Search results for: local coronary artery disease

Authors: Emily Moskwa, Delene Weber, Jacob Arnold, Guy M. Robinson, Douglas K. Bardsley

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Management strategies to reduce the risks to human life and property from wildfire are key contemporary concerns, with a growing literature exploring these issues from a social research perspective. Efforts range from narrowly focused examinations, such as comparing the level of community support for vegetation clearance with that of controlled burning, to broader considerations of what constitutes effective fire management policy and education campaigns. However, little analysis is available that integrates the social component of risk mitigation and the influence of educational materials with the biodiversity conservation strategies so often needed in fire-prone ecosystems found on the periphery of urban areas. Indeed many communities living on the fringe of Australian cities face major issues relating to an increased risk of wildfire events and a decline in local biodiversity. Inadequate policy and planning, and a lack of awareness or information, exacerbate this risk. This has brought forward an emerging governance challenge that requires the mitigation of wildfire risk while simultaneously supporting improved conservation practices in these urban-fringe areas. Focusing on the perceptions and experiences of residents of the Lower Eyre Peninsula in South Australia, this study analyses data collected from a series of semi-structured interviews with landholders (n=20) living in rural and urban-fringe areas surrounding the city of Port Lincoln, a city with a growing population and one that has faced a number of very large fires in recent years. In South Australia, new policies have assigned increased responsibility on individual landholders to manage their land and prepare themselves for a wildfire event, potentially to the detriment of the surrounding native vegetation. Our findings indicate the value of gaining a more nuanced understanding of the perceptions and behaviours of landholders living in areas of high fire risk, who often choose to live there in order to be close to the natural environment. Many interviewees demonstrated a high awareness of wildfire risk as a result of their past experience with fire, and the majority considered themselves to be well-prepared in the event of a future fire. Community interactions and educational programs were found to be effective in raising awareness of risk; however, negative trust relationships with government authorities and low exposure to information concerning biodiversity resulted in an overall misunderstanding of the relationship between risk mitigation and biodiversity protection. The study offers insights into how catastrophic fires are reframing perceptions of what constitutes effective vegetation management. It provides recommendations to assist with the development of education strategies that concurrently address wildfire management and biodiversity conservation, and contribute towards environmentally-informed and risk conscious governance.

Keywords: biodiversity conservation, risk, peri-urban planning, wildfire management

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Authors: Sukhvinder Kaur, Ashok Agarwal

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Background: For the first time in 2009, India was able to generate estimates of HIV incidence (the number of new HIV infections per year). Analysis of epidemic projections helped in revealing that the number of new annual HIV infections in India had declined by more than 50% during the last decade (GOI Ministry of Health and Family Welfare, 2010). Then, National AIDS Control Organisation (NACO) planned to scale up its efforts in generating projections through epidemiological analysis and modelling by taking recent available sources of evidence such as HIV Sentinel Surveillance (HSS), India Census data and other critical data sets. Recently, NACO generated current round of HIV estimates-2012 through globally recommended tool “Spectrum Software” and came out with the estimates for adult HIV prevalence, annual new infections, number of people living with HIV, AIDS-related deaths and treatment needs. State level prevalence and incidence projections produced were used to project consequences of the epidemic in spectrum. In presence of HIV estimates generated at state level in India by NACO, USIAD funded PIPPSE project under the leadership of NACO undertook the estimations and projections to district level using same Spectrum software. In 2011, adult HIV prevalence in one of the high prevalent States, Maharashtra was 0.42% ahead of the national average of 0.27%. Considering the heterogeneity of HIV epidemic between districts, two districts of Maharashtra – Thane and Mumbai were selected to estimate and project the number of People-Living-with-HIV/AIDS (PLHIV), HIV-prevalence among adults and annual new HIV infections till 2017. Methodology: Inputs in spectrum included demographic data from Census of India since 1980 and sample registration system, programmatic data on ‘Alive and on ART (adult and children)’,‘Mother-Baby pairs under PPTCT’ and ‘High Risk Group (HRG)-size mapping estimates’, surveillance data from various rounds of HSS, National Family Health Survey–III, Integrated Biological and Behavioural Assessment and Behavioural Sentinel Surveillance. Major Findings: Assuming current programmatic interventions in these districts, an estimated decrease of 12% points in Thane and 31% points in Mumbai among new infections in HRGs and migrants is observed from 2011 by 2017. Conclusions: Project also validated decrease in HIV new infection among one of the high risk groups-FSWs using program cohort data since 2012 to 2016. Though there is a decrease in HIV prevalence and new infections in Thane and Mumbai, further decrease is possible if appropriate programme response, strategies and interventions are envisaged for specific target groups based on this evidence. Moreover, evidence need to be validated by other estimation/modelling techniques; and evidence can be generated for other districts of the state, where HIV prevalence is high and reliable data sources are available, to understand the epidemic within the local context.

Keywords: HIV sentinel surveillance, high risk groups, projections, new infections

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Authors: Karimova Sitora Yuldashevna

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The August 2021 resurgence of Taliban as a ruling force in Afghanistan once again challenged the global community into dealing with an unprecedentedly unlike-minded government. To express their disapproval of the new regime, Western governments and intergovernmental institutions have suspended their infrastructural projects and other forms of support. Moreover, the Afghan offshore reserves were frozen, and Afghanistan was disconnected from the international financial system, which impeded even independent aid agencies’ work. The already poor provision of aid was then further complicated with political conditionality. The purpose of this paper is to investigate the efficacy of conditional aid policy in the Afghan peacebuilding under Taliban rule and provide recommendations to international donors on further course of action. Arguing that conditionality of aid is a counterproductive factor in the peacebuilding process, this paper employs scholarly literature on peacebuilding alongside reports from International non-governmental organizations INGOs who operate directly in Afghanistan. The existing debate on peacebuilding in Afghanistan revolves around aid as a means of building democratic foundation for achieving peace on communal and national levels and why the previous attempts to do so were unsuccessful. This paper focuses on how to recalibrate the approach to aid provision and peacebuilding in the new reality. In the early 2000s, amid the weak Post-Cold War international will for a profound engagement in the conflict, humanitarian and development aid became the new means of achieving peace. Aid agencies provided resources directly to communities, minimizing the risk of local disputes. Through subsidizing education, governance reforms, and infrastructural projects, international aid accelerated school enrollment, introduced peace education, funded provincial council and parliamentary elections, and helped rebuild a conflict-torn country.When the Taliban seized power, the international community called on them to build an inclusive government based on respect for human rights, particularly girls’ and women’s schooling and work, as a condition to retain the aid flow. As the Taliban clearly failed to meet the demands, development aid was withdrawn. Some key United Nation agencies also refrained from collaborating with the de-facto authorities. However, contrary to the intended change in Talibs’ behavior, such a move has only led to further deprivation of those whom the donors strived to protect. This is because concern for civilians has always been the second priority for the warring parties. This paper consists of four parts. First, it describes the scope of the humanitarian crisis that began in Afghanistan in 2001. Second, it examines the previous peacebuilding attempts undertaken by the international community and the contribution that the international aid had in the peacebuilding process. Third, the paper describes the current regime and its relationships with the international donors. Finally, the paper concludes with recommendations for donors who would have to be more realistic and reconsider their priorities. While it is certainly not suggested that the Taliban regime is legitimized internationally, the crisis calls upon donors to be more flexible in collaborating with the de-facto authorities for the sake of the civilians.

Keywords: Afghanistan, international aid, donors, peacebuilding

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Authors: Desere Kokt

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Hospitality establishments worldwide are bearing the brunt of the effects of Covid-19. As the hospitality industry is looking to recover, emphasis is placed on rejuvenating the industry. This is especially pertinent for economic development in areas of high unemployment, such as the Free State province of South Africa. The province is not a main tourist area and thus depends on the influx of tourists. The province has great scenic beauty with many accommodation establishments that provide job opportunities to the local population. The two main economic hubs of the Free State province namely Bloemfontein and Clarens, were the focus of the investigation. The emphasis was on graded accommodation establishments as they must adhere to the quality principles of the Tourism Grading Council of South Africa (TGCSA) to obtain star grading. The hospitality industry is known for being labour intensive, and employees need to be available to cater for the needs of paying customers. This is referred to as ‘emotional labour’ and implies that employees need to manage their feelings and emotions as part of performing their jobs. The focus of this study was thus on psychological factors related to working in the hospitality industry – specifically psychological contract and psychological capital and its impact on the commitment of employees in graded accommodation establishments. Employee commitment can be explained as a psychological state that binds the individual to the organisation and involves a set of psychological relationships that include affective (emotions), normative (perceived obligation) and continuance (staying with the organisation) dimensions. Psychological contract refers to the reciprocal beliefs and expectations between the employer and the employee and consists of transactional and rational contracts. Transactional contracts are associated with the economic exchange, and contractional issues related to the employment contract and rational contracts relate to the social exchange between the employee and the organisation. Psychological capital refers to an individual’s positive psychology state of development that is characterised by self-efficiency (having confidence in doing one’s job), optimism (being positive and persevering towards achieving one’s goals), hope (expectations for goals to succeed) and resilience (bouncing back to attain success when beset by problems and adversity). The study employed a quantitative research approach, and a structured questionnaire was used to gather data from respondents. The study was conducted during the Covid-19 pandemic, which hampered the data gathering efforts of the researchers. Many accommodation establishments were either closed or temporarily closed, which meant that data gathering was an intensive and laborious process. The main researcher travelled to the various establishments to collect the data. Nine hospitality establishments participated in the study, and around 150 employees were targeted for data collection. Ninety-two (92) questionnaires were completed, which represents a response rate of 61%. Data were analysed using descriptive and inferential statistics, and partial least squares structural equation modelling (PLS-SEM) was applied to examine the relationship between the variables.

Keywords: employee commitment, hospitality industry, psychological contract, psychological capital

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Authors: Muhammad Karim Ahmadzai

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Floods are natural phenomena and are an integral part of the water cycle. The majority of them are the result of climatic conditions, but are also affected by the geology and geomorphology of the area, topography and hydrology, the water permeability of the soil and the vegetation cover, as well as by all kinds of human activities and structures. However, from the moment that human lives are at risk and significant economic impact is recorded, this natural phenomenon becomes a natural disaster. Flood management is now a key issue at regional and local levels around the world, affecting human lives and activities. The majority of floods are unlikely to be fully predicted, but it is feasible to reduce their risks through appropriate management plans and constructions. The aim of this Case Study is to identify, and map areas of flood risk in the Khinch District of Panjshir Province, Afghanistan specifically in the area of Peshghore, causing numerous damages. The main purpose of this study is to evaluate the contribution of remote sensing technology and Geographic Information Systems (GIS) in assessing the susceptibility of this region to flood events. Panjsher is facing Seasonal floods and human interventions on streams caused floods. The beds of which have been trampled to build houses and hotels or have been converted into roads, are causing flooding after every heavy rainfall. The streams crossing settlements and areas with high touristic development have been intensively modified by humans, as the pressure for real estate development land is growing. In particular, several areas in Khinch are facing a high risk of extensive flood occurrence. This study concentrates on the construction of a flood susceptibility map, of the study area, by combining vulnerability elements, using the Analytical Hierarchy Process/ AHP. The Analytic Hierarchy Process, normally called AHP, is a powerful yet simple method for making decisions. It is commonly used for project prioritization and selection. AHP lets you capture your strategic goals as a set of weighted criteria that you then use to score projects. This method is used to provide weights for each criterion which Contributes to the Flood Event. After processing of a digital elevation model (DEM), important secondary data were extracted, such as the slope map, the flow direction and the flow accumulation. Together with additional thematic information (Landuse and Landcover, topographic wetness index, precipitation, Normalized Difference Vegetation Index, Elevation, River Density, Distance from River, Distance to Road, Slope), these led to the final Flood Risk Map. Finally, according to this map, the Priority Protection Areas and Villages and the structural and nonstructural measures were demonstrated to Minimize the Impacts of Floods on residential and Agricultural areas.

Keywords: flood hazard, flood risk map, flood mitigation measures, AHP analysis

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Authors: Dmitriy Yu. Korulkin, Raissa A. Muzychkina

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The last decade the growth of severe and disseminated forms of inflammatory diseases is observed in Kazakhstan, in particular, septic shock, which progresses on 3-15% of patients with infectious complications of postnatal period. In terms of the rate of occurrence septic shock takes third place after hemorrhagic and cardiovascular shock, in terms of lethality it takes first place. The structure of obstetric sepsis has significantly changed. Currently the first place is taken by postabortive sepsis (40%) that is connected with usage of imperfect methods of artificial termination of pregnancy in late periods (intraamnial injection of sodium chloride, glucose). The second place is taken by postnatal sepsis (32%); the last place is taken by septic complications of caesarean section (28%). In this connection, search for and assessment of effectiveness of new medicines for treatment of postoperative infectious complications, having biostimulating effect and speeding up regeneration processes, is very promising and topical. Essential oil was obtained by the method hydrodistillation air-dry aerial part of Sedum L. plants using Clevenger apparatus. Pilot batch of plant medicinal product based on Sedum essential oils was produced by Chimpharm JSC, Santo Member of Polpharma Group (Kazakhstan). During clinical test of the plant medicinal product based on Sedum L. essential oils 37 female patients at the age from 35 to 57 with clinical signs of complicated postoperative processes and 12 new mothers with clinical signs of inflammatory process on sutures on anterior abdominal wall after caesarean section and partial disruption of surgical suture line on perineum were examined. Medicine usage methods - surgical wound treatment 2 times a day, treatment with other medicines of local action was not performed. Before and after treatment general clinical test, determination of immune status, bacterioscopic test of wound fluid was performed to all women, medical history data was taken into account, wound cleansing and healing time, full granulations, side effects and complications, satisfaction with the used medicine was assessed. On female patients with inflammatory infiltration and partial disruption of surgical suture line anesthetic wound healing effect of plant medicinal product based on Sedum L. essential oils was observed as early as on the second day after beginning of using it, wound cleansing took place, as a rule, within the first row days. Hyperemia in the area of suture line also was not observed for 2-3-d day of usage of medicine, good constant course was observed. The absence of clinical effect on this group of patients was not registered. The represented data give evidence of that clinical effect was accompanied with normalization of changed laboratory findings. No allergic responses or side effects were observed during usage of the plant medicinal products based on Sedum L. essential oils.

Keywords: antiinflammatory, bioactive substances, essential oils, isolation, sedum L., wound healing

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Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon

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The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.

Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling

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Authors: Andrey Cherdantsev, Mikhail Cherdantsev, Sergey Isaenkov, Dmitriy Markovich

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In annular gas-liquid flow, liquid flows as a film along pipe walls sheared by high-velocity gas stream. Film surface is covered by large-scale disturbance waves which affect pressure drop and heat transfer in the system and are necessary for entrainment of liquid droplets from film surface into the core of gas stream. Disturbance waves are a highly complex and their properties are affected by numerous parameters. One of such aspects is flow development, i.e., change of flow properties with the distance from the inlet. In the present work, this question is studied using brightness-based laser-induced fluorescence (BBLIF) technique. This method enables one to perform simultaneous measurements of local film thickness in large number of points with high sampling frequency. In the present experiments first 50 cm of upward and downward annular flow in a vertical pipe of 11.7 mm i.d. is studied with temporal resolution of 10 kHz and spatial resolution of 0.5 mm. Thus, spatiotemporal evolution of film surface can be investigated, including scenarios of formation, acceleration and coalescence of disturbance waves. The behaviour of disturbance waves' velocity depending on phases flow rates and downstream distance was investigated. Besides measuring the waves properties, the goal of the work was to investigate the interrelation between disturbance waves properties and integral characteristics of the flow such as interfacial shear stress and flow rate of dispersed phase. In particular, it was shown that the initial acceleration of disturbance waves, defined by the value of shear stress, linearly decays with downstream distance. This lack of acceleration which may even lead to deceleration is related to liquid entrainment. Flow rate of disperse phase linearly grows with downstream distance. During entrainment events, liquid is extracted directly from disturbance waves, reducing their mass, area of interaction to the gas shear and, hence, velocity. Passing frequency of disturbance waves at each downstream position was measured automatically with a new algorithm of identification of characteristic lines of individual disturbance waves. Scenarios of coalescence of individual disturbance waves were identified. Transition from initial high-frequency Kelvin-Helmholtz waves appearing at the inlet to highly nonlinear disturbance waves with lower frequency was studied near the inlet using 3D realisation of BBLIF method in the same cylindrical channel and in a rectangular duct with cross-section of 5 mm by 50 mm. It was shown that the initial waves are generally two-dimensional but are promptly broken into localised three-dimensional wavelets. Coalescence of these wavelets leads to formation of quasi two-dimensional disturbance waves. Using cross-correlation analysis, loss and restoration of two-dimensionality of film surface with downstream distance were studied quantitatively. It was shown that all the processes occur closer to the inlet at higher gas velocities.

Keywords: annular flow, disturbance waves, entrainment, flow development

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Authors: Shomaila Sadaf, Margarethe Olbertz-Siitonen

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This study looks at identity and othering in discourses around sensitive issues in social media. More specifically, the study explores the multimodal resources and narratives through which the other is formed, and identities are ascribed in online spaces. As an integral part of social life, media spaces have become an important site for negotiating and ascribing identities. In line with recent research, identity is seen hereas constructions of belonging which go hand in hand with processes of in- and out-group formations that in some cases may lead to othering. Previous findings underline that identities are neither fixed nor limited but rather contextual, intersectional, and interactively achieved. The goal of this study is to explore and develop an understanding of how people co-construct the ‘other’ and ascribe certain identities in social media using multiple modes. In the beginning of the year 2018, the British government decided to include relationships, sexual orientation, and sex education into the curriculum of state funded primary schools. However, the addition of information related to LGBTQ+in the curriculum has been met with resistance, particularly from religious parents.For example, the British Muslim community has voiced their concerns and protested against the actions taken by the British government. YouTube has been used by news companies to air video stories covering the protest and narratives of the protestors along with the position ofschool officials. The analysis centers on a YouTube video dealing with the protest ofa local group of parents against the addition of information about LGBTQ+ in the curriculum in the UK. The video was posted in 2019. By the time of this study, the videos had approximately 169,000 views andaround 6000 comments. In deference to multimodal nature of YouTube videos, this study utilizes multimodal discourse analysis as a method of choice. The study is still ongoing and therefore has not yet yielded any final results. However, the initial analysis indicates a hierarchy of ascribing identities in the data. Drawing on multimodal resources, the media works with social categorizations throughout the documentary, presenting and classifying involved conflicting parties in the light of their own visible and audible identifications. The protesters can be seen to construct a strong group identity as Muslim parents (e.g., clothing and reference to shared values). While the video appears to be designed as a documentary that puts forward facts, the media does not seem to succeed in taking a neutral position consistently throughout the video. At times, the use of images, soundsand language contributes to the formation of “us” vs. “them”, where the audience is implicitly encouraged to pick a side. Only towards the end of the documentary this problematic opposition is addressed and critically reflected through an expert interview that is – interestingly – visually located outside the previously presented ‘battlefield’. This study contributes to the growing understanding of the discursive construction of the ‘other’ in social media. Videos available online are a rich source for examining how the different social actors ascribe multiple identities and form the other.

Keywords: identity, multimodal discourse analysis, othering, youtube

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Authors: Sharmila Parmanand

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This paper examines dominant media representations of prostitution in the Philippines and interrogates sex workers’ interactions with the media establishment. This analysis of how sex workers are constituted in media, often as both innocent victims and immoral actors, contributes to an understanding of public discourse on sex work in the Philippines, where decriminalisation has recently been proposed and sex workers are currently classified as potential victims under anti-trafficking laws but also as criminals under the penal code. The first part is an analysis of media coverage of two prominent themes on prostitution: first, raid and rescue operations conducted by law enforcement; and second, prostitution on military bases and tourism hotspots. As a result of pressure from activists and international donors, these two themes often define the policy conversations on sex work in the Philippines. The discourses in written and televised news reports and documentaries from established local and international media sources that address these themes are explored through content analysis. Conclusions are drawn based on specific terms commonly used to refer to sex workers, how sex workers are seen as performing their cultural roles as mothers and wives, how sex work is depicted, associations made between sex work and public health, representations of clients and managers and ‘rescuers’ such as the police, anti-trafficking organisations, and faith-based groups, and which actors are presumed to be issue experts. Images of how prostitution is used as a metaphor for relations between the Philippines and foreign nations are also deconstructed, along with common tropes about developing world female subjects. In general, sex workers are simultaneously portrayed as bad mothers who endanger their family’s morality but also as long-suffering victims who endure exploitation for the sake of their children. They are also depicted as unclean, drug-addicted threats to public health. Their managers and clients are portrayed as cold, abusive, and sometimes violent, and their rescuers as moral and altruistic agents who are essential for sex workers’ rehabilitation and restoration as virtuous citizens. The second part explores sex workers’ own perceptions of their interactions with media, through interviews with members of the Philippine Sex Workers Collective, a loose organisation of sex workers around the Philippines. They reveal that they are often excluded by media practitioners and that they do not feel that they have space for meaningful self-revelation about their work when they do engage with journalists, who seem to have an overt agenda of depicting them as either victims or women of loose morals. In their assessment, media narratives do not necessarily reflect their lived experiences, and in some cases, coverage of rescues and raid operations endangers their privacy and instrumentalises their suffering. Media representations of sex workers may produce subject positions such as ‘victims’ or ‘criminals’ and legitimize specific interventions while foreclosing other ways of thinking. Further, in light of media’s power to reflect and shape public consciousness, it is a valuable academic and political project to examine whether sex workers are able to assert agency in determining how they are represented.

Keywords: discourse analysis, news media, sex work, trafficking

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Authors: Josephine R. Migalbin

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Halal is an Arabic word meaning "lawful" or "permitted". When it comes to food and consumables, Halal is the dietary standard of Muslims. The Autonomous Region in Muslim Mindanao (ARMM) has a comparative advantage when it comes to Halal Industry because it is the only Muslim region in the Philippines and the natural starting point for the establishment of a halal industry in the country. The region has identified goat production not only for domestic consumption but for export market. Goat production is one of its strengths due to cultural compatibility. There is a high demand for goats during Ramadhan and Eid ul-Adha. The study aimed to provide an overview of the ARMM Halal Goat Industry; to map out the specific supply chain of halal goat, and to analyze the performance of the halal goat supply chain in terms of efficiency, flexibility, and overall responsiveness. It also aimed to identify areas for improvement in the supply chain such as behavioural, institutional, and process to provide recommendations for improvement in the supply chain towards efficient and effective production and marketing of halal goats, subsequently improving the plight of the actors in the supply chain. Generally, the raising of goats is characterized by backyard production (92.02%). There are four interrelated factors affecting significantly the production of goats which are breeding prolificacy, prevalence of diseases, feed abundance and pre-weaning mortality rate. The institutional buyers are mostly traders, restaurants/eateries, supermarkets, and meat shops, among others. The municipalities of Midsayap and Pikit in another region and Parang are the major goat sources and the municipalities in ARMM among others. In addition to the major supply centers, Siquijor, an island province in the Visayas is becoming a key source of goats. Goats are usually gathered by traders/middlemen and brought to the public markets. Meat vendors purchase them directly from raisers, slaughtered and sold fresh in wet markets. It was observed that there is increased demand at 2%/year and that supply is not enough to meet the demand. Farm gate price is 2.04 USD to 2.11 USD/kg liveweight. Industry information is shared by three key participants - raisers, traders and buyers. All respondents reported that information is through personal built-upon past experiences and that there is no full disclosure of information among the key participants in the chain. The information flow in the industry is fragmented in nature such that no total industry picture exists. In the last five years, numerous local and foreign agencies had undertaken several initiatives for the development of the halal goat industry in ARMM. The major issues include productivity which is the greatest challenge, difficulties in accessing technical support channels and lack of market linkage and consolidation. To address the various issues and concerns of the various industry players, there is a need to intensify appropriate technology transfer through extension activities, improve marketing channels by grouping producers, strengthen veterinary services and provide capital windows to improve facilities and reduce logistics and transaction costs in the entire supply chain.

Keywords: autonomous region in Muslim Mindanao, halal, halal goat industry, supply chain improvement

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Authors: Kitti Supchukun, Kris Angkanaporn, Teerapong Yata

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The product innovation using a nutraceutical delivery system on improving the growth performance of broilers is the product planning and development to solve the antibiotics banning policy incurred in the local and global livestock production system. Restricting the use of antibiotics can reduce the quality of chicken meat and increase pathogenic bacterial contamination. Although other alternatives were used to replace antibiotics, the efficacy was inconsistent, reflecting on low chicken growth performance and contaminated products. The product innovation aims to effectively deliver the selected active ingredients into the body. This product is tested on the pharmaceutical lab scale and on the farm-scale for market feasibility in order to create product innovation using the nutraceutical delivery system model. The model establishes the product standardization and traceable quality control process for farmers. The study is performed using mixed methods. Starting with a qualitative method to find the farmers' (consumers) demands and the product standard, then the researcher used the quantitative research method to develop and conclude the findings regarding the acceptance of the technology and product performance. The survey has been sent to different organizations by random sampling among the entrepreneur’s population including integrated broiler farm, broiler farm, and other related organizations. The mixed-method results, both qualitative and quantitative, verify the user and lead users' demands since they provide information about the industry standard, technology preference, developing the right product according to the market, and solutions for the industry problems. The product innovation selected nutraceutical ingredients that can solve the following problems in livestock; bactericidal, anti-inflammation, gut health, antioxidant. The combinations of the selected nutraceutical and nanostructured lipid carriers (NLC) technology aim to improve chemical and pharmaceutical components by changing the structure of active ingredients into nanoparticle, which will be released in the targeted location with accurate concentration. The active ingredients in nanoparticle form are more stable, elicit antibacterial activity against pathogenic Salmonella spp and E.coli, balance gut health, have antioxidant and anti-inflammation activity. The experiment results have proven that the nutraceuticals have an antioxidant and antibacterial activity which also increases the average daily gain (ADG), reduces feed conversion ratio (FCR). The results also show a significant impact on the higher European Performance Index that can increase the farmers' profit when exporting. The product innovation will be tested in technology acceptance management methods from farmers and industry. The production of broiler and commercialization analyses are useful to reduce the importation of animal supplements. Most importantly, product innovation is protected by intellectual property.

Keywords: nutraceutical, nano structure lipid carrier, anti-microbial drug resistance, broiler, Salmonella

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Authors: Maria L. G. Lourenço, Keylla H. N. P. Pereira, Viviane Y. Hibaru, Fabiana F. Souza, João C. P. Ferreira, Simone B. Chiacchio, Luiz H. A. Machado

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The neonatal care of cats and dogs represents a challenge to veterinarians due to the small size of the newborns and their physiological particularities. In addition, many Veterinary Medicine colleges around the world do not include neonatology in the curriculum, which makes it less likely for the veterinarian to have basic knowledge regarding neonatal care and worsens the clinical care these patients receive. Therefore, lack of assistance and negligence have become frequent in the field, which contributes towards the high mortality rates. This study aims at describing cases and the main conditions pertaining to the neonatology clinical routine in cats and dogs, highlighting the importance of specialized care in this field of Veterinary Medicine. The study included 808 neonates admitted to the São Paulo State University (UNESP) Veterinary Hospital, Botucatu, São Paulo, Brazil, between January 2018 and November 2019. Of these, 87.3% (705/808) were dogs and 12.7% (103/808) were cats. Among the neonates admitted, 57.3% (463/808) came from emergency c-sections due to dystocia, 8.7% (71/808) cane from vaginal deliveries with obstetric maneuvers due to dystocia, and 34% (274/808) were admitted for clinical care due to neonatal conditions. Among the neonates that came from emergency c-sections and vaginal deliveries, 47.3% (253/534) was born in respiratory distress due to severe hypoxia or persistent apnea and required resuscitation procedure, such as the Jen Chung acupuncture point (VG26), oxygen therapy with mask, pulmonary expansion with resuscitator, heart massages and administration of emergency medication, such as epinephrine. On the other hand, in the neonatal clinical care, the main conditions and alterations observed in the newborns were omphalophlebitis, toxic milk syndrome, neonatal conjunctivitis, swimmer puppy syndrome, neonatal hemorrhagic syndrome, pneumonia, trauma, low weight at birth, prematurity, congenital malformations (cleft palate, cleft lip, hydrocephaly, anasarca, vascular anomalies in the heart, anal atresia, gastroschisis, omphalocele, among others), neonatal sepsis and other local and systemic bacterial infections, viral infections (feline respiratory complex, parvovirus, canine distemper, canine infectious traqueobronchitis), parasitical infections (Toxocara spp., Ancylostoma spp., Strongyloides spp., Cystoisospora spp., Babesia spp. and Giardia spp.) and fungal infections (dermatophytosis by Microsporum canis). The most common clinical presentation observed was the neonatal triad (hypothermia, hypoglycemia and dehydration), affecting 74.6% (603/808) of the patients. The mortality rate among the neonates was 10.5% (85/808). Being knowledgeable about neonatology is essential for veterinarians to provide adequate care for these patients in the clinical routine. Adding neonatology to college curriculums, improving the dissemination of information on the subject, and providing annual training in neonatology for veterinarians and employees are important to improve immediate care and reduce the mortality rates.

Keywords: neonatal care, puppies, neonatal, conditions

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Authors: Wei Xu, Abdo S. Haidar, Jianxin Gao

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Prosthetic socket is a component that connects the residual limb of an amputee with an artificial prosthesis. It is widely recognized as the most critical component that determines the comfort of a patient when wearing the prosthesis in his/her daily activities. Through the socket, the body weight and its associated dynamic load are distributed and transmitted to the prosthesis during walking, running or climbing. In order to achieve a good-fit socket for an individual amputee, it is essential to obtain the biomechanical properties of the residual limb. In current clinical practices, this is achieved by a touch-and-feel approach which is highly subjective. Although there have been significant advancements in prosthetic technologies such as microprocessor controlled knee and ankle joints in the last decade, the progress in designing a comfortable socket has been rather limited. This means that the current process of socket design is still very time-consuming, and highly dependent on the expertise of the prosthetist. Supported by the state-of-the-art sensor technologies and numerical simulations, a new socket design system is being developed to help prosthetists achieve rapid design of comfortable sockets for above knee amputees. This paper reports the research work related to establishing biomechanical models for socket design. Through numerical simulation using finite element method, comprehensive relationships between pressure on residual limb and socket geometry were established. This allowed local topological adjustment for the socket so as to optimize the pressure distributions across the residual limb. When the full body weight of a patient is exerted on the residual limb, high pressures and shear forces between the residual limb and the socket occur. During numerical simulations, various hyperplastic models, namely Ogden, Yeoh and Mooney-Rivlin, were used, and their effectiveness in representing the biomechanical properties of soft tissues of the residual limb was evaluated. This also involved reverse engineering, which resulted in an optimal representative model under compression test. To validate the simulation results, a range of silicone models were fabricated. They were tested by an indentation device which yielded the force-displacement relationships. Comparisons of results obtained from FEA simulations and experimental tests showed that the Ogden model did not fit well the soft tissue material indentation data, while the Yeoh model gave the best representation of the soft tissue mechanical behavior under indentation. Compared with hyperplastic model, the result showed that elastic model also had significant errors. In addition, normal and shear stress distributions on the surface of the soft tissue model were obtained. The effect of friction in compression testing and the influence of soft tissue stiffness and testing boundary conditions were also analyzed. All these have contributed to the overall goal of designing a good-fit socket for individual above knee amputees.

Keywords: above knee amputee, finite element simulation, hyperplastic model, prosthetic socket

Procedia PDF Downloads 187

Authors: Noelia L. Alchapar, Cláudia C. Pezzuto, Erica N. Correa

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Mitigating urban overheating is key to achieving the environmental and energy sustainability of cities. The management of the optical properties of the materials that make up the urban envelope -roofing, pavement, and facades- constitutes a profitable and effective tool to improve the urban microclimate and rehabilitate urban areas. Each material that makes up the urban envelope has a different capacity to reflect received solar radiation, which alters the fraction of solar radiation absorbed by the city. However, the paradigm of increasing solar reflectance in all areas of the city without distinguishing their relative position within the urban canyon can cause serious problems of overheating and discomfort among its inhabitants. The hypothesis that supports the research postulates that not all reflective technologies that contribute to urban radiative cooling favor the thermal comfort conditions of pedestrians to equal measure. The objective of this work is to determine to what degree the management of the optical properties of the facades modifies outdoor thermal comfort, given that the mitigation potential of materials with high reflectance in facades is strongly conditioned by geographical variables and by the geometric characteristics of the urban profile aspect ratio (H/W). This research was carried out under two climatic contexts, that of the city of Mendoza-Argentina and that of the city of Campinas-Brazil, according to the Köppen climate classification: BWk and Cwa, respectively. Two areas in two different climatic contexts (Mendoza - Argentina and Campinas - Brazil) were selected. Both areas have comparable urban morphology patterns. These areas are located in a region with low horizontal building density and residential zoning. The microclimatic conditions were monitored during the summer period with temperature and humidity fixed sensors inside vial channels. The microclimate model was simulated in ENVI-Met V5. A grid resolution of 3.5 x 3.5 x 3.5m was used for both cities, totaling an area of 145x145x30 grids. Based on the validated theoretical model, ten scenarios were simulated, modifying the height of buildings and the solar reflectivity of facades. The solar reflectivity façades ranges were: low (0.3) and high (0.75). The density scenarios range from 1th to the 5th level. The study scenarios' performance was assessed by comparing the air temperature, physiological equivalent temperature (PET), and thermal climate index (UTCI). As a result, it is observed that the behavior of the materials of the urban outdoor space depends on complex interactions. Many urban environmental factors influence including constructive characteristics, urban morphology, geographic locations, local climate, and so forth. The role of the vertical urban envelope is decisive for the reduction of urban overheating. One of the causes of thermal gain is the multiple reflections within the urban canyon, which affects not only the air temperature but also the pedestrian thermal comfort. One of the main findings of this work leads to the remarkable importance of considering both the urban warming and the thermal comfort aspects of pedestrians in urban mitigation strategies.

Keywords: materials facades, solar reflectivity, thermal comfort, urban cooling

Procedia PDF Downloads 79

Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

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Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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

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

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

Procedia PDF Downloads 97

Authors: Shirley S. Ho, Alisius X. L. D. Leong, Jiemin Looi, Agnes S. F. Chuah

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Nuclear energy is a contentious technology that has attracted much public debate over the years. The prominence of nuclear energy in Southeast Asia (SEA) has burgeoned due to the surge of interest and plans for nuclear development in the region. Understanding public perceptions of nuclear energy in SEA is pertinent given the limited number of studies conducted. In particular, five SEA nations – Singapore, Malaysia, Indonesia, Thailand, and Vietnam are of immediate interest as that they are amongst the most economically developed or developing nations in the SEA region. High energy demands from economic development in these nations have led to considerations of adopting nuclear energy as an alternative source of energy. This study aims to explore whether differences in the nuclear developmental stage in each country affects public perceptions of nuclear energy. In addition, this study seeks to find out about the type and importance of communication credibility as a judgement heuristic in facilitating message acceptance across these five countries. Credibility of a communication channel is a crucial component influencing public perception, acceptance, and attitudes towards nuclear energy. Aside from simply identifying the frequently used communication channels, it is of greater significance to understand public perception of source and media credibility. Given the lack of studies conducted in SEA, this exploratory study adopts a qualitative approach to elicit a spectrum of opinions and insights regarding the key communication aspects influencing public perceptions of nuclear energy. Specifically, the capitals of each of the abovementioned countries - Kuala Lumpur, Bangkok, and Hanoi - were selected, with the exception of Singapore, an island city-state, and Yogyakarta, the most populous island of Indonesia to better understand public perception towards nuclear energy. Focus group discussions were utilized as the mode of data collection to elicit a wide variety of viewpoints held by the participants, which is well-suited for exploratory research. In total, 156 participants took part in the 13 focus group discussions. The participants were either local citizens or permanent residents aged between 18 and 69 years old. Each of the focus groups consists of 8-10 participants, including both male and female participants. The transcripts from each focus group were analysed using NVivo 10, and the text was organised according to the emerging themes or categories. The general public in all the countries was familiar but had no in-depth knowledge with nuclear energy. Four dimensions of nuclear energy communication were identified based on the focus group discussions: communication channels, perceived credibility of sources, circumstances for discussion, and discussion style. The first dimension, communication channels refers to the medium through which participants receive information about nuclear energy. Four types of media emerged from the discussions. They included online and social media, broadcast media, print media, and word-of- mouth (WOM). Collectively, across all five countries, participants were found to engage in different types of knowledge acquisition and information seeking behavior depending on the communication channels used.

Keywords: nuclear energy, public perception, communication, Southeast Asia, source credibility

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Authors: Margareta Simina Stanc, Aurel Mototolea, Tiberiu Potarniche

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Sacidava archeological site is located in Dobrudja region, Romania, on a hill on the right bank of the Danube - the Musait point, located at about 5 km north-east from Dunareni village. The place-name documents the fact that, prior to the Roman conquest, in the area, there was a Getic settlement. The location of the Sacidava was made possible by corroborating the data provided by the ancient sources with the epigraphic documents (the milial pillar during the time of Emperor Decius). The tegular findings attest that an infantry unit, cohors I Cilicum milliaria equitata, as well as detachments from Legio V Macedonica and Legio XI Claudia, were confined to Sacidava. During the period of the Dominion, the garrison of the fortification is the host of a cavalry unit: cuneus equitum scutariorum. In the immediate vicinity to the Roman fortress, to the east, were identified two other fortifications: a Getic settlement (4th-1st century B.C.) and an Early Medieval settlement (9th-10th century A.C.). The archaeological material recovered during the research is represented by ceramic forms such as amphoras, jugs, pots, cups, plates, to which are added oil lamps, some of them typologically new at the time of discovery. Local ceramic shapes were also founded, worked by hand or by wheel, considered un-Romanized or in the course of Romanization. During the time of the Principality, Sacidava it represented an important military outpost serving mainly the city of Tropaeum Traiani, controlling also the supply and transport on the Danube limes in the Moesic sector. This role will determine the development of the fortress and the appearance of extramuros civil structures, thus becoming an important landmark during the 5th-6th centuries A.C., becoming a representation of power of the Roman empire in an area of continuous conflict. During recent archaeological researches, faunal remains were recovered, and their analysis allowed to estimate the animal resources and subsistence practices (animal husbandry, hunting, fishing) in the settlement. The methodology was specific to archaeozoology, mainly consisting of anatomical, taxonomical, and taphonomical identifications, recording, and quantification of the data. The remains of domestic mammals have the highest proportion indicating the importance of animal husbandry; the predominant species are Bos taurus, Ovis aries/Capra hircus, and Sus domesticus. Fishing and hunting were of secondary importance in the subsistence economy of the community. Wild boar and the red deer were the most frequently hunted species. Just a few fish bones were recovered. Thus, the ancient city of Sacidava is proving to be an important element of cultural heritage of the south-eastern part of Romania, for whose conservation and enhancement efforts must be made, especially by landscape reconstruction.

Keywords: archaeozoology, landscape reconstruction, limes, military outpost

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Authors: B. Ozarisoy, E. Ampatzi, G. Z. Lancaster

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This research project is undertaken in the Turkish Republic of Northern Cyprus (T.R.N.C). The study focuses on identifying refurbishment activities capable of diagnosing and detecting the underlying problems alongside the challenges offered by the buildings’ typology in addition to identifying the correct construction materials in the refurbishment process which allow for the maximisation of expected energy savings. Attention is drawn to, the level of awareness and understanding of refurbishment activity that needs to be raised in the current construction process alongside factors that include the positive environmental impact and the saving of energy. The approach here is to look at buildings that have been built by private construction companies that have already been refurbished by occupants and to suggest additional control mechanisms for retrofitting that can further enhance the process of renewal. The objective of the research is to investigate the occupants’ behaviour and role in the refurbishment activity; to explore how and why occupants decide to change building components and to understand why and how occupants consider using energy-efficient materials. The present work is based on data from this researcher’s first-hand experience and incorporates the preliminary data collection on recent housing sector statistics, including the year in which housing estates were built, an examination of the characteristics that define the construction industry in the T.R.N.C., building typology and the demographic structure of house owners. The housing estates are chosen from 16 different projects in four different regions of the T.R.N.C. that include urban and suburban areas. There is, therefore, a broad representation of the common drivers in the property market, each with different levels of refurbishment activity and this is coupled with different samplings from different climatic regions within the T.R.N.C. The study is conducted through semi-structured interviews to identify occupants’ behaviour as it is associated with refurbishment activity. The interviews provide all the occupants’ demographic information, needs and intentions as they relate to various aspects of the refurbishment process. This research paper presents the results of semi-structured interviews with 70 homeowners in a selected group of 16 housing estates in five different parts of the T.R.N.C. The people who agreed to be interviewed in this study are all residents of single or multi-family housing units. Alongside the construction process and its impact on the environment, the results point out the need for control mechanisms in the housing sector to promote and support the adoption of retrofit strategies and minimize non-controlled refurbishment activities, in line with diagnostic information of the selected buildings. The expected solutions should be effective, environmentally acceptable and feasible given the type of housing projects under review, with due regard for their location, the climatic conditions within which they were undertaken, the socio-economic standing of the house owners and their attitudes, local resources and legislative constraints. Furthermore, the study goes on to insist on the practical and long-term economic benefits of refurbishment under the proper conditions and why this should be fully understood by the householders.

Keywords: construction process, energy-efficiency, refurbishment activity, retrofitting

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Authors: Szerena Vajkovszki

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Among the relatively large volume of literature, the role and perception of women in Buddhism have been examined from various perspectives such as theology, history, anthropology, and feminism. When Buddhism spread to the West, women had a major role in its adaption and development. The meeting of different cultures and social structures had the fruit of a necessity to change. As Buddhism gained attention in the West, it produced a Buddhist feminist identity across national and ethnic boundaries. So globalization produced a contemporary cross-cultural Buddhist Women. The aim of the research is to find out the new role of such a Buddhist woman in aging societies. More precisely to understand what effect this contemporary Buddhist religion may have, direct or indirect, on fertility. Our worldwide aging society, especially in developed countries, including members of EU, raise sophisticated sociological and economic issues and challenges to be met. As declining fertility has outstanding influence underlying this trend, numerous studies have attempted to identify, describe, measure and interpret contributing factors of the fertility rate, out of which relatively few revealed the impact of religion. Among many religious guidelines, we can separate two major categories: direct and indirect. The aim of this research was to understand what are the most crucial identified (family values, gender related behaviors, religious sentiments) and not yet identified most influential contributing contemporary Buddhist religious factors. Above identifying these direct or indirect factors, it is also important to understand to what extent and how do they influence fertility, which requires a wider (inter-discipline) perspective. As proved by previous studies religion has also an influential role in health, mental state, well-being, working activity and many other components that are also related to fertility rates. All these components are inter-related, hence direct and indirect religious effects can only be well understood, if we figure out all necessary fields and their interaction. With the help of semi-structured opened interviews taking place in different countries, it was showed that indeed Buddhism has significant direct and indirect effect on fertility, hence the initial hypothesis was proved. However, the interviews showed an overall positive effect, the results could only serve for a general understanding about how Buddhism affects fertility. Evolution of Buddhism’s direct and indirect influence may vary in different nations and circumstances according to their specific environmental attributes. According to the local patterns, with special regard to women’s position and role in the society, outstandingly indirect influences could show diversifications. So it is advisory to investigate more for a deeper and clearer understanding of how Buddhism function in different socioeconomic circumstances. For example, in Hungary after the period of secularization more and more people tended to be attracted toward some transcendent values which could be an explanation for the rising number of Buddhists in the country. The present research could serve as a general starting point or a common basis for further specific national investigations how contemporary Buddhism affects fertility.

Keywords: contemporary Buddhism, cross-cultural woman, fertility, gender roles, religion

Procedia PDF Downloads 134

Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

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Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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Authors: Varun Joshi, M. S. Rawat

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The Indian Himalayan Region (IHR) is inherently fragile and susceptible to landslide hazard due to its extremely weak geology, highly rugged topography and heavy monsoonal rainfall. One of the most common hazards in the IHR is landslide, and this event is particularly frequent in Himalayan states of India i.e. Jammu & Kashmir, Himachal Pradesh, Uttarakhand, Sikkim, Manipur and Arunachal Pradesh. Landslides are mostly triggered by extreme rainfall events but the incidence increases during monsoon months (June to September). Natural slopes which are otherwise stable but they get destabilized due to anthropogenic activities like construction of various developmental activities and deforestation. These activities are required to fulfill the developmental needs and upliftment of societal status in the region. Landslides also trigger during major earthquakes and reported most observable and damaging phenomena. Studies indicate that the landslide phenomenon has increased many folds due to developmental activities in Himalayan region. Gradually increasing and devastating consequences of landslides turned into one of the most important hydro-geological hazards in Himalayan states especially in Uttarakhand and Sikkim states of India. The recent most catastrophic rainfall in June 2013 in Uttarakhand lead to colossal loss of life and property. The societal damage due to this incident is still to be recovered even after three years. Sikkim earthquake of September 2011 is witnessed for triggering of large number of coseismic landslides. The rescue and relief team faced huge problem in helping the trapped villagers in remote locations of the state due to road side blockade by landslides. The recent past incidences of landslides in Uttarakhand, as well as Sikkim states, created a new domain of research in terms of understanding the phenomena of landslide and management of disaster in such situation. Every year at many locations landslides trigger which force dwellers to either evacuate their dwelling or lose their life and property. The communication and transportation networks are also severely affected by landslides at several locations. Many times the drinking water supply disturbed and shortage of daily need household items reported during monsoon months. To minimize the severity of landslide in IHR requires in-depth research and developmental planning. For most of the areas in the present study, landslide hazard zonation is done on 1:50,000 scale. The land use planning maps on extensive basis are not available. Therefore, there is a need of large-scale landslide hazard zonation and land use planning maps. If the scientist conduct research on desired aspects and their outcome of research is utilized by the government in developmental planning then the incidents of landslide could be minimized, subsequent impact on society, life and property would be reduced. Along with the scientific research, there is another need of awareness generation in the region for stake holders and local dwellers to combat with the landslide hazard, if triggered in their location.

Keywords: coseismic, Indian Himalayan Region, landslide hazard zonation, Sikkim, societal, Uttarakhand

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Authors: Delsy Salinas, Andreia Garcês, Augusto Silva, Paula Brilhante Simões

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Urinary tract infection (UTI) is a common disease affecting dogs and cats in both community and hospital environment. Bacteria is the most frequent agent isolated, fewer than 1% of infections are due to parasitic, fungal, or viral agents. Common symptoms and laboratory abnormalities includeabdominal pain, pyrexia, renomegaly, and neutrophilia with left shift. A rapid and precise identification of the bacterial agent is still a challenge in veterinarian laboratories. Therefore, this cross-sectional study aims to describe bacterial colony patterns of urine samples by using chromID™ CPS® EliteAgar (BioMérieux, France) from canine and feline specimens submitted to a veterinary laboratory in Portugal (INNO Veterinary Laboratory, Braga)from January to March2022. All urine samples were cultivated in CPS Elite Agar with calibrated 1 µL inoculating loop and incubated at 37ºC for 18-24h. Color,size, and shape (regular or irregular outline)were recorded for all samples. All colonies were classified as Gram-negative or Gram-positive bacteriausing Gram stain (PREVI® Color BioMérieux, France) and determined if they were pure colonies. Identification of bacteria species was performed using GP and GN cards inVitek 2® Compact(BioMérieux, France). A total of 256/1003 submitted urine samples presented bacterial growth, from which 172 isolates were included in this study. The sample’s population included 111 dogs (n=45 males and n=66 females) and 61 cats (n=35 males and n=26 females). The most frequent isolated bacteria wasEscherichia coli (44,7%), followed by Proteus mirabilis (13,4%). All Escherichia coli isolates presented red to burgundy colonies, a colony diameter between 2 to 6 mm, and regular or irregular outlines. Similarly, 100% of Proteus mirabilis isolates were dark yellow colonies with a diffuse pigment and the same size and shape as Escherichia coli. White and pink pale colonies where Staphylococcus species exclusively and S. pseudintermedius was the most frequent (8,2 %). Cian to blue colonies were mostly Enterococcusspp. (8,2%) and Streptococcus spp. (4,6%). Beige to brown colonies were Pseudomonas aeruginosa (2,9%) and Citrobacter spp. (1,2%).Klebsiella spp.,Serratia spp. and Enterobacter spp were green colonies. All Gram-positive isolates were 1 to 2 mm diameter long and had a regular outline, meanwhile, Gram-negative rods presented variable patterns. This results showed that theprevalence of E coli and P. mirabilis as uropathogenic agents follows the same trends in Europe as previously described in other studies. Both agents presented a particular color pattern in CPS Elite Agar to identify them without needing complementary tests. No other bacteria genus could be correlated strongly to a specific color pattern, and similar results have been observed instudies using human’s samples. Chromogenic media shows a great advantage for common urine bacteria isolation than traditional COS, McConkey, and CLEDAgar mediums in a routine context, especially when mixed fermentative Gram-negative agents grow simultaneously. In addition, CPS Elite Agar is versatile for Artificial Intelligent Reading Plates Systems. Routine veterinarian laboratories could use CPS Elite Agar for a rapid screening for bacteria identification,mainlyE coli and P.mirabilis, saving 6h to 10h of automatized identification.

Keywords: cats, CPS elite agar, dogs, urine pathogens

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Authors: Burmansyah Muhammad, Supriyoto Supriyoto

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Crop yield, quality and food safety are three important components that all estate and food crops must put into consideration to lifting the economic value. These measurements should be evaluated because marketplace demand is simultaneously changing and farmers must adapt quickly to remain competitive. The increase in economic value could be done by producing high quality product that aligns with harvest collector preferences. The purpose of this study is to examine the causal effects of value added farming in agriculture economic aspects towards crop yield, quality and food security. This research is using descriptive survey research by employing data from small-scale cocoa farmers listed to off-taker company, located on Sulawesi area of Indonesia. The questionnaire was obtained from 650 cocoa farmers, selected randomly. Major findings of the study indicate that 78% of respondents agree that agriculture inputs have positive effect on crop yield, quality and food safety. The study recommended that cocoa stakeholders should ensure access to agriculture inputs in first priority and then followed by ensuring access to cocoa supply chain trader and micro-financing. Value Added Farming refers to lifting the economic value of a commodity through particular intervention. Regarding access to agriculture inputs, one of significant intervention is fertilization and plant nutrition management, both organic and inorganic fertilizer. Small-scale cocoa farmers can get access to fertilizer intervention through establishment of demo farm. Ordinary demo farm needs large area, selective requirements, lots of field resources and centralization impact. On the contrary, satellite demo farm is developing to wide-spread the impact of agriculture economic aspects and also the involvement in number of farmers. In Sulawesi Project, we develop leveling strata of small-scale demo farm with group of farmers and local cooperative. With this methodology, all of listed small-scale farmers can get access to agriculture input, micro-financing and how to deliver quality output. PT Pupuk Kaltim is member firm of holding company PT Pupuk Indonesia, private company belongs to the government of Indonesia. The company listed as Indonesia's largest producer of urea fertilizers, besides ammonia, Compound Fertilizer (NPK) and biological fertilizers. To achieve strategic objectives, the company has distinguished award such as SNI Platinum, SGS Award IFA Protect and Sustain Stewardship and Gold Rank of Environment Friendly Company. This achievement has become the strategic foundation for our company to energize value added farming in sustaining food security program. Moreover, to ensure cocoa sustainability farming the company has developed partnership with international companies and Non-Government Organization (NGO).

Keywords: fertilizer and plant nutrition management, good agriculture practices, agriculture economic aspects, value-added farming

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Authors: Justine A. Lloyd

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Since the onset of the Syrian Civil War in 2011, the ancient city of Dura-Europos has faced widespread destruction and looting. The site is one of many places in the country the terrorist group ISIS has specifically targeted, allegedly due to its particular representations of Syrian history and culture. However, looted art and artifacts are the extremist group’s second largest source of income, only after oil. The protection of this site is important to both academics and the millions who have called Syria a home, as it aids in the nation’s sense of identity, reveals developments in the arts, and contributes to humanity’s collective history. At a time when Syria’s culture is being flattened, this sense of cultural expression is especially important to maintain. Creating an awareness of the magnitude of the issue at hand begins with an examination of the rich history of the ancient fortress city. Located on the western bank of the Euphrates River, Dura-Europos contains artifacts dating back to the Hellenistic, Parthian, and Roman periods. Though a great deal of the art and artifacts have remained safe in institutions such as the National Museum of Damascus and the Yale University Art Gallery, hundreds of looting pits and use of heavy machinery on the site has severely set back the investigative progress made by archaeologists over the last century, as well as the prospect of future excavation. Further research draws on the current destruction of the site by both ISIS and opportunists involved with the black market. Because Dura-Europos is located in a war stricken region, the acquisition of data and possibility of immediate action is particularly challenging. Resources gained from local reports, in addition to technology such as satellite imagery, however, have provided a firm starting point for the evaluation of the state of the site. The Syrian Ministry of Culture, UNESCO, and numerous Syrian and global organizations provide insight into the historic city’s past, present issues, and future plans to ensure that the cultural integrity of the site is upheld. Though over seventy percent of Dura-Europos has been completely decimated, this research challenges the notion that physically destroyed sites are lost forever. This paper assesses preventative measures that can take place to ensure the preservation of the site’s art and architecture, including examining possible solutions to the damage, such as digital reconstruction, replication, and distribution of information through exhibitions and other forms of publically accessible information. In order to investigate any possible retribution, research also includes the necessary information pertaining the global laws and regulations dealing with cultural heritage, as it directly affects the ways in which this situation can be dealt with. With the countless experts and citizens dedicated to the importance of cultural heritage, the prospect of honoring and valuing elements of Dura-Europos is possible—whether physically preserved or otherwise.

Keywords: antiquities law, archaeological sites, restitution, Syrian Civil War

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Authors: Rajkumar Ghosh, Bhabani Prasad Mukhopadhay

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Groundwater contamination with fluoride has emerged as a global concern affecting millions of people, leading to the widespread occurrence of fluorosis. It affects bones and teeth, leading to dental and skeletal fluorosis. This study presents a comprehensive analysis of the relationship between groundwater contamination and fluorosis. It delves into the causes of fluoride contamination in groundwater, its spatial distribution, and adverse health impacts of fluorosis on affected communities. Fluoride contamination in groundwater can be attributed to both natural and anthropogenic sources. Geogenic sources involve the dissolution of fluoride-rich minerals present in the aquifer materials. On the other hand, anthropogenic activities such as industrial discharges, agricultural practices, and improper disposal of fluoride-containing waste contribute to the contamination of groundwater. The spatial distribution of fluoride contamination varies widely across different regions and geological formations. High fluoride levels are commonly observed in areas with fluorine-rich geological deposits. Additionally, agricultural and industrial centres often exhibit elevated fluoride concentrations due to anthropogenic contributions. Excessive fluoride ingestion during tooth development leads to dental fluorosis, characterized by enamel defects, discoloration, and dental caries. The severity of dental fluorosis varies based on fluoride exposure levels during tooth development. Long-term consumption of fluoride-contaminated water causes skeletal fluorosis, resulting in bone and joint pain, decreased joint mobility, and skeletal deformities. In severe cases, skeletal fluorosis can lead to disability and reduced quality of life. Various defluoridation techniques such as activated alumina, bone char, and reverse osmosis have been employed to reduce fluoride concentrations in drinking water. These methods effectively remove fluoride, but their implementation requires careful consideration of cost, maintenance, and sustainability. Diversifying water sources, such as rainwater harvesting and surface water supply, can reduce the reliance on fluoride-contaminated groundwater, especially in regions with high fluoride concentrations. Groundwater contamination with fluoride remains a significant public health challenge, leading to the widespread occurrence of fluorosis globally. This scientific report emphasizes the importance of understanding the relationship between groundwater contamination and fluorosis. Implementing effective mitigation strategies and preventive measures is crucial to combat fluorosis and ensure sustainable access to safe drinking water for communities worldwide. Collaborative efforts between government agencies, local communities, and scientific researchers are essential to address this issue and safeguard the health of vulnerable populations. Additionally, the report explores various mitigation strategies and preventive measures to address the issue and offers recommendations for sustainable management of groundwater resources to combat fluorosis effectively.

Keywords: fluorosis, fluoride contamination, groundwater contamination, groundwater resources

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Authors: Lauren Beth Birney

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BOP-CCERS is a consortium of scientists, K-16 New York City students, faculty, academicians, teachers, stakeholders, STEM Industry professionals, CBO’s, NPO’s, citizen scientists, and local businesses working in partnership to restore New York Harbor’s oyster populations while at the same time providing clean water in New York Harbor. BOP-CCERS gives students an opportunity to learn hands-on about environmental stewardship as well as environmental law and policy by giving students real responsibility. The purpose of this REU will allow for the BOP CCERS Project to further broaden its parameters into the focus of environmental law and policy where further change can be affected. Creating opportunities for undergraduates to work collaboratively with graduate students in law and policy and envision themselves in STEM careers in the field of law continues to be of importance in this project. More importantly, creating opportunities for underrepresented students to pursue careers in STEM Education has been a goal of the project over the last ten years. By raising the level of student interest in community-based citizen science integrated into environmental law and policy, a more diversified workforce will be fostered through the momentum of this dynamic program. The continuing climate crisis facing our planet calls for 21st-century skill development that includes learning and innovation skills derived from critical thinking, which will help REU students address the issues of climate change facing our planet. The demand for a climate-friendly workforce will continue to be met through this community-based citizen science effort. Environmental laws and policies play a crucial role in protecting humans, animals, resources, and habitats. Without these laws, there would be no regulations concerning pollution or contamination of our waterways. Environmental law serves as a mechanism to protect the land, air, water, and soil of our planet. To protect the environment, it is crucial that future policymakers and legal experts both understand and value the importance of environmental protection. The Environmental Law and Policy REU provides students with the opportunity to learn, through hands-on work, the skills, and knowledge needed to help foster a legal workforce centered around environmental protection while participating alongside the BOP CCERS researchers in order to gain research experience. Broadening this area to law and policy will further increase these opportunities and permit students to ultimately affect and influence larger-scale change on a global level while further diversifying the STEM workforce. Students’ findings will be shared at the annual STEM Institute at Pace University in August 2022. Basic research methodologies include qualitative and quantitative analysis performed by the research team. Early findings indicate that providing students with an opportunity to experience, explore and participate in environmental science programs such as these enhances their interests in pursuing STEM careers in Law and Policy, with the focus being on providing opportunities for underserved, marginalized, and underrepresented populations.

Keywords: environmental restoration science, citizen science, environmental law and policy, STEM education

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Authors: Nejmeddine Ouhichi, Fethi Lachaal, Radhouane Hamdi, Olivier Grunberger

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Located in Cap Bon peninsula (Tunisia), the Lebna dam was built in 1987 to balance local water salt intrusion taking place in the coastal aquifer of Korba. The first intention was to reduce coastal groundwater over-pumping by supplying surface water to a large irrigation system. The unpredicted beneficial effect was recorded with the occurrence of a direct localized recharge to the coastal aquifer by leakage through the geological material of the southern bank of the lake. The hydrological balance of the reservoir dam gave an estimation of the annual leakage volume, but dynamic processes and sound quantification of recharge inputs are still required to understand the localized effect of the recharge in terms of piezometry and quality. Present work focused on simulating the recharge process to confirm the hypothesis, and established a sound quantification of the water supply to the coastal aquifer and extend it to multi-annual effects. A spatial frame of 30km² was used for modeling. Intensive outcrops and geophysical surveys based on 68 electrical resistivity soundings were used to characterize the aquifer 3D geometry and the limit of the Plio-quaternary geological material concerned by the underground flow paths. Permeabilities were determined using 17 pumping tests on wells and piezometers. Six seasonal piezometric surveys on 71 wells around southern reservoir dam banks were performed during the 2019-2021 period. Eight monitoring boreholes of high frequency (15min) piezometric data were used to examine dynamical aspects. Model boundary conditions were specified using the geophysics interpretations coupled with the piezometric maps. The dam-groundwater flow model was performed using Visual MODFLOW software. Firstly, permanent state calibration based on the first piezometric map of February 2019 was established to estimate the permanent flow related to the different reservoir levels. Secondly, piezometric data for the 2019-2021 period were used for transient state calibration and to confirm the robustness of the model. Preliminary results confirmed the temporal link between the reservoir level and the localized recharge flow with a strong threshold effect for levels below 16 m.a.s.l. The good agreement of computed flow through recharge cells on the southern banks and hydrological budget of the reservoir open the path to future simulation scenarios of the dilution plume imposed by the localized recharge. The dam reservoir-groundwater flow-model simulation results approve a potential for storage of up to 17mm/year in existing wells, under gravity-feed conditions during level increases on the reservoir into the three years of operation. The Lebna dam groundwater flow model characterized a spatiotemporal relation between groundwater and surface water.

Keywords: leakage, MODFLOW, saltwater intrusion, surface water-groundwater interaction

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Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

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In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.

Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation

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