Search results for: health system outcomes
Commenced in January 2007
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Edition: International
Paper Count: 27001

Search results for: health system outcomes

271 Neurodiversity in Post Graduate Medical Education: A Rapid Solution to Faculty Development

Authors: Sana Fatima, Paul Sadler, Jon Cooper, David Mendel, Ayesha Jameel

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Background: Neurodiversity refers to intrinsic differences between human minds and encompasses dyspraxia, dyslexia, attention deficit hyperactivity disorder, dyscalculia, autism spectrum disorder, and Tourette syndrome. There is increasing recognition of neurodiversity in relation to disability/diversity in medical education and the associated impact on training, career progression, and personal and professional wellbeing. In addition, documented and anecdotal evidence suggests that medical educators and training providers in all four nations (UK) are increasingly concerned about understanding neurodiversity and identifying and providing support for neurodivergent trainees. Summary of Work: A national Neurodiversity Task and Finish group were established to survey Health Education England local office Professional Support teams about insights into infrastructure, training for educators, triggers for assessment, resources, and intervention protocols. This group drew from educational leadership, professional and personal neurodiverse expertise, occupational medicine, employer human resource, and trainees. An online, exploratory survey was conducted to gather insights from supervisors and trainers across England using the Professional Support Units' platform. Summary of Results: This survey highlighted marked heterogeneity in the identification, assessment, and approaches to support and management of neurodivergent trainees and highlighted a 'deficit' approach to neurodiversity. It also demonstrated a paucity of educational and protocol resources for educators and supervisors in supporting neurodivergent trainees. Discussions and Conclusions: In phase one, we focused on faculty development. An educational repository for all supervising trainees using a thematic approach was formalised. This was guided by our survey findings specific for neurodiversity and took a triple 'A' approach: awareness, assessment, and action. This is further supported by video material incorporating stories in training as well as mobile workshops for trainers for more immersive learning. The subtle theme from both the survey and Task and finish group suggested a move away from deficit-focused methods toward a positive holistic, interdisciplinary approach within a biopsychosocial framework. Contributions: 1. Faculty Knowledge and basic understanding of neurodiversity are key to supporting trainees with known or underlying Neurodiverse conditions. This is further complicated by challenges around non-disclosure, varied presentations, stigma, and intersectionality. 2. There is national (and international) inconsistency in the approach to how trainees are managed once a neurodiverse condition is suspected or diagnosed. 3. A carefully constituted and focussed Task and Finish group can rapidly identify national inconsistencies in neurodiversity and implement rapid educational interventions. 4. Nuanced findings from surveys and discussion can reframe the approach to neurodiversity; from a medical model to a more comprehensive, asset-based, biopsychosocial model of support, fostering a cultural shift, accepting 'diversity' in all its manifestations, visible and hidden.

Keywords: neurodiversity, professional support, human considerations, workplace wellbeing

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270 Role of Civil Society Institutions in Promoting Peace and Pluralism in the Rural, Mountainous Region of Pakistan

Authors: Mir Afzal

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Introduction: Pakistan is a country with an ever-increasing population of largely diverse ethnic, cultural, religious and sectarian divisions. Whereas diversity is seen as a strength in many societies, in Pakistan, it has become a source of conflict and more a weakness than a strength due to lack of understanding and divisions based on ethnic, cultural, political, religious, and sectarian branding. However, amid conflicts and militancy across the country, the rural, mountainous communities in the Northern Areas of Pakistan enjoy not only peace and harmony but also a continuous process of social and economic transformation supported by strong civil society institutions. These community-based institutions have organized the rural, mountainous people of diverse ethnic and religious backgrounds into village organizations, women organizations, and Local Support Organizations engaged in self-help development and peace building in the region. The Study and its Methodology: A qualitative study was conducted in one district of the Northern Pakistan to explore the contributions of the civil society institutions (CSIs) and community-based organizations to uplifting the educational and socio-economic conditions of the people with an ultimate aim of developing a thriving, peaceful and pluralistic society in this mountainous region. The study employed an eclectic set of tools, including interviews, focused group discussions, observations of CSIs’ interventions, and analysis of documents, to generate rich data on the overall role and contributions of CSIs in promoting peace and pluralism in the region. Significance of the Study: Common experiences and empirical studies reveal that such interventions by CSIs have not only contributed to the socio-economic, educational, health and cultural development of these regions but these interventions have really transformed the rural, mountainous people into organized and forward looking communities. However, how such interventions have contributed to promoting pluralism and appreciation for diversity in these regions had been an unexplored but significant area. Therefore this qualitative research study funded by the Higher Education Commission of Pakistan was carried out by the Aga Khan University Institute for Educational Development to explore the role and contributions of CSIs in promoting peace and pluralism and appreciations for diversity in one district of Northern Pakistan which is home to people of different ethnic, religious, cultural and social backgrounds. Findings and Conclusions: The study has a comprehensive list of findings and conclusions covering various aspects of CSIs and their contributions to the transformation and peaceful co-existence of rural communities in the regions. However, this paper discusses only four major contributions of CSIs, namely enhancing economic capacity, community mobilization and organization, increasing access and quality of education, and building partnerships. It also discusses the factors influencing the role of CSIs, the issues, implications, and recommendations for CSIs, policy makers, donors and development agencies, and researchers. The paper concludes that by strengthening strong networks of CSIs and community based organizations, Pakistan will not only uplift its socio-economic attainments but it will also be able to address the critical challenges of terrorism, sectarianism, and other divisions and conflicts in its various regions.

Keywords: civil society, Pakistan, peace, rural

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269 Decrease in Olfactory Cortex Volume and Alterations in Caspase Expression in the Olfactory Bulb in the Pathogenesis of Alzheimer’s Disease

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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268 Exploitation Pattern of Atlantic Bonito in West African Waters: Case Study of the Bonito Stock in Senegalese Waters

Authors: Ousmane Sarr

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The Senegalese coasts have high productivity of fishery resources due to the frequency of intense up-welling system that occurs along its coast, caused by the maritime trade winds making its waters nutrients rich. Fishing plays a primordial role in Senegal's socioeconomic plans and food security. However, a global diagnosis of the Senegalese maritime fishing sector has highlighted the challenges this sector encounters. Among these concerns, some significant stocks, a priority target for artisanal fishing, need further assessment. If no efforts are made in this direction, most stock will be overexploited or even in decline. It is in this context that this research was initiated. This investigation aimed to apply a multi-modal approach (LBB, Catch-only-based CMSY model and its most recent version (CMSY++); JABBA, and JABBA-Select) to assess the stock of Atlantic bonito, Sarda sarda (Bloch, 1793) in the Senegalese Exclusive Economic Zone (SEEZ). Available catch, effort, and size data from Atlantic bonito over 15 years (2004-2018) were used to calculate the nominal and standardized CPUE, size-frequency distribution, and length at retentions (50 % and 95 % selectivity) of the species. These relevant results were employed as input parameters for stock assessment models mentioned above to define the stock status of this species in this region of the Atlantic Ocean. The LBB model indicated an Atlantic bonito healthy stock status with B/BMSY values ranging from 1.3 to 1.6 and B/B0 values varying from 0.47 to 0.61 of the main scenarios performed (BON_AFG_CL, BON_GN_Length, and BON_PS_Length). The results estimated by LBB are consistent with those obtained by CMSY. The CMSY model results demonstrate that the SEEZ Atlantic bonito stock is in a sound condition in the final year of the main scenarios analyzed (BON, BON-bt, BON-GN-bt, and BON-PS-bt) with sustainable relative stock biomass (B2018/BMSY = 1.13 to 1.3) and fishing pressure levels (F2018/FMSY= 0.52 to 1.43). The B/BMSY and F/FMSY results for the JABBA model ranged between 2.01 to 2.14 and 0.47 to 0.33, respectively. In contrast, The estimated B/BMSY and F/FMSY for JABBA-Select ranged from 1.91 to 1.92 and 0.52 to 0.54. The Kobe plots results of the base case scenarios ranged from 75% to 89% probability in the green area, indicating sustainable fishing pressure and an Atlantic bonito healthy stock size capable of producing high yields close to the MSY. Based on the stock assessment results, this study highlighted scientific advice for temporary management measures. This study suggests an improvement of the selectivity parameters of longlines and purse seines and a temporary prohibition of the use of sleeping nets in the fishery for the Atlantic bonito stock in the SEEZ based on the results of the length-base models. Although these actions are temporary, they can be essential to reduce or avoid intense pressure on the Atlantic bonito stock in the SEEZ. However, it is necessary to establish harvest control rules to provide coherent and solid scientific information that leads to appropriate decision-making for rational and sustainable exploitation of Atlantic bonito in the SEEZ and the Eastern Atlantic Ocean.

Keywords: multi-model approach, stock assessment, atlantic bonito, SEEZ

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267 Introducing, Testing, and Evaluating a Unified JavaScript Framework for Professional Online Studies

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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266 An Integrated Approach to the Carbonate Reservoir Modeling: Case Study of the Eastern Siberia Field

Authors: Yana Snegireva

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Carbonate reservoirs are known for their heterogeneity, resulting from various geological processes such as diagenesis and fracturing. These complexities may cause great challenges in understanding fluid flow behavior and predicting the production performance of naturally fractured reservoirs. The investigation of carbonate reservoirs is crucial, as many petroleum reservoirs are naturally fractured, which can be difficult due to the complexity of their fracture networks. This can lead to geological uncertainties, which are important for global petroleum reserves. The problem outlines the key challenges in carbonate reservoir modeling, including the accurate representation of fractures and their connectivity, as well as capturing the impact of fractures on fluid flow and production. Traditional reservoir modeling techniques often oversimplify fracture networks, leading to inaccurate predictions. Therefore, there is a need for a modern approach that can capture the complexities of carbonate reservoirs and provide reliable predictions for effective reservoir management and production optimization. The modern approach to carbonate reservoir modeling involves the utilization of the hybrid fracture modeling approach, including the discrete fracture network (DFN) method and implicit fracture network, which offer enhanced accuracy and reliability in characterizing complex fracture systems within these reservoirs. This study focuses on the application of the hybrid method in the Nepsko-Botuobinskaya anticline of the Eastern Siberia field, aiming to prove the appropriateness of this method in these geological conditions. The DFN method is adopted to model the fracture network within the carbonate reservoir. This method considers fractures as discrete entities, capturing their geometry, orientation, and connectivity. But the method has significant disadvantages since the number of fractures in the field can be very high. Due to limitations in the amount of main memory, it is very difficult to represent these fractures explicitly. By integrating data from image logs (formation micro imager), core data, and fracture density logs, a discrete fracture network (DFN) model can be constructed to represent fracture characteristics for hydraulically relevant fractures. The results obtained from the DFN modeling approaches provide valuable insights into the East Siberia field's carbonate reservoir behavior. The DFN model accurately captures the fracture system, allowing for a better understanding of fluid flow pathways, connectivity, and potential production zones. The analysis of simulation results enables the identification of zones of increased fracturing and optimization opportunities for reservoir development with the potential application of enhanced oil recovery techniques, which were considered in further simulations on the dual porosity and dual permeability models. This approach considers fractures as separate, interconnected flow paths within the reservoir matrix, allowing for the characterization of dual-porosity media. The case study of the East Siberia field demonstrates the effectiveness of the hybrid model method in accurately representing fracture systems and predicting reservoir behavior. The findings from this study contribute to improved reservoir management and production optimization in carbonate reservoirs with the use of enhanced and improved oil recovery methods.

Keywords: carbonate reservoir, discrete fracture network, fracture modeling, dual porosity, enhanced oil recovery, implicit fracture model, hybrid fracture model

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265 Official Seals on the Russian-Qing Treaties: Material Manifestations and Visual Enunciations

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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264 Subway Ridership Estimation at a Station-Level: Focus on the Impact of Bus Demand, Commercial Business Characteristics and Network Topology

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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263 A Case for Strategic Landscape Infrastructure: South Essex Estuary Park

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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262 Analysis of Potential Associations of Single Nucleotide Polymorphisms in Patients with Schizophrenia Spectrum Disorders

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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261 Autonomous Strategic Aircraft Deconfliction in a Multi-Vehicle Low Altitude Urban Environment

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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260 Engineering Design of a Chemical Launcher: An Interdisciplinary Design Activity

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

Procedia PDF Downloads 122
259 A Community Solution to Address Extensive Nitrate Contamination in the Lower Yakima Valley Aquifer

Authors: Melanie Redding

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Historic widespread nitrate contamination of the Lower Yakima Valley aquifer in Washington State initiated a community-based effort to reduce nitrate concentrations to below-drinking water standards. This group commissioned studies on characterizing local nitrogen sources, deep soil assessments, drinking water, and assessing nitrate concentrations at the water table. Nitrate is the most prevalent groundwater contaminant with common sources from animal and human waste, fertilizers, plants and precipitation. It is challenging to address groundwater contamination when common sources, such as agriculture, on-site sewage systems, and animal production, are widespread. Remediation is not possible, so mitigation is essential. The Lower Yakima Valley is located over 175,000 acres, with a population of 56,000 residents. Approximately 25% of the population do not have access to safe, clean drinking water, and 20% of the population is at or below the poverty level. Agriculture is the primary economic land-use activity. Irrigated agriculture and livestock production make up the largest percentage of acreage and nitrogen load. Commodities include apples, grapes, hops, dairy, silage corn, triticale, alfalfa and cherries. These commodities are important to the economic viability of the residents of the Lower Yakima Valley, as well as Washington State. Mitigation of nitrate in groundwater is challenging. The goal is to ensure everyone has safe drinking water. There are no easy remedies due to the extensive and pervasiveness of the contamination. Monitoring at the water table indicates that 45% of the 30 spatially distributed monitoring wells exceeded the drinking water standard. This indicates that there are multiple sources that are impacting water quality. Washington State has several areas which have extensive groundwater nitrate contamination. The groundwater in these areas continues to degrade over time. However, the Lower Yakima Valley is being successful in addressing this health issue because of the following reasons: the community is engaged and committed; there is one common goal; there has been extensive public education and outreach to citizens; and generating credible data using sound scientific methods. Work in this area is continuing as an ambient groundwater monitoring network is established to assess the condition of the aquifer over time. Nitrate samples are being collected from 170 wells, spatially distributed across the aquifer. This research entails quarterly sampling for two years to characterize seasonal variability and then continue annually afterward. This assessment will provide the data to statistically determine trends in nitrate concentrations across the aquifer, over time. Thirty-three of these wells are monitoring wells that are screened across the aquifer. The water quality from these wells are indicative of activities at the land surface. Additional work is being conducted to identify land use management practices that are effective in limiting nitrate migration through the soil column. Tracking nitrate in the soil column every season is an important component of bridging land-use practices with the fate and transport of nitrate through the subsurface. Patience, tenacity, and the ability to think outside the box are essential for dealing with widespread nitrate contamination of groundwater.

Keywords: community, groundwater, monitoring, nitrate

Procedia PDF Downloads 177
258 Coil-Over Shock Absorbers Compared to Inherent Material Damping

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

Procedia PDF Downloads 114
257 A Rapid Assessment of the Impacts of COVID-19 on Overseas Labor Migration: Findings from Bangladesh

Authors: Vaiddehi Bansal, Ridhi Sahai, Kareem Kysia

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Overseas labor migration is currently one of the most important contributors to the economy of Bangladesh and is a highly profitable form of labor for Gulf Cooperative Council (GCC) countries. In 2019, 700,159 migrant workers from Bangladeshtraveled abroad for employment. GCC countries are a major destination for Bangladeshi migrant workers, with Saudi Arabia being the most common destination for Bangladeshi migrant workers since 2016. Despite the high rate of migration between these countries every year, the OLR industry remains complex and often leaves migrants susceptible to human trafficking, forced labor, and modern slavery. While the prevalence of forced labor among Bangladeshi migrants in GCC countries is still unknown, the IOM estimates international migrant workers comprise one fourth of the victims of forced labor. Moreover, the onset of the global COVID-19 pandemic has exposed migrant workers to additional adverse situations, making them even more vulnerable to forced labor and health risks. This paper presents findings from a rapid assessment of the impacts of COVID-19 on OLR in Bangladesh, with an emphasis on the increased risk of forced labor among vulnerable migrant worker populations, particularly women.Rapid reviews are a useful approach to swiftly provide actionable evidence for informed decision-making during emergencies, such as the COVID-19 pandemic. The research team conducted semi-structured key information interviews (KIIs) with a range of stakeholders, including government officials, local NGOs, international organizations, migration researchers, and formal and informal recruiting agencies, to obtain insights on the multi-facted impacts of COVID-19 on the OLR sector. The research team also conducted a comprehensive review of available resources, including media articles, blogs, policy briefs, reports, white papers, and other online content, to triangulate findings from the KIIs. After screening for inclusion criteria, a total of 110 grey literature documents were included in the review. A total of 31 KIIs were conducted, data from which was transcribed and translated from Bangla to English, andanalyzed using a detailed codebook. Findings indicate that there was limited reintegration support for returnee migrants. Facing increasing amounts of debt, financial insecurity, and social discrimination, returnee migrants, were extremely vulnerable to forced labor and exploitation. Growing financial debt and limited job opportunities in their home country will likely push migrants to resort to unsafe migration channels. Evidence suggests that women, who are primarily domestic works in GCC countries, were exposed to increased risk of forced labor and workplace violence. Due to stay-at-home measures, women migrant workers were tasked with additional housekeeping working and subjected to longer work hours, wage withholding, and physical abuse. In Bangladesh, returnee women migrant workers also faced an increased risk of domestic violence.

Keywords: forced labor, migration, gender, human trafficking

Procedia PDF Downloads 115
256 Using Statistical Significance and Prediction to Test Long/Short Term Public Services and Patients' Cohorts: A Case Study in Scotland

Authors: Raptis Sotirios

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Health and social care (HSc) services planning and scheduling are facing unprecedented challenges due to the pandemic pressure and also suffer from unplanned spending that is negatively impacted by the global financial crisis. Data-driven can help to improve policies, plan and design services provision schedules using algorithms assist healthcare managers’ to face unexpected demands using fewer resources. The paper discusses services packing using statistical significance tests and machine learning (ML) to evaluate demands similarity and coupling. This is achieved by predicting the range of the demand (class) using ML methods such as CART, random forests (RF), and logistic regression (LGR). The significance tests Chi-Squared test and Student test are used on data over a 39 years span for which HSc services data exist for services delivered in Scotland. The demands are probabilistically associated through statistical hypotheses that assume that the target service’s demands are statistically dependent on other demands as a NULL hypothesis. This linkage can be confirmed or not by the data. Complementarily, ML methods are used to linearly predict the above target demands from the statistically found associations and extend the linear dependence of the target’s demand to independent demands forming, thus groups of services. Statistical tests confirm ML couplings making the prediction also statistically meaningful and prove that a target service can be matched reliably to other services, and ML shows these indicated relationships can also be linear ones. Zero paddings were used for missing years records and illustrated better such relationships both for limited years and in the entire span offering long term data visualizations while limited years groups explained how well patients numbers can be related in short periods or can change over time as opposed to behaviors across more years. The prediction performance of the associations is measured using Receiver Operating Characteristic(ROC) AUC and ACC metrics as well as the statistical tests, Chi-Squared and Student. Co-plots and comparison tables for RF, CART, and LGR as well as p-values and Information Exchange(IE), are provided showing the specific behavior of the ML and of the statistical tests and the behavior using different learning ratios. The impact of k-NN and cross-correlation and C-Means first groupings is also studied over limited years and the entire span. It was found that CART was generally behind RF and LGR, but in some interesting cases, LGR reached an AUC=0 falling below CART, while the ACC was as high as 0.912, showing that ML methods can be confused padding or by data irregularities or outliers. On average, 3 linear predictors were sufficient, LGR was found competing RF well, and CART followed with the same performance at higher learning ratios. Services were packed only if when significance level(p-value) of their association coefficient was more than 0.05. Social factors relationships were observed between home care services and treatment of old people, birth weights, alcoholism, drug abuse, and emergency admissions. The work found that different HSc services can be well packed as plans of limited years, across various services sectors, learning configurations, as confirmed using statistical hypotheses.

Keywords: class, cohorts, data frames, grouping, prediction, prob-ability, services

Procedia PDF Downloads 234
255 A Comprehensive Survey of Artificial Intelligence and Machine Learning Approaches across Distinct Phases of Wildland Fire Management

Authors: Ursula Das, Manavjit Singh Dhindsa, Kshirasagar Naik, Marzia Zaman, Richard Purcell, Srinivas Sampalli, Abdul Mutakabbir, Chung-Horng Lung, Thambirajah Ravichandran

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Wildland fires, also known as forest fires or wildfires, are exhibiting an alarming surge in frequency in recent times, further adding to its perennial global concern. Forest fires often lead to devastating consequences ranging from loss of healthy forest foliage and wildlife to substantial economic losses and the tragic loss of human lives. Despite the existence of substantial literature on the detection of active forest fires, numerous potential research avenues in forest fire management, such as preventative measures and ancillary effects of forest fires, remain largely underexplored. This paper undertakes a systematic review of these underexplored areas in forest fire research, meticulously categorizing them into distinct phases, namely pre-fire, during-fire, and post-fire stages. The pre-fire phase encompasses the assessment of fire risk, analysis of fuel properties, and other activities aimed at preventing or reducing the risk of forest fires. The during-fire phase includes activities aimed at reducing the impact of active forest fires, such as the detection and localization of active fires, optimization of wildfire suppression methods, and prediction of the behavior of active fires. The post-fire phase involves analyzing the impact of forest fires on various aspects, such as the extent of damage in forest areas, post-fire regeneration of forests, impact on wildlife, economic losses, and health impacts from byproducts produced during burning. A comprehensive understanding of the three stages is imperative for effective forest fire management and mitigation of the impact of forest fires on both ecological systems and human well-being. Artificial intelligence and machine learning (AI/ML) methods have garnered much attention in the cyber-physical systems domain in recent times leading to their adoption in decision-making in diverse applications including disaster management. This paper explores the current state of AI/ML applications for managing the activities in the aforementioned phases of forest fire. While conventional machine learning and deep learning methods have been extensively explored for the prevention, detection, and management of forest fires, a systematic classification of these methods into distinct AI research domains is conspicuously absent. This paper gives a comprehensive overview of the state of forest fire research across more recent and prominent AI/ML disciplines, including big data, classical machine learning, computer vision, explainable AI, generative AI, natural language processing, optimization algorithms, and time series forecasting. By providing a detailed overview of the potential areas of research and identifying the diverse ways AI/ML can be employed in forest fire research, this paper aims to serve as a roadmap for future investigations in this domain.

Keywords: artificial intelligence, computer vision, deep learning, during-fire activities, forest fire management, machine learning, pre-fire activities, post-fire activities

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254 Impact of COVID-19 on Study Migration

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

Procedia PDF Downloads 127
253 LncRNA-miRNA-mRNA Networks Associated with BCR-ABL T315I Mutation in Chronic Myeloid Leukemia

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

Procedia PDF Downloads 159
252 Influence of the Local External Pressure on Measured Parameters of Cutaneous Microcirculation

Authors: Irina Mizeva, Elena Potapova, Viktor Dremin, Mikhail Mezentsev, Valeri Shupletsov

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The local tissue perfusion is regulated by the microvascular tone which is under the control of a number of physiological mechanisms. Laser Doppler flowmetry (LDF) together with wavelet analyses is the most commonly used technique to study the regulatory mechanisms of cutaneous microcirculation. External factors such as temperature, local pressure of the probe on the skin, etc. influence on the blood flow characteristics and are used as physiological tests to evaluate microvascular regulatory mechanisms. Local probe pressure influences on the microcirculation parameters measured by optical methods: diffuse reflectance spectroscopy, fluorescence spectroscopy, and LDF. Therefore, further study of probe pressure effects can be useful to improve the reliability of optical measurement. During pressure tests variation of the mean perfusion measured by means of LDF usually is estimated. An additional information concerning the physiological mechanisms of the vascular tone regulation system in response to local pressure can be obtained using spectral analyses of LDF samples. The aim of the present work was to develop protocol and algorithm of data processing appropriate for study physiological response to the local pressure test. Involving 6 subjects (20±2 years) and providing 5 measurements for every subject we estimated intersubject and-inter group variability of response of both averaged and oscillating parts of the LDF sample on external surface pressure. The final purpose of the work was to find special features which further can be used in wider clinic studies. The cutaneous perfusion measurements were carried out by LAKK-02 (SPE LAZMA Ltd., Russia), the skin loading was provided by the originally designed device which allows one to distribute the pressure around the LDF probe. The probe was installed on the dorsal part of the distal finger of the index figure. We collected measurements continuously for one hour and varied loading from 0 to 180mmHg stepwise with a step duration of 10 minutes. Further, we post-processed the samples using the wavelet transform and traced the energy of oscillations in five frequency bands over time. Weak loading leads to pressure-induced vasodilation, so one should take into account that the perfusion measured under pressure conditions will be overestimated. On the other hand, we revealed a decrease in endothelial associated fluctuations. Further loading (88 mmHg) induces amplification of pulsations in all frequency bands. We assume that such loading leads to a higher number of closed capillaries, higher input of arterioles in the LDF signal and as a consequence more vivid oscillations which mainly are formed in arterioles. External pressure higher than 144 mmHg leads to the decrease of oscillating components, after removing the loading very rapid restore of the tissue perfusion takes place. In this work, we have demonstrated that local skin loading influence on the microcirculation parameters measured by optic technique; this should be taken into account while developing portable electronic devices. The proposed protocol of local loading allows one to evaluate PIV as far as to trace dynamic of blood flow oscillations. This study was supported by the Russian Science Foundation under project N 18-15-00201.

Keywords: blood microcirculation, laser Doppler flowmetry, pressure-induced vasodilation, wavelet analyses blood

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251 Exposing The Invisible

Authors: Kimberley Adamek

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According to the Council on Tall Buildings, there has been a rapid increase in the construction of tall or “megatall” buildings over the past two decades. Simultaneously, the New England Journal of Medicine has reported that there has been a steady increase in climate related natural disasters since the 1970s; the eastern expansion of the USA's infamous Tornado Alley being just one of many current issues. In the future, this could mean that tall buildings, which already guide high speed winds down to pedestrian levels would have to withstand stronger forces and protect pedestrians in more extreme ways. Although many projects are required to be verified within wind tunnels and a handful of cities such as San Francisco have included wind testing within building code standards, there are still many examples where wind is only considered for basic loading. This typically results in and an increase of structural expense and unwanted mitigation strategies that are proposed late within a project. When building cities, architects rarely consider how each building alters the invisible patterns of wind and how these alterations effect other areas in different ways later on. It is not until these forces move, overpower and even destroy cities that people take notice. For example, towers have caused winds to blow objects into people (Walkie-Talkie Tower, Leeds, England), cause building parts to vibrate and produce loud humming noises (Beetham Tower, Manchester), caused wind tunnels in streets as well as many other issues. Alternatively, there exist towers which have used their form to naturally draw in air and ventilate entire facilities in order to eliminate the needs for costly HVAC systems (The Met, Thailand) and used their form to increase wind speeds to generate electricity (Bahrain Tower, Dubai). Wind and weather exist and effect all parts of the world in ways such as: Science, health, war, infrastructure, catastrophes, tourism, shopping, media and materials. Working in partnership with a leading wind engineering company RWDI, a series of tests, images and animations documenting discovered interactions of different building forms with wind will be collected to emphasize the possibilities for wind use to architects. A site within San Francisco (due to its increasing tower development, consistently wind conditions and existing strict wind comfort criteria) will host a final design. Iterations of this design will be tested within the wind tunnel and computational fluid dynamic systems which will expose, utilize and manipulate wind flows to create new forms, technologies and experiences. Ultimately, this thesis aims to question the amount which the environment is allowed to permeate building enclosures, uncover new programmatic possibilities for wind in buildings, and push the boundaries of working with the wind to ensure the development and safety of future cities. This investigation will improve and expand upon the traditional understanding of wind in order to give architects, wind engineers as well as the general public the ability to broaden their scope in order to productively utilize this living phenomenon that everyone constantly feels but cannot see.

Keywords: wind engineering, climate, visualization, architectural aerodynamics

Procedia PDF Downloads 358
250 Preliminary Characterization of Hericium Species Sampled in Tuscany, Italy

Authors: V. Cesaroni, C. Girometta, A. Bernicchia, M. Brusoni, F. Corana, R. M. Baiguera, C. M. Cusaro, M. L. Guglielminetti, B. Mannucci, H. Kawagishi, C. Perini, A. M. Picco, P. Rossi, E. Salerni, E. Savino

Abstract:

Fungi of the genus Hericium contain various compounds with antibacterial activity, cytotoxic effect on cancer cells and bioactive molecules. Some of the active metabolites stimulate the synthesis of the Nerve Growth Factor (NGF). Recently, the effect of dietary supplement based on Hericium erinaceus on recognition memory and on hippocampal mossy fiber-CA3 neurotransmission was published. The aim of this study was to investigate the presence of Hericium species on Italian territory in order to isolate the strains for further studies and applications. The first step was to collect Hericium sporophores in Tuscany: H. alpestre Pers., H. coralloides (Scop.) Pers. and H. erinaceus (Bull.) Pers. were the species present. The strains of H. alpestre (H.a.1), H. coralloides (H.c.1) and H. erinaceus (H.e.1 & H.e.2) have been isolated in pure culture and preserved in the collection of the University of Pavia (MicUNIPV). The DNA sequences obtained from the strains were compared to other sequences found in international databases. Therefore, it was possible to construct a phylogenetic tree that highlights the clear separation in clades of the sequences and the molecular identification of our strains with the species of Hericium considered. The second step was to cultivate indoor and outdoor H. erinaceus in order to obtain as many sporophores as possible for further chemical analysis. All the procedures for H. erinaceus cultivation have been followed. Among the available recipes for indoor H. erinaceus cultivation, it was used a substrate formulation contained 70% oak sawdust, 20% rice bran, 10% wheat straw, 1% CaCO3 and 1% sucrose. The bioactive compounds present in the mycelia and in the sporophores of H. erinaceus were chemically analyzed in collaboration with the Centro Grandi Strumenti of the University of Pavia using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS). The materials to be analyzed were previously freeze-dried and then extracted with an alcoholic procedure. Preliminary chromatographic analysis revealed the presence of potentially bioactive and structurally different secondary metabolites such as polysaccharides, erinacins, ericenones, steroids and other terpenoids. Ericenones C and D (in sporophores) and erinacin A (in mycelium) have been identified by comparison with the respective standards. These molecules are known to have effects on the Central Nervous System (CNS) cells, which is the main objective of our studies. Thanks to the high sensitivity in the detection of bioactive compounds of H. erinaceus, it will be possible to use the To obtain lyophilized mycelium and the respective culture broth, 4 small pieces (about 5 mm2) of the respective H.e.1 or H.c.1 strains, taken from the margin of growing cultures (MEA), were inoculated into 1 liter of 2% ME (malt extract, Biokar Diagnostics). The static liquid cultures were kept at 24 °C in the dark chamber and fungi grew for one month. 10 replicates for each strain have been done. The method proposed as an analytical screening protocol to determine the optimal growth conditions of the fungus and to improve the production chain of H. erinaceus. These results encourage to carry out chemical analyzes also on H. alpestre and H. coralloides in order to evaluate the presence of bioactive compounds in these two species.

Keywords: Hericium species, Hercium erinaceus bioactive compounds, medicinal mushrooms, mushroom cultivation

Procedia PDF Downloads 143
249 Functions and Challenges of New County-Based Regional Plan in Taiwan

Authors: Yu-Hsin Tsai

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

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

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248 Autophagy Promotes Vascular Smooth Muscle Cell Migration in vitro and in vivo

Authors: Changhan Ouyang, Zhonglin Xie

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In response to proatherosclerotic factors such as oxidized lipids, or to therapeutic interventions such as angioplasty, stents, or bypass surgery, vascular smooth muscle cells (VSMCs) migrate from the media to the intima, resulting in intimal hyperplasia, restenosis, graft failure, or atherosclerosis. These proatherosclerotic factors also activate autophagy in VSMCs. However, the functional role of autophagy in vascular health and disease remains poorly understood. In the present study, we determined the role of autophagy in the regulation of VSMC migration. Autophagy activity in cultured human aortic smooth muscle cells (HASMCs) and mouse carotid arteries was measured by Western blot analysis of microtubule-associated protein 1 light chain 3 B (LC3B) and P62. The VSMC migration was determined by scratch wound assay and transwell migration assay. Ex vivo smooth muscle cell migration was determined using aortic ring assay. The in vivo SMC migration was examined by staining the carotid artery sections with smooth muscle alpha actin (alpha SMA) after carotid artery ligation. To examine the relationship between autophagy and neointimal hyperplasia, C57BL/6J mice were subjected to carotid artery ligation. Seven days after injury, protein levels of Atg5, Atg7, Beclin1, and LC3B drastically increased and remained higher in the injured arteries three weeks after the injury. In parallel with the activation of autophagy, vascular injury-induced neointimal hyperplasia as estimated by increased intima/media ratio. The en face staining of carotid artery showed that vascular injury enhanced alpha SMA staining in the intimal cells as compared with the sham operation. Treatment of HASMCs with platelet-derived growth factor (PDGF), one of the major factors for vascular remodeling in response to vascular injury, increased Atg7 and LC3 II protein levels and enhanced autophagosome formation. In addition, aortic ring assay demonstrated that PDGF treated aortic rings displayed an increase in neovessel formation compared with control rings. Whole mount staining for CD31 and alpha SMA in PDGF treated neovessels revealed that the neovessel structures were stained by alpha SMA but not CD31. In contrast, pharmacological and genetic suppression of autophagy inhibits VSMC migration. Especially, gene silencing of Atg7 inhibited VSMC migration induced by PDGF. Furthermore, three weeks after ligation, markedly decreased neointimal formation was found in mice treated with chloroquine, an inhibitor of autophagy. Quantitative morphometric analysis of the injured vessels revealed a marked reduction in the intima/media ratio in the mice treated with chloroquine. Conclusion: Autophagy activation increases VSMC migration while autophagy suppression inhibits VSMC migration. These findings suggest that autophagy suppression may be an important therapeutic strategy for atherosclerosis and intimal hyperplasia.

Keywords: autophagy, vascular smooth muscle cell, migration, neointimal formation

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247 Intercultural Initiatives and Canadian Bilingualism

Authors: Muna Shafiq

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Growth in international immigration is a reflection of increased migration patterns in Canada and in other parts of the world. Canada continues to promote itself as a bilingual country, yet the bilingual French and English population numbers do not reflect this platform. Each province’s integration policies focus only on second language learning of either English or French. Moreover, since English Canadians outnumber French Canadians, maintaining, much less increasing, English-French bilingualism appears unrealistic. One solution to increasing Canadian bilingualism requires creating intercultural communication initiatives between youth in Quebec and the rest of Canada. Specifically, the focus is on active, experiential learning, where intercultural competencies develop outside traditional classroom settings. The target groups are Generation Y Millennials and Generation Z Linksters, the next generations in the career and parenthood lines. Today, Canada’s education system, like many others, must continually renegotiate lines between programs it offers its immigrant and native communities. While some purists or right-wing nationalists would disagree, the survival of bilingualism in Canada has little to do with reducing immigration. Children and youth immigrants play a valuable role in increasing Canada’s French and English speaking communities. For instance, a focus on more immersion, over core French education programs for immigrant children and youth would not only increase bilingual rates; it would develop meaningful intercultural attachments between Canadians. Moreover, a vigilant increase of funding in French immersion programs is critical, as are new initiatives that focus on experiential language learning for students in French and English language programs. A favorable argument supports the premise that other than French-speaking students in Québec and elsewhere in Canada, second and third generation immigrant students are excellent ambassadors to promote bilingualism in Canada. Most already speak another language at home and understand the value of speaking more than one language in their adopted communities. Their dialogue and participation in experiential language exchange workshops are necessary. If the proposed exchanges take place inter-provincially, the momentum to increase collective regional voices increases. This regional collectivity can unite Canadians differently than nation-targeted initiatives. The results from an experiential youth exchange organized in 2017 between students at the crossroads of Generation Y and Generation Z in Vancouver and Quebec City respectively offer a promising starting point in assessing the strength of bringing together different regional voices to promote bilingualism. Code-switching between standard, international French Vancouver students, learn in the classroom versus more regional forms of Quebec French spoken locally created regional connectivity between students. The exchange was equally rewarding for both groups. Increasing their appreciation for each other’s regional differences allowed them to contribute actively to their social and emotional development. Within a sociolinguistic frame, this proposed model of experiential learning does not focus on hands-on work experience. However, the benefits of such exchanges are as valuable as work experience initiatives developed in experiential education. Students who actively code switch between French and English in real, not simulated contexts appreciate bilingualism more meaningfully and experience its value in concrete terms.

Keywords: experiential learning, intercultural communication, social and emotional learning, sociolinguistic code-switching

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246 Sorbitol Galactoside Synthesis Using β-Galactosidase Immobilized on Functionalized Silica Nanoparticles

Authors: Milica Carević, Katarina Banjanac, Marija ĆOrović, Ana Milivojević, Nevena Prlainović, Aleksandar Marinković, Dejan Bezbradica

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Nowadays, considering the growing awareness of functional food beneficial effects on human health, due attention is dedicated to the research in the field of obtaining new prominent products exhibiting improved physiological and physicochemical characteristics. Therefore, different approaches to valuable bioactive compounds synthesis have been proposed. β-Galactosidase, for example, although mainly utilized as hydrolytic enzyme, proved to be a promising tool for these purposes. Namely, under the particular conditions, such as high lactose concentration, elevated temperatures and low water activities, reaction of galactose moiety transfer to free hydroxyl group of the alternative acceptor (e.g. different sugars, alcohols or aromatic compounds) can generate a wide range of potentially interesting products. Up to now, galacto-oligosaccharides and lactulose have attracted the most attention due to their inherent prebiotic properties. The goal of this study was to obtain a novel product sorbitol galactoside, using the similar reaction mechanism, namely transgalactosylation reaction catalyzed by β-galactosidase from Aspergillus oryzae. By using sugar alcohol (sorbitol) as alternative acceptor, a diverse mixture of potential prebiotics is produced, enabling its more favorable functional features. Nevertheless, an introduction of alternative acceptor into the reaction mixture contributed to the complexity of reaction scheme, since several potential reaction pathways were introduced. Therefore, the thorough optimization using response surface method (RSM), in order to get an insight into different parameter (lactose concentration, sorbitol to lactose molar ratio, enzyme concentration, NaCl concentration and reaction time) influences, as well as their mutual interactions on product yield and productivity, was performed. In view of product yield maximization, the obtained model predicted optimal lactose concentration 500 mM, the molar ratio of sobitol to lactose 9, enzyme concentration 0.76 mg/ml, concentration of NaCl 0.8M, and the reaction time 7h. From the aspect of productivity, the optimum substrate molar ratio was found to be 1, while the values for other factors coincide. In order to additionally, improve enzyme efficiency and enable its reuse and potential continual application, immobilization of β-galactosidase onto tailored silica nanoparticles was performed. These non-porous fumed silica nanoparticles (FNS)were chosen on the basis of their biocompatibility and non-toxicity, as well as their advantageous mechanical and hydrodinamical properties. However, in order to achieve better compatibility between enzymes and the carrier, modifications of the silica surface using amino functional organosilane (3-aminopropyltrimethoxysilane, APTMS) were made. Obtained support with amino functional groups (AFNS) enabled high enzyme loadings and, more importantly, extremely high expressed activities, approximately 230 mg proteins/g and 2100 IU/g, respectively. Moreover, this immobilized preparation showed high affinity towards sorbitol galactoside synthesis. Therefore, the findings of this study could provided a valuable contribution to the efficient production of physiologically active galactosides in immobilized enzyme reactors.

Keywords: β-galactosidase, immobilization, silica nanoparticles, transgalactosylation

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245 Challenges, Responses and Governance in the Conservation of Forest and Wildlife: The Case of the Aravali Ranges, Delhi NCR

Authors: Shashi Mehta, Krishan Kumar Yadav

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This paper presents an overview of issues pertaining to the conservation of the natural environment and factors affecting the coexistence of the forest, wildlife and people. As forests and wildlife together create the basis for economic, cultural and recreational spaces for overall well-being and life-support systems, the adverse impacts of increasing consumerism are only too evident. The IUCN predicts extinction of 41% of all amphibians and 26% of mammals. The major causes behind this threatened extinction are Deforestation, Dysfunctional governance, Climate Change, Pollution and Cataclysmic phenomena. Thus the intrinsic relationship between natural resources and wildlife needs to be understood in totality, not only for the eco-system but for humanity at large. To demonstrate this, forest areas in the Aravalis- the oldest mountain ranges of Asia—falling in the States of Haryana and Rajasthan, have been taken up for study. The Aravalis are characterized by extreme climatic conditions and dry deciduous forest cover on intermittent scattered hills. Extending across the districts of Gurgaon, Faridabad, Mewat, Mahendergarh, Rewari and Bhiwani, these ranges - with village common land on which the entire economy of the rural settlements depends - fall in the state of Haryana. Aravali ranges with diverse fauna and flora near Alwar town of state of Rajasthan also form part of NCR. Once, rich in biodiversity, the Aravalis played an important role in the sustainable co-existence of forest and people. However, with the advent of industrialization and unregulated urbanization, these ranges are facing deforestation, degradation and denudation. The causes are twofold, i.e. the need of the poor and the greed of the rich. People living in and around the Aravalis are mainly poor and eke out a living by rearing live-stock. With shrinking commons, they depend entirely upon these hills for grazing, fuel, NTFP, medicinal plants and even drinking water. But at the same time, the pressure of indiscriminate urbanization and industrialization in these hills fulfils the demands of the rich and powerful in collusion with Government agencies. The functionaries of federal and State Governments play largely a negative role supporting commercial interests. Additionally, planting of a non- indigenous species like prosopis juliflora across the ranges has resulted in the extinction of almost all the indigenous species. The wildlife in the area is also threatened because of the lack of safe corridors and suitable habitat. In this scenario, the participatory role of different stakeholders such as NGOs, civil society and local community in the management of forests becomes crucial not only for conservation but also for the economic wellbeing of the local people. Exclusion of villagers from protection and conservation efforts - be it designing, implementing or monitoring and evaluating could prove counterproductive. A strategy needs to be evolved, wherein Government agencies be made responsible by putting relevant legislation in place along with nurturing and promoting the traditional wisdom and ethics of local communities in the protection and conservation of forests and wild life in the Aravali ranges of States of Haryana and Rajasthan of the National Capital Region, Delhi.

Keywords: deforestation, ecosystem, governance, urbanization

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244 Quantified Metabolomics for the Determination of Phenotypes and Biomarkers across Species in Health and Disease

Authors: Miroslava Cuperlovic-Culf, Lipu Wang, Ketty Boyle, Nadine Makley, Ian Burton, Anissa Belkaid, Mohamed Touaibia, Marc E. Surrette

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Metabolic changes are one of the major factors in the development of a variety of diseases in various species. Metabolism of agricultural plants is altered the following infection with pathogens sometimes contributing to resistance. At the same time, pathogens use metabolites for infection and progression. In humans, metabolism is a hallmark of cancer development for example. Quantified metabolomics data combined with other omics or clinical data and analyzed using various unsupervised and supervised methods can lead to better diagnosis and prognosis. It can also provide information about resistance as well as contribute knowledge of compounds significant for disease progression or prevention. In this work, different methods for metabolomics quantification and analysis from Nuclear Magnetic Resonance (NMR) measurements that are used for investigation of disease development in wheat and human cells will be presented. One-dimensional 1H NMR spectra are used extensively for metabolic profiling due to their high reliability, wide range of applicability, speed, trivial sample preparation and low cost. This presentation will describe a new method for metabolite quantification from NMR data that combines alignment of spectra of standards to sample spectra followed by multivariate linear regression optimization of spectra of assigned metabolites to samples’ spectra. Several different alignment methods were tested and multivariate linear regression result has been compared with other quantification methods. Quantified metabolomics data can be analyzed in the variety of ways and we will present different clustering methods used for phenotype determination, network analysis providing knowledge about the relationships between metabolites through metabolic network as well as biomarker selection providing novel markers. These analysis methods have been utilized for the investigation of fusarium head blight resistance in wheat cultivars as well as analysis of the effect of estrogen receptor and carbonic anhydrase activation and inhibition on breast cancer cell metabolism. Metabolic changes in spikelet’s of wheat cultivars FL62R1, Stettler, MuchMore and Sumai3 following fusarium graminearum infection were explored. Extensive 1D 1H and 2D NMR measurements provided information for detailed metabolite assignment and quantification leading to possible metabolic markers discriminating resistance level in wheat subtypes. Quantification data is compared to results obtained using other published methods. Fusarium infection induced metabolic changes in different wheat varieties are discussed in the context of metabolic network and resistance. Quantitative metabolomics has been used for the investigation of the effect of targeted enzyme inhibition in cancer. In this work, the effect of 17 β -estradiol and ferulic acid on metabolism of ER+ breast cancer cells has been compared to their effect on ER- control cells. The effect of the inhibitors of carbonic anhydrase on the observed metabolic changes resulting from ER activation has also been determined. Metabolic profiles were studied using 1D and 2D metabolomic NMR experiments, combined with the identification and quantification of metabolites, and the annotation of the results is provided in the context of biochemical pathways.

Keywords: metabolic biomarkers, metabolic network, metabolomics, multivariate linear regression, NMR quantification, quantified metabolomics, spectral alignment

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243 Adapting Hazard Analysis and Critical Control Points (HACCP) Principles to Continuing Professional Education

Authors: Yaroslav Pavlov

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In the modern world, ensuring quality has become increasingly important in various fields of human activity. One universal approach to quality management, proven effective in the food industry, is the HACCP (Hazard Analysis and Critical Control Points) concept. Based on principles of preventing potential hazards to consumers at all stages of production, from raw materials to the final product, HACCP offers a systematic approach to identifying, assessing risks, and managing critical control points (CCPs). Initially used primarily for food production, it was later effectively adapted to the food service sector. Implementing HACCP provides organizations with a reliable foundation for improving food safety, covering all links in the food chain from producer to consumer, making it an integral part of modern quality management systems. The main principles of HACCP—hazard identification, CCP determination, effective monitoring procedures, corrective actions, regular checks, and documentation—are universal and can be adapted to other areas. The adaptation of the HACCP concept is relevant for continuing professional education (CPE) with certain reservations. Specifically, it is reasonable to abandon the term ‘hazards’ as deviations in CCPs do not pose dangers, unlike in food production. However, the approach through CCP analysis and the use of HACCP's main principles for educational services are promising. This is primarily because it allows for identifying key CCPs based on the value creation model of a specific educational organization and consequently focusing efforts on specific CCPs to manage the quality of educational services. This methodology can be called the Analysis of Critical Points in Educational Services (ACPES). ACPES offers a similar approach to managing the quality of educational services, focusing on preventing and eliminating potential risks that could negatively impact the educational process, learners' achievement of set educational goals, and ultimately lead to students rejecting the organization's educational services. ACPES adapts proven HACCP principles to educational services, enhancing quality management effectiveness and student satisfaction. ACPES includes identifying potential problems at all stages of the educational process, from initial interest to graduation and career development. In ACPES, the term "hazards" is replaced with "problematic areas," reflecting the specific nature of the educational environment. Special attention is paid to determining CCPs—stages where corrective measures can most effectively prevent or minimize the risk of failing educational goals. The ACPES principles align with HACCP's principles, adjusted for the specificities of CPE. The method of the learner's journey map (variation of Customer Journey Map, CJM) can be used to overcome the complexity of formalizing the production chain in educational services. CJM provides a comprehensive understanding of the learner's experience at each stage, facilitating targeted and effective quality management. Thus, integrating the learner's journey map into ACPES represents a significant extension of the methodology's capabilities, ensuring a comprehensive understanding of the educational process and forming an effective quality management system focused on meeting learners' needs and expectations.

Keywords: quality management, continuing professional education, customer journey map, HACCP

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242 Assessing the Threat of Dual Citizenship to State Interests: A Case Study of Sri Lanka

Authors: Kasuri Kaushalya Pathirana Pahamunu Pathirannehelage

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Recent changes in the international system challenged the traditional idea of citizenship, prompting a need for a clearer definition. With the rapid globalization and shifting geopolitical dynamics, the concept of dual citizenship has emerged as a focal point of debate regarding its implications for state interests. As borders become less rigid and people identify with multiple nationalities, the traditional idea of citizenship is changing. This change is especially important given the increased connections between countries and the challenges that sovereign states face. While many countries accept dual citizenship, others are hesitant, seeing it as a potential threat to their national goals. This difference underscores the complicated relationship between national interests and the evolving concept of citizenship in the modern world. This study seeks to critically assess whether dual citizenship represents a significant threat to sovereign states by examining its effects across economic, social, and political sectors. Employing qualitative methodologies, including the analysis of published articles, reports, government acts, and a mix of primary and secondary sources, this research delves into the complexities surrounding dual citizenship. The findings reveal a nuanced landscape, showcasing both positive and negative impacts on state sovereignty and international cooperation. By exploring the tension between multinationalism and state interests, particularly through the lens of Sri Lanka’s evolving policies, this study aims to contribute valuable insights to the fields of political science and international relations, ultimately addressing the question of dual citizenship's implications for state interests. The evolving framework of dual citizenship in Sri Lanka provides a unique opportunity to examine its implications for various aspects of the nation. Specifically, this study will analyse the impact of dual citizenship on the country's economy, international cooperation, and social development. By exploring these dimensions, the research aims to provide a comprehensive understanding of how dual citizenship influences not only individual rights but also broader state interests and development goals within the context of globalization. It’s crucial to assess the potential threats posed by dual citizenship, as it can impact national security, economic stability, social unity, and political issues within countries. Understanding these effects is important for policymakers and researchers as they work to balance globalization with the need to protect state sovereignty. Dual citizenship presents a complex interplay of challenges and benefits to state interests, influencing critical areas such as international cooperation and state sovereignty. On the one hand, it can foster stronger ties between nations, enhance economic collaboration, and encourage cultural exchange, ultimately contributing to more robust international relationships. On the other hand, it may create tensions related to national identity, complicate governance, and raise concerns about loyalty and allegiance, which can challenge the notion of state sovereignty. As countries navigate these dual realities, it becomes essential to carefully assess and manage the implications of dual citizenship. By doing so, states can harness the potential advantages while addressing the associated risks, ultimately striving for a balance that promotes both national interests and international relations.

Keywords: dual citizenship, globalization, sustainable development, nationalism

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