Search results for: post pandemic period
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 9873

Search results for: post pandemic period

183 The Impact of Trade on Stock Market Integration of Emerging Markets

Authors: Anna M. Pretorius

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The emerging markets category for portfolio investment was introduced in 1986 in an attempt to promote capital market development in less developed countries. Investors traditionally diversified their portfolios by investing in different developed markets. However, high growth opportunities forced investors to consider emerging markets as well. Examples include the rapid growth of the “Asian Tigers” during the 1980s, growth in Latin America during the 1990s and the increased interest in emerging markets during the global financial crisis. As such, portfolio flows to emerging markets have increased substantially. In 2002 7% of all equity allocations from advanced economies went to emerging markets; this increased to 20% in 2012. The stronger links between advanced and emerging markets led to increased synchronization of asset price movements. This increased level of stock market integration for emerging markets is confirmed by various empirical studies. Against the background of increased interest in emerging market assets and the increasing level of integration of emerging markets, this paper focuses on the determinants of stock market integration of emerging market countries. Various studies have linked the level of financial market integration with specific economic variables. These variables include: economic growth, local inflation, trade openness, local investment, budget surplus/ deficit, market capitalization, domestic bank credit, domestic institutional and legal environment and world interest rates. The aim of this study is to empirically investigate to what extent trade-related determinants have an impact on stock market integration. The panel data sample include data of 16 emerging market countries: Brazil, Chile, China, Colombia, Czech Republic, Hungary, India, Malaysia, Pakistan, Peru, Philippines, Poland, Russian Federation, South Africa, Thailand and Turkey for the period 1998-2011. The integration variable for each emerging stock market is calculated as the explanatory power of a multi-factor model. These factors are extracted from a large panel of global stock market returns. Trade related explanatory variables include: exports as percentage of GDP, imports as percentage of GDP and total trade as percentage of GDP. Other macroeconomic indicators – such as market capitalisation, the size of the budget deficit and the effectiveness of the regulation of the securities exchange – are included in the regressions as control variables. An initial analysis on a sample of developed stock markets could not identify any significant determinants of stock market integration. Thus the macroeconomic variables identified in the literature are much more significant in explaining stock market integration of emerging markets than stock market integration of developed markets. The three trade variables are all statistically significant at a 5% level. The market capitalisation variable is also significant while the regulation variable is only marginally significant. The global financial crisis has highlighted the urgency to better understand the link between the financial and real sectors of the economy. This paper comes to the important finding that, apart from the level of market capitalisation (as financial indicator), trade (representative of the real economy) is a significant determinant of stock market integration of countries not yet classified as developed economies.

Keywords: emerging markets, financial market integration, panel data, trade

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182 Rapid Building Detection in Population-Dense Regions with Overfitted Machine Learning Models

Authors: V. Mantey, N. Findlay, I. Maddox

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The quality and quantity of global satellite data have been increasing exponentially in recent years as spaceborne systems become more affordable and the sensors themselves become more sophisticated. This is a valuable resource for many applications, including disaster management and relief. However, while more information can be valuable, the volume of data available is impossible to manually examine. Therefore, the question becomes how to extract as much information as possible from the data with limited manpower. Buildings are a key feature of interest in satellite imagery with applications including telecommunications, population models, and disaster relief. Machine learning tools are fast becoming one of the key resources to solve this problem, and models have been developed to detect buildings in optical satellite imagery. However, by and large, most models focus on affluent regions where buildings are generally larger and constructed further apart. This work is focused on the more difficult problem of detection in populated regions. The primary challenge with detecting small buildings in densely populated regions is both the spatial and spectral resolution of the optical sensor. Densely packed buildings with similar construction materials will be difficult to separate due to a similarity in color and because the physical separation between structures is either non-existent or smaller than the spatial resolution. This study finds that training models until they are overfitting the input sample can perform better in these areas than a more robust, generalized model. An overfitted model takes less time to fine-tune from a generalized pre-trained model and requires fewer input data. The model developed for this study has also been fine-tuned using existing, open-source, building vector datasets. This is particularly valuable in the context of disaster relief, where information is required in a very short time span. Leveraging existing datasets means that little to no manpower or time is required to collect data in the region of interest. The training period itself is also shorter for smaller datasets. Requiring less data means that only a few quality areas are necessary, and so any weaknesses or underpopulated regions in the data can be skipped over in favor of areas with higher quality vectors. In this study, a landcover classification model was developed in conjunction with the building detection tool to provide a secondary source to quality check the detected buildings. This has greatly reduced the false positive rate. The proposed methodologies have been implemented and integrated into a configurable production environment and have been employed for a number of large-scale commercial projects, including continent-wide DEM production, where the extracted building footprints are being used to enhance digital elevation models. Overfitted machine learning models are often considered too specific to have any predictive capacity. However, this study demonstrates that, in cases where input data is scarce, overfitted models can be judiciously applied to solve time-sensitive problems.

Keywords: building detection, disaster relief, mask-RCNN, satellite mapping

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181 A Model for Analysing Argumentative Structures and Online Deliberation in User-Generated Comments to the Website of a South African Newspaper

Authors: Marthinus Conradie

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The conversational dynamics of democratically orientated deliberation continue to stimulate critical scholarship for its potential to bolster robust engagement between different sections of pluralist societies. Several axes of deliberation that have attracted academic attention include face-to-face vs. online interaction, and citizen-to-citizen communication vs. engagement between citizens and political elites. In all these areas, numerous researchers have explored deliberative procedures aimed at achieving instrumental goals such a securing consensus on policy issues, against procedures that prioritise expressive outcomes such as broadening the range of argumentative repertoires that discursively construct and mediate specific political issues. The study that informs this paper, works in the latter stream. Drawing its data from the reader-comments section of a South African broadsheet newspaper, the study investigates online, citizen-to-citizen deliberation by analysing the discursive practices through which competing understandings of social problems are articulated and contested. To advance this agenda, the paper deals specifically with user-generated comments posted in response to news stories on questions of race and racism in South Africa. The analysis works to discern and interpret the various sets of discourse practices that shape how citizens deliberate contentious political issues, especially racism. Since the website in question is designed to encourage the critical comparison of divergent interpretations of news events, without feeding directly into national policymaking, the study adopts an analytic framework that traces how citizens articulate arguments, rather than the instrumental effects that citizen deliberations might exert on policy. The paper starts from the argument that such expressive interactions are particularly crucial to current trends in South African politics, given that the precise nature of race and racism remain contested and uncertain. Centred on a sample of 2358 conversational moves in 814 posts to 18 news stories emanating from issues of race and racism, the analysis proceeds in a two-step fashion. The first stage conducts a qualitative content analysis that offers insights into the levels of reciprocity among commenters (do readers engage with each other or simply post isolated opinions?), as well as the structures of argumentation (do readers support opinions by citing evidence?). The second stage involves a more fine-grained discourse analysis, based on a theorisation of argumentation that delineates it into three components: opinions/conclusions, evidence/data to support opinions/conclusions and warrants that explicate precisely how evidence/data buttress opinions/conclusions. By tracing the manifestation and frequency of specific argumentative practices, this study contributes to the archive of research currently aggregating around the practices that characterise South Africans’ engagement with provocative political questions, especially racism and racial inequity. Additionally, the study also contributes to recent scholarship on the affordances of Web 2.0 software by eschewing a simplistic bifurcation between cyber-optimist vs. pessimism, in favour of a more nuanced and context-specific analysis of the patterns that structure online deliberation.

Keywords: online deliberation, discourse analysis, qualitative content analysis, racism

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180 Molecular Detection and Antibiotics Resistance Pattern of Extended-Spectrum Beta-Lactamase Producing Escherichia coli in a Tertiary Hospital in Enugu, Nigeria

Authors: I. N. Nwafia, U. C. Ozumba, M. E. Ohanu, S. O. Ebede

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Antibiotic resistance is increasing globally and has become a major health challenge. Extended-spectrum beta-lactamase is clinically important because the ESBL gene are mostly plasmid encoded and these plasmids frequently carry genes encoding resistance to other classes of antimicrobials thereby limiting antibiotic options in the treatment of infections caused by these organisms. The specific objectives of this study were to determine the prevalence of ESBLs production in Escherichia coli, to determine the antibiotic susceptibility pattern of ESBLs producing Escherichia coli, to detect TEM, SHV and CTX-M genes and the risk factors to acquisition of ESBL producing Escherichia coli. The protocol of the study was approved by Health Research and Ethics committee of the University of Nigeria Teaching Hospital (UNTH), Enugu. It was a descriptive cross-sectional study that involved all hospitalized patients in UNTH from whose specimens Escherichia coli was isolated during the period of the study. The samples analysed were urine, wound swabs, blood and cerebrospinal fluid. These samples were cultured in 5% sheep Blood agar and MacConkey agar (Oxoid Laboratories, Cambridge UK) and incubated at 35-370C for 24 hours. Escherichia coli was identified with standard biochemical tests and confirmed using API 20E auxanogram (bioMerieux, Marcy 1'Etoile, France). The antibiotic susceptibility testing was done by disc diffusion method and interpreted according to the Clinical and Laboratory Standard Institute guideline. ESBL production was confirmed using ESBL Epsilometer test strips (Liofilchem srl, Italy). The ESBL bla genes were detected with polymerase chain reaction, after extraction of DNA with plasmid mini-prep kit (Jena Bioscience, Jena, Germany). Data analysis was with appropriate descriptive and inferential statistics. One hundred and six isolates (53.00%) out of the 200 were from urine, followed by isolates from different swabs specimens 53(26.50%) and the least number of the isolates 4(2.00) were from blood (P value = 0.096). Seventy (35.00%) out of the 200 isolates, were confirmed positive for ESBL production. Forty-two (60.00%) of the isolates were from female patients while 28(40.00%) were from male patients (P value = 0.13). Sixty-eight (97.14%) of the isolates were susceptible to imipenem while all of the isolates were resistant to ampicillin, chloramphenicol and tetracycline. From the 70 positive isolates the ESBL genes detected with polymerase chain reaction were blaCTX-M (n=26; 37.14%), blaTEM (n=7; 10.00%), blaSHV (n=2; 2.86%), blaCTX-M/TEM (n=7; 10.0%), blaCTX-M/SHV (n=14; 20.0%) and blaCTX-M/TEM/SHV (n=10; 14.29%). There was no gene detected in 4(5.71%) of the isolates. The most associated risk factors to infections caused by ESBL producing Escherichia coli was previous antibiotics use for the past 3 months followed by admission in the intensive care unit, recent surgery, and urinary catheterization. In conclusion, ESBLs was detected in 4 of every 10 Escherichia coli with the predominant gene detected being CTX-M. This knowledge will enable appropriate measures towards improvement of patient health care, antibiotic stewardship, research and infection control in the hospital.

Keywords: antimicrobial, Escherichia coli, extended spectrum beta lactamase, resistance

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179 “laws Drifting Off While Artificial Intelligence Thriving” – A Comparative Study with Special Reference to Computer Science and Information Technology

Authors: Amarendar Reddy Addula

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Definition of Artificial Intelligence: Artificial intelligence is the simulation of mortal intelligence processes by machines, especially computer systems. Explicit operations of AI comprise expert systems, natural language processing, and speech recognition, and machine vision. Artificial Intelligence (AI) is an original medium for digital business, according to a new report by Gartner. The last 10 times represent an advance period in AI’s development, prodded by the confluence of factors, including the rise of big data, advancements in cipher structure, new machine literacy ways, the materialization of pall computing, and the vibrant open- source ecosystem. Influence of AI to a broader set of use cases and druggies and its gaining fashionability because it improves AI’s versatility, effectiveness, and rigidity. Edge AI will enable digital moments by employing AI for real- time analytics closer to data sources. Gartner predicts that by 2025, further than 50 of all data analysis by deep neural networks will do at the edge, over from lower than 10 in 2021. Responsible AI is a marquee term for making suitable business and ethical choices when espousing AI. It requires considering business and societal value, threat, trust, translucency, fairness, bias mitigation, explainability, responsibility, safety, sequestration, and nonsupervisory compliance. Responsible AI is ever more significant amidst growing nonsupervisory oversight, consumer prospects, and rising sustainability pretensions. Generative AI is the use of AI to induce new vestiges and produce innovative products. To date, generative AI sweats have concentrated on creating media content similar as photorealistic images of people and effects, but it can also be used for law generation, creating synthetic irregular data, and designing medicinals and accoutrements with specific parcels. AI is the subject of a wide- ranging debate in which there's a growing concern about its ethical and legal aspects. Constantly, the two are varied and nonplussed despite being different issues and areas of knowledge. The ethical debate raises two main problems the first, abstract, relates to the idea and content of ethics; the alternate, functional, and concerns its relationship with the law. Both set up models of social geste, but they're different in compass and nature. The juridical analysis is grounded on anon-formalistic scientific methodology. This means that it's essential to consider the nature and characteristics of the AI as a primary step to the description of its legal paradigm. In this regard, there are two main issues the relationship between artificial and mortal intelligence and the question of the unitary or different nature of the AI. From that theoretical and practical base, the study of the legal system is carried out by examining its foundations, the governance model, and the nonsupervisory bases. According to this analysis, throughout the work and in the conclusions, International Law is linked as the top legal frame for the regulation of AI.

Keywords: artificial intelligence, ethics & human rights issues, laws, international laws

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178 Auditory Rehabilitation via an VR Serious Game for Children with Cochlear Implants: Bio-Behavioral Outcomes

Authors: Areti Okalidou, Paul D. Hatzigiannakoglou, Aikaterini Vatou, George Kyriafinis

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Young children are nowadays adept at using technology. Hence, computer-based auditory training programs (CBATPs) have become increasingly popular in aural rehabilitation for children with hearing loss and/or with cochlear implants (CI). Yet, their clinical utility for prognostic, diagnostic, and monitoring purposes has not been explored. The purposes of the study were: a) to develop an updated version of the auditory rehabilitation tool for Greek-speaking children with cochlear implants, b) to develop a database for behavioral responses, and c) to compare accuracy rates and reaction times in children differing in hearing status and other medical and demographic characteristics, in order to assess the tool’s clinical utility in prognosis, diagnosis, and progress monitoring. The updated version of the auditory rehabilitation tool was developed on a tablet, retaining the User-Centered Design approach and the elements of the Virtual Reality (VR) serious game. The visual stimuli were farm animals acting in simple game scenarios designed to trigger children’s responses to animal sounds, names, and relevant sentences. Based on an extended version of Erber’s auditory development model, the VR game consisted of six stages, i.e., sound detection, sound discrimination, word discrimination, identification, comprehension of words in a carrier phrase, and comprehension of sentences. A familiarization stage (learning) was set prior to the game. Children’s tactile responses were recorded as correct, false, or impulsive, following a child-dependent set up of a valid delay time after stimulus offset for valid responses. Reaction times were also recorded, and the database was in Εxcel format. The tablet version of the auditory rehabilitation tool was piloted in 22 preschool children with Νormal Ηearing (ΝΗ), which led to improvements. The study took place in clinical settings or at children’s homes. Fifteen children with CI, aged 5;7-12;3 years with post-implantation 0;11-5;1 years used the auditory rehabilitation tool. Eight children with CI were monolingual, two were bilingual and five had additional disabilities. The control groups consisted of 13 children with ΝΗ, aged 2;6-9;11 years. A comparison of both accuracy rates, as percent correct, and reaction times (in sec) was made at each stage, across hearing status, age, and also, within the CI group, based on presence of additional disability and bilingualism. Both monolingual Greek-speaking children with CI with no additional disabilities and hearing peers showed high accuracy rates at all stages, with performances falling above the 3rd quartile. However, children with normal hearing scored higher than the children with CI, especially in the detection and word discrimination tasks. The reaction time differences between the two groups decreased in language-based tasks. Results for children with CI with additional disability or bilingualism varied. Finally, older children scored higher than younger ones in both groups (CI, NH), but larger differences occurred in children with CI. The interactions between familiarization of the software, age, hearing status and demographic characteristics are discussed. Overall, the VR game is a promising tool for tracking the development of auditory skills, as it provides multi-level longitudinal empirical data. Acknowledgment: This work is part of a project that has received funding from the Research Committee of the University of Macedonia under the Basic Research 2020-21 funding programme.

Keywords: VR serious games, auditory rehabilitation, auditory training, children with cochlear implants

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177 Tuberculous Osteomyelitis Mimicking Tumours and Tumour-Like Lesions of Bone: Clinico-Radiologic Study of 22 Patients

Authors: Parveen Kundu, Zile Singh, Kunika Kundu, Swaran Kaur

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Context: Tuberculous osteomyelitis is a relatively uncommon condition that can present with various clinical and radiological features, often mimicking bone tumors or tumor-like lesions. In endemic countries like India, tuberculosis should be considered as a potential differential diagnosis for lytic bone lesions. This study aimed to highlight the different presentations of tuberculosis that can mimic tumors or tumor-like lesions in bone and emphasize the successful outcome of antitubercular therapy (ATT) in treating these cases. Research Aim: The main objective of this research was to explore the varied presentations of tuberculosis that mimic bone tumors or tumor-like lesions both clinically and radiologically, focusing on different bones. The study aimed to raise awareness among clinicians about this possibility and highlight the importance of histopathological confirmation before initiating treatment for lytic bone lesions. Methodology: This study utilized a retrospective review of 22 patients with suspected lytic bone lesions, who were subsequently diagnosed with tuberculous osteomyelitis through histopathological examination. The cases were collected over a period of ten years. Eleven cases required curettage for extensive lesions with sequestrations, while all 22 patients received 12 months of antitubercular therapy. Findings: The study included 14 male and 8 female patients, ranging in age from 3 to 61 years, with an average age of 22.05. The clinical and radiological presentations varied, with examples including bone cysts in the metaphyseal area of long bones, lesions resembling chondroblastomas, giant cell tumors, and osteoid osteoma, as well as multifocal lytic lesions resembling metastasis or multiple myeloma. One patient had lesions in both the clavicle and hand. Lesions mimicking chondromas were also observed in the phalanges of the hand and foot metatarsal. All patients showed resolution of the lesions and no residual disability following ATT. Theoretical Importance: This study highlights the importance of considering tuberculosis as a potential differential diagnosis for lytic bone lesions, particularly in endemic regions. It emphasizes the need for histopathological confirmation to accurately diagnose tuberculous osteomyelitis, as this is considered the gold standard. Data Collection and Analysis Procedures: Data for this study were collected retrospectively from medical records and radiological images of the 22 patients. The cases were analyzed based on clinical presentation, radiological findings, and histopathological confirmation. The outcomes of antitubercular therapy were also assessed. The data were summarized and presented descriptively. Question Addressed: This study aimed to address the question of how tuberculosis can mimic different bone tumors and tumor-like lesions clinically and radiologically. It also aimed to assess the successful outcome of antitubercular therapy in treating these cases. Conclusion: Tuberculous osteomyelitis can present with varied clinical and radiological features, often mimicking bone tumors or tumor-like lesions. Clinicians should consider tuberculosis as a potential diagnosis for lytic bone lesions, especially in endemic areas. Histopathological confirmation is essential for accurate diagnosis. Antitubercular therapy is an effective treatment for tuberculous osteomyelitis, leading to the resolution of the lesions with no residual disability.

Keywords: tuberculosis, tumor, curettage, bone

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176 Effect of Renin Angiotensin Pathway Inhibition on the Efficacy of Anti-programmed Cell Death (PD-1/L-1) Inhibitors in Advanced Non-small Cell Lung Cancer Patients- Comparison of Single Hospital Retrospective Assessment to the Published Literature

Authors: Esther Friedlander, Philip Friedlander

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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC

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175 Evaluation of Wheat Varieties for Water Use Efficiency under Staggering Sowing Times and Variable Irrigation Regimes under Timely and Late Sown Conditions

Authors: Vaibhav Baliyan, S. S. Parihar

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With the rise in temperature during reproductive phase and moisture stress, winter wheat yields are likely to decrease because of limited plant growth, higher rate of night respiration, higher spikelet sterility or number of grains per spike and restricted embryo development thereby reducing grain number. Crop management practices play a pivotal role in minimizing adverse effects of terminal heat stress on wheat production. Amongst various agronomic management practices, adjusting sowing date, crop cultivars and irrigation scheduling have been realized to be simple yet powerful, implementable and eco-friendly mitigation strategies to sustain yields under elevated temperature conditions. Taking into account, large variability in wheat production in space and time, a study was conducted to identify the suitable wheat varieties under both early and late planting with suitable irrigation schedule for minimizing terminal heat stress effect and thereby improving wheat production. Experiments were conducted at research farms of Indian Agricultural Research Institute, New Delhi, India, separately for timely and late sown conditions with suitable varieties with staggering dates of sowing from 1st November to 30th November in case of timely sown and from 1st December to 31st December for late sown condition. The irrigation schedule followed for both the experiments were 100% of ETc (evapotranspiration of crop), 80% of ETc and 60% of ETc. Results of the timely sown experiment indicated that 1st November sowing resulted in higher grain yield followed by 10th November. However, delay in sowing thereafter resulted in gradual decrease in yield and the maximum reduction was noticed under 30th November sowing. Amongst the varieties, HD3086 produced higher grain yield compared to other varieties. Irrigation applied based on 100% of ETc gave higher yield comparable to 80% of ETc but both were significantly higher than 60% of ETc. It was further observed that even liberal irrigation under 100% of ETc could not compensate the yield under delayed sowing suggesting that rise in temperature beyond January adversely affected the growth and development of crop as well as forced maturity resulting in significant reduction of yield attributing characters due to terminal heat stress. Similar observations were recorded under late sown experiment too. Planting on 1st December along with 100% ETc of irrigation schedule resulted in significantly higher grain yield as compared to other dates and irrigation regimes. Further, it was observed that reduction in yield under late sown conditions was significantly large than the timely sown conditions irrespective of the variety grown and irrigation schedule followed. Delayed sowing resulted in reducing crop growth period and forced maturity in turn led to significant deterioration in all the yield attributing characters and there by reduction in yield suggesting that terminal heat stress had greater impact on yield under late sown crop than timely sown due to temperature rise coinciding with reproductive phase of the crop.

Keywords: climate, irrigation, mitigation, wheat

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174 Surface Adjustments for Endothelialization of Decellularized Porcine Pericardium

Authors: M. Markova, E. Filova, O. Kaplan, R. Matejka, L. Bacakova

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The porcine pericardium is used as a material for cardiac and aortic valves substitutes. Current biological aortic heart valve prosthesis have a limited lifetime period because they undergo degeneration. In order to make them more biocompatible and prolong their lifetime it is necessary to reseed the decellularized prostheses with endothelial cells and with valve interstitial cells. The endothelialization of the prosthesis-surface may be supported by suitable chemical surface modification of the prosthesis. The aim of this study is to prepare bioactive fibrin layers which would both support endothelialization of porcine pericardium and enhance differentiation and maturation of the endothelial cells seeded. As a material for surface adjustments we used layers of fibrin with/without heparin and some of them with adsorbed or chemically bound FGF2, VEGF or their combination. Fibrin assemblies were prepared in 24-well cell culture plate and were seeded with HSVEC (Human Saphenous Vein Endothelial Cells) at a density of 20,000 cells per well in EGM-2 medium with 0.5% FS and without heparin, without FGF2 and without VEGF; medium was supplemented with aprotinin (200 U/mL). As a control, surface polystyrene (PS) was used. Fibrin was also used as homogeneous impregnation of the decellularized porcine pericardium throughout the scaffolds. Morphology, density, and viability of the seeded endothelial cells were observed from micrographs after staining the samples by LIVE/DEAD cytotoxicity/viability assay kit on the days 1, 3, and 7. Endothelial cells were immunocytochemically stained for proteins involved in cell adhesion, i.e. alphaV integrin, vinculin, and VE-cadherin, markers of endothelial cells differentiation and maturation, i.e. von Willebrand factor and CD31, and for extracellular matrix proteins typically produced by endothelial cells, i.e. type IV collagen and laminin. The staining intensities were subsequently quantified using a software. HSVEC cells grew on each of the prepared surfaces better than on control surface. They reached confluency. The highest cell densities were obtained on the surface of fibrin with heparin and both grow factors used together. Intensity of alphaV integrins staining was highest on samples with remained fibrin layer, i.e. on layers with lower cell densities, i.e. on fibrin without heparin. Vinculin staining was apparent, but was rather diffuse, on fibrin with both FGF2 and VEGF and on control PS. Endothelial cells on all samples were positively stained for von Willebrand factor and CD31. VE-cadherin receptors clusters were best developed on fibrin with heparin and growth factors. Significantly stronger staining of type IV collagen was observed on fibrin with heparin and both growth factors. Endothelial cells on all samples produced laminin-1. Decellularized pericardium was homogeneously filled with fibrin structures. These fibrin-modified pericardium samples will be further seeded with cells and cultured in a bioreactor. Fibrin layers with/without heparin and with adsorbed or chemically bound FGF2, VEGF or their combination are good surfaces for endothelialization of cardiovascular prostheses or porcine pericardium based heart valves. Supported by the Ministry of Health, grants No15-29153A and 15-32497A, and the Grant Agency of the Czech Republic, project No. P108/12/G108.

Keywords: aortic valves prosthesis, FGF2, heparin, HSVEC cells, VEGF

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173 An Epidemiological Study on Cutaneous Melanoma, Basocellular and Epidermoid Carcinomas Diagnosed in a Sunny City in Southeast Brazil in a Five-Year Period

Authors: Carolina L. Cerdeira, Julia V. F. Cortes, Maria E. V. Amarante, Gersika B. Santos

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Skin cancer is the most common cancer in several parts of the world; in a tropical country like Brazil, the situation isn’t different. The Brazilian population is exposed to high levels of solar radiation, increasing the risk of developing cutaneous carcinoma. Aimed at encouraging prevention measures and the early diagnosis of these tumors, a study was carried out that analyzed data on cutaneous melanomas, basal cell, and epidermoid carcinomas, using as primary data source the medical records of 161 patients registered in one pathology service, which performs skin biopsies in a city of Minas Gerais, Brazil. All patients diagnosed with skin cancer at this service from January 2015 to December 2019 were included. The incidence of skin carcinoma cases was correlated with the identification of histological type, sex, age group, and topographic location. Correlation between variables was verified by Fisher's exact test at a nominal significance level of 5%, with statistical analysis performed by R® software. A significant association was observed between age group and type of cancer (p=0.0085); age group and sex (0.0298); and type of cancer and body region affected (p < 0.01). Those 161 cases analyzed comprised 93 basal cell carcinomas, 66 epidermoid carcinomas, and only two cutaneous melanomas. In the group aged 19 to 30 years, the epidermoid form was most prevalent; from 31 to 45 and from 46 to 59 years, the basal cell prevailed; in 60-year-olds or over, both types had higher frequencies. Associating age group and sex, in groups aged 18 to 30 and 46 to 59 years, women were most affected. In the 31-to 45-year-old group, men predominated. There was a gender balance in the age group 60-year-olds or over. As for topography, there was a high prevalence in the head and neck, followed by upper limbs. Relating histological type and topography, there was a prevalence of basal cell and epidermoid carcinomas in the head and neck. In the chest, the basal cell form was most prevalent; in upper limbs, the epidermoid form prevailed. Cutaneous melanoma affected only the chest and upper limbs. About 82% of patients 60-year-olds or over had head and neck cancer; from 46 to 59 and 60-year-olds or over, the head and neck region and upper limbs were predominantly affected; the distribution was balanced in the 31-to 45-year-old group. In conclusion, basal cell carcinoma was predominant, whereas cutaneous melanoma was the rarest among the types analyzed. Patients 60-year-olds or over were most affected, showing gender balance. In young adults, there was a prevalence of the epidermoid form; in middle-aged patients, basal cell carcinoma was predominant; in the elderly, both forms presented with higher frequencies. There was a higher incidence of head and neck cancers, followed by malignancies affecting the upper limbs. The epidermoid type manifested significantly in the upper limbs. Body regions such as the thorax and lower limbs were less affected, which is justified by the lower exposure of these areas to incident solar radiation.

Keywords: basal cell carcinoma, cutaneous melanoma, skin cancer, squamous cell carcinoma, topographic location

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172 Delivering Safer Clinical Trials; Using Electronic Healthcare Records (EHR) to Monitor, Detect and Report Adverse Events in Clinical Trials

Authors: Claire Williams

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

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

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171 An Eco-Systemic Typology of Fashion Resale Business Models in Denmark

Authors: Mette Dalgaard Nielsen

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The paper serves the purpose of providing an eco-systemic typology of fashion resale business models in Denmark while pointing to possibilities to learn from its wisdom during a time when a fundamental break with the dominant linear fashion paradigm has become inevitable. As we transgress planetary boundaries and can no longer continue the unsustainable path of over-exploiting the Earth’s resources, the global fashion industry faces a tremendous need for change. One of the preferred answers to the fashion industry’s sustainability crises lies in the circular economy, which aims to maximize the utilization of resources by keeping garments in use for longer. Thus, in the context of fashion, resale business models that allow pre-owned garments to change hands with the purpose of being reused in continuous cycles are considered to be among the most efficient forms of circularity. Methodologies: The paper is based on empirical data from an ongoing project and a series of qualitative pilot studies that have been conducted on the Danish resale market over a 2-year time period from Fall 2021 to Fall 2023. The methodological framework is comprised of (n) ethnography and fieldwork in selected resale environments, as well as semi-structured interviews and a workshop with eight business partners from the Danish fashion and textiles industry. By focusing on the real-world circulation of pre-owned garments, which is enabled by the identified resale business models, the research lets go of simplistic hypotheses to the benefit of dynamic, vibrant and non-linear processes. As such, the paper contributes to the emerging research field of circular economy and fashion, which finds itself in a critical need to move from non-verified concepts and theories to empirical evidence. Findings: Based on the empirical data and anchored in the business partners, the paper analyses and presents five distinct resale business models with different product, service and design characteristics. These are 1) branded resale, 2) trade-in resale, 3) peer-2-peer resale, 4) resale boutiques and consignment shops and 5) resale shelf/square meter stores and flea markets. Together, the five business models represent a plurality of resale-promoting business model design elements that have been found to contribute to the circulation of pre-owned garments in various ways for different garments, users and businesses in Denmark. Hence, the provided typology points to the necessity of prioritizing several rather than single resale business model designs, services and initiatives for the resale market to help reconfigure the linear fashion model and create a circular-ish future. Conclusions: The article represents a twofold research ambition by 1) presenting an original, up-to-date eco-systemic typology of resale business models in Denmark and 2) using the typology and its eco-systemic traits as a tool to understand different business model design elements and possibilities to help fashion grow out of its linear growth model. By basing the typology on eco-systemic mechanisms and actual exemplars of resale business models, it becomes possible to envision the contours of a genuine alternative to business as usual that ultimately helps bend the linear fashion model towards circularity.

Keywords: circular business models, circular economy, fashion, resale, strategic design, sustainability

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170 Classical Music Unplugged: The Future of Classical Music Performance: Tradition, Technology, and Audience Engagement

Authors: Orit Wolf

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Classical music performance is undergoing a profound transformation, marked by a confluence of technological advancements and evolving cultural dynamics. This academic paper explores the multifaceted changes and challenges faced by classical music performance, considering the impact of artificial intelligence (AI) along with other vital factors shaping this evolution. In the contemporary era, classical music is experiencing shifts in performance practices. This paper delves into these changes, emphasizing the need for adaptability within the classical music world. From repertoire selection and concert formats to artistic expression, performers and institutions navigate a delicate balance between tradition and innovation. We explore how these changes impact the authenticity and vitality of classical music performances. Furthermore, the influence of AI in the classical music concert world cannot be underestimated. AI technologies are making inroads into various aspects, from composition assistance to rehearsal and live performances. This paper examines the transformative effects of AI, considering how it enhances precision, adaptability, and creative exploration for musicians. We explore the implications for composers, performers, and the overall concert experience while addressing ethical concerns and creative opportunities. In addition to AI, there is the importance of cross-genre interactions within the classical music sphere. Mash-ups and collaborations with artists from diverse musical backgrounds are redefining the boundaries of classical music and creating works that resonate with a wider and more diverse audience. The benefits of cross-pollination in classical music seem crucial, offering a fresh perspective to listeners. As an active concert artist, Orit Wolf will share how the expectations of classical music audiences are evolving. Modern concertgoers seek not only exceptional musical performances but also immersive experiences that may involve technology, multimedia, and interactive elements. This paper examines how classical musicians and institutions are adapting to these changing expectations, using technology and innovative concert formats to deliver a unique and enriched experience to their audiences. As these changes and challenges reshape the classical music world, the need for a harmonious coexistence of tradition, technology, and innovation becomes evident. Musicians, composers, and institutions are striving to find a balance that ensures classical music remains relevant in a rapidly changing cultural landscape while maintaining the value it brings to compositions and audiences. This paper, therefore, aims to explore the evolving trends in classical music performance. It considers the influence of AI as one element within the broader context of change, highlighting the necessity of adaptability, cross-genre interactions, and a response to evolving audience expectations. By doing so, the classical music world can navigate this transformative period while preserving its timeless traditions and adding value to both performers and listeners. Orit Wolf, an international concert pianist, fulfils her vision to bring this music in new ways to mass audiences and will share her personal and professional experience as an artist who goes on stage and makes disruptive concerts.

Keywords: cross culture collaboration, music performance and ai, classical music in the digital age, classical concerts, innovation and technology, performance innovation, audience engagement in classical concerts

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169 Forced Immigration to Turkey: The Socio-Spatial Impacts of Syrian Immigrants on Turkish Cities

Authors: Tolga Levent

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Throughout the past few decades, forced immigration has been a significant problem for many developing countries. Turkey is one of those countries, which has experienced lots of forced immigration waves in the Republican era. However, the ongoing forced immigration wave of Syrians started with Syrian Civil War in 2011, is strikingly influential due to its intensity. In six years, approximately 3,4 million Syrians have entered to Turkey and presented high-level spatial concentrations in certain cities proximate to the Syrian border. These concentrations make Syrians and their problems relatively visible, especially in those cities. The problems of Syrians in Turkish cities could be associated with all dimensions of daily lives. Within economical dimension, high rates of Syrian unemployment push them to informal jobs offering very low wages. The financial aids they continuously demand from public authorities trigger anti-Syrian behaviors of local communities. Moreover, their relatively limited social adaptation capacities increase integration problems within social dimension day by day. Even, there are problems related to public health dimension such as the reappearance of certain child's illnesses due to the insufficiency of vaccination of Syrian children. These problems are significant but relatively easy to be prevented by using different types of management strategies and structural policies. However, there are other types of problems -urban problems- emerging with socio-spatial impacts of Syrians on Turkish cities in a very short period of time. There are relatively limited amount of studies about these impacts since they are difficult to be comprehended. The aim of the study, in this respect, is to understand these rapidly-emerging impacts and urban problems resulted from this massive immigration influx and to discuss new qualities of urban planning facing them. In the first part, there is a brief historical consideration of forced immigration waves in Turkey. These waves are important to make comparison with the ongoing immigration wave and to understand its significance. The second part is about quantitative and qualitative analyses of the spatial existence of Syrian immigrants in the city of Mersin, as an example of cities where Syrians are highly concentrated. By using official data from public authorities, quantitative statistical analyses are made to detect spatial concentrations of Syrians at neighborhood level. As methods of qualitative research, observations and in-depth interviews are used to define socio-spatial impacts of Syrians. The main results show that there emerges 'cities in cities' though sharp socio-spatial segregations which change density surfaces; produce unforeseen land-use patterns; result in inadequacies of public services and create degradations/deteriorations of urban environments occupied by Syrians. All these problems are significant; however, Turkish planning system does not have a capacity to cope with them. In the final part, there is a discussion about new qualities of urban planning facing these impacts and urban problems. The main point of discussion is the possibility of resilient urban planning under the conditions of uncertainty and unpredictability fostered by immigration crisis. Such a resilient planning approach might provide an option for countries aiming to cope with negative socio-spatial impacts of massive immigration influxes.

Keywords: cities, forced immigration, Syrians, urban planning

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168 Implementation of Real-World Learning Experiences in Teaching Courses of Medical Microbiology and Dietetics for Health Science Students

Authors: Miriam I. Jimenez-Perez, Mariana C. Orellana-Haro, Carolina Guzman-Brambila

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As part of microbiology and dietetics courses, students of medicine and nutrition analyze the main pathogenic microorganisms and perform dietary analyzes. The course of microbiology describes in a general way the main pathogens including bacteria, viruses, fungi, and parasites, as well as their interaction with the human species. We hypothesize that lack of practical application of the course causes the students not to find the value and the clinical application of it when in reality it is a matter of great importance for healthcare in our country. The courses of the medical microbiology and dietetics are mostly theoretical and only a few hours of laboratory practices. Therefore, it is necessary the incorporation of new innovative techniques that involve more practices and community fieldwork, real cases analysis and real-life situations. The purpose of this intervention was to incorporate real-world learning experiences in the instruction of medical microbiology and dietetics courses, in order to improve the learning process, understanding and the application in the field. During a period of 6 months, medicine and nutrition students worked in a community of urban poverty. We worked with 90 children between 4 and 6 years of age from low-income families with no access to medical services, to give an infectious diagnosis related to nutritional status in these children. We expect that this intervention would give a different kind of context to medical microbiology and dietetics students improving their learning process, applying their knowledge and laboratory practices to help a needed community. First, students learned basic skills in microbiology diagnosis test during laboratory sessions. Once, students acquired abilities to make biochemical probes and handle biological samples, they went to the community and took stool samples from children (with the corresponding informed consent). Students processed the samples in the laboratory, searching for enteropathogenic microorganism with RapID™ ONE system (Thermo Scientific™) and parasites using Willis and Malloy modified technique. Finally, they compared the results with the nutritional status of the children, previously measured by anthropometric indicators. The anthropometric results were interpreted by the OMS Anthro software (WHO, 2011). The microbiological result was interpreted by ERIC® Electronic RapID™ Code Compendium software and validated by a physician. The results were analyses of infectious outcomes and nutritional status. Related to fieldwork community learning experiences, our students improved their knowledge in microbiology and were capable of applying this knowledge in a real-life situation. They found this kind of learning useful when they translate theory to a real-life situation. For most of our students, this is their first contact as health caregivers with real population, and this contact is very important to help them understand the reality of many people in Mexico. In conclusion, real-world or fieldwork learning experiences empower our students to have a real and better understanding of how they can apply their knowledge in microbiology and dietetics and help a much- needed population, this is the kind of reality that many people live in our country.

Keywords: real-world learning experiences, medical microbiology, dietetics, nutritional status, infectious status.

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167 Implementing Equitable Learning Experiences to Increase Environmental Awareness and Science Proficiency in Alabama’s Schools and Communities

Authors: Carly Cummings, Maria Soledad Peresin

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Alabama has a long history of racial injustice and unsatisfactory educational performance. In the 1870s Jim Crow laws segregated public schools and disproportionally allocated funding and resources to white institutions across the South. Despite the Supreme Court ruling to integrate schools following Brown vs. the Board of Education in 1954, Alabama’s school system continued to exhibit signs of segregation, compounded by “white flight” and the establishment of exclusive private schools, which still exist today. This discriminatory history has had a lasting impact of the state’s education system, reflected in modern school demographics and achievement data. It is well known that Alabama struggles with education performance, especially in science education. On average, minority groups scored the lowest in science proficiency. In Alabama, minority populations are concentrated in a region known as the Black Belt, which was once home to countless slave plantations and was the epicenter of the Civil Rights Movement. Today the Black Belt is characterized by a high density of woodlands and plays a significant role in Alabama’s leading economic industry-forest products. Given the economic importance of forestry and agriculture to the state, environmental science proficiency is essential to its stability; however, it is neglected in areas where it is needed most. To better understand the inequity of science education within Alabama, our study first investigates how geographic location, demographics and school funding relate to science achievement scores using ArcGIS and Pearson’s correlation coefficient. Additionally, our study explores the implementation of a relevant, problem-based, active learning lesson in schools. Relevant learning engages students by connecting material to their personal experiences. Problem-based active learning involves real-world problem-solving through hands-on experiences. Given Alabama’s significant woodland coverage, educational materials on forest products were developed with consideration of its relevance to students, especially those located in the Black Belt. Furthermore, to incorporate problem solving and active learning, the lesson centered around students using forest products to solve environmental challenges, such as water pollution- an increasing challenge within the state due to climate change. Pre and post assessment surveys were provided to teachers to measure the effectiveness of the lesson. In addition to pedagogical practices, community and mentorship programs are known to positively impact educational achievements. To this end, our work examines the results of surveys measuring educational professionals’ attitudes toward a local mentorship group within the Black Belt and its potential to address environmental and science literacy. Additionally, our study presents survey results from participants who attended an educational community event, gauging its effectiveness in increasing environmental and science proficiency. Our results demonstrate positive improvements in environmental awareness and science literacy with relevant pedagogy, mentorship, and community involvement. Implementing these practices can help provide equitable and inclusive learning environments and can better equip students with the skills and knowledge needed to bridge this historic educational gap within Alabama.

Keywords: equitable education, environmental science, environmental education, science education, racial injustice, sustainability, rural education

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166 Development of a Conceptual Framework for Supply Chain Management Strategies Maximizing Resilience in Volatile Business Environments: A Case of Ventilator Challenge UK

Authors: Elena Selezneva

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Over the last two decades, an unprecedented growth in uncertainty and volatility in all aspects of the business environment has caused major global supply chain disruptions and malfunctions. The effects of one failed company in a supply chain can ripple up and down the chain, causing a number of entities or an entire supply chain to collapse. The complicating factor is that an increasingly unstable and unpredictable business environment fuels the growing complexity of global supply chain networks. That makes supply chain operations extremely unpredictable and hard to manage with the established methods and strategies. It has caused the premature demise of many companies around the globe as they could not withstand or adapt to the storm of change. Solutions to this problem are not easy to come by. There is a lack of new empirically tested theories and practically viable supply chain resilience strategies. The mainstream organizational approach to managing supply chain resilience is rooted in well-established theories developed in the 1960-1980s. However, their effectiveness is questionable in currently extremely volatile business environments. The systems thinking approach offers an alternative view of supply chain resilience. Still, it is very much in the development stage. The aim of this explorative research is to investigate supply chain management strategies that are successful in taming complexity in volatile business environments and creating resilience in supply chains. The design of this research methodology was guided by an interpretivist paradigm. A literature review informed the selection of the systems thinking approach to supply chain resilience. Therefore, an explorative single case study of Ventilator Challenge UK was selected as a case study for its extremely resilient performance of its supply chain during a period of national crisis. Ventilator Challenge UK is intensive care ventilators supply project for the NHS. It ran for 3.5 months and finished in 2020. The participants moved on with their lives, and most of them are not employed by the same organizations anymore. Therefore, the study data includes documents, historical interviews, live interviews with participants, and social media postings. The data analysis was accomplished in two stages. First, data were thematically analyzed. In the second stage, pattern matching and pattern identification were used to identify themes that formed the findings of the research. The findings from the Ventilator Challenge UK case study supply management practices demonstrated all the features of an adaptive dynamic system. They cover all the elements of supply chain and employ an entire arsenal of adaptive dynamic system strategies enabling supply chain resilience. Also, it is not a simple sum of parts and strategies. Bonding elements and connections between the components of a supply chain and its environment enabled the amplification of resilience in the form of systemic emergence. Enablers are categorized into three subsystems: supply chain central strategy, supply chain operations, and supply chain communications. Together, these subsystems and their interconnections form the resilient supply chain system framework conceptualized by the author.

Keywords: enablers of supply chain resilience, supply chain resilience strategies, systemic approach in supply chain management, resilient supply chain system framework, ventilator challenge UK

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165 Multiple Primary Pulmonary Meningiomas: A Case Report

Authors: Wellemans Isabelle, Remmelink Myriam, Foucart Annick, Rusu Stefan, Compère Christophe

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Primary pulmonary meningioma (PPM) is a very rare tumor, and its occurrence has been reported only sporadically. Multiple PPMs are even more exceptional, and herein, we report, to the best of our knowledge, the fourth case, focusing on the clinicopathological features of the tumor. Moreover, the possible relationship between the use of progesterone–only contraceptives and the development of these neoplasms will be discussed. Case Report: We report a case of a 51-year-old female presenting three solid pulmonary nodules, with the following localizations: right upper lobe, middle lobe, and left lower lobe, described as incidental findings on computed tomography (CT) during a pre-bariatric surgery check-up. The patient revealed no drinking or smoking history. The physical exam was unremarkable except for the obesity. The lesions ranged in size between 6 and 24 mm and presented as solid nodules with lobulated contours. The largest lesion situated in the middle lobe had mild fluorodeoxyglucose (FDG) uptake on F-18 FDG positron emission tomography (PET)/CT, highly suggestive of primary lung neoplasm. For pathological assessment, video-assisted thoracoscopic middle lobectomy and wedge resection of the right upper nodule was performed. Histological examination revealed relatively well-circumscribed solid proliferation of bland meningothelial cells growing in whorls and lobular nests, presenting intranuclear pseudo-inclusions and psammoma bodies. No signs of anaplasia were observed. The meningothelial cells expressed diffusely Vimentin, focally Progesterone receptors and were negative for epithelial (cytokeratin (CK) AE1/AE3, CK7, CK20, Epithelial Membrane Antigen (EMA)), neuroendocrine markers (Synaptophysin, Chromogranin, CD56) and Estrogenic receptors. The proliferation labelling index Ki-67 was low (<5%). Metastatic meningioma was ruled out by brain and spine magnetic resonance imaging (MRI) scans. The third lesion localized in the left lower lobe was followed-up and resected three years later because of its slow but significant growth (14 mm to 16 mm), alongside two new infra centimetric lesions. Those three lesions showed a morphological and immunohistochemical profile similar to previously resected lesions. The patient was disease-free one year post-last surgery. Discussion: Although PPMs are mostly benign and slow-growing tumors with an excellent prognosis, they do not present specific radiological characteristics, and it is difficult to differentiate it from other lung tumors, histopathologic examination being essential. Aggressive behavior is associated with atypical or anaplastic features (WHO grades II–III) The etiology is still uncertain and different mechanisms have been proposed. A causal connection between sexual hormones and meningothelial proliferation has long been suspected and few studies examining progesterone only contraception and meningioma risk have all suggested an association. In line with this, our patient was treated with Levonorgestrel, a progesterone agonist, intra-uterine device (IUD). Conclusions: PPM, defined by the typical histological and immunohistochemical features of meningioma in the lungs and the absence of central nervous system lesions, is an extremely rare neoplasm, mainly solitary and associating, and indolent growth. Because of the unspecific radiologic findings, it should always be considered in the differential diagnosis of lung neoplasms. Regarding multiple PPM, only three cases are reported in the literature, and this is the first described in a woman treated by a progesterone-only IUD to the best of our knowledge.

Keywords: pulmonary meningioma, multiple meningioma, meningioma, pulmonary nodules

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164 Application of Discrete-Event Simulation in Health Technology Assessment: A Cost-Effectiveness Analysis of Alzheimer’s Disease Treatment Using Real-World Evidence in Thailand

Authors: Khachen Kongpakwattana, Nathorn Chaiyakunapruk

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Background: Decision-analytic models for Alzheimer’s disease (AD) have been advanced to discrete-event simulation (DES), in which individual-level modelling of disease progression across continuous severity spectra and incorporation of key parameters such as treatment persistence into the model become feasible. This study aimed to apply the DES to perform a cost-effectiveness analysis of treatment for AD in Thailand. Methods: A dataset of Thai patients with AD, representing unique demographic and clinical characteristics, was bootstrapped to generate a baseline cohort of patients. Each patient was cloned and assigned to donepezil, galantamine, rivastigmine, memantine or no treatment. Throughout the simulation period, the model randomly assigned each patient to discrete events including hospital visits, treatment discontinuation and death. Correlated changes in cognitive and behavioral status over time were developed using patient-level data. Treatment effects were obtained from the most recent network meta-analysis. Treatment persistence, mortality and predictive equations for functional status, costs (Thai baht (THB) in 2017) and quality-adjusted life year (QALY) were derived from country-specific real-world data. The time horizon was 10 years, with a discount rate of 3% per annum. Cost-effectiveness was evaluated based on the willingness-to-pay (WTP) threshold of 160,000 THB/QALY gained (4,994 US$/QALY gained) in Thailand. Results: Under a societal perspective, only was the prescription of donepezil to AD patients with all disease-severity levels found to be cost-effective. Compared to untreated patients, although the patients receiving donepezil incurred a discounted additional costs of 2,161 THB, they experienced a discounted gain in QALY of 0.021, resulting in an incremental cost-effectiveness ratio (ICER) of 138,524 THB/QALY (4,062 US$/QALY). Besides, providing early treatment with donepezil to mild AD patients further reduced the ICER to 61,652 THB/QALY (1,808 US$/QALY). However, the dominance of donepezil appeared to wane when delayed treatment was given to a subgroup of moderate and severe AD patients [ICER: 284,388 THB/QALY (8,340 US$/QALY)]. Introduction of a treatment stopping rule when the Mini-Mental State Exam (MMSE) score goes below 10 to a mild AD cohort did not deteriorate the cost-effectiveness of donepezil at the current treatment persistence level. On the other hand, none of the AD medications was cost-effective when being considered under a healthcare perspective. Conclusions: The DES greatly enhances real-world representativeness of decision-analytic models for AD. Under a societal perspective, treatment with donepezil improves patient’s quality of life and is considered cost-effective when used to treat AD patients with all disease-severity levels in Thailand. The optimal treatment benefits are observed when donepezil is prescribed since the early course of AD. With healthcare budget constraints in Thailand, the implementation of donepezil coverage may be most likely possible when being considered starting with mild AD patients, along with the stopping rule introduced.

Keywords: Alzheimer's disease, cost-effectiveness analysis, discrete event simulation, health technology assessment

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163 A Study on the Chemical Composition of Kolkheti's Sphagnum Peat Peloids to Evaluate the Perspective of Use in Medical Practice

Authors: Al. Tsertsvadze. L. Ebralidze, I. Matchutadze. D. Berashvili, A. Bakuridze

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Peatlands are landscape elements, they are formed over a very long period by physical, chemical, biologic, and geologic processes. In the moderate zone of Caucasus, the Kolkheti lowlands are distinguished by the diversity of relictual plants, a high degree of endemism, orographic, climate, landscape, and other characteristics of high levels of biodiversity. The unique properties of the Kolkheti region lead to the formation of special, so-called, endemic peat peloids. The composition and properties of peloids strongly depend on peat-forming plants. Peat is considered a unique complex of raw materials, which can be used in different fields of the industry: agriculture, metallurgy, energy, biotechnology, chemical industry, health care. They are formed in permanent wetland areas. As a result of decay, higher plants remain in the anaerobic area, with the participation of microorganisms. Peat mass absorbs soil and groundwater. Peloids are predominantly rich with humic substances, which are characterized by high biological activity. Humic acids stimulate enzymatic activity, regenerative processes, and have anti-inflammatory activity. Objects of the research were Kolkheti peat peloids (Ispani, Anaklia, Churia, Chirukhi, Peranga) possessing different formation phases. Due to specific physical and chemical properties of research objects, the aim of the research was to develop analytical methods in order to study the chemical composition of the objects. The research was held using modern instrumental methods of analysis: Ultraviolet-visible spectroscopy and Infrared spectroscopy, Scanning Electron Microscopy, Centrifuge, dry oven, Ultraturax, pH meter, fluorescence spectrometer, Gas chromatography-mass spectrometry (GC-MS/MS), Gas chromatography. Based on the research ration between organic and inorganic substances, the spectrum of micro and macro elements, also the content of minerals was determined. The content of organic nitrogen was determined using the Kjeldahl method. The total composition of amino acids was studied by a spectrophotometric method using standard solutions of glutamic and aspartic acids. Fatty acid was determined using GC (Gas chromatography). Based on the obtained results, we can conclude that the method is valid to identify fatty acids in the research objects. The content of organic substances in the research objects was held using GC-MS. Using modern instrumental methods of analysis, the chemical composition of research objects was studied. Each research object is predominantly reached with a broad spectrum of organic (fatty acids, amino acids, carbocyclic and heterocyclic compounds, organic acids and their esters, steroids) and inorganic (micro and macro elements, minerals) substances. Modified methods used in the presented research may be utilized for the evaluation of cosmetological balneological and pharmaceutical means prepared on the base of Kolkheti's Sphagnum Peat Peloids.

Keywords: modern analytical methods, natural resources, peat, chemistry

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162 Improved Approach to the Treatment of Resistant Breast Cancer

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

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161 Evaluation of Toxicity of Cerium Oxide on Zebrafish Developmental Stages

Authors: Roberta Pecoraro, Elena Maria Scalisi

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Engineered Nanoparticles (ENPs) and Nanomaterials (ENMs) concern an active research area and a sector in full expansion. They have physical-chemical characteristics and small size that improve their performance compared to common materials. Due to the increase in their production and their subsequent release into the environment, new strategies are emerging to assess risk of nanomaterials. NPs can be released into the environment through aquatic systems by human activities and exert toxicity on living organisms. We evaluated the potential toxic effect of cerium oxide (CeO2) nanoparticles because it’s used in different fields due to its peculiar properties. In order to assess nanoparticles toxicity, Fish Embryo Toxicity (FET) test was performed. Powders of CeO2 NPs supplied by the CNR-IMM of Catania are indicated as CeO2 type 1 (as-prepared) and CeO2 type 2 (modified), while CeO2 type 3 (commercial) is supplied by Sigma-Aldrich. Starting from a stock solution (0.001g/10 ml dilution water) of each type of CeO2 NPs, the other concentration solutions were obtained adding 1 ml of the stock solution to 9 ml of dilution water, leading to three different solutions of concentration (10-4, 10-5, 10-6 g/ml). All the solutions have been sonicated to avoid natural tendency of NPs to aggregate and sediment. FET test was performed according to the OECD guidelines for testing chemicals using our internal protocol procedure. A number of eight selected fertilized eggs were placed in each becher filled with 5 ml of each concentration of the three types of CeO2 NPs; control samples were incubated only with dilution water. Replication was performed for each concentration. During the exposure period, we observed four endpoints (embryo coagulation, lack of formation of somites, failure to lift the yolk bag, no heartbeat) by a stereomicroscope every 24 hours. Immunohistochemical analysis on treated larvae was performed to evaluate the expression of metallothioneins (MTs), Heat Shock Proteins 70 (HSP70) and 7-ethoxyresorufin-O-diethylase (EROD). Our results have not shown evident alterations on embryonic development because all embryos completed the development and the hatching of the eggs, started around the 48th hour after exposure, took place within the last observation at 72 hours. A good reactivity, both in the embryos and in the newly hatched larvae, was found. The presence of heartbeat has also been observed in embryos with reduced mobility confirming their viability. A higher expression of EROD biomarker was observed in the larvae exposed to the three types of CeO2, showing a clear difference with the control. A weak positivity was found for MTs biomarker in treated larvae as well as in the control. HSP70 are expressed homogeneously in all the type of nanoparticles tested but not too much greater than control. Our results are in agreement with other studies in the literature, in which the exposure of Danio rerio larvae to other metal oxide nanoparticles does not show adverse effects on survival and hatching time. Further studies are necessary to clarify the role of these NPs and also to solve conflicting opinions.

Keywords: Danio rerio, endpoints, fish embryo toxicity test, metallic nanoparticles

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160 An Observation of Patient-Professional Communication in the Cambodian Dental Setting

Authors: Christina Tran, Lu Khoo, Andrea Waylen

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Introduction: The evolution of the dental consultation from paternalism to partnership has been well documented in developed Western countries. Great emphasis is now placed on the importance of empowering patients to make decisions regarding their care, obtaining informed consent, and maintaining patient privacy and confidentiality. With the majority of communication occurring non-verbally, clinicians often adopt behaviours which suggest an approachable and positive attitude. However, evidence indicates that in Asia, a paternalistic model may be favored in medicine. The power imbalance occurring in doctor-patient relationships worldwide may be exacerbated by various factors in Southeast Asia: the strong hierarchical culture, and the large education gap between doctor and patient. Further insight into this matter can be gained by observing patient-dentist communication in Cambodia. The dentist:population ratio in Cambodia is approximately 1:33,000, with rural areas remaining extremely underserviced. We have carried out an observational study of communication in a voluntary dental clinic in Cambodia with the aim of describing whether the patient-dentist relationship follows a paternalistic or patient-centred model. Method: Over a period of two weeks, two clinicians provided dental care as part of a voluntary program in two Cambodian settings: a temporary, rural clinic and a permanent clinic in Phnom Penh. The clinicians independently recorded their experiences in diaries, making observations on the verbal and non-verbal communication between patients and staff. General observations such as the clinic environment were also made. The diaries were then compared and analyzed using a thematic approach. Results: The overall themes that emerged were regarding the clinic environment, verbal communication, and non-verbal communication. Regarding the clinic environment, the rural clinic was arranged in order to easily direct patients from one dentist to another, with little emphasis on continuous patient care. There was also little consideration for patient privacy: patients were often treated in the presence of many observers, including other waiting patients. However, the permanent clinic was structured to allow greater patient privacy, with continuous patient care occurring throughout the appointment. Regarding verbal communication, there was a strongly paternalistic approach to gaining consent and giving instruction. Patients rarely asked questions regarding their treatment, with dentists doing little to encourage patient involvement. Non-verbal communication between patients and dentists was generally paternalistic, with the dentist often addressing the supine patient from above. Patients often avoided making eye-contact, which may have indicated discomfort or lack of engagement. Both adult and paediatric patients rarely raised verbal concerns regarding pain during treatment, despite displaying non-verbal signs of experiencing pain. Anxious paediatric patients were sometimes managed with physical restraint by their mothers to facilitate treatment. Conclusion: Patient-professional communication in the Cambodian dental setting was observed to be generally paternalistic in nature, although more patient-centred aspects were observed in the established, urban setting. However, it should be noted that these observations are subjective in nature, and that the patients’ actual perceptions of their communication experience were unexplored. Further observations in variety of dental settings in Cambodia are needed before any definitive conclusions can be made.

Keywords: patient-dentist communication, paternalism, patient-centered, non-verbal communication

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159 Cellular Mechanisms Involved in the Radiosensitization of Breast- and Lung Cancer Cells by Agents Targeting Microtubule Dynamics

Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

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Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

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158 Enabling and Ageing-Friendly Neighbourhoods: An Eye-Tracking Study of Multi-Sensory Experience of Senior Citizens in Singapore

Authors: Zdravko Trivic, Kelvin E. Y. Low, Darko Radovic, Raymond Lucas

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Our understanding and experience of the built environment are primarily shaped by multi‐sensory, emotional and symbolic modes of exchange with spaces. Associated sensory and cognitive declines that come with ageing substantially affect the overall quality of life of the elderly citizens and the ways they perceive and use urban environment. Reduced mobility and increased risk of falls, problems with spatial orientation and communication, lower confidence and independence levels, decreased willingness to go out and social withdrawal are some of the major consequences of sensory declines that challenge almost all segments of the seniors’ everyday living. However, contemporary urban environments are often either sensory overwhelming or depleting, resulting in physical, mental and emotional stress. Moreover, the design and planning of housing neighbourhoods hardly go beyond the passive 'do-no-harm' and universal design principles, and the limited provision of often non-integrated eldercare and inter-generational facilities. This paper explores and discusses the largely neglected relationships between the 'hard' and 'soft' aspects of housing neighbourhoods and urban experience, focusing on seniors’ perception and multi-sensory experience as vehicles for design and planning of high-density housing neighbourhoods that are inclusive and empathetic yet build senior residents’ physical and mental abilities at different stages of ageing. The paper outlines methods and key findings from research conducted in two high-density housing neighbourhoods in Singapore with aims to capture and evaluate multi-sensorial qualities of two neighbourhoods from the perspective of senior residents. Research methods employed included: on-site sensory recordings of 'objective' quantitative sensory data (air temperature and humidity, sound level and luminance) using multi-function environment meter, spatial mapping of patterns of elderly users’ transient and stationary activity, socio-sensory perception surveys and sensorial journeys with local residents using eye-tracking glasses, and supplemented by walk-along or post-walk interviews. The paper develops a multi-sensory framework to synthetize, cross-reference, and visualise the activity and spatio-sensory rhythms and patterns and distill key issues pertinent to ageing-friendly and health-supportive neighbourhood design. Key findings show senior residents’ concerns with walkability, safety, and wayfinding, overall aesthetic qualities, cleanliness, smell, noise, and crowdedness in their neighbourhoods, as well as the lack of design support for all-day use in the context of Singaporean tropical climate and for inter-generational social interaction. The (ongoing) analysis of eye-tracking data reveals the spatial elements of senior residents’ look at and interact with the most frequently, with the visual range often directed towards the ground. With capacities to meaningfully combine quantitative and qualitative, measured and experienced sensory data, multi-sensory framework shows to be fruitful for distilling key design opportunities based on often ignored aspects of subjective and often taken-for-granted interactions with the familiar outdoor environment. It offers an alternative way of leveraging the potentials of housing neighbourhoods to take a more active role in enabling healthful living at all stages of ageing.

Keywords: ageing-friendly neighbourhoods, eye-tracking, high-density environment, multi-sensory approach, perception

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157 Finite Element Analysis of Human Tarsals, Meta Tarsals and Phalanges for Predicting probable location of Fractures

Authors: Irfan Anjum Manarvi, Fawzi Aljassir

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Human bones have been a keen area of research over a long time in the field of biomechanical engineering. Medical professionals, as well as engineering academics and researchers, have investigated various bones by using medical, mechanical, and materials approaches to discover the available body of knowledge. Their major focus has been to establish properties of these and ultimately develop processes and tools either to prevent fracture or recover its damage. Literature shows that mechanical professionals conducted a variety of tests for hardness, deformation, and strain field measurement to arrive at their findings. However, they considered these results accuracy to be insufficient due to various limitations of tools, test equipment, difficulties in the availability of human bones. They proposed the need for further studies to first overcome inaccuracies in measurement methods, testing machines, and experimental errors and then carry out experimental or theoretical studies. Finite Element analysis is a technique which was developed for the aerospace industry due to the complexity of design and materials. But over a period of time, it has found its applications in many other industries due to accuracy and flexibility in selection of materials and types of loading that could be theoretically applied to an object under study. In the past few decades, the field of biomechanical engineering has also started to see its applicability. However, the work done in the area of Tarsals, metatarsals and phalanges using this technique is very limited. Therefore, present research has been focused on using this technique for analysis of these critical bones of the human body. This technique requires a 3-dimensional geometric computer model of the object to be analyzed. In the present research, a 3d laser scanner was used for accurate geometric scans of individual tarsals, metatarsals, and phalanges from a typical human foot to make these computer geometric models. These were then imported into a Finite Element Analysis software and a length refining process was carried out prior to analysis to ensure the computer models were true representatives of actual bone. This was followed by analysis of each bone individually. A number of constraints and load conditions were applied to observe the stress and strain distributions in these bones under the conditions of compression and tensile loads or their combination. Results were collected for deformations in various axis, and stress and strain distributions were observed to identify critical locations where fracture could occur. A comparative analysis of failure properties of all the three types of bones was carried out to establish which of these could fail earlier which is presented in this research. Results of this investigation could be used for further experimental studies by the academics and researchers, as well as industrial engineers, for development of various foot protection devices or tools for surgical operations and recovery treatment of these bones. Researchers could build up on these models to carryout analysis of a complete human foot through Finite Element analysis under various loading conditions such as walking, marching, running, and landing after a jump etc.

Keywords: tarsals, metatarsals, phalanges, 3D scanning, finite element analysis

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156 A Nutrient Formulation Affects Brain Myelination in Infants: An Investigative Randomized Controlled Trial

Authors: N. Schneider, M. Bruchhage, M. Hartweg, G. Mutungi, J. O Regan, S. Deoni

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Observational neuroimaging studies suggest differences between breast-fed and formula-fed infants in developmental myelination, a key brain process for learning and cognitive development. However, the possible effects of a nutrient formulation on myelin development in healthy term infants in an intervention study have not been investigated. Objective was, therefore, to investigate the efficacy of a nutrient formulation with higher levels of myelin-relevant nutrients as compared to a control formulation with lower levels of the same nutrients on brain myelination and cognitive development in the first 6 months of life. The study is an ongoing randomized, controlled, double-blind, two-center, parallel-group clinical trial with a nonrandomized, non-blinded arm of exclusively breastfed infants. The current findings result from a staged statistical analysis at 6 months; the recruitment and intervention period has been completed for all participants. Follow-up visits at 12, 18 and 24 months are still ongoing. N= 81 enrolled full term, neurotypical infants of both sexes were randomized into either the investigational (N= 42) or the control group (N= 39), and N= 108 children in the breast-fed arm served as a natural reference group. The effect of a blend of docosahexaenoic acid, arachidonic acid, iron, vitamin B12, folic acid as well as sphingomyelin from a uniquely proceed whey protein concentrate enriched in alpha-lactalbumin and phospholipids in an infant nutrition product matrix was investigated. The main outcomes for the staged statistical analyses at 6 months included brain myelination measures derived from MRI. Additional outcomes were brain volume, cognitive development and safety. The full analyses set at 6 months comprised N= 66 infants. Higher levels of myelin-relevant nutrients compared to lower levels resulted in significant differences in myelin structure, volume, and rate of myelination as early as 3 and 6 months of life. The cross-sectional change of means between groups for whole-brain myelin volume was 8.4% for investigational versus control formulation (3.5% versus the breastfeeding reference) group at 3 months and increased to 36.4% for investigational versus control formulation (14.1% versus breastfeeding reference) at 6 months. No statistically significant differences were detected for early cognition scores. Safety findings were largely similar across groups. This is the first pediatric nutritional neuroimaging study demonstrating the efficacy of a myelin nutrient blend on developmental myelination in well-nourished term infants. Myelination is a critical process in learning and development. The effects were demonstrated across the brain, particularly in temporal and parietal regions, known to be functionally involved in sensory, motor and language skills. These first results add to the field of nutritional neuroscience by demonstrating early life nutrition benefits for brain architecture which may be foundational for later cognitive and behavioral outcomes. ClinicalTrials.gov Identifier: NCT03111927 (Infant Nutrition and Brain Development - Full-Text View - ClinicalTrials.gov).

Keywords: brain development, infant nutrition, MRI, myelination

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155 Interpretable Deep Learning Models for Medical Condition Identification

Authors: Dongping Fang, Lian Duan, Xiaojing Yuan, Mike Xu, Allyn Klunder, Kevin Tan, Suiting Cao, Yeqing Ji

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Accurate prediction of a medical condition with straight clinical evidence is a long-sought topic in the medical management and health insurance field. Although great progress has been made with machine learning algorithms, the medical community is still, to a certain degree, suspicious about the model's accuracy and interpretability. This paper presents an innovative hierarchical attention deep learning model to achieve good prediction and clear interpretability that can be easily understood by medical professionals. This deep learning model uses a hierarchical attention structure that matches naturally with the medical history data structure and reflects the member’s encounter (date of service) sequence. The model attention structure consists of 3 levels: (1) attention on the medical code types (diagnosis codes, procedure codes, lab test results, and prescription drugs), (2) attention on the sequential medical encounters within a type, (3) attention on the medical codes within an encounter and type. This model is applied to predict the occurrence of stage 3 chronic kidney disease (CKD3), using three years’ medical history of Medicare Advantage (MA) members from a top health insurance company. The model takes members’ medical events, both claims and electronic medical record (EMR) data, as input, makes a prediction of CKD3 and calculates the contribution from individual events to the predicted outcome. The model outcome can be easily explained with the clinical evidence identified by the model algorithm. Here are examples: Member A had 36 medical encounters in the past three years: multiple office visits, lab tests and medications. The model predicts member A has a high risk of CKD3 with the following well-contributed clinical events - multiple high ‘Creatinine in Serum or Plasma’ tests and multiple low kidneys functioning ‘Glomerular filtration rate’ tests. Among the abnormal lab tests, more recent results contributed more to the prediction. The model also indicates regular office visits, no abnormal findings of medical examinations, and taking proper medications decreased the CKD3 risk. Member B had 104 medical encounters in the past 3 years and was predicted to have a low risk of CKD3, because the model didn’t identify diagnoses, procedures, or medications related to kidney disease, and many lab test results, including ‘Glomerular filtration rate’ were within the normal range. The model accurately predicts members A and B and provides interpretable clinical evidence that is validated by clinicians. Without extra effort, the interpretation is generated directly from the model and presented together with the occurrence date. Our model uses the medical data in its most raw format without any further data aggregation, transformation, or mapping. This greatly simplifies the data preparation process, mitigates the chance for error and eliminates post-modeling work needed for traditional model explanation. To our knowledge, this is the first paper on an interpretable deep-learning model using a 3-level attention structure, sourcing both EMR and claim data, including all 4 types of medical data, on the entire Medicare population of a big insurance company, and more importantly, directly generating model interpretation to support user decision. In the future, we plan to enrich the model input by adding patients’ demographics and information from free-texted physician notes.

Keywords: deep learning, interpretability, attention, big data, medical conditions

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154 Removing Maturational Influences from Female Youth Swimming: The Application of Corrective Adjustment Procedures

Authors: Clorinda Hogan, Shaun Abbott, Mark Halaki, Marcela Torres Catiglioni, Goshi Yamauchi, Lachlan Mitchell, James Salter, Michael Romann, Stephen Cobley

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Introduction: Common annual age-group competition structures unintentionally introduce participation inequalities, performance (dis)advantages and selection biases due to the effect of maturational variation between youth swimmers. On this basis, there are implications for improving performance evaluation strategies. Therefore the aim was to: (1) To determine maturity timing distributions in female youth swimming; (2) quantify the relationship between maturation status and 100-m FC performance; (3) apply Maturational-based Corrective Adjustment Procedures (Mat-CAPs) for removal of maturational status performance influences. Methods: (1) Cross-sectional analysis of 663 female (10-15 years) swimmers who underwent assessment of anthropometrics (mass, height and sitting height) and estimations of maturity timing and offset. (2) 100-m front-crawl performance (seconds) was assessed at Australian regional, state, and national-level competitions between 2016-2020. To determine the relationship between maturation status and 100-m front-crawl performance, MO was plotted against 100-m FC performance time. The expected maturity status - performance relationship for females aged 10-15 years of age was obtained through a quadratic function (y = ax2 + bx + c) from unstandardized coefficients. The regression equation was subsequently used for Mat-CAPs. (3) Participants aged 10-13 years were categorised into maturity-offset categories. Maturity offset distributions for Raw (‘All’, ‘Top 50%’ & ‘Top 25%’) and Correctively Adjusted swim times were examined. Chi-square, Cramer’s V and ORs determined the occurrence of maturation biases for each age group and selection level. Results—: (1) Maturity timing distributions illustrated overrepresentation of ‘normative’ maturing swimmers (11.82 ± 0.40 years), with a descriptive shift toward the early maturing relative to the normative population. (2) A curvilinear relationship between maturity-offset and swim performance was identified (R2 = 0.53, P < 0.001) and subsequently utilised for Mat-CAPs. (3) Raw maturity offset categories identified partial maturation status skewing towards biologically older swimmers at 10/11 and 12 years, with effect magnitudes increasing in the ‘Top 50%’ and ‘25%’ of performance times. Following Mat-CAPs application, maturity offset biases were removed in similar age groups and selection levels. When adjusting performance times for maturity offset, Mat-CAPs was successful in mitigating against maturational biases until approximately 1-year post Peak Height Velocity. The overrepresentation of ‘normative’ maturing female swimmers contrasted with the substantial overrepresentation of ‘early’ maturing male swimmers found previously in 100-m front-crawl. These findings suggest early maturational timing is not advantageous in females, but findings associated with Aim 2, highlight how advanced maturational status remained beneficial to performance. Observed differences between female and male maturational biases may relate to the differential impact of physiological development during pubertal years. Females experience greater increases of fat mass and potentially differing changes in body shape which can negatively affect swim performance. Conclusions: Transient maturation status-based participation and performance advantages were apparent within a large sample of Australian female youth 100-m FC swimmers. By removing maturity status performance biases within female youth swimming, Mat-CAPs could help improve participation experiences and the accuracy of identifying genuinely skilled female youth swimmers.

Keywords: athlete development, long-term sport participation, performance evaluation, talent identification, youth competition

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