Search results for: development process

Authors: Abdou Elhendy

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Numerous study have shown the efficacy of the percutaneous intervention (PCI) and coronary stenting in improving left ventricular function and relieving exertional angina. Furthermore, PCI remains the main line of therapy in acute myocardial infarction. Improvement of procedural techniques and new devices have resulted in an increased number of PCI in those with difficult and extensive lesions, multivessel disease as well as total occlusion. Immediate and late outcome may be compromised by acute thrombosis or the development of fibro-intimal hyperplasia. In addition, progression of coronary artery disease proximal or distal to the stent as well as in non-stented arteries is not uncommon. As a result, complications can occur, such as acute myocardial infarction, worsened heart failure or recurrence of angina. In a stent, restenosis can occur without symptoms or with atypical complaints rendering the clinical diagnosis difficult. Routine invasive angiography is not appropriate as a follow up tool due to associated risk and cost and the limited functional assessment. Exercise and pharmacologic stress testing are increasingly used to evaluate the myocardial function, perfusion and adequacy of revascularization. Information obtained by these techniques provide important clues regarding presence and severity of compromise in myocardial blood flow. Stress echocardiography can be performed in conjunction with exercise or dobutamine infusion. The diagnostic accuracy has been moderate, but the results provide excellent prognostic stratification. Adding myocardial contrast agents can improve imaging quality and allows assessment of both function and perfusion. Stress radionuclide myocardial perfusion imaging is an alternative to evaluate these patients. The extent and severity of wall motion and perfusion abnormalities observed during exercise or pharmacologic stress are predictors of survival and risk of cardiac events. According to current guidelines, stress echocardiography and radionuclide imaging are considered to have appropriate indication among patients after PCI who have cardiac symptoms and those who underwent incomplete revascularization. Stress testing is not recommended in asymptomatic patients, particularly early after revascularization, Coronary CT angiography is increasingly used and provides high sensitive for the diagnosis of coronary artery stenosis. Average sensitivity and specificity for the diagnosis of in stent stenosis in pooled data are 79% and 81%, respectively. Limitations include blooming artifacts and low feasibility in patients with small stents or thick struts. Anatomical and functional cardiac imaging modalities are corner stone for the assessment of patients after PCI and provide salient diagnostic and prognostic information. Current imaging techniques cans serve as gate keeper for coronary angiography, thus limiting the risk of invasive procedures to those who are likely to benefit from subsequent revascularization. The determination of which modality to apply requires careful identification of merits and limitation of each technique as well as the unique characteristic of each individual patient.

Keywords: coronary artery disease, stress testing, cardiac imaging, restenosis

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Authors: Ola Hall, Ibrahim Wahab, Thorsteinn Rognvaldsson, Mattias Ohlsson

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The subfield of poverty and welfare estimation that applies machine learning tools and methods on satellite imagery is a nascent but rapidly growing one. This is in part driven by the sustainable development goal, whose overarching principle is that no region is left behind. Among other things, this requires that welfare levels can be accurately and rapidly estimated at different spatial scales and resolutions. Conventional tools of household surveys and interviews do not suffice in this regard. While they are useful for gaining a longitudinal understanding of the welfare levels of populations, they do not offer adequate spatial coverage for the accuracy that is needed, nor are their implementation sufficiently swift to gain an accurate insight into people and places. It is this void that satellite imagery fills. Previously, this was near-impossible to implement due to the sheer volume of data that needed processing. Recent advances in machine learning, especially the deep learning subtype, such as deep neural networks, have made this a rapidly growing area of scholarship. Despite their unprecedented levels of performance, such models lack transparency and explainability and thus have seen limited downstream applications as humans generally are apprehensive of techniques that are not inherently interpretable and trustworthy. While several studies have demonstrated the superhuman performance of AI models, none has directly compared the performance of such models and human readers in the domain of poverty studies. In the present study, we directly compare the performance of human readers and a DL model using different resolutions of satellite imagery to estimate the welfare levels of demographic and health survey clusters in Tanzania, using the wealth quintile ratings from the same survey as the ground truth data. The cluster-level imagery covers all 608 cluster locations, of which 428 were classified as rural. The imagery for the human readers was sourced from the Google Maps Platform at an ultra-high resolution of 0.6m per pixel at zoom level 18, while that of the machine learning model was sourced from the comparatively lower resolution Sentinel-2 10m per pixel data for the same cluster locations. Rank correlation coefficients of between 0.31 and 0.32 achieved by the human readers were much lower when compared to those attained by the machine learning model – 0.69-0.79. This superhuman performance by the model is even more significant given that it was trained on the relatively lower 10-meter resolution satellite data while the human readers estimated welfare levels from the higher 0.6m spatial resolution data from which key markers of poverty and slums – roofing and road quality – are discernible. It is important to note, however, that the human readers did not receive any training before ratings, and had this been done, their performance might have improved. The stellar performance of the model also comes with the inevitable shortfall relating to limited transparency and explainability. The findings have significant implications for attaining the objective of the current frontier of deep learning models in this domain of scholarship – eXplainable Artificial Intelligence through a collaborative rather than a comparative framework.

Keywords: poverty prediction, satellite imagery, human readers, machine learning, Tanzania

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Authors: Ja-Keoung Koo, Kensuke Nakamura, Hyohun Kim, Dongwha Shin, Yeonseok Kim, Ji-Su Ahn, Byung-Woo Hong

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The machine learning techniques based on a convolutional neural network (CNN) have been actively developed and successfully applied to a variety of image analysis tasks including reconstruction, noise reduction, resolution enhancement, segmentation, motion estimation, object recognition. The classical visual information processing that ranges from low level tasks to high level ones has been widely developed in the deep learning framework. It is generally considered as a challenging problem to derive visual interpretation from high dimensional imagery data. A CNN is a class of feed-forward artificial neural network that usually consists of deep layers the connections of which are established by a series of non-linear operations. The CNN architecture is known to be shift invariant due to its shared weights and translation invariance characteristics. However, it is often computationally intractable to optimize the network in particular with a large number of convolution layers due to a large number of unknowns to be optimized with respect to the training set that is generally required to be large enough to effectively generalize the model under consideration. It is also necessary to limit the size of convolution kernels due to the computational expense despite of the recent development of effective parallel processing machinery, which leads to the use of the constantly small size of the convolution kernels throughout the deep CNN architecture. However, it is often desired to consider different scales in the analysis of visual features at different layers in the network. Thus, we propose a CNN model where different sizes of the convolution kernels are applied at each layer based on the random projection. We apply random filters with varying sizes and associate the filter responses with scalar weights that correspond to the standard deviation of the random filters. We are allowed to use large number of random filters with the cost of one scalar unknown for each filter. The computational cost in the back-propagation procedure does not increase with the larger size of the filters even though the additional computational cost is required in the computation of convolution in the feed-forward procedure. The use of random kernels with varying sizes allows to effectively analyze image features at multiple scales leading to a better generalization. The robustness and effectiveness of the proposed CNN based on random kernels are demonstrated by numerical experiments where the quantitative comparison of the well-known CNN architectures and our models that simply replace the convolution kernels with the random filters is performed. The experimental results indicate that our model achieves better performance with less number of unknown weights. The proposed algorithm has a high potential in the application of a variety of visual tasks based on the CNN framework. Acknowledgement—This work was supported by the MISP (Ministry of Science and ICT), Korea, under the National Program for Excellence in SW (20170001000011001) supervised by IITP, and NRF-2014R1A2A1A11051941, NRF2017R1A2B4006023.

Keywords: deep learning, convolutional neural network, random kernel, random projection, dimensionality reduction, object recognition

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Authors: Euripides Antoniades

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In 1821 the Greek Revolution movement, under the political influence that arose from the French revolution, and the corresponding movements in Italy, Germany and America, requested the liberation of the nation and the establishment of an independent national state. Published topics in the British press regarding the Greek Revolution, focused on : a) the right of the Greeks to claim their freedom from Turkish domination in order to establish an independent state based on the principle of national autonomy, b) criticism regarding Turkish rule as illegal and the power of the Ottoman Sultan as arbitrary, c) the recognition of the Greek identity and its distinction from the Turkish one and d) the endorsement Greeks as the descendants of ancient Greeks. The advantage of newspaper as a media is sharing information and ideas and dealing with issues in greater depth and detail, unlike other media, such as radio or television. The London Times is a print publication that presents, in chronological or thematic order, the news, opinions or announcements about the most important events that have occurred in a place during a specified period of time. This paper employs the rich archive of The London Times archive by quoting extracts from publications of that period, to convey the British public perspective regarding the Greek Revolution from its beginning until the London Protocol of 1828. Furthermore, analyses the publications of the British newspaper in terms of the number of references to the Greek revolution, front page and editorial references as well as the size of publications on the revolution during the period 1821-1828. A combination of qualitative and quantitative content analysis was applied. An attempt was made to record Greek Revolution references along with the usage of specific words and expressions that contribute to the representation of the historical events and their exposure to the reading public. Key finds of this research reveal that a) there was a frequency of passionate daily articles concerning the events in Greece, their length, and context in The London Times, b) the British public opinion was influenced by this particular newspaper and c) the newspaper published various news about the revolution by adopting the role of animator of the Greek struggle. For instance, war events and the battles of Wallachin and Moldavia, Hydra, Crete, Psara, Mesollogi, Peloponnese were presented not only for informing the readers but for promoting the essential need for freedom and the establishment of an independent Greek state. In fact, this type of news was the main substance of the The London Times’ structure, establishing a positive image about the Greek Revolution contributing to the European diplomatic development such as the standpoint of France, - that did not wish to be detached from the conclusions regarding the English loans and the death of Alexander I of Russia and his succession by the ambitious Nicholas. These factors offered a change in the attitude of the British and Russians respectively assuming a positive approach towards Greece. The Great Powers maintained a neutral position in the Greek-Ottoman conflict, same time they engaged in Greek power increasement by offering aid.

Keywords: Greece, revolution, newspaper, the London times, London, great britain, mass media

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Authors: Bernice Jeanne Lottering, Yi-Wen Lin

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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.

Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception

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Authors: Anna Höfer, Johannes Herrmann, Patrick Meybohm, Christopher Lotz

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Mitochondria are pivotal for energy supply and regulation of cellular functions. Deficiencies of mitochondrial metabolism have been implicated in diverse stressful conditions including infections. Platelets are key mediators for thrombo-inflammation during development and resolution of acute respiratory distress syndrome (ARDS). Previous data point to an exhausted platelet phenotype in critically-ill patients with coronavirus 19 disease (COVID-19) impacting the course of disease. The objective of this work was to characterize platelet mitochondrial metabolism in patients suffering from COVID-19 ARDSA longitudinal analysis of platelet mitochondrial metabolism in 24 patients with COVID-19 induced ARDS compared to 35 healthy controls (ctrl) was performed. Blood samples were analyzed at two time points (t1=day 1; t2=day 5-7 after study inclusion). The activity of mitochondrial citrate synthase was photometrically measured. The impact of oxidative stress on mitochondrial permeability was assessed by a photometric calcium-induced swelling assay and the activity of superoxide dismutase (SOD) by a SOD assay kit. The amount of protein carbonylation and the activity of mitochondria complexes I-IV were photometrically determined. Levels of interleukins (IL)-1α, IL-1β and tumor necrosis factor (TNF-) α were measured by a Multiplex assay kit. Median age was 54 years, 63 % were male and BMI was 29.8 kg/m2. SOFA (12; IQR: 10-15) and APACHE II (27; IQR: 24-30) indicated critical illness. Median Murray Score was 3.4 (IQR: 2.8-3.4), 21/24 (88%) required mechanical ventilation and V-V ECMO support in 14/24 (58%). Platelet counts in ARDS did not change during ICU stay (t1: 212 vs. t2: 209 x109/L). However, mean platelet volume (MPV) significantly increased (t1: 10.6 vs. t2: 11.9 fL; p<0.0001). Citrate synthase activity showed no significant differences between ctrl and ARDS patients. Calcium induced swelling was more pronounced in patients at t1 compared to t2 and to ctrl (50µM; t1: 0.006 vs. ctrl: 0.016 ΔOD; p=0.001). The amount of protein carbonylation as marker for irreversible proteomic modification constantly increased during ICU stay and compared to ctrl., without reaching significance. In parallel, superoxid dismutase activity gradually declined during ICU treatment vs. ctrl (t2: - 29 vs. ctrl.: - 17 %; p=0.0464). Complex I analysis revealed significantly stronger activity in ARDS vs. ctrl. (t1: 0.633 vs. ctrl.: 0.415 ΔOD; p=0.0086). There were no significant differences in complex II, III or IV activity in platelets from ARDS patients compared to ctrl. IL-18 constantly increased during the observation period without reaching significance. IL-1α and TNF-α did not differ from ctrl. However, IL-1β levels were significantly elevated in ARDS (t1: 16.8; t2: 16.6 vs. ctrl.: 12.4 pg/mL; p1=0.0335, p2=0.0032). This study reveals new insights in platelet mitochondrial metabolism during COVID-19 caused ARDS. it data point towards enhanced platelet activity with a pronounced turnover rate. We found increased activity of mitochondria complex I and evidence for enhanced oxidative stress. In parallel, protective mechanisms against oxidative stress were narrowed with elevated levels of IL-1β likely causing a pro-apoptotic environment. These mechanisms may contribute to platelet exhaustion in ARDS.

Keywords: acute respiratory distress syndrome (ARDS), coronavirus 19 disease (COVID-19), oxidative stress, platelet mitochondrial metabolism

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Authors: José Antonio Donaire Benito, Konstantina Zerva

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Historically, cities have been places where people from many nations and cultures have met and settled together, while population flows and density have had a significant impact on urban dynamics. Cities' high density of social, cultural, business offerings, everyday services, and other amenities not intended for tourists draw not only tourists but a wide range of city users as well. With the coordination of city rhythms and the porosity of the community, city users order and frame their urban experience. From one side, recent literature focuses on the shift in urban tourist experience from 'having' a holiday through 'doing' activities to 'becoming' a local by experiencing a part of daily life. On the other hand, there is a debate on the 'touristification of everyday life', where middle and upper class urban dwellers display attitudes and behaviors that are virtually undistinguishable from those of visitors. With the advent of globalization and technological advances, modern society has undergone a radical transformation that has altered mobility patterns within it, blurring the boundaries between tourism and everyday life, work and leisure, and "hosts" and "guests". Additionally, the presence of other 'temporary city' users, such as commuters, digital nomads, second home owners, and migrants, contributes to a more complex transformation of tourist cities. Moving away from this traditional clear distinction between 'hosts' and 'guests', which represents a more static view of tourism, and moving towards a more liquid narrative of mobility, academics on tourism development are embracing the New Mobilities Paradigm. The latter moves beyond the static structures of the modern world and focuses on the ways in which social entities are made up of people, machines, information, and images in a moving system. In light of this fluid interdependence between tourists and guests, a question arises as to whether overtourism, which is considered as the underlying cause of citizens' perception of a lower urban quality of life, is a fair representation of perceived mobility excessiveness, place consumption disruptiveness, and residents displacement. As a representative example of an overtourism narrative, Barcelona was chosen as a study area for this purpose, focusing on the incoming city users to reflect in depth the variety of people who contribute to mobility flows beyond those residents already have. Several statistical data have been analyzed to determine the number of national and international visitors to Barcelona at some point during the day in 2019. Specifically, tracking data gathered from mobile phone users within the city are combined with tourist surveys, urban mobility data, zenithal data capture, and information about the city's attractions. The paper shows that tourists are only a small part of the different incoming city users that daily enter Barcelona; excursionists, commuters, and metropolitans also contribute to a high mobility flow. Based on the diversity of incoming city users and their place consumption, it seems that the city's urban experience is more likely to be impacted by over-mobility tan over-tourism.

Keywords: city users, density, new mobilities paradigm, over-tourism.

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Authors: Noorh Albadi, Salha Khayyat

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People's moods and well-being are affected by their environment. The built environment impacts one's level of activity and health. In order to enhance users' physical health, sustainable design strategies have been developed for the physical environment to improve users' health. This study aimed to determine whether adult resorts in Saudi Arabia meet standards that ensure physical wellness to identify the needed requirements. It will be significant to the Ministry of Tourism, Sports, developers, and designers. Physical activity affects human health physically and mentally. In Saudi Arabia, the percentage of people who practiced sports in the Kingdom in 2019 was 20.04% - males and females older than 15. On the other hand, there is a lack of physical activity in Saudi Arabia; 90% of the Kingdom's population spends more than two hours sitting down without moving, which puts them at risk of contracting a non-communicable disease. The lack of physical activity and movement led to an increase in the rate of obesity among Saudis by 59% in 2020 and consequently could cause chronic diseases or death. The literature generally endorses that leading an active lifestyle improves physical health and affects mental health. Therefore, the United Nations has set 17 sustainable development goals (SDGs) to ensure healthy lives and promote well-being for all ages. One of SDG3's targets is reducing mortality, which can be achieved by raising physical activity. In order to support sustainable design, many rating systems and strategies have been developed, such as WELL building, Leadership in Energy and Environmental Design, (LEED), Active design strategies, and RIPA plan of work. The survey was used to gather qualitative and quantitative information. It was designed based on the Active Design and WELL building theories targeting beach resorts visitors, professional and beginner athletes, and non-athletics to ask them about the beach resorts they visited in the Kingdom and whether they met the criteria of sports resorts and healthy and active design theories, in addition to gathering information about the preferences of physical activities in the Saudi society in terms of the type of activities that young people prefer, where they prefer to engage in and under any thermal and light conditions. The final section asks about the design of residential units in beach sports resorts, the data collected from 127 participants. Findings revealed that participants prefer outdoor activities in moderate weather and sunlight or the evening with moderate and sufficient lighting and that no beach sports resorts in the country are constructed to support sustainable design criteria for physical activity. Participants agreed that several measures that lessen tension at beach resorts and enhance movement and activity are needed by Saudi society. The study recommends designing resorts that meet the sustainable design criteria regarding physical activity in Saudi Arabia to increase physical activity to achieve psychological and physical benefits and avoid psychological and physical diseases related to physical inactivity.

Keywords: sustainable design, SDGs, active design strategies, well building, beach resort design

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Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

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Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

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Authors: Zenaida Chitu, Roxana Bojariu, Liliana Velea, Roxana Burcea

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A number of studies show that extreme air temperature affects mortality related to cardiovascular diseases, particularly among elderly people. In Romania, the summer thermal discomfort expressed by Universal Thermal Climate Index (UTCI) is highest in the Southern part of the country, where Bucharest, the largest Romanian urban agglomeration, is also located. The urban characteristics such as high building density and reduced green areas enhance the increase of the air temperature during summer. In Bucharest, as in many other large cities, the effect of heat urban island is present and determines an increase of air temperature compared to surrounding areas. This increase is particularly important during heat wave periods in summer. In this context, the researchers performed a temperature-mortality analysis based on daily deaths related to cardiovascular diseases, recorded between 2010 and 2019 in Bucharest. The temperature-mortality relationship was modeled by applying distributed lag non-linear model (DLNM) that includes a bi-dimensional cross-basis function and flexible natural cubic spline functions with three internal knots in the 10th, 75th and 90th percentiles of the temperature distribution, for modelling both exposure-response and lagged-response dimensions. Firstly, this study applied this analysis for the present climate. Extrapolation of the exposure-response associations beyond the observed data allowed us to estimate future effects on mortality due to temperature changes under climate change scenarios and specific assumptions. We used future projections of air temperature from five numerical experiments with regional climate models included in the EURO-CORDEX initiative under the relatively moderate (RCP 4.5) and pessimistic (RCP 8.5) concentration scenarios. The results of this analysis show for RCP 8.5 an ensemble-averaged increase with 6.1% of heat-attributable mortality fraction in future in comparison with present climate (2090-2100 vs. 2010-219), corresponding to an increase of 640 deaths/year, while mortality fraction due to the cold conditions will be reduced by 2.76%, corresponding to a decrease by 288 deaths/year. When mortality data is stratified according to the age, the ensemble-averaged increase of heat-attributable mortality fraction for elderly people (> 75 years) in the future is even higher (6.5 %). These findings reveal the necessity to carefully plan urban development in Bucharest to face the public health challenges raised by the climate change. Paper Details: This work is financed by the project URCLIM which is part of ERA4CS, an ERA-NET initiated by JPI Climate, and funded by Ministry of Environment, Romania with co-funding by the European Union (Grant 690462). A part of this work performed by one of the authors has received funding from the European Union’s Horizon 2020 research and innovation programme from the project EXHAUSTION under grant agreement No 820655.

Keywords: cardiovascular diseases, climate change, extreme air temperature, mortality

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Authors: M. Velana, G. Rinkenauer

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Nowadays, nurses are facing unprecedented amounts of pressure due to the ongoing global health demands. Work-related stress can cause a high physical and psychological workload, which can lead, in turn, to burnout. On the physiological level, stress triggers an initial activation of the sympathetic nervous and adrenomedullary systems resulting in increases in cardiac activity. Furthermore, activation of the hypothalamus-pituitary-adrenal axis provokes endocrine and immune changes leading to the release of cortisol and cytokines in an effort to re-establish body balance. Based on the current state of the literature, it has been identified that resilience and mindfulness exercises among nurses can effectively decrease stress and improve mood. However, it is still unknown what relaxation techniques would be suitable for and to what extent would be effective to decrease psychophysiological arousal deriving from either a physiological or a psychological stressor. Moreover, although cardiac activity and cortisol are promising candidates to examine the effectiveness of relaxation to reduce stress, it still remains to shed light on the role of cytokines in this process so as to thoroughly understand the body’s response to stress and to relaxation. Therefore, the main aim of the present study is to develop a comprehensive experimental paradigm and assess different relaxation techniques, namely progressive muscle relaxation and a mindfulness exercise originating from cognitive therapy by means of biofeedback, under highly controlled laboratory conditions. An experimental between-subject design will be employed, where 120 participants will be randomized either to a physiological or a psychological stress-related experiment. Particularly, the cold pressor test refers to a procedure in which the participants have to immerse their non-dominant hands into ice water (2-3 °C) for 3 min. The participants are requested to keep their hands in the water throughout the whole duration. However, they can immediately terminate the test in case it would be barely tolerable. A pre-test anticipation phase and a post-stress period of 3 min, respectively, are planned. The Trier Social Stress Test will be employed to induce psychological stress. During this laboratory stressor, the participants are instructed to give a 5-min speech in front of a committee of communication specialists. Before the main task, there is a 10-min anticipation period. Subsequently, participants are requested to perform an unexpected arithmetic task. After stress exposure, the participants will perform one of the relaxation exercises (treatment condition) or watch a neutral video (control condition). Electrocardiography, salivary samples, and self-report will be collected at different time points. The preliminary results deriving from the pilot study showed that the aforementioned paradigm could effectively induce stress reactions and that relaxation might decrease the impact of stress exposure. It is of utmost importance to assess how the human body responds under different stressors and relaxation exercises so that an evidence-based intervention could be transferred in a clinical setting to improve nurses’ general health. Based on suggestive future laboratory findings, the research group plans to conduct a pilot-level randomized study to decrease stress and promote well-being among nurses who work in the stress-riddled environment of a hospital located in Northern Germany.

Keywords: nurses, psychophysiology, relaxation, stress

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Authors: Ana L. M. Pavan, Guilherme Giacomini, Allan F. F. Alves, Marcela De Oliveira, Fernando A. B. Neto, Maria E. D. Rosa, Andre P. Trindade, Diana R. De Pina

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Mammography is a worldwide image modality used to diagnose breast cancer, even in asymptomatic women. Due to its large availability, mammograms can be used to measure breast density and to predict cancer development. Women with increased mammographic density have a four- to sixfold increase in their risk of developing breast cancer. Therefore, studies have been made to accurately quantify mammographic breast density. In clinical routine, radiologists perform image evaluations through BIRADS (Breast Imaging Reporting and Data System) assessment. However, this method has inter and intraindividual variability. An automatic objective method to measure breast density could relieve radiologist’s workload by providing a first aid opinion. However, pectoral muscle is a high density tissue, with similar characteristics of fibroglandular tissues. It is consequently hard to automatically quantify mammographic breast density. Therefore, a pre-processing is needed to segment the pectoral muscle which may erroneously be quantified as fibroglandular tissue. The aim of this work was to develop an automatic algorithm to segment and extract pectoral muscle in digital mammograms. The database consisted of thirty medio-lateral oblique incidence digital mammography from São Paulo Medical School. This study was developed with ethical approval from the authors’ institutions and national review panels under protocol number 3720-2010. An algorithm was developed, in Matlab® platform, for the pre-processing of images. The algorithm uses image processing tools to automatically segment and extract the pectoral muscle of mammograms. Firstly, it was applied thresholding technique to remove non-biological information from image. Then, the Hough transform is applied, to find the limit of the pectoral muscle, followed by active contour method. Seed of active contour is applied in the limit of pectoral muscle found by Hough transform. An experienced radiologist also manually performed the pectoral muscle segmentation. Both methods, manual and automatic, were compared using the Jaccard index and Bland-Altman statistics. The comparison between manual and the developed automatic method presented a Jaccard similarity coefficient greater than 90% for all analyzed images, showing the efficiency and accuracy of segmentation of the proposed method. The Bland-Altman statistics compared both methods in relation to area (mm²) of segmented pectoral muscle. The statistic showed data within the 95% confidence interval, enhancing the accuracy of segmentation compared to the manual method. Thus, the method proved to be accurate and robust, segmenting rapidly and freely from intra and inter-observer variability. It is concluded that the proposed method may be used reliably to segment pectoral muscle in digital mammography in clinical routine. The segmentation of the pectoral muscle is very important for further quantifications of fibroglandular tissue volume present in the breast.

Keywords: active contour, fibroglandular tissue, hough transform, pectoral muscle

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Authors: Elisabetta Cianfanelli, Maria Claudia Coppola, Margherita Tufarelli

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Design practices throughout history return a critical understanding of society since they always conveyed values and meanings aimed at (re)framing reality by acting in everyday life: here, design gains cultural and normative character, since its artifacts, services, and environments hold the power to intercept, influence and inspire thoughts, behaviors, and relationships. In this sense, design can be persuasive, engaging in the production of worlds and, as such, acting in the space between poietics and politics so that chasing preferable futures and their aesthetic strategies becomes a matter full of political responsibility. This resonates with contemporary landscapes of radical interdependencies challenging designers to focus on complex socio-technical systems and to better support values such as equality and justice for both humans and nonhumans. In fact, it is in times of crisis and structural uncertainty that designers turn into visionaries at the service of society, envisioning scenarios and dwelling in the territories of imagination to conceive new fictions and frictions to be added to the thickness of the real. Here, design’s main tasks are to develop options, to increase the variety of choices, to cultivate its role as scout, jester, agent provocateur for the public, so that design for transformation emerges, making an explicit commitment to society, furthering structural change in a proactive and synergic manner. However, the exploration of possible futures is both a trap and a trampoline because, although it embodies a radical research tool, it raises various challenges when the design process goes further in the translation of such vision into an artefact - whether tangible or intangible -, through which it should deliver that bit of future into everyday experience. Today designers are making up new tools and practices to tackle current wicked challenges, combining their approaches with other disciplinary domains: futuring through design, thus, rises from research strands like speculative design, design fiction, and critical design, where the blending of design approaches and futures thinking brings an action-oriented and product-based approach to strategic insights. The contribution positions at the intersection of those approaches, aiming at discussing design’s tools of inquiry through which it is possible to grasp the agency of imagined futures into present time. Since futures are not remote, they actively participate in creating path-dependent decisions, crystallized into designed artifacts par excellence, prototypes, and their conceptual other, provotypes: with both being unfinished and multifaceted, the first ones are effective in reiterating solutions to problems already framed, while the second ones prove to be useful when the goal is to explore and break boundaries, bringing closer preferable futures. By focusing on some provotypes throughout history which challenged markets and, above all, social and cultural structures, the contribution’s final aim is understanding the knowledge produced by provotypes, understood as design spaces where designs’s humanistic side might help developing a deeper sensibility about uncertainty and, most of all, the unfinished feature of societal artifacts, whose experimentation would leave marks and traces to build up f(r)ictions as vital sparks of plurality and collective life.

Keywords: speculative design, provotypes, design knowledge, political theory

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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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Authors: Maggie Hall, Haley O'Neill

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The U.S. faces a severe shortage of abortion providers, exacerbated by the June 2022 Dobbs v. Jackson Women’s Health Organization decision. Midwives, especially certified nurse midwives, are well-positioned to fill this gap in abortion care. However, a lack of clinical education and training prevents midwives from exercising their full scope of practice. National and international organizations that set obstetrics and midwifery education standards, including the International Confederation of Midwives, American College of Obstetricians and Gynecologists, and American Public Health Association, call for expansion of midwifery-managed abortion care through the first trimester. In the U.S., midwifery programs are accredited based on compliance with ACME standards and compliance is a prerequisite for the American Midwifery Certification Board exams. We conducted a literature review of studies in the last five years regarding abortion didactic and clinical education barriers via CINAHL, EBSCO and PubMed database reviews. We gave preference for primary sources within the last five years; however, due to the rapid changes in abortion education and access, we also included literature from 2012-2022. We evaluated ACME-accredited programs in relation to their geography within abortion-protected or restricted states and assessed state-specific barriers to abortion care education and provision as clinical students. There are 43 AMCB-accredited midwifery schools in 28 states across the U.S. Twenty schools (47%) are in the 15 states in which advanced practice clinicians can provide non-surgical abortion care, such as medication abortion and MVA procedures. Twenty-four schools (56%) are in the 16 states in which abortion care provision is restricted to Licensed Physicians and cannot offer in-state clinical training opportunities for midwifery students. Six schools are in the five states in which abortion is completely banned and are geographically concentrated in the southernmost region of the U.S., including Alabama, Kentucky, Louisiana, Tennessee, and Texas. Subsequently, these programs cannot offer in-state clinical training opportunities for midwifery students. Notably, there are seven ACME programs in six states that do not restrict abortion access by gestational age, including Colorado, Connecticut, Washington, D.C., New Jersey, New Mexico, and Oregon. These programs may be uniquely positioned for midwifery involvement in abortion care beyond the first trimester. While the following states don’t house ACME programs, abortion care can be provided by advanced practice clinicians in Rhode Island, Delaware, Hawaii, Maine, Maryland, Montana, New Hampshire, and Vermont, offering clinical placement and/or new ACME program development opportunities. We identify existing barriers to clinical education and training opportunities for midwifery-managed abortion care, which are both geographic and institutional in nature. We recommend expansion and standardization of clinical education and training opportunities for midwifery-managed abortion care in ACME-accredited programs to improve access to abortion care. Midwifery programs and teaching hospitals need to expand education, training, and residency opportunities for midwifery students to strengthen access to midwife-managed abortion care. ACNM and ACME should re-evaluate accreditation criteria and the implications of ACME programs in states where students are not able to learn abortion care in clinical contexts due to state-specific abortion restrictions.

Keywords: midwifery education, abortion, abortion education, abortion access

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Authors: V. Giacometti, R. Mirabelli, V. Patera, D. Pinci, A. Sarti, A. Sciubba, G. Traini, M. Marafini

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The particle therapy (PT) is a very modern technique of non invasive radiotherapy mainly devoted to the treatment of tumours untreatable with surgery or conventional radiotherapy, because localised closely to organ at risk (OaR). Nowadays, PT is available in about 55 centres in the word and only the 20\% of them are able to treat with carbon ion beam. However, the efficiency of the ion-beam treatments is so impressive that many new centres are in construction. The interest in this powerful technology lies to the main characteristic of PT: the high irradiation precision and conformity of the dose released to the tumour with the simultaneous preservation of the adjacent healthy tissue. However, the beam interactions with the patient produce a large component of secondary particles whose additional dose has to be taken into account during the definition of the treatment planning. Despite, the largest fraction of the dose is released to the tumour volume, a non-negligible amount is deposed in other body regions, mainly due to the scattering and nuclear interactions of the neutrons within the patient body. One of the main concerns in PT treatments is the possible occurrence of secondary malignant neoplasm (SMN). While SMNs can be developed up to decades after the treatments, their incidence impacts directly life quality of the cancer survivors, in particular in pediatric patients. Dedicated Treatment Planning Systems (TPS) are used to predict the normal tissue toxicity including the risk of late complications induced by the additional dose released by secondary neutrons. However, no precise measurement of secondary neutrons flux is available, as well as their energy and angular distributions: an accurate characterization is needed in order to improve TPS and reduce safety margins. The project MONDO (MOnitor for Neutron Dose in hadrOntherapy) is devoted to the construction of a secondary neutron tracker tailored to the characterization of that secondary neutron component. The detector, based on the tracking of the recoil protons produced in double-elastic scattering interactions, is a matrix of thin scintillating fibres, arranged in layer x-y oriented. The final size of the object is 10 x 10 x 20 cm3 (squared 250µm scint. fibres, double cladding). The readout of the fibres is carried out with a dedicated SPAD Array Sensor (SBAM) realised in CMOS technology by FBK (Fondazione Bruno Kessler). The detector is under development as well as the SBAM sensor and it is expected to be fully constructed for the end of the year. MONDO will make data tacking campaigns at the TIFPA Proton Therapy Center of Trento, at the CNAO (Pavia) and at HIT (Heidelberg) with carbon ion in order to characterize the neutron component and predict the additional dose delivered on the patients with much more precision and to drastically reduce the actual safety margins. Preliminary measurements with charged particles beams and MonteCarlo FLUKA simulation will be presented.

Keywords: secondary neutrons, particle therapy, tracking detector, elastic scattering

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Authors: Davit Pipoyan, Meline Beglaryan, Nicolò Merendino

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Mining industry is one of the priority sectors of Armenian economy. Along with the solution of some socio-economic development, it brings about numerous environmental problems, especially toxic element pollution, which largely influences the safety of agricultural products. In addition, accumulation of toxic elements in agricultural products, mainly in edible parts of plants represents a direct pathway for their penetration into the human food chain. In Armenia, the share of plant origin food in overall diet is significantly high, so estimation of dietary intakes of toxic trace elements via consumption of selected fruits and vegetables are of great importance for observing the underlying health risks. Therefore, the present study was aimed to assess dietary exposure of potentially toxic trace elements through the intake of locally grown fruits and vegetables in Akhtala community (Armenia), where not only mining industry is developed, but also cultivation of fruits and vegetables. Moreover, this investigation represents one of the very first attempts to estimate human dietary exposure of potentially toxic trace elements in the study area. Samples of some commonly grown fruits and vegetables (fig, cornel, raspberry, grape, apple, plum, maize, bean, potato, cucumber, onion, greens) were randomly collected from several home gardens located near mining areas in Akhtala community. The concentration of Cu, Mo, Ni, Cr, Pb, Zn, Hg, As and Cd in samples were determined by using an atomic absorption spectrophotometer (AAS). Precision and accuracy of analyses were guaranteed by repeated analysis of samples against NIST Standard Reference Materials. For a diet study, individual-based approach was used, so the consumption of selected fruits and vegetables was investigated through food frequency questionnaire (FFQ). Combining concentration data with contamination data, the estimated daily intakes (EDI) and cumulative daily intakes were assessed and compared with health-based guidance values (HBGVs). According to the determined concentrations of the studied trace elements in fruits and vegetables, it can be stressed that some trace elements (Cu, Ni, Pb, Zn) among the majority of samples exceeded maximum allowable limits set by international organizations. Meanwhile, others (Cr, Hg, As, Cd, Mo) either did not exceed these limits or still do not have established allowable limits. The obtained results indicated that only for Cu the EDI values exceeded dietary reference intake (0.01 mg/kg/Bw/day) for some investigated fruits and vegetables in decreasing order of potato > grape > bean > raspberry > fig > greens. In contrast to this, for combined consumption of selected fruits and vegetables estimated cumulative daily intakes exceeded reference doses in the following sequence: Zn > Cu > Ni > Mo > Pb. It may be concluded that habitual and combined consumption of the above mentioned fruits and vegetables can pose a health risk to the local population. Hence, further detailed studies are needed for the overall assessment of potential health implications taking into consideration adverse health effects posed by more than one toxic trace element.

Keywords: daily intake, dietary exposure, fruits, trace elements, vegetables

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Authors: Milos Travar, Jovana Nikolov, Andrej Vranicar, Natasa Todorovic

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Over the years, High Purity Germanium (HPGe) detectors proved to be an excellent practical tool and, as such, have established their today's wide use in low background γ-spectrometry. One of the advantages of gamma-ray spectrometry is its easy sample preparation as chemical processing and separation of the studied subject are not required. Thus, with a single measurement, one can simultaneously perform both qualitative and quantitative analysis. One of the most prominent features of HPGe detectors, besides their excellent efficiency, is their superior resolution. This feature virtually allows a researcher to perform a thorough analysis by discriminating photons of similar energies in the studied spectra where otherwise they would superimpose within a single-energy peak and, as such, could potentially scathe analysis and produce wrongly assessed results. Naturally, this feature is of great importance when the identification of radionuclides, as well as their activity concentrations, is being practiced where high precision comes as a necessity. In measurements of this nature, in order to be able to reproduce good and trustworthy results, one has to have initially performed an adequate full-energy peak (FEP) efficiency calibration of the used equipment. However, experimental determination of the response, i.e., efficiency curves for a given detector-sample configuration and its geometry, is not always easy and requires a certain set of reference calibration sources in order to account for and cover broader energy ranges of interest. With the goal of overcoming these difficulties, a lot of researches turned towards the application of different software toolkits that implement the Monte Carlo method (e.g., MCNP, FLUKA, PENELOPE, Geant4, etc.), as it has proven time and time again to be a very powerful tool. In the process of creating a reliable model, one has to have well-established and described specifications of the detector. Unfortunately, the documentation that manufacturers provide alongside the equipment is rarely sufficient enough for this purpose. Furthermore, certain parameters tend to evolve and change over time, especially with older equipment. Deterioration of these parameters consequently decreases the active volume of the crystal and can thus affect the efficiencies by a large margin if they are not properly taken into account. In this study, the optimisation method of two HPGe detectors through the implementation of the Geant4 toolkit developed by CERN is described, with the goal of further improving simulation accuracy in calculations of FEP efficiencies by investigating the influence of certain detector variables (e.g., crystal-to-window distance, dead layer thicknesses, inner crystal’s void dimensions, etc.). Detectors on which the optimisation procedures were carried out were a standard traditional co-axial extended range detector (XtRa HPGe, CANBERRA) and a broad energy range planar detector (BEGe, CANBERRA). Optimised models were verified through comparison with experimentally obtained data from measurements of a set of point-like radioactive sources. Acquired results of both detectors displayed good agreement with experimental data that falls under an average statistical uncertainty of ∼ 4.6% for XtRa and ∼ 1.8% for BEGe detector within the energy range of 59.4−1836.1 [keV] and 59.4−1212.9 [keV], respectively.

Keywords: HPGe detector, γ spectrometry, efficiency, Geant4 simulation, Monte Carlo method

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Authors: Priya Nangia, Sanchita Bansal

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As fashion cycles become more rapid, some segments of the fashion industry have adopted increasingly unsustainable production processes to keep up with demand and enhance profit margins. The growing threat to environmental and social wellbeing posed by unethical fast fashion practices and the need to integrate the targets of SDGs into this industry necessitates a shift in the fashion industry's unsustainable nature, which can only be accomplished in the long run if consumers support sustainable fashion by purchasing it. Fast fashion is defined as low-cost, trendy apparel that takes inspiration from the catwalk or celebrity culture and rapidly transforms it into garments at high-street stores to meet consumer demand. Given the importance of identity formation to many consumers, the desire to be “fashionable” often outweighs the desire to be ethical or sustainable. This paradox exemplifies the tension between the human drive to consume and the will to do so in moderation. Previous research suggests that there is an attitude-behavior gap when it comes to determining consumer purchasing behavior, but to the best of our knowledge, no study has analysed how to encourage customers to shift from fast to slow fashion. Against this backdrop, the aim of this study is twofold: first, to identify and examine the factors that impact consumers' decisions to engage in sustainable fashion, and second, the authors develop a comprehensive framework for conceptualizing and encouraging researchers and practitioners to foster sustainable consumer behavior. This study used a systematic approach to collect data and analyse literature. The approach included three key steps: review planning, review execution, and findings reporting. Authors identified the keywords “sustainable consumption” and “sustainable fashion” and retrieved studies from the Web of Science (WoS) (126 records) and Scopus database (449 records). To make the study more specific, the authors refined the subject area to management, business, and economics in the second step, retrieving 265 records. In the third step, the authors removed the duplicate records and manually reviewed the articles to examine their relevance to the research issue. The final 96 research articles were used to develop this study's systematic scheme. The findings indicate that societal norms, demographics, positive emotions, self-efficacy, and awareness all have an effect on customers' decisions to purchase sustainable apparel. The authors propose a framework, denoted by the acronym SHIFT, in which consumers are more likely to engage in sustainable behaviors when the message or context leverages the following factors: (s)social influence, (h)habit formation, (i)individual self, (f)feelings, emotions, and cognition, and (t)tangibility. Furthermore, the authors identify five broad challenges that encourage sustainable consumer behavior and use them to develop novel propositions. Finally, the authors discuss how the SHIFT framework can be used in practice to drive sustainable consumer behaviors. This research sought to define the boundaries of existing research while also providing new perspectives on future research, with the goal of being useful for the development and discovery of new fields of study, thereby expanding knowledge.

Keywords: consumer behavior, fast fashion, sustainable consumption, sustainable fashion, systematic literature review

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Authors: Abdul Wohab

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Context: The role of religion in the transformation of Bangladesh society has been significant since 1975. There has been a rise in religious presence, particularly Islam, in both private and public spheres supported by the state apparatuses. In 2009, a 'secular' political party came into power for the second time since independence and initiated the modernization of religious education systems. This research focuses on the transformation observed among the educated middle class who now prefer their children to attend modern, English medium madrasas that offer both religion-based and secular education. Research Aim: This research aims to investigate two main questions: a) what motivates the educated middle class to send their children to madrasa education? b) To what extent can it be argued that Bangladeshi society is transforming from its secular nature to being more religious?Methodology: The research applies a combination of primary and secondary methods. Case studies serve as the primary method, allowing for an in-depth exploration of the motivations of the educated middle class. The secondary method involves analyzing published news articles, op-eds, and websites related to madrasa education, as well as studying the reading syllabus of Aliya and Qwami madrasas in Bangladesh. Findings: Preliminary findings indicate that the educated middle class chooses madrasa education for reasons such as remembering and praying for their departed relatives, keeping their children away from substance abuse, fostering moral and ethical values, and instilling respect for seniors and relatives. The research also reveals that religious education is believed to help children remain morally correct according to the Quran and Hadith. Additionally, the establishment of madrasas in Bangladesh is attributed to economic factors, with demand and supply mechanisms playing a significant role. Furthermore, the findings suggest that government-run primary education institutions in rural areas face more challenges in enrollment compared to religious educational institutions like madrasas. Theoretical Importance: This research contributes to the understanding of societal transformation and the role of religion in this process. By examining the case of Bangladesh, it provides insights into how religion influences education choices and societal values. Data Collection and Analysis Procedures: Data for this research is collected through case studies, including interviews and observations of educated middle-class families who send their children to madrasas. In addition, analysis is conducted on relevant published materials such as news articles, op-eds, and websites. The reading syllabus of Aliya and Qwami madrasas is also analyzed to gain a comprehensive understanding of the education system. Questions Addressed: The research addresses two questions: a) what motivates the educated middle class to choose madrasa education for their children? b) To what extent can it be argued that Bangladeshi society is transforming from its secular nature to being more religious?Conclusion: The preliminary findings of this research highlight the motivations of the educated middle class in opting for madrasa education, including the desire to maintain religious traditions, promote moral values, and provide a strong foundation for their children. It also suggests that Bangladeshi society is experiencing a transformation towards a more religious orientation. This research contributes to the understanding of societal changes and the role of religion within Bangladesh, shedding light on the complex dynamics between religion and education.

Keywords: madrasa education, transformation, Bangladesh, religion and society, education

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Authors: Jan C. Droste, Justine Burns, Nithin Narayan

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Introduction: Life-threatening detrimental effects of inappropriate adrenaline (epinephrine) administration, e.g., by giving the wrong dose, in the context of anaphylaxis management is well documented in the medical literature. Half of the fatal anaphylactic reactions in the UK are iatrogenic, and the median time to a cardio-respiratory arrest can be as short as 5 minutes. It is therefore imperative that hospital doctors of all grades have active and accurate knowledge of the correct route, site, and dosage of administration of adrenaline. Given this time constraint and the potential fatal outcome with inappropriate management of anaphylaxis, it is alarming that surveys over the last 15 years have repeatedly shown only a minority of doctors to have accurate knowledge of adrenaline administration as recommended by the UK Resuscitation Council guidelines (2008 updated 2012). This comparison of survey results of the medical workforce over several years in a small NHS District General Hospital was conducted in order to establish the effect of the employment of multiple educational methods regarding adrenaline administration in anaphylaxis in adults. Methods: Between 2010 and 2017, several education methods and tools were used to repeatedly inform the medical workforce (doctors and advanced clinical practitioners) in a single district general hospital regarding the treatment of anaphylaxis in adults. Whilst the senior staff remained largely the same cohort, junior staff had changed fully in every survey. Examples included: (i) Formal teaching -in Grand Rounds; during the junior doctors’ induction process; advanced life support courses (ii) In-situ simulation training performed by the clinical skills simulation team –several ad hoc sessions and one 3-day event in 2017 visiting 16 separate clinical areas performing an acute anaphylaxis scenario using actors- around 100 individuals from multi-disciplinary teams were involved (iii) Hospital-wide distribution of the simulation event via the Trust’s Simulation Newsletter (iv) Laminated algorithms were attached to the 'crash trolleys' (v) A short email 'alert' was sent to all medical staff 3 weeks prior to the survey detailing the emergency treatment of anaphylaxis (vi) In addition, the performance of the surveys themselves represented a teaching opportunity when gaps in knowledge could be addressed. Face to face surveys were carried out in 2010 ('pre-intervention), 2015, and 2017, in the latter two occasions including advanced clinical practitioners (ACP). All surveys consisted of convenience samples. If verbal consent to conduct the survey was obtained, the medical practitioners' answers were recorded immediately on a data collection sheet. Results: There was a sustained improvement in the knowledge of the medical workforce from 2010 to 2017: Answers improved regarding correct drug by 11% (84%, 95%, and 95%); the correct route by 20% (76%, 90%, and 96%); correct site by 40% (43%, 83%, and 83%) and the correct dose by 45% (27%, 54%, and 72%). Overall, knowledge of all components -correct drug, route, site, and dose-improved from 13% in 2010 to 62% in 2017. Conclusion: This survey comparison shows knowledge of the medical workforce regarding adrenaline administration for treatment of anaphylaxis in adults can be considerably improved by employing a variety of educational methods.

Keywords: adrenaline, anaphylaxis, epinephrine, medical education, patient safety

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Authors: Shilpi Bora, Abhirup Chatterjee, Debkumar Chakrabarti

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Organizations of all the sectors around the world are increasingly revisiting their workplace strategies with due concern for women working therein. Limited office space and rigid work arrangements contribute to lesser job satisfaction and greater work impoundments for any organization. Flexible workspace strategies are indispensable to accommodate the progressive rise of modular workstations and involvement of women. Today’s generation of employees deserves malleable office environments with employee-friendly job conditions and strategies. The workplace nowadays stands on rapid organizational changes in progressive and flexible work culture. Occupational well-being practices need to keep pace with the rapid changes in office-based work. Working at the office (workspace) with awkward postures or for long periods can cause pain, discomfort, and injury. The world is stirring towards the era of globalization and progress. The 4000 women police personnel constitute less than one per cent of the total police strength of India. Lots of innovative fields are growing fast, and it is important that we should accommodate women in those arenas. The timeworn trends should be set apart to set out for fresh opportunities and possibilities of development and success through more involvement of women in the workplace. The notion of women policing is gaining position throughout the world, and various countries are putting solemn efforts to mainstream women in policing. As the role of women policing in a society is budding, and thus it is also notable that the accessibility of women at general police stations should be considered. Accordingly, the impact of workspace at police station on the employee productivity has been widely deliberated as a crucial contributor to employee satisfaction leading to better functional motivation. Thus the present research aimed to look into the office workstation design of police station with reference to womanhood specific issues to uplift occupational wellbeing of the policewomen. Personal interview and individual responses collected through administering to a subjective assessment questionnaire on thirty women police as well as to have their views on these issues by purposive non-probability sampling of women police personnel of different ranks posted in Guwahati, Assam, India. Scrutiny of the collected data revealed that office design has a substantial impact on the policewomen job satisfaction in the police station. In this study, the workspace was designed in such a way that the set of factors would impact on the individual to ensure increased productivity. Office design such as furniture, noise, temperature, lighting and spatial arrangement were considered. The primary feature which affected the productivity of policewomen was the furniture used in the workspace, which was found to disturb the everyday and overall productivity of policewomen. Therefore, it was recommended to have proper and adequate ergonomics design intervention to improve the office design for better performance. This type of study is today’s need-of-the-hour to empower women and facilitate their inner talent to come up in service of the nation. The office workspace design also finds critical importance at several other occupations also – where office workstation needs further improvement.

Keywords: office workspace design, policewomen, womanhood concerns at workspace, occupational wellbeing

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Authors: Petra Hypšová, Martin Seitl

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One of the challenges of forensic psychology is to detect deception during a face-to-face interview. In addition to the classical approaches of monitoring the utterance and its components, detection is also sought by observing behavioral and physiological changes that occur as a result of the increased emotional and cognitive load caused by the production of distorted information. Typical are changes in facial temperature, eye movements and their fixation, pupil dilation, emotional micro-expression, heart rate and its variability. Expanding technological capabilities have opened the space to detect these psychophysiological changes and behavioral manifestations through non-contact technologies that do not interfere with face-to-face interaction. Non-contact deception detection methodology is still in development, and there is a lack of studies that combine multiple non-contact technologies to investigate their accuracy, as well as studies that show how different types of lies produced by different interviewers affect physiological and behavioral changes. The main objective of this study is to apply a specific non-contact technology for deception detection. The next objective is to investigate scenarios in which non-contact deception detection is possible. A series of psychophysiological experiments using infrared thermal imaging, eye tracking and behavioral analysis with FaceReader 9.0 software was used to achieve our goals. In the laboratory experiment, 16 adults (12 women, 4 men) between 18 and 35 years of age (SD = 4.42) were instructed to produce alternating prepared and spontaneous truths and lies. The baseline of each proband was also measured, and its results were compared to the experimental conditions. Because the personality of the examiner (particularly gender and facial appearance) to whom the subject is lying can influence physiological and behavioral changes, the experiment included four different interviewers. The interviewer was represented by a photograph of a face that met the required parameters in terms of gender and facial appearance (i.e., interviewer likability/antipathy) to follow standardized procedures. The subject provided all information to the simulated interviewer. During follow-up analyzes, facial temperature (main ROIs: forehead, cheeks, the tip of the nose, chin, and corners of the eyes), heart rate, emotional expression, intensity and fixation of eye movements and pupil dilation were observed. The results showed that the variables studied varied with respect to the production of prepared truths and lies versus the production of spontaneous truths and lies, as well as the variability of the simulated interviewer. The results also supported the assumption of variability in physiological and behavioural values during the subject's resting state, the so-called baseline, and the production of prepared and spontaneous truths and lies. A series of psychophysiological experiments provided evidence of variability in the areas of interest in the production of truths and lies to different interviewers. The combination of technologies used also led to a comprehensive assessment of the physiological and behavioral changes associated with false and true statements. The study presented here opens the space for further research in the field of lie detection with non-contact technologies.

Keywords: emotional expression decoding, eye-tracking, functional infrared thermal imaging, non-contact deception detection, psychophysiological experiment

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Authors: Wanchalerm Patanacharoenwong, Panaya Sudta, Prachya Bumrungkun

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The paper focuses on the development of a system that combines Internet of Things (IoT) technologies and deep learning algorithms for anomaly detection in residential Electric Vehicle (EV) charging in smart cities. With the increasing number of EVs, ensuring efficient and reliable charging systems has become crucial. The aim of this research is to develop an integrated IoT and deep learning system for detecting anomalies in residential EV charging and enhancing EV load profiling and event detection in smart cities. This approach utilizes IoT devices equipped with infrared cameras to collect thermal images and household EV charging profiles from the database of Thailand utility, subsequently transmitting this data to a cloud database for comprehensive analysis. The methodology includes the use of advanced deep learning techniques such as Recurrent Neural Networks (RNN) and Long Short-Term Memory (LSTM) algorithms. IoT devices equipped with infrared cameras are used to collect thermal images and EV charging profiles. The data is transmitted to a cloud database for comprehensive analysis. The researchers also utilize feature-based Gaussian mixture models for EV load profiling and event detection. Moreover, the research findings demonstrate the effectiveness of the developed system in detecting anomalies and critical profiles in EV charging behavior. The system provides timely alarms to users regarding potential issues and categorizes the severity of detected problems based on a health index for each charging device. The system also outperforms existing models in event detection accuracy. This research contributes to the field by showcasing the potential of integrating IoT and deep learning techniques in managing residential EV charging in smart cities. The system ensures operational safety and efficiency while also promoting sustainable energy management. The data is collected using IoT devices equipped with infrared cameras and is stored in a cloud database for analysis. The collected data is then analyzed using RNN, LSTM, and feature-based Gaussian mixture models. The approach includes both EV load profiling and event detection, utilizing a feature-based Gaussian mixture model. This comprehensive method aids in identifying unique power consumption patterns among EV owners and outperforms existing models in event detection accuracy. In summary, the research concludes that integrating IoT and deep learning techniques can effectively detect anomalies in residential EV charging and enhance EV load profiling and event detection accuracy. The developed system ensures operational safety and efficiency, contributing to sustainable energy management in smart cities.

Keywords: cloud computing framework, recurrent neural networks, long short-term memory, Iot, EV charging, smart grids

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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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Authors: Alemayehu Hailemicael Mezgebe, A. J. Solomon Raju

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Context: Lake Chamo is a significant lake in the Ethiopian Rift Valley, known for its diversity of wildlife and vegetation. However, the lake is facing various threats due to human activities and global effects. The poor management of resources could lead to food insecurity, ecological degradation, and loss of biodiversity. Research Aim: The aim of this study is to analyze the environmental implications of lake level changes using GIS and remote sensing. The research also aims to examine the floristic composition of the lakeside vegetation and propose spatially oriented environmental planning for the sustainable utilization of the biodiversity resources. Methodology: The study utilizes multi-temporal satellite images and aerial photographs to analyze the changes in the lake area over the past 45 years. Geospatial analysis techniques are employed to assess land use and land cover changes and change detection matrix. The composition and role of the lakeside vegetation in the ecological and hydrological functions are also examined. Findings: The analysis reveals that the lake has shrunk by 14.42% over the years, with significant modifications to its upstream segment. The study identifies various threats to the lake-wetland ecosystem, including changes in water chemistry, overfishing, and poor waste management. The study also highlights the impact of human activities on the lake's limnology, with an increase in conductivity, salinity, and alkalinity. Floristic composition analysis of the lake-wetland ecosystem showed definite pattern of the vegetation distribution. The vegetation composition can be generally categorized into three belts namely, the herbaceous belt, the legume belt and the bush-shrub-small trees belt. The vegetation belts collectively act as different-sized sieve screen system and calm down the pace of incoming foreign matter. This stratified vegetation provides vital information to decide the management interventions for the sustainability of lake-wetland ecosystem.Theoretical Importance: The study contributes to the understanding of the environmental changes and threats faced by Lake Chamo. It provides insights into the impact of human activities on the lake-wetland ecosystem and emphasizes the need for sustainable resource management. Data Collection and Analysis Procedures: The study utilizes aerial photographs, satellite imagery, and field observations to collect data. Geospatial analysis techniques are employed to process and analyze the data, including land use/land cover changes and change detection matrices. Floristic composition analysis is conducted to assess the vegetation patterns Question Addressed: The study addresses the question of how lake level changes and human activities impact the environmental health and biodiversity of Lake Chamo. It also explores the potential opportunities and threats related to water utilization and waste management. Conclusion: The study recommends the implementation of spatially oriented environmental planning to ensure the sustainable utilization and maintenance of Lake Chamo's biodiversity resources. It emphasizes the need for proper waste management, improved irrigation facilities, and a buffer zone with specific vegetation patterns to restore and protect the lake outskirt.

Keywords: buffer zone, geo-spatial, lake chamo, lake level changes, sustainable utilization

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Authors: Shiv Kumar

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In the shifting scenario of postmodern age that foregrounds the multiplicity of meanings and discourses, the present research article seeks to investigate various paradigm shift of contemporary performances concerning Haryanvi Saangs, so-called folk plays, which are being performed widely in the regional territory of Haryana, a northern state of India. Folk arts cannot be studied efficiently by using the tools of literary criticism because it differs from the literature in many aspects. One of the most essential differences is that literary works invariably have an author. Folk works, on the contrary, never have an author. The situation is quite clear: either we acknowledge the presence of folk art as a phenomenon in the social and cultural history of people, or we do not acknowledge it and argue it is a poetical or art of fiction. This paper is an effort to understand the performative tradition of Saang which is traditionally known as Saang, Swang or Svang became a popular source for instruction and entertainment in the region and neighbouring states. Scholars and critics have long been debating about the origin of the word swang/svang/saang and their relationship to the Sanskrit word –Sangit, which means singing and music. But in the cultural context of Haryana, the word Saang means ‘to impersonate’ or ‘to imitate’ or ‘to copy someone or something’. The stories they portray are derived for the most part from the same myths, tales, epics and from the lives of Indian religious and folk heroes. Literally, the use of poetic sense, the implication of prose style and elaborate figurative technique are worthwhile to compile the productivity of a performance. All use music and song as an integral part of the performance so that it is also appropriate to call them folk opera. These folk plays are performed strictly by aboriginal people in the state. These people, sometimes denominated as Saangi, possess a culture distinct from the rest of Indian folk performances. The concerned form is also known with various other names like Manch, Khayal, Opera, Nautanki. The group of such folk plays can be seen as a dynamic activity and performed in the open space of the theatre. Nowadays, producers contributed greatly in order to create a rapidly growing musical outlet for budding new style of folk presentation and give rise to the electronic focus genre utilizing many musicians and performers who had to become precursors of the folk tradition in the region. Moreover, the paper proposes to examine available sources relative to this article, and it is believed to draw some different conclusions. For instance, to be a spectator of ongoing performances will contribute to providing enough guidance to move forward on this root. In this connection, the paper focuses critically upon the major performative aspects of Haryanvi Saang in relation to several inquiries such as the study of these plays in the context of Indian literary scenario, gender visualization and their dramatic representation, a song-music tradition in folk creativity and development of Haryanvi dramatic art in the contemporary socio-political background.

Keywords: folk play, indigenous, performance, Saang, tradition

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Authors: Rowshan Mamtaz, Shuvo Ahmed, Imran Noor, Sumaiya Rahman, Prithvi Shams, Fahmida Gulshan

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Last few decades have witnessed a phenomenal rise in the use of electrical and electronic equipment globally in our everyday life. As these items reach the end of their lifecycle, they turn into e-wastes and contribute to the waste stream. Bangladesh, in conformity with the global trend and due to its ongoing rapid growth, is also using electronics-based appliances and equipment at an increasing rate. This has caused a corresponding increase in the generation of e-wastes. Bangladesh is a developing country; its overall waste management system, is not yet efficient, nor is it environmentally sustainable. Most of its solid wastes are disposed of in a crude way at dumping sites. Addition of e-wastes, which often contain toxic heavy metals, into its waste stream has made the situation more difficult and challenging. Assessment of generation of e-wastes is an important step towards addressing the challenges posed by e-wastes, setting targets, and identifying the best practices for their management. Understanding and proper management of e-wastes is a stated item of the Sustainable Development Goals (SDG) campaign, and Bangladesh is committed to fulfilling it. A better understanding and availability of reliable baseline data on e-wastes will help in preventing illegal dumping, promote recycling, and create jobs in the recycling sectors and thus facilitate sustainable e-waste management. With this objective in mind, the present study has attempted to estimate the amount of e-wastes and its future generation trend in Bangladesh. To achieve this, sales data on eight selected electrical and electronic products (TV, Refrigerator, Fan, Mobile phone, Computer, IT equipment, CFL (Compact Fluorescent Lamp) bulbs, and Air Conditioner) have been collected from different sources. Primary and secondary data on the collection, recycling, and disposal of the e-wastes have also been gathered by questionnaire survey, field visits, interviews, and formal and informal meetings with the stakeholders. Material Flow Analysis (MFA) method has been applied, and mathematical models have been developed in the present study to estimate e-waste amounts and their future trends up to the year 2035 for the eight selected electrical and electronic equipment. End of life (EOL) method is adopted in the estimation. Model inputs are products’ annual sale/import data, past and future sales data, and average life span. From the model outputs, it is estimated that the generation of e-wastes in Bangladesh in 2018 is 0.40 million tons and by 2035 the amount will be 4.62 million tons with an average annual growth rate of 20%. Among the eight selected products, the number of e-wastes generated from seven products are increasing whereas only one product, CFL bulb, showed a decreasing trend of waste generation. The average growth rate of e-waste from TV sets is the highest (28%) while those from Fans and IT equipment are the lowest (11%). Field surveys conducted in the e-waste recycling sector also revealed that every year around 0.0133 million tons of e-wastes enter into the recycling business in Bangladesh which may increase in the near future.

Keywords: Bangladesh, end of life, e-waste, material flow analysis

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Authors: Su Mon Saw, Joe Rothnagel

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Short open reading frames (sORFs) located in 5’UTR of mRNAs are known as uORFs. Characterization of uORF-encoded peptides (uPEPs) i.e., a subset of short open reading frame encoded peptides (sPEPs) and their translation regulation lead to understanding of causes of genetic disease, proteome complexity and development of treatments. Existence of uORFs within cellular proteome could be detected by LC-MS/MS. The ability of uORF to be translated into uPEP and achievement of uPEP identification will allow uPEP’s characterization, structures, functions, subcellular localization, evolutionary maintenance (conservation in human and other species) and abundance in cells. It is hypothesized that a subset of sORFs are translatable and that their encoded sPEPs are functional and are endogenously expressed contributing to the eukaryotic cellular proteome complexity. This project aimed to investigate whether sORFs encode functional peptides. Liquid chromatography-mass spectrometry (LC-MS) and bioinformatics were thus employed. Due to probable low abundance of sPEPs and small in sizes, the need for efficient peptide enrichment strategies for enriching small proteins and depleting the sub-proteome of large and abundant proteins is crucial for identifying sPEPs. Low molecular weight proteins were extracted using SDS-PAGE from Human Embryonic Kidney (HEK293) cells and Strong Cation Exchange Chromatography (SCX) from secreted HEK293 cells. Extracted proteins were digested by trypsin to peptides, which were detected by LC-MS/MS. The MS/MS data obtained was searched against Swiss-Prot using MASCOT version 2.4 to filter out known proteins, and all unmatched spectra were re-searched against human RefSeq database. ProteinPilot v5.0.1 was used to identify sPEPs by searching against human RefSeq, Vanderperre and Human Alternative Open Reading Frame (HaltORF) databases. Potential sPEPs were analyzed by bioinformatics. Since SDS PAGE electrophoresis could not separate proteins <20kDa, this could not identify sPEPs. All MASCOT-identified peptide fragments were parts of main open reading frame (mORF) by ORF Finder search and blastp search. No sPEP was detected and existence of sPEPs could not be identified in this study. 13 translated sORFs in HEK293 cells by mass spectrometry in previous studies were characterized by bioinformatics. Identified sPEPs from previous studies were <100 amino acids and <15 kDa. Bioinformatics results showed that sORFs are translated to sPEPs and contribute to proteome complexity. uPEP translated from uORF of SLC35A4 was strongly conserved in human and mouse while uPEP translated from uORF of MKKS was strongly conserved in human and Rhesus monkey. Cross-species conserved uORFs in association with protein translation strongly suggest evolutionary maintenance of coding sequence and indicate probable functional expression of peptides encoded within these uORFs. Translation of sORFs was confirmed by mass spectrometry and sPEPs were characterized with bioinformatics.

Keywords: bioinformatics, HEK293 cells, liquid chromatography-mass spectrometry, ProteinPilot, Strong Cation Exchange Chromatography, SDS-PAGE, sPEPs

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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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