Search results for: computers and humans
Commenced in January 2007
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Edition: International
Paper Count: 1327

Search results for: computers and humans

157 Exposure to Radon on Air in Tourist Caves in Bulgaria

Authors: Bistra Kunovska, Kremena Ivanova, Jana Djounova, Desislava Djunakova, Zdenka Stojanovska

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The carcinogenic effects of radon as a radioactive noble gas have been studied and show a strong correlation between radon exposure and lung cancer occurrence, even in the case of low radon levels. The major part of the natural radiation dose in humans is received by inhaling radon and its progenies, which originates from the decay chain of U-238. Indoor radon poses a substantial threat to human health when build-up occurs in confined spaces such as homes, mines and caves and the risk increases with the duration of radon exposure and is proportional to both the radon concentration and the time of exposure. Tourist caves are a case of special environmental conditions that may be affected by high radon concentration. Tourist caves are a recognized danger in terms of radon exposure to cave workers (guides, employees working in shops built above the cave entrances, etc.), but due to the sensitive nature of the cave environment, high concentrations cannot be easily removed. Forced ventilation of the air in the caves is considered unthinkable due to the possible harmful effects on the microclimate, flora and fauna. The risks to human health posed by exposure to elevated radon levels in caves are not well documented. Various studies around the world often detail very high concentrations of radon in caves and exposure of employees but without a follow-up assessment of the overall impact on human health. This study was developed in the implementation of a national project to assess the potential health effects caused by exposure to elevated levels of radon in buildings with public access under the National Science Fund of Bulgaria, in the framework of grant No КП-06-Н23/1/07.12.2018. The purpose of the work is to assess the radon level in Bulgarian caves and the exposure of the visitors and workers. The number of caves (sampling size) was calculated for simple random selection from total available caves 65 (sampling population) are 13 caves with confidence level 95 % and confidence interval (margin of error) approximately 25 %. A measurement of the radon concentration in air at specific locations in caves was done by using CR-39 type nuclear track-etch detectors that were placed by the participants in the research team. Despite the fact that all of the caves were formed in karst rocks, the radon levels were rather different from each other (97–7575 Bq/m3). An assessment of the influence of the orientation of the caves in the earth's surface (horizontal, inclined, vertical) on the radon concentration was performed. Evaluation of health hazards and radon risk exposure causing by inhaling the radon and its daughter products in each surveyed caves was done. Reducing the time spent in the cave has been recommended in order to decrease the exposure of workers.

Keywords: tourist caves, radon concentration, exposure, Bulgaria

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156 CSPG4 Molecular Target in Canine Melanoma, Osteosarcoma and Mammary Tumors for Novel Therapeutic Strategies

Authors: Paola Modesto, Floriana Fruscione, Isabella Martini, Simona Perga, Federica Riccardo, Mariateresa Camerino, Davide Giacobino, Cecilia Gola, Luca Licenziato, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari

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Canine and human melanoma, osteosarcoma (OSA), and mammary carcinomas are aggressive tumors with common characteristics making dogs a good model for comparative oncology. Novel therapeutic strategies against these tumors could be useful to both species. In humans, chondroitin sulphate proteoglycan 4 (CSPG4) is a marker involved in tumor progression and could be a candidate target for immunotherapy. The anti-CSPG4 DNA electrovaccination has shown to be an effective approach for canine malignant melanoma (CMM) [1]. An immunohistochemistry evaluation of CSPG4 expression in tumour tissue is generally performed prior to electrovaccination. To assess the possibility to perform a rapid molecular evaluation and in order to validate these spontaneous canine tumors as the model for human studies, we investigate the CSPG4 gene expression by RT qPCR in CMM, OSA, and canine mammary tumors (CMT). The total RNA was extracted from RNAlater stored tissue samples (CMM n=16; OSA n=13; CMT n=6; five paired normal tissues for CMM, five paired normal tissues for OSA and one paired normal tissue for CMT), retro-transcribed and then analyzed by duplex RT-qPCR using two different TaqMan assays for the target gene CSPG4 and the internal reference gene (RG) Ribosomal Protein S19 (RPS19). RPS19 was selected from a panel of 9 candidate RGs, according to NormFinder analysis following the protocol already described [2]. Relative expression was analyzed by CFX Maestro™ Software. Student t-test and ANOVA were performed (significance set at P<0.05). Results showed that gene expression of CSPG4 in OSA tissues is significantly increased by 3-4 folds when compared to controls. In CMT, gene expression of the target was increased from 1.5 to 19.9 folds. In melanoma, although an increasing trend was observed, no significant differences between the two groups were highlighted. Immunohistochemistry analysis of the two cancer types showed that the expression of CSPG4 within CMM is concentrated in isles of cells compared to OSA, where the distribution of positive cells is homogeneous. This evidence could explain the differences in gene expression results.CSPG4 immunohistochemistry evaluation in mammary carcinoma is in progress. The evidence of CSPG4 expression in a different type of canine tumors opens the way to the possibility of extending the CSPG4 immunotherapy marker in CMM, OSA, and CMT and may have an impact to translate this strategy modality to human oncology.

Keywords: canine melanoma, canine mammary carcinomas, canine osteosarcoma, CSPG4, gene expression, immunotherapy

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155 The Application of Raman Spectroscopy in Olive Oil Analysis

Authors: Silvia Portarena, Chiara Anselmi, Chiara Baldacchini, Enrico Brugnoli

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Extra virgin olive oil (EVOO) is a complex matrix mainly composed by fatty acid and other minor compounds, among which carotenoids are well known for their antioxidative function that is a key mechanism of protection against cancer, cardiovascular diseases, and macular degeneration in humans. EVOO composition in terms of such constituents is generally the result of a complex combination of genetic, agronomical and environmental factors. To selectively improve the quality of EVOOs, the role of each factor on its biochemical composition need to be investigated. By selecting fruits from four different cultivars similarly grown and harvested, it was demonstrated that Raman spectroscopy, combined with chemometric analysis, is able to discriminate the different cultivars, also as a function of the harvest date, based on the relative content and composition of fatty acid and carotenoids. In particular, a correct classification up to 94.4% of samples, according to the cultivar and the maturation stage, was obtained. Moreover, by using gas chromatography and high-performance liquid chromatography as reference techniques, the Raman spectral features further allowed to build models, based on partial least squares regression, that were able to predict the relative amount of the main fatty acids and the main carotenoids in EVOO, with high coefficients of determination. Besides genetic factors, climatic parameters, such as light exposition, distance from the sea, temperature, and amount of precipitations could have a strong influence on EVOO composition of both major and minor compounds. This suggests that the Raman spectra could act as a specific fingerprint for the geographical discrimination and authentication of EVOO. To understand the influence of environment on EVOO Raman spectra, samples from seven regions along the Italian coasts were selected and analyzed. In particular, it was used a dual approach combining Raman spectroscopy and isotope ratio mass spectrometry (IRMS) with principal component and linear discriminant analysis. A correct classification of 82% EVOO based on their regional geographical origin was obtained. Raman spectra were obtained by Super Labram spectrometer equipped with an Argon laser (514.5 nm wavelenght). Analyses of stable isotope content ratio were performed using an isotope ratio mass spectrometer connected to an elemental analyzer and to a pyrolysis system. These studies demonstrate that RR spectroscopy is a valuable and useful technique for the analysis of EVOO. In combination with statistical analysis, it makes possible the assessment of specific samples’ content and allows for classifying oils according to their geographical and varietal origin.

Keywords: authentication, chemometrics, olive oil, raman spectroscopy

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154 The Beneficial Effects of Inhibition of Hepatic Adaptor Protein Phosphotyrosine Interacting with PH Domain and Leucine Zipper 2 on Glucose and Cholesterol Homeostasis

Authors: Xi Chen, King-Yip Cheng

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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

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153 Pixel Façade: An Idea for Programmable Building Skin

Authors: H. Jamili, S. Shakiba

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Today, one of the main concerns of human beings is facing the unpleasant changes of the environment. Buildings are responsible for a significant amount of natural resources consumption and carbon emissions production. In such a situation, this thought comes to mind that changing each building into a phenomenon of benefit to the environment. A change in a way that each building functions as an element that supports the environment, and construction, in addition to answering the need of humans, is encouraged, the way planting a tree is, and it is no longer seen as a threat to alive beings and the planet. Prospect: Today, different ideas of developing materials that can smartly function are realizing. For instance, Programmable Materials, which in different conditions, can respond appropriately to the situation and have features of modification in shape, size, physical properties and restoration, and repair quality. Studies are to progress having this purpose to plan for these materials in a way that they are easily available, and to meet this aim, there is no need to use expensive materials and high technologies. In these cases, physical attributes of materials undertake the role of sensors, wires and actuators then materials will become into robots itself. In fact, we experience robotics without robots. In recent decades, AI and technology advances have dramatically improving the performance of materials. These achievements are a combination of software optimizations and physical productions such as multi-materials 3D printing. These capabilities enable us to program materials in order to change shape, appearance, and physical properties to interact with different situations. nIt is expected that further achievements like Memory Materials and Self-learning Materials are also added to the Smart Materials family, which are affordable, available, and of use for a variety of applications and industries. From the architectural standpoint, the building skin is significantly considered in this research, concerning the noticeable surface area the buildings skin have in urban space. The purpose of this research would be finding a way that the programmable materials be used in building skin with the aim of having an effective and positive interaction. A Pixel Façade would be a solution for programming a building skin. The Pixel Facadeincludes components that contain a series of attributes that help buildings for their needs upon their environmental criteria. A PIXEL contains series of smart materials and digital controllers together. It not only benefits its physical properties, such as control the amount of sunlight and heat, but it enhances building performance by providing a list of features, depending on situation criteria. The features will vary depending on locations and have a different function during the daytime and different seasons. The primary role of a PIXEL FAÇADE can be defined as filtering pollutions (for inside and outside of the buildings) and providing clean energy as well as interacting with other PIXEL FACADES to estimate better reactions.

Keywords: building skin, environmental crisis, pixel facade, programmable materials, smart materials

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152 An E-Maintenance IoT Sensor Node Designed for Fleets of Diverse Heavy-Duty Vehicles

Authors: George Charkoftakis, Panagiotis Liosatos, Nicolas-Alexander Tatlas, Dimitrios Goustouridis, Stelios M. Potirakis

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E-maintenance is a relatively new concept, generally referring to maintenance management by monitoring assets over the Internet. One of the key links in the chain of an e-maintenance system is data acquisition and transmission. Specifically for the case of a fleet of heavy-duty vehicles, where the main challenge is the diversity of the vehicles and vehicle-embedded self-diagnostic/reporting technologies, the design of the data acquisition and transmission unit is a demanding task. This clear if one takes into account that a heavy-vehicles fleet assortment may range from vehicles with only a limited number of analog sensors monitored by dashboard light indicators and gauges to vehicles with plethora of sensors monitored by a vehicle computer producing digital reporting. The present work proposes an adaptable internet of things (IoT) sensor node that is capable of addressing this challenge. The proposed sensor node architecture is based on the increasingly popular single-board computer – expansion boards approach. In the proposed solution, the expansion boards undertake the tasks of position identification by means of a global navigation satellite system (GNSS), cellular connectivity by means of 3G/long-term evolution (LTE) modem, connectivity to on-board diagnostics (OBD), and connectivity to analog and digital sensors by means of a novel design of expansion board. Specifically, the later provides eight analog plus three digital sensor channels, as well as one on-board temperature / relative humidity sensor. The specific device offers a number of adaptability features based on appropriate zero-ohm resistor placement and appropriate value selection for limited number of passive components. For example, although in the standard configuration four voltage analog channels with constant voltage sources for the power supply of the corresponding sensors are available, up to two of these voltage channels can be converted to provide power to the connected sensors by means of corresponding constant current source circuits, whereas all parameters of analog sensor power supply and matching circuits are fully configurable offering the advantage of covering a wide variety of industrial sensors. Note that a key feature of the proposed sensor node, ensuring the reliable operation of the connected sensors, is the appropriate supply of external power to the connected sensors and their proper matching to the IoT sensor node. In standard mode, the IoT sensor node communicates to the data center through 3G/LTE, transmitting all digital/digitized sensor data, IoT device identity, and position. Moreover, the proposed IoT sensor node offers WiFi connectivity to mobile devices (smartphones, tablets) equipped with an appropriate application for the manual registration of vehicle- and driver-specific information, and these data are also forwarded to the data center. All control and communication tasks of the IoT sensor node are performed by dedicated firmware. It is programmed with a high-level language (Python) on top of a modern operating system (Linux). Acknowledgment: This research has been co-financed by the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship, and Innovation, under the call RESEARCH—CREATE—INNOVATE (project code: T1EDK- 01359, IntelligentLogger).

Keywords: IoT sensor nodes, e-maintenance, single-board computers, sensor expansion boards, on-board diagnostics

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151 The Socio-Emotional Vulnerability of Professional Rugby Union Athletes

Authors: Hannah Kuhar

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This paper delves into the attitudes of professional and semi-professional rugby union athletes in regard to socio-emotional vulnerability, or the willingness to express the full spectrum of human emotion in a social context. Like all humans, athletes of all sports regularly experience feelings of shame, powerlessness, and loneliness, and often feel unable to express such feelings due to factors including lack of situational support, absence of adequate expressive language and lack of resource. To this author’s knowledge, however, no previous research has considered the particular demographic of professional rugby union athletes, despite the sport’s immense popularity and economic contribution to global communities. Hence, this paper aims to extend previous research by exploring the experiences of professional rugby union athletes and their unwillingness and inability to express socio-emotional vulnerability. By having a better understanding of vulnerability in rugby and sports, this paper is able to contribute to the growing field of mental health and wellbeing research, particularly towards the emerging themes of resilience and belonging. Based on qualitative fieldwork conducted over a period of seven months across France and Australia, via the mechanisms of semi-structured interview and observation, this work uses the field theory framework of Pierre Bourdieu to construct an analysis of multidisciplinary thought. Approaching issues of gender, sexuality, physicality, education, and family, this paper shows that socio-emotional vulnerability is experienced by all players regardless of their background, in a variety of ways. Common themes and responses are drawn to show the universality of rugby’s pitfalls, which have previously been limited to specific demographics in isolation of their broader contexts. With the author themselves a semi-professional athlete, the provision of unique ‘insider’ access facilitates a deeper and more comprehensive understanding of first-hand athlete experiences, often unexplored within the context of the academic arena. The primary contention of this paper is to argue that by celebrating socio-emotional vulnerability, there becomes an opportunity to improve on-field team outcomes. Ultimately, players play better when they feel supported by their teammates, and this logic extends to the outcome of the team when socio-emotional team initiatives are widely embraced. The creation of such a culture requires deliberate and purposeful efforts, where player ownership and buy-in are high. Further study in this field may assist teams to better understand the elements which contribute to strong team culture and to strong results on the pitch.

Keywords: rugby, vulnerability, athletes, France, Bourdieu

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150 Space Tourism Pricing Model Revolution from Time Independent Model to Time-Space Model

Authors: Kang Lin Peng

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Space tourism emerged in 2001 and became famous in 2021, following the development of space technology. The space market is twisted because of the excess demand. Space tourism is currently rare and extremely expensive, with biased luxury product pricing, which is the seller’s market that consumers can not bargain with. Spaceship companies such as Virgin Galactic, Blue Origin, and Space X have been charged space tourism prices from 200 thousand to 55 million depending on various heights in space. There should be a reasonable price based on a fair basis. This study aims to derive a spacetime pricing model, which is different from the general pricing model on the earth’s surface. We apply general relativity theory to deduct the mathematical formula for the space tourism pricing model, which covers the traditional time-independent model. In the future, the price of space travel will be different from current flight travel when space travel is measured in lightyear units. The pricing of general commodities mainly considers the general equilibrium of supply and demand. The pricing model considers risks and returns with the dependent time variable as acceptable when commodities are on the earth’s surface, called flat spacetime. Current economic theories based on the independent time scale in the flat spacetime do not consider the curvature of spacetime. Current flight services flying the height of 6, 12, and 19 kilometers are charging with a pricing model that measures time coordinate independently. However, the emergence of space tourism is flying heights above 100 to 550 kilometers that have enlarged the spacetime curvature, which means tourists will escape from a zero curvature on the earth’s surface to the large curvature of space. Different spacetime spans should be considered in the pricing model of space travel to echo general relativity theory. Intuitively, this spacetime commodity needs to consider changing the spacetime curvature from the earth to space. We can assume the value of each spacetime curvature unit corresponding to the gradient change of each Ricci or energy-momentum tensor. Then we know how much to spend by integrating the spacetime from the earth to space. The concept is adding a price p component corresponding to the general relativity theory. The space travel pricing model degenerates into a time-independent model, which becomes a model of traditional commodity pricing. The contribution is that the deriving of the space tourism pricing model will be a breakthrough in philosophical and practical issues for space travel. The results of the space tourism pricing model extend the traditional time-independent flat spacetime mode. The pricing model embedded spacetime as the general relativity theory can better reflect the rationality and accuracy of space travel on the universal scale. The universal scale from independent-time scale to spacetime scale will bring a brand-new pricing concept for space traveling commodities. Fair and efficient spacetime economics will also bring to humans’ travel when we can travel in lightyear units in the future.

Keywords: space tourism, spacetime pricing model, general relativity theory, spacetime curvature

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149 Preliminary Analysis on the Distribution of Elements in Cannabis

Authors: E. Zafeiraki, P. Nisianakis, K. Machera

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Cannabis plant contains 113 cannabinoids and it is commonly known for its psychoactive substance tetrahydrocannabinol or as a source of narcotic substances. The recent years’ cannabis cultivation also increases due to its wide use both for medical and industrial purposes as well as for uses as para-pharmaceuticals, cosmetics and food commodities. Depending on the final product, different parts of the plant are utilized, with the leaves and bud (seeds) being the most frequently used. Cannabis can accumulate various contaminants, including heavy metals, both from the soil and the water in which the plant grows. More specifically, metals may occur naturally in the soil and water, or they can enter into the environment through fertilizers, pesticides and fungicides that are commonly applied to crops. The high probability of metals accumulation in cannabis, combined with the latter growing use, raise concerns about the potential health effects in humans and consequently lead to the need for the implementation of safety measures for cannabis products, such as guidelines for regulating contaminants, including metals, and especially the ones characterized by high toxicity in cannabis. Acknowledging the above, the aim of the current study was first to investigate metals contamination in cannabis samples collected from Greece, and secondly to examine potential differences in metals accumulation among the different parts of the plant. To our best knowledge, this is the first study presenting information on elements in cannabis cultivated in Greece, and also on the distribution pattern of the former in the plant body. To this end, the leaves and the seeds of all the samples were initially separated and dried and then digested with Nitric acid (HNO₃) and Hydrochloric acid (HCl). For the analysis of these samples, an Inductive Coupled Plasma-Mass Spectrometry (ICP-MS) method was developed, able to quantify 28 elements. Internal standards were added at a constant rate and concentration to all calibration standards and unknown samples, while two certified reference materials were analyzed in every batch to ensure the accuracy of the measurements. The repeatability of the method and the background contamination were controlled by the analysis of quality control (QC) standards and blank samples in every sequence, respectively. According to the results, essential metals, such as Ca, Zn and Mg, were detected at high levels. On the contrary, the concentration of high toxicity metals, like As (average: 0.10ppm), Pb (average: 0.36ppm), Cd (average: 0.04ppm), and Hg (average: 0.012ppm) were very low in all the samples, indicating that no harmful effects on human health can be caused by the analyzed samples. Moreover, it appears that the pattern of contamination of metals is very similar in all the analyzed samples, which could be attributed to the same origin of the analyzed cannabis, i.e., the common soil composition, use of fertilizers, pesticides, etc. Finally, as far as the distribution pattern between the different parts of the plant is concerned, it was revealed that leaves present a higher concentration in comparison to seeds for all metals examined.

Keywords: cannabis, heavy metals, ICP-MS, leaves and seeds, elements

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148 Nuclear Near Misses and Their Learning for Healthcare

Authors: Nick Woodier, Iain Moppett

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Background: It is estimated that one in ten patients admitted to hospital will suffer an adverse event in their care. While the majority of these will result in low harm, patients are being significantly harmed by the processes meant to help them. Healthcare, therefore, seeks to make improvements in patient safety by taking learning from other industries that are perceived to be more mature in their management of safety events. Of particular interest to healthcare are ‘near misses,’ those events that almost happened but for an intervention. Healthcare does not have any guidance as to how best to manage and learn from near misses to reduce the chances of harm to patients. The authors, as part of a larger study of near-miss management in healthcare, sought to learn from the UK nuclear sector to develop principles for how healthcare can identify, report, and learn from near misses to improve patient safety. The nuclear sector was chosen as an exemplar due to its status as an ultra-safe industry. Methods: A Grounded Theory (GT) methodology, augmented by a scoping review, was used. Data collection included interviews, scenario discussion, field notes, and the literature. The review protocol is accessible online. The GT aimed to develop theories about how nuclear manages near misses with a focus on defining them and clarifying how best to support reporting and analysis to extract learning. Near misses related to radiation release or exposure were focused on. Results: Eightnuclear interviews contributed to the GT across nuclear power, decommissioning, weapons, and propulsion. The scoping review identified 83 articles across a range of safety-critical industries, with only six focused on nuclear. The GT identified that nuclear has a particular focus on precursors and low-level events, with regulation supporting their management. Exploration of definitions led to the recognition of the importance of several interventions in a sequence of events, but that do not solely rely on humans as these cannot be assumed to be robust barriers. Regarding reporting and analysis, no consistent methods were identified, but for learning, the role of operating experience learning groups was identified as an exemplar. The safety culture across nuclear, however, was heard to vary, which undermined reporting of near misses and other safety events. Some parts of the industry described that their focus on near misses is new and that despite potential risks existing, progress to mitigate hazards is slow. Conclusions: Healthcare often sees ‘nuclear,’ as well as other ultra-safe industries such as ‘aviation,’ as homogenous. However, the findings here suggest significant differences in safety culture and maturity across various parts of the nuclear sector. Healthcare can take learning from some aspects of management of near misses in nuclear, such as how they are defined and how learning is shared through operating experience networks. However, healthcare also needs to recognise that variability exists across industries, and comparably, it may be more mature in some areas of safety.

Keywords: culture, definitions, near miss, nuclear safety, patient safety

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147 Oncolytic H-1 Parvovirus Entry in Cancer Cells through Clathrin-Mediated Endocytosis

Authors: T. Ferreira, A. Kulkarni, C. Bretscher, K. Richter, M. Ehrlich, A. Marchini

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H-1 protoparvovirus (H-1PV) is a virus with inherent oncolytic and oncosuppressive activities while remaining non-pathogenic in humans. H-1PV was the first oncolytic parvovirus to undergo clinical testing. Results from trials in patients with glioblastoma or pancreatic carcinoma showed an excellent safety profile and first signs of efficacy. H-1PV infection is vastly dependent on cellular factors, from cell attachment and entry to viral replication and egress. Hence, we believe that the characterisation of the parvovirus life cycle would ultimately help further improve H-1PV clinical outcome. In the present study, we explored the entry pathway of H-1PV in cervical HeLa and glioma NCH125 cancer cell lines. Electron and confocal microscopy showed viral particles associated with clathrin-coated pits and vesicles, providing the first evidence that H-1PV cell entry occurs through clathrin-mediated endocytosis. Accordingly, we observed that by blocking clathrin-mediated endocytosis with hypertonic sucrose, chlorpromazine, or pitstop 2, H-1PV transduction was markedly decreased. Accordingly, siRNA-mediated knockdown of AP2M1, which retains a crucial role in clathrin-mediated endocytosis, verified the reliance of H-1PV on this route to enter HeLa and NCH125 cancer cells. By contrast, we found no evidence of viral entry through caveolae-mediated endocytosis. Indeed, pre-treatment of cells with nystatin or methyl-β-cyclodextrin, both inhibitors of caveolae-mediated endocytosis, did not affect viral transduction levels. Unexpectedly, siRNA-mediated knockdown of caveolin-1, the main driver of caveolae-mediated endocytosis, increased H-1PV transduction, suggesting caveolin-1 is a negative modulator of H-1PV infection. We also show that H-1PV entry is dependent on dynamin, a protein responsible for mediating the scission of vesicle neck and promoting further internalisation. Furthermore, since dynamin inhibition almost completely abolished H-1PV infection, makes it unlikely that H-1PV uses macropinocytosis as an alternative pathway to enter cells. After viral internalisation, H-1PV passes through early to late endosomes as observed by confocal microscopy. Inside these endocytic compartments, the acidic environment proved to be crucial for a productive infection. Inhibition of acidification of pH dramatically reduced H-1PV transduction. Besides, a fraction of H-1PV particles was observed inside LAMP1-positive lysosomes, most likely following a non-infectious route. To the author's best knowledge, this is the first study to characterise the cell entry pathways of H-1PV. Along these lines, this work will further contribute to understand H-1PV oncolytic properties as well as to improve its clinical potential in cancer virotherapy.

Keywords: clathrin-mediated endocytosis, H-1 parvovirus, oncolytic virus, virus entry

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146 Evotrader: Bitcoin Trading Using Evolutionary Algorithms on Technical Analysis and Social Sentiment Data

Authors: Martin Pellon Consunji

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Due to the rise in popularity of Bitcoin and other crypto assets as a store of wealth and speculative investment, there is an ever-growing demand for automated trading tools, such as bots, in order to gain an advantage over the market. Traditionally, trading in the stock market was done by professionals with years of training who understood patterns and exploited market opportunities in order to gain a profit. However, nowadays a larger portion of market participants are at minimum aided by market-data processing bots, which can generally generate more stable signals than the average human trader. The rise in trading bot usage can be accredited to the inherent advantages that bots have over humans in terms of processing large amounts of data, lack of emotions of fear or greed, and predicting market prices using past data and artificial intelligence, hence a growing number of approaches have been brought forward to tackle this task. However, the general limitation of these approaches can still be broken down to the fact that limited historical data doesn’t always determine the future, and that a lot of market participants are still human emotion-driven traders. Moreover, developing markets such as those of the cryptocurrency space have even less historical data to interpret than most other well-established markets. Due to this, some human traders have gone back to the tried-and-tested traditional technical analysis tools for exploiting market patterns and simplifying the broader spectrum of data that is involved in making market predictions. This paper proposes a method which uses neuro evolution techniques on both sentimental data and, the more traditionally human-consumed, technical analysis data in order to gain a more accurate forecast of future market behavior and account for the way both automated bots and human traders affect the market prices of Bitcoin and other cryptocurrencies. This study’s approach uses evolutionary algorithms to automatically develop increasingly improved populations of bots which, by using the latest inflows of market analysis and sentimental data, evolve to efficiently predict future market price movements. The effectiveness of the approach is validated by testing the system in a simulated historical trading scenario, a real Bitcoin market live trading scenario, and testing its robustness in other cryptocurrency and stock market scenarios. Experimental results during a 30-day period show that this method outperformed the buy and hold strategy by over 260% in terms of net profits, even when taking into consideration standard trading fees.

Keywords: neuro-evolution, Bitcoin, trading bots, artificial neural networks, technical analysis, evolutionary algorithms

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145 Impact of the Achyranthes aspera (Amaranthaceae) Extracts on the Survival and Histological Architecture of the Midgut Epithelial Tissue of Early Fourth Instars of Aedes aegypti (Diptera: Culicidae)

Authors: Aarti Sharma, Sarita Kumar, Pushplata Tripathi

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Aedes aegypti L. is one of the most important insect vectors in the world transmitting several diseases of concern; dengue fever, dengue haemorrhagic fever and yellow fever. Though since ages the control of dengue vector is primarily relied upon the use of synthetic chemical insecticides, the continued and indiscriminate use of insecticides for their control has received wide public apprehension because of multifarious problems including insecticide resistance, resurgence of pest species, environmental pollution, toxic hazards to humans and non-target organisms. These problems have necessitated the need to explore and develop alternative strategies using eco-friendly and bio-degradable plant products. Bio-insecticides, despite being the focus of research nowadays, have not been investigated much regarding their physiological effects on the mosquitoes. Thus, the present studies were carried out to investigate the anti-mosquito potential of the leaf and stem hexane extracts of Achyranthes aspera against early fourth instars of Aedes aegypti L and their effects on the histological architecture of their midgut. The larvicidal bioassays conducted with the A. aspera leaf hexane extracts revealed the respective LC30, LC50 and LC90 values of 66.545 ppm, 82.555 ppm, 139.817 ppm while the assays with stem hexane extracts resulted in respective values of 54.982 ppm, 68.133 ppm, 115.075 ppm. The studies clearly indicate the efficacy of extracts as larvicidal agents against Ae. aegypti, the stem extracts being found more effective than the leaf extracts. When the larvae assayed with extracts were investigated for the modifications in the histo-architecture of the midgut, the studies showed significant damage, shrinkage, distortion and vacuolization of gut tissues and peritrophic membrane causing disintegration of epithelial cells and cytoplasmic organelles; extent of toxicity and damage varied depending upon the concentration and exposure time period. These changes revealed appreciable stomach poison potential of A. aspera extracts against Ae. aegypti larvae, which may have also caused adverse impact on the growth and development of larvae. These effects were also found to be more pronounced with the stem extract than the leaf extract. Our findings may prove significant suggesting the use of A. aspera extract as a bio-insecticide against early fourth instar larvae of Ae. aegypti. Further studies are needed to identify the bioactive component in the extracts and to ascertain the use of component in the fields as anti-mosquito control agent.

Keywords: Achyranthes aspera, Aedes aegypti, histological architecture, larvicidal, midgut, stomach poison

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144 Ex-vivo Bio-distribution Studies of a Potential Lung Perfusion Agent

Authors: Shabnam Sarwar, Franck Lacoeuille, Nadia Withofs, Roland Hustinx

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After the development of a potential surrogate of MAA, and its successful application for the diagnosis of pulmonary embolism in artificially embolized rats’ lungs, this microparticulate system were radiolabelled with gallium-68 to synthesize 68Ga-SBMP with high radiochemical purity >99%. As a prerequisite step of clinical trials, 68Ga- labelled starch based microparticles (SBMP) were analysed for their in-vivo behavior in small animals. The purpose of the presented work includes the ex-vivo biodistribution studies of 68Ga-SBMP in order to assess the activity uptake in target organs with respect to time, excretion pathways of the radiopharmaceutical, %ID/g in major organs, T/NT ratios, in-vivo stability of the radiotracer and subsequently the microparticles in the target organs. Radiolabelling of starch based microparticles was performed by incubating it with 68Ga generator eluate (430±26 MBq) at room temperature and pressure without using any harsh reaction condition. For Ex-vivo biodistribution studies healthy White Wistar rats weighing between 345-460 g were injected intravenously 68Ga-SBMP 20±8 MBq, containing about 2,00,000-6,00,000 SBMP particles in a volume of 700µL. The rats were euthanized at predefined time intervals (5min, 30min, 60min and 120min) and their organ parts were cut, washed, and put in the pre-weighed tubes and measured for radioactivity counts through automatic Gamma counter. The 68Ga-SBMP produced >99% RCP just after 10-20 min incubation through a simple and robust procedure. Biodistribution of 68Ga-SBMP showed that initially just after 5 min post injection major uptake was observed in the lungs following by blood, heart, liver, kidneys, bladder, urine, spleen, stomach, small intestine, colon, skin and skeleton, thymus and at last the smallest activity was found in brain. Radioactivity counts stayed stable in lungs with gradual decrease with the passage of time, and after 2h post injection, almost half of the activity were seen in lungs. This is a sufficient time to perform PET/CT lungs scanning in humans while activity in the liver, spleen, gut and urinary system decreased with time. The results showed that urinary system is the excretion pathways instead of hepatobiliary excretion. There was a high value of T/NT ratios which suggest fine tune images for PET/CT lung perfusion studies henceforth further pre-clinical studies and then clinical trials should be planned in order to utilize this potential lung perfusion agent.

Keywords: starch based microparticles, gallium-68, biodistribution, target organs, excretion pathways

Procedia PDF Downloads 145
143 The Impact of HKUST-1 Metal-Organic Framework Pretreatment on Dynamic Acetaldehyde Adsorption

Authors: M. François, L. Sigot, C. Vallières

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Volatile Organic Compounds (VOCs) are a real health issue, particularly in domestic indoor environments. Among these VOCs, acetaldehyde is frequently monitored in dwellings ‘air, especially due to smoking and spontaneous emissions from the new wall and soil coverings. It is responsible for respiratory complaints and is classified as possibly carcinogenic to humans. Adsorption processes are commonly used to remove VOCs from the air. Metal-Organic Frameworks (MOFs) are a promising type of material for high adsorption performance. These hybrid porous materials composed of metal inorganic clusters and organic ligands are interesting thanks to their high porosity and surface area. The HKUST-1 (also referred to as MOF-199) is a copper-based MOF with the formula [Cu₃(BTC)₂(H₂O)₃]n (BTC = benzene-1,3,5-tricarboxylate) and exhibits unsaturated metal sites that can be attractive sites for adsorption. The objective of this study is to investigate the impact of HKUST-1 pretreatment on acetaldehyde adsorption. Thus, dynamic adsorption experiments were conducted in 1 cm diameter glass column packed with 2 cm MOF bed height. MOF were sieved to 630 µm - 1 mm. The feed gas (Co = 460 ppmv ± 5 ppmv) was obtained by diluting a 1000 ppmv acetaldehyde gas cylinder in air. The gas flow rate was set to 0.7 L/min (to guarantee a suitable linear velocity). Acetaldehyde concentration was monitored online by gas chromatography coupled with a flame ionization detector (GC-FID). Breakthrough curves must allow to understand the interactions between the MOF and the pollutant as well as the impact of the HKUST-1 humidity in the adsorption process. Consequently, different MOF water content conditions were tested, from a dry material with 7 % water content (dark blue color) to water saturated state with approximately 35 % water content (turquoise color). The rough material – without any pretreatment – containing 30 % water serves as a reference. First, conclusions can be drawn from the comparison of the evolution of the ratio of the column outlet concentration (C) on the inlet concentration (Co) as a function of time for different HKUST-1 pretreatments. The shape of the breakthrough curves is significantly different. The saturation of the rough material is slower (20 h to reach saturation) than that of the dried material (2 h). However, the breakthrough time defined for C/Co = 10 % appears earlier in the case of the rough material (0.75 h) compared to the dried HKUST-1 (1.4 h). Another notable difference is the shape of the curve before the breakthrough at 10 %. An abrupt increase of the outlet concentration is observed for the material with the lower humidity in comparison to a smooth increase for the rough material. Thus, the water content plays a significant role on the breakthrough kinetics. This study aims to understand what can explain the shape of the breakthrough curves associated to the pretreatments of HKUST-1 and which mechanisms take place in the adsorption process between the MOF, the pollutant, and the water.

Keywords: acetaldehyde, dynamic adsorption, HKUST-1, pretreatment influence

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142 Exploring the Relationship Between Helicobacter Pylori Infection and the Incidence of Bronchogenic Carcinoma

Authors: Jose R. Garcia, Lexi Frankel, Amalia Ardeljan, Sergio Medina, Ali Yasback, Omar Rashid

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Background: Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that affects nearly half of the population worldwide and humans serve as the principal reservoir. Infection rates usually follow an inverse relationship with hygiene practices and are higher in developing countries than developed countries. Incidence varies significantly by geographic area, race, ethnicity, age, and socioeconomic status. H. pylori is primarily associated with conditions of the gastrointestinal tract such as atrophic gastritis and duodenal peptic ulcers. Infection is also associated with an increased risk of carcinogenesis as there is evidence to show that H. pylori infection may lead to gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. It is suggested that H. pylori infection may be considered as a systemic condition, leading to various novel associations with several different neoplasms such as colorectal cancer, pancreatic cancer, and lung cancer, although further research is needed. Emerging evidence suggests that H. pylori infection may offer protective effects against Mycobacterium tuberculosis as a result of non-specific induction of interferon- γ (IFN- γ). Similar methods of enhanced immunity may affect the development of bronchogenic carcinoma due to the antiproliferative, pro-apoptotic and cytostatic functions of IFN- γ. The purpose of this study was to evaluate the correlation between Helicobacter pylori infection and the incidence of bronchogenic carcinoma. Methods: The data was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate the patients infected versus patients not infected with H. pylori using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale for the purpose of academic research. Standard statistical methods were used. Results:-Between January 2010 and December 2019, the query was analyzed and resulted in 163,224 in both the infected and control group, respectively. The two groups were matched by age range and CCI score. The incidence of bronchogenic carcinoma was 1.853% with 3,024 patients in the H. pylori group compared to 4.785% with 7,810 patients in the control group. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.367 (0.353 - 0.383) with a confidence interval of 95%. The two groups were matched by treatment and incidence of cancer, which resulted in a total of 101,739 patients analyzed after this match. The incidence of bronchogenic carcinoma was 1.929% with 1,962 patients in the H. pylori and treatment group compared to 4.618% with 4,698 patients in the control group with treatment. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.403 (0.383 - 0.425) with a confidence interval of 95%.

Keywords: bronchogenic carcinoma, helicobacter pylori, lung cancer, pathogen-associated molecular patterns

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141 The Development of Group Counseling Program for Elderly's Caregivers by Base on Person-Centered Theory to Promoting for the Resilience Quotient in Elderly People

Authors: Jirapan Khruesarn, Wimwipa Boonklin

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Background: Currently, Thailand has an aging population. In 2017, the elderly population was over 11.14 million. There will be an increase in the number of elderly people, 8.39 million, some people grumble to themselves and have conflicts with their offspring or those close to them. It is a source of stress. Mental health promotion should be given to the elderly in order to cope with these changes. Due to the family characteristics of Thai society, these family members will act as caregivers for the elderly. Therefore, a group-counseling program based on Personnel-Centered Theory for Elderly Caregivers in Mental Health Promotion for Older People in Na Kaeo Municipality, Kau Ka District, Lampang Province, has been developed to compare the elderly care behavior before and after the participation. Methods: This research was study for 20 elderly' caregiver: Those aimed to compare the before and after use of group program for caregiver to promoting for the elderly by the following methods: Step 1 Establish a framework for evaluating elderly care behaviors and develop a group counseling program for promote mental health for elderly on: 1) Body 2) Willpower 3) Social and community management and 4) Organizing learning process. Step 2 Assessing an Elderly Care Behaviors by using "The behavior assessment on caring for the elderly" and assessing the mental health power level of the elderly and follow the counseling program 9 times and compare of the elderly care behaviors before and after joined a group program, and compare of mental health level of caregiver attends a group program. Results: This study is developing a group counseling program to promoting for the resilience quotient in elderly people that the results of the study could be summarized as follows: 1) Before the elderly's caregivers join a group counseling program: Mental health promotion behaviors of the elderly were at the high level of (3.32), and after: were at the high level of (3.44). 2) Before the elderly's caregiver attends a group counseling program: the mental health level of the elderly the mean score was (47.85 percent), and the standard deviation was (0.21 percent) and after. The elderly had a higher score of (51.45 percent) In summary, after the elderly caregivers joined the group, the elderly are higher in all aspects promote mental health for elderly and the statistically significance at the 0.05, It shows that programs are fit for personal and community condition in promoting the mental health of the elderly because this theory has the idea that: Humans have the ability to use their intelligence to solve problems or make decisions effectively, And member of group counseling program have ventured and express grievances that the counselor is a facilitator who focuses on personal development by building relationships among people. In other words, the factors contributing to higher levels of elderly care behaviors is group counseling, that isn't a hypothetical process but focus on building relationships that are based on mutual trust and Unconditional acceptance.

Keywords: group counseling base on person-centered theory, elderly person, resilience quotient: RQ, caregiver

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140 Harnessing Clinical Trial Capacity to Mitigate Zoonotic Diseases: The Role of Expert Scientists in Ethiopia

Authors: Senait Belay Adugna, Mirutse Giday, Tsegahun Manyazewal

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Background: The emergence and resurgence of zoonotic diseases have continued to be a major threat to global health and the economy. Developing countries are particularly vulnerable due to agricultural expansions and the domestication of animals by humans. Scientifically sound clinical trials are important to find better ways to prevent, diagnose, and treat zoonotic diseases, while there is a lack of evidence to inform the clinical trials’ capacity and practice in countries highly affected by the diseases. This study aimed to investigate researchers’ perceptions and experiences in conducting clinical trials on zoonotic diseases in Ethiopia. Methods: This study employed a descriptive, qualitative study design. It included major academic and research institutions in Ethiopia that had active engagements in veterinary and public health research. It included the National Veterinary Institute, the National Animal Health Diagnostic and Investigation Center, the College of Veterinary Medicine at Addis Ababa University, the Ethiopian Public Health Institute, the Armauer Hansen Research Institute, and the College of Health Sciences at Addis Ababa University. In-depth interviews were conducted with 14 senior researcher investigators in the institutions who hold a proven exhibit primarily leading research activities or research units. Data were collected from October 2019 to April 2020. Data analysis was undertaken using open code 4.03 for qualitative data analysis. Results: Five major themes, with 18 sub-themes, emerged from the in-depth interview in connection. These were: challenges in the prevention, control, and treatment of zoonotic diseases; One Health approach to mitigate zoonotic diseases; personal and institutional experiences in conducting clinical trials on zoonotic diseases; barriers in conducting clinical trials towards zoonotic diseases; and strategies that promote conducting clinical trials on zoonotic diseases. Conducting clinical trials on zoonotic diseases in Ethiopia is hampered by a lack of clearly articulated ethics and regulatory frameworks, trial experts, financial resources, and good governance. Conclusions: In Ethiopia, conducting clinical trials on zoonotic diseases deserves due attention. Strengthening institutional and human resources capacity is a precondition to harnessing effective implementation of clinical trials on zoonotic diseases in the country. In Ethiopia, where skilled human resource is scarce, the One Health approach has the potential to form multidisciplinary teams to systematically improve clinical trials capacity and outcomes in the country.

Keywords: Ethiopia, clinical triak, zoonoses, disease

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139 Basal Cell Carcinoma: Epidemiological Analysis of a 5-Year Period in a Brazilian City with a High Level of Solar Radiation

Authors: Maria E. V. Amarante, Carolina L. Cerdeira, Julia V. Cortes, Fiorita G. L. Mundim

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Basal cell carcinoma (BCC) is the most prevalent type of skin cancer in humans. It arises from the basal cells of the epidermis and cutaneous appendages. The role of sunlight exposure as a risk factor for BCC is very well defined due to its power to influence genetic mutations, in addition to having a suppressor effect on the skin immune system. Despite showing low metastasis and mortality rates, the tumor is locally infiltrative, aggressive, and destructive. Considering the high prevalence rate of this carcinoma and the importance of early detection, a retrospective study was carried out in order to correlate the clinical data available on BBC, characterize it epidemiologically, and thus enable effective prevention measures for the population. Data on the period from January 2015 to December 2019 were collected from the medical records of patients registered at one pathology service located in the southeast region of Brazil, known as SVO, which delivers skin biopsy results. The study was aimed at correlating the variables, sex, age, and subtypes found. Data analysis was performed using the chi-square test at a nominal significance level of 5% in order to verify the independence between the variables of interest. Fisher's exact test was applied in cases where the absolute frequency in the cells of the contingency table was less than or equal to five. The statistical analysis was performed using the R® software. Ninety-three basal cell carcinoma were analyzed, and its frequency in the 31-to 45-year-old age group was 5.8 times higher in men than in women, whereas, from 46 to 59 years, the frequency was found 2.4 times higher in women than in men. Between the ages of 46 to 59 years, it should be noted that the sclerodermiform subtype appears more than the solid one, with a difference of 7.26 percentage points. Reversely, the solid form appears more frequently in individuals aged 60 years or more, with a difference of 8.57 percentage points. Among women, the frequency of the solid subtype was 9.93 percentage points higher than the sclerodermiform frequency. In males, the same percentage difference is observed, but sclerodermiform is the most prevalent subtype. It is concluded in this study that, in general, there is a predominance of basal cell carcinoma in females and in individuals aged 60 years and over, which demonstrates the tendency of this tumor. However, when rarely found in younger individuals, the male gender prevailed. The most prevalent subtype was the solid one. It is worth mentioning that the sclerodermiform subtype, which is more aggressive, was seen more frequently in males and in the 46-to 59-year-old range.

Keywords: basal cell carcinoma, epidemiology, sclerodermiform basal cell carcinoma, skin cancer, solar radiation, solid basal cell carcinoma

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138 Weapon-Being: Weaponized Design and Object-Oriented Ontology in Hypermodern Times

Authors: John Dimopoulos

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This proposal attempts a refabrication of Heidegger’s classic thing-being and object-being analysis in order to provide better ontological tools for understanding contemporary culture, technology, and society. In his work, Heidegger sought to understand and comment on the problem of technology in an era of rampant innovation and increased perils for society and the planet. Today we seem to be at another crossroads in this course, coming after postmodernity, during which dreams and dangers of modernity augmented with critical speculations of the post-war era take shape. The new era which we are now living in, referred to as hypermodernity by researchers in various fields such as architecture and cultural theory, is defined by the horizontal implementation of digital technologies, cybernetic networks, and mixed reality. Technology today is rapidly approaching a turning point, namely the point of no return for humanity’s supervision over its creations. The techno-scientific civilization of the 21st century creates a series of problems, progressively more difficult and complex to solve and impossible to ignore, climate change, data safety, cyber depression, and digital stress being some of the most prevalent. Humans often have no other option than to address technology-induced problems with even more technology, as in the case of neuron networks, machine learning, and AI, thus widening the gap between creating technological artifacts and understanding their broad impact and possible future development. As all technical disciplines and particularly design, become enmeshed in a matrix of digital hyper-objects, a conceptual toolbox that allows us to handle the new reality becomes more and more necessary. Weaponized design, prevalent in many fields, such as social and traditional media, urban planning, industrial design, advertising, and the internet in general, hints towards an increase in conflicts. These conflicts between tech companies, stakeholders, and users with implications in politics, work, education, and production as apparent in the cases of Amazon workers’ strikes, Donald Trump’s 2016 campaign, Facebook and Microsoft data scandals, and more are often non-transparent to the wide public’s eye, thus consolidating new elites and technocratic classes and making the public scene less and less democratic. The new category proposed, weapon-being, is outlined in respect to the basic function of reducing complexity, subtracting materials, actants, and parameters, not strictly in favor of a humanistic re-orientation but in a more inclusive ontology of objects and subjects. Utilizing insights of Object-Oriented Ontology (OOO) and its schematization of technological objects, an outline for a radical ontology of technology is approached.

Keywords: design, hypermodernity, object-oriented ontology, weapon-being

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137 Armed Forces Special Powers Act and Human Rights in Nagaland

Authors: Khrukulu Khusoh

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The strategies and tactics used by governments throughout the world to counter terrorism and insurgency over the past few decades include the declaration of states of siege or martial law, enactment of anti-terrorist legislation and strengthening of judicial powers. Some of these measures taken have been more successful than the other, but some have proved counterproductive, alienating the public from the authorities and further polarizing an already fractured political environment. Such cases of alienation and polarization can be seen in the northeastern states of India. The Armed Forces (Special Powers) Act which was introduced to curb insurgency in the remote jungles of the far-flung areas has remained a telling tale of agony in the north east India. Grievous trauma to humans through encounter killings, custodial deaths, unwarranted torture, exploitation of women and children in several ways have been reported in Nagaland, Manipur and other northeastern states where the Indian army has been exercising powers under the Armed Forces (Special Powers) Act. While terrorism and the insurgency are destructive of human rights, counter-terrorism does not necessarily restore and safeguard human rights. This special law has not proven effective particularly in dealing with terrorism and insurgency. The insurgency has persisted in the state of Nagaland even after sixty years notwithstanding the presence of a good number of special laws. There is a need to fight elements that threaten the security of a nation, but the methods chosen should be measured, otherwise the fight is lost. There has been no review on the effectiveness or failure of the act to realize its intended purpose. Nor was there any attempt on the part of the state to critically look at the violation of rights of innocent citizens by the state agencies. The Indian state keeps enacting laws, but none of these could be effectively applied as there was the absence of clarity of purpose. Therefore, every new law which has been enacted time and again to deal with security threats failed to bring any solution for the last six decades. The Indian state resorts to measures which are actually not giving anything in terms of strategic benefits but are short-term victories that might result in long-term tragedies. Therefore, right thinking citizens and human rights activists across the country feel that introduction of Armed Forces (Special Powers) Act was as much violation of human rights and its continuation is undesirable. What worried everyone is the arbitrary use, or rather misuse of power by the Indian armed forces particularly against the weaker sections of the society, including women. After having being subjected to indiscriminate abuse of that law, people of the north-east India have been demanding its revocation for a long time. The present paper attempts to critically examine the violation of human rights under Armed Forces (Special Powers) Act. It also attempts to bring out the impact of Armed Forces (Special Powers) Act on the Naga people.

Keywords: armed forces, insurgency, special laws, violence

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136 Development of Loop Mediated Isothermal Amplification (Lamp) Assay for the Diagnosis of Ovine Theileriosis

Authors: Muhammad Fiaz Qamar, Uzma Mehreen, Muhammad Arfan Zaman, Kazim Ali

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Ovine Theileriosis is a world-wide concern, especially in tropical and subtropical areas, due to having tick abundance that has received less awareness in different developed and developing areas due to less worth of sheep, low to the middle level of infection in different small ruminants herd. Across Asia, the prevalence reports have been conducted to provide equivalent calculation of flock and animal level prevalence of Theileriosisin animals. It is a challenge for veterinarians to timely diagnosis & control of Theileriosis and famers because of the nature of the organism and inadequacy of restricted plans to control. All most work is based upon the development of such a technique which should be farmer-friendly, less expensive, and easy to perform into the field. By the timely diagnosis of this disease will decrease the irrational use of the drugs, and other plan was to determine the prevalence of Theileriosis in District Jhang by using the conventional method, PCR and qPCR, and LAMP. We quantify the molecular epidemiology of T.lestoquardiin sheep from Jhang districts, Punjab, Pakistan. In this study, we concluded that the overall prevalence of Theileriosis was (32/350*100= 9.1%) in sheep by using Giemsa staining technique, whereas (48/350*100= 13%) is observed by using PCR technique (56/350*100=16%) in qPCR and the LAMP technique have shown up to this much prevalence percentage (60/350*100= 17.1%). The specificity and sensitivity also calculated in comparison with the PCR and LAMP technique. Means more positive results have been shown when the diagnosis has been done with the help of LAMP. And there is little bit of difference between the positive results of PCR and qPCR, and the least positive animals was by using Giemsa staining technique/conventional method. If we talk about the specificity and sensitivity of the LAMP as compared to PCR, The cross tabulation shows that the results of sensitivity of LAMP counted was 94.4%, and specificity of LAMP counted was 78%. Advances in scientific field must be upon reality based ideas which can lessen the gaps and hurdles in the way of scientific research; the lamp is one of such techniques which have done wonders in adding value and helping human at large. It is such a great biological diagnostic tools and has helped a lot in the proper diagnosis and treatment of certain diseases. Other methods for diagnosis, such as culture techniques and serological techniques, have exposed humans with great danger. However, with the help of molecular diagnostic technique like LAMP, exposure to such pathogens is being avoided in the current era Most prompt and tentative diagnosis can be made using LAMP. Other techniques like PCR has many disadvantages when compared to LAMP as PCR is a relatively expensive, time consuming, and very complicated procedure while LAMP is relatively cheap, easy to perform, less time consuming, and more accurate. LAMP technique has removed hurdles in the way of scientific research and molecular diagnostics, making it approachable to poor and developing countries.

Keywords: distribution, thelaria, LAMP, primer sequences, PCR

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135 Developing a Roadmap by Integrating of Environmental Indicators with the Nitrogen Footprint in an Agriculture Region, Hualien, Taiwan

Authors: Ming-Chien Su, Yi-Zih Chen, Nien-Hsin Kao, Hideaki Shibata

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The major component of the atmosphere is nitrogen, yet atmospheric nitrogen has limited availability for biological use. Human activities have produced different types of nitrogen related compounds such as nitrogen oxides from combustion, nitrogen fertilizers from farming, and the nitrogen compounds from waste and wastewater, all of which have impacted the environment. Many studies have indicated the N-footprint is dominated by food, followed by housing, transportation, and goods and services sectors. To solve the impact issues from agricultural land, nitrogen cycle research is one of the key solutions. The study site is located in Hualien County, Taiwan, a major rice and food production area of Taiwan. Importantly, environmentally friendly farming has been promoted for years, and an environmental indicator system has been established by previous authors based on the concept of resilience capacity index (RCI) and environmental performance index (EPI). Nitrogen management is required for food production, as excess N causes environmental pollution. Therefore it is very important to develop a roadmap of the nitrogen footprint, and to integrate it with environmental indicators. The key focus of the study thus addresses (1) understanding the environmental impact caused by the nitrogen cycle of food products and (2) uncovering the trend of the N-footprint of agricultural products in Hualien, Taiwan. The N-footprint model was applied, which included both crops and energy consumption in the area. All data were adapted from government statistics databases and crosschecked for consistency before modeling. The actions involved with agricultural production were evaluated and analyzed for nitrogen loss to the environment, as well as measuring the impacts to humans and the environment. The results showed that rice makes up the largest share of agricultural production by weight, at 80%. The dominant meat production is pork (52%) and poultry (40%); fish and seafood were at similar levels to pork production. The average per capita food consumption in Taiwan is 2643.38 kcal capita−1 d−1, primarily from rice (430.58 kcal), meats (184.93 kcal) and wheat (ca. 356.44 kcal). The average protein uptake is 87.34 g capita−1 d−1, and 51% is mainly from meat, milk, and eggs. The preliminary results showed that the nitrogen footprint of food production is 34 kg N per capita per year, congruent with the results of Shibata et al. (2014) for Japan. These results provide a better understanding of the nitrogen demand and loss in the environment, and the roadmap can furthermore support the establishment of nitrogen policy and strategy. Additionally, the results serve to develop a roadmap of the nitrogen cycle of an environmentally friendly farming area, thus illuminating the nitrogen demand and loss of such areas.

Keywords: agriculture productions, energy consumption, environmental indicator, nitrogen footprint

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134 Harrison’s Stolen: Addressing Aboriginal and Indigenous Islanders Human Rights

Authors: M. Shukry

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According to the United Nations Declaration of Human Rights in 1948, every human being is entitled to rights in life that should be respected by others and protected by the state and community. Such rights are inherent regardless of colour, ethnicity, gender, religion or otherwise, and it is expected that all humans alike have the right to live without discrimination of any sort. However, that has not been the case with Aborigines in Australia. Over a long period of time, the governments of the State and the Territories and the Australian Commonwealth denied the Aboriginal and Indigenous inhabitants of the Torres Strait Islands such rights. Past Australian governments set policies and laws that enabled them to forcefully remove Indigenous children from their parents, which resulted in creating lost generations living the trauma of the loss of cultural identity, alienation and even their own selfhood. Intending to reduce that population of natives and their Aboriginal culture while, on the other hand, assimilate them into mainstream society, they gave themselves the right to remove them from their families with no hope of return. That practice has led to tragic consequences due to the trauma that has affected those children, an experience that is depicted by Jane Harrison in her play Stolen. The drama is the outcome of a six-year project on lost children and which was first performed in 1997 in Melbourne. Five actors only appear on the stage, playing the role of all the different characters, whether the main protagonists or the remaining cast, present or non-present ones as voices. The play outlines the life of five children who have been taken from their parents at an early age, entailing a disastrous negative impact that differs from one to the other. Unknown to each other, what connects between them is being put in a children’s home. The purpose of this paper is to analyse the play’s text in light of the 1948 Declaration of Human Rights, using it as a lens that reflects the atrocities practiced against the Aborigines. It highlights how such practices formed an outrageous violation of those natives’ rights as human beings. Harrison’s dramatic technique in conveying the children’s experiences is through a non-linear structure, fluctuating between past and present that are linked together within each of the five characters, reflecting their suffering and pain to create an emotional link between them and the audience. Her dramatic handling of the issue by fusing tragedy with humour as well as symbolism is a successful technique in revealing the traumatic memory of those children and their present life. The play has made a difference in commencing to address the problem of the right of all children to be with their families, which renders the real meaning of having a home and an identity as people.

Keywords: aboriginal, audience, Australia, children, culture, drama, home, human rights, identity, Indigenous, Jane Harrison, memory, scenic effects, setting, stage, stage directions, Stolen, trauma

Procedia PDF Downloads 275
133 Natural Mexican Zeolite Modified with Iron to Remove Arsenic Ions from Water Sources

Authors: Maritza Estela Garay-Rodriguez, Mirella Gutierrez-Arzaluz, Miguel Torres-Rodriguez, Violeta Mugica-Alvarez

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Arsenic is an element present in the earth's crust and is dispersed in the environment through natural processes and some anthropogenic activities. Naturally released into the environment through the weathering and erosion of sulphides mineral, some activities such as mining, the use of pesticides or wood preservatives potentially increase the concentration of arsenic in air, water, and soil. The natural arsenic release of a geological material is a threat to the world's drinking water sources. In aqueous phase is found in inorganic form, as arsenate and arsenite mainly, the contamination of groundwater by salts of this element originates what is known as endemic regional hydroarsenicism. The International Agency for Research on Cancer (IARC) categorizes the inorganic As within group I, as a substance with proven carcinogenic action for humans. It has been found the presence of As in groundwater in several countries such as Argentina, Mexico, Bangladesh, Canada and the United States. Regarding the concentration of arsenic in drinking water according to the World Health Organization (WHO) and the Environmental Protection Agency (EPA) establish maximum concentrations of 10 μg L⁻¹. In Mexico, in some states as Hidalgo, Morelos and Michoacán concentrations of arsenic have been found in bodies of water around 1000 μg L⁻¹, a concentration that is well above what is allowed by Mexican regulations with the NOM-127- SSA1-1994 that establishes a limit of 25 μg L⁻¹. Given this problem in Mexico, this research proposes the use of a natural Mexican zeolite (clinoptilolite type) native to the district of Etla in the central valley region of Oaxaca, as an adsorbent for the removal of arsenic. The zeolite was subjected to a conditioning with iron oxide by the precipitation-impregnation method with 0.5 M iron nitrate solution, in order to increase the natural adsorption capacity of this material. The removal of arsenic was carried out in a column with a fixed bed of conditioned zeolite, since it combines the advantages of a conventional filter with those of a natural adsorbent medium, providing a continuous treatment, of low cost and relatively easy to operate, for its implementation in marginalized areas. The zeolite was characterized by XRD, SEM/EDS, and FTIR before and after the arsenic adsorption tests, the results showed that the modification methods used are adequate to prepare adsorbent materials since it does not modify its structure, the results showed that with a particle size of 1.18 mm, an initial concentration of As (V) ions of 1 ppm, a pH of 7 and at room temperature, a removal of 98.7% was obtained with an adsorption capacity of 260 μg As g⁻¹ zeolite. The results obtained indicated that the conditioned zeolite is favorable for the elimination of arsenate in water containing up to 1000 μg As L⁻¹ and could be suitable for removing arsenate from pits of water.

Keywords: adsorption, arsenic, iron conditioning, natural zeolite

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132 Safety Assessment of Traditional Ready-to-Eat Meat Products Vended at Retail Outlets in Kebbi and Sokoto States, Nigeria

Authors: M. I. Ribah, M. Jibir, Y. A. Bashar, S. S. Manga

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Food safety is a significant and growing public health problem in the world and Nigeria as a developing country, since food-borne diseases are important contributors to the huge burden of sickness and death of humans. In Nigeria, traditional ready-to-eat meat products (RTE-MPs) like balangu, tsire, guru and dried meat products like kilishi, dambun nama, banda, were reported to be highly appreciated because of their eating qualities. The consumption of these products was considered as safe due to the treatments that are usually involved during their production process. However, during processing and handling, the products could be contaminated by pathogens that could cause food poisoning. Therefore, a hazard identification for pathogenic bacteria on some traditional RTE-MPs was conducted in Kebbi and Sokoto States, Nigeria. A total of 116 RTE-MPs (balangu-38, kilishi-39 and tsire-39) samples were obtained from retail outlets and analyzed using standard cultural microbiological procedures in general and selective enrichment media to isolate the target pathogens. A six-fold serial dilution was prepared and using the pour plating method, colonies were counted. Serial dilutions were selected based on the prepared pre-labeled Petri dishes for each sample. A volume of 10-12 ml of molten Nutrient agar cooled to 42-45°C was poured into each Petri dish and 1 ml each from dilutions of 102, 104 and 106 for every sample was respectively poured on a pre-labeled Petri plate after which colonies were counted. The isolated pathogens were identified and confirmed after series of biochemical tests. Frequencies and percentages were used to describe the presence of pathogens. The General Linear Model was used to analyze data on pathogen presence according to RTE-MPs and means were separated using the Tukey test at 0.05 confidence level. Of the 116 RTE-MPs samples collected, 35 (30.17%) samples were found to be contaminated with some tested pathogens. Prevalence results showed that Escherichia coli, salmonella and Staphylococcus aureus were present in the samples. Mean total bacterial count was 23.82×106 cfu/g. The frequency of individual pathogens isolated was; Staphylococcus aureus 18 (15.51%), Escherichia coli 12 (10.34%) and Salmonella 5 (4.31%). Also, among the RTE-MPs tested, the total bacterial counts were found to differ significantly (P < 0.05), with 1.81, 2.41 and 2.9×104 cfu/g for tsire, kilishi, and balangu, respectively. The study concluded that the presence of pathogenic bacteria in balangu could pose grave health risks to consumers, and hence, recommended good manufacturing practices in the production of balangu to improve the products’ safety.

Keywords: ready-to-eat meat products, retail outlets, public health, safety assessment

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131 Life Cycle Assessment of a Parabolic Solar Cooker

Authors: Bastien Sanglard, Lou Magnat, Ligia Barna, Julian Carrey, Sébastien Lachaize

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Cooking is a primary need for humans, several techniques being used around the globe based on different sources of energy: electricity, solid fuel (wood, coal...), fuel or liquefied petroleum gas. However, all of them leads to direct or indirect greenhouse gas emissions and sometimes health damage in household. Therefore, the solar concentrated power represent a great option to lower the damages because of a cleaner using phase. Nevertheless, the construction phase of the solar cooker still requires primary energy and materials, which leads to environmental impacts. The aims of this work is to analyse the ecological impacts of a commercialaluminium parabola and to compare it with other means of cooking, taking the boiling of 2 litres of water three times a day during 40 years as the functional unit. Life cycle assessment was performed using the software Umberto and the EcoInvent database. Calculations were realized over more than 13 criteria using two methods: the international panel on climate change method and the ReCiPe method. For the reflector itself, different aluminium provenances were compared, as well as the use of recycled aluminium. For the structure, aluminium was compared to iron (primary and recycled) and wood. Results show that climate impacts of the studied parabola was 0.0353 kgCO2eq/kWh when built with Chinese aluminium and can be reduced by 4 using aluminium from Canada. Assessment also showed that using 32% of recycled aluminium would reduce the impact by 1.33 and 1.43 compared to the use of primary Canadian aluminium and primary Chinese aluminium, respectively. The exclusive use of recycled aluminium lower the impact by 17. Besides, the use of iron (recycled or primary) or wood for the structure supporting the reflector significantly lowers the impact. The impact categories of the ReCiPe method show that the parabola made from Chinese aluminium has the heaviest impact - except for metal resource depletion - compared to aluminium from Canada, recycled aluminium or iron. Impact of solar cooking was then compared to gas stove and induction. The gas stove model was a cast iron tripod that supports the cooking pot, and the induction plate was as well a single spot plate. Results show the parabolic solar cooker has the lowest ecological impact over the 13 criteria of the ReCiPe method and over the global warming potential compared to the two other technologies. The climate impact of gas cooking is 0.628kgCO2/kWh when used with natural gas and 0.723 kgCO2/kWh when used with a bottle of gas. In each case, the main part of emissions came from gas burning. Induction cooking has a global warming potential of 0.12 kgCO2eq/kWh with the electricity mix of France, 96.3% of the impact being due to electricity production. Therefore, the electricity mix is a key factor for this impact: for instance, with the electricity mix of Germany and Poland, impacts are 0.81kgCO2eq/kWh and 1.39 kgCO2eq/kWh, respectively. Therefore, the parabolic solar cooker has a real ecological advantages compared to both gas stove and induction plate.

Keywords: life cycle assessement, solar concentration, cooking, sustainability

Procedia PDF Downloads 138
130 Serological IgG Testing to Diagnose Alimentary Induced Diseases and Monitoring Efficacy of an Individual Defined Diet in Dogs

Authors: Anne-Margré C. Vink

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Background: Food-related allergies and intolerances are frequently occurring in dogs. Diagnosis and monitoring according to ‘Golden Standard’ of elimination efficiency are time-consuming, expensive, and requires expert clinical setting. In order to facilitate rapid and robust, quantitative testing of intolerance, and determining the individual offending foods, a serological test is implicated. Method: As we developed Medisynx IgG Human Screening Test ELISA before and the dog’s immune system is most similar to humans, we were able to develop Medisynx IgG Dog Screening Test ELISA as well. In this study, 47 dogs suffering from Canine Atopic Dermatitis (CAD) and several secondary induced reactions were included to participate in serological Medisynx IgG Dog Screening Test ELISA (within < 0,02 % SD). Results were expressed as titers relative to the standard OD readings to diagnose alimentary induced diseases and monitoring the efficacy of an individual eliminating diet in dogs. Split sample analysis was performed by independently sending 2 times 3 ml serum under two unique codes. Results: The veterinarian monitored these dogs to check dog’ results at least at 3, 7, 21, 49, 70 days and after period of 6 and 12 months on an individual negative diet and a positive challenge (retrospectively) at 6 months. Data of each dog were recorded in a screening form and reported that a complete recovery of all clinical manifestations was observed at or less than 70 days (between 50 and 70 days) in the majority of dogs(44 out of 47 dogs =93.6%). Conclusion: Challenge results showed a significant result of 100% in specificity as well as 100% positive predicted value. On the other hand, sensitivity was 95,7% and negative predictive value was 95,7%. In conclusion, an individual diet based on IgG ELISA in dogs provides a significant improvement of atopic dermatitis and pruritus including all other non-specific defined allergic skin reactions as erythema, itching, biting and gnawing at toes, as well as to several secondary manifestations like chronic diarrhoea, chronic constipation, otitis media, obesity, laziness or inactive behaviour, pain and muscular stiffness causing a movement disorders, excessive lacrimation, hyper behaviour, nervous behaviour and not possible to stay alone at home, anxiety, biting and aggressive behaviour and disobedience behaviour. Furthermore, we conclude that a relatively more severe systemic candidiasis, as shown by relatively higher titer (class 3 and 4 IgG reactions to Candida albicans), influence the duration of recovery from clinical manifestations in affected dogs. These findings are consistent with our preliminary human clinical studies.

Keywords: allergy, canine atopic dermatitis, CAD, food allergens, IgG-ELISA, food-incompatibility

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129 Understanding the Diversity of Antimicrobial Resistance among Wild Animals, Livestock and Associated Environment in a Rural Ecosystem in Sri Lanka

Authors: B. M. Y. I. Basnayake, G. G. T. Nisansala, P. I. J. B. Wijewickrama, U. S. Weerathunga, K. W. M. Y. D. Gunasekara, N. K. Jayasekera, A. W. Kalupahana, R. S. Kalupahana, A. Silva- Fletcher, K. S. A. Kottawatta

Abstract:

Antimicrobial resistance (AMR) has attracted significant attention worldwide as an emerging threat to public health. Understanding the role of livestock and wildlife with the shared environment in the maintenance and transmission of AMR is of utmost importance due to its interactions with humans for combating the issue in one health approach. This study aims to investigate the extent of AMR distribution among wild animals, livestock, and environment cohabiting in a rural ecosystem in Sri Lanka: Hambegamuwa. One square km area at Hambegamuwa was mapped using GPS as the sampling area. The study was conducted for a period of five months from November 2020. Voided fecal samples were collected from 130 wild animals, 123 livestock: buffalo, cattle, chicken, and turkey, with 36 soil and 30 water samples associated with livestock and wildlife. From the samples, Escherichia coli (E. coli) was isolated, and their AMR profiles were investigated for 12 antimicrobials using the disk diffusion method following the CLSI standard. Seventy percent (91/130) of wild animals, 93% (115/123) of livestock, 89% (32/36) of soil, and 63% (19/30) of water samples were positive for E. coli. Maximum of two E. coli from each sample to a total of 467 were tested for the sensitivity of which 157, 208, 62, and 40 were from wild animals, livestock, soil, and water, respectively. The highest resistance in E. coli from livestock (13.9%) and wild animals (13.3%) was for ampicillin, followed by streptomycin. Apart from that, E. coli from livestock and wild animals revealed resistance mainly against tetracycline, cefotaxime, trimethoprim/ sulfamethoxazole, and nalidixic acid at levels less than 10%. Ten cefotaxime resistant E. coli were reported from wild animals, including four elephants, two land monitors, a pigeon, a spotted dove, and a monkey which was a significant finding. E. coli from soil samples reflected resistance primarily against ampicillin, streptomycin, and tetracycline at levels less than in livestock/wildlife. Two water samples had cefotaxime resistant E. coli as the only resistant isolates out of 30 water samples tested. Of the total E. coli isolates, 6.4% (30/467) was multi-drug resistant (MDR) which included 18, 9, and 3 isolates from livestock, wild animals, and soil, respectively. Among 18 livestock MDRs, the highest (13/ 18) was from poultry. Nine wild animal MDRs were from spotted dove, pigeon, land monitor, and elephant. Based on CLSI standard criteria, 60 E. coli isolates, of which 40, 16, and 4 from livestock, wild animal, and environment, respectively, were screened for Extended Spectrum β-Lactamase (ESBL) producers. Despite being a rural ecosystem, AMR and MDR are prevalent even at low levels. E. coli from livestock, wild animals, and the environment reflected a similar spectrum of AMR where ampicillin, streptomycin, tetracycline, and cefotaxime being the predominant antimicrobials of resistance. Wild animals may have acquired AMR via direct contact with livestock or via the environment, as antimicrobials are rarely used in wild animals. A source attribution study including the effects of the natural environment to study AMR can be proposed as this less contaminated rural ecosystem alarms the presence of AMR.

Keywords: AMR, Escherichia coli, livestock, wildlife

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128 A Computational Approach to Screen Antagonist’s Molecule against Mycobacterium tuberculosis Lipoprotein LprG (Rv1411c)

Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

Procedia PDF Downloads 245