Search results for: massively parallel sequencing
571 Randomized Controlled Study of the Antipyretic Efficacy of Oral Paracetamol, Intravenous Paracetamol, and Intramuscular Diclofenac
Authors: Firjeeth C. Paramba, Vamanjore A. Naushad, Nishan K. Purayil, Osama H. Mohammed, Prem Chandra
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Background: Fever is a common problem in adults visiting the emergency department. Extensive studies have been done in children comparing the efficacy of various antipyretics. However, studies on the efficacy of antipyretic drugs in adults are very scarce. To the best of our knowledge, no controlled trial has been carried out comparing the antipyretic efficacy of paracetamol (oral and intravenous) and intramuscular diclofenac in adults. Methods: In this parallel-group, open-label trial, participants aged 14–75 years presenting with fever who had a temperature of more than 38.5°C were enrolled and treated. Participants were randomly allocated to receive treatment with 1,000 mg oral paracetamol (n=145), 1,000 mg intravenous paracetamol (n=139), or 75 mg intramuscular diclofenac (n=150). The primary outcome was degree of reduction in mean oral temperature at 90 minutes. The efficacy of diclofenac versus oral and intravenous paracetamol was assessed by superiority comparison. Analysis was done using intention to treat principles. Results: After 90 minutes, all three groups showed a significant reduction in mean temperature, with intramuscular diclofenac showing the greatest reduction (−1.44 ± 0.43, 95% confidence interval [CI] −1.4 to −2.5) and oral paracetamol the least (−1.08 ± 0.51, 95% CI −0.99 to −2.2). After 120 minutes, there was a significant difference observed in the mean change from baseline temperature between the three treatment groups (P, 0.0001). Significant changes in temperature were observed in favor of intramuscular diclofenac over oral and intravenous paracetamol at each time point from 60 minutes through 120 minutes inclusive. Conclusion: Both intramuscular diclofenac and intravenous paracetamol showed superior antipyretic activity than oral paracetamol. However, in view of its ease of administration, intramuscular diclofenac can be used as a first-choice antipyretic in febrile adults in the emergency department.Keywords: antipyretic, intramuscular, intravenous, paracetamol, diclofenac, emergency department
Procedia PDF Downloads 371570 Exploring the ‘Many Worlds’ Interpretation in Both a Philosophical and Creative Literary Framework
Authors: Jane Larkin
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Combining elements of philosophy, science, and creative writing, this investigation explores how a philosophically structured science-fiction novel can challenge the theory of linearity and singularity of time through the ‘many worlds’ theory. This concept is addressed through the creation of a research exegesis and accompanying creative artefact, designed to be read in conjunction with each other in an explorative, interwoven manner. Research undertaken into scientific concepts, such as the ‘many worlds’ interpretation of quantum mechanics and diverse philosophers and their ideologies on time, is embodied in an original science-fiction narrative titled, It Goes On. The five frames that make up the creative artefact are enhanced not only by five leading philosophers and their philosophies on time but by an appreciation of the research, which comes first in the paper. Research into traditional approaches to storytelling is creatively and innovatively inverted in several ways, thus challenging the singularity and linearity of time. Further nonconventional approaches to literary techniques include an abstract narrator, embodied by time, a concept, and a figure in the text, whose voice and vantage point in relation to death furthers the unreliability of the notion of time. These further challenge individuals’ understanding of complex scientific and philosophical views in a variety of ways. The science-fiction genre is essential when considering the speculative nature of It Goes On, which deals with parallel realities and is a fantastical exploration of human ingenuity in plausible futures. Therefore, this paper documents the research-led methodology used to create It Goes On, the application of the ‘many worlds’ theory within a framed narrative, and the many innovative techniques used to contribute new knowledge in a variety of fields.Keywords: time, many-worlds theory, Heideggerian philosophy, framed narrative
Procedia PDF Downloads 83569 Effect of Cladding Direction on Residual Stress Distribution in Laser Cladded Rails
Authors: Taposh Roy, Anna Paradowska, Ralph Abrahams, Quan Lai, Michael Law, Peter Mutton, Mehdi Soodi, Wenyi Yan
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In this investigation, a laser cladding process with a powder feeding was used to deposit stainless steel 410L (high strength, excellent resistance to abrasion and corrosion, and great laser compatibility) onto railhead (higher strength, heat treated hypereutectoid rail grade manufactured in accordance with the requirements of European standard EN 13674 Part 1 for R400HT grade), to investigate the development and controllability of process-induced residual stress in the cladding, heat-affected zone (HAZ) and substrate and to analyse their correlation with hardness profile during two different laser cladding directions (across and along the track). Residual stresses were analysed by neutron diffraction at OPAL reactor, ANSTO. Neutron diffraction was carried out on the samples in longitudinal (parallel to the rail), transverse (perpendicular to the rail) and normal (through thickness) directions with high spatial resolution through the thickness. Due to the thick rail and thin cladding, 4 mm thick reference samples were prepared from every specimen by Electric Discharge Machining (EDM). Metallography across the laser claded sample revealed four distinct zones: The clad zone, the dilution zone, HAZ and the substrate. Compressive residual stresses were found in the clad zone and tensile residual stress in the dilution zone and HAZ. Laser cladding in longitudinally cladding induced higher tensile stress in the HAZ, whereas transversely cladding rail showed lower tensile behavior.Keywords: laser cladding, residual stress, neutron diffraction, HAZ
Procedia PDF Downloads 272568 Comparison of Different Methods of Microorganism's Identification from a Copper Mining in Pará, Brazil
Authors: Louise H. Gracioso, Marcela P.G. Baltazar, Ingrid R. Avanzi, Bruno Karolski, Luciana J. Gimenes, Claudio O. Nascimento, Elen A. Perpetuo
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Introduction: Higher copper concentrations promote a selection pressure on organisms such as plants, fungi and bacteria, which allows surviving only the resistant organisms to the contaminated site. This selective pressure keeps only the organisms most resistant to a specific condition and subsequently increases their bioremediation potential. Despite the bacteria importance for biosphere maintenance, it is estimated that only a small fraction living microbial species has been described and characterized. Due to the molecular biology development, tools based on analysis 16S ribosomal RNA or another specific gene are making a new scenario for the characterization studies and identification of microorganisms in the environment. News identification of microorganisms methods have also emerged like Biotyper (MALDI / TOF), this method mass spectrometry is subject to the recognition of spectroscopic patterns of conserved and features proteins for different microbial species. In view of this, this study aimed to isolate bacteria resistant to copper present in a Copper Processing Area (Sossego Mine, Canaan, PA) and identifies them in two different methods: Recent (spectrometry mass) and conventional. This work aimed to use them for a future bioremediation of this Mining. Material and Methods: Samples were collected at fifteen different sites of five periods of times. Microorganisms were isolated from mining wastes by culture enrichment technique; this procedure was repeated 4 times. The isolates were inoculated into MJS medium containing different concentrations of chloride copper (1mM, 2.5mM, 5mM, 7.5mM and 10 mM) and incubated in plates for 72 h at 28 ºC. These isolates were subjected to mass spectrometry identification methods (Biotyper – MALDI/TOF) and 16S gene sequencing. Results: A total of 105 strains were isolated in this area, bacterial identification by mass spectrometry method (MALDI/TOF) achieved 74% agreement with the conventional identification method (16S), 31% have been unsuccessful in MALDI-TOF and 2% did not obtain identification sequence the 16S. These results show that Biotyper can be a very useful tool in the identification of bacteria isolated from environmental samples, since it has a better value for money (cheap and simple sample preparation and MALDI plates are reusable). Furthermore, this technique is more rentable because it saves time and has a high performance (the mass spectra are compared to the database and it takes less than 2 minutes per sample).Keywords: copper mining area, bioremediation, microorganisms, identification, MALDI/TOF, RNA 16S
Procedia PDF Downloads 374567 A Case Study: Effect of Low Carbs High Fats Diet (Also Known as LCHF Diet) Combined with Fried Foods in Extra Virgin Olive Oil in Patient with Type 2 Diabetes and Central Obesity
Authors: Cristian Baldini
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‘Diabesity’ is a term for diabetes occurring in the context of obesity. The positive effect of LCHF diets (low-carb, high-fat diets) is well documented: LCHF diets are at least as effective as other dietary strategies for reducing body weight, improving glycaemic control, and reducing both hyperinsulinaemia and blood glucose (reduction of HbA1c) in type 2 diabetes and have unique positive effects on blood lipid concentrations and cardiovascular risk factors. Also, in obese insulin-resistant women, food fried in extra-virgin olive oil significantly reduced both insulin and C-peptide responses after a meal. This case study shows that if combined, both dietary strategies produce a strong effect on blood glucose, resulting in a “forced” reduction of exogenous insulin injection to avoid the problem of hypoglycaemia. Blood tests after three months of this dietary treatment show how HbA1c, triglycerides, and blood lipid profile (LDL, HDL, Total Cholesterol) are improved despite the reduction of exogenous insulin injection of 80% with a parallel body weight decrease of 15%. For continuous glucose monitoring (CGM), the patient used FreeStyle Libre before and after the dietary treatment. In order to check general body functions and glycosuria, the patient used the urine test Multistix 10 SG Siemens.Keywords: diabetes, obesity, diabesity, fat, fried foods
Procedia PDF Downloads 75566 Improving Fault Tolerance and Load Balancing in Heterogeneous Grid Computing Using Fractal Transform
Authors: Saad M. Darwish, Adel A. El-Zoghabi, Moustafa F. Ashry
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The popularity of the Internet and the availability of powerful computers and high-speed networks as low-cost commodity components are changing the way we use computers today. These technical opportunities have led to the possibility of using geographically distributed and multi-owner resources to solve large-scale problems in science, engineering, and commerce. Recent research on these topics has led to the emergence of a new paradigm known as Grid computing. To achieve the promising potentials of tremendous distributed resources, effective and efficient load balancing algorithms are fundamentally important. Unfortunately, load balancing algorithms in traditional parallel and distributed systems, which usually run on homogeneous and dedicated resources, cannot work well in the new circumstances. In this paper, the concept of a fast fractal transform in heterogeneous grid computing based on R-tree and the domain-range entropy is proposed to improve fault tolerance and load balancing algorithm by improve connectivity, communication delay, network bandwidth, resource availability, and resource unpredictability. A novel two-dimension figure of merit is suggested to describe the network effects on load balance and fault tolerance estimation. Fault tolerance is enhanced by adaptively decrease replication time and message cost while load balance is enhanced by adaptively decrease mean job response time. Experimental results show that the proposed method yields superior performance over other methods.Keywords: Grid computing, load balancing, fault tolerance, R-tree, heterogeneous systems
Procedia PDF Downloads 488565 Aesthetic Preference and Consciousness in African Theatre: A Performance Appraisal of Tyrone Terrence's a Husband's Wife
Authors: Oluwatayo Isijola
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The destructive influence of Europe on Africa has also taken a tow on the aesthetic essence of the African Art, which centres on morality and value for human life. In a parallel vein, the adverse turn of this influence on the dramaturgy of some contemporary African plays, poses impedance to audience consciousness in performance engagements. Through the spectrum of African Aesthetics, this study attempts a performance appraisal of A Husband’s wife; an unpublished play written by Tyrone Terence for the African audience. The researcher proffers two variant textual interpretations of the play to evaluate performance engagement in its default realistic mode, which holds an unresolved 'Medean-impulse', and another wherein the resolution is treated to a paradigm shift for aesthetic preference. The investigation employs the mixed method, which combines the quantitative and qualitative methodologies. Keen observation on the reactions and responses of audience members that were engaged in both performances, and on-the-spot interview with selected audience members, were the primary sources for the qualitative data. However, quantitative data was captured in an on-the-spot survey with the instrument of the questionnaire served to a sample population of the audience. The study observes that the preference for African aesthetics as exemplified in the second performance which deployed a paradigm shift did enhance audience consciousness. Hinging on performance aesthetic theory, the paper recommends that all such African plays bestowed with the shortcoming of African aesthetics, should be appropriately treated to paradigm shifts for performance engagement, in the interest of enhancing audience consciousness in the Nigerian Theatre.Keywords: African aesthetics, audience consciousness, paradigm shift, median-impulse
Procedia PDF Downloads 332564 Biocellulose Template for 3D Mineral Scaffolds
Authors: C. Busuioc, G. Voicu, S. I. Jinga
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The field of tissue engineering brings new challenges in terms of proposing original solutions for ongoing medical issues, improving the biological performances of existing clinical systems and speeding the healing process for a faster recovery and a more comfortable life as patient. In this context, we propose the obtaining of 3D porous scaffolds of mineral nature, dedicated to bone repairing and regeneration purposes or employed as bioactive filler for bone cements. Thus, bacterial cellulose - calcium phosphates composite materials have been synthesized by successive immersing of the polymeric membranes in the precursor solution containing Ca2+ and [PO4]3- ions. The mineral phase deposited on the surface of biocellulose fibers was varied as amount through the number of immersing cycles. The intermediary composites were subjected to thermal treatments at different temperatures in order to remove the organic part and provide the formation of a self-sustained 3D architecture. The resulting phase composition consists of common phosphates, while the morphology largely depends on the preparation parameters. Thus, the aspect of the 3D mineral scaffolds can be tuned from a loose microstructure composed of large grains connected via monocrystalline nanorods to a trabecular pattern crossed by parallel internal channels, just like the natural bone. The bioactivity and biocompatibility of the obtained materials have been also assessed, with encouraging results in the clinical use direction. In conclusion, the compositional, structural, morphological and biological characterizations sustain the suitability of the reported biostructures for integration in hard tissue engineering applications.Keywords: bacterial cellulose, bone reconstruction, calcium phosphates, mineral scaffolds
Procedia PDF Downloads 194563 Identification and Characterization of Antimicrobial Peptides Isolated from Entophytic Bacteria and Their Activity against Multidrug-Resistance Gram-Negative Bacteria in South Korea
Authors: Maryam Beiranvand
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Multi-drug resistance in various microorganisms has increased globally in many healthcare facilities. Less effective antimicrobial activity of drug therapies for infection control becomes trouble. Since 1980, no new type of antimicrobial drug has been identified, even though combinations of antibiotic drugs have been discovered almost every decade. Between 1981 and 2006, over 70% of novel pharmaceuticals and chemical agents came from natural sources. Microorganisms have yielded almost 22,000 natural compounds. The identification of antimicrobial components from endophytes bacteria could help overcome the threat posed by multi-drug resistant strains. The project aims to analyze and identify antimicrobial peptides isolated from entophytic bacteria and their activity against multidrug-resistant Gram-negative bacteria in South Korea. Endophytic Paenibacillus polymyxa. 4G3 isolated from the plant, Gynura procumbery exhibited considerable antimicrobial activity against Methicillin-resistant Staphylococcus aureus, and Escherichia coli. The Rapid Annotations using Subsystems Technology showed that the total size of the draft genome was 5,739,603bp, containing 5178 genes with 45.8% G+C content. Genome annotation using antiSMASH version 6.0.0 was performed, which predicted the most common types of non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS). In this study, diethyl aminoethyl cellulose (DEAEC) resin was used as the first step in purifying for unknown peptides, and then the target protein was identified using hydrophilic and hydrophobic solutions, optimal pH, and step-by-step tests for antimicrobial activity. This crude was subjected to C18 chromatography and elution with 0, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% methanol, respectively. Only the fraction eluted with 20% -60% methanol demonstrated good antimicrobial activity against MDR E. coli. The concentration of the active fragment was measured by the Brad-ford test, and Protein A280 - Thermo Fisher Scientific at the end by examining the SDS PAGE Resolving Gel, 10% Acrylamide and purity were confirmed. Our study showed that, based on the combined results of the analysis and purification. P polymyxa. 4G3 has a high potential exists for producing novel functions of polymyxin E and bacitracin against bacterial pathogens.Keywords: endophytic bacteria, antimicrobial activity, antimicrobial peptide, whole genome sequencing analysis, multi -drug resistance gram negative bacteria
Procedia PDF Downloads 74562 Leukocyte Transcriptome Analysis of Patients with Obesity-Related High Output Heart Failure
Authors: Samantha A. Cintron, Janet Pierce, Mihaela E. Sardiu, Diane Mahoney, Jill Peltzer, Bhanu Gupta, Qiuhua Shen
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High output heart failure (HOHF) is characterized a high output state resulting from an underlying disease process and is commonly caused by obesity. As obesity levels increase, more individuals will be at risk for obesity-related HOHF. However, the underlying pathophysiologic mechanisms of obesity-related HOHF are not well understood and need further research. The aim of the study was to describe the differences in leukocyte transcriptomes of morbidly obese patients with HOHF and those with non-HOHF. In this cross-sectional study, the study team collected blood samples, demographics, and clinical data of six patients with morbid obesity and HOHF and six patients with morbid obesity and non-HOHF. The study team isolated the peripheral blood leukocyte RNA and applied stranded total RNA sequencing. Differential gene expression was calculated, and Ingenuity Pathway Analysis software was used to interpret the canonical pathways, functional changes, upstream regulators, and mechanistic and causal networks that were associated with the significantly different leukocyte transcriptomes. The study team identified 116 differentially expressed genes; 114 were upregulated, and 2 were downregulated in the HOHF group (Benjamini-Hochberg adjusted p-value ≤ 0.05 and log2(fold-change) of ±1). The differentially expressed genes were involved with cell proliferation, mitochondrial function, erythropoiesis, erythrocyte stability, and apoptosis. The top upregulated canonical pathways associated with differentially expressed genes were autophagy, adenosine monophosphate-activated protein kinase signaling, and senescence pathways. Upstream regulator GATA Binding Protein 1 (GATA1) and a network associated with nuclear factor kappa-light chain-enhancer of activated B cells (NF-kB) were also identified based on the different leukocyte transcriptomes of morbidly obese patients with HOHF and non-HOHF. To the author’s best knowledge, this is the first study that reported the differential gene expression in patients with obesity-related HOHF and demonstrated the unique pathophysiologic mechanisms underlying the disease. Further research is needed to determine the role of cellular function and maintenance, inflammation, and iron homeostasis in obesity-related HOHF.Keywords: cardiac output, heart failure, obesity, transcriptomics
Procedia PDF Downloads 54561 European Union Health Policy and the Response to COVID-19 Pandemic: Building a European Health Union
Authors: Aikaterini Tsalampouni
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The European Union has long been the most developed model of economic and political integration that has brought a common market, a common currency and a standardization of national policies in certain areas in consistent with EU values and principles. To this direction, there is a parallel process of social integration that effect public policy decisions of member states. Even though social policy, i.e. social protection and moreover healthcare policy, still remains in state's responsibility to develop, EU applies different mechanisms in order to influence health policy systems, since from a more federalist point of view, EU ought to expand its regulatory and legislative roles in as many policy areas as possible. Recently, the pandemic has become a turning point for health care provision and at the same time has also highlighted the need to strengthen the EU’s role in coordinating health care. This paper analyses the EU health policy in general, as well as the response to COVID-19 pandemic with an attempt to identify indications of interaction between EU policies and the promotion of sustainable and resilient health systems. More analytically, the paper investigates the EU binding legal instruments, non-binding legal instruments, monitoring and assessment instruments and instruments for co-financing concerning health care provision in member states and records the evolution of health policies before and during the COVID-19 pandemic. The paper concludes by articulating some remarks regarding the improvement of health policy in EU. Since the ability to deal with a pandemic depends on continuous and increased investment in health systems, the involvement of the EU can lead to a policy convergence, necessary for the resilience of the systems, maintaining at the same time, a strong health policy framework in Europe.Keywords: EU health policy, EU response to COVID-19, European Health Union, health systems in Europe
Procedia PDF Downloads 112560 Opto-Electronic Properties and Structural Phase Transition of Filled-Tetrahedral NaZnAs
Authors: R. Khenata, T. Djied, R. Ahmed, H. Baltache, S. Bin-Omran, A. Bouhemadou
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We predict structural, phase transition as well as opto-electronic properties of the filled-tetrahedral (Nowotny-Juza) NaZnAs compound in this study. Calculations are carried out by employing the full potential (FP) linearized augmented plane wave (LAPW) plus local orbitals (lo) scheme developed within the structure of density functional theory (DFT). Exchange-correlation energy/potential (EXC/VXC) functional is treated using Perdew-Burke and Ernzerhof (PBE) parameterization for generalized gradient approximation (GGA). In addition to Trans-Blaha (TB) modified Becke-Johnson (mBJ) potential is incorporated to get better precision for optoelectronic properties. Geometry optimization is carried out to obtain the reliable results of the total energy as well as other structural parameters for each phase of NaZnAs compound. Order of the structural transitions as a function of pressure is found as: Cu2Sb type → β → α phase in our study. Our calculated electronic energy band structures for all structural phases at the level of PBE-GGA as well as mBJ potential point out; NaZnAs compound is a direct (Γ–Γ) band gap semiconductor material. However, as compared to PBE-GGA, mBJ potential approximation reproduces higher values of fundamental band gap. Regarding the optical properties, calculations of real and imaginary parts of the dielectric function, refractive index, reflectivity coefficient, absorption coefficient and energy loss-function spectra are performed over a photon energy ranging from 0.0 to 30.0 eV by polarizing incident radiation in parallel to both [100] and [001] crystalline directions.Keywords: NaZnAs, FP-LAPW+lo, structural properties, phase transition, electronic band-structure, optical properties
Procedia PDF Downloads 435559 Comprehensive Longitudinal Multi-omic Profiling in Weight Gain and Insulin Resistance
Authors: Christine Y. Yeh, Brian D. Piening, Sarah M. Totten, Kimberly Kukurba, Wenyu Zhou, Kevin P. F. Contrepois, Gucci J. Gu, Sharon Pitteri, Michael Snyder
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Three million deaths worldwide are attributed to obesity. However, the biomolecular mechanisms that describe the link between adiposity and subsequent disease states are poorly understood. Insulin resistance characterizes approximately half of obese individuals and is a major cause of obesity-mediated diseases such as Type II diabetes, hypertension and other cardiovascular diseases. This study makes use of longitudinal quantitative and high-throughput multi-omics (genomics, epigenomics, transcriptomics, glycoproteomics etc.) methodologies on blood samples to develop multigenic and multi-analyte signatures associated with weight gain and insulin resistance. Participants of this study underwent a 30-day period of weight gain via excessive caloric intake followed by a 60-day period of restricted dieting and return to baseline weight. Blood samples were taken at three different time points per patient: baseline, peak-weight and post weight loss. Patients were characterized as either insulin resistant (IR) or insulin sensitive (IS) before having their samples processed via longitudinal multi-omic technologies. This comparative study revealed a wealth of biomolecular changes associated with weight gain after using methods in machine learning, clustering, network analysis etc. Pathways of interest included those involved in lipid remodeling, acute inflammatory response and glucose metabolism. Some of these biomolecules returned to baseline levels as the patient returned to normal weight whilst some remained elevated. IR patients exhibited key differences in inflammatory response regulation in comparison to IS patients at all time points. These signatures suggest differential metabolism and inflammatory pathways between IR and IS patients. Biomolecular differences associated with weight gain and insulin resistance were identified on various levels: in gene expression, epigenetic change, transcriptional regulation and glycosylation. This study was not only able to contribute to new biology that could be of use in preventing or predicting obesity-mediated diseases, but also matured novel biomedical informatics technologies to produce and process data on many comprehensive omics levels.Keywords: insulin resistance, multi-omics, next generation sequencing, proteogenomics, type ii diabetes
Procedia PDF Downloads 427558 A Corpus-Based Study of Subtitling Religious Words into Arabic
Authors: Yousef Sahari, Eisa Asiri
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Hollywood films are produced in an open and liberal context, and when subtitling for a more conservative and closed society such as an Arabic society, religious words can pose a thorny challenge for subtitlers. Using a corpus of 90 Hollywood films released between 2000 and 2018 and applying insights from Descriptive Translation Studies (Toury, 1995, 2012) and the dichotomy of domestication and foreignization, this paper investigates three main research questions: (1) What are the dominant religious terms and functions in the English subtitles? (2) What are the dominant translation strategies used in the translation of religious words? (3) Do these strategies tend to be SL-oriented or TL-oriented (domesticating or foreignising)? To answer the research questions above, a quantitative and qualitative analysis of the corpus is conducted, in which the researcher adopts a self-designed, parallel, aligned corpus of ninety films and their Arabic subtitles. A quantitative analysis is performed to compare the frequencies and distribution of religious words, their functions, and the translation strategies employed by the subtitlers of ninety films, with the aim of identifying similarities or differences in addition to identifying the impact of functions of religious terms on the use of subtitling strategies. Based on the quantitative analysis, a qualitative analysis is performed to identify any translational patterns in Arabic translations of religious words and the possible reasons for subtitlers’ choices. The results show that the function of religious words has a strong influence on the choice of subtitling strategies. Also, it is found that foreignization strategies are applied in about two-thirds of the total occurrences of religious words.Keywords: religious terms, subtitling, audiovisual translation, modern standard arabic, subtitling strategies, english-arabic subtitling
Procedia PDF Downloads 166557 Development of the Religious Out-Group Aggression Scale
Authors: Rylle Evan Gabriel Zamora, Micah Dennise Malia, Abygail Deniese Villabona
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When examining studies on aggression, the studies about individual aggression vastly outnumbers those studies on group aggression. Given the nature of aggression to be violent and cyclical, and the amount violent events that have occurred in the near present, the study of group aggression is relevant now more than ever. This discrepancy is parallel with the number of valid and reliable psychological tests that measure group aggression. Throughout history, one of the biggest causes of group based violence and aggression is religion. This is particularly true within the context of the Philippines as there are a large number of religious groups. Thus, this study aimed to develop a standardized test that measures an individual’s tendency to be aggressive to those who are in conflict with his or her religious beliefs. This study employs a test development design that employs a qualitative phase to ensure the validity of the scale. Thus, the study was divided into three phases. First is a pilot test wherein an instrument was designed from existing literature which was then administered to 173 respondents from the four largest religious groups in the Philippines. After extensive factor analysis and reliability testing, new items were then formed from the qualitative data collected from eight participants, consisting of two individuals per religious group. The final testing integrates all statistically significant items from the first phase, and the newly formed items from the second phase, which was then administered to 200 respondents. The results were then tested further for reliability using Cronbach’s alpha and validity through factor analysis. The items that were proven to be significant were then combined to create a final instrument that may be used by future studies.Keywords: religious aggression, group aggression, test development, psychological assessment, social psychology
Procedia PDF Downloads 293556 3D Geomechanical Model the Best Solution of the 21st Century for Perforation's Problems
Authors: Luis Guiliana, Andrea Osorio
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The lack of comprehension of the reservoir geomechanics conditions may cause operational problems that cost to the industry billions of dollars per year. The drilling operations at the Ceuta Field, Area 2 South, Maracaibo Lake, have been very expensive due to problems associated with drilling. The principal objective of this investigation is to develop a 3D geomechanical model in this area, in order to optimize the future drillings in the field. For this purpose, a 1D geomechanical model was built at first instance, following the workflow of the MEM (Mechanical Earth Model), this consists of the following steps: 1) Data auditing, 2) Analysis of drilling events and structural model, 3) Mechanical stratigraphy, 4) Overburden stress, 5) Pore pressure, 6) Rock mechanical properties, 7) Horizontal stresses, 8) Direction of the horizontal stresses, 9) Wellbore stability. The 3D MEM was developed through the geostatistic model of the Eocene C-SUP VLG-3676 reservoir and the 1D MEM. With this data the geomechanical grid was embedded. The analysis of the results threw, that the problems occurred in the wells that were examined were mainly due to wellbore stability issues. It was determined that the stress field change as the stratigraphic column deepens, it is normal to strike-slip at the Middle Miocene and Lower Miocene, and strike-slipe to reverse at the Eocene. In agreement to this, at the level of the Eocene, the most advantageous direction to drill is parallel to the maximum horizontal stress (157º). The 3D MEM allowed having a tridimensional visualization of the rock mechanical properties, stresses and operational windows (mud weight and pressures) variations. This will facilitate the optimization of the future drillings in the area, including those zones without any geomechanics information.Keywords: geomechanics, MEM, drilling, stress
Procedia PDF Downloads 272555 Thin Films of Glassy Carbon Prepared by Cluster Deposition
Authors: Hatem Diaf, Patrice Melinon, Antonio Pereira, Bernard Moine, Nicholas Blanchard, Florent Bourquard, Florence Garrelie, Christophe Donnet
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Glassy carbon exhibits excellent biological compatibility with live tissues meaning it has high potential for applications in life science. Moreover, glassy carbon has interesting properties including 'high temperature resistance', hardness, low density, low electrical resistance, low friction, and low thermal resistance. The structure of glassy carbon has long been a subject of debate. It is now admitted that glassy carbon is 100% sp2. This term is a little bit confusing as long sp2 hybridization defined from quantum chemistry is related to both properties: threefold configuration and pi bonding (parallel pz orbitals). Using plasma laser deposition of carbon clusters combined with pulsed nano/femto laser annealing, we are able to synthesize thin films of glassy carbon of good quality (probed by G band/ D disorder band ratio in Raman spectroscopy) without thermal post annealing. A careful inspecting of Raman signal, plasmon losses and structure performed by HRTEM (High Resolution Transmission Electron Microscopy) reveals that both properties (threefold and pi orbitals) cannot coexist together. The structure of the films is compared to models including schwarzites based from negatively curved surfaces at the opposite of onions or fullerene-like structures with positively curved surfaces. This study shows that a huge collection of porous carbon named vitreous carbon with different structures can coexist.Keywords: glassy carbon, cluster deposition, coating, electronic structure
Procedia PDF Downloads 317554 Critically Sampled Hybrid Trigonometry Generalized Discrete Fourier Transform for Multistandard Receiver Platform
Authors: Temidayo Otunniyi
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This paper presents a low computational channelization algorithm for the multi-standards platform using poly phase implementation of a critically sampled hybrid Trigonometry generalized Discrete Fourier Transform, (HGDFT). An HGDFT channelization algorithm exploits the orthogonality of two trigonometry Fourier functions, together with the properties of Quadrature Mirror Filter Bank (QMFB) and Exponential Modulated filter Bank (EMFB), respectively. HGDFT shows improvement in its implementation in terms of high reconfigurability, lower filter length, parallelism, and medium computational activities. Type 1 and type 111 poly phase structures are derived for real-valued HGDFT modulation. The design specifications are decimated critically and over-sampled for both single and multi standards receiver platforms. Evaluating the performance of oversampled single standard receiver channels, the HGDFT algorithm achieved 40% complexity reduction, compared to 34% and 38% reduction in the Discrete Fourier Transform (DFT) and tree quadrature mirror filter (TQMF) algorithm. The parallel generalized discrete Fourier transform (PGDFT) and recombined generalized discrete Fourier transform (RGDFT) had 41% complexity reduction and HGDFT had a 46% reduction in oversampling multi-standards mode. While in the critically sampled multi-standard receiver channels, HGDFT had complexity reduction of 70% while both PGDFT and RGDFT had a 34% reduction.Keywords: software defined radio, channelization, critical sample rate, over-sample rate
Procedia PDF Downloads 143553 Molecular Characterization of Two Thermoplastic Biopolymer-Degrading Fungi Utilizing rRNA-Based Technology
Authors: Nuha Mansour Alhazmi, Magda Mohamed Aly, Fardus M. Bokhari, Ahmed Bahieldin, Sherif Edris
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Out of 30 fungal isolates, 2 new isolates were proven to degrade poly-β-hydroxybutyrate (PHB). Enzyme assay for these isolates indicated the optimal environmental conditions required for depolymerase enzyme to induce the highest level of biopolymer degradation. The two isolates were basically characterized at the morphological level as Trichoderma asperellum (isolate S1), and Aspergillus fumigates (isolate S2) using standard approaches. The aim of the present study was to characterize these two isolates at the molecular level based on the highly diverged rRNA gene(s). Within this gene, two domains of the ribosome large subunit (LSU) namely internal transcribed spacer (ITS) and 26S were utilized in the analysis. The first domain comprises the ITS1/5.8S/ITS2 regions ( > 500 bp), while the second domain comprises the D1/D2/D3 regions ( > 1200 bp). Sanger sequencing was conducted at Macrogen (Inc.) for the two isolates using primers ITS1/ITS4 for the first domain, while primers LROR/LR7 for the second domain. Sizes of the first domain ranged between 594-602 bp for S1 isolate and 581-594 bp for S2 isolate, while those of the second domain ranged between 1228-1238 bp for S1 isolate and 1156-1291 for S2 isolate. BLAST analysis indicated 99% identities of the first domain of S1 isolate with T. asperellum isolates XP22 (ID: KX664456.1), CTCCSJ-G-HB40564 (ID: KY750349.1), CTCCSJ-F-ZY40590 (ID: KY750362.1) and TV (ID: KU341015.1). BLAST of the first domain of S2 isolate indicated 100% identities with A. fumigatus isolate YNCA0338 (ID: KP068684.1) and strain MEF-Cr-6 (ID: KU597198.1), while 99% identities with A. fumigatus isolate CCA101 (ID: KT877346.1) and strain CD1621 (ID: JX092088.1). Large numbers of other T. asperellum and A. fumigatus isolates and strains showed high level of identities with S1 and S2 isolates, respectively, based on the diversity of the first domain. BLAST of the second domain of S1 isolate indicated 99 and 100% identities with only two strains of T. asperellum namely TR 3 (ID: HM466685.1) and G (ID: KF723005.1), respectively. However, other T. species (ex., atroviride, hamatum, deliquescens, harzianum, etc.) also showed high level of identities. BLAST of the second domain of S2 isolate indicated 100% identities with A. fumigatus isolate YNCA0338 (ID: KP068684.1) and strain MEF-Cr-6 (ID: KU597198.1), while 99% identities with A. fumigatus isolate CCA101 (ID: KT877346.1) and strain CD1621 (ID: JX092088.1). Large numbers of other A. fumigatus isolates and strains showed high level of identities with S2 isolate. Overall, the results of molecular characterization based on rRNA diversity for the two isolates of T. asperellum and A. fumigatus matched those obtained by morphological characterization. In addition, ITS domain proved to be more sensitive than 26S domain in diversity profiling of fungi at the species level.Keywords: Aspergillus fumigates, Trichoderma asperellum, PHB, degradation, BLAST, ITS, 26S, rRNA
Procedia PDF Downloads 158552 De Novo Assembly and Characterization of the Transcriptome from the Fluoroacetate Producing Plant, Dichapetalum Cymosum
Authors: Selisha A. Sooklal, Phelelani Mpangase, Shaun Aron, Karl Rumbold
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Organically bound fluorine (C-F bond) is extremely rare in nature. Despite this, the first fluorinated secondary metabolite, fluoroacetate, was isolated from the plant Dichapetalum cymosum (commonly known as Gifblaar). However, the enzyme responsible for fluorination (fluorinase) in Gifblaar was never isolated and very little progress has been achieved in understanding this process in higher plants. Fluorinated compounds have vast applications in the pharmaceutical, agrochemical and fine chemicals industries. Consequently, an enzyme capable of catalysing a C-F bond has great potential as a biocatalyst in the industry considering that the field of fluorination is virtually synthetic. As with any biocatalyst, a range of these enzymes are required. Therefore, it is imperative to expand the exploration for novel fluorinases. This study aimed to gain molecular insights into secondary metabolite biosynthesis in Gifblaar using a high-throughput sequencing-based approach. Mechanical wounding studies were performed using Gifblaar leaf tissue in order to induce expression of the fluorinase. The transcriptome of the wounded and unwounded plant was then sequenced on the Illumina HiSeq platform. A total of 26.4 million short sequence reads were assembled into 77 845 transcripts using Trinity. Overall, 68.6 % of transcripts were annotated with gene identities using public databases (SwissProt, TrEMBL, GO, COG, Pfam, EC) with an E-value threshold of 1E-05. Sequences exhibited the greatest homology to the model plant, Arabidopsis thaliana (27 %). A total of 244 annotated transcripts were found to be differentially expressed between the wounded and unwounded plant. In addition, secondary metabolic pathways present in Gifblaar were successfully reconstructed using Pathway tools. Due to lack of genetic information for plant fluorinases, a transcript failed to be annotated as a fluorinating enzyme. Thus, a local database containing the 5 existing bacterial fluorinases was created. Fifteen transcripts having homology to partial regions of existing fluorinases were found. In efforts to obtain the full coding sequence of the Gifblaar fluorinase, primers were designed targeting the regions of homology and genome walking will be performed to amplify the unknown regions. This is the first genetic data available for Gifblaar. It has provided novel insights into the mechanisms of metabolite biosynthesis and will allow for the discovery of the first eukaryotic fluorinase.Keywords: biocatalyst, fluorinase, gifblaar, transcriptome
Procedia PDF Downloads 273551 Self-Efficacy Perceptions of Pre-Service Art and Music Teachers towards the Use of Information and Communication Technologies
Authors: Agah Tugrul Korucu
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Information and communication technologies have become an important part of our daily lives with significant investments in technology in the 21st century. Individuals are more willing to design and implement computer-related activities, and they are the main component of computer self-efficacy and self-efficacy related to the fact that the increase in information technology, with operations in parallel with these activities more successful. The Self-efficacy level is a significant factor which determines how individuals act in events, situations and difficult processes. It is observed that individuals with higher self-efficacy perception of computers who encounter problems related to computer use overcome them more easily. Therefore, this study aimed to examine self-efficacy perceptions of pre-service art and music teachers towards the use of information and communication technologies in terms of different variables. Research group consists of 60 pre-service teachers who are studying at Necmettin Erbakan University Ahmet Keleşoğlu Faculty of Education Art and Music department. As data collection tool of the study; “personal information form” developed by the researcher and used to collect demographic data and "the perception scale related to self-efficacy of informational technology" are used. The scale is 5-point Likert-type scale. It consists of 27 items. The Kaiser-Meyer-Olkin (KMO) sample compliance value is found 0.959. The Cronbach alpha reliability coefficient of the scale is found to be 0.97. computer-based statistical software package (SPSS 21.0) is used in order to analyze the data collected by data collection tools; descriptive statistics, t-test, analysis of variance are used as statistical techniques.Keywords: self-efficacy perceptions, teacher candidate, information and communication technologies, art teacher
Procedia PDF Downloads 325550 ALEF: An Enhanced Approach to Arabic-English Bilingual Translation
Authors: Abdul Muqsit Abbasi, Ibrahim Chhipa, Asad Anwer, Saad Farooq, Hassan Berry, Sonu Kumar, Sundar Ali, Muhammad Owais Mahmood, Areeb Ur Rehman, Bahram Baloch
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Accurate translation between structurally diverse languages, such as Arabic and English, presents a critical challenge in natural language processing due to significant linguistic and cultural differences. This paper investigates the effectiveness of Facebook’s mBART model, fine-tuned specifically for sequence-tosequence (seq2seq) translation tasks between Arabic and English, and enhanced through advanced refinement techniques. Our approach leverages the Alef Dataset, a meticulously curated parallel corpus spanning various domains to capture the linguistic richness, nuances, and contextual accuracy essential for high-quality translation. We further refine the model’s output using advanced language models such as GPT-3.5 and GPT-4, which improve fluency, coherence, and correct grammatical errors in translated texts. The fine-tuned model demonstrates substantial improvements, achieving a BLEU score of 38.97, METEOR score of 58.11, and TER score of 56.33, surpassing widely used systems such as Google Translate. These results underscore the potential of mBART, combined with refinement strategies, to bridge the translation gap between Arabic and English, providing a reliable, context-aware machine translation solution that is robust across diverse linguistic contexts.Keywords: natural language processing, machine translation, fine-tuning, Arabic-English translation, transformer models, seq2seq translation, translation evaluation metrics, cross-linguistic communication
Procedia PDF Downloads 6549 Human Rights to Environment: The Constitutional and Judicial Perspective in India
Authors: Varinder Singh
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The primitive man had not known anything like human rights. In the later centuries of human progress with the development of scientific and technological knowledge, the growth of population and the tremendous changes in the human environment, the laws of nature that maintained the Eco-balance crumbled. The race for better and comfortable life landed mankind in a vicious circle. It created environmental imbalance, unplanned and uneven development, breakdown of self-sustaining village economy, mushrooming of shanty towns and slums, widening the chasm between the rich and the poor, over-exploitation of natural resources, desertification of arable lands, pollution of different kinds, heating up of earth and depletion of ozone layer. Modem International Life has been deeply marked and transformed by current endeavors to meet the needs and fulfill the requirements of protection of human person and of the environment. Such endeavors have been encouraged by the widespread recognition that protection of human being and the environment reflects common superior values and constitutes a common concern of mankind. The parallel evolutions of human rights protection and environmental protection disclose some close affinities. There was the occurrence of process of internationalization of both human rights protection and environmental protection, the former beginning with the 1948 Universal Declaration of Human Rights, the latter with the 1972 Stockholm Declaration on the Human Environment.It is now well established that it is the basic human right of every individual to live in a pollution free environment with full human dignity. The judiciary has so far pronounced a number of judgments in this regard. The Supreme Court in view of various laws relating to environment protection and the constitutional provision has held that right to pollution free environment. Article-21 is the heart of the fundamental rights and has received expanded meanings from time to time.Keywords: human rights, law, environment, polluter
Procedia PDF Downloads 222548 Aseismic Stiffening of Architectural Buildings as Preventive Restoration Using Unconventional Materials
Authors: Jefto Terzovic, Ana Kontic, Isidora Ilic
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In the proposed design concept, laminated glass and laminated plexiglass, as ”unconventional materials”, are considered as a filling in a steel frame on which they overlap by the intermediate rubber layer, thereby forming a composite assembly. In this way vertical elements of stiffening are formed, capable for reception of seismic force and integrated into the structural system of the building. The applicability of such a system was verified by experiments in laboratory conditions where the experimental models based on laminated glass and laminated plexiglass had been exposed to the cyclic loads that simulate the seismic force. In this way the load capacity of composite assemblies was tested for the effects of dynamic load that was parallel to assembly plane. Thus, the stress intensity to which composite systems might be exposed was determined as well as the range of the structure stiffening referring to the expressed deformation along with the advantages of a particular type of filling compared to the other one. Using specialized software whose operation is based on the finite element method, a computer model of the structure was created and processed in the case study; the same computer model was used for analyzing the problem in the first phase of the design process. The stiffening system based on composite assemblies tested in laboratories is implemented in the computer model. The results of the modal analysis and seismic calculation from the computer model with stiffeners applied showed an efficacy of such a solution, thus rounding the design procedures for aseismic stiffening by using unconventional materials.Keywords: laminated glass, laminated plexiglass, aseismic stiffening, experiment, laboratory testing, computer model, finite element method
Procedia PDF Downloads 77547 CO₂/CH₄ Exchange Studies on Shales to Assess the Potential for CO₂ Storage and Enhanced Shale Gas Recovery
Authors: Mateusz Kudasik, Katarzyna Kozieł
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The work included detailed studies of CO₂/CH₄ exchange on a shale core from the Lewino-1G2 well (Poland) from a depth of 3408 m. The sample permeability coefficients were determined under conditions of confining pressure from 5 MPa to 35 MPa. These studies showed that at a confining pressure of 35 MPa – corresponding to a depth of about 1000 m, the shale core was impermeable in the direction perpendicular to the bedding, and in the direction parallel to the bedding, the sample had very low permeability (k∞=0.001 mD). The sorption tests performed showed low sorption capacities, which amounted to a maximum of 1.28 cm³/g in relation to CO₂ and 0.87 cm³/g to CH₄ at a pressure of 1.4 MPa. The most important study used to assess the possibilities of CO₂ storage and gas recovery from shale rocks were the CO₂/CH₄ exchange experiments, which were carried out under confining pressure conditions of 5 MPa and 30 MPa. These experiments were carried out on a unique apparatus, which makes it possible to apply a confining pressure corresponding to in situ conditions. The obtained results made it possible to carry out a comprehensive balance of gas exchange during the injection of CO₂ into the shale sample, with simultaneous recovery of CH₄. Based on the conducted sorption and gas exchange studies on the core sample under confining pressure conditions, it was found that in situ conditions, at the depths of shale gas occurrence in Poland of 3000-4000 m, where the confining pressure can be about 100 MPa: (i) poorly developed pore structure, (ii) very low permeability, and (iii) low sorption properties, make shale rocks poorly predisposed to the application of CO₂ storage technology with simultaneous recovery of CH₄. Without the stimulation of CO₂/CH₄ exchange rates through fracturing processes, the effectiveness of CO₂-ESGR technology on shale rock is very low. The research presented in this work is extremely important from the point of view of precise assessment of the potential of CO₂-ESGR technology.Keywords: shale gas, shale rocks, CO₂/CH₄ exchange, permeability, sorption, CO₂, CH₄
Procedia PDF Downloads 4546 The Image Redefinition of Urban Destinations: The Case of Madrid and Barcelona
Authors: Montserrat Crespi Vallbona, Marta Domínguez Pérez
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Globalization impacts on cities and especially on their centers, especially on those spaces more visible and coveted. Changes are involved in processes such as touristification, gentrification or studentification, in addition of shop trendiness. The city becomes a good of interchange rather than a communal good for its inhabitants and consequently, its value is monetized. So, these different tendencies are analyzed: on one hand, the presence of tourists, the home rental increase, the explosion of businesses related to tourism; on the other hand; the return of middle classes or gentries to the center in a socio-spatial model that has changed highlighting the centers by their culture and their opportunities as well as by the value of public space and centrality; then, the interest of students (national and international) to be part of these city centers as dynamic groups and emerging classes with a higher purchasing power and better cultural capital than in the past; and finally, the conversion of old stores into modern ones, where vintage trend and the renewal of antiquity is the essence. All these transforming processes impact the European cities and redefine their image. All these trends reinforce the impression and brand of the urban center as an attractive space for investment, keeping such nonsense meaningful. These four tendencies have been spreading correlatively impacting the centers and transforming them involving the displacement of former residents of these spaces and revitalizing the center that is financed and commercialized in parallel. The cases of Madrid and Barcelona as spaces of greater evidence in Spain of these tendencies serve to illustrate these processes and represent the spearhead. Useful recommendations are presented to urban planners to find the conciliation of communal and commercialized spaces.Keywords: gentrification, shop trendiness, studentification, touristification
Procedia PDF Downloads 170545 Impact of a Novel Technique of S-Shaped Tracheostoma in Pediatric Tracheostomy in Intensive Care Unit on Success and Procedure Related Complications
Authors: Devendra Gupta, Sushilk K. Agarwal, Amit Kesari, P. K. Singh
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Objectives: Pediatric patients often may experience persistent respiratory failure that requires tracheostomy placement in Pediatric ICU. We have designed a technique of tracheostomy in pediatric patients with S-shaped incision on the tracheal wall with higher success rate and lower complication rate. Technique: Following general anesthesia and positioning of the patient, the trachea was exposed in midline by a vertical skin incision. In order to make S-shaped tracheostoma, second tracheal ring was identified. The conventional vertical incision was made in second tracheal ring and then extended at both its ends laterally in the inter-cartilaginous space parallel to the tracheal cartilage in the opposite direction to make the incision S-shaped. The trachea was dilated with tracheal dilator and appropriate size of tracheostomy tube was then placed into the trachea. Results: S-shaped tracheostomy was performed in 20 children with mean age of 6.25 years (age range is 2-7) requiring tracheostomy placement. The tracheostomy tubes were successfully placed in all the patients in single attempt. There was no incidence of significant intra-operative bleeding, subcutaneous emphysema, vocal cord palsy or pneumothorax. Two patients developed pneumonia and expired within a year. However, there was no incidence of tracheo-esophageal fistula, suprastomal collapse or difficulty in decannulation on one year of follow up related to our technique. One patient developed late trachietis managed conservatively. Conclusion: S-shaped tracheoplasty was associated with high success rate, reduced risk of the early and late complications in pediatric patients requiring tracheostomy.Keywords: peatrics, tracheostomy, ICU, tracheostoma
Procedia PDF Downloads 263544 Refractory T-Cell Prolymphocytic Leukemia with JAK3 Mutation: In Vitro and Clinical Synergy of Tofacitinib and Ruxolitinib
Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz
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T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3
Procedia PDF Downloads 309543 MicroRNA Drivers of Resistance to Androgen Deprivation Therapy in Prostate Cancer
Authors: Philippa Saunders, Claire Fletcher
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INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft
Procedia PDF Downloads 141542 DNA Damage and Apoptosis Induced in Drosophila melanogaster Exposed to Different Duration of 2400 MHz Radio Frequency-Electromagnetic Fields Radiation
Authors: Neha Singh, Anuj Ranjan, Tanu Jindal
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Over the last decade, the exponential growth of mobile communication has been accompanied by a parallel increase in density of electromagnetic fields (EMF). The continued expansion of mobile phone usage raises important questions as EMF, especially radio frequency (RF), have long been suspected of having biological effects. In the present experiments, we studied the effects of RF-EMF on cell death (apoptosis) and DNA damage of a well- tested biological model, Drosophila melanogaster exposed to 2400 MHz frequency for different time duration i.e. 2 hrs, 4 hrs, 6 hrs,8 hrs, 10 hrs, and 12 hrs each day for five continuous days in ambient temperature and humidity conditions inside an exposure chamber. The flies were grouped into control, sham-exposed, and exposed with 100 flies in each group. In this study, well-known techniques like Comet Assay and TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) Assay were used to detect DNA damage and for apoptosis studies, respectively. Experiments results showed DNA damage in the brain cells of Drosophila which increases as the duration of exposure increases when observed under the observed when we compared results of control, sham-exposed, and exposed group which indicates that EMF radiation-induced stress in the organism that leads to DNA damage and cell death. The process of apoptosis and mutation follows similar pathway for all eukaryotic cells; therefore, studying apoptosis and genotoxicity in Drosophila makes similar relevance for human beings as well.Keywords: cell death, apoptosis, Comet Assay, DNA damage, Drosophila, electromagnetic fields, EMF, radio frequency, RF, TUNEL assay
Procedia PDF Downloads 167