quality of life reductions inflicted by high care costs. Methods: We studied the guidelines set forth by the American Academy of Dermatology for the treatment of BCC. A PubMed literature search was conducted to identify the costs of each recommended therapy. We discuss costs alongside treatment efficacy and side-effect profile. Results: Surgical treatment for BCC can be cost-effective if the appropriate treatment is selected for the presenting tumor. Curettage and electrodesiccation can be used in low-grade, low-recurrence tumors in aesthetically unimportant areas. The benefits of cost-conscious care are not likely to be outweighed by the risks of poor cosmesis or tumor return ($471 BCC of the cheek). When tumor burden is limited, MMS offers better cure rates and lower recurrence rates than surgical excision, and with comparable costs (MMS $1263; SE $949). Surgical excision with permanent sections may be indicated when tumor burden is more extensive or if molecular testing is necessary. The utility of surgical excision with frozen sections, which costs substantially more than MMS without comparable outcomes, is less clear (SE with frozen sections $2334-$3085). Less data exists on non-surgical treatments for BCC. These techniques cost less, but recurrence-risk is high. Side-effects of nonsurgical treatment are limited to local skin reactions, and cosmesis is good. Cryotherapy, 5-FU, and MAL-PDT are all more affordable than surgery, but high recurrence rates increase risk of secondary financial and psychosocial burden (recurrence rates 21-39%; cost $100-270). Radiation therapy offers better clearance rates than other nonsurgical treatments but is associated with similar recurrence rates and a significantly larger financial burden ($2591-$3460 BCC of the cheek). Treatments for advanced or metastatic BCC are extremely costly, but few patients require their use, and the societal cost burden remains low. Vismodegib and sonidegib have good response rates but substantial side effects, and therapy should be combined with multidisciplinary care and palliative measures. Expert-review has found sonidegib to be the less expensive and more efficacious option (vismodegib $128,358; sonidegib $122,579). Platinum therapy, while not FDA-approved, is also effective but expensive (~91,435). Immunotherapy offers a new line of treatment in patients intolerant of hedgehog inhibitors ($683,061). Conclusion: Dermatologists working within resource-compressed practices and with resource-limited patients must prudently manage the healthcare dollar. Surgical therapies for BCC offer the lowest risk of recurrence at the most reasonable cost. Non-surgical therapies are more affordable, but high recurrence rates increase the risk of secondary financial and psychosocial burdens. Treatments for advanced BCC are incredibly costly, but the low incidence means the overall cost to the system is low.

Keywords: nonmelanoma skin cancer, basal cell skin cancer, squamous cell skin cancer, cost of care

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